GENERAL MEDICAL COUNCIL
FITNESS TO PRACTISE PANEL (MISCONDUCT)
Thursday 26 July 2007
Regents Place, 350 Euston Road, London NW1 3JN
Chairman: Dr Surendra Kumar, MB BS FRCGP
Panel Members: Mrs Sylvia Dean
Ms Wendy Golding
Dr Parimala Moodley
Dr Stephen Webster
Legal Assessor: Mr Nigel Seed QC
WAKEFIELD, Dr Andrew Jeremy
WALKER-SMITH, Professor John Angus
MURCH, Professor Simon Harry
(Transcript of the shorthand notes of T. A. Reed & Co.
Tel No: 01992 465900)
A P P E A R A N C E S
MS SALLY SMITH QC and MR CHRIS MELLOR and MR OWAIN THOMAS of counsel, instructed by Messrs Field Fisher Waterhouse, solicitors, appeared on behalf of the General Medical Council.
MR KIERAN COONAN QC and MR NEIL SHELDON of counsel, instructed by Messrs RadcliffesLeBrasseur, Solicitors, appeared on behalf of Dr Wakefield who was present.
MR STEPHEN MILLER QC and MS ANDREA LINDSAY-STRUGO of counsel, instructed by Messrs Eastwoods, Solicitors, appeared on behalf of Professor Walker-Smith who was present.
MR ADRIAN HOPKINS QC and MR RICHARD PARTRIDGE of counsel, instructed by Messrs Berrymans, Solicitors, appeared on behalf of Professor Murch who was present.
I N D E X
DR STUART EDWARD PEGG, Continued
Cross-examined by MR MILLER (cont) 1
Cross-examined by MR COONAN 4
Cross-examined by MR HOPKINS 44
Re-examined by MS SMITH 52
Questioned by THE COMMITTEE 64
Further cross-examined by MR COONAN 76
Further cross-examined by MR MILLER 77
THE CHAIRMAN: Good morning, everyone. Mr Miller, you were in the middle of cross-examining this witness.
DR MICHAEL STUART PEGG, Sworn
Cross-examined by MR MILLER
MR MILLER: No, sir, I am not in the middle; I am very close to the end. Dr Pegg, I want to ask you about the correspondence in 1998, which is in bundle 3. Could you just turn to page 928? Page 930 is more appropriate, in fact. It is the same letter. On 9 July you were sent a letter by Professor Zuckerman, who is the Dean of the Medical School.
A Page 931?
Q Page 929. The question was that you were sent on 9 July a copy of a letter to Professor Sir David Hull, which was the 930 or 928 letter. Do you have page 930 there?
Q Do not worry about Professor Zuckerman’s letter for the moment. It is Professor Hull I am asking about. His concern was as to the ethical position of continuing to investigate children in what he said was the absence of long-term bowel disorder. It is the second paragraph really.
“In the light of the initial findings and the evidence that as a group the children do not suffer long term bowel disorder, it would seem difficult to justify such invasive studies on clinical grounds.”
Then the last paragraph:
“I see that the investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust. If the studies are continuing I would be grateful if I could see the Ethics Committee position on the investigations, especially if they have reviewed their position in the light of the reported findings. If you thought it helpful the Ethics Committee of the Royal College of Paediatrics and Child Health could give an independent view.”
So you were copied into a letter, on the face of it a personal letter, sent by David Hull to Professor Zuckerman.
Q Did you also receive shortly after that, on 15 July, on page 940, a letter from Professor Walker-Smith with a request for Ethical Committee approval?
Q We can see from the chronology, putting the correspondence together, that that letter from Professor Walker-Smith to you followed hot on the heels of a copy of a letter of the same date, 15 July, which had been sent by Professor Zuckerman to Professor Walker-Smith. The body of the letter says that it was copied to you, and if you look at that, it is on page 939, second paragraph:
“I am reassured that the children with autism” – this is obviously a response to a letter he has had from Professor Walker-Smith – “are investigated according to the clinical need and their clinical management. Nevertheless, it would be prudent to obtain ethical approval if, as I understand it, Andy Wakefield is collecting cases for report by publication, which is therefore a research project.”
Although it is not cc’d to you, we see from the last sentence, “I am copying my letter to Roy Pounder, Mark Berelowitz and Michael Pegg”. So on the same day there is a letter copied to you in which Professor Zuckerman is advising Professor Walker-Smith to obtain ethical approval and on that very day he writes to you requesting it, saying that it wd be prudent to obtain ethical approval. Did you get both of those letters?
Q Can we then just turn to page 940, the letter itself, the one that you got from Professor Walker-Smith, one of the ones that was addressed to you rather than copied to you. As you have already observed, the heading is not the same as 17296. It is headed “Autism and Non-Specific Colitis and Lymphoid Nodular Hyperplasia”.
“Further to our original study, we are now continuing to see such children by clinical need and performing ileo-colonoscopy and limited blood tests in order to decide whether to give such children Mesalazine. As Dr Wakefield is carefully analyzing our results and some of the biopsies taken are being used for research (we already have research permission for taking extra biopsies in children who we colonoscope) I would like formally to request Ethical Committee approval for our clinical research analysis of these children who we are continuing to see by clinical need.”
Did you reply to that letter, Dr Pegg?
A I do not know. Let us have a look.
Q If you did, it would be in the Royal Free Hospital Ethics Committee correspondence, would it not?
A Are you trying to make me find it or…
Q No, no. I have not been able to find it. Do you know whether you did.
A I have not got it.
Q It would either have been a Maureen Carroll letter or it would have been one of your personal letters written from your desk if you did.
A If I have not got it, then I do not know.
Q He is asking for ethical approval for clinical research analysis and in terms of timing, this was after Professor Hull had written to Professor Zuckerman and Professor Zuckerman had passed that on to you, and you had been made aware of the correspondence at the same time between Professor Zuckerman and Professor Walker-Smith where Professor Zuckerman had said it would be prudent to obtain ethical approval. That is the timing of it, is it not?
A What is the timing? Sorry. I cannot actually work out what the question is.
Q I think it wd be more helpful, Dr Pegg, if you did not flick through the correspondence when the question is being asked. If you listen to the question, it is a relatively simple one. In terms of timing, that request from Professor Walker-Smith was after Professor Hull had written to Professor Zuckerman, because you had been sent a copy of that, and you passed on a copy of his letter, and you had been made aware of the correspondence at the same time between Professor Zuckerman and Professor Walker-Smith in which Professor Zuckerman had said it would be prudent for Professor Walker-Smith to obtain ethical approval.
Q Taking matters forward, Professor Zuckerman, as we have seen, had written to you a short letter saying “I would like to have your comments on this” and you responded on 24 July 1998, which is at page 951. We looked at this letter yesterday. It is quite a long letter. In the first paragraph you give the history that it was first considered at an Ethics Committee meeting on 13 November.
“The committee was very conscious of the requirement to avoid non-therapeutic research of more than minimal risk in young children. We therefore asked for reassurance that the investigations that were to be carried out in this study were clinically indicated and were not being carried out just for research. Professor Walker-Smith gave me that written reassurance…”
and you quote it.
“Thus at the ethics meeting in December there was no real ethical issue to address. The children were having the investigations as part of normal clinical practice and the ethics committee was involved purely because the cases were being collected for report by publication. The study was therefore approved.”
On 22 July 1998, ie two days before this letter, the ethics committee reviewed this study again following a report by Professor Walker-Smith, so you understood that letter which we have looked at of 15 July as being a report from Professor Walker-Smith consequent upon the study.
Q This study was now entitled “Autism and Non-Specific Colitis and Lymphoid Nodular Hyperplasia” so by that stage you had identified the fact that it had a different name.
“Again, Professor Walker-Smith gave us reassurance that only clinically indicated investigations wd be carried out:
‘I would like formally to request Ethical Committee approval for our clinical research analysis of these children who we are continuing to see by clinical need.’
Again, the ethics committee approved the study on the understanding that all that was being approved was data collection.”
It may be that there is an approval – I have not seen it – but clearly you are saying only nine days later that the committee had considered it and approved it by that time.
Q Then you revert back to what Professor Hull had said in his letter:
“’I see that the investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust.’
“This is, of course, incorrect. We did not approve the investigations. We approved data collection from clinically indicated investigations. It is not, at present, the role of an ethics committee to question clinicians’ judgement as to what are and what are not [independent] investigations. However we do not just take the word of the investigator, rather we ask for independent expert review of all applications. In this case Dr Owen Epstein provided a review of the project and I have a letter from him ‘strongly supporting’ the study.”
MISS SMITH: I am sorry. Mr Miller said “independent investigations”. It says “clinically indicated investigations.”
MR MILLER: Thank you very much. “Independent expert review of all applications.” So you reiterate the point in that letter that you had made earlier that you do not just take the word of the investigator on the clinical aspect of it as well as all other aspects of it; you ask for a review from somebody not involved. In this case, that review came from Dr Owen Epstein.
Cross-examined by MR COONAN
MR COONAN: Good morning, Dr Pegg. Can we please start by looking at the pro forma application? If you turn to page 200 in volume 1, I want to embark on a preliminary exercise to try and get some sense out of the order in which these documents have been photocopied in the bundle. Pages 200 and 201 clearly go together in sequence, do they not?
Q Then if we look at the bottom of page 201, the heading of that is “Scientific Background” and there is a pro forma question drafted by you.
Q Then what follows on page 202 is a typed in account of the scientific background, and we see that on page 202 through to 207 – yes?
Q If we go to the top of page 208, it is the continuation, is it not, of paragraph 5 that we saw on the bottom of page 201?
Q So so far all the documents are in sequence. Would you agree?
Q Then we go to 208 and 209 and 210. All those are in sequence, are they not?
Q If keep your finger on page 210, I am going to suggest to you that we have to go to page 232 to get the next document in sequence. The reason I suggest that is, if you get your bearings by looking at the bottom of page 210, it is then concerned with the handout, and the handout immediately follows on 232. Do you see?
A Would not 211 come first? Page 211 says “If you agree to let your child take part, please sign the attached things” so 211 is a request to the parents preceding them looking at the handout.
Q I follow that and we will come to it in a minute, because I am going to come back to 211, but 232 immediately follows, I suggest, page 210 because it is part of paragraph 14 on page 210. Do you see?
Q Part of paragraph 14, and we get the continuation of paragraph 14 on page 233, because it begins again at paragraph 15.
Q My point is that page 232 and 233 necessarily follow page 210.
A If you say so. I wd say the little letter there is an invitation which would naturally precede the piece of information that the information relates to. It is just that one has been copied and pasted and the other has been stuck in at the next place.
Q Dr Pegg, all possible constructions 11 years down the line are possible of course, but I am just looking at the logical construction of these documents. Page 211 might actually, might it not, be a stand-alone document, a loose document attached to the pro forma?
A Is it a loose document attached in the same way that the scientific bit was attached? Computers were different in those days. You did not bother to cut and paste everything, did you? You just stuck bits in where you put them.
Q That is exactly what I am speaking about. The sequence I am talking about has a representation of the material which has been typed in accordance with your pro forma question.
A There probably really was no original order to this. It was just a bundle of documents sent to the ethics committee.
Q You say that, Dr Pegg, but you see, this problem that I am dealing with would not be a problem if we had the original documents available, would it?
A The original documents would have been in a random order as much as the photocopies were.
Q Where are the originals, please?
A The originals would have been shredded a long time ago.
Q That is the problem, is it not?
A We shred at three years.
Q Frankly, I put your mind at rest. It does not matter for my purposes whether page 211 comes immediately after 210 or it is a freestanding document at all. I am just trying to make sense of how this bundle of documents might be read. Can I go back now to page 212? Pages 212 to 231 can be read as one single document, can they not?
Q The reason I suggest that is that we can see, as it were, sub-numbering on the bottom of the pages. If you start at page 213, you will see the number 2 and you follow it all the way through to page 231, turning sideways on, page number 20. Do you see that?
Q So we can take that as a stand-alone document and when the Panel are looking at this and looking at the pro forma element, mentally, it is as well to take out pages 212-231 and put them on one side.
Q Let me go back to the sequencing. So if we have taken out up to page 231 and put it on one side, we continue, pages 232, 233 and then 235, and yesterday the learned Legal Assessor raised the point that 234 must be out of sequence. That must be right, must it not?
A Well, I shall not argue.
Q Well, it must be right. It is not a question of arguing. It must be right.
A Well, the consent form goes with the information sheet.
Q Yes. Well, I do not dispute that.
A The information sheet has just finished, obviously the consent form should really be stuck in above 15 but nobody has bothered to paste it there, so they have just stuck it in at the next place, because we always insist that consent forms and information sheets go together.
Q Absolutely. Well, that makes sense.
A So I think correctly the consent form is at 234.
Q Well, I think I have made the point and I think the Panel have understood it, and the learned Legal Assessor made the point yesterday. I do not want to prolong it. Now, looking at page 234, that is, on its face, a consent form which is directed to at least research elements in a study, is it not?
A I suppose so, yes. Well, it does not mention the word “research” in it, but it refers back to a form with “research” written on it, yes.
Q Because it is not a consent form that would be used for an individual investigation, such as a lumbar puncture or a biopsy or an MRI; this is a document which has another purpose, does it not?
Q We will come back to that. Now, before leaving this preliminary look at this pro forma, I would now like, please, to take you to page 212 first, because this is in the stand alone document headed “Proposed clinical and scientific study”, on page 212. All right?
Q On page 213 we see a great deal of information, as also on page 214, and yesterday you told us, when you were asked by Mr Miller to look at the potential roles and responsibilities of the people mentioned on page 200 – just turn back for a minute and keep your finger on page 213, please – you were asked about the potential roles of those people on page 200, and you said, and I summarise I hope fairly, that you did not know about that because it could be just other people in the department.
Q Now, if we turn to page 213 we can get, I suggest, quite a good picture of what the individual roles and responsibilities were. Let us go through them. Under the main heading of “Investigators” we see first of all the role of the Department of Paediatric Gastroenterology, and there are four people mentioned in that department, are there not?
Q Professor Walker-Smith (Professor), Dr Simon Murch (as he then was), Dr Alan Phillips and Dr David Casson, and their responsibilities in relation to those four people are set out:
“Referral and co-ordination of patient admission for investigation.
Clinical evaluation” – note that word “clinical evaluation” – “procurement of blood, urine and serum samples.
Colonoscopy, and tissue procurement/processing.”
Now, that was a clear description of the responsibilities of those clinicians, was it not?
Q It is pretty obvious, reading even from that part of the document, that the document was concerned with clinical matters.
Q Let us move on. “Department of Histopathology & Medicine” - that is at the Royal Free, yes?
Q “and Department of Molecular Chemistry, University of Greenwich”. We see an asterisk there, and if you drop down to the bottom of the page you will see a reference to the Norwood Laboratory at the School of Molecular Biology & Chemistry at the Woolwich Campus of the University of Greenwich.
Q We see the people who are concerned with matters in respect of those two departments: Dr Andy Wakefield, Senior Lecturer and co-ordinating investigator; Dr Amar Dhillon, now Professor Dhillon, Senior Lecturer and Consultant Histopathologist; Dr Linnell, cobalamin studies (he is an honorary research scientist); and Professor Bruce, Professor of Biological Chemistry; Dr Subhani, dealing with a concept called complement studies – more about that later – Mr Chadwick, concerned with molecular studies. So in relation to that part of the document, that is a clear reference to those who would be involved with what I may call laboratory matters. Yes?
Q The science, yes?
A Yes. You made a statement, or is it a question?
Q It is a question.
Q Following on from that we can see how the author of this document set out the responsibilities of those who were concerned with the science. If you look at the top of page 214, under “Responsibilities”, let us look at them:
“Evaluation and description of histopathological changes.”
That is, in a word, looking down the microscope, is it not?
Q “RNA studies for identification of measles and rubella viruses.” That is laboratory work, is it not?
Q Then “Cobalamin studies”; that too is laboratory work connected with vitamin B12, is it not?
Q Then we move on to the next level of investigators and the Department of Child Psychiatry: “Dr Mark Berelowitz (Consultant Psychiatrist)” – and I direct your attention to what is then written – “co-ordinating investigator”. Do you see that?
Q His responsibility, if we drop down, was the confirmation and characterisation of features of disintegrative disorder. Finally, in the Department of Neurology, Dr Harvey, Consultant Neurologist and once again co-ordinating investigator, and his responsibility was a full neurological assessment and investigation. Now, you received this document and did you appreciate the breadth of responsibilities of these four separate departments involving a university and involving a hospital of renown in London?
Q I want now to look a little more closely, please, at the pro forma itself. A useful place to start obviously would be at page 200. This was an application for ethical approval for a study which was to start, obviously, in the future, was it not?
A I think that is probably right.
Q On the face of it, this was not an application expressed to be for data collection.
Q You agree with my proposition.
Q Now, as we go through this I want you, please, just to bear in mind two factors; first of all, on the one hand, what you understood by this application, and, on the other, what the researchers intended, because there may not, I am going to suggest to you, have been a meeting of minds on this. So just bear that in mind as we go through it. Now, this document is a somewhat daunting document, is it not?
A It is not as daunting as it is nowadays. It is quite simple compared to the applications we do at the moment; they are 57 pages. So this is not particularly daunting as ethics committees applications go, no.
Q Well, then, my path is going to be somewhat easier, because I think you told us yesterday that you did read it all up and you came to understand what it was about.
Q Then yesterday you said it arrived on your desk in a format that was somewhat unfortunate, which was the way you described it yesterday, “common but unfortunate”; what did you mean by that?
Q Yesterday you described it as being in a format which was somewhat unfortunate although common.
A Can you put that back in the context of what were the questions before that, because I cannot quite work out – where were we in context?
Q Well, let us just start again rather than referring back to what you said. Was it in a format which was a common one at that time?
Q Was it a format which was in some respects unclear?
A Not particularly.
Q All right. Then I shall proceed on the basis that at any rate at some stage you read it up, understood what it was all about and that would have informed your actions thereafter, would it not?
Q Can you vouch for other members of your Committee, did they understand that?
A Well, I cannot say whether other people twelve years ago understood an application.
Q Well, with respect, you can, because you had meetings with them and you are able to say whether, from your observations at that time, they understood it.
A I doubt whether the hospital chaplain would understand the protocol in this study, no, but that is not his job on the Committee.
Q I follow that, but equally of course the Panel will understand that it is not your decision, it is the Panel’s decision, is it not?
Q So in order to make a decision the members of the Panel have to understand it, do they not?
A A lay member sitting on a committee will not understand the science of this. The lay member will read the information sheet and see if that is a suitable piece of paper to be put in front of a lay person, but the lay member will not understand the science of this study. That is why it goes out to scientific review. So the answer to the question is no, they will not all understand.
Q Now, what is quite clear from this documentation, I suggest, is that, and you can pick it up at page 212, it was a proposed clinical and scientific study.
Q So there is an element of duality about it, is there not?
Q The fact that there is an element of duality about it is not uncommon; that is quite a frequent occurrence, is it not?
Q Very often, certainly in 1996 and I have no doubt today, applications are put in to ethics committees which describe the clinical context in which the opportunity for research is then taken – yes?
Q Throughout the operation following the granting of EC approval it is anticipated that that duality will continue; in other words, that you have the carrying out of clinically indicated investigations as a backdrop superimposed on which there are research investigations. Correct?
Q The fact, and this is important, the fact that there may be research elements, and in particular laboratory research elements, does not per se convert clinically necessary investigations into research, does it?
Q Now, looking at this pro forma application in the round, I am going to suggest to you, and particularly the medical members on the Panel will be able to judge this for themselves of course, but there is quite clearly a sketched in clinical context in the document itself, is there not?
Q I think for the purposes of these next questions you might care to have open page 209. The answer at the bottom of the page is further support, is it not, for the fact that there the authors – and I stress that, “authors” – of this document are saying that there are clinically indicated procedures, yes?
Q In addition, and I am going back now to the concept of duality, it is quite clear, is it not, from this document that there are research elements to it.
Q I do not know whether at the time, Dr Pegg, you, as it were, identified or teased out the elements which were clearly research elements, but quite obviously at the bottom of page 209 the authors of the document have clearly, I suggest, identified some elements which are clearly pure research, have they not, right at the bottom?
Q I hope the Panel can follow.
“Additional intestinal biopsies (5 per patient) will be taken for viral analysis”.
Q “DNA for genotyping will use blood cells isolated from the routine blood sample”,
Q There are other elements in this document which I suggest clearly represent research elements. Did you in fact identify them yourself when you looked at this?
Q Let us just look at them. It might be helpful to look at page 221. If you look at the fifth bullet point down, and pick it up half-way into the bullet point,
“immuno-histo chemistry for measles virus N-protein and rubella virus as described previously. Other studies will be performed as indicated, (eg GAGs, T-cell markers etc”.
Pure research. Yes?
Q Next bullet point,
“Ultrastructural analysis of mucosal biopsies for more subtle changes”.
Pure research. Yes?
Q Then the next bullet point,
“RNA extraction” –
pausing there, that is a reference back to page 209 –
“from frozen biopsies and amplification of measles and rubella virus RNAs”.
There is reference to Appendix 1 which is in this document. That again is pure research, is it not?
Q Right at the bottom of the page, I am just going to put this to you and ask for your comment, there is a reference to ADI – autism diagnostic interview. Did you make an assessment about that, as to whether that was research or clinically indicated?
Q So you did not make an assessment either way.
A I would not have made an assessment of every single line of this pro forma. I probably would not even have seen that, so the answer to your question is no.
Q Fair enough. Over the page, page 222, paragraph 3 at the top. This is Dr Harvey’s territory and you see a reference there to cytokine measurements. Again, pure research.
A Is that a question or a statement?
Q A question.
A Is it pure research? Yes, it is pure research. I thought you were making statements.
Q It is the inflexion in my voice.
A I thought you were making statements.
Q If you agree with it, then say so. I think you agree that that is research.
Q Then if we look at paragraph 4, the cobalamin studies, Dr Linnell. That again is research.
Q At 4.2, did you consider whether that might be research or clinically indicated.
Q So you did not consider either way?
A I answered the question that we probably would not have looked at this document inch by inch in the way you are doing now.
Q Right, well that may take us some way, but I am doing it now so that we can mark out the territory. Let us move on.
A This document would not have been circulated to the members of the ethics committee. It would have been on the table at the meeting, I think. If we are talking about the protocol, the protocol is tabled. The ethics document is circulated.
Q You see, Dr Pegg, this document that I have just been going through, is part of the document headed, “Proposed clinical and scientific study”, which is intended no doubt by the person who sent it to you to inform you as to the nature of the application.
A Information for the committee should be in the application form. The application form is what the committee considers. Many researchers provide Lever Arch files which are full of tables like this which are tabled at the meeting for information, but it is not expected, for example, that lay members or people without a scientific interest in the subject will go through a protocol. The expectation is that all that information is placed in lay language in the information sheet for people who cannot read these things. So going through these inch by inch, the committee would not have gone through it inch by inch in the way you are doing.
Q But a number of matters arise out of that. Those who were responsible for sending this material in, may have had an expectation that the ethics committee would look at this.
A They could not have had an expectation that lay members would read forms like this. The expectation is that when you apply to an ethics committee you will put your application in lay terms in the application form. The application form should contain everything you are doing.
Q You see, if you look at page 201 there is a request for an account of the scientific background, and you have agreed that page 202 through to page 207 in fact is material which was in the body of the pro forma.
A That is in the body of the pro forma, yes.
Q And you will see that it involves numerous references – I am not going to take you through them; the Panel can see it – to the underlying science which is intended at the very least to be available to the whole Panel.
A Yes. Remember the Panel is not assessing science, this is information. The science has been assessed by Dr Epstein. It is not up to the ethics committee to assess the science that you mentioned a moment ago.
Q Now we understand how you run the committees, but the exercise that I am about still has an important value, I suggest, and we will come to it in due course. Let us go back to page 222. Of course you had this document and you told us that you read up about it and understood what was afoot. At paragraph 4.3, “Plasma total homocystine”, again if one looks at it, that is a clear research element, is it not?
A It looks like it.
Q And paragraph 4.4, “Plasma total cobalamin”, again pure research.
A I do not know what cobalamin is. If you say it is research, it is research, yes.
Q And 4.5, again, another aspect of the cobalamin studies, again clear research.
Q Finally, for my purposes, this concept of complement studies. That again is clear research, is it not?
Q The next step in this was that Mr Stevens, at page 241 obviously read the material which had been placed in front of him. Let us assume and proceed in accordance with your evidence that the 20-odd pages were not in front of him. Let us assume that for the minute. But he looks at this and reads what has been written in those pages that were placed in front of him and he says – I think it is important to look at the precise terms of this –
“The project requires children to undergo an intensive regime. It would be helpful for this to be debated at the committee in order to confirm that the benefits of the regime in terms of clinical care of the individual children involved and the contribution to knowledge about the ‘syndrome’ support the proper approach”.
Obviously everybody is going to applaud Mr Stevens’ question. Quite rightly. It is the ethics committee operating as it should be. You would agree with that, would you not?
Q The reference by Mr Stevens to an “intensive regime” – I just highlight that – can only have been a reference to those clinical elements such as lumbar puncture, colonoscopy and MRI.
Q He cannot have been referring to the laboratory work, can he?
Q In other words, he cannot have been referring to laboratory tests on blood, urine, or to immunohistochemistry following biopsy, can he?
Q And he cannot have been referring to any laboratory work on CSF having been obtained from lumbar puncture.
Q It is against that background, he having raised this question, that you then write to Professor Walker-Smith on 15 October at page 265a – this is the green document which I think should be in front of you. Do you have that, Dr Pegg?
Q In that letter you say, in paragraph 2,
“It is a very intensive regime involving some unpleasant investigations – LP, endoscopy, MRI etc., some of which may require a general anaesthetic”.
You deal with the concerns in connection with those investigations which Mr Stevens has raised and which you are now conveying to Professor Walker-Smith.
Q In the second part of that paragraph, you say this,
“Your submission” –
that is a clear reference to the protocol, is it not?
A If you say so. We are writing in response to the application form, but you say it is the protocol. I mean, you can interpret the thing as you feel.
Q I will be corrected. If you want to use the term “pro forma”, then let us use that. It is a clear reference, is it not, to the pro forma application?
Q So I will read that into it,
“Your [pro forma] application indicates that all these tests” –
note that phrase, “all these tests” –
“would be carried out (apart from 5 extra biopsies and some extra blood)”.
Then you go on to ask him whether he can confirm that the child would undergo this regimen even if it was not in the trial. In that letter, as I say, you have picked up exactly and accurately Mr Stevens’ concerns, but you have put to one side the reference to five extra biopsies and some extra blood, which is a complete lift from page 209 at the bottom, is it not?
A A complete what?
Q It is a complete “lift” from page 209. If you turn to page 209 but keep your finger in 265a, you will see what I mean.
Q Right at the bottom of the page you will see the pro forma and you have agreed that those set aside factors – the intestinal biopsies, five per patient, and the blood tests – are research and were therefore recognised by you as being outwith the question you were putting to Professor Walker-Smith.
Q In other words, and this is my expression so agree or disagree if you like, but in that letter to him you had deliberately and clearly ring-fenced elements which were pure research.
Q I suggest that your deliberate act was perfectly correct and accurate and proper. So that when Professor Walker-Smith replied, at page 291 on 11 November, he was replying specifically to the terms of that letter, was he not?
Q In paragraph 2 of that reply he says,
“Clearly this is an intensive regime with procedures that could be regarded as ‘high’ risk”.
Pausing there, that is a clear reference to the clinical investigations you had highlighted in your letter, LP, endoscopy and MRI. Correct?
Q I am going to drop down to the last four lines,
“We have so far investigated 5 such children on a clinical need basis”,
and then over the page,
“I can confirm that children would have these investigations” –
I draw attention to that phrase, “these investigations” –
“even if there were no trial”.
What Professor Walker-Smith was doing was saying quite clearly to you, was he not, that the investigations that both you and Mr Stevens had highlighted would have been done in any event on the basis of clinical need.
Q Therefore this letter, and your letter cannot be read as any reference by Professor Walker-Smith to investigations of a purely research nature being carried out in any event, can it?
Q Then we come, please, to the approval letter at page 358. The approval letter addressed to Professor Walker-Smith. I just note in passing it was not copied to Dr Wakefield but for these purposes I am not concerned with that. I just want to look at the body of the letter. I want you, please, as we go through this, to have in mind what you have agreed, that in the correspondence which had passed between you and Professor Walker Smith so far, that correspondence had addressed only the clinical investigations and the research elements had been ring-fenced and had not been the subject of correspondence between you and Walker-Smith. All right?
Q On the face of this document, as you agreed yesterday in answer to questions by Mr Miller, there is no reference whatsoever to the fact that approval had been granted in relation to data collection only, is there?
Q And you have agreed that, on the face of the documents, nor was the application in the pro forma an application for data collection only, was it?
Q There is nothing in this letter which therefore excludes approval for those matters which we have agreed were ring-fenced of a research nature, is there?
Q The authors put in an application for approval for those research elements, you have agreed. This letter approves the project, and I am going to suggest to you therefore, Dr Pegg, on its face it approves at least the research elements, does it not?
Q If therefore it approves the research elements, it cannot be said that all this letter does is approve data collection, can it?
Q If this letter is to be construed as approving merely data collection, as you have agreed, the reference to a requirement that the Schilling test be removed is illogical.
Q The reference to the requirement of modifying the lumbar puncture consent form is illogical.
Q The existence of the research consent form that we looked at at the beginning of my cross-examination would be illogical, would it not?
Q And a requirement in the body of this approval letter that you insisted on being in the clinical notes. That is consistent, is it not, with a requirement in respect of at least of research elements which are laboratory-based?
Q When one looks again at the other elements in this letter, there are numerous references to the project – do you see the second line – being approved?
Q You see in paragraph numbered 1 a reference to the existence, as you considered it to be, of a trial.
Q In the latter part of the letter references to a requirement to report adverse events is illogical if this is simply for data collection, is it not?
Q The requirement to send in any proposed amendments to the initial application is illogical if it is concerned only with data collection.
Q I think we have reached a stage where you have accepted that this letter should be read as granting permission for the carrying out of laboratory-based investigations and data collection at least. Is that not right?
A So you say, yes.
Q It is not what I am saying. I am suggesting that to you and I think you have agreed.
A Yes. I have said “yes” to everything, yes.
Q You have agreed.
Q I just want to have a look with you, please, in so far as it may be necessary later on to have a look at this concept of data collection, because yesterday you appeared to be saying that if a clinician or a researcher, or both, simply wish to look at clinical information which has been generated as a result of clinically indicated investigation – no research; pure clinical data – that required ethical committee approval.
Q Does it, Dr Pegg?
Q Where do we find authority for that proposition?
A How do you mean, authority?
Q Where do I find a support for the proposition that if somebody wishes to write up post facto a series of cases of material which has been generated purely in accordance with investigations done on the basis of clinical need – so no research, but to write up a case series, having collected the data – requires EC permission and approval. Where do I find that?
A Writing up a prospective series of cases would be considered research.
Q Was it considered research in 1996?
A You refer back to the document seen yesterday for the requirements of it. I do not have them in front of me.
Q I am going to ask you, please, to tell us.
A The first line I think will say “research on NHS patients”.
Q Take your time. I want to be told, please, where we find the authority for this.
A If someone will give me the page, it will be on the Department of Health paper.
Q Let us look. If you go to volume 4, if we look first of all at the Royal College of Physicians document.
A Sorry. The Department of Health one has more authority.
Q All right. Let us look at that. That is tab 5 in this bundle at page 128 and following.
A “An LREC must be consulted about any research involving NHS patients.”
Q Which page are you looking at?
A Page 131, section 1.3.
A Research on NHS patients.
Q Yes. I am not disputing for a minute that any research proposal involving NHS patients should go before an EC committee. Of course that is right, but the big question is whether or not writing up a case series prospectively on data which has been generated by clinically indicated tests is research. It begs the whole question, does it not?
A Anybody nowadays – not nowadays; anybody wishing to do a prospective gathering of information, using information for purposes the patients did not originally intend that information, making that information available to other people that the patient may not have considered in the first place, is a research study.
Q Dr Pegg, built into the inquiry I am making of you, of course, is the fact that when a case series is drafted that patients are anonymised so there is no way that anybody could know who they are. Take that as a given. I am suggesting to you that in 1996, if I, as a clinician, wanted to write up a series of five cases coming through my department as to what was found, and provided that anonymity is cast iron, I would not need EC approval to do that.
A I would disagree with you.
Q Do you accept that in 1996 there was a different view afoot about this?
A I accept there were different standards.
Q No, that is not what I am saying. Do you accept that there were different views in 1996 about this possible requirement?
Q You do not?
A I am saying a prospective series that… It is different to a series of case reports. Case reports are different. Case reports are something that happens and then you write it up but you did not know before you started that you were going to write it up. If you set out to do a series of cases that you know you are going to publish in a respectable journal, I would say that you need ethics committee approval.
Q So the distinction between us is whether or not you intend at the outset to write it up.
A Let me explain. If you embark on involving an ordinary patient and then suddenly discover something very interesting after you have treated the patient, of course you could not get ethics committee approval because you did not know that that interesting happening was going to happen. However, if you embark on a series of data gathering knowing from the outset that this is going to generate information that you wish to publish, then you need ethics committee approval. It is whether it is the intention when you started. Whether it is a series of case reports – as I say, case reports… I may put a patient to sleep tomorrow and something very interesting happens. I will write it up. I do not need ethics committee approval because when I put the patient to sleep I did not know this exciting thing was going to happen. So the question is when they set out to do this, when did they suddenly find this exciting happening or when they set out to do it did they know that they were going to aim at a respectable journal? We are talking about patients’ information going to places where the patient did not ever intend it going. That is the difference between… This is why you need ethics committee approval, to keep people’s anonymity, so people know that doctors are carrying out research.
Q Dr Pegg, that brings the matter with greater clarity. It depends upon the intention at the time that you are judging the matter, as you have explained.
A Yes. If you had no intention of doing any papers, something exciting happened, you put a colonoscope in and you saw something exciting, you think, “Yippee! I will do another one” and see that exciting thing, yes, you can write up a case report of two cases.
Q You used the phrase “case report”. I used the phrase “case series”.
A I would say there is a definite distinction in journalese on “case report”. A case report is a case you write up retrospectively, so I would say that when you use the word “case report” you must consider what I call the retrospective thing, that you have done it, it was interesting, you write it up. It still does not mean you do not tell the patient. Nowadays, a journal editor will not accept a case report without the patient’s permission. He will not need ethics committee approval but he will expect the patient who is the subject of the case report to have agreed to the report being written up.
Q Dr Pegg, just let us leave out 2007, if we may. We are talking about 1996. I just want to make sure that when you use the words “case report”, I use the phrase “case series” but I want you to know that I was using it in exactly the same way. You may tick me off for not using the phrase “case report” when I used the word “case series” but I mean the same as you do.
A When I say “case report” I mean a case that is written up retrospectively. When I say “a series of cases” I am using it in the context that you have embarked on gathering a series of cases which are going to be interesting.
Q So in a nutshell, looking at the matter retrospectively, if you have found something interesting as you are going through clinical practice, you are entitled to write the material up, call it a case report or a case series, whatever it may be, but in those circumstances, you do not need ethics committee approval.
A If you unexpectedly find something exciting, of interest, you can write it up. It is your mindset when you start it. If you had no inkling you were going to discover this when you started, then you can write it up, yes.
MR COONAN: Sir, I see the time. I will be some time yet.
THE CHAIRMAN: I think it is probably time for us to have a short adjournment. First of all, Dr Pegg, I think you now understand – I have given this warning many times before – that you are still under oath and you are still in the middle of giving evidence. Someone will look after you for a drink but please make sure that you do not discuss this case with anyone. We will now adjourn and resume at quarter past eleven.
(A short break)
THE CHAIRMAN: Mr Coonan.
MR COONAN: Dr Pegg, I just want to look again with you briefly, please, at the point we were discussing just before we had the break. You were highlighting for us the distinction between on the one hand a retrospective look at cases of interest which are bundled together as a series of case reports for which EC approval was not required, and, on the other hand, and again the intention you said was a crucial distinguishing feature, intending to write up the material, and for these purposes of course you have got to bear in mind that we are talking about, the premise is, all material which is clinically generated, all right, and you said that EC approval was required for that latter category.
Q Now, I just want to look, please, with you at---
A It does not always have to be clinically generated. A series of questions – well, yes, let us not bother.
Q I understood you to be saying that even if the material is purely clinically generated, no research, that therefore you needed EC approval if you intend to write up the material later. That is as I understood---
A Yes to that one.
Q Okay. Now, I want to look, please, at the position in 1996. It is a document we have not looked at. If you look at volume 4, tab 8, beginning at page 198, please. Now, you can see at the bottom of page 198 that was a publication “Guidelines on the practice of Ethics Committees” published by the Royal College of Physicians in August 1996. Now, just pausing there for a minute, when you gave your evidence yesterday you told the Panel the documents and guidelines that you did rely on. You did not refer to this. This was published in August 1996. You were considering this application between September and December 1996. Did you refer to this document?
A I do not know.
Q It is a document, do you agree, which should have informed your deliberations?
A If you look at the plethora of documents at that time, many contradicting each other, we could not look at all of them.
Q Well, I understand the human condition, but---
A We took the Department of Health’s document as having higher authority than the others. The College of Physicians brought one out, the Medical Research Council brought one out, the paediatric people brought one out. Because nature abhors a vacuum, many guidelines are brought out, and many were unfortunately contradictory.
Q Well, that does not make for an easy life.
A That was the position at the time, but the thing is when you have so much contradictory information you try and take one with the best authority, which is the Department of Health’s guideline.
Q No doubt everyone is in the same boat.
A Yes, but this is just an opinion, it is a guideline, like anybody else’s. Anybody could have brought one out, and did.
Q Let us just look at one part of this, please, to see the extent to which it might assist the Panel in their assessment of these matters. If you go to page 232, and I take you to paragraph 6.22, I am going to have to read it, I am afraid:
“Most guidelines” – and there is a footnote to the guidelines there referred to, and I will not bother to read them out – “state that all medical research, including the use of anonymous or confidentially kept records, must be subject to review by an independent REC” – and then there is a proviso set out in the body of the document – “This advice has implications for other groups such as non-medical bodies conducting research in, for example, nutrition and the social sciences.”
A Hold on, I am lost. 232 you said?
Q 232, paragraph 6.22.
Q If you just want to read it to yourself, I do not want to read it out on the transcript again, just to get your bearings.
Q “6.23 A working party with a strong lay membership concluded that to require formal ethical review of research involving personal medical records or stored biological samples alone is likely to delay or even inhibit valuable research: they further recommended, provided that such research is carried out with scrupulous confidentiality, it is by its nature harmless and does not require submission to an LREC. Council of the [Royal College of Physicians] approved this report and agreed to publish it to facilitate wider discussion; it is summarised in Appendix B and has been published in full.”
We see a reference there to a publication by the College in 1994. Then over the page at 233 at 6.24:
“The College is conscious that differences of opinion on what should and what need not be subject to formal ethical review may pose difficulties for RECs, but it is of the nature of ethics that such differences occur, and achieving consensus can be difficult.”
Do you agree with the sentiments in 6.24?
Q Again, if you keep your finger on page 232 and just then go to page 264, you will see the reference there to Appendix B, and much of what is set out in Appendix B is, as was anticipated, summarised on page 232 that I have read out. I take it up in the second paragraph:
“Research involving access to medical records, registers, or existing biological samples only, without direct patient contact or involvement, is not considered to require individual patient consent or independent ethical approval provided that:
explicit consent to access a patient’s records is obtained from the ….. custodian ….. or from the patient’s clinician: the decision to access personal medical information should not be left to the sole discretion of the investigator;
confidentiality is assured …..
the recipient of the information is a senior professional” and so on.
So there we see a situation, if we go back to 232 really and work on the basis of the summary, that there are those circumstances therein set out where EC approval is not required, and that cuts across the circumstances that you were describing before we had the break, does it not?
Q I suppose you would say, “Well, that is another example of there being differences of opinion as to what was required and what was not”?
A Yes. I mean, if you look at this, it says research on this thing, and I think it is quite interesting that you have a document here allowing you to research on biological samples in 1998, and you know what happened next when people took that and researched on hearts and brains and things, so, as you can see, that 1998 I think was a very late time to have---
Q This was 96.
A That is what I say; even this time, I think this was a very late time to have this opinion. This was very, you know, “doctor knows best”. It was out of date even when it was written. Okay, the physicians wrote it. I am just saying the physicians were out of date. But on the Bolam test, and all that, yes, you have got another medical opinion. Whether it is a reasonable medical opinion, I do not know. Just because it comes out of the physicians does not mean that it is something that we agreed with.
A A lot of ethics committees were probably ahead of the medical establishment, who were still in that sort of backward feeling that doctor knows best, the sort of feeling that disappeared from this country, I think, in the late 90s, with Bristol’s and Alder Hey’s and things. This is part of that sort of era, an old-fashioned attitude.
Q Well, Dr Pegg, thank you for that sort of Cook’s tour of the terrain of the late 90s, but in 1996, given your view about the fact that the RCP are out of touch, one is bound to put to you an observation that strikes me at least, “Well, if that is right, what on earth is the poor clinician to do?”
MS SMITH: Is that a question?
MR COONAN: Yes.
A There was a vacuum.
Q Thank you. I suppose your comment applies equally to the researcher, does it not? Is that right?
Q Now, Dr Pegg, let us leave guidelines and so forth alone for the moment. Could I ask you, please, to have in front of you volume 3. Yesterday, and indeed this morning with Mr Miller, you looked at a series of pieces of correspondence beginning on page 929, and the Panel have looked at the detail of this so I am not going to take you to the detail, I just want to look at the milestones. On 9 July 1998, so this is about 18 months after the letter of approval that we looked at this morning was issued, suddenly out of the blue you get this letter form Professor Zuckerman, attaching or enclosing a letter from Professor Sir David Hull, and the contents of that can be read on 930 and you have been taken to those. In response to the receipt of that material you summonsed a meeting of the Ethics Committee, and we know that because you said that that is what you would do, on page 949, is that right?
A Well, “summonsed” is rather a hard word. We had a meeting and we looked at it at the next meeting.
Q All right. Well, if you do not like the word, “convened”?
A It was discussed at the next Ethics Committee meeting.
Q You had a meeting and one of the products of the meeting we see is the letter on page 951 dated 24 July 1998, when you replied substantially to Professor Zuckerman, yes?
Q This letter is the first time, as we see from the second page, 952, the last paragraph:
“We did not approve the investigations. We approved data collection clinically indicated investigations.”
Q That is the first time, is it not, that the idea that the Committee was only approving data collection surfaces?
Q That letter, in saying “We did not approve the investigations”, if it was to have been wholly accurate should have said, should it not, that “We approved the research investigations”, as you have agreed with me this morning that you did?
A Are you referring to the biopsies?
Q I am referring to those elements of research that you had ring-fenced.
A Well, the biopsies were approved in a different application, yes, but they were approved, yes.
Q They were approved by you.
A Yes, but not as part of this application. We have seen the forms relating to those earlier.
Q Yes, but you did not have those forms at that time.
A The biopsies had been approved for many years before – I think actually sitting on my desk still in 1995.
Q Well, we have not heard that they were. The first time that we have had that document produced was yesterday.
Q At any rate, I am just relying of course on the evidence you gave this morning, when you said that the Committee in fact approved research investigations. Now, in the light of that, why did you not tell Professor Zuckerman that the Committee had approved research investigations?
A The investigations in – what is his name? – Professor Hull’s letter were more ---
Q 930, I think, is the reference.
A The letter was technically incorrect is the answer to your question.
Q Your letter was technically incorrect?
A It was technically incorrect in that the investigations of minimal risk were not included.
Q Thank you. Strictly, that letter should have included a reference, should it not, to those research matters?
A As you have already said, we are looking at 1996 not now.
Q That may be, but in order to give Professor Sir David Hull the fullest possible picture, strictly it should have been there, should it not?
A As I have said, the letter was technically incorrect.
Q Well, I will just ask you one more time because I shall be making submissions on this later, and I give you every chance; do you think it should have been there?
A The letter, I have agreed, was incorrect.
Q Thank you. Now, can I just move to a different topic, and I would ask you, please, just to look at the green document which is numbered 86c.
THE CHAIRMAN: Bundle 1.
MR COONAN: Bundle 1, sir, yes. This grant of ethical committee approval, which is numbered 162-95, was an approval which was capable of running continuously throughout the period with which we are concerned, was it not?
Q We see that it relates to the taking of two extra mucosal biopsies, and we see that in the main heading, two extra ones, during the course of colonoscopy in children, and the taking of those two extra for research would therefore permit histology to be taken, is that right?
A It did not state what they were going to be used for, so by inference they could be used for anything.
Q Well, in the light of that answer it therefore follows logically, it is a matter of common sense, that it at least extended to histology, yes?
A Well, as I say, the ethics committee is concerned with the risk to the child, therefore it has approved the biopsies. Whatever you use them for is not going to increase the risk to the patient. You can list a hundred things they can do with those and I will answer “Yes” to every single one of your questions, so if you give the list I will answer “Yes” to your questions.
Q I will give you enormous reassurance because there are only two particular matters on my list that I want to put in front of you. The first, as I said a minute ago, is histology.
A As I said, I would say yes to that.
Q The second one is immunohistochemistry.
A I will say yes to that. It does not matter what you say.
Q It is just that I am using your evidence to assist the Panel.
A There is no relevance to an ethics committee as to what you do with them, because except for genetic research which was not even here in that era, we are not worried, it is no risk to the child whatever you do with those things. So that is not really our concern. It is just the taking of them that we are concerned with, so you can do what you like with them.
Q Just to complete the picture on the biopsy front – just go back to volume 1 in the pro forma application at page 209, right at the bottom of the page, Dr Pegg, if you have got it, in terms of biopsies the difference between 162/95 and 172/96 is the fact that the people concerned with this study wanted to take an additional biopsy. Do you see that at the bottom of the page 209?
Q Can I now move on to page 366aa? This is the green document. Dr Wakefield is writing to you on 3 February 1997, so this is, just to get our bearings, about four weeks after the approval letter was sent by you. Right?
Q You will see that this is relating to the granting, as you can see Dr Wakefield saying in the first paragraph, granting of ethics committee approval for our study. Do you see that, and the setting out of his understanding that approval for the study had been granted.
Q In the second paragraph he refers to a pilot study that clearly had been running. Do you see that?
Q He sets out some of the features that the pilot study has demonstrated. Pilot studies are not unusual in a tertiary referral centre, are they?
Q They are very frequently conducted against the backdrop of a clinical protocol.
A I do not know. How else would they be conducted?
Q I am just asking you if that is the case.
A If you are going to conduct a study, you must have a protocol, therefore how else are you going to conduct the study if you do not have a protocol.
Q The protocol that is applied is very often no more than a scheme setting out the clinical investigations that would be done on the basis of clinical need.
A Then I would say it is not a study. It is just treating patients. If you had no intention of doing research, I would say that is just a plan, a care plan you could describe that as rather than a study. It is how you would treat a normal patient. You have a list of things and this is how we treat people for that condition.
Q The protocol that is often used would set out in terms of treating the patient according to clinical need, in a fairly regimented way that which the clinicians were going to do.
A Yes. But you would not call it a study. You would call it a protocol or a care plan or something like that. A study would imply some kind of research element. As you say, you are not doing research yet. When you are in hospital for any condition there are now protocols which tell you how you do it.
Q It would at this stage beg the question what the research element might be, it could be a laboratory research element, could it not?
A It could be anything. There is no research element because it is a method of treating a patient which you have laid out as a protocol.
Q Yes. If there is a research element to clinically indicated investigations in the laboratory, of course one needs ethical committee approval for the research element, does not one?
Q But you would not need ethics committee approval for matters which are clearly being done in accordance with clinical need.
A I think I have answered that before.
Q The second part of this letter concerns Dr Wakefield’s addressing the question of the need to study intestinal permeability. You see that just half-way down.
Q That on any view is a pure research element, is it not?
A It can be research, yes.
Q What he was doing, if we construe this letter reasonably, I suggest, is seeking an amendment to study 172/96 in order to add to it an intestinal permeability element. That is what he was doing.
A Yes, he was amending that study to put a research element in it, yes.
Q Can you now recall, Dr Pegg, the circumstances of your response? I say “yours”, the committee’s response to that application?
Q Do you remember there being a separate application that Dr Wakefield made in respect of this element of intestinal permeability?
A I cannot recall any.
Q And that was then granted.
A No. Unless it is in the paperwork. If it is here in the paperwork please lead me to it. I cannot say how I replied to this letter unless you can direct me to my reply in this paperwork. I am not going on a hunt the paper thing, is it there or isn’t it.
Is there a reply somewhere?
Q We have only got the documents we have been supplied with and in the documents we were supplied with, first of all this letter was not there. Mr Miller produced this. The letter to you was not there, and nor was there a response. So that is all I can help you with. I have not been supplied with any documents.
A Therefore, did Dr Wakefield have a response from me?
Q I have not got a document.
A Then it is obvious I never received this. I cannot prove I did not receive it. I cannot prove I did receive it. We do not know whether I received it or replied to it.
Q For my purposes all I wanted to suggest to you, and nothing may turn on it, I do not know, it is early days --
A I cannot really give an opinion on something I may not have had an original opinion on.
Q Do you still have all these files, Dr Pegg?
A We shred files after three years according to our standing orders.
Q So if we were to engage in a paper trail, are we going to come to a full stop?
A There is no paper. There is electronics, but no paper.
Q You say all the paperwork has been shredded. When you were approached by the solicitors acting on behalf of the General Medical Council to provide a statement, you were able to lay your hands on some material, were you not?
A Printed off CDs.
Q Let us look at that. Are there CDs in relation, for example, to this type of application?
A I do not know what is on the CDs.
Q When you say all the documents have been shredded --
A The documents are archived on the CDs prior to shredding. When the requests were made, we printed out everything relating to 172/96. Should you wish to take a CD for many hours and look to see if there is a reply, then that would be possible on application to the health authority.
Q So it is not simply a case of the fact that the cupboard is bare because all the documents have been shredded. There may be something on CD.
A Yes. As I say, there is no paper trail but there is an electronic trail.
Q Just two short points on this before we move on to another larger topic. If you look at page 940 in volume 3 – this is Professor Walker-Smith’s letter to you of 15 July 1998 and he is clearly speaking on behalf of himself and his co-workers --
“Further to our original study”,
Do you see that?
Q You pointed out yesterday and indeed this morning the fact that the heading had changed, the title.
Q It is and was at that time in 1996-98, common that titles of studies changed before publication of data. Do you agree?
A They might have done.
Q The only real time that you would expect to be notified formally of any change would be if there was a substantial change really to the body of the protocol.
Q At that time that was very much left up to the subjective decision by the people responsible for the protocol as to whether, in their opinion, there was substantial change.
A Was and still is.
Q There was no definition at that time as to what “substantial change” actually meant. Is that right?
Q One of the matters which occurred during the course of your evidence yesterday concerned the possible meeting that you had with Dr Wakefield before the approval. I think we had better turn up, in volume 1, page 235. I think the position reached yesterday on your evidence was that, firstly, there was the first meeting of the committee on 13 November.
Q On that day you made a note,
“further discussion required. Meeting with Dr Wakefield”,
and then a reference to removing Schilling and “modify consent form”. I just want to clarify this, that that was a note of an intention to meet with Dr Wakefield.
A I think so.
Q You say that you think so --
A It would seem logical from me writing “13/11/96” at a meeting held on 13/11. It is unlikely I met him on the day of the committee meeting since we meet at six o’clock at night.
Q I am just going to read to you. Do you have your witness statement in front of you, Dr Pegg?
Q Can you tell me the date of your witness statement? Is it signed?
A There is no date on it.
Q Right at the end – I am sorry, I should have taken you to it – the last page, is your signature there?
Q What is the date?
A There is no date.
Q No date?
Q When did you make the statement? Some time last year?
A I do not know as there is no date on it. It may be if the General Medical Council solicitors were there, they will be able to tell you the date.
MR COONAN: They will. I am working on the assumption it was some time last year or early this year. If I am wrong somebody will tell me.
THE LEGAL ASSESSOR: The supplementary statement has the date of November 2006, so presumably it was before then.
MR COONAN: I am working on the basis it is in fact 2006. If that is right, Dr Pegg, that it was written in 2006, the way you were putting it then, if you look at paragraph 23, and you are dealing in the second sentence with the note at page 235 in our bundle, you say there,
“there is a reference to the fact that I intended to have a meeting with Dr Wakefield on the protocol”.
Q So it looks as if that was your view, that it was a note of you intending to meet. Right?
Q If I can deal with this as shortly as I can, the position is that you cannot recall the content of any such meeting. Is that fair?
Q I think you can put the document to one side.
A I was reading what you were saying.
Q It is difficult to concentrate on both. You cannot recall, you say, the content of any meeting. It follows, does it not, from that, that you cannot recall if you actually raised the question of the Schilling test.
A There is no evidence I raised anything with him, so therefore that is right. We do not know what the thing was. There is no point asking another question as to whether I raised the modified consent form, which could be your next question. There is no evidence, because this is before it, we do not have the faintest idea what I spoke to him about.
Q Again, it is just to lay out a few pieces of evidence in connection with this. It is right, is it not, that there is no note of any meeting?
A I think I answered that in the last question, yes. It is not a court of law where you have got writers. I met with him. No, there are no notes.
Q Forgive my laboured approach.
A I think we are agreed there was no reference from me. I had written nothing, nowhere, nothing is hiding.
Q I am doing this for a purpose.
A OK. As I say, all I have written is, “remove Schilling. Modify consent”. I wrote that at the meeting.
Q On 13 November.
A It says so, 13 November 1996.
Q So you see, if there is no documentation to indicate that you actually had a meeting with Dr Wakefield, it raises the point----
A I know I had a meeting with him. I can see it at my desk in the department. So let us say we know I met with him. He can probably say he met with me. You can ask him. But we know there was a meeting. We do not know what was discussed. We might have talked about the weather or anything.
Q I see. So you might even have talked about the weather.
A We might have talked about anything, yes. We may well not have talked about Schilling tests and consent forms, even though I had written it on the form. I might have just ignored that as something that I just did at the end of the committee.
Q So a meeting of really no consequence at all.
A A meeting of no consequence probably occurred, yes.
Q Thank you very much. Dr Pegg, can I take you again, still in volume 1, please, to page 200. We have looked at it before. We can see there for a minute how this document is structured. In paragraph 1 it deals with the personnel. We have looked at that. Then on page 201 it sets out the title. Then in 3 the objective and in 4 the design and in 5 the scientific background, which then is set out in the following pages, until we come out the other end at page 208. Then we deal with the question about radioactive substances in paragraph 6, and in paragraph 7 radiological investigations, in paragraph 8 the numbers of subjects, and then on page 209, which is where we want to park for a minute, in paragraph 10 the question of controls, nil, and then in paragraph 10 “Substances to be given to subjects.” As you said yesterday, this paragraph is about things to be given to the subjects, in contrast to paragraph 11, which are questions about procedures or samples to be taken. So in one paragraph we are giving and in the other we are taking. Yes?
Q You will see in paragraph 10 the way this is structured. “Substances” – note that word. That is the introduction to the whole of this topic. “Substances to be given to subjects” and the question put in, drafted by you, special diets, drugs, isotopic traces, etc, and the answer which has been typed in is a reference to the cyanocobalamin as the Schilling test, and that is therefore a clear reference to a substance, the cyanocobalamin, is it not?
Q The next question typed by you, set out by you, drafted by you, “state dose” – “of the substance” we can insert. “Mode of administration, frequency, trial or exemption certificate number, product licence, any precautions ie storage.” All those questions, multiple questions, are directed at substances, are they not?
Q Your next question, drafted by you, which is a subheading as part of the main heading: “How are the substances for this study being provided, and how is the study being funded?” that is the question.
Q “Clinical research at the Royal Free Hospital (E.C.R.).”
Q That question, question 10, is directed at substances and the financial provision of the substances, is it not?
A I would say the part of the sentence after the comma after “provided” is referring to the whole study, not the substances.
Q Then why did you not ask the question as a separate question?
A Because it has been sloppily drafted but the question still says “How is the study being funded?” They are words, they are English and you are asking how the study is being funded. It might be in another question. You have already pointed out I have two 22s or something on this form, but I think it is quite clear there is one sentence, whether it is within something, outside it, it says, “How is the study being funded?” It does not say how the cyanocobalamin is being funded. It is saying “How is the whole study being funded?”
Q As you say, this is sloppily drafted, is it not?
A Yes, but it still says “How is the study being funded?” which is intelligible to anybody reading it.
Q We can see what it says. I am just concerned with context and drafting. If you want to ask a question about how a study, writ large, is to be funded or sponsored, it is sensible to ask a direct question, is it not?
A A direct question is asked here.
Q You may think it is being asked, Dr Pegg, but it is a sub-part of a question about substances.
A It still says, “How is the study being funded?” It does not say “How are the substances being funded?” it says, “How is the study being funded?” Yes, it has not got a little number in front of it but it does say, “How is the study being funded?” It does not say, “How is the substance being funded?” The word “study” is there.
Q All right. The Panel hear what you say. The typed in answer, “Clinical research at the Royal Free Hospital (ECR)” is an expression not only used here but is being used elsewhere. If you would like to turn in the same bundle to first of all page 95, this is an application which is dated 18 April 1996 and it has the code 77-96 at the top right-hand corner. Let us just look at it for a minute. The responsible consultants are first of all Professor Dhillon; Andrew Wakefield, and then signed by the head of department, Professor Revell, and towards the bottom of the page the signature of the collaborating department head denoting approval, Professor Pounder, and the signature there you see identical to the signature on page 200 that we looked at yesterday with Mr Miller.
A Yes, that shows that it was Pounder but I did not know that then.
Q If we move through this, we see that at the end of the documentation, on page 99, it appears to have been signed by Professor Dhillon.
Q On page 98 the same question: “How are the substances for this study being provided and how is the study being funded?” and it says “Clinical Research funds at the Royal Free Hospital & School of Medicine” so almost identical phraseology. Yes?
A Yes, and there are no substances there but he understood that it meant “How is the study being funded?” There are no substances there. So he obviously had the intelligence to understand that question.
Q That is an important distinction.
A Yes. Some people may not have understood the words “How is the study being funded?” They are difficult words, yes.
Q Thank you very much. That is helpful of you, Dr Pegg. Looking at the expression, if you like, on 77, 96, or indeed, let us go back to page 209, “Clinical research at the Royal Free Hospital.” In your experience, in relation to applications for EC approval, the use of that expression, “clinical research” or “clinical research funds Royal free Hospital” was a common expression, was it not?
Q That sort of expression was apt to include NHS money, NHS funds. Yes?
A I would say for brevity here that it would include any funds within the coffers of the Royal Free Hospital which then get paid to the research. So the Royal Free has taken in money from everywhere – Medical Research Council, gifts, everything – has looked at it, laundered it and paid it out to the research, but the Royal Free is taking in the money and paying it out for the research. The money could come from anywhere, before we go through a massive list of where money can come from.
Q Dr Pegg, I am not going to burden you with a massive list. If I can be permitted, however, just to dabble in a few elements, first of all, NHS money, money from the medical school – yes?
A That is not NHS money. That would have come from the medical school.
Q Exactly. NHS; medical school funds.
A It says Royal free funds. Normally they say when they come from the medical school. You notice Dhillon has put “Royal Free Hospital & School of Medicine.” Wakefield has carefully put “NHS” here. He is indicating these are NHS funds; they are not medical school funds.
Q What he has said is “Clinical research Royal Free Hospital”.
A And you pointed out Dr Dhillon’s study says “Clinical research funds Royal Free Hospital & School of Medicine.” They are two different places although they share the same building.
Q Absolutely, but the reference to the Royal Free Hospital of course can cover special trustees’ funds.
A Yes, it can.
Q The special trustees’ funds – I think this is really what you were referring to – can cover a multitude of funding sources, can it not?
A Yes. It is convenient for us because they have verified the funding resources. They realise they are okay. It takes the burden off us worrying where the funds are coming from.
Q Yesterday you were talking in the course of your evidence about a requirement to declare funding from the Legal Aid Board and in so far as you say there was a requirement to declare funding from the Legal Aid Board, that would have to be the product of answering that question, question 10 on page 209, must it not?
A I do not quite understand. Can you phrase that in an intelligible way? If the Legal Aid Board… I will just answer what I think you have said.
Q Can I put the question again? It is much better if I put the question again. If you are saying that there was a requirement to declare Legal Aid Board funding, the requirement to declare it would have to fit in as an answer to the question, question 10, would it not?
A Yes, if Legal Aid funding was coming directly into this study, yes.
Q If it is coming directly into it.
A If the hospital has a bucket of funds to which there might be Legal Aid funds, tin cans and the high street, no, I do not ask the hospital to tell me. I think there is a thing here, if Wakefield was getting money, cheques in his pocket, direct from Legal Aid fund to this study, that is directly in the study. If the cheques are coming in to the special trustees, no, I do not want to know where it comes from because somebody has verified the source of the funds, the special trustees or whoever. So maybe I can qualify my thing because – I am not going to qualify it, no. Direct funding to the study from the Legal Aid Board, yes, I would like to know that because I am the only person on the line who has seen that funding. If it is passed through the finance departments of the Royal Free Hospital, then somebody else has looked at the origin of the funds.
Q So if that is right, if that is the position, others have scrutinised it.
A Others have scrutinised it and said it is a proper source of funds. I do not know where the special trustees get their funds from. I cannot verify that it has not been stolen, pinched or anything. They verify it themselves.
Q Thank you very much, Dr Pegg. The other aspect of this concerns – leaving aside funding for the minute – the idea that if Dr Wakefield was involved – and I put that word in inverted commas, “involved” – potentially at least in litigation. Do you say in 1996 that you would have wanted him to declare that in this document?
A I do not think I ever said that if he was involved in litigation I would want him to declare it in the document. I am not the clinical governance leader of the hospital. I am running an ethics committee.
Q Yes, I agree.
A No, I do not ask for people’s records when they apply for the ethics committee. If he was involved in litigation, the answer is no, I would not expect him to tell me.
THE CHAIRMAN: Can you just wait for the question before you answer.
MR COONAN: I am not concerned with litigation in the sense of Dr Wakefield being on the receiving end of criminal…
A You know, I thought it was some critical…
Q Just let us put that out of the way. You were asked yesterday by Ms Smith about the proposition that if Dr Wakefield was involved in litigation concerning this study, in other words, was potentially acting on behalf of children who may be involved in this forthcoming study, the proposition was put to you as to whether you would expect Dr Wakefield to declare that fact on the ethics committee application. Do you remember that being asked of you?
A Was it not in the context of funding?
Q That is the point.
A I think it was in the context of funding. I am sure what I said was if the funds came from the Legal Aid Board, not whether he was involved with them. I go back to it in the answer yes to the fact that if he has Legal Aid Board funds coming directly to the study, he would put it down.
Q Just bear with me, Dr Pegg. It is an important matter, and forgive my laboured approach, once again. Do I understand you to be saying that, in so far as Legal Aid Board funding has been dealt with through the hospital and the medical school, one or the other, or through the finance department, if they are satisfied about that, first of all you would not expect him to put that down?
A I cannot question… As I say, you have Legal Aid Board funding, you have all sorts of funding coming to the hospital. I think my safeguards are the hospital looks at where things come from. So I would say that I do not want to know if it has been through a third party before coming to me. That is the answer, yes.
Q So the answer is “Yes”?
A Yes is the answer.
Q Now, quite apart from the funding - put the funding issue to one side, or assume that funding is being dealt with properly through the hospital finance department as you have described, assume that – if it is the case that Dr Wakefield was involved in litigation as an expert on behalf of children who may be involved in this study, would you expect him to declare that fact on this form?
A Could you just say that once more and then I will be able to give the right answer to it?
Q I will, and I am going to take it slowly. I am going to ask you, please, to assume that any aspect of funding is being dealt with satisfactorily through the finance department of the hospital, so that you are not burdened with the question of funding, all right?
Q Given that, if it be the case that Dr Wakefield had been instructed or engaged as an expert in litigation involving the manufacturers of the vaccine, MMR vaccine, would you expect him to declare that fact on this form?
A I would not expect him to declare it unless providing evidence of it was an objective of the study, in which case it would have to be inserted in section 3. If Dr Wakefield was, by the by, involved in litigation, no. If, however, he was one of the objectives of the study, and it says under “Objectives” was to provide evidence for such a case, then it would be an objective of the study, but if he was just involved in litigation completely unconnected with the study, just like if you got a parking fine, I think, no, I would not.
Q I am not concerned with parking fines.
A No, but, as I say, it depends on the objective of why he was involved with them. If the objective of the study was to provide information for the Legal Aid Board, then you would stick it under 3, because 3 tells you all the things you want to get out of this study. Here we have testing a scientific hypothesis. If one of the objectives was to obtain evidence for the Legal Aid Board, you would put it under 3 “To obtain evidence for the Legal Aid Board”.
Q Now, that is concerned with defining an objective.
A Why you do the study, yes.
Q Following that line of argument, it may of course not be the prime objective. Would you still expect that to be written down?
A Any objective. It says “Objective”. I want to know why you are doing the study. We need to know that because the parents, or whoever is part of the study, wants to know why it is being done. So if you are doing a study because you just want to push back the frontiers of medicine, put it down. If you want to do the study to provide information to the Legal Aid Board, you put it down, and then we would ensure that that was translated to the information sheet. You must put down why you are doing it, and you put them all down. On lots of forms the objective runs to a page. You have got the primary objectives of a study. Where you are doing a drug trial, the primary objective is to see if the drug works. The secondary objective is to see how it is excreted. So you have primary and secondary objectives. I want to know why you are doing the study.
Q Now, that of course is, if I may say so, a statement of the ideal world, is it not?
A Well, I am not a policeman, I ask the question. It says “Objective”, it is another English word; it says “Why are you doing this study?” It only says “eg hypothesis”. That is not exclusive. It says “Why are you doing it?”, and I expect you to stick down why you are doing it.
Q Dr Pegg, if the question of another objective is examined, it could be described potentially, could it not, as a conflict of interests?
A Whose conflict of interests, sorry? I am not with you on that at all.
Q Well, it might be described, might it not, as a conflict of interest on the part of Dr Wakefield?
A If he was involved in litigation?
Q It might be.
A It might be, yes.
Q You see, if an ethics committee is concerned about conflicts of interest, it is the business of an ethics committee, is it not, to ask a direct questions about conflicts of interest, is it not?
Q There is no question in this pro forma about conflict of interest, is there?
A Again, 1966 (sic), 2007, we all declare conflicts of interest, probably half the people here have declared conflicts of interest to be here, and I think we are in a different era, so we were not thinking about conflicts of interest in that time that it would be a question on a form. When I wrote it, I wrote it for guidance. Conflict of interest was not something you asked in that---
THE CHAIRMAN: You actually mean 1996 not 1966.
A 1996. Like I say, it was not a question that was normally asked, and the answer therefore to your question is “No”.
MR COONAN: Absolutely. So in 1996 the whole question of a conflict of interest is not on the radar, is it?
A No, not necessarily, no. Conflict of interest depends. If you take an example of a drug company, the people in a trial would want to know who put the money up basically. The drug company put the money up, the drug company has a vested interest in the trial, therefore they read the form with the scepticism that a drug company is involved, yes.
Q That is about funding.
Q That is to one side. That is funding. I am now concerned with somebody who is potentially acting as an expert in litigation. I think your answer is, correct me if I am wrong, that “In 1996 we would not be concerned to address the question of potential conflicts of interest in a form like this”; is that right?
A I would say in drafting this form we have not – forms are always one step behind, you might say, what has happened. When we drafted this form we were not thinking about conflicts like that. It has to happen once for a form to have it. So, you know, you have one thing that happens, a form will change. It is what you were thinking about in 1996. It was not on our radar as thinking that somebody could do a thing like that. We are a bit innocent, you might say, and we always respond to things rather than having a suspicious mind. We expect a certain probity and we cannot write a form to cover everything.
Q I think the short answer, Dr Pegg---
A No, we did not think of it.
Q That was an idea, the idea that one did not think about these things in 1996, which was prevalent amongst the profession, was it not?
A I think in 1996 you expected a standard that nowadays we have to legislate for, you might say. We expected a standard from doctors. The forms were not written in what I call a defensive medical manner. It is a relatively amateurish form. Nowadays it has got 56 pages, it is written by a computer and everything has been thought of. This is an ethics committee in 1996 trying to do a job; we cannot think of all these things. So you have got your answer.
Q Dr Pegg, the purpose of my questions is not to criticise the Ethics Committee, so I do not want you to be defensive about it.
A As I say, it is to realise that in that era it is a different job. It is difficult to put ourselves back twelve years. We did not think about it, yes, I have answered the question.
Q Well, the fact is, let us try once more, that at the time this document could fairly be seen to represent the expectations of the profession in dealing with potential conflicts of interest in ethics committee applications: answer “Yes” or “No”.
A The document was at its time a standard document, yes.
Q That is not the question I asked. The question I asked was is it a fair representation of the expectations of the profession in 1996? Answer “Yes” or “No”.
A I think it is an expectation, yes, of the profession at the time. We had not thought of these other things.
Q Thank you very much. So against that background and in the light of your answers can we look now for completeness at volume 4, at page 124. This is the Royal College of Physicians document, and, as you have said, not a document that is, as it were, at the top of the hierarchy of approach that you adopted.
Q Let us look at it in any event in the light of your answers. If we look at paragraph 17.4:
“personal payments, both amount and nature ….. to investigators and their pecuniary relationship with any sponsoring company have ethic implications [and] should be reported to [ECs] ….. The same applies to payments to departments and to institutions” and so forth.
Then in 17.5, “Declaration of interest”:
“Personal involvement in a company is also an interest that should be declared.”
That is what the College was saying. The plain fact is that the EC pro forma applying in 96, I suggest, charted its own course irrespective of these suggestions, would you agree?
A It followed the national guidance.
Q Yes. At page 141, this is the Department of Health document, paragraph 3.15, again we have looked at it before and I do not think I need go through this again, and also 3.16, but the point I just want to establish with you, Dr Pegg, is that your ethics committee form was the mechanism by which all these guidelines and recommendations are channelled through to members of the profession, are they not?
A To members of the Committee.
Q And also to members of the profession.
Q Can I take you, please, to 1083 in volume 3. This is an application to your Committee made in May 1999.
A Sorry, which page are we at?
Q 1083. The application was given a code number, and we can see that on the next page at 1084, it was application 122-99, and if we pick this up at 1086, and if we just have a clip together, 1086-1095 represents, does it not, the pro forma utilised in May 1999 for this application?
Q So 1086-1095. We can see, can we not, even on a cursory basis, that there have been significant changes in the layout and content of this form compared with 172-96?
A I continually revised it.
Q Yes, indeed. Again, obviously the Panel will be able to see this for themselves, but with your assistance may I just detain you for a minute: paragraph 1, 2 and 3, self-evident, no significant change there perhaps; a direct question at number 4, do you see that, and it is an important direct question, “Who is sponsoring the study?”, on page 1086, do you see that?
Q So it is a stand alone stark question, is it not?
Q Then we move on to 1089, details about the size of the study, questions about human subjects and patient records. Then on page 1090, again, if I may say so, Dr Pegg, a clear series of main headings with carefully delineated sub-questions, do you see?
A I think this is the first major edition I did after becoming chairman. I did a major change of the form, but I did not do it immediately I became chairman.
Q Then there are questions about how the control subject should be selected, recruited; specific questions about inclusion and exclusion criteria; questions about payment to research subjects. Then on page 1091 a series of specific clear questions, do you agree?
Q Paragraph 17, an important question:
“Will any of the subjects be from one of the following vulnerable groups?
Children under 18”
Do you see that?
A Yes. Well, I wrote it so I know it. I wrote this as the first major improvement when I became chairman.
Q Dr Pegg, all I may say is I applaud it. I am not criticising it.
A I think it demonstrates how ethics committees were changing at that time.
Q Absolutely. Then turn to 1092, paragraph 18, a question about the substances. You can see there that it is a stand-alone question. There is no subsidiary question there about finance, is there?
Q It is a stand-alone question. Paragraph 19, important questions clearly set out about the possible involvement of a pharmaceutical company, and then in paragraph 21 a very important question, if I may say so,
“Please list those procedures in the study to which subjects will be exposed indicating those which will be part of normal care and those that will be additional (e.g. taking more samples than would otherwise be necessary). Please also indicate where treatment is withheld as a result of taking part in the project”.
Leaving the last sentence out for the minute, the major sentence deals with our friend duality, does it not?
Q Then on page 1093,
“Are there any particular ethical problems or considerations that you consider to be important or difficult with the proposed study”.
This is a new question, is it not?
Q It has the effect at least of putting a burden upon the applicant to declare what he or she may think to be particular ethical issues which occur to them. Yes?
Q Then on page 1094, questions about the sponsorship of this research proposal and crucially questions about sponsoring by the Medical School or a pharmaceutical company. So that I think is all I need take you to. I think we can agree, Dr Pegg, and there is no criticism involved in this – it is not a loaded question – it is a vast improvement on 172/96, is it not?
A As I wrote this and inherited the other I could say nothing other than yes. I think it charts the history of ethics committees in that part of the nineties.
Q The fact is that the whole of the ethical environment has changed substantially in about the last 11 or 12 years, has it not?
A I think this was the beginning of the change. When this form was written, whatever date this one has, it all started then and changed dramatically.
Q May 1999.
A Yes. The government were just beginning to show an interest in us.
Q The environment and the pace of appreciation, since about 1999, has really gathered pace, has it not?
A Computers started to write letters for me rather than me having to do it at my desk and getting it wrong.
Q Do you have a pro forma which is any different to the one we have just been looking at now?
Q Radically different?
A The current one runs to about 60 pages. It is held on a large computer database and you can get it at NRES dot something
Q The one we have just been looking at, 122/99, runs to about 11 pages.
A Yes. It is enormous, the current one. It has thought of every devious possibility. Everything they can do has been thought of and put on it now.
Q It is a very comprehensive document.
Q Again, without wishing to labour the point, your document, the current one, is a reflection of the duties, burdens and expectations that are to be placed on the profession as in 2007.
A I think it is a reflection on Acts of Parliament. At this time we had no Acts of Parliament relating to us. Now we have got European directives and Acts of Parliament. People have shown interest in us.
Q There is just one question I would like to ask you about. In volume 4, if you turn again to the fly sheet, it is at page 1098, we are back to the college publication of August 1996, and if you go to 258 you will see that after a series of observations in the text, which I am not going to take you to – they are there to be read – under the heading of “Good Clinical practice”, you will see at 11.13 the heading,
“Suggested checklist for information to be provided to RECs”.
Items 1 to 5 are self-evident and non-contentious, and then in paragraph 6,
“State the sponsorship for the study and the financial arrangements between sponsor and investigator for the research contract or agreement”.
Then if you turn to page 259 you will see a series of paragraphs. Again, for my purposes I am not going to ask you to deal with them, they are there to be read, but at paragraph 21 in this checklist is the comment,
“State any ‘interest’ i.e. of profit, personal or departmental financial or otherwise relating to the study”.
That was in the latter part of 1996, as I say. Presumably, I do not know, you tell us, did you rely on this document, at least to some degree, in drafting your pro forma for 122/99 that we looked at in volume 3?
A I would have taken advice from many places, from other ethics committees, looking at their forms, stealing things off their forms. It may or may not have informed me because I think, if you looked at all the guidelines at that time, they were all changing, so guidelines coming out in August 1996 would not really have been translated in a form for about a year by the time you have written it, passed it and played around with it.
Q We are looking at a pro forma in operation in 1999. Would you have expected all that to be translated into that?
A I think you will probably find most of that in it, or most of what we agreed with. You must realise that you are looking at lots of people’s opinion of what should be on a form. We have not yet got to the national form which comes in the early part of this century, this millennium.
Q I do not want to be disrespectful here and I do not want to use, as it were, journalistic language, but is the approach a bit of pick and mix to suit your purposes?
A I do not think going on to the form, my first thing, if looking at it and trying to get a consensus of good practice can be described as “pick and mix”, then it is. But what we try to do – just because they have a guideline and somebody else has another one, at that time the national form was still some time in the distance so we had to create our own interim ones before national authorities became interested.
Q It is a limited exercise this and will not take more than a minute, but if you could just keep open 258 and 259 and have with you again the study 122/99.
A What page is that?
Q It is in volume 3. It starts at page 1084, just to get your bearings. That is the fly sheet, and then we turn in – we have looked at this already – and we see page 1086 at the bottom. Do you have that?
Q Then if you have open page 258 in volume 4, you can see item number 6 and then you see question 4 on 1086.
Q There appears to be a pretty good marrying up of the advice on page 258 with the question you pose on page 1086. Correct?
Q If you turn the page to page 259 and look at paragraph 21, and look at the specificity of those pieces of advice in paragraph 21, could you tell me whereabouts that is translated in 122/99?
A It probably is not.
Q It probably is not?
A If you look at the number of things in these guidelines and imagine yourself translating them into questions on ethics forms, the ethics form would be 100 pages long if you took everything from everybody’s guidelines and stuck it in your ethics form. Until there was national consensus, which comes in about 2002, I do not even think the current form is as specific as this. I am guessing, but I do not think the national form is even as specific as this now, because there is an actual limit to the amount of questions you can actually put in these forms without killing off research completely. So the answer to your question is no, I have not stuck it in.
I think you have to rely on a certain probity of the applicant. We cannot make forms for all scenarios.
Q Dr Pegg, this is not a criticism.
A As I say, an ethics committee has to facilitate research and by writing massive forms we are not doing the first part of our means, to facilitate research. There was a view at one time that we should have massive forms to stop up research, but we have moved away from that way. We could write defensive forms 100 pages long and nobody would ever do research.
Q I was lighting upon, if you like, in paragraph 21, the statement, “State any interest, i.e”, and it goes on with various specific provisions.
Q When one looks at 122/99, question 24 on page 1093 is, I suggest, the nearest one gets to an attempt to encapsulate the principles in paragraph 21. Do you see?
A It is an open question to try and mop up all these other things.
MR COONAN: Dr Pegg, thank you very much indeed. I am sorry to have detained you for so long.
THE CHAIRMAN: It is now getting close to five minutes to one, which will be lunch times. Dr Pegg, my usual reminder, and I am sure you remember it by heart by now, that you are in the middle of giving evidence, still under oath so please do not discuss this case with anyone.
To help you, to tell you about the procedure, Mr Hopkins on behalf of Professor Murch will be entitled to ask you any questions when we resume the hearing. Following that, Ms Smith on behalf of the General Medical Council will re-examine you, and after that, if there are any questions from the Panel members, I will introduce them to you. That will be the process that we are going to follow.
There is something that I now have to announce. There have been certain requests coming and that is why I have to make this announcement, and I hope it will be helpful to clarify our position in relation to the release and publication of transcripts of the hearings.
The General Medical Council does not publish transcripts of these hearings. However, we will provide a copy of the transcript to any enquirer on request when the hearing has concluded. Any further dissemination of these transcripts or subsequent publication is at present a matter for the recipient. We do not release transcripts to any third parties while a hearing is ongoing except in exceptional circumstances. We do however provide transcripts for the parties to the proceedings on a daily basis in certain circumstances. The purpose of releasing the transcripts in this way is to enable the parties to review the evidence and to present the remainder of their case. We do not expect these transcripts to be disseminated further or to be published at this point and we would not grant permission for any publication of this material.
Our priority must be the integrity of the ongoing proceedings and to ensure that the evidence of any further witnesses could not be seen to be tainted in any way.
I hope you all find that helpful.
MS SMITH: Sir, perhaps I can raise one matter. I am concerned about a witness that we have waiting. She is a general practitioner. She has come down from Newcastle and of course we are not sitting tomorrow. I think we all have a responsibility to give a reasonably clear estimate of how long we are likely to be this afternoon, because if there is no prospect of reaching her, then obviously someone needs to know to be able to tell her now.
I wonder if we could have some sort of estimate from Mr Hopkins, if he would be so kind. I can give one as far as re-examination is concerned. I do not know whether the Panel have formulated in their own minds whether they are going to have a great many questions or a few. As I say, it would be very helpful if we could tell her. If we are not going to reach her, we really should tell her that that is the position, or indeed if we are going to reach her but not by any means finish her then obviously she needs to know because she needs to come back on Monday.
THE CHAIRMAN: I can only speak on my own behalf at this stage, and I certainly have a few questions, but it is always possible that those questions may actually already be answered by the time my turn comes, and I always take my turn right at the end of Panel’s questions. I have not yet spoken to my Panel members but I suspect that there will be a certain number of questions for Dr Pegg from Panel members.
MR HOPKINS: I am happy to give an indication. I am sure Dr Pegg will be relieved to know that I do not need to cover the same sort of ground that has been covered. At the outside, half an hour, and maybe less depending on the answers I receive.
MS SMITH: I think I am probably likely to be – it is a little difficult to estimate until I have heard Mr Hopkins – about half an hour, perhaps 20 minutes in re-examination. So if the Panel, as a very rough estimate, were to take half an hour, we are probably talking half past three. I do not know what your view would be as to whether you wanted to start the doctor then. I do not think we would finish her, but you could start her.
THE CHAIRMAN: I am just wondering, even on those estimates, even if we all stick to it very strictly – as I said, I have not yet spoken to my fellow members about the number of questions they wish to ask – I think you are absolutely right -- we are going to be at least midway through the afternoon, if not longer. I suspect it may be appropriate under the circumstances, and of course it is entirely a matter for you how you wish to handle it, to start with this new witness on Monday morning. Apart from the fact that the time will be taken by further questions, there is a fair bit of information that the Panel has got to assimilate and synthesise in their own mind. Starting on a totally new area virtually at the tail end of the day might not be the appropriate way to go ahead. As I say, I will leave it entirely in your hands.
MS SMITH: Thank you, sir. Obviously someone has to speak to that witness and see what her difficulties are. Thank you for that indication. We will let you know after lunch.
THE CHAIRMAN: That is a helpful discussion. It is now one o’clock. We will now adjourn and resume at two o’clock. Dr Pegg, I have already given you the warning, so please observe it as strictly as you can.
CROSS-EXAMINED BY MR HOPKINS
MR HOPKINS: Good afternoon, Dr Pegg. As you know, I ask questions on behalf of Professor Murch, as he now is. Can I just go back to deal with Professor Murch’s association with your committee, just to set the scene for that first of all. Is it right that prior to Professor Murch, or Dr Murch, as he then was, joining that committee, a Dr Berelowitz had been a member of the committee?
A I do not know.
Q Do you know of Dr Berelowitz?
A I am acquainted with Dr Berelowitz.
Q Do you recall him ever being a member of your committee?
Q Professor Murch became a member of your committee in the late summer of 1996. Is that right?
A That, again, I do not know.
Q Can I just see if I can jog your memory a little bit? He had transferred from Bart’s to the Royal Free in September of 1995. Does that fit with your recollection?
A I have no recollection.
Q I suggest that he started actively becoming a member of your committee in or about August or September of 1996, about a year after being at the Royal Free.
A If you say so.
THE CHAIRMAN: Sorry. There is a difficulty with that kind of an answer.
A I am not agreeing, I am not disagreeing. I have no knowledge.
Q You have to actually then say those words rather than saying, “If you say so.”
A I have no knowledge.
Q I think that actually creates difficulty for all of us.
A I have no knowledge.
MR HOPKINS: But you do recall there was a time when he became a member of your committee?
A I recall he was a member of the committee when I became chair, I think, but even that I am not sure of.
Q When do you remember becoming chair of the committee?
A That is a question I need notice of.
Q Are you able to help us at all?
A Not really, no. Nobody has asked me that in all the time I have been preparing my information.
Q You told us that members of the committee, when they joined the Ethics Committee, would not undergo any formal training. Is that right?
A Not at that time.
Q So back in 1996 they would learn the job on the hoof, as it were?
Q If any members of the committee, any of the medical members, were involved in any way with an application for ethical approval, that created, obviously, a potential conflict of interest. Is that right?
Q Therefore, the procedure was that those individuals would not participate in the committee’s deliberations on that application.
A That was the convention at that time.
Q Yes, and not only would they not deliberate with the committee, but they would not actually be sent the committee papers, would they?
A They would not be sent it and they would not be in the room.
Q Can we just see in respect of project 17296 about the circulation of the papers. If we look at page 240 of bundle 1, this is a form dealing with the circulation of the 17296 project to committee members receiving the documentation. Is that right?
Q In the middle of the page we see the distribution list.
Q You have already told us about the individuals on there. It is clear, reading that list, that Professor Murch was not included in the distribution of this pro forma.
Q We can see – same point – if we turn to page 241, again, a similar copy, this time sent to Mr Stevens, and again, it is clear that Professor Murch’s name does not appear on the distribution list, and I think the same at page 244.
Q What that means is that prior to the 13 November 1996 meeting that you had, for proper reasons, Professor Murch would not have been circulated with these committee papers.
A That is right.
Q At that meeting on 13 November 1996, he would not have been expected to take part or be present during the discussion. Is that right?
A I think the minutes reflect that.
Q Indeed they do. If we just turn on to page 294, we see, do we not, at paragraph 5 the reference to the 17296 project and, as you rightly point out, the minutes say that he left the room whilst the submission was discussed.
Q That, again, was perfectly proper and what was expected.
A That was expected at that time, yes.
Q If we then turn on to the minutes for the 18 December 1996 meeting which approved the project at page 343, these are the minutes for that meeting. Is that right?
Q At the top of the page it lists those present and we see under the Apologies section that Dr Murch was not attending that meeting at all.
A That is right.
Q As you have told this Panel, you did not correspond with Dr Murch about this project at all.
Q Can we then turn to the pro forma itself at page 200? Dr Pegg, I am going to ask for your indulgence; I am going to cover a bit of the ground that has been covered with you but you will appreciate why in due course. We see, do we not, on this page that it was signed off by three heads of department? First of all, under section 1, about halfway down the page, the squiggle that has now been identified as Professor Pounder.
Q If we go lower down the page, we then see for the collaborating departments it has been signed off by Dr Harvey for the Department of Neurology.
Q And Dr Berelowitz for the Department of Child Health (Child Psychiatry).
Q Was the purpose in these individuals signing off to represent that they knew of and were supporting the contents in this pro forma?
A The heads of department sign to signify that they know the activity is going on in their department.
Q Would you expect the signatories that we see on this page to have checked the contents of the document they are signing to represent whether or not it was true to their knowledge or belief?
A In practical terms, we discovered that most signatories never read it.
Q So you would not have taken such signatures to represent any declaration as to their belief as to the contents of this pro forma?
A No, we took it to signify that they knew that the research was going on in their department.
Q Very well. The only other signature that we see on here is that of Dr Wakefield, which is towards the back of this document, page 233. Is that right?
Q He is signing off there next to the description “signature of investigator”.
Q If we go back to page 200, clearly, we see reference to Professor Walker Smith and reference to Dr Murch under “Responsible Consultants”.
Q There is no space on this document for them to be signing it off, is there?
Q Does it follow from that that there is no representation from either of them on the face of this document that they had checked through it and that it was accurate to the best of their knowledge and belief?
A As far as the way this document is constituted, they may not even have known it existed.
Q Indeed so.
A You could put anybody’s name there.
Q So the fact that they are named on here as responsible consultants you would not be taking to mean that they had checked through the details of what is in this pro forma?
A I would expect the responsible consultants would have checked it through. I would not have expected that somebody would put an application in without showing it to the other people. He wrote their names down. Again, we are in a different era.
Q Let us deal with 1996.
A I would expect the names of the responsible consultants to have checked the documentation. Their name is there; they are responsible for it.
Q I wanted to explore that with you for a moment. First of all, I think you have agreed with me there is no section on this document for them to sign.
A That is right.
Q There is no section for them to sign that they have read it.
Q There is no section for them to sign to represent that they agree with its contents.
Q There are, as you have pointed out, sections on here for heads of department to sign.
Q But even when they sign it, you would not be taking them to have read it all the way through.
Q Is the reality not this: it rather depends what went on in the background by way of discussion between the named individuals as to what they did or did not know of the contents of this pro forma.
A A researcher could put down any name he liked there. We just had to take his word for it that he discussed it with them.
Q Can I then move on to the meaning of “responsible consultant” with you. I think you would accept that that term, “responsible consultant”, is not defined anywhere in this pro forma document.
Q I think it follows from what you have told the Panel today and yesterday that no guidance was sent out with this pro forma document either to the lead researcher or to the responsible consultants about their role or function; none by you.
A No. We had guidance at that time.
Q You had guidance; there were national guidelines. I am simply seeking to establish whether you sent out with such a pro forma any guidance.
A The Ethics Committee had a guidance form to go with it, yes.
Q Have we got a copy?
A It would not even exist nowadays. It does not exist but we have always had a little bit of guidance to go with it.
Q Just so I understand what you are saying, there was a document that your committee had established that went with this pro forma document. Is that right?
A Yes. It was only a very short few pages of A4 that helped the completion of the document.
Q I think, Dr Pegg, you will appreciate that we have not been shown any such copy of----
A I would not think I could even find one to show you.
Q Is this another of the documents that would have been archived in some way?
A No. These documents would have just been trashed. When they were superseded, they would have been thrown away. We have moved office many times since this time.
Q The guidance that was two or three pages, you say, covered what sort of thing?
A It just gave simple instructions how to fill in the sections, but do not ask me any questions about it. All I know is I had a couple of pages ofA4.
Q I am going to press you a little bit because we can see on the face of the pro forma the questions that are being asked, and you have been taken through it quite a few times. You can see that after questions there may be in brackets “for example” and a list of the things you might be looking for. What other information would have gone with the pro forma to assist the person filling it out?
A They would have just had two or three sides of A4 to help them fill in the various questions.
Q What sort of information would have assisted them that was not on the face of the form already?
A All I can tell you now is I had such a form. I have not the faintest idea what is on it.
Q The form would have gone with the pro forma to the person filling out the form.
A It would have gone with the blanks, yes, the empty ones. We then provided a floppy disk so that they could fill this one in.
Q Can I then explore with you what the concept of “responsible consultant” did or did not mean? First of all, it would be taken to mean that that individual would be participating in the project in some way.
A I think you would say that, yes.
Q Just looking at it from Dr Murch’s point of view, as a member of your Ethics Committee, it would have been right, would it not, for him to flag up on this document or to ask for it to be flagged up on this document that he would be participating in some way in the proposed study?
A Well, he has put his name on the front.
Q Indeed, I am looking at one of the reasons why that would be appropriate, and what I am suggesting to you is because of the potential conflict of interest for him as a member of your Committee, it would be right for him to have been identified on this pro forma as associated with the study?
Q The extent of a responsible consultant’s participation in the study rather depends on the rest of the information that is given in the pro forma document.
Q I think it follows from what you have told me the nature and extent of the duties of a responsible consultant are not identified or defined in the pro forma document.
Q Can we just look at what the concept did not mean. Do you agree that a responsible consultant would not be regarded as responsible for matters outside his or her control, such as the actions of other independent professional people named in the project?
Q In other words, a responsible consultant was not acting as a guarantee or guarantor as to the conduct of others.
A That is right.
Q You would not expect a responsible consultant to be present at each and every assessment of a patient entered into this project.
Q You would not expect a responsible consultant to participate in or be present at each and every investigation listed in this project?
A You would probably find no consultant at most of them.
Q Indeed, projects such as this function on the basis of team working, is that right?
Q Now, this project 172-96 envisaged a role for four departments, as we have seen – paediatric, gastroenterology department, where Professor Walker-Smith and Professor Murch worked, the academic department where Dr Wakefield worked, the Department of Neurology where Dr Harvey worked, and the Department of Child Health where Dr Berelowitz worked.
Q As such, you would have expected, would you not, a division of responsibility according to expertise?
Q Let us just deal with the Department of Child Health, and I think it was Mr Coonan covered some of this ground this morning, so I will take it fairly shortly, if I may. If we go to page 202 we see there is a section, second paragraph down, “Disintegrative disorder (Heller’s disease)”, and then goes on to describe it. We can see from that that clearly there are psychiatric issues associated with disintegrative disorder, would that be fair?
Q Would you have expected on reading this document that the advice on the definition of disintegrative disorder and autism and secondary autism and behavioural definitions that we see referred to here, that that advice would have fallen within the expertise of the Department of Child Health?
A You could have done, yes. Department of Child Health could have expertise in mental things.
Q Indeed, if we turn on to page 221, towards the bottom of that page at paragraph number 2, four lines up from the bottom, we see a reference to neuropsychiatric studies and then Dr Berelowitz’s name alongside that.
Q It then goes on to describe “Confirmation and characterisation of disintegrative disorder features of”, and then under that “Child and Adolescent psychiatric assessment”, and under that “Autism diagnostic interview”.
Q Would it be fair to say that, on reading this document, issues relating to the confirmation and characterisation of disintegrative disorder would have been seen as falling within the remit of Dr Berelowitz’s department?
Q We turn to look at the Department of Neurology, turning to page 222, top of the page, paragraph 3, and we see there, do we not, a reference to neurological and neuroradiological studies and Dr Harvey’s name associated with that?
Q Then we see a whole list of things under that section:
“Full clinical examination: ….. (MRI), Lumbar puncture and CSF antibody profile (measles:rubella), cytokine measurement ….. (EEG) with visual, somatosensory and brain stem auditory evoked potentials.”
Q Again, would it be reasonable to infer that all these matters were falling within the expertise of the Department of Neurology?
A I doubt whether a neurologist would perform a lumbar puncture on a child. I would say a lumbar puncture on a child would fall within the expertise of a paediatrician, not of a neurologist. I would not let Harvey near a child with a needle.
Q That may well be the actual performance of the procedure---
A Yes. The Department of Paediatrics would have to be – “Full clinical examination”, I think there would be a lot of paediatric input into this. Dr Harvey could not have done this on his own.
Q I am not suggesting there was not paediatric input, and, as we have seen in this document, it is clear there are a whole list of clinical examinations and investigations that the paediatricians were doing as well.
A I think a paediatrician, for example, would do a much better job of a neurological examination on a child than Dr Harvey would.
Q That may or may not be so. It is not the point I---
A To put a child in a magnetic resonant imager would be more a paediatrician doing it than Dr Harvey, so I think the answer is no.
Q Well, Dr Pegg, just listen to the question I want to put to you first. Is the situation not this, that this document is representing that the advice on investigations to be undertaken from a neurological point of view is falling within the expertise of the Department of Neurology?
A The advice, yes.
Q Would you therefore accept that this passage at the top of page 222 is indicating that the investigations we see listed there are being advised upon by the Department of Neurology?
A If you use the words “advised upon” and not “practically carried out”, I would agree with you.
Q Yes. I am not on about the practicalities of its performance, but the advice to do it.
Q So can I then come back to this issue of the limits on a responsible consultant’s responsibility. I think you have agreed with me that a responsible consultant is not a guarantor for matters outside his or her personal control?
Q Is not responsible for medical issues outside his or her expertise?
Q Would not be responsible for the advice of a collaborating department, such as the neurology department?
A If you emphasise the word “advice”.
Q Yes. Would not be responsible for the advice therefore of a neurologist as to what investigation should be performed?
A Can you say that last one again?
Q Would not be responsible for the advice from the neurology department as to what investigation should be performed?
Q Similarly, would not be responsible for the advice of the child psychiatry
department as to the assessment from a psychiatric point of view?
MR HOPKINS: Sir, may I have just one moment, please. (After a pause) Dr Pegg, you will be pleased to know that that was the last question.
THE CHAIRMAN: Dr Pegg, as I explained to you earlier, it will be now up to Ms Smith on behalf of the GMC to re-examine you, so I am now going to hand you over to Ms Smith.
Re-examined by MS SMITH
Q Dr Pegg, I know you must be getting tired and think there can be no more questions in the world to be asked, but I do have a few for you, I am afraid, and they are going to be rather all over the place, for which I apologise, but I am going to ask you questions which have arisen out of questions which have been asked of you by the three defence counsel in the order they have asked. I do not expect you to remember them for a moment right from the beginning, but I will identify the area that I want you to look at, and, as I say, I am sorry if it is a bit all over the place. First of all, just a short matter. You were asked about the permission for standard research biopsies that was given to Professor Walker-Smith, do you recall, when he arrives at the Royal Free?
Q I do not think I need to take you to the document because I am sure you remember it, but what I wanted to ask you was this: approval was given for Professor Walker-Smith to take research biopsies on what was described in the letter as chairman’s action.
A That is right.
Q Can you just tell us what that means?
A Some things did not need to go to the full Committee. I can see this one has already been passed by another ethics committee, and you are just transferring to the Royal Free, so there is no need to involve the full Royal Free Ethics Committee.
Q When you say it does not need to go to the full Committee, does the chairman in fact take decisions in regard to relatively standard uncontroversial matters off his own bat, so to speak?
A He did then.
Q Yes. You were also asked by Mr Miller in fact about how you know who did what in effect in the ethics application, and then Mr Coonan this morning took you to page 213 of the ethics application to assist you in regard to that. Can you just go to 213, please.
Q Would that have been some indication to the Ethics Committee as to how responsibilities were being allocated?
Q Could you also go on to page 231. That is the timetable document and we can see on it that the investigations are set out day by day and that there are asterisks by those that Dr Wakefield was going to arrange, which are indicated as being the white cells isolated for DNA extraction, MRI, lumbar puncture in Malcolm Ward, EEG and evoked responses, and Dr Berelowitz in the Department of Psychiatry and Dr Harvey in the Department of Neurology, so in broad terms the neurologically based aspects. Then we see a cross by “Paediatric Gastroenterology”. Are you with me?
Q So did that give the Committee some assistance as to how the responsibilities were going to pan out in respect of this study?
A Well, it names Harvey and Berelowitz, yes.
Q It also indicates to you who was going to be arranging what of the---
A If you say “arranging” not “doing”.
Q Of course, absolutely. As far as you were concerned when you were looking at this study were you looking at it in terms of independent spheres or were you looking at it as an overall study with different people taking different parts?
A I think we looked at the totality of it rather than the individual sections.
Q Mr Miller also asked you about disintegrative disorder, and you say you recall mugging it up, I think was the expression you used, at the time. If we just look back to page 215, we can see there is quite a detailed explanation set out there. Would your mugging up have involved reading the explanations that you were given in the application form?
A It would have been reading everything about it so that at least one member of the Committee understood the condition.
Q Absolutely. Now, going on to another matter, page 291, you will remember this letter. This is the letter that Professor Walker-Smith sent to you in relation to the nature of the test that was being performed. It starts off, as we see, “Many thanks for your letter”, so it was apparent that it was responding to something, was it not?
Q We now have the letter, of course, that it was responding to, and if you could just keep your finger in that one and go back to 265a, which is on the green sheets, I just want to ask you one or two questions about that letter, because of course it was produced yesterday and it is the first time you have seen it for a very long time. Now you have seen it again, does it in any way change your interpretation of the letter that Professor Walker-Smith sent to you, the one I first referred you to on page 291?
A How do you mean “change the interpretation”?
Q Well, does it make you view the letter from Professor Walker-Smith in any different light?
A Oh, I see what you mean. No, not really.
Q He seems certainly to have been replying to your paragraph numbers, and if we look at paragraph 2 on page 265a you identify what was concerning you, and you particularly highlight what you describe as “unpleasant investigations”, and they are the lumbar puncture, the endoscopy, the MRI, and you said “etc. some of which may require general anaesthetic”.
Q So if we look at page 291 and we see paragraph 2, Professor Walker-Smith’s answer, did you understand him to be answering your concerns in respect of all the tests that you had identified?
A All the tests that I had written on the piece of paper, yes, but then I put “etc” so---
Q “Etc”, I accept, can cover an awful lot or not very much, but at any rate, the tests that you have actually identified. In other words, not just the gastroenterological tests, but the tests you have identified as being the ones you were worried about as being unpleasant.
Q We know from 265a that when you wrote to Professor Walker-Smith you actually photocopied and sent with that letter guidelines.
Q It would appear someone has written at the top, BPA, that is the British Paediatric Association, is that correct?
A That is correct.
Q August 1992. Was it usual for you to go to the lengths when writing to an investigator of photocopying and enclosing guidelines?
A I often stick things in with my letters, yes.
Q You asked in your letter, back in 265a, at 2(b), whether the benefit to the child would be more than “slight or uncertain”.
A That is right.
Q If we look over at the guidelines, in the middle of the page, Mr Miller read out to you where it starts, “high risk”. Do you see where I am?
Q And he read out down to, “intended to benefit the child concerned”. If we go on,
“It would be unethical to submit child subjects to more than minimal risk when the procedure offers no benefit to them or only a slight or very uncertain one”.
Was that what you were referring to in your letter?
A Yes, that is where I got this from.
Q At that stage, was that one of the matters that was worrying you, in conjunction as you say with what you describe as unpleasant investigations?
A I think at that stage we had two things to consider. If he had said that the investigations were not clinically indicated and were part of research, we would have had to move on to what I call stage two. If they were investigations of more than minimal risk, we would have to move into the high risk, which of course you are allowed to carry out if there is benefit to the patient. So it was moving on. It was a second question, so if the first question had been answered that all the tests were research, then I would have to move on, as I say, to stage two, to see if such research could be justified. If you could justify that there was significant benefit to the subject, then you can actually carry out high risk research.
Q But applying that to children, doctor, is there not a third stage in relation to defining the degree of risk?
A I think if he had responded to this letter that the investigations were not part of general care, then there probably would have been much further discussion and communication.
Q You identify in one of your other letters that you should not generally carry out research which is more than minimal risk unless there is a significant benefit analysis. Is that correct?
A Yes. I mean, if this research had been all pure research and there was a significant benefit to the children, then it may have been possible to carry it out as research.
Q Would you then have had to discuss it and consider it further?
A I think one would have gone on to further discussion.
Q One very short point in relation to the Schilling test which you were asked about, if I can just remind you, on page 358 you were asked about this because one of the conditions of ultimate approval was that the Schilling test was to be removed from the protocol. Do you recall that?
A That was because they did not have a licence, yes.
Q Because there was no licence. Mr Miller asked you whether that was a clinical diagnostic test. I want to ask you, in respect of the Schilling test, but it could also be asked in respect of any of these tests, can one say in isolation whether they are clinical and diagnostic or not, or does it depend on the reason for which the investigator is carrying them out?
A The Schilling test has a purpose in normal medicine. I do not know if it is carried out now, but at that time people had a clinical need to have a Schilling test. It was not a pure research thing. It showed the permeability of the guts to certain vitamins. Lots of people had Schilling tests as part of normal patient care.
Q The same could be said, indeed, of lumbar puncture, MRI, EEG or indeed colonoscopy.
Q If we just look back at page 232, please, which is the patient information sheet that was attached to the ethics application, we see at the bottom the reference to the carrying out of what I think is the Schilling test, “towards the end of the week”. Is that right, that that is the Schilling test?
Q If a Schilling test was no longer being done on patients, for whatever reason, would that have to be removed from the patient information sheet?
A It would have been logical to have done so.
Q Can I ask you, doctor – and we do not need to look at any documents you will be pleased to hear to answer this – does your research ethics committee, or any research ethics committee have any role at all to play in relation to clinical medicine?
A We do not concern ourselves with things that are purely clinical, no.
Q For your committee to become involved with a clinician in the hospital or a researcher in the hospital, what is the fundamental requirement?
A Carrying out research on NHS patients.
Q If a doctor is simply doing – if “doing” is the right word – clinical medicine; in other words, he is doing what lay people understand to be medicine, i.e. you go and see the doctor because there is something wrong with you and he helps to diagnose it and hopefully put it right, if that is occurring, is there any reason at all for a doctor to have anything to do with your committee?
Q If investigations are, for whatever reason, thought to be clinically indicated, would you expect a research ethics committee to refer to them at all when giving permission for research aspects of the study?
Q Lastly – sorry these are very obvious questions – if a doctor has for some reason, best known to himself, some reason for making an adjustment in the clinical treatment of a patient, would that be something you would concern yourself with or he would expect to come to you in respect of?
Q As far as this application is concerned, considerable emphasis has been put on and there has been much discussion of the letter that Professor Walker-Smith sent to you and which I have just referred you to in relation to the tests being clinically indicated, but had that in fact been a consistent position since the application was put in, that the investigations were clinically indicated?
A It said that on the original application.
Q If I can ask you to look on to page 940, volume 3, you will remember that this is Professor Walker-Smith’s later letter in July 1998 asking for ethical committee approval for the continuing research, he says in that letter again that children are being seen by virtue of clinical need. He said,
“As Dr Wakefield is carefully analysing our results and some of the biopsies taken are being used for research, I would like formally to request ethics committee approval”.
Did that accord with what you thought you had given ethical approval for, the careful analysis of results?
A Yes, it did. He confirms that he is seeking ethical approval only for the analysis of the clinical research. He is saying he sees the children for clinical need, and he is saying the only extra thing is the colonoscopy biopsies which as we have seen have already been approved under another heading.
Q Lastly – a short matter arising out of that – as far as the independent review by Mr Epstein was concerned, Dr Epstein, Mr Miller said that you did not just take your own decision as a committee, you took a view on all aspects of the study. Is that in fact correct? Is that what you were relying on Dr Epstein for, all aspects of the study?
A You are relying on him for the science of the study. When you have that three page outline of the analysis of the disintegrative disorder, we cannot make a decision that this is something worthwhile. That is what you are asking Dr Epstein. You are not really asking him to make an analysis of the ethics society. Purely, is it good science? Is it worth doing?
Q Mr Coonan put a question to you at the start of when he was asking you questions about the application form, and he suggested that it was daunting, and you made the response that they were a lot more daunting now.
Q I just want to go back, if we may, to one of the minutes of the ethics committee, just literally a random sample. Can we go to page 293? This happens to be the minutes of 13 November. If you go to page 294 we see the study in the middle with which we have been concerned in this committee room. But can you just look down, doctor – and I hope I do not make a fool of myself with my pronunciation – but looking at some of the other studies that you had to consider in that same meeting,
“A study to assess the safety and immunogenicity of three batches of hepatitis A – typhoid combined vaccine in hepatitis A seronegative adults”.
“Investigation of the bioenergetics of skeletal muscle in myopathic disorders using NIR spectroscopy”.
“Oesophageal sensitivity testing via balloon insufflation in patients with non-cardiac chest pain, gastro-oesophageal reflux disease, oesophageal dysmotility, functional dyspepsia and irritable bowel syndrome”,
“An open, single-centre study to evaluate the efficacy and safety of a tacrolimus (Prograf) based immunosuppressive regimen in adult allograft recipients who are experiencing hypertrichosis secondary to cyclosporine based therapy”.
I could go on for some time and you will be pleased to hear I am not going to. If you just look through the next pages, you see a number of studies with similar lengthy titles, and now perhaps I can ask you this. Was there anything in fact particularly daunting about this particular application?
A Not from our point of view. I mean also this shows the workload of a committee at that time, 23 major drug trials in one afternoon, which should never have been allowed to happen but we had no other way of dealing with it.
Q You said in answer to Mr Coonan’s questions about whether the committee understood these applications, you made the comment that the hospital chaplain, with all due respect to him, probably did not understand and of course you had lay members.
A Most members would not have understood anything about the science of any of these applications.
Q Is it in fact anything to do with the remit of your committee to understand it except in the terms as to how it rebounds on the patient?
A In no way can we understand for a meeting 23 research applications which go from hepatitis A to the use of tacrolimus for renal transplants. That is why you put it out for scientific evaluation. You want to know, does this science work? Then we will look at it, mainly to look at the information sheet and see that what is being done to the patients is correctly described.
Q Is what is being done to the patient what is important to you as a committee?
A The main thing for us is to make sure that the risks to the patient are in proportion to what is being carried out. Some studies are very risky and you allow them. Other studies with less risk you would not allow because it depends on what the ultimate research aim is.
Q If you have a collaboration on a research project between clinicians and researchers, is that a common situation?
Q Do you expect them all to be clear about what are or what are not research or clinical investigations?
A In most studies there is not a particular problem with categorising. If you are trying a new drug, everything is research, because the whole thing is research. So with most studies it is not something to consider. If you look at most of these, these are all pure research. Everything in most of these studies is research. The second one, you are testing a vaccine, well the whole thing is research.
Q Was the distinction in the context of this study an important one?
A It was important. I do not think there is another example on here but we do get lots of studies where all they are asking is to collect the information and publish it and in those studies then it is important to know what is research and what is normal care.
Q If we just look at page 200 again, the start of this application, and we go to the paragraph that we looked at before, paragraph 11, we see the question which is the question that you drafted at the time,
“Would the procedure(s) or sample(s) be taken, especially for this investigation, or as part of normal patient care?”
In this instance it has been indicated, as we know, that all the procedures were clinically indicated and the majority of the samples. Then we see that there is an additional intestinal biopsy, five per patient, taken for viral analysis, but the indication that as far as the blood was concerned, it did not require an additional sample.
A That is the important point, yes.
Q So as far as that is concerned, the suggestion is that it is research done on a sample for clinical purposes. Is that correct?
A You had to stick a needle into the child to take the blood. We are only interested really, in looking after patients, did they have an extra needle stuck into them, which is the important aspect, not what you did with the one sample when you took it out.
Q In that particular instance it does not appear that you were being requested to give permission for, for instance, a research blood sample.
A A sample has already been taken.
Q For clinical reasons. One of the matters that you were asked about at some length was the position as to whether research ethics committee approval was needed for the writing up of a study and you were taken, if you remember, to a Royal College of Physicians document. Can I just ask you to look at page 29 in bundle 4? Again, just to orientate you, this is a report of the Royal College of Physicians on research involving patients of January 1990. If we look under Medical Practice and Research, in paragraph 2.4 in the middle of the paragraph:
“In general however, where an effort is made to formalise the acquisition of information gained in the course of medical practice this may be considered to be at least a component of research. A retrospective review of case records is usually to be regarded as research, particularly where this is undertaken systematically according to a formal protocol or when an individual other than the person who constructed the records undertakes the analysis. Any activity which affects the patient in any way which is additional to ordinary medical practice is to be regarded as research.”
Was that your understanding of the position as far as reviews of case records at least are concerned?
A I think it describes it. Basically what it says is if there is any formal protocol, which means that you thought about it before you did it rather than just had an interesting case come into your practice.
Q Mr Coonan asked you about page 76, the guidelines there. Sorry. That is the 1990 version. He asked you about page 232 at paragraph 6.22 and 6.23 and he was making the point that by that stage – those guidelines were produced in August 1996, so that is about a month before the application to your ethics committee in September 1996 – the Royal College of Physicians at 6.22 and 6.23 were making the point that their working party was suggesting that perhaps research ethics committee approval was not necessary in those circumstances. Do you recall the passage between you?
Q He also asked, perhaps not rhetorically; perhaps he asked you actually, what was the poor old clinician or the researcher supposed to know about what they were supposed to do, and I wanted to ask you this: if a clinician or a researcher at the Royal Free Hospital has some uncertainty about what is required of them from the Royal Free Research Ethics Committee, can they come and ask you?
A Most of my life is people asking me, and the piece of paper we usually used, as I have said before, the one with the greatest authority, was the Department of Health publication. It is interesting you have pointed it out to me; a publication from the early Nineties has a higher standard than the College of Physicians. The College of Physicians in 1966 are not requiring ethical review. The Department of Health in 1992 does want ethical review. It shows the difference between the approach of the physicians and the approach of the Department of Health.
Q Yes, that is one helpful point but in addition to that, we all know, and indeed, you have very fairly acknowledged, Dr Pegg, that ethics is inevitably an area where it is open to interpretations but as far as people who are under the auspices of your ethics committee are concerned, are you open to having inquiries made about how you are interpreting the ethical requirements?
A I get them every day to this day. In that era we referred them to what we called “the Red book”, which was the Department of Health guidelines.
Q We know you had a meeting with Dr Wakefield and you have told us that you cannot remember what was said at it, and you said in answer to Mr Coonan’s questions that the meeting may have been of no consequence at all. In view of the fact that you have noted that you were having that meeting on the pro forma for project 17296----
MR COONAN: I do object. This is cross-examination. In the light of the answer given, I am not sure how my learned friend can seek to go behind the answers that the witness has given. He said it could have been about the weather; it could have been anything. Further questions now directed to this are pure cross-examination.
THE LEGAL ASSESSOR: Until I have heard the full question I am not in a position to advise.
MS SMITH: The question that I was going to ask was: in view of the fact that you have noted the meeting with Dr Wakefield on the pro forma for application 17296, does that assist you at all as to what the conversation was about?
MR COONAN: It is leading and it is cross-examination.
THE LEGAL ASSESSOR: My advice is it does not seem to advance matters over the answer he has already given. It is a matter for you, Chairman, but he has given an answer to that question in the context of that comment on that document.
THE CHAIRMAN: Ms Smith, are you content with the advice that we have just had form the Legal Assessor on that?
MS SMITH: Yes, sir.
THE CHAIRMAN: Thank you.
MS SMITH: You have been asked a great many questions, doctor, about the application form for 17296. Can I just ask you just to go back to basics for a moment on this form. You have told us that you drafted it. Who is it drafted for?
A For the researchers.
Q Generally speaking, what is the seniority of people who apply to the ethics committee?
A Anybody from a medical student to the Dean can apply.
Q If someone applying to the ethics committee identifies an ethical issue of some kind that is not expressly provided for in the form, do you have any expectations as to what they should do in that regard?
A They could either flag it up on the application or come and see me before they make the application.
Q Do you regard researchers as being absolved from responsibility as far as any ethical dilemma they may identify by an absence of an express question in relation to that on the application form?
A I would have thought if they were applying to an ethics committee they would have had some consideration of ethics in their mind when they made the application.
Q I wanted to ask you a few questions about that part of the application form which refers to the funding of the study. Mr Coonan asked you to look at the terms in one other form. If you go to volume 1, at page 98, this is the form that he took you to and it is an application by Professor Dhillon and Dr Wakefield. On page 98, the same question in the same terms, substances to be given, and the answer was “none” and when we see the question underneath, “How are the substances being provided and how is the study being funded?” we see “Clinical research funds at the Royal Free.” Is that correct?
Q If I could ask you to look at the other one, which is on page 137, if you look at page 182, this is an application by Dr Wakefield and Professor Pounder, and we see the form at page 137, the same question, substances to be given and the answer is “nil”. “How are the substances being provided and how is the study being funded?” and we see that it says “Wellcome Trust.”
MR COONAN: It is signed by Dr Morris on page 139, not by Dr Wakefield.
MS SMITH: Yes. That is perfectly correct. Dr Morris has signed at the end and Dr Wakefield and Professor Pounder’s names appear as the responsible consultants on page 132, but what I wanted to ask you about that generally, doctor, is in regard to this question of how is the study funded, first of all, do you expect it to be answered accurately?
Q If a researcher makes a particular application for a research grant for a particular project and obtains funding for it, do you expect that funding to be declared?
A We expect all sources of funding to be declared, yes.
Q You say that when the source of funding is given as the Royal Free Hospital, you assume that there has been some scrutiny by the special trustees. You assume there has been some scrutiny by them or by the fund into which it is paid. Is that correct?
Q But we see in this one on page 137 that there is actually an identification to the Wellcome Trust.
A So the funding is obviously coming directly to the researcher from the Wellcome Trust and we recognise the Wellcome Trust as an ethical source of funds, as you might say. We will often get applications where it says Medical Research Council, Wellcome Trust, where presumably sums are coming straight into the department’s fund.
Q As far as any funding by the Legal Aid Board is concerned, would that have been uncharted territory as far as you were concerned?
Q You were asked about any possible involvement in the litigation and the words Mr Coonan used were “if an expert in litigation in respect of children involved in the study”, litigation relating to the MMR manufacturers, was how he put the question. How I put it, which I think is no different, but I want to put it as fairly as I can, was if research is in any way associated with a legal action, would you expect it to be referred to, and you said that if one of the objects was obtaining evidence for any sort of litigation, you would expect that to be in paragraph 3 or whatever it is.
A I said it would be the objective that would determine.
Q Yes, and you said, “I need to know because the parents need to know” and I wanted to ask you why. The parents of course are applicable in this study because it is small children but why did you think that the parents would need to know that if it was one of the objects of the study?
A I would have thought the parents would need to know the objectives of any research. If the objective of research is to improve the treatment of disease, they might view it in a different way to if the objectives of the research were to provide evidence for the Legal Aid Board. In the first case they might consider that their child or the group of children would benefit. In the second case they might not see so much benefit. So I think it is important that the information is there under the objectives.
Q Yes. Mr Coonan took you in volume 4 to page 124 of the guidelines. I would ask you just to turn that up, please. That is the section on payments, declaration of interests, and the role of the ethics committee. He took you through that. What he did not do was to go back, which I would ask you to do, to page 99. Doctor, this is the 1990 document.
Q Mr Coonan took you to that paragraph and he then took you on to the 1996 document, but looking at this in 1990, do we see under the suggested format for applications the same provisions in relation to number xiii, “State any ‘interest’, i.e. of profit, personal or departmental, financial or otherwise, relating to the study.”
Q You said on a number of occasions when you were being asked questions about this – three occasions that I noted down – “We have to rely on the probity of the applicant.” I want to ask you this: did the form set out to cover any eventuality in respect of a research application and the information that should be given with regard to it by the doctor?
A I think that form at the time did not cover every possible eventuality, no.
Q Can you explain a little further what you mean by relying on the probity of the doctor?
A You assumed that someone was filling it out in good faith, and even though you have not asked every tiny little question, would provide you with information that he thought was relevant to your consideration of the application.
Q Would you just excuse me for a moment, please. (After a pause) Sorry, Doctor, just one last matter. If you go back to the application form, page 200, and you must be beginning to know it by heart now, but I wanted to ask you about the patient information sheet and the consent form. The patient information sheet is at 232, as you know, and following on from it is the consent form.
Q If there is any aspect of a project which involves research, does the patient, or in this instance of course the patient’s parents, have to be informed of that?
Q Do they have to sign a consent form which indicates that they understand that aspect which is research?
MS SMITH: Thank you for your patience, and now you only have the Panel left to ask you some questions. Thank you.
THE CHAIRMAN: Actually I have been talking to the Panel members over the lunchtime about how we are going to conduct this. I think the best way forward would be that I think we will now adjourn for about half an hour, and that would actually mean about fifteen minutes obviously tea break, but we would spend about fifteen minutes to organise our papers and our own questions. We are not legally trained like you all are, and rather than jumping from one place to the other, if we could spend about maybe fifteen minutes to organise our questions in some kind of an order, it will probably help us and I am sure it will probably help Dr Pegg as well.
MS SMITH: Yes. You will probably be a lot shorter and more effective than we are, sir, so I think we are all happy with that.
THE CHAIRMAN: So it is about 25 past and we will now adjourn and resume at 5 to 4. That will, as I have said, include our mid-afternoon break as well. Dr Pegg, once again, you are still under oath and still in the middle of the examination, therefore please do not discuss this case with anybody. So we are now adjourned, and for part of it we will be in camera when we are going through our own documents, and we will resume at 5 to 4.
(The Panel adjourned for a short time)
MR COONAN: Sir, before you get under way, could I just mention one small matter? Dr Wakefield is absent at the moment and may be absent for the rest of the afternoon. He is not well, and has been unwell since about half-past one with a very serious migraine, and I am in effect letting you know that he cannot be here. It is no disrespect for you, but he needs to sit in a room on his own quietly until he recovers.
THE CHAIRMAN: Well, we obviously understand this and sympathise with him for this, but can I just ask you this question, that obviously he is entitled to be present throughout the hearing as one of the defendants; are you content for us to continue in his absence?
MR COONAN: Absolutely.
THE CHAIRMAN: Thank you. I think that is helpful. Dr Pegg, as you know it is now the Panel’s time to ask you the questions, and if there are any questions from any of the Panel members, then I am going to introduce them to you. Dr Webster is the medical member.
Questioned by THE PANEL
DR WEBSTER: With regard to the independent reviewer, this seems to be a person with enormous responsibility.
THE CHAIRMAN: Dr Webster, just speak a little louder because I think there may be people on this end of the table that might be struggling.
DR WEBSTER: The independent reviewer from the scientific aspect is somebody with enormous responsibility, yet this is somebody that is chosen by the person applying for approval.
A That is right.
Q This project, and I am sure many others, covers several medical fields, yet you get the opinion of just one person.
A That was the system, and it is not dissimilar today.
Q Do you ever back that up by seeking additional opinions from different specialties, or different hospitals, different departments?
A We are allowed to seek other opinions yes.
Q Do you ever do it?
A We have done this year in a couple of applications, yes.
Q Is that a minority of cases?
A I think this year we have only done it once, in which case it was an extremely newsworthy high-profile application that we sought independent advice.
Q Looking at the protocol and the timetable, the neurology and the child psychiatric assessments seem to come at the end rather than at the beginning, yet the entry criteria depend very much on the sort of developmental problems of the children. Did it occur to anybody that this might be the wrong way round?
A I think that is really a scientific question rather than an ethical question.
Q The third one might be a stupid question. When you wrote your letter of approval of the project you said you wanted the Schilling test dropped. Does that mean you did not want Schilling tests on any of the patients at all?
A That was the agreement, yes.
Q That seemed to be for sort of bureaucratic rather than clinical or ethical reasons.
A It would have delayed things, I think, yes.
Q Yet in the project itself, in the outline of the project, it is actually B12 which links the gut and the brain.
A Again, a scientific thing, but the researchers wished to drop it.
DR WEBSTER: Thank you very much.
THE CHAIRMAN: Ms Golding is the lay member.
MS GOLDING: Good afternoon. I just want to stay with the reviewer. Did he produce a report for the Committee at all?
A No, only the letter.
Q In file 1, page 366a, there is mention of a pilot study on this page. Did you know that there was a pilot study going on?
A Sorry, we are on?
Q In bundle 1---
A FTP1, yes.
Q ---page 366a. It is one of the green pages.
THE CHAIRMAN: 366aa. It is one of the green papers.
A Mine are numbered differently. Yes, I have got it.
MS GOLDING: It says there “The pilot study”; did you know there was a pilot study for this particular research?
A I do not think those words registered when we read this. These researchers have many, many, many studies going at the same time, and this letter did not refer to any particular study as being the pilot study, so we did not pursue that.
Q I am not sure I understand. Did you take in that the pilot study mentioned there related to reference 172-96?
A I do not think we thought about which was a pilot study at all.
Q If this was a pilot study for that reference, would approval be required from the Committee?
A If you do a pilot study you need ethical approval, yes.
Q As far as you are concerned, you did not know that there was a pilot study going on for that reference?
A “[A] pilot study has demonstrated”; now, what they refer to as that pilot study is not defined here. It could have been any of the other multiple studies, the pilot study. We just, as I say, took the facts of that sentence and did not bother to look back for a pilot study, no. I think in the context of the time, when you consider an ethics committee doing 20 a month, each piece of paper that comes in you do not read every single word and refer back to things.
Q Okay. You said that you understood the purpose of the study was data collection.
Q Where in the application form did you get that idea?
A The fact that they were not asking permission for the investigations. That only left the data collection.
Q Sorry, not asking permission for?
A In the application they stated that the various investigations were done by clinical need, therefore they obviously were not asking for those to be approved, therefore all that would have left was the data collection.
Q As part of the remit for the Committee, reports are supposed to be received at the end of the project or the study.
A They are supposed to be sent every year and at the end of the study.
Q Did you receive any reports at all?
A That I cannot say. It was very rare at that time to receive any reports from anybody.
Q Was it clear from the application that the study related specifically to autistic children?
A I would say it did, yes.
Q It did?
MS GOLDING: Thank you very much.
THE CHAIRMAN: Dr Moodley is the medical member.
DR MOODLEY: Dr Pegg, I am going to go back to the expert reviewer. You said in response to a question that the task of the expert reviewer was to ensure that it was good science.
Q Can you explain what you mean by “good science”?
A You saw the outline of the study, which of course would not be intelligible to, say, a lay person. You therefore need somebody to say that there is a research question to be answered and that there is a need to answer that research question, and that this is a proper way of answering that question. So you are really asking the reviewer is this a reasonable way of doing it, because you do not know that it is a reasonable way of answering the question.
Q So would you have expected them to examine the methodology?
A We would have expected them to do everything, the statistics, methodology, everything, yes.
Q And the recruitment of subjects?
A Anything on the scientific side of the study.
Q And your expert reviewer was a gastroenterologist, and the subjects of the study were children with disintegrative disorder.
A A large amount of the study related to their intestinal system, colonoscopy biopsies. A large proportion of the study related to their intestinal system and of course the applicants were gastroenterologists so it would be reasonable to send, if you have an application from a consultant in gastroenterology it would be reasonable to send it to an expert in gastroenterology.
Q Despite what has been described as invasive tests being done on children?
A How do you mean, “despite”?
Q In the protocol they agree that these are intensive tests done on children.
Q But it was not thought appropriate to send it to a paediatrician or a child psychiatrist?
A As I say, not at that time. Of course, if this came to me tomorrow I would have to send it to a paediatrician.
Q One other question about the information leaflet. When you were going to discuss with Dr Wakefield the changes to the information leaflet, it was around the risks from lumbar puncture. Was there any thought given to possible risk from colonoscopy or general anaesthetic?
A I think the committee felt that the lumbar puncture was not well described; that the others were better described. I am trying to think why they singled that one out rather than the others. I think they felt that the information on the lumbar puncture was not sufficient.
MRS DEAN: Can I ask you to begin by looking at the application form on page 200? What I want some clarification on is a point here. You were asked, I think, about the signatures of department heads, that is the Department of Neurology and the Department of Child Health at the bottom of that page, and I believe you were asked to what extent their signatures could be taken to mean that these people were aware of the details of the protocol. I have a note that you said at the time, “In practical terms, we discovered that these signatories never read it”.
What I need clarification about is, did you mean that in general terms you discovered that --
A I am not saying that Peter Harvey did not read it, if that is what you are saying, no. What I am saying is that the reason these signatures are in the form, whatever the form says, is that we discovered that Department A would use the resources of Department B without telling Department B that it was using its resources. That is the reason for the question. If you are in a neurology department, if you wanted to carry out neurological investigations, it was polite to let the neurology department know. Now in this case it was not a question of that but there have been many other studies where people are doing MRI tests and things without another department knowing that they are going on. There are often funding issues involved in this. The signature actually meant that the neurology department knew it was going on in their department.
Q Thank you, that is very helpful. If you turn to page 201, at the top we have paragraph 2, the title, paragraph 3 objective, and that was standard, was it not, for all such applications?
Q You have told us that very often the title of a project might change and that really that did not matter too much as long as the protocol did not change greatly.
A It did not matter then, no. If you changed the title now, you usually need to have a minor amendment made in a formal manner, but in that era they did not bother. But even now it would still be considered a minor amendment to change the title.
Q I wanted to ask about paragraph 3 and the objective. What would happen if the objective of a project changed? Would you expect someone to come back to you for further approval?
A I think if the objective changed, you would probably find that there would be changes within the study to achieve the new objective. It would be difficult to change the objective of a study without, say, changing the tests that you were doing or the samples that you were taking, so I would consider that a complete change of objective would be a material change to the study.
Q I am not thinking about a complete change, but perhaps one part of the objective might be dropped or some link may no longer be pursued or something added.
A It is trying to work out the feeling at the time, because of course nowadays you only have to remove a full stop or something and it is a minor amendment because it is all held on computers and you cannot change anything without unlocking a computer. In that era, if a researcher dropped something, he may not consider that worth tell you about because he may think if they dropped a test there is no ethical issue to dropping a test. The only ethical issue would be if you added a test. So they may well not consider that removing a test in the objective was something that you needed to come back to an ethics committee for. You are removing something that a patient has to do, not adding it.
Q Thank you, that is helpful. I apologise for returning to something my colleagues mentioned, but I wanted to talk about the scientific adviser. As I understand it, the ethics committee required an independent review from a scientific adviser, in this case Dr Epstein, to ensure good science. As a lay member what I understand that to mean, amongst other things, is that the methodology set out in the proposal would test the hypothesis. Is that right?
A Yes. In answer to the question, do you have enough people to answer the question, all the little details of carrying out a trial.
Q I want to ask you about the Schilling test. We know that that was removed from the protocol because of the need to get a licence and the delay that was anticipated. I wonder, did you as a committee think to ask Dr Epstein what his view was about the effect the removal of that test might have on the extent to which the hypothesis in this application could be tested?
A No, we did not.
Q Can I ask you why not?
A A large number of protocols were changed as they passed through the ethics committee and had various changes done to them. For example, a drug company protocol might in a year have six amendments coming in. The pure practicalities of sending each of those amendments out to the scientific adviser would preclude one doing that.
Q Can I ask you to look at page 235? I want to ask you something about your note there concerning the meeting with Dr Wakefield. I understand you have told us that you have no memory whatsoever --
A That was obviously written at the end of the meeting. I think we are agreed on that. At the end of the meeting I wrote that I should meet Dr Wakefield to talk about the Schilling test and the consent form. I remember meeting Dr Wakefield. I do not remember the actual conversation that I had with him at the time.
Q I want to ask one or two questions about that. First of all, is there anything at all about your memory of that meeting that helps you to place it in time?
A I think the only time you can place it is between 13/11 and 18/12. I cannot see any other piece of paper or something which would say it is before that or after that. So no, I really cannot place the time of that.
Q If I can ask you something else which may or may not help. Was Dr Wakefield a person that you often met with?
A No. I think probably when I met him was probably the first time I had clapped eyes on him.
Q It was probably the first time?
A Yes. I am an anaesthetist and exist in operating theatres. Our paths would never have crossed.
Q Thank you, that is helpful. There is just one other thing I wanted clarification on. Page 358, this is a letter that you wrote to Professor Walker-Smith with the decision. Yesterday you were asked I think by Mr Miller, or you were taken to the sentence that begins,
“As you may be aware this application was discussed at length at two committees”.
Q You made the comment that Professor Walker-Smith would not know of course that the discussion was lengthy, but that he would have known that it was discussed at two committee meetings. I wonder if you could elaborate on why you say that?
A After the first committee meeting, he received a letter from me asking – i.e. he knew it was not approved at the first committee meeting. Therefore it would have had to have gone, logically, to a second meeting and therefore he must have known that it went to two committee meetings, the first that did not pass it and the second that passed it. He would not have known, of course, that the discussions were at length, so maybe I was assuming something he did not know.
Q If I can follow on from that, the letter that you sent to him, is that the letter at page 291? Sorry, that is a reply.
A I think it is a green one.
Q That is page 265a. Is that the letter you are referring to?
A That would be the letter I wrote after the committee meeting, yes. No, sorry, that is the letter I wrote – we have agreed this – after I received the comments of the lay member of the committee, because it is dated before the meeting.
Q I am trying to discover in my papers, and I am sorry because I do not want to set you off on a paper chase, but it is your recollection, is it, that you spoke to Professor Walker Smith after the committee meeting?
A I think we worked out yesterday that that letter could not have been written after the meeting; that that letter, correct me if I am wrong, relates to me writing to Professor Walker-Smith having received the comments of one of the lay members of the committee.
Q You do not recall writing again until afterwards?
A No. Even though we discussed it at the committee, I think that letter encapsulated what we actually discussed. The lay member actually identified all the points that needed to be brought up, so a further letter was not necessary.
MRS DEAN: Thank you very much.
THE CHAIRMAN: Dr Pegg, I also have a few questions so forgive me for holding you for a little longer. Can I first of all start with your ethics committee? I think what you said in your evidence was that in 1996 the committee members did not have any training.
A That is right.
Q But today ethics committee members do have formal training.
Q I know we are not actually concerned with today’s ethics committees so far as this case is concerned, but I want to put the whole thing into a proper perspective. Can you give me brief details, what training do present-day ethics committee members have?
A You have to have a formal training within six months of joining a committee on a recognised course. King’s College run one. There are various courses recognised for the training of ethics committee members. You must attend one of those within six months of attending. Everybody on the committee must demonstrate at least one session of CME for every year they are on the committee, and we regularly hold once a year a training session for members so that we can tick that box.
Q How long is that formal course? You said they had to do one course within six months of joining the committee.
A King’s one is three days, but because some people who join ethics committees cannot do that, there are intensive one-day courses.
Q Could you possibly briefly give me some of the details that are done during those three days?
A It usually consists of, first, you have a didactic lecture, then you break out and you are given obviously wrong application forms which you then discuss and come back. So it is a series of didactic lectures mixed in with…
Q Practical work.
A …practical work, yes.
Q I think you also said in your evidence that nevertheless, even though they were without training, it was with the same vigour that the members of the ethical committee looked at the applications at that time. How is that possible, if today you know the things that you should be looking for, but at that time it was without those members knowing what they should be looking for? How could they be looking with the same vigour?
A Most of the people had been on the committee for many years and my perception of committees then and now is that the discussion that we have of any item has changed little since we introduced mandatory training.
Q So it is with experience that they learned at that stage?
Q Of course, during the first six months, year, two years, if there was any new member…
A The idea of ethics committees is you make sure that you have continuous rolling membership changing but I think the education of new members is as much of the system as… At that time there was not a large body of legislation, for example, relating to ethics committees. There was no legislation relating to ethics committees. There was no legal background, whereas nowadays in your didactic sessions you would have to be taught the actual legal background of an ethics committee, what legislation… There are more rules and regulation whereas of course, in times when there was no legal legislation… My opinion is, in terms of the way things are discussed, it is very little different now from then. At that time, of course, there were considerably more professional members of ethics committees who were familiar with research, whereas nowadays… I think we had two lay members. Now we are moving to a situation – we have not quite got there – of one third lay. We are moving, as in all committees, almost like yours, where lay members will comprise 50 per cent of an ethics committee. When you put a lay member on a committee, they are going to need considerably more training than when you put a professional member on a committee, so I think I can say that the vigour at that time was probably as great as it is now.
Q Nevertheless, of course, it was one of the lay members who actually asked the most pertinent questions at that particular time, notwithstanding your comments about the lay members?
A Yes. I think you put “lay” in inverted commas. Let us say he was not a doctor but in his career he had a large involvement with hospital R&D departments, so he is not actually the man on the Clapham omnibus; he is somebody who for many years has been running hospital research and development departments. So “lay” – he is not a lay member in the true sense.
Q Can I now just move on to that particular time, now I understand how the ethical committee functioned at that time. The other thing you said was that at that time your shelf was full of all kinds of guidelines.
A That is right.
Q And they are long gone. Did I understand right that, so far as this particular research was concerned, it was the Department of Health guidelines that you were concentrating upon rather than any other guidelines?
A It is like law, I think. You have to look at the authority of a guideline and I think that Department of Health guideline, as we saw, there was disagreement between the physicians’ guidelines and the Department of Health guideline.
Q But if you look at it in detail, there are slight differences but no major differences.
A Still we considered the “red book” as we called it was the first one to look at. Now they have been completely replaced by one single folder called standing orders of ethics committees, which has everything in it.
Q Was it actually the case that in every case then you were only looking at the red book or the Department of Health guidelines rather than any other guidelines, or was it that you were using different guidelines for different projects?
A You saw in this project we consulted the guidelines from the Paediatric Association. You remember that was photocopied in with one of my answers. So I think you dipped into guidelines as and when, as you might say. You might not need to read guidelines of a certain type because you have not had an application in that discipline, so they were all on the shelf and we dipped into them as we required information.
Q I think you actually also said that the documents which you got for the research were not actually circulated to all the members, the documents in full.
A Even to this day, members only get the application form. The researchers are supposed to put on the application form everything pertinent. Supporting documentation for a drugs study probably looks like the stuff sitting next door to me here now.
Q If I remember rightly – I have looked at some of the documents but I cannot ask you to look at the page number because I do not know where it is – it was eight or ten copies of these documents that you were requesting from the researchers.
A Yes. We want them to do our photocopying for us.
Q If you are not circulating those to the other members, why do you need all those copies?
A Which one are you referring to?
Q That is why I said I cannot actually give you the page.
A I think you are referring to my new one rather tan my old one.
Q All right.
A If I remember rightly, my new one is basically a new standard I applied a couple of years after I took post. In the front of my new one is a list of documents that have to be supplied. The old one had no such list.
Q I see. So you were not actually asking them to supply you either eight copies of the documents or ten copies of the documents?
A I think we actually did our own photocopying then. They sent us one set of everything. It was only when after a couple of years standards changed and then you saw on what you call the improved application form, on the front of that is a very much more definite thing as to what we need and what we want.
Q Thank you. I think that is probably the case. I do not have the page reference. A last question on this protocol. We have had conflicting evidence from you, I believe. Yesterday you actually said that the very first protocol, the 1996 protocol, was devised by you.
A I think the 1996 – I am speaking from memory now – it might have been mod… It is what I ended up with from the previous chairman.
Q I got yesterday that you actually said that it was devised by you but today you said you inherited it.
A It was written by an ethics committee chairman. My feeling is that I actually did not write that first one. I wrote the second one about a year after I----
Q That was 1999.
A After I took the chair, it needed sorting out so I wrote… Nobody had changed that form at all.
Q So that was more inherited rather than devised.
A That was an inherited form, and the problem with that form of course, as we have asked various questions about how things appear, is that of course the researcher could format it in any way they wanted. It was a form that you could play with and do what you liked with.
Q Thank you. Can I now ask you to look at page number 313, volume 1. This letter, if I remember rightly, you described as a cut and paste job.
A This letter is… The middle bit is standard.
Q From where to where?
A “I refer” to “1984”. You would have put the name of the researcher in. You would put the number and you would write the title. You would then discover that the middle bit from the words “I refer to your recent application” down to the words “Data Protection Act 1984” would just be sitting there in the middle of the form.
Q On these ones, of course, the dates are different. I am still not quite clear and this is why I am asking you these questions. It says that the application was approved at the meeting on 13 November 1996.
A Yes. It is completely wrong. I do not know if we have any evidence that this was ever sent. Only the other side could say that.
Q The only thing I can say is that this paper has been provided to us with the other papers and we have to look at all these documents.
Q What I actually want to know is that this letter was sent on 14 November; the date you have said was actually changed.
A We said that letter was created on 14 November.
Q It actually says “Your application was approved at the meeting on 13 November.”
A Yes, it is complete nonsense. This letter was created on 14 November. It does not appear to have been signed and I do not know whether it was sent.
Q I am still not quite clear. I am sorry to ask you these questions. I just want to understand where the whole thing lies. This letter actually says “I am pleased to inform you that this was approved.”
A Yes, it is complete rubbish.
Q This will be a standard wording for the applications which are approved.
Q This application was not approved.
Q So how could it be a cut and paste job? Was it sent or not sent? I do not know
where I stand with this particular letter.
A We do not know where we stand with it, whether she sent it, whether she had it ready to send. She often created things before. Where it fits in I cannot help you.
Q Even without the chairman’s direction?
A All I know is that in the bundle that you have and I have there is a letter. The letter says – and it is unsigned – that the application was approved, which we know it was not. Whether it was sent, received, I do not know. I do not know whether the other side has received a copy of this letter or whether it was not sent; whether a secretary created letters. I do not know her systems. Did she create a letter for every application the committee did just to be ready to send them out? I do not know. It is an unsigned letter from her saying it is approved.
Q But it is on the Royal Free NHS Trust letterhead.
Q Can I now ask you to look at page 358. This is a letter from yourself to Professor Walker-Smith, giving the approval.
Q Again, I just want to be clear about the evidence, because I think we have heard different things from you yesterday and today about this data collection, including your answer given just now to one of my colleagues. Having gone through this, there is no mention of data collection on the application or on the protocol for approval.
A That is right.
Q There is no mention of data collection on this one that you have given the approval.
Q There is no mention of data collection on this letter of approval that you have sent.
A No. Well, we have already been through that, yes.
Q I know, but I think you are still giving the answer, and I just want to understand, because I think your answer just now to one of my colleagues was that you gave the approval for data collection only. I want to have the real answer, where exactly do we stand on this; was the approval given for data recollection, even though the application was made for research, not only for data recollection, and also that the approval letter was actually sent without data collection mentioned on this?
A Well, what was approved was what was applied for.
Q In the application there was no mention about data recollection.
A No, but in the application, if you take it at its word, you are approving a study which – let us take it at its face value; this approves a study. Move back to what is a study. The study is a series of investigations on patients, all of which, except for two mucosal biopsies, are part of patient care. So let us say I have not said it is for data collection. So I have approved what I have been sent. What I have been sent is an application to carry out a research study. In that research study are various invasive procedures. All of the invasive procedures are clinically indicated. We have ticked that box. So I have approved a research study consisting of clinically indicated procedures. Right? Whatever is left, when you have taken out, whatever is left I have approved.
Q You have gone through that, you are quite right. The point is that I just want to be---
A Clearly, if you look at my letter as it stands, I agree it does not say that it is data collection. I agree I approve the study subject to the three things I put. Therefore you look back at the study. What was the study? The study was an investigation on children. All the investigations on the children, bar the one we have said, were clinically indicated, so I basically approved everything but the clinically indicated---
Q Apart from some extra blood tests and extra biopsies.
Q So they were not actually data collection.
A Well, what is left of the study when you have taken out the clinically indicated investigations? What is left? It is basically the data collection.
Q Now, the three things that you mentioned, and again it is because of the conflicting answers that we have received from you, and that is actually one of the things that you have actually said, the Schilling test to be removed from the protocol, and I think, between yesterday and today, there are two different answers that we have had from you. Once you actually said that it was basically because of the researchers, that they wanted it to be removed, and on the other occasion you have said it is because of the licence difficulty, and that you mention in the letter as well, and thirdly whether it could cause some delay.
A I think they all ride together. The researchers wished to remove it because of the delay of applying for the licence. The researchers did not want to remove it because it was not indicated, the researchers wanted to remove it because the timescale of getting that licence to use a radioactive material was---
Q They did not put anything in writing to you about it?
A No, but to get an ARSAC licence at that time took a long time, and the researchers did not consider that this test was so important that we could wait for a licence to use a radioactive substance.
Q At the same time I think if this test was needed on the clinical need basis---
A Well, they said that it could be dropped.
Q ---they would not need an extra licence.
Q I think, referring to your previous answer, as most of these investigations are, at least on the paper as we see it, mostly on a clinical need basis---
A It is the same illogicality as 3.
A It is the same illogicality as the lumbar puncture that we agreed was an illogicality yesterday.
Q My last question, page 940, and this is in FTP3, I think what I got from your evidence about this was that you did not notice, because of the volume of the work, the change of the title on this letter, the change of the title of this study.
A That is right.
Q When did you actually notice this eventually, that the title was in fact changed?
A I have a feeling it was the Dean’s letter, I think. The first evidence of me noticing a title change, I think, was when I wrote to the Dean, and you remember a piece of paper where I say I notice its title has changed.
A So the date of that letter will be the time I noted that the title had changed.
THE CHAIRMAN: Thank you. That was my last question, so thank you for your help. I am now going to ask all the counsel if they have any further questions, and I am going to start with Ms Smith first of all on behalf of the GMC. Any questions of clarification?
MS SMITH: No, thank you.
THE CHAIRMAN: No. Mr Coonan.
Further cross-examined by MR COONAN
Q Just two very short matters. One really is not a question, but really to help you, sir, because you raised the question about the references to numerous documents. I think, and Dr Pegg can do it of course, if you look at volume 3, page 1083 I think may be the answer.
THE CHAIRMAN: Sorry, page number?
MR COONAN: 1083. Have you got that Dr Pegg?
Q The reference there of Dr Wakefield referring to seventeen copies, and if you move on to page 1085 you will see the requirement in your new form, right at the top, the requirement of “Seventeen copies of each of the following”. Do you see that?
A Which page are you on about?
A Seventeen, yes.
Q Right at the top. I just wanted to draw your attention to that. The only other matter I wanted to raise was this: the chairman raised the question of the letter of 14 November, which, on the face of it, was addressed to Dr Wakefield, telling him of the approval, and the chairman asked you some questions about that, and I just want to draw your attention to what you said when you were first taxed about this by Field Fisher Waterhouse in again last year we assume. If you have got your statement there, the first statement, do you see paragraph 28?
Q When you were first asked about this and you looked at the documents via Field Fisher Waterhouse you said:
“A letter was sent to Dr Wakefield by the Secretary of the LREC dated 14 November 1996 informing him the application 172” – and then there is a typo – “172-96 had been approved at the meeting on 13 November for a period of two years. I attach this letter” – and you do so – “This approval was subject to the various reservations raised by the members.”
That was your first response, was it not, when you looked at these documents?
MS SMITH: Please would you go to the second sentence.
MR COONAN: If I am asked to of course I will. The solicitors went back to you in November 2006 and asked you some further questions about it. If you look at paragraph 25 you said,
“I do not know why the letter dated 14 November 1996 was sent to Dr Wakefield. If the letter was sent, it was sent in error”.
Of course there is no reference in either of those two statements to any difficulties with your secretary or any speculation about the conduct of your secretary, is there?
A No, all it says is, if it was sent, it was an error.
MR COONAN: Thank you very much. Sir, that is all I ask.
Further cross-examined by MR MILLER
MR MILLER: Dr Pegg, you have confidently asserted in answers you have given to the Panel that the researchers wished to drop the Schilling test because of the difficulties that they would have had in getting an ARSAC licence, and there was a lot of delay involved in getting them in those days. That is your final word on it to the Panel.
Q If you look at the position as far as the documents are concerned, the letter of 11 November 1996 from Professor Walker-Smith, page 291, written almost a month after your letter to him, starts with the sentence,
“Despite extensive inquiries we could not find out what ARSAC means”.
We do not see any response from you to him explaining what it means, do we?
A There is no written response, no.
Q You told the Panel earlier that you have no recollection of the content of your conversation with Dr Wakefield, if it took place, so how can you say, with the confidence you appear to have, that the researchers were keen to drop it because of the delays involved in getting an ARSAC licence?
A It is my impression from what I remember that they wanted to drop it because they could not get an ARSAC licence. If you maintain that that was not the reason they dropped it, and they dropped it because they no longer required it, then I will not argue with you.
Q You use the word “they”. As far as your evidence goes, there was only one conversation that could have taken place with Dr Wakefield.
A Shall we say that the researchers dropped it. The researchers in the end did not want to do the B12 test, did they, for some reason? I am venturing that I think, from my knowledge, that it was a product of the licence. You are suggesting that it is not that. It does not matter if they wanted to drop that piece of research.
Q I suggested to you that it was a condition which you imposed, that the Schilling test should go.
A After agreement. The Schilling test compared with the rest of the study is not a particularly invasive thing. You eat something and put a Geiger counter on them. Therefore it would have been illogical for me to have said, “Drop the Schilling test”, unless there was a problem with the licence.
MR MILLER: That is all I ask.
THE CHAIRMAN: Mr Hopkins?
MR HOPKINS: I have no questions.
THE CHAIRMAN: Dr Pegg, you will be relieved to know that you are now released. Can I thank you on behalf of this Panel for giving us your two very valuable days and giving us the benefit of your evidence. Thank you again. You are now released.
(The witness withdrew)
THE CHAIRMAN: Ms Smith, it seems that we took the right decision not to keep the witness waiting.
MS SMITH: Yes, we did.
THE CHAIRMAN: It is now five minutes to five o’clock. We are not sitting tomorrow. The next day for the hearing is on Monday, so we shall resume on Monday. But if possible, could you give us the batting order for Monday?
MS SMITH: I can tell you who the two witnesses are who are going to be coming on Monday. I cannot yet tell you which one we are going to be calling first. One is a general practitioner, Dr Shillam, and the other is Mrs Cowie, who is a representative from the Legal Aid Board. As I say I have not yet quite resolved which one is coming first.
THE CHAIRMAN: Thank you again. We shall resume at 9.30 on Monday morning.
(The Panel adjourned until 9.30 a.m. on Monday, 30 July 2007)