GENERAL MEDICAL COUNCIL
FITNESS TO PRACTISE PANEL (MISCONDUCT)
Monday 14 April 2008
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 not 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
ANDREW JEREMY WAKEFIELD, continued
Cross-examined by MS SMITH 1
THE CHAIRMAN: Good morning, everyone. Good morning, Dr Wakefield. Yes, Ms Smith.
ANDREW JEREMY WAKEFIELD
Cross-examined by MS SMITH, continued
Q Thank you, sir. Dr Wakefield, just to remind you and to remind us all, on Friday afternoon I had embarked on a sort of overview chronology of the project with which we are involved. We looked at the genesis of the hypothesis and the formulation of the protocol. You have told us that there was a draft protocol round October 1995. The early one we have is the one ultimately sent to the Legal Aid Board by Mr Barr and that is undated. You accept that you gave it to Mr Barr some time, I think it is fair to say, between January 1996 and the beginning of June 1996 when he sent it on the Legal Aid Board. I have suggested to you, and we have dealt with it, that it was exclusively in the language of research. We then looked, you will recall, at the correspondence in relation to the first children to be seen. I had asked you about correspondence in Child 2 and Child 3’s records, which was in April and May 1996. You will recall that we concluded on Friday afternoon with the letter that Professor Walker-Smith wrote, saying that you were the inspiration behind the work, and you have given us your response to that. I think by April you accept that the protocol was at an advanced stage of preparation if not entirely finished. Just to remind ourselves, you said that by reference to the document which has been put in by Mr Miller. It is FTP1, please, at page 93a. I think your evidence is that that particular note to the various collaborators suggests to you that at that time you were pretty near to a final stage of the protocol. Is that correct?
A That is correct.
Q That is April and, as I say, we dealt with Child 3 in May. Then, on 6 June 1996, we know that the draft protocol that you had prepared was sent to the Legal Aid Board by Mr Barr. If you go on, still in FTP1 to page 103 that, as I say, is the first copy that we have of the protocol. It was attached to the costing proposal and, of course, I will be going back to that in a while but I think you accept that that is the draft of the one that you were awaiting the completion of before booking in the children?
A Yes. Mr Barr has included that document in his submissions to the Legal Aid Board. However, the proposed protocol that he submitted is not correctly referred to in this letter because, of course, as we see the Legal Aid Board protocol was a study of five children with autism and five with Crohn's disease. The protocol that was ultimately to become 172/96 is concerned solely and specifically with the issue of children with autism.
Q We understand that that is your position but at present I am simply asking you not about the Legal Aid Board aspect of the protocol, but simply that this protocol at page 104, attached to the letter at page 103, which Mr Barr sent to the Legal Aid Board was indeed a draft of the one that you were awaiting completing before you booked in the children?
A That is correct.
Q Before you investigated the children. Is that correct?
A That is correct.
Q The next thing that we know chronologically, that happens to have been sent to the Legal Aid Board by Mr Barr on 6 June 1996, so we can date it to that extent. You have told us you would have sent it to Mr Barr some time prior to that. The next thing chronologically is that Professor Walker-Smith sees Child 2. That is on 24 June 1996. The Panel will recall that that is the second time in outpatients, the first having been the one you have told us about in August 1995. Professor Walker-Smith then writes to you, and I would like us just to look at the Royal Free Hospital records for Child 2, please. That is page 162. This is Professor Walker-Smith’s letter to you, as I say, of 21 June 1996.
I at last saw . I think he is now the most appropriate child to begin our programme. Can we discuss together the most appropriate date? I think September might suit [Mrs 2] best.”
Then there are details relating to the colonoscopy.
“I think she would like a copy of the protocol that we are using. I don’t know whether you think it is appropriate for you to send her that or whether I should.”
I think that you would accept that that is a reference either to the protocol that we have just identified in draft, or it may be by then to the completed protocol. Is that correct?
Q Then the next chronological child is that on July 4, 1996 you write to Professor Walker-Smith with regard to Child 4. I would just like to look at his Royal Free Hospital records, please, at page 26. This is you to Professor Walker-Smith:
Please can I pass on this referral which has come to me from Dr Tapsfield. [Child 4] sounds like a good candidate for our forthcoming study.”
Again, that is a reference – “forthcoming study” – to the same study as the protocol applied that you have sent to Mrs 2, or that Professor Walker-Smith sent to Mrs 2?
A That is correct. The clinical and scientific investigation.
Q It would appear, would it not, from these letters that there was an arrangement between you that they would all come in as part of some sort of arrangement?
A Yes. The arrangement that was in place by this stage was the clinical protocol, that is for the purpose of investigation of the clinical symptoms of the children in order to establish whether or not they had a bowel disease, and the adjunct experimental aspects to that research-based elements under my control.
Q If these are clinical admissions to see if these children have some sort of gastrointestinal disease, Dr Wakefield, why do you need to coordinate the referrals in this way? What is your involvement in the coordination of referrals?
A As can be seen from the details of that protocol, the coordination of the admissions was under the control, appropriately, of the clinicians, not of me. It was my job, my duty, to make sure that as and when they did come in the research elements were in placed; that is, the facility to analyse their biopsies. To that extent, being that this was an integrated, multidisciplinary programme, it is entirely appropriate that Professor Walker-Smith should be keeping me informed in this way.
Q If we look back at FTP1, please, at page 116, we are still at this stage in the draft protocol rather than the finished protocol, although the wording in this paragraph is identical: This is paragraph (ii):
“Referrals will be coordinated by AJW”
that is you –
“JW-S and SM”
Professor Murch –
“such that they will be admitted for colonoscopy preparation on a Sunday afternoon. Patients and their parent(s) will remain in hospital for one week. 24 hour urine collection … All blood tests …. On Tuesday, psychiatric and neurological assessment will take place.”
That rather suggests, does it not, that for some reason you were envisaged to be – as indeed we can see from these documents you were – involved in the coordination of the clinical referral?
A There is a distinction between referral and admission. Referral, in this context, applies to the fact that the parents were making contact with me in the first instance and that I was passing that request for referral back to the practitioner for consideration for further referral to Professor Walker-Smith. Admission had nothing whatsoever to do with me. This is an entirely clinical matter and is routinely conducted for all patients and it is not a process in which I was involved at all, other than to be informed of the matter of fact. I should just add that according to the protocol, that is 172/96, when the decision had been made to admit a patient, I had agreed to make contact with the secretaries of Dr Berelowitz and Dr Harvey to let them know that a patient was due for admission.
Q You see, still on page 116, Dr Wakefield, although you say admission and referral are two different matters, it does not appear that that was in your mind when you drafted the paragraph at (ii), does it:
“Referrals will be coordinated by AJW, JW-S and SM, such that they will be admitted for colonoscopy preparation on a Sunday afternoon.”
A As I say, my role in this was to pass referrals, or potential referrals, to Professor Walker-Smith. The admission process was entirely – I repeat entirely – under the control of the clinicians.
Q We will obviously have to revert to that matter, particularly when we are looking at individual children, but just for present purposes, can I carry on with the chronology? We know that Child 1 was actually admitted for investigation on 21 July 1996. If you want to check that on your D8 you are very welcome to do so. The next thing we know, in August 1996, an application for project 172/96 was signed off by your head of department, Professor Pounder. If we look at FTP1, please, at page 200, you will see the signing off by Professor Pounder at the top of page on 6 August 1996. Then, if you go to page 212, that is the now completed protocol. Is that correct?
A As we have seen, it is the completed protocol for submission to the ethics committee. It is, in fact, something that underwent further revision later on, but yes, for the purposes of the ethics committee application, this is the completed protocol.
Q So we know, do we not, that that application to the ethics committee was signed off by Professor Pounder when only one child had been seen in Professor Walker-Smith’s department – only one child had been investigated?
Q If we just look back at your D8, your list of investigations, we are now the best part of a year on from Child 2’s initial clinical referral to Professor Walker-Smith at St Bartholomews which we know to have been… His first outpatient appointment was in August 1995. Is that correct?
Q So this problem, which you have told us required clinical investigation gastroenterologically that Child 2 had in August 1995 still has not been investigated on what you say was a clinical need basis until a year later?
A Just reverting to Child 2, I had recommended that an effort to get referral for this child by the general practitioner to Professor Walker-Smith at St Bartholomews was undertaken purely on the basis of his symptoms. You will remember that Professor Walker-Smith did not consider this child to have intestinal inflammation at that time. That may well have been the case during that time, and it is impossible to date or to provide documentary evidence. Further children came forward. It was decided to conduct a clinical and scientific investigation and such was the complexity of the children’s presentations, such was the uncertainty surrounding the possibly link between bowel and brain and how one might approach it that a great deal of diligence, consultation and reference to expert colleagues, was necessary. Rather than being delayed for other reasons, this was an effort in a nutshell to get it right.
Q And Child 2 was not the only one, of course, because you have told us of a consistent story that parents were giving you, phoning with an urgent need, as you perceived it, to investigate gastrointestinal problems and yet whoever was responsible for the decision to defer their referral – and their appears to be some doubt about that – but whoever was responsible for it, the fact is that none of them begin to be investigated until the period we have now reached.
A As I sought to make clear last week, the fact that there was an inquiry from a parent did not necessarily imply urgent need, but there were many, many inquiries. Many of those did not turn into a referral ultimately and what we see in those that did come forward was a perception, at least on the part of the general practitioner or the community paediatrician, for such a programme, such an investigation, to be conducted.
Q The truth is, is it not, Dr Wakefield, that you decided having heard, as you tell us these consistent stories that you would, whether in collaboration with Professor Walker-Smith or not, defer this until you had set up a research programme in which to look at them under, investigate them under?
A No. As I have said before, what this required was due diligence applied to an understanding of the possibly neurological problems these children had, possible psychiatric problems these children had, the neurodevelopmental problems that they had and other aspects that required, purely on clinical grounds alone, a great deal of collaboration and consideration, consultant with colleagues.
Q That is what ---
A That is what took the time.
Q That requirement on clinical grounds alone was not apparently of sufficient urgency as far as any of the doctors involved were concerned that it required some kind of investigation prior to the setting up of this elaborate study.
A This really probably is not a question for me, because I was not involved clinically. So it is a question which is probably better resolved by Professor Walker-Smith himself. What I can say, having sat in on the discussions, is that it was far better to get it right from the outset, or at least make an honest attempt to get it right from the outset, than it was to act prematurely and fail to understand what was going on.
Q I think you will agree that the protocol which was submitted to the ethics committee – that is the one which starts at page 212 in FTP1 – mirrors in most respects as far as the narrative is concerned that which was submitted by Mr Barr to the Legal Aid Board, which is at page 104.
A Yes, it does.
Q I do not want to embark on a tedious exercise, Dr Wakefield, of going through it and I entirely accept that there are minor alterations in the way in which it is set out textually, but generally speaking we are agreed that it does. Can I suggest to you that the major differences are that you have inserted into the ethics committee protocol the details, if you like, of the two postulated research hypotheses. They are at page 220 and 221 and they do not, I suggest – and you are very welcome to check – but I think you will find they do not exist in the original draft, those box diagrams. Do you accept that?
A Yes. I have not looked, because I do not have the page number, but if you say so, I am very happy to accept that.
Q There is not a page number because they do not exist in the other document. The diagrams I am talking about, as I just told you, are at pages 220 and 221. You have those, do you, so you know what I am talking about?
Q As I say, they do not exist in the initial draft. The other thing which does not exist in the initial draft, I think you will accept, is appendix 1, which is the virology which is attached to the back of the final protocol. That starts at page 226 and that appendix 1, if you look back at page 111, you can see at the bottom of the first paragraph “Using appropriate controls” and then there is in brackets “Appendix 1”, but that appendix has not actually found its way into that draft, so the details which were included in appendix 1 ultimately for the ethics committee, the virology studies, are not attached to this draft. If you go to page 120, you get to the end of the draft and you will see there is no appendix 1 attached to it.
A The appendix 1 at page 226 is the one referred to on page 221, I agree. You are saying it does not find its way into the earlier draft?
Q What I am suggesting to you is that the earlier draft refers to appendix 1, but does not actually attach it to the back of it and that was the detail of the virology studies.
A It was not sent to the Legal Aid Board, that is correct.
Q We neither of us know precisely what was sent to the Legal Aid Board, do we, but it does not appear to be attached to the back of the draft protocol which was sent to the Legal Aid Board?
A That is correct.
Q I am not trying to catch you out in any way, Dr Wakefield. I am trying to establish the factual background to some questions I want to ask you and I am simply referring to the differences between the two protocols, that is all, because, as we know, one is a draft and one is the final version. I have suggested to you now that the development of your hypothesis into an explanation in the graphs was not present in the original; the virology studies in appendix 1 were not present in the original as we see it. Lastly, I think you would accept that the timetable of the investigation of the children which is attached to the ethics committee application at page 231 equally is not part of the draft that was apparently sent to the Legal Aid Board. We do not have that timetable.
Q Reverting to the draft version, if we just go back to the beginning of that, please, which is at page 104, if you look at that and keep a finger in page 212, which is the ethics committee application version, the title is identical, is it not?
A It is.
Q The responsibilities of the department, if you go on to page 105 and 213, are the same: the investigators are set out and their responsibilities are the same.
Q The analysis of disintegrative disorder, we will revert to that, if we may, but just in terms of the draft at page 108 and the final version at page 215, they are broadly the same.
Q If you go on to page 110, again, the envisagement of the role of “Complement, measles and disintegrative disorder” is in similar terms. Is that correct?
Q Lastly, the actual investigations which were envisaged, which are at pages 113 (the draft) and 221 (the final version) are the same.
Q As far as the earlier protocol is concerned, in relation to the basics of the project – there is a difference between us as to whether it was research or not – as far as the basics of your clinical and scientific study are concerned, they were the same.
A Yes, in essence they were.
Q That is August 1996. Then in September 1996, Professor Walker-Smith writes to Dr Spratt in relation to Child 9. If you would, I would like you to look at the local hospital records, volume 2, for Child 9, please. That is the letter that Professor Walker-Smith writes to Dr Spratt. He says:
“ … I have heard from Dr Wakefield that there is a child called [Child 9] who is resident in XXX whose parents would be quite keen for us to investigate the child in our protocol. I am just wondering whether you think that this is at all appropriate. If you felt it appropriate, I would be happy to see the child.”
Then we see:
“Just in case you may be interested, I am enclosing a copy of Dr Wakefield’s detailed proposal.”
Attached to that, we see at the next page, page 184, is the proposal to which he is referring. I suggest to you – and I think you will accept – that this is the version that was sent to the ethics committee. If it helps you in the identification, if we look at page 198, we see appendix 1 attached and if we look at page 203, we see the timetable attached. Is that correct?
Q So it would appear that this was being sent to Child 9 because you had provided the details of the child to Professor Walker-Smith and, if he was going to be investigated, he was going to be investigated under the terms of that protocol. Is that fair?
A No. Firstly, as with all other potential referrals, the parents had made contact with me and had described their child’s problems as they perceived them, including the problems with vitamin B12 absorption, which you may remember. I, as was my duty, passed this information on to Professor Walker-Smith. Professor Walker-Smith, by way of information to a colleague, passed on the protocol in evolution, as it was, in fact the complete stage by then, to a colleague by way of background. This is again for information. The protocol itself was not prescriptive, but it was a broad outline of the thinking and the investigations that were proposed as part of 172-96. It has been suggested that in some way the formulation of 172-96 and its submission and approval – at least, this is my inference – took priority over the clinical well-being of the children and yet that is illogical, because as Ms Smith has pointed out, the children started to be admitted for clinical evaluation long before the approval was either submitted or approved. So it was the clinical imperative that took precedence and not the research.
Q Can we revert, Dr Wakefield, to the question that I asked you, which was directly in relation to this particular child? I read the letter out to you, but I am very happy to do so again.
“I have heard from Dr Wakefield that there is a child called [Child 9] who is resident in XXX whose parents would be quite keen for us to investigate the child in our protocol.”
He then says he wonders if Dr Spratt thinks it is appropriate and he says, if he felt it appropriate he would be happy to see the child. Then he says:
“Just in case you may be interested, I am enclosing a copy of Dr Wakefield’s detailed proposal.”
The question I asked you was if this child – if this child – were to be admitted, the plan was to admit him and give him the investigations that are set out in the protocol which was sent to Dr Spratt.
A No. Again, there are two elements to this: investigation of the child, and bearing in mind that Professor Walker-Smith was responsible for the clinical aspects, he is there referring, I would imagine, to investigation of this child in our protocol. What he refers to in the second paragraph is a copy of Dr Wakefield’s detailed proposal. At that stage it was a proposal. It was a proposal which was to go before the ethics committee for their consideration and approval or not. There is a clear difference between those two things.
Q You are contending, are you, that when this was sent to Dr Spratt, it was sent for information only. Is that what you are saying?
A Well, it is not my letter and I am therefore not able to offer any further insights into it.
Q It is plainly referring, I suggest to you, to a proposal that this child come in for the investigations set out in the protocol and accompanying it is the protocol.
A Again, it is a matter of fact that this child did come in for clinical investigation and there are certainly elements of the proposal that ultimately came to be approved by the ethics committee that were not undertaken in this child. The clinical investigations most certainly were.
Q Let us look at the next one, September 1996. Child 12 was referred to you and to Professor Walker-Smith – and I am not concerned for the moment about the precise detail of the letter – but we know that Mrs 12 in October 1996 was sent a protocol by her solicitors, and if we look please at FTP1 page 246, this is a letter from Mr Barr. I appreciate it is not your letter and you may not have known it was sent, but the fact is, and this is all I want to ask you about, it enclosed a proposed clinical and scientific study and if we look at the next page we see the nature of that study. I suggest to you – and you are very welcome to check it again – by reference to the lack of an appendix 1 and a timetable on the back, that that copy that was sent to Mrs 12 by the solicitors was the draft copy, the same as the copy that Mr Barr apparently sent to the Legal Aid Board.
Q I am not going to go to the correspondence with you now but I am sure you recall that Mrs 12, having seen Professor Walker-Smith, wrote letters to both you and Professor Walker-Smith about what she thought about the investigations the child was to undergo, whether he should have them or not, and she does indeed refer to having studied your protocol.
A That is correct, and just to make it clear this protocol was sent to Mrs 12 without anyone’s authority, presumably from Richard Barr by way of information. One of the problems that arises in these circumstances if it is provided without information is that it can lead to perception of what that represents that may or may not be the case, and it is not surprising that Mrs 12 perceived this to be research or subsumed under the title of what might be called research. Again, it is not an issue in which I was involved at the time.
Q Let us look, in the light of that answer, at Child JS if you please; local hospital records for JS at volume 1, page 144. This is a letter, you may recall, that Mrs JS wrote to Dr Mills in relation to symptoms that JS had and we are now in November 1996, so we are six weeks on from Child 12 that we have just been looking at. She says:
“I have, this week, heard from Dr Andy Wakefield who has sent me the enclosed information about Heller’s disease. This sounds so much like JS’s history that we find it most alarming.”
She is of course at that stage asking for referral from Dr Mills, but if we look at the attached document, page 145 – again, to orientate you, Dr Wakefield, this is the draft again, not the final document, that you gave to Mr Barr and which fetched up with the Legal Aid Board. This was sent by you to Mrs JS, is that correct?
A That is correct.
Q You are now suggesting that because Mrs 12 gets her document from Mr Barr that that is how she becomes confused, but you too are sending this document out apparently to give information to this mother relevant to her child.
A Again, for the Panel let me explain. The key – I have no problem in principle with Mr Barr communicating this information to parents, but if it goes out without the appropriate information then it can lead to confusion. In this case it was me who was providing to Mrs JS this protocol and it will have gone with explanation from me, and the particular reference in this document and the reason for sending it to her was the fact that her child’s history was remarkably similar to that described as Heller’s disease or disintegrative disorder. It was that information, my distillation of the writings of Professor Rutter and others on this, that was the reason for me sending this document. It is specific and it is referred to by her in her letter to Dr Mills.
Q But this was in the context, was it not, of Mrs JS considering at least referral of her child to the Royal Free?
A It was by way of providing information on Heller’s disease specifically so that she might compare that with her son’s history and communicate that information to Dr Mills.
Q When she read this document, Dr Wakefield, you are not seriously suggesting that she would simply have read the little bit about Heller’s disease and not looked at the rest, which sets out an extensive programme of investigations that you envisaged for children who you thought might have Heller’s disease, disintegrative disorder, whatever you like to call it, and those investigations were set out at page 154, were they not, of the JS document.
A Whether or not she read it does not go to the issue of why it was sent and the reason for sending it, as I have said, was to provide her with some background to Heller’s disease which was entirely consistent, at least in my inexpert opinion, with the description of her child.
Q So the fact that Mrs JS then wishes, quite understandably, to have her child admitted to the Royal Free for investigation of this very condition you are saying is nothing to do with you, is that the line you are taking?
A No, I am not saying that at all. I clearly have not been clear: Mrs JS approached me in exactly the same was as other parents had done, seeking help, seeking referral, and I will have told her exactly the same as I told the other parents, that she should seek a referral to Professor Walker-Smith, in other words she made a spontaneous request for help for her child. It is merely in the context of the description of Heller’s disease that I felt it was congruent at least with her child’s story. I did not expect – although she may well have read the rest of it – for her to have understood the complexities of PCR or the various investigations that would be undertaken, but of course it was in her remit to ask me if she had any questions. I see no further correspondence to that effect.
Q Given that we have agreed that the description of disintegrative disorder in this protocol is identical to that in the final protocol that was submitted to the ethics committee, and given that we have agreed that by now the ethics committee application had been signed off with the finalised protocol, why are you sending to Mrs JS this draft version?
A Because the draft version contained explicitly the description of Heller’s disease that is found similarly in the final version.
Q Is found identically in the final version.
A There was no reason to change what was an historical description of a disease.
Q I understand that, you are not answering the question I am asking, Dr Wakefield, which is why was she not sent the final version? Why was she only sent the draft that had arrived with Mrs 12 by the Richard Barr route?
A Because I imagined that what it contained was adequate for the purposes of describing Heller’s disease in the document itself. I had no reason to – that is it.
Q Are you saying you remember making a deliberate choice to send her this one rather than the other one, is that what you are saying, or are you saying they were in your view interchangeable?
A In the context of the description of Heller’s disease they were entirely interchangeable.
Q If we could look at the JS Royal Free records, Dr Wakefield, and reminding you that the letter we have just been looking at in the local hospital records is 6 November 1996, would you look at the Royal Free records for the same child, please, at page 76? This is a letter of the same day, the very day that Mrs JS is writing to Dr Mills you are writing to Professor Walker-Smith:
This is a child I would like to be included in our study if you consider him suitable. His community paediatrician … was initially enthusiastic … seems to have gone cold. Nonetheless, [he] has been awarded Legal Aid who will pay for the investigations and this is in hand. I would be grateful if you would therefore arrange to see him as an outpatient to assess him for possible investigation in our trial.”
You tell us you were just producing this document as information to Mrs JS, Dr Wakefield, and this had nothing to do with the referral of her child for these particular investigations?
Q Would you like to explain to us how you come to that conclusion, given the letter at page 76 in the Royal Free records which makes it plain that you wanted to investigate this child?
A Yes, it was sent by way of information, giving her the background to what I considered to be a condition similar to that of her child. If this was sent out, as I understand you are suggesting, to encourage people to become part of the trial why was it not sent to every parent, every doctor? It was not, it was sent specifically in this context because his history was in my opinion so consistent with that of Heller’s disease that it described – likely described – what he was suffering from.
Q And you wanted – “would like” the child to be included in the study – “our study” you say to Professor Walker-Smith; in other words, investigated under this protocol.
A It seemed appropriate to me by virtue of this child’s history of gastrointestinal and developmental problems that he would be suitable for investigation clinically and experimentally in a laboratory setting under my control, the latter part. That is the information that I am directly communicating to Professor Walker-Smith with the caveat if he considers him clinically suitable. It seemed to me to be entirely straightforward. Again, it is important to note that the initial request for referral came from the parent, Dr Mills asked me to make contact with him to provide information and I did that.
Q Dr Wakefield, I have taken you through a number of versions of this protocol which fetch up with the parents whose children ultimately fetch up being investigated in Professor Walker-Smith’s department at the Royal Free. I suggest to you that the fact is that these children were investigated under a protocol that you had produced to support your research hypothesis and you produced that both for the purposes of the litigation and for the purposes of your ultimate ethics committee application under 17296.
A Perhaps I should go back again and try and make it clear. The imperative for the investigation of these children, according to a well thought out clinical protocol, decided upon by clinicians, was the overriding aim and, as an adjunct to that, there were scientific investigations included in the same protocol. As Dr Pegg has said in evidence it is entirely usual – not his exact words – it is commonplace for the clinical investigations to be described in a protocol submitted to his committee because without that description it would not make sense – for example, the provenance of a biopsy in the absence of describing the fact that the child was going to undergo colonoscopy. So what was described in the protocol – and I have been emphatic in this – was that this was a clinical and scientific protocol, and that was what was said to the parents, in this case by way of information about the background to Heller’s disease which I felt her child may have had.
Q I have suggested to you that the early protocol in draft and the Legal Aid Board study and the protocol submitted to 17296 and indeed the study ultimately written up in the Lancet are all part and parcel of the same research study, and I want to ask you at this point in particular about two letters which I suggest demonstrate that very clearly. Would you go to FTP2, please, page 471? This is a letter you wrote in May 1997, Dr Wakefield, to Mr Phipps, and he was the director of finance, as we can see at the top of the letter, at the Royal Free Hampstead Trust, the hospital trust, is that correct?
A That is correct.
Q If we look at the very end of the letter, just to remind you of the purpose of it all, it was an important letter, was it not, because you were asking him if he would indicate a willingness to receive the Legal Aid Board funds, and at that time you were aware that the medical school had some misgivings about doing so, were uncomfortable about accepting the money, is that correct?
A That is correct.
Q So it was an important letter which presumably you would have drafted carefully because you were explaining, were you not, to Mr Phipps what it was all about and it was important that if he had misgivings expressed that he really did understand what it was all about, is that fair?
A It was, in contrast to a letter to a medical or scientific colleague, a letter to an accountant and that needs to be taken into consideration in the context of what is written, yes.
Q It is an important letter. Mr Coonan took you through it in sections, in small sections, and I am going to do the same with you because I want to be clear that I understand what you are saying about this letter. Before I do so, I wonder if I might invite both you and the Panel just to read it through quickly again so you remind yourself of the terms of it. (Pause for reading) Now, Dr Wakefield, you are clearly saying, are you not, in that letter that 172/96 and the Legal Aid Board study are the same study as the clinical and scientific study which you say was written up in The Lancet. That is the clear message of that letter?
A It is not clear to me.
Q I will take you through it section by section as Mr Coonan did. Before I do so, one general point. You use the term “recruitment”:
“Children for this investigation have been recruited as ECRs from all over the country…”.
“Recruitment” is very much the language of research, is it not? “Recruiting patients for a study” is not what you do, I suggest, in clinical medicine?
A The mechanism by which the children came to the Royal Free has been described in some detail. The word “recruitment” is an unfortunate one, and it is an error or an inadequate description by me, and you have heard time and time again that the actual process by which these children came was following spontaneous contact and request by the parents, the GP/paediatrician’s approval of a clinical referral, Professor Walker-Smith. This letter should be seen in that context.
Q When you say it is “an unfortunate description”, Dr Wakefield, you mean it is certainly an unfortunate description on your present explanation as to how these children ended up being investigated at the Royal Free?
A The evidence for how the children came to be seen has been demonstrated throughout the clinical records so, once again, the word “recruitment” does not accurately reflect that process.
Q I am going to look at this. As I say, I would like to break it up as Mr Coonan did. If anyone wants to look at that later, it is Day 50/2. If we may, we will look at paragraph 1 first of all, where you say:
“My group, The Inflammatory Bowel Disease Study Group, is currently involved in the investigation of a cohort of children with regressive autism and inflammatory bowel disease. The study is being undertaken in collaboration with Professor John Walker-Smith in the Department of Paediatric Gastroenterology. The study has provided some ground-breaking insights into the mechanisms of autistic spectrum disorders, and in particular, the role of intestinal inflammation in this condition.”
You have told us that when you said that, you were referring, indeed, to The Lancet children who had been seen under the clinical and scientific protocol in that first paragraph. Is that correct?
A No. You will note that this letter is 23 May 1997.
A That is beyond the time of approval of 172/96, which was in December 1996. Beyond that time, many more children had in fact been seen. So this letter encompasses both the early children and, with more specific reference to currently the children who were seen beyond The Lancet 12.
Q And then we go on. Can we just look at the first five or six sentences of paragraph 2:
“Children for this investigation have been recruited as ECRs from all over the country and indeed, as private patients from the United States of America. In order to initiate the study, Martine Else and the Special Trustees of the Royal Free Hampstead NHS Trust were kind enough to set up an account to fund Ms Rosalind Sim as the technician to process the samples taken from the children.
This has proved to be most successful and will continue to be a major source of revenue for the Trust itself.”
And you told Mr Coonan that that was applying to the same study as the first paragraph. In other words, to the scientific and clinical study?
A Yes. Ms Sim’s research activities involved the analysis of biopsies at that stage either for the presence of viruses or by way of characterisation of the disease process. That was an element that specifically under my remit and was a research element.
Q Then we go on from there onwards to the end of the paragraph:
“In addition, we have been awarded a grant of some £50,000 by the Legal Aid Board to investigate the possible association of this syndrome with the MMR vaccine. This money has been provided through Dawbarns Solicitors (see enclosed documentation) for the express purpose of performing the study outlined in the enclosed protocol. This protocol, as you will see, has been approved and passed by the Ethics Committee of the Trust. The cheque for the first instalment of this grant was initially paid into the Medical School, but queries have been raised by The Dean, since this source of funding has never been obtained before. I have discussed this with both Professor Pounder and Cenghiz Tarhan and we are agreed that the money would be more appropriately located in the account currently held to pay for Ms Sim, since this account pays the existing expenses of the same study (ie salary).”
You told us, when Mr Coonan took you to that passage, that you were then talking about the Legal Aid Board study, as you obviously are, and you say that that has ethics committee approval, and you said that the ethics committee approval is indeed 172/96, because the viral detection for the LAB study was subsumed under 172/96. Is that correct?
A Yes. The same study refers to Rosalind Sim’s detection of the virus in the tissues. That is the purpose of the LAB study.
Q The section which ends up referring to the same study must mean the study that you referred to in the beginning paragraph and a half, must it not?
A It is a fact that the LAB pilot study, at least in part – that part that refers to the five children with autism, as opposed to the five children with Crohn's, was subsumed under 172/96, that is the ability to analyse biopsies for viral material. It is also a fact that it was subsumed under 162/95, although that is not material to this current discussion.
Q But you say in the middle of that paragraph, doctor:
“This money has been provided … for the express purpose of performing the study outlined in the enclosed protocol.”
Then, at the end of the paragraph, you refer to “the same study”. You can only mean by that the enclosed protocol was the 172/96 protocol, was it not?
A The documentation provided to Mr Phipps would have been the entire documentation, including the LAB costings proposal and the LAB protocol. Again, with respect, I am communicating to an accountant in what I am hoping are relatively uncomplicated terms the fact that the documentary evidence that is provided to him is supported by a current ethical approval and describes to him in some detail for the purposes of the LAB pilot study what it is we intend to undertake.
Q But, Dr Wakefield, you are very enthusiastic, if I may say so, about analysing the precise words of the documents that we are looking at. Where do we see in that document any reference to there having been two separate protocols attached to it? There is none, is there? You refer very specifically to “protocol” in the singular.
A I have referred to “the enclosed documentation”, and that will necessarily have included the documents relevant to the LAB pilot study.
Q Let us go on to the next paragraph, please, the third paragraph.
“I should add that the conduct of this study and the discoveries we have made have elevated the Royal Free Hospital to great heights in the world of autism research. The clinical profile that it has provided has greatly benefited the Trust. We are receiving referrals on a daily basis and the funding provided by the Trustees will continue to help us investigate these patients appropriately.”
And you said to Mr Coonan that when you got to that bit of the letter, where you say “this study”, that was a reference to the clinical and scientific protocol under which The Lancet children were seen.
A The funding provided by the Trustees, if the Panel will remember, was to pay for the salary of Ms Rosalind Sim, whose job was divided into two parts; one was what we considered to be the appropriate scientific investigation of the disease process itself, that is characterisation of the disease, the different cells that made up the inflammatory process. That was a large part of her work. The other part was viral detection including, but not exclusive to, measles virus. That funding provided by the Trustees continued to help us investigate these children appropriately. That is a correct statement. That is my position.
Q That is your position, but not on the point that you were asked, Dr Wakefield. What did you mean? Which study were you talking about when you said, “I should add that the conduct of this study and the discoveries we have made have elevated the Royal Free Hospital…”, et cetera, down to, on the next page, “…investigate these patients appropriately.” Because when Mr Coonan broke it up for you in that way, you said you were then referring back not to the Legal Aid Board study, which is in the preceding paragraph but back to the start of the letter. You were there referring to The Lancet children.
A I am referring there, if you like retrospectively, to what the Special Trustees’ funding has enabled us to do to that point.
Q Can we go on to the next page? There we get the last bit that Mr Coonan put to you, after “investigate these patients appropriately”, we get:
“The study itself, although commissioned by the Legal Aid Board, seeks only to establish the validity of the parents' claims of an association with MMR or not, and not to provide a specific answer, that is that vaccine as the cause. This is the only condition upon which we undertook to do the study and the Legal Aid Board have agreed to it.”
You have told us, and indeed it must be the case, that you are there referring once more to the Legal Aid Board study covered– in so far as it was – by 172/96?
A There I am referring to the prospective study envisaged and funded by the Legal Aid Board, pending the approval of that funding by the Special Trustees, specifically for the purpose of viral detection.
Q This was a letter, you told us, in which you hoped to make things clear to the director of finance at the hospital, who you were asking to accept money which had a question mark over it, if you like, by the school – the medical school – in relation to the involvement of Legal Aid Board money. That is what you were asking him to do. That is correct, is it not?
A I am trying to help him without, becoming overly complex to an accountant, to accept the money on the basis that it will be used for the Legal Aid Board pilot study. I have at the end asked if there are any queries, that he should not hesitate to contact me. I hope, therefore, that he was satisfied at that stage that the Legal Aid Board study would be funded from the funds received and potentially approved by him and Mr Else for the purpose of viral detection, as set out in the protocol provided to him.
Q Dr Wakefield, if you go through the letter in this way saying that in various different paragraphs of it you are referring to “study” in different ways, and you have now told us you were not referring to one protocol, you were referring to two protocols although you only refer to one protocol, how would you expect that to be remotely intelligible to Mr Phipps?
A I imagine what I was trying to do was to describe to him a continuous process. He at least seems to have been satisfied, on the basis that I do not see him referring back to me, specifically on these matters.
Q May I suggest to you that the reason that he did not refer back to you he is because he read that letter as any normal human being would read it, I suggest, namely that you are plainly referring to one and the same study throughout?
A How he interpreted it I simply cannot say. The documents that were provided to him will clearly have been essential his assimilation and interpretation of what this letter meant. It was open to him with those documents to hand to come back to me if he had any concerns.?
Q As I understand it, you say that the Legal Aid Board protocol was relating to viral detection studies only; in other words, they did not have any clinical elements to it.
A Again, I will come back for the Panel’s benefit to what was asked of me in the first place by Mr Barr. He asked me how I would go about trying to determine whether there was a causal relationship between MMR vaccine and the particular syndromes of either Crohn's disease or, in this case, autistic enterocolitis, or autism with bowel disease. I pointed out to him that my approach would be to conduct a viral investigation study. He asked me to provide a summary of costings which included all potential costs. I asked him what he meant by that because as far as I was concerned, the viral detection studies is a laboratory element, and will involve the cost of a technician, and the reagents to do that analysis. He said to me, “What about the costs of clinical investigation? What about reports from colleagues?” At the time, I did not see that these would be necessary at all because, in fact, the children merited investigation or would only be admitted for investigation based upon clinical indication. That was an absolute. So the investigations being clinically merited would mean that their clinical investigations being covered by the National Health Service, but in the unlikely event that that was not the case, then there should be funding available to cover those costs. This issue only ever arose once, and that was in the context of Child JS and, as a matter of fact, the funding was not required from the Legal Aid Board for that child’s care. So to the extent of my intention, yes, that was purely a viral detection study.
Q Thank you. Dr Wakefield, can I stop you there – I do not want to inhibit you from saying anything that you want to to the Panel, but you are, I do warn you, going to have to come back to this in very considerable detail later on. The only questions that I am asking you at the moment, which I think you have ultimately answered, was that as far as you were concerned, the investigations that you did on behalf of the Legal Aid Board were viral, were virology, were virological studies?
A Yes. They were exclusively viral.
Q Thank you. I want you to look – if you remember, I told you we are half-way through an exercise of looking at two letters. We have looked at the first one. I want you now to look at the second one, which is a letter that you wrote to Mr Else at page 493. Can I make it clear to you. I know this letter talks about conflicts of interests. Again, we are going to come back to that. I am not asking you about that aspect at the moment. May we look at that letter? This is to Mr Else.
Further to our conversation the other day and your subsequent letter, I am writing to confirm that there is no conflict of interest in relation to the Legal Aid funding for our clinical study of children with autism and intestinal inflammation.”
That is what you are saying the Legal Aid Board were funding – a clinical study. That is what the letter says, does it not?
A Clearly the use of the word “clinical” is inappropriate there.
Q Like the use of the word “recruitment” in the last letter. Inappropriate to what you are now telling the Panel.
A There are a number of ambiguities and imperfections in the use of the English language in this correspondence. It was written, as the Panel will appreciate, at a time when one did not anticipate that it would be scrutinised in quite the detail that it has been. However, the letter is important, because it says to Martin Else that – and one has to understand that this study has not started, the Legal Aid Board study has not started, it is not under way and yet by this stage, as referred to in the final paragraph, The Lancet paper, the clinical analysis of the first 12 children, the case series, has already been submitted. The funding is not yet available for the start of the Legal Aid Board study. Therefore by definition it could not have started.
Q I think we all understand that that is your case, Dr Wakefield, and we will be coming to it. I can tell you it is not accepted for one moment that the Legal Aid Board study had not started. You have anticipated the next question which I have for you, which is in relation to that last paragraph. Perhaps we can finish with the first paragraph to begin with. You now accept that to refer to Legal Aid funding for a clinical study of children with autism and intestinal inflammation is not what you now say you were using the Legal Aid Board money for and, if we go on to the last paragraph:
“Please find enclosed a coy of our first paper submitted to The Lancet concerning the children under investigation. This has been an extremely successful study and has clearly demonstrated a new pathology in these children ….”
Again, I suggest to you that that is clearly saying in the context of an overall letter and given what you said in the first paragraph that the Legal Aid Board funded children are being written up in The Lancet and had been written up by virtue of an Legal Aid Board funded clinical study of their difficulties.
A Again, I am afraid I do not read it as that. It says:
“Please find enclosed a copy of our first paper submitted to The Lancet concerning the children under investigation. This has been an extremely successful study …”
That refers back to the clinical case series and presumably some of the children who have been seen now up to the date of 3 July 1997 which has, as stated, demonstrated what looks to be a new pathology. That is a measure of its success.
Q It is the same study as the one you refer to in the first paragraph.
A No, it is not. On the contrary, by this stage clinically some 40 or 50 children will have been seen. The Legal Aid Board pilot study refers specifically to five children with Crohn's disease and five children with autism and was a viral analysis study. The success inherent in this study or referred to in this is to the description of an apparently new bowel disease in these children.
Q You see, there may be a distinction, Dr Wakefield, and I suggest to you that there is, between what you said to Mr Phipps and Mr Else at the time and what you are now saying. I suggest to you that at the time both those letters make it clear that you yourself were treating the clinical and scientific study, the 172-96 study and the Legal Aid Board study which was a part of it and The Lancet paper, as all part and parcel of the same study and that is why these letters refer in both to “the study”.
A No. I am very happy to go through for the sake of the Panel in great detail what the difference is between these various elements are. I am happy to do that at some length.
Q You have been through it in great detail, Dr Wakefield, and I am suggesting to you that that detail, that interpretation that you have put on it, is a retrospective interpretation and that in order to get out of a sensible and straightforward interpretation, you have to embark on this tortuous exercise of picking out bits of letters and telling us they refer to different studies and different protocols rather than reading them overall.
A Let me step back from that, because it was not me who was picking through elements of letters, but let me just say that for the sake of clarity, The Lancet 12 was a case series and it preceded, the initiation of that case series, preceded the submission and approval of 172-96 and indeed the examination of those first 12 children was instrumental in defining what the ultimate protocol was to be. Investigation of those children took place on clinical grounds and it involved an assimilation of the clinical histories and the clinical findings and that was assimilated, and some research, adjunct research, which involved detailed analysis of biopsies, that was then submitted to The Lancet as a case series. It had funding from ECRs and there were small elements of funding from the children’s charity for MMA estimations.
The Legal Aid Board pilot study, a different thing altogether, was an analysis of biopsies for the presence or absence of measles virus on five children with Crohn’s and five children with autism. That study, permission for which was subsumed under 172-96, did not start and could not start by definition until the funding for that study was available. Until that time, the investigations on the biopsies conducted as part of my research were conducted by Rosalind Sim and funded by the special trustees of the hospital. It would have been entirely inappropriate to conduct such studies and describe the provenance of the funding for those studies to another source had it, for example, not been the case. It could not, it would not be appropriate, to describe the early viral detection studies funded by the special trustees as part of the Legal Aid Board pilot study. I have tried to separate these issues out in order to assist the Panel and we seem to have come back to a position where they have been conflated once again into the same thing for the purpose of sustaining the charge, but they were not.
MS SMITH: Sir, I see it is nearly 11 o’clock. I am turning on to another section, so if you were going to have a break, this would be I think the appropriate moment to do so.
THE CHAIRMAN: Thank you very much, Ms Smith. We will now adjourn for our mid-morning break. We will resume at 11.20. Once again, Dr Wakefield, you are still under oath, so please do not discuss this case.
(The Panel adjourned for a short time)
THE CHAIRMAN: Ms Smith?
MS SMITH: Dr Wakefield, I want to turn on and look with you, if I may, at the actual 172-96 ethics committee application which was made. First of all, I want to ask you some questions generally and then we will look specifically at the information which was given in the form. We do not need to look at the documents for us all to recall that it was signed off in August 1996 by Professor Pounder. That signing off, we can assume, meant that he was satisfied at least in overall terms that all was in order and presumably that it was in its final form.
Q At the time it was signed off, we have already agreed that only one child had actually been investigated. What I want to ask you is this. Is it your case that you then saw all the other Lancet children and then you started to do project 172-96, or is it your case that you never did 172-96 at all?
A That is a very interesting question. The reason is that when it actually had been approved and at the start of its enactment, a number of elements had not been done or were never done, for a variety of reasons. They were research elements. Really, the only research element that continued was in fact the biopsy analysis. This has been something of a matter of discussion, because the biopsy analysis was clearly covered by Professor Walker-Smith’s existing approval 162-95. So theoretically, the research that we did beyond that point, or that I did beyond that point, and indeed was done in Professor Murch’s laboratory, was in fact covered under 162-95. Nonetheless, we had two approvals for that: 172-96 beyond 18 December, 19 December – I cannot remember which – and the pre-existing 162-95.
Q Is it your case, Dr Wakefield, that you saw all The Lancet children and then you started 172-96, or is it your case that you never did 172-96 at all?
A I think in pragmatic terms, the former. The children, The Lancet 12, were not part of 172-96 and that beyond that point, at least the research that I was conducting was covered by 172-96.
Q Let us just explore that. From the outset of this study, you were thinking about ethics committee approval. Is that correct?
A That is correct from my research perspective, yes.
Q You submitted an extremely detailed document to the ethics committee, the application and the final protocol.
A Sufficiently comprehensive that it covered what we intended to do, yes.
Q It must have taken a considerable amount of time and effort prior to August 1996 when it was signed off.
A Yes, it did. It took a lot of consideration. It took a lot of interaction with colleagues, discussion with experts, which resulted in the final synthesis of 172-96.
Q So that prior to August 1996, you must have been thinking about both the final terms of the protocol and the ethics committee application.
Q You told us on Day 48/51 that the reason for the application to the ethics committee for approval was to deal with what you described as the “brand-new research elements which were not approved under the existing analysis of biopsies.” Is that correct?
A Yes. There were additional research elements which from all of our perspectives, but certainly from mine, required approval.
Q I already suggested to you on Friday and I think we are agreed that those elements which you say ultimately needed 172-96 approval were present in the early draft protocol which we have seen.
A They were present in the research aspects of the protocol as part of the evolution of the process, yes.
Q Whatever may be the position as to the precise date of that protocol, they are certainly formulated in the protocol that gets sent to Mr Barr which he ultimately sends to the Legal Aid Board, the first draft.
A The headings, if not the detail, yes.
Q So they were not brand-new; you had always known that you wanted to do them, to give you the absolutely benefit of the doubt, at least since the latter part of the first half of 1996.
A They were new with respect to the fact that they were not contained within 162-95. They were not addressed in any existing ethical committee application and therefore for that treason they required an independent approval.
Q But you said that you made the application to the ethics committee for approval because of brand-new research elements.
A Brand-new in as much as they had not been conducted before and required an independent ethical approval, correct.
Q Why would you want to implement the original draft protocol under the 162-95 approval which did not allow you to do what you already envisaged that you were going to do under 172-96?
A 162-95 allowed the conduct of research on biopsies. In order to understand or try and understand the complexity of what might be going on in these children, it was envisaged by me largely that further research investigation such as the complement genetics would be required, that 162-95 and the biopsy analysis was not in itself sufficient to provide any insights into that. So new research elements such as the complement genetics were added in to create the overall protocol of 172-96.
Q Why not just apply for ethics committee approval to do the entire investigation and defer your programme of investigation on the children until you had ethics committee approval?
A Sorry. I misunderstood the question.
Q Why not just apply for ethics committee approval and defer your programme of investigations of these children until you had that approval?
A The reason that the children were investigated was on the basis of clinical need – and this is a clinical question best referred to the clinicians – but the imperative was for their clinical well-being to be evaluated. So that was the driving factor; that was not something that could in the opinion of the clinicians await approval for a research investigation. It was entirely appropriate and contained within 162-95 that research investigations might be conducted on biopsies. The additional research elements had no bearing whatsoever on the clinical well-being of the children and
were part of what was deferred and ultimately most were never undertaken as part of 172-96. I am not sure I have answered your question, but I am finding it difficult to quite understand.
Q I am quite happy to put it to you again, Dr Wakefield. What I am asking you is: why did you start, if you like, to implement your original draft protocol? Why not wait until you had ethics committee approval for 172-96 and then do all the investigations which you envisaged? Why start on the children? That is what I am asking.
A It was not my decision. The decision, as I say, was driven by the clinical imperative.
Q But you see, the trouble with that answer is that there was no sign, was there, of the clinical imperative that you are now relying on in relation to the seeing of these children? We have already looked at the correspondence this morning and we have seen references by both you and Professor Walker-Smith to waiting until the protocol was completed and then putting them in a study.
A What Professor Walker-Smith was referring to in that context was optimising as far as possible the clinical investigation of the children so that they could be examined as comprehensively as possible to provide a clinical diagnosis. That is why it was initiated in my opinion – and again, Professor Walker-Smith will be able to speak to this – but it is precisely because of the clinical imperative that it was initiated under existing approvals before such time as 172-96 was approved. It may be that 172-96 would never have been approved, but that does not obviate the clinical need for investigation of these children.
Q So you are saying that the clinical imperative was such that it required the investigation of these children prior to the finalisation of your application to the ethics committee but that there was not sufficient clinical imperative to get these children in until you had finally formulated your clinical and scientific study.
A Again, all I can speak to is the research elements of the protocol, the rest of the question is better directed to the clinicians.
Q Perhaps I could ask you the next question which is once you have got ethics committee approval – and we know that you did get it as of January 1996 (sic) – why do you not start using it, why do you go on not using it in respect of the remainder of the children in the Lancet?
MR COONAN: The reference should be January 1997 not January 1996.
MS SMITH: Thank you very much, 1997. Do you want the question put again?
A If you could, please.
Q What I said to you was once you had got ethics committee approval – which is January 1997 – why do you go on not using it for the remainder of the children in the Lancet, why do you not use it for the remaining children that you have?
A I would imagine that at that stage the natural hiatus that I referred to before was at the point of referral of a certain number of children, even though the first 12 had been referred and the clinical decision had been taken for their investigation. Once the letter was received from Dr Pegg indicating that approval had been given, Professor Walker-Smith convened a meeting to discuss the contents of that letter. That letter or the experience prior to that letter had led to the perception that certain tests were no longer required and, additionally, I felt that measuring intestinal permeability as a research test might give us valuable further information. As I say, the first 12 represented the pilot clinical experience of these children that defined the subsequent investigations. There was no need, in light of the fact that the children had already been referred by that point, for them to be investigated under 172-96. As I have referred to earlier, 172-96 was finally refined into its ultimate working document with the removal of the neurological tests. The intestinal permeability was not included, it was part of a separate application, but that is really the reason why 12 children were written up as a case series in the Lancet.
Q Dr Wakefield, you keep underlining the fact that you were responsible for the research elements and that is what I am asking you about. We have established that in the first draft of this clinical and scientific protocol that we have you set out the research that you wanted to do which ultimately fetches up in 172-96, that is correct, is it not?
A That is correct.
Q So that from your point of view as a researcher is what you needed to do on these children.
A It is what I wished to do in order to adequately test the hypothesis that I put forward.
Q Are you telling us that having got your ethics committee approval you agreed with the clinicians that you would not do those tests for which you had ethics committee approval?
A No, the ability to conduct the tests – and if I understand you correctly one is referring to the further scientific investigations – the complement genetics, the B12 metabolites requires that you have adequate funding and willing collaborators. Ultimately, either one or both of those were not available and so those elements of the studies were not undertaken. In contrast the research on the biopsies had proven extremely interesting and had diverted our efforts further into that analysis and that, again, as I have said in my evidence, is the purpose of a pilot study, it is to direct the way in which your further researches go.
Q We are agreed, are we not, that four or possibly five of The Lancet children were those on whom you were conducting the Legal Aid Board studies?
A Ultimately, yes.
Q And the Legal Aid Board studies were 172-96 approved, you have told us.
A The approval, the ability to conduct the analysis on the biopsies, was subsumed under 172-96, yes.
Q Then once you have your ethics committee approval you are in a position, are you not, where at least in respect of the Legal Aid Board children you were conducting 172-96 investigations?
A The analysis of biopsies was conducted in a research setting by Ros Sim under 162-95 pursuant to the admission of the children, starting with Child 1 and carrying on from that point. The enactment of the Legal Aid Board study, the precise terms of the Legal Aid Board study, viral detection, started in September/October 1997 when the funding for that study ultimately became available to be spent.
Q I am going to revert to just how much you knew about 162-95, Dr Wakefield, a little later if I may, but I want to be clear first of all about exactly what you are saying. You are saying you began the investigations on The Lancet children, you got ethics committee approval for 172-96 in January 1997, you continued on The Lancet children without availing yourself of the approval you had, is that correct?
A Could you repeat the last bit?
Q You continued on the children after you had got ethics committee approval without availing yourself of that approval.
A Without availing myself.
Q Without using the approvals you had under 172-96.
A In your opening question of this session you asked me which was it and we were using 172-96. In my opinion we could have used either but my work was conducted, I felt, from that point on under 172-96.
Q So that means that the last four of The Lancet children, in other words those after January 1997, were indeed on your own case 172-96.
A If I can stand back again for the purposes of the Panel and explain that the key element as far as I was concerned is that for the research elements that I was undertaking in my laboratory there was an existing appropriate ethical approval, and that is the case at all times in the investigation of these children.
Q What you said on Day 49 at page 23, Dr Wakefield, was that you understood that after ethics committee approval it meant that the research elements set out in the application over and above the biopsy and analysis could now be started on patients admitted after this point. That is what you said, was that your understanding?
A That is absolutely correct. Those additional research elements – and I will define again what they are – by memory the complement genetics, the study of vitamin B12 coenzymes were now permissible beyond the date of approval of 172-96 and they could theoretically therefore be conducted.
Q In fact, as I understood from your previous answer, you are saying that after that you did carry out those investigations, perfectly legitimately, under your ethics committee approval 172-96.
A No, in fact those investigations – I obviously did not make it clear – those additional investigations were never performed. I include, for example, cytokine analysis in cerebrospinal fluid, it was never performed, complement genetics: never performed; vitamin B12 coenzymes: never performed, so what really continued was the analysis of biopsies and that was approved under 162-95 and under 172-96.
Q So you are saying that you conceived from the outset of the earliest protocol that we have a wish to undertake scientific analysis on these children. You over the ensuing months drafted an ethics committee application, you put that ethics committee application in, you got permission under that ethics committee application but you never carried out the investigations on the children after you had that approval. That is your position, is it?
A The additional research elements, over and above the analysis of biopsies, as set out in the protocol, were not undertaken.
Q So you went to all that trouble and then you did not do them. Why not?
A Ms Smith, I travelled the world in order to try and identify collaborators who would help us with this project. Let me just give you an example of the complement genetics studies. I first approached a Dr Law at Oxford University and after initially enlisting his help he decided that what he could do was not going to contribute further to this work. He did recommend a Professor Knauff in Hamburg, in Germany, and so I flew to Hamburg to meet with Professor Knauff. I lectured to his unit and I again tried to recruit him to collaborate in this; he was initially keen but the costs of such a collaboration were such that we could not raise the funding to do it. There was no lack of will on my part, no lack of intention, but purely for practical reasons these tests could not be undertaken and therefore the hypothesis as set out could not be fully tested.
Q Then how is it that you come to make an application to the ethics committee setting out very clearly who all your scientific collaborators are going to be and where your funding is coming from and get approval on that basis? If we look at page 213 we see the collaborators set out, Dr Wakefield.
A What one does not set out is where the funding is coming from. The purpose of that document that Professor Walker-Smith submitted was to ascertain the costings, how much would each individual element of the study cost. Again, let me step back and give you an example. If you are putting in an application to the Wellcome Trust then you need to not only articulate the hypothesis and complete the protocol but you need to provide costings, that is a preliminary exercise. You also, for many granting bodies, have to demonstrate evidence of ethical approval having been granted for that study; you cannot presume that you are ultimately going to get that funding, it may simply be that when reviewed that grant is considered inadequate or irrelevant or not biologically plausible. That is not a question or a reflection of a lack of intent on the part of the researcher.
Q Would you look at page 122 in FTP1? I am going to ask you a lot of questions later on, obviously, about this costing proposal, Dr Wakefield, and I am not at this stage making any points in relation to what you asked the Legal Aid Board for, but the point I am making is that you have told us that you did have funding from the Legal Aid Board for the vitamin B12 and complement studies, and we can see them referred to there, a combination of molecular, histochemical and vitamin B12 and complement studies. So at some point, we are all agreed, you did have that money and used it for that purpose.
A No, the funding that we were allocated – not even allocated, we were awarded – from Richard Barr, that he was awarded from the Legal Aid Board – we were awarded up to £55,000 for the conduct of that study, not £55,000 but up to £55,000. Detailed in the setting up costs are the laboratory elements of that for the viral detection studies. That was the only certain costs, the other research elements outlined there were never billed.
Q Doctor, I do understand that and, as I say, I do not want to stop you but I will come on and give you every opportunity to explain that to the panel. I am interested in that first part of your answer just for the present purposes because what I am suggesting to you is that certainly so far as the Legal Aid Board children were concerned you had funding to do the virological tests that you have told us were permitted under ethics committee approval 172-96. The only question I am asking you at the moment is why if you have funding and ethics committee approval you are telling us that you never did 172-96 investigations even on the four children who were covered by the Legal Aid Board study.
A We did, we did the detailed viral analysis which consumed the entire cost – the setting up cost that is, of £26,500.
Q Absolutely, so you did do the 172-96 investigations that you were given permission to do, the research investigations, on the four children and maybe five, as we have discussed, who ultimately end up in The Lancet paper. That is the only point I am making; in other words 172-96 on your account must have covered four of The Lancet children and, as you appreciate, we are suggesting it covered all of them, but that is another issue.
A I have made it absolutely clear that the analysis of the biopsies as part of the Legal Aid Board study in terms of ethical approval was subsumed under 172-96. That is not at issue.
Q You see, this is all extremely complicated, Dr Wakefield; may I put to you a rather simpler explanation, and that is this. The truth is that you had, as we have discussed, what you believed was an inspiration. You came up with a hypothesis, in accordance with the normal course of events, as we have discussed, you devised a protocol, you sought ethics committee approval for that protocol and the reality is that you – by you I mean you and the clinicians – started work before they had approval on children who did not merit the entry criteria under that study.
A Who did not merit what, sorry?
Q The entry criteria under that study. In other words you went through all the hoops of seeking ethics committee approval but then you began to investigate children before you had approval and, furthermore, you investigated children who did not fit properly with the entry criteria for the study.
A I think Dr Horton in his evidence made the iterative process of clinical science quite clear, and that is that you have a group of children presenting over a period of time with a specific constellation of signs and symptoms that merit clinical investigation and, in parallel with that, maybe the evolution of a thought process about what the constellation of symptoms is due to, what the interrelationship of those symptoms might be, and that there is an initial clinical pilot study. I am sure we will go to it, but there are key documents from both Professor Walker-Smith and from myself to Dr Pegg of the ethics committee appraising him of the sequential emergence of the bowel disease in the children in the clinical pilot study.
That clinical pilot study defines your subsequent approach to the investigation of these children, including research elements that form what is to become, in this case, 172/96. That is the natural process of the evolution of what we were doing.
Q That is one way of approaching a research investigation, is it not, Dr Wakefield? I accept it is one way, but what I am suggesting to you is that it is not the way that you were going. What you were doing was evolving a protocol, applying for ethics committee approval for that protocol and that you got ethics committee approval for that protocol but had already started on both your research and the clinical investigations of these children?
A I am afraid Ms Smith is wrong. We made it absolutely clear, as I have said on repeated occasions, to the chairman of the ethics committee how many children had actually been seen as part of the pilot study and what the findings in those children were, referring specifically to Professor Walker-Smith’s letter to Dr Pegg confirming that these children were undergoing investigation on the basis of clinical need. In other words, there was a complete openness with the chairman of the ethics committee that a group of children which formed the pilot study had been seen and evaluated prior to the approval of 172/96. I am slightly perplexed as to why, having disclosed all that information in some detail to Dr Pegg, it should not be construed that we were starting 172/96 in advance of his Committee’s approval. Moreover, the consent forms contained within the children’s records that the Committee have been taken to many times were explicitly part of 162/95, a pre-existing ethical approval given by Dr Pegg’s Committee.
Q I am going to address all those aspects with you, Dr Wakefield, but I am sure that you will appreciate that we have to work through the documents in some kind of chronology and I want to look first of all, if I may, at the actual ethics committee application before I go on to ask you about the correspondence subsequently with Dr Pegg. Could you go that, if you please, at FTP1 at page 200. Page 200 is the first page of the actual application. Would you keep your finger in that, and go to page 233, we see that the document is ultimately signed off by you. Is that correct?
A That is correct.
Q If we go to the protocol – for instance, if we look at page 213 which is the clinical and scientific study protocol that was attached to it – we see that you are named half way down the page as a senior lecturer and coordinating investigator. As I understand it, that role meant that you were coordinating all the investigations which are set out both on that page and the top of page 214. Is that correct?
A No, it is not correct. What I was responsible for coordinating was the collaborative multi-disciplinary interaction.
Q If we go on to page 223 – we have looked at this briefly – but you also had a responsibility to coordinate referrals for admission. We see that set out:
“ii. Referrals will be co-ordinated by [you], JW-S [Professor Walker-Smith] and SM [Professor Murch]…”
such that they will be admitted for colonoscopy preparation, et cetera. Is that correct?
A Yes. I have described the circumstances of my involvement in the coordination.
Q I am sure that you will accept, with me, they are not just empty titles. They did actually mean that you had an overarching role, if you like, as you have described in relation to the coordination, and that you were a responsible consultant in addition, responsible for the carrying out of the study along with Professor Murch and Professor Walker-Smith. And we see that extra title on page 200. Is that correct “Responsible consultant(s)”?
A Yes. Over and above my role in coordinating the multidisciplinary team, my specific responsibilities are set out in this document.
Q If we turn on to look at the title, which is on page 201:
“A New Paediatric Syndrome: Enteritis and Disintegrative Disorder following Measles/Rubella Vaccination.”
That puts the emphasis, does it not, both on the fact that this was a new paediatric syndrome and that there was as an essential part of the study an intention to investigate the possible link with vaccination?
A I have referred earlier in my evidence to the fact that this title was incomplete – a word was missing, or two words were missing – and the correct full title is on page 212 in the document that accompanied this:
“A New Syndrome: Enteritis and Disintegrative Disorder following Measles and Measles/Rubella Vaccination?”
Q Leaving aside that mistake that you say had occurred just for the moment, for the purposes of these question, the fact is that that title, whether or not it involves a mistake – which I will look at with you in a moment – makes it clear that an essential part of the study that you were undertaking was to investigate the possible link with vaccination?
A That is correct.
Q And certainly on its reading, it is clearly a study into children who were vaccinated and only those children, on its reading?
A No. Again, this must be seen in the context of the correct title found on page 212.
Q I will come back to it, if I may, Dr Wakefield. I just want to go through the bare facts of the document first. We have an objective, and that says:
“We will test the hypothesis that in genetically susceptible children, measles vaccination is associated with persistent enteric (and possibly CNS) infection, enteritis and malabsorption of vitamin B12.”
So that that objective clearly, again, involves at least – I will come back to the issue in relation to wild measles – looking at children who have undergone measles vaccination?
Q The two features of the presenting children which are emphasised both in the design of the study and, indeed, in the selection criteria are that they will manifest disintegrative disorder and, secondly, that they will have signs and symptoms of gastrointestinal disease, and we see that in paragraph 4. Sorry – are you with me? Paragraph 4 on page 201 under “Design of the Study”. I am in the second sentence:
“Children … who manifest disintegrative disorder and symptoms and signs of intestinal disease will be admitted to Malcolm ward for a period of one week..”.
A That is correct, and this clearly does not imply necessarily a firm diagnosis of disintegrative disorder but manifestation of that disorder, and signs and symptoms of intestinal disease, correct.
Q The plan, as we go on down the page, is for a standard approach, is it not? I.e., there is no suggestion in that of tailoring to the individual. That is a standardised set of tests which it was envisaged the children would undertake?
A It is not necessarily prescriptive. It is determined by the clinical indication, the clinical tests in particular are to be determined by the individual child’s clinical presentation. That is a clinical issue and, again, will be dealt with, I am sure, far more appropriately by the clinicians.
Q Nonetheless, there is a pattern of investigations which it is envisaged will be carried out – a list, if you like, of investigations?
A There is a compendious list of investigations that may be applied if the appropriate indication is there.
Q Because, of course, it was not known to you at that time what form this new syndrome, this potential disorder, took or what the intestinal or cerebral pathology might have been underlying it?
A That is correct.
Q You could not adopt a standardised approach unless you had simply decided that, as a research project, the children were, with ethics committee approval, to undergo those investigations?
A Again, this is straying onto areas in which I have little expertise. My tests, my laboratory investigations as an adjunct to the clinical investigations, clearly could only be performed if the samples became available through that clinical investigation. In that respect also, it was not a prescriptive set of investigations from my perspective.
Q But those investigations, if we just run through them: assessment for disintegrative disorder, routine ileocolonscopy and endoscopy, barium meal follow-through, MRI, EEG and evoked potentials; lumbar puncture, serology (for blood testing) and vitamin B12 studies – they were a prerequisite for these particular research tests that you wished to do, were they not? The actual investigations on the children obviously a prerequisite?
A The adequate testing of any hypothesis in a study does not necessarily mean that in every child the conduct of that test is a prerequisite.
Q That is not actually what I said to you, Dr Wakefield. I am making a point which even you I do not think you disagree with, simple as it was, which is quite simply that you cannot do investigation, you cannot do your research on these children if they had not undergone the tests so you did not have the samples. It is just a fact, is it not?
A As I pointed out earlier, yes.
Q We see a full protocol is attached and that is the document at page 212 that we have already looked at. It is, as I understand it, the finalised clinical and scientific study?
A The final document submitted at the time, yes.
Q I want to ask you first of all about disintegrative disorder, and then I will come on to the MR matter that you have touched on. As far as disintegrative disorder was concerned, if we look at page 208 it is a fact, is it not, that that was a selection criterion for the study – presence of disintegrative disorder?
A This is clarified over the page, at the top of the page:
“All subjects will be under the age of 16, and all will manifest disintegrative symptoms and signs to differing extents.”
Q That does not erode the selection criteria in any way, does it, Dr Wakefield? That is simply saying they may have it to different degrees or be at different stages?
A It is trying to characterise the somewhat difficult nature of making that diagnosis, yes.
Q But it does not erode what you are envisaging as the selection criteria, which is the presence in some shape or form of disintegrative disorder?
A According to the information that we had been given by Dr Mark Berelowitz, yes.
Q You mention Dr Berelowitz, but I want to ask you in fairly brief terms what was behind what you said about disintegrative disorder in here. May I underline that I am interested in what you knew then in 1996, not what you know now, if there is a difference. There is a very careful definition, it would be fair to say, drawn in the ethics committee application and indeed in the protocol, because one echoes the other, of what was meant by disintegrative disorder. We can see that at page 202 – a careful definition?
A That is correct, yes.
Q I think that you will confirm that from the heading “disintegrative disorder” down to the penultimate paragraph which ends “sometimes language is eventually regained”. I am sorry – are you with me? I am on page 202. Do you see the heading “Disintegrative disorder” under “Introduction”?
A I do.
Q And if you go down to the end of the penultimate paragraph you see it says:
“… sometimes language is eventually regained.”
Then it goes on:
“Evidence is accumulating…”.
Are you with me?
A I have it.
Q That initially section is lifted – I do not mean this critically – but it is copied verbatim from Professor Rutter’s chapter in the text book that we have referred to? Is that correct?
A That is correct, yes.
Q I am not going to take you to it in the light of that agreement between us, but just so the Panel remember. It is at FTP6, page 460a, and it is the 1994 textbook, “Child and Adolescent Psychiatry” Presumably you went to that book initially because it was in effect the Bible?
A I went for it because I was directed to it by Dr Berelowitz.
Q You would not, in 1996, have regarded yourself as having any expertise with regard to child psychiatry?
A Absolutely none.
Q As far as that chapter is concerned, I think we had better just look at it briefly, because you have told us you read it at the time. It is FTP6, page 460a. That is a chapter which is a chapter from the textbook and it refers as well at the end, as you would expect, to a number of preceding papers which we looked at with Professor Rutter. Would you have read the entire Rutter chapter, Dr Wakefield? The entire chapter rather than just the extract on disintegrative disorder?
A Sorry. Could you take me to the page.
Q I am so sorry. Page 460a.
A I am afraid I cannot remember how much of it I read at this stage but I most certainly read the relevant part.
Q Because the portion on disintegrative disorder, which is at page 460m is a sub-heading, is it not, dealing with one of the differential diagnoses within the autism spectrum? If you look at page 460l, you will see what I mean. There is a heading, “Differential diagnosis of autism and other pervasive development disorders”?
A Yes. The only reason for my confusion is that in that paragraph on page 202, I refer to “Reviewed by Rutter et al” reference 1; and the reference is Rutter, Taylor and Hirsor in Child and Adolescent Psychiatry. The one I believe I have in front of me now, unless I have it wrong, is Catherine Lord and Michael Rutter.
Q One is the book title – it has been pointed out to me, Dr Wakefield – and one is the chapter title. It was a compendium.
A Thank you for clarifying that.
Q I hope you can take it from me that the agreement that you came to with me, that it is a verbatim representation. The little sub-heading on disintegrative disorder is a verbatim representation from the document in the ethics committee application.
Q If we look at the left-hand column on page 460m, we see just halfway down, the third paragraph starts:
“Differential diagnosis consists of discriminating autism from other psychiatric and developmental conditions that lead to abnormalities in language, play and social development. Often it is helpful to begin chronologically and to consider if there was ever a period of normal development. If there was a period of clearly normal development extending beyond 2 years, the possibilities of elective mutism, disintegrative disorder and schizophrenia in children must be considered.”
Then it sets out the various differential diagnoses and we can see them under subheadings: elective mutism, Rett’s syndrome, disintegrative disorder and then on the next page schizophrenia, receptive-expressive language disorders, severe psychosocial deprivation, Wing’s triad and Asperger’s. Are you with me?
Q It makes it clear – and this is the only point I want to ask you – as someone who is not an expert on the subject, it makes it clear that the whole issue of regression is a complex one. Would that be fair?
A Really, again I am putting myself in the position that I was in at the time, rather than trying to give you an opinion on what I may or may not know now. The issue of regression at the time was considered to be by Dr Berelowitz a relatively straightforward one. As I mentioned, he ---
Q Can I stop you there, Dr Wakefield, because I am not asking you what Dr Berelowitz thought. I deliberately started the question by saying you have told us you are a non-expert, you have read the chapter and I am simply asking you, as a non expert, this would have struck you as being a complex area.
A No, because what I knew was what had been presented to me by Dr Berelowitz and his colleague.
Q So you were not relying on Professor Rutter’s book; you were relying on Dr Berelowitz?
A What Dr Berelowitz said was not something that could be directly put into black and white in a protocol. However, what Dr Berelowitz said was entirely consistent with what is set out in this chapter. Therefore there was no need for me, as an inexpert, to modify it in any way. But the concept of regression as presented to me and to my colleagues in paediatric gastroenterology was of a different trajectory in the development of children with classic Kanner’s autism, that is, they were never right from the beginning, there was no period of normal development, in contrast with children with disintegrative disorder in whom there was a period of near normal or normal development followed by loss of skill. Additionally, there was the presence of gastrointestinal problems and in particular loss of faecal continence that made this diagnosis of disintegrative disorder one that Dr Berelowitz felt was appropriate for these children.
Q Can we just come back to you for a moment, Dr Wakefield? If you had read this chapter – I am only trying to establish the most basic understanding of you reading this chapter as a non-expert and perhaps it would be easier if I just suggest to you what is apparent from this chapter. Firstly, I suggested to you that it makes clear that the issue of regression is a complex one and, as I understand it, I do not think you accept that. In any event, you would have known, if you had read it, that a quarter to a third of cases of autism involve some sort of regression, because it sets it out in there. Would that be fair?
A It was not something that was explained or consistent with Dr Berelowitz’s explanation of the developmental trajectory. Nonetheless, as a complete novice in this area, it seemed appropriate to quote directly from Professor Rutter’s chapter.
Q Equally, you would have been aware, would you not, that disintegrative disorder was an acknowledged separate category at the time in the classification of psychiatric disorders? Indeed, we can see in this chapter that it is a differential diagnosis and it falls into a category of its own, as do many of the other definitions.
A Yes, and at the time Dr Berelowitz endorsed his selection of the choice of disintegrative disorder on the basis that those diagnostic criteria as set out in DSM4 or ICD10, the only diagnosis that encompassed the word “regression” was disintegrative disorder and therefore he suggested that by definition disintegrative disorder was the likely diagnosis.
Q So you knew that it was in a separate category. That is the only point I am trying to ascertain from you. You were aware yourself, as a non-expert, reading Professor Rutter’s chapter, that disintegrative disorder was a differential diagnosis falling into a separate psychiatric classification. That is all I am asking, Dr Wakefield.
A I am not sure, unless it is in that extract, which I do not remember verbatim now, as to whether it was precisely a different classification. I cannot say that.
Q But you would nonetheless have been able to see from that that it was one of a number of differential diagnoses that Professor Rutter was setting out as one of a number of diagnoses which might apply to children with some sort of behavioural disorder on the autistic spectrum?
A I cannot remember precisely. I do know that my guidance was from Dr Berelowitz.
Q If your guidance from Dr Berelowitz was different from Professor Rutter’s chapter, it does not appear that when you were drafting both the scientific and clinical protocol and the ethics committee application that you were relying on something different that Dr Berelowitz was saying, does it, because all we see is the verbatim account of disintegrative disorder from Professor Rutter’s chapter in his book?
A Yes. One has to bear in mind that Dr Berelowitz is a co-signatory to this document, had read it in detail and was of the opinion at least that what had been set out there in relation to disintegrative disorder was consistent with his own opinion.
Q Were you aware, Dr Wakefield, of the important distinction in relation to whether particular investigations might be appropriate or not, i.e. that a child with disintegrative disorder might well be thought to be suffering from some sort of progressive neurological disorder which would in itself point towards the investigation of the cerebro spinal fluid?
A The issue that Dr Berelowitz raised in the meeting and which is reiterated in Professor Rutter’s chapter was the association with infection, that in rare instances this rare disorder is associated infection. To that extent, the clinicians and for other reasons, such as mitochondrial disorders, decided that analysis of the cerebrospinal fluid was appropriate. But beyond that, as a non-expert and not someone involved in the clinical decision making process, I am afraid I am not able to offer you any further insight.
Q In any event, as far as the ethics committee application was concerned, the entry criteria was explicitly set out to be disintegrative disorder and you were apparently using Professor Rutter’s definitions of disintegrative disorder when that was decided on as one of the entry criteria.
A When Dr Berelowitz decided that that was an appropriate allocation for this diagnosis, it was included in the protocol.
Q You understood, and I think it is implicit in the answer you gave me, that it was a very serious condition, disintegrative disorder.
A According to the information that we had received.
Q And a very rare one?
A Historically it had been considered to be very rare, yes.
Q And one with a very much worse prognosis than autism?
A I am not sure of the extent to which I knew that. I cannot say unless it is contained within that abstract from Professor Rutter’s textbook.
Q You are telling us that you learned from Dr Berelowitz as well as Professor Rutter, and Dr Berelowitz in relation to in particular to Child 10 made the very point that it has a very much worse prognosis than autism. Is that your understanding?
A I am sorry. I cannot remember now the extent to which I was aware of the outcome of the various conditions.
Q I think you would accept, Dr Wakefield, that none of the children who were written up in The Lancet in fact had disintegrative disorder.
A Based upon what I knew then, I am not in a position to say, because clearly when this document was written, until Dr Berelowitz lectured to us, I knew very little about it. Now, based upon what I know now, no, I would not accept it. In fact, the prevailing opinion now amongst experts around the world, in contrast with Professor Rutter, is that they are a continuum of the same problem.
Q At the time you wrote The Lancet paper, no-one who saw these children at the Royal Free ever said that any of them had disintegrative disorder, did they? At the time you wrote up the The Lancet paper.
A That is correct.
Q If – and I understand that it is a factual issue between us and I am going to come to that in some detail – those children were part of 172-96, The Lancet children, I think you would accept that no attempt was made to analyse whether they met the entry criteria for disintegrative disorder as an initial step, at the start of the investigations that they each underwent.
A Again, there is a conflation here of 172-96 and of The Lancet children.
Q Dr Wakefield, I absolutely understand that. I understand you want to talk about that and we will talk about it at some length, but I prefaced the question – perhaps you will just humour me for a moment – by saying that if 172-96 covered The Lancet children. That is a factual premise I understand you do not accept, but I am asking you just for the sake of this question, if they were part of 172-96, would you accept that no attempt was made to analyse whether they had disintegrative disorder at the outset of the investigations they underwent?
A No attempt. There was an attempt to understand their behavioural developmental diagnosis undertaken by Dr Berelowitz. The extent to which that was complete and comprehensive was beyond my knowledge or understanding at the time. I did not know anything about child psychiatry and what went into determining whether a child did or did not have such a disorder, but it was my understanding and it was in large part based upon the history and the history of something that was elicited by Professor Walker-Smith and independently in many of the children or most of the children by Dr Berelowitz.
Q But not, I think you will accept, as far as their behavioural disorders were concerned, prior to them undergoing the investigations which they underwent at the Royal Free. In other words, not at the beginning, but after they had had colonoscopies and in some cases lumbar punctures.
A No. My understanding was that the key feature of disintegrative disorder based upon the standard criteria at the time was the presence of an episode of normal development followed by regression. That is something that someone as experienced as Professor Walker-Smith was perfectly entitled to elicit and opine on in his evaluation of the children.
Q Despite the complexities of the issue that I have already put to you as to how you define periods of regression and what the various differential diagnoses are as defined by Professor Rutter, you are saying when he saw these patients in outpatients, he, Professor Walker-Smith, had sufficient experience to make a judgment as to whether they fulfilled an entry criteria if, as a matter of fact, that existed, of disintegrative disorder. That is what you are telling us, is it?
A Given that classical autism, according to at least the criteria set out in the standard text, is distinguished or may be distinguished from disintegrative disorder based upon regression and given that that was consistent with Dr Berelowitz’s opinion, then it seems to me relatively mundane for someone with Professor Walker-Smith’s experience to determine whether a child could speak, whether they were faecally and urinary incontinent or not, whether they had social interaction and play and whether they lost those.
Q So you are saying that it would not have been relying on what Dr Berelowitz thought when he saw the children, because we know that in respect of all those children he saw that he did not see them until later on in the week of investigations. You are saying that that judgment as to their psychiatric condition and as to whether that qualified them for an entry criteria, if such a thing existed, of disintegrative disorder was something which was done by Professor Walker-Smith. Is that what you are saying?
A No, what I am saying is that Professor Walker-Smith with his huge clinical experience was in a position to determine whether the history merited a differential diagnosis of disintegrative disorder and therefore whether a child merited investigation on that basis. That was my understanding at the time and I have no reason to change that.
Q I would like to take you on to the other term that we have to discuss in relation to the MMR measles as opposed to MR distinction. You have told the Panel – indeed you alluded to it a bit earlier when I was asking you questions – that there is a mistake in the title at page 201.
A Yes, there are in effect two things missing: one is the inclusion of measles as an infection and the other is the question mark at the end.
Q Sorry, the other is?
A The presence of a question mark. In other words, it is posing, if you like, a hypothetical situation on page 212.
Q If we go on to the introduction on page 202:
“There are indications of the emergence of a new syndrome … The syndrome has been linked – anecdotally but consistently – with either measles or measles/rubella vaccination. It appears to occur in previously well and developmentally normal children following exposure to these vaccines.”
Are you telling us that there is a mistake in both the title and in the introduction, Dr Wakefield, as to what the study was going to be into, that it should have been covering wild measles?
A “Vaccines” refers to vaccines containing the measles and rubella components, so it could be monovalent measles, monovalent rubella, the combined measles/rubella vaccine or indeed MMR.
Q But you are saying that the application was intended to cover a study which looked not only into measles or rubella vaccination but also into wild measles virus. Is that right?
A That is implicit in the larger document, yes.
Q In that case, you are telling us that that title is a mistake because there is no reference there to wild measles, is there? Plainly the title on page 201 is referring to measles/rubella vaccination.
A The ethics committee were provided with both documents and were able to derive the correct interpretation from this particular document.
Q Doctor, are you seriously saying you made a mistake in relation to the most important aspect of all, in other words, the nature of the new syndrome which was the subject of the entire hypothesis, that you made a mistake when you inserted it in the ethics committee application?
A I would take issue with the fact that this was the most important element; it was certainly an important element but if you look at the two documents together then they require reconciliation and the reconciliation is in the more detailed document at page 202.
Q But the document throughout, the ethics committee application, is plainly referring in plain English to measles vaccination or measles/rubella vaccination, is it not? Where do we find anywhere in it a reference to wild measles virus?
A On page 202, “with either measles or measles/rubella vaccination”. The reason that this was put in was for the very reason that Dr Berelowitz had drawn our attention to the association between measles encephalitis and disintegrative disorder and this is referred to again in Professor Rutter’s textbook.
Q Dr Wakefield, if you look at the rest of that sentence, are we going to have to chop this up into individual sentences as well? It says:
“The syndrome has been linked – anecdotally but consistently – with either measles or measles/rubella vaccination. It appears to occur in previously well and developmentally normal children following exposure to these vaccines.”
A Yes, I believe I said “these vaccines” refers to either the measles vaccine, the rubella vaccine, the combined measles/rubella vaccine or the MMR vaccine. It is – and I think this term has been used previously – an umbrella term under which those various vaccine components are described.
Q But it does not make any reference to wild measles and you are now telling us that this was a study into wild, natural, measles.
A It says “with either measles or measles/rubella”.
Q “With either measles or measles/rubella vaccination” – can you read the next sentence, please?
A “It appears to occur in previously well and developmentally normal children following exposure to these vaccines.”
Q Which vaccines?
Q Exactly, measles or measles/rubella.
A If that were in the singular, if I had put vaccination, then it would mean measles/rubella vaccine, but it is an umbrella term that encompasses measles vaccine, rubella vaccine, measles and rubella vaccine. This is made clear I believe later on, if you will bear with me…
Q We will go through the protocol, doctor, in those circumstances. We have looked at the introduction on page 202 and if we look at paragraph 3 on page 201, this is the objective and I think even you will accept that the hypothesis which it is intended to test is a rather important piece of information for the ethics committee. We see:
“We will test the hypothesis that in genetically susceptible children measles vaccination is associated with …”
There is no reference there to wild measles, is there?
A Let me again try and clarify for the Panel what may appear to be at first a complex issue. You will note that vaccination or exposure status has no part of the inclusion criteria: why? Because if you include children across the board, whatever their exposure, whether they have been exposed to measles as a disease, not exposed at all or exposed to measles in the form of a vaccine, then what you are able to do in the analysis of your data is to see whether the disease syndrome – let us say bowel inflammation – segregates with the children with measles vaccine exposure. To preclude those children or to preclude other children who have had just measles or no obvious exposure at all limits your ability to determine, to test your hypothesis, that the specific syndrome is associated with the vaccine exposure and so in defining the hypothesis you do not limit it to a particular exposure. I hope that is at least relatively clear.
Q Page 202, please, the bottom of the page, where we have the heading “Complement, measles and disintegrative disorder”.
“The association between measles vaccine and disintegrative disorder has been noted independently by Warren et al in Utah, where they have linked susceptibility to this condition …”
That is certainly just talking about the vaccine, is it not, it is not a reference to wild measles?
A That is talking about someone else’s work.
Q Yes, I understand that, I am just asking you, that is certainly referring to the measles vaccine.
A Yes, that is where someone else has conducted a study which has made the association with the vaccine specifically.
Q Page 204, your “Working hypotheses” at the bottom of the page:
“The possible link between an environmental insult (measles/rubella vaccine) in a previously healthy child who may be genetically susceptible to responding inappropriately to the viruses … several working hypotheses to be proposed.”
That again is a clear reference to the measles/rubella vaccine and not to any other form of measles virus.
A This goes back to my original statement about the hypothesis and the design and testing of that hypothesis is that you do not preclude children who have had other exposures, because by including them what it effectively allows you to do is to test the hypothesis if those exposed to the measles vaccine are the ones with the specific syndrome and those who are not exposed do not have it.
Q Page 205, your two models.
A Again, these are really again an attempt to simplify and articulate that hypothesis.
Q Both of them refer exclusively to vaccination, doctor.
A Which, as I have referred to now on separate occasions, is entirely appropriate and does not preclude the inclusion of children who are not vaccinated.
Q Page 211, an important document, we have all agreed, information to the parents, drafted by you at a very early stage, and we see the heading:
“Information to be given to parents/guardians of patients taking part in the study of enteritis and disintegrative disorder following measles/rubella vaccination”.
A Yes, I have referred to the fact that this document was inadequate and was never in fact used. There are a number of problems with it, not least of which is that it does not fully set out the hypotheses as earlier articulated in the document.
Q Page 232, which is the one I think you prefer, the patient information sheet that you were anxious to go to yesterday.
A I think here on the fourth line:
“The problem has been associated – anecdotally but consistently – with measles or measles/rubella vaccination.”
Again, that is setting out in umbrella terms what we believe may be going on.
Q Yes, may we go on, please.
“We, at the Royal Free, have now looked into the background medical and scientific literature concerning this problem, and have formulated the hypothesis that in certain (perhaps genetically susceptible) children, live-virus vaccines may produce long-term inflammation of the intestine and failure to absorb …”
Doctor, are we really arguing about whether this is talking about vaccines or wild measles?
A Sorry, can you say that again?
Q Are we really arguing about whether this document is referring to vaccines or wild measles or both?
A For the very reasons that I have sought to explain, yes.
“… in certain (perhaps genetically susceptible) children, live-virus vaccines may produce inflammation of the intestine …”
This is to parents. Are you telling me that the parents were meant to understand from that that their children did not necessarily have to be vaccinated at all, that it might be wild measles?
A It is a fact that the great majority of children had received one or other of the vaccines, that is simply a quirk of history, that the majority of children are now vaccinated. It does not preclude the possibility, nor should it, that based upon the historical evidence as set out in this document, referred to by Rutter and others, wild measles may cause this problem.
Q Page 236. Dr Epstein, consultant gastroenterologist, to whom you turned to give reassurance, if you like, to the ethics committee as to the appropriateness of this study:
“I have reviewed your proposal to study enteritis and disintegrative disorder following measles-rubella vaccination.”
Did Dr Epstein make a mistake as well as to the basic hypothesis that you were pursuing?
A I cannot speak to Dr Epstein’s understanding because this is his document.
Q You can speak to whether it appears to you to be an error, and on your contention, Dr Wakefield, it must be, must it not?
A It depends on whether it reflects his understanding of the document or not.
Q If we go on, please, to 366aa. I will come back to the substance of this letter; I know you would like to tell the Panel about it and I am very happy for you to do so, but for the purpose of pursuing the present point, by this time you are now saying that the study was enterocolitis and disintegrative disorder following MMR vaccination.
A Sorry, I do not have the document.
Q Document 366aa is a letter which you referred to earlier this morning, which is a letter that you wrote to Dr Pegg about amendments to 172/96.
A I am sorry, I misheard.
Q As I say, doctor, I will come back to this in relation to the information that it gives to the ethics committee. That is not at the moment what I am concerned with, I am just asking you about the reference at the start which appears to be a letter from you to Dr Pegg where you are explicitly saying that the study was into enterocolitis and disintegrative disorder following, now, MMR vaccine but still clearly specific to vaccines.
A I think if one reads this letter correctly, the italics is the start of the title of the syndrome “A new paediatric syndrome: enteritis and disintegrative disorder ref 172/96” and then not in italics “on enterocolitis and disintegrative disorder following MMR vaccination”. That may well reflect the fact that by that stage virtually all of the children for whom parents had made a temporal association had had the MMR vaccination.
Q You see, doctor, I have to suggest to you that this contention by you that wild measles was covered by this study is wholly contrary to the documents that I have just gone through with you and that you are trying to distance yourself from your research interest at this time, which was plainly into vaccines.
A I appreciate you have to put that to me; the answer is no, my interest is measles in fact and that is borne out by the historical literature that I have published on measles and inflammatory bowel disease, so I have a specific interest in the biology and pathology of measles virus.
Q Which culminated in a paper in 1995 which we have all heard about which was the very issue of whether Crohn’s disease was implicated in measles vaccination.
A That is correct. The other thing to bear in mind, just as a matter of fact – in reference to Child 10, for example – there was a situation in which the doctor had noted “measles infection” and the parents had noted “measles infection” as the apparent trigger for the onset of the child’s problem. There is an example, albeit unusual, of a very good reason for addressing the issue of measles, natural measles, in this context as well.
Q You see, in addition, I suggest, to just trying to distance yourself from your research interest at this time into vaccines, I suggest you are also trying to distance your research under 172/96 from the Legal Aid Board study which I think you would accept was undoubtedly in vaccines?
A I am not trying to distance myself from this at all. I have an explicit interest in the possibility that vaccines, in the form, for example, of MMR, are associated with this syndrome. What I am trying to do in a scientific way is to be all-encompassing, based upon the historical literature; to be inclusive rather than exclusive; to incorporate rather than to distance. I think the interpretation is inaccurate.
MS SMITH: Sir, I am turning, to a matter which is closely related to what we have just been discussing, but a slightly different aspect of the vaccination issue and I think this would be a convenient moment to break, if we may, rather than for me to embark on that.
THE CHAIRMAN: It is now five to one, so we will now adjourn for lunch and resume at five minutes to do.
MS SMITH: Thank you, sir.
THE CHAIRMAN: Dr Wakefield, once again, you are still on oath.
MS SMITH: I wonder – it would be quite helpful, if I may respectfully ask, what sort of time you would like me to finish this afternoon, because I will try and get it to a convenient break. It may be that you feel it is too early to say.
THE CHAIRMAN: I am quite happy to go on until four o’clock. I am just slightly concerned because Dr Wakefield is one of the defendant doctors and has been giving evidence for quite a few days. Cross-examination by the nature of it is much more stressful than the other parts of adducing the evidence. I will be quite happy to go along with your experience on these issues. My personal view would be that perhaps anywhere between 3.30 and 4.00 would probably be the right time.
MS SMITH: Obviously we have a lot of material to cover. I go on until I am told to stop. May I suggest that we go on, say, until three o’clock and then ask Dr Wakefield how he feels, because only he can say.
THE CHAIRMAN: I think that is probably the best way to go along with it. I have already given my assurance to Dr Wakefield that if at any stage you start feeling that you do need a bit of a rest, then you really need to be quite frank and tell us. It will not weigh in any way against you for giving your part of the evidence. Please just tell us that you then need a break, or that you have had enough for the day. As I have said earlier, although I cannot give you absolutely categorical assurance that we will accept that, I think the Panel will consider very sympathetically any such request coming from your end.
It is actually now one o’clock, so we will now resume at two o’clock and I think we will take that issue as time goes on. Thank you. We will resume at two o’clock.
THE CHAIRMAN: Good afternoon, all of you. I believe the Legal Assessor is going to point out a correction on the transcript.
THE LEGAL ASSESSOR: This was drawn to my attention by Mr Thomas. It is the transcript for Friday, Day 58 at page 52. It is at the top of the page, where there is an intervention from me during Ms Smith’s cross-examination. It is the last sentence, which reads:
“I now understand you are now implying that.”
It is a typing error. It should read:
“I now understand you are not implying that.”
I remember that is what I said, and Mr Thomas certainly recorded that that is what I said. I trust everybody else agrees that that is what I said. Perhaps that can be noted. Thank you.
THE CHAIRMAN: Thank you very much indeed. Any comments on any from any of the lawyers representing the doctors? (None) Ms Smith, are you happy with that?
MS SMITH: Yes, thank you.
THE CHAIRMAN: You can continue now.
MS SMITH: Thank you. Dr Wakefield, we are just turning to the issue of vaccine, if we may, leaving aside the point we have been discussing the distinction between the wild virus and the vaccine. As far as the vaccines are concerned, there are three possible candidates, if you like, in relation to measles vaccination: the measles vaccine itself, which as we heard earlier is a monovalent vaccine; the MR vaccine, measles/rubella, which is measles and German measles/rubella combined, and the MMR which is measles, mumps and rubella. Is that correct?
A That is correct, yes.
Q It is a subject which you studied comprehensively because you have told us that you were concerned with various safety studies at that time, so you were well aware of the distinctions between the three?
A I am sorry. I am finding it very difficult to hear.
THE CHAIRMAN: The volume of the sound has definitely gone down.
MS SMITH: I hope it is the microphone rather than me. Is that any better?
Q What I was suggesting to you was that it was a subject that you studied comprehensively, as you have told us, in the context of the various safety studies in relation to different vaccines, and you were well aware of the distinctions between the three. Is that fair? You knew the difference between the three?
A Yes, yes.
Q And as far as the distinction between MMR and MR, you were aware that children aged 5 to 15 who had missed out on the original MMR campaign were subjected to a six-week campaign of vaccination with MR in anticipation of the possibility of a measles epidemic. Is that correct?
Q You were aware of that at the time that we are talking about?
Q Did you have an understanding at that time, because we are now in the period of the ethics committee application, so we know that you had met with Mr Barr and had taken on a role as an expert in the litigation. Were you aware of the investigation by the lawyers into both those vaccines?
A Yes, I was.
Q Can we just look at FTP2, please, at page 430. This happens, Dr Wakefield, to be a Dawbarns report to the Legal Aid Board on the multiparty arrangements in relation to class litigation. I am not going to look at the rest of it now. I just want to see whether the history as it is set out there accords with your understanding. We see:
“Families whose children have been vaccinated with the MMR (Mumps, Measles and Rubella) vaccine or MR (Measles Rubella) vaccine believe that their children’s problems have been caused by those vaccines.
The MMR vaccine was introduced in the autumn of 1988. There followed a sustained campaign to have all children vaccinated with this triple antigen vaccine.
Late in 1994 the Department of Health claimed that they feared an epidemic of measles and decided to vaccinate 7 million children with the MR vaccine.”
It then goes into the rubella component. It says:
“The Legal Aid Board initially granted our firms the contract to manage the MMR claims. Subsequently the contract was extended to cover the claims involving the MR vaccines.”
As I say, this was a report that was done for the purposes of the Legal Aid Board by Dawbarns, but I just wanted to ask you whether the facts, as they were set out there, accorded with your understanding in relation to the litigation?
A Yes, broadly I think they did.
Q Thank you. From the point of view of any work that was being done on the causative factors in the litigation, the distinction was quite an important one, was it not, because the older the child, the easier it was, if you like, to see if there had been a significant regression which coincided with the vaccination?
A It is correct to say that if a child had been developing normally for four years and regressed, that would be something that was very obvious. Again, my experience of detecting or observing regression was extremely limited, and confined to the stories given by the parents, so the distinction… I am sorry. I am unable to really help. Was the distinction an important one? Not necessarily. If the history was clear of normal development followed by regression, then that would apply or that may be evident following either vaccination.
Q But the older the child – it is not the nature of the vaccination, it is just the fact – that MR vaccine was given to school-aged children between 5 and 15, and the older the child, one does not have to be a genius in child psychiatry to understand this point, the older the child the easier it is going to be to appreciate significant regression because they will have got farther; they will be speaking better – all those things which go with being an older child. Is that right?
A It is potentially more obvious, yes.
A It is potentially more obvious, yes.
Q Indeed that very point is made by the lawyers. Can we look at page 461, please, in the same bundle? This is, again, a May 1997 newsletter which is prepared by Dawbarns. I appreciate you may not have seen it. I am just asking you whether this is a position with which you would agree. We see “Causation” in the middle of the page.
“Proving vaccine injury is difficult.”
This is talking about proving it in the context of ligation.
“Children are often vaccinated at a young age, before they have had a chance to establish a health track record. In addition, problems with development caused by other factors are often not apparent until 15-24 months or even later. This can coincide with the age at which the MMR vaccine is administered.”
Then it says:
“Until recently the only available course appeared to be to call upon experts to give their opinions as to whether or not a particular vaccine caused injury, and support their views by fairly vague criteria.
The studies of Dr Wakefield and his team … could well prove (at least so far as inflammatory bowel disease is concerned), that it is the vaccine which is causing the injury.”
They then go into various other tests which they hope will establish the link. Then it says – and this is the part that I wanted to ask you about:
“Another important factor is that our group of cases includes the children who were vaccinated in the November 1994 schools vaccination campaign.”
That, I think, is a clear reference to the MR campaign. Is that right?
A I would imagine it is, yes.
“Those children (many of whom were in their teens) have a clear record of childhood health. Most of them had no significant health problems until they were vaccinated. The two groups complement each other. The fact of vaccine damage to older children helps to support the view that the same mechanisms of damage are present to cause injury to younger children.”
That is Mr Barr looking at it, I understand, from the point of view of the causation in the litigation, but it is an explanation of the point that I have put to you, namely that it is going to be easier to detect – whatever the reason you are looking for it, it is going to be easier to make the association with the vaccine in older children?
A Not necessarily. I cannot speak to what Mr Barr is referring to here, but Ms Smith referred specifically to developmental problems and I am not aware of any of the children that we looked at who, following MR, developed development problems. They developed bowel problems which later turned out to be consistent with Crohn's disease and I think there are two issues going on here, and the term “health” of the child in the last paragraph, the third line, may well embrace bowel symptoms and Crohn's disease rather than being developmental symptoms. Again, it is not my document and I cannot speak for what Mr Barr is saying.
Q But it is a very simple point, Dr Wakefield. The same applies, does it not? If you have an older child who has bowel problems, they are more able to articulate and say what is the matter and so the association is an easier one to draw. That is the only point I am making.
A I am afraid I am not sufficiently expert in child health to give an opinion.
Q You see, it is not just litigation, is it? For the purposes of your research, had you been able to do the investigations with which you were concerned to explore the hypothesis that we have discussed, it would have been easier with older children?
Easier to make an association between the symptoms that they had and the vaccine that they had undergone?
A Again, in the context of gastrointestinal symptoms, I do not necessarily think that a child developing chronic diarrhoea, mucus, blood or the like at 15-18 months is more difficult to ascertain than a child developing it later on. In the context of bowel problems I do not know. In the context of developmental problems, you may well be right, but I am not an expert and this is not my document, so I am not entirely sure what Mr Barr is referring to here.
Q I have left that now, and I am saying for the purposes of your research, which I think even you would accept is something you can express a view on, it was easier if it were in relation to older children? It was easier to make the connection. You have picked on symptoms which I entirely agree would be apparent whatever age you were, but if you are talking about things like articulation, for instance, of abdominal pain – just as an example – it is going to be easier if the child is older and you can him “What is the matter?” Why he is crying and where the pain is. You do not have to be an expert in child health, do you?
A Provided that the child was capable of speaking and that they were not previously rendered autistic. Perhaps the one circumstance with which I was concerned and is relevant is the child who has been re-challenged, which I mentioned before, where there had been an onset of symptoms following initial exposure, which one could entirely reasonably put down to coincidence, and then a re-exposure some time later followed by a recrudescence and exacerbation of those symptoms. That phenomena of re-challenge is not consistent with coincidence until proven otherwise. So that is the only circumstance in which the age may – the older age, because they have been old enough to be re-vaccinated – provide a clue.
Q Assist us as to why it is that the entire ethics committee application form and the finished clinical and scientific protocol refer to the MR vaccine, i.e. that which is given to older children, rather than to the MMR vaccine?
A It does not. It is an umbrella term which I think has been used earlier in the prosecution case for including vaccines that have in them the measles and/or rubella component. The reason is that both of those viruses, measles and rubella, have historically been associated with developmental disorders in children, measles in the context of disintegrative disorder specifically and rubella in the context of maternal rubella exposure during pregnancy with an increased risk of autism in the infant. It was for that reason, the biological plausibility that the measles and rubella components have previously been implicated in childhood developmental disorders, that they were included under this umbrella. Mumps as far as I am aware has not and certainly as far as I was aware at that time.
Q Doctor, I imagine you would acknowledge, as a scientist, that a degree of precision in relation to the documents you are filling in is important.
A Yes, it is.
Q Why is it that nowhere in any of those documents do we see a reference to MMR vaccine?
A Because the issue of the exposure, with the particular emphasis on measles, has been presented in that way, for the reasons that I suggest. Let me put it another way. In the knowledge that the only exposure of the children with autism, at least as far as I am aware in the first 12, had been to the MMR vaccine, it would make absolutely no logical sense whatsoever to test a hypothesis for a vaccine to which none of them had been exposed.
Q I think we can agree on that. The next thing I was going to ask you was, if these children were part of 172-96 – and I know that is an issue between us – if they were, they did not meet the entry criteria which underpinned the study, namely, having had the MR vaccine. They had all of them, with the exception of Child 4, who had also had the measles jab, the single monovalent measles vaccine, they had all had MMR, had they not?
A There are two things there. Firstly, these children were not under 172-96. That is entirely speculative and therefore I am not going to enter into that. But if we look at the inclusion criteria, it does not require any exposure at all. It does not require any specific exposure; no measles, natural measles, MR, MMR. It is not one of the inclusion criteria of 172-96. I reiterate, they are a diagnosis of disintegrative disorder, gastrointestinal symptoms and a parental desire for the investigations to be undertaken.
Q The title of the project, which formulates your hypothesis, you are telling us, where it plainly makes it perfectly clear that the children are to have had MR, you are telling us now was a mistake. That is your position?
A No. Before the break I tried to explain why the testing of a hypothesis should not exclude children whose exposures might have been other than to the candidate vaccine. Let me try and put it more clearly. If we looked at 50 children, irrespective of their exposures, and we found that on analysis of the data, the 25 who had MMR had bowel inflammation of a particular sort, and the 25 who did not have MMR, did not have any particular exposure at all other than – sorry, excluding MMR – and they did not have inflammation, then we would be entitled to draw the inference that the bowel disease is associated with MMR vaccination. That would be a testing, if you like, of the hypothesis. So the title and the hypothesis do not preclude the entry of children into the trial who did not have MMR vaccine.
Q When you were answering these questions to Mr Coonan, Dr Wakefield, you expressly said that the title was a mistake. You are now, as I understand it, giving us a pretty elaborate explanation as to why it is not a mistake and you are saying what you meant to say. Which are you saying? That it is a mistake or it is not a mistake?
A The mistake was the omission of measles virus representing the natural infection and the question mark at the end, not the interpretation of the measles/rubella vaccination.
Q So this mistaken title, where they get a title of a project which says “A new paediatric syndrome: enteritis and disintegrative disorder following measles/rubella vaccination”, that that is not what you really meant. Is that what you are saying?
A No. What I am saying is that is what I meant in the larger protocol including measles and the question mark. That is what I meant. What I did not mean measles/rubella vaccination to mean was the preclusion of MMR exposure, preclusion of MR exposure or the preclusion of the single measles vaccine exposure.
Q Let us get back to the ethics committee application, please. I would like to look at the timetable, which is set out at page 231 of FTP1. The timetable which was envisaged for this study, Dr Wakefield, I appreciate that the actual specific days, given busy doctors’ diaries, you may not have regarded as being sacrosanct, but what I want to ask you about is the sequence and the sequence is clear, is it not? The first day, the Sunday, is the consenting and the history and the examination and then on the Monday it envisaged colonoscopy, lumbar puncture, MRI and the next day EEG, the next day, barium meal and follow through, presumably having got an idea of what was going on with the colonoscopy, and then Dr Berelowitz to see them and then the next day, Dr Harvey and then the next day is the end. The sequence, the plan, is clear, that Dr Berelowitz and Dr Harvey were going to see these children after they had had these investigations.
A That is correct, yes.
Q It is also clear that you were to arrange the asterisked investigations. We can see that.
Q I suggest to you that the asterisk in each case plainly refers to the box, not to the item. So that you will arrange – we will talk about what we mean by “arrange” in a moment, but looking at the timetable – you were to arrange the MRI and the lumbar puncture on Malcolm Ward just as in the next box you were to arrange the EEG and the evoked responses.
A No, I am afraid you have misinterpreted the designation.
Q How do you explain the fact that the asterisk is at the top of the list of investigations? You are saying it just applied to the MRI, but you are accepting that it applied to both the EEG and the evoked responses.
A The answer is really very straightforward. The MRI is undertaken not on Malcolm Ward, but in the department of radiology. The EEG and the evoked responses are performed at one and the same time in the department of electrophysiology; they require just one arrangement. The lumbar puncture, as I mentioned in my direct examination, was to be undertaken by the clinician immediately following the colonoscopy under the same sedation and at that time it was to be done on Malcolm Ward, when the patient returned from the endoscopy suite to Malcolm Ward. In other words, it was inherently arranged by virtue of its sequential conduct after and under the same sedation as the colonoscopy. It did not require an arrangement by me in any shape, manner or form and I had no input into this sequence of investigations. This was clinical decision making.
Q Going on with the asterisks, you were to arrange Dr Berelowitz and Dr Harvey after these investigations had taken place.
A Again, the sequence was a decision taken by those respective clinicians. My role simply – and it was not in any way to make a clinical referral, but as I have said repeatedly, it was to make contact with the secretaries of those respective doctors so that they could put in the doctors’ diaries the fact that a child was to be admitted the following week.
Q I will investigate what you actually meant by the word “arrange” in a moment, doctor. Before we get to that point, you have accepted you were the co-coordinating investigator and you have accepted and indeed we can see it on the document that you were one of the consultants responsible for this protocol. You have told us you do not accept a responsibility to ensure, for instance, that the children met the entry criteria because of disintegrative disorder, because you are saying you relied on Dr Berelowitz. I have to suggest to you that you were responsible for a project which did not even provide for a psychiatric assessment prior to the investigation of the children and, as I understand the answer to that to me earlier this morning, you are saying you were not relying on Dr Berelowitz at all, you were relying on Professor Walker-Smith’s assessment.
A Let me just make it absolutely clear. My overall responsibility was as co-ordinating investigator. That meant co-ordinating the interaction between the various participants, the various collaborators on this project. I had no role whatsoever at any stage in clinical decision making, either as part of the protocol or on behalf of the individual child. The order of investigations was decided appropriately by the respective clinicians and that is the way it worked. I had no clinical role whatsoever. My specific responsibilities in this protocol were for the research aspects and, in particular, the biopsy related research.
Q Doctor, you are not saying that you did not bear a responsibility for the design of this study, are you?
A No, I am not saying that.
Q The design of the study as opposed to clinical decisions.
A No, I am not saying that. I was responsible for the design of the research aspects of this study and I had no role in designing the clinical aspects of the study.
Q Doctor, this has a timetable attached to it which was sent to the ethics committee to inform them as to the way in which this study was to pan out, if you like, and that, I suggest to you, involves the design of it. You designed it in a way where, according to it, neither Dr Berelowitz nor Dr Harvey were to see the children until after they had undergone investigations. That was the way the study was designed.
A The clinical aspects of the study were not in any way designed by me. I constructed a table into which I entered the decisions made by the clinicians. That is the extent of my involvement in the production of this table. I had no role in any decision making process as to the timetable or indeed the clinical investigations which the children underwent.
Q As far as the design of the study is concerned, you cannot divide off the research from the clinical in any event, can you, because the study was designed overall with a clear plan which you signed up to as to the way in which the investigations would be carried out and not only was it designed so that Dr Berelowitz would not see the child, but it was also designed in such a way that the lumbar punctures were taking place prior to the involvement of the paediatric neurologist. That is just a fact on the document, is it not?
A Once again, I had absolutely no input whatsoever into the sequence of investigations, the clinical investigations, and no involvement whatsoever in the choice of the investigations. That was not my role. My role was to determine what research investigations might be useful in elucidating the nature of this disease process.
Q Doctor, you were a senior researcher and you have told us that you actually filled in the boxes. You designed this form, in fact. Are you telling us that?
A I created the table and filled in the elements of the table according to the decisions taken by the clinician.
Q But when you looked at it, did it not strike you that these children who were being entered into a study according to the provisions of 172-96 on this design would be having invasive investigations before anyone had either confirmed their behavioural diagnosis or made a decision as to whether it was appropriate for them to have a lumbar puncture?
A It was not my remit to determine, to concord with, to overturn decisions made by expert clinical colleagues, that was not my role.
Q I am sorry, we are not talking about individual children at this stage, are we, we are talking about the design of a study, you were not applying it to particular clinical instances, particular children, and whether they needed this or they did not need this, you were looking at what, as I understand it from the evidence you gave us on Friday, was your expertise, which is designing studies in order to test scientific hypotheses.
A That is confined in this specific instance to the research elements of the study.
Q Are you saying to us that it never occurred to you that the design of the study subjected children to all the invasive tests at the beginning before they had had a diagnosis or been seen by a paediatric neurologist? Are you saying that it never occurred to you that that was a rather unhappy design, doctor, whether you were responsible for actually deciding on it or not?
A I was specifically not responsible for designing it or for adjudicating on the decisions of my clinical colleagues who met and discussed this at great length in coming to their determination of how the clinical studies should be conducted. I had no role in that process whatsoever and it was not my role at all to adjudicate on the merits of when and where these studies were conducted.
Q Nobody is suggesting you should have adjudicated on it but did you not have a role to play as a responsible consultant and coordinating investigator in questioning it, in saying “Hang on a minute” – if as you say they drafted it – “how come we are doing all this before these children have had their behavioural diagnosis assessed”? It is not a very sophisticated point, is it?
A That would be assuming a clinical role to which I was not entitled.
Q Why is it a clinical role? You are telling us – and indeed you have underlined the fact – that you felt highly responsible for these children. They were being admitted into a study, whether we call it research or clinical, you design the study, albeit with input from your clinical colleagues, your clinical colleagues have not seen the children, how do you tell us it was not part of your role to make sure that the design of this study – the design – was appropriate to the research that you wanted to undergo?
A There were two elements to the design of the study. One was the clinical aspect, for which I was not responsible but for which my expert colleagues were responsible and for which they were entirely equipped to determine the sequence of investigations the children should undergo. I set out in the protocol that my specific responsibilities were for the research element and that was the element for which I was specifically and solely responsible.
Q You had only seen a handful of children at that stage. I cannot recall the exact number but there had been three or four referred and we know – and you agreed this morning – that only one had been investigated at that stage. You are designing a study and at that stage you do not know what the individual clinical indications for any of these children are going to be according to the clinicians, do you? You are not worrying about an individual when you design a study, you are worrying about the study being cohesive.
A No, it is for the clinicians to determine whether the investigations they have included in this study are appropriate in any individual child. It is my role to design and conduct the adjunct research investigations and it is my role to coordinate the various collaborators so that, for example, at a Tuesday meeting we might meet to discuss a particular aspect of the document.
Q So that we are clear, Dr Wakefield, I understand you are saying that when these children came individually it was up to the clinicians to decide whether they should undergo these investigations, I understand that. What I want to be clear about is are you also saying that it was up to the clinicians, Professor Walker-Smith and Professor Murch alone, to design the sequence of events prior to applying them to any individual children? In other words, page 231 is nothing to do with you, it is all down to them, is that what you are saying?
A No, I am not saying that. Included in that decision-making process about when the children would be seen was Dr Berelowitz and Dr Harvey.
Q So you are saying it was down to the clinicians but not just Professor Walker-Smith and Professor Murch.
Q And the sequence is absolutely nothing to do with you.
Q So although you are the coordinating investigator and although you are a responsible consultant, as far as you are concerned your responsibility ends in that narrow way that you have told us, and even if you had thought that this was absolutely bizarre you would not have said so because it was not your responsibility, is that what you are saying?
A No. I had no role, no responsibility, in determining the sequence of investigations, determined not by a bizarre set of individual clinicians but by a highly experienced, deeply concerned and very well-motivated group of doctors.
Q So you are saying it did not worry you, you never thought they might be odd because as far as you were concerned if the clinicians thought that was the right thing to do you would not question it further, as far as the sequence is concerned. That is your position.
A The Panel will appreciate that these decisions were based upon a long period of consultation and meetings between colleagues that ultimately resulted in the sequences shown.
Q The clear indication of this document, doctor, was that you were going to be arranging – in the sense I suggest of deciding – that Dr Berelowitz and Dr Harvey should see these children as we see set out there. You say that arranging does not mean you had any role in ordering them, is that correct?
A That is absolutely correct, I did not make any clinical referral to any doctor, nor was that my place. My role was specifically in letting the secretary know that a particular child would be coming the following week and to enter that into their diary.
Q I am not suggesting that you did it as part of a clinical role, doctor, I am suggesting that you did it as part of a research role, namely that you were organising and arranging and ordering Dr Berelowitz’s and Dr Harvey’s assessments as part of the research protocol.
Q Your explanation as I understand it with regard to the tests, you said – this is Day 48, 44B, for those who want a note – that Professor Walker-Smith’s team were very busy and you offered
“… in a purely clerking role to arrange those tests. In other words, if there had been a clinical decision to undertake the MRI and likewise the EEG, then I would … go to the department with the form completed so that that test could be conducted.”
Is that correct?
A I had offered to undertake that role and in many of the instances in the first 12 children where EEG was to be ordered by the clinicians I enacted the role of arranging that test. I most certainly did not order any tests, I would not have been capable of doing that, it was not my role and it was under the jurisdiction of the paediatricians and Dr Harvey, in their discussions, to come to that decision and for that test to be done.
Q So that is your clerking role in relation to the MRI and the EEG. As far as Dr Berelowitz and Dr Harvey were concerned you say that “arrange” meant that you offered to make contact with their secretaries that a particular patient was coming in, is that correct?
A That is correct, the arranging role was purely an administrative role as in the manner of a ward clerk, and these arrangements are now undertaken by just such a person, a ward clerk.
Q Dr Wakefield, we started off yesterday by looking at your job description and you accepted with me that you were at that time a senior academic and an honorary consultant, you were research director of the IBD Study Group charged with achieving a worldwide reputation through extensive research and the raising of grants, you have a secretary whom you share, you had a research nurse, you had a large team working under you, are you truly telling this Panel that you suddenly decided to act as the ward clerk and take on the role of physically carrying the MRI and EEG forms to the departments and that was all you did?
Q I have to suggest to you that that is absolute nonsense, why should you have felt it necessary to take upon yourself an entirely administrative, clerking role?
A I suppose the answer might be, without wishing to sound somewhat sanctimonious, that there is a great deal of room for humility in the medical profession and I had no problem whatsoever with undertaking lowly tasks like this if in the event it would help already very, very busy colleagues in paediatric gastroenterology.
Q You are suggesting that you were not busy, are you, that you had so much time that you could afford to take on what you describe as lowly roles with humility as well as carrying out the job for which you had overall responsibility?
A I had enough time, yes.
Q This is just you, is it not, trying to place a terribly narrow construction on the word “arranged” as indeed you do with many words to absolve yourself from a responsibility that you plainly take on, according to page 231, namely to be in charge of the neuropsychiatric aspects of this research trial.
A No, the investigations were only ever arranged by me when a clinical decision for their conduct had been taken by others.
Q So far as Dr Berelowitz and Dr Harvey are concerned you say that all you did with them was to contact their secretaries and you say that with regard to both of them the decisions were made by the clinicians as to their involvement, is that right?
A That is correct.
Q Where do we see anywhere any reference to that, Dr Wakefield, to the fact that the clinical decisions were to be made by the doctors who saw the children on their admission, the gastroenterologists?
A I cannot remember precisely how it operated but I believe that once the decision had been taken then a junior doctor such as Dr Casson would make contact and let me know which child was coming in and what the procedure was to be.
Q If you look at FTP1, page 114, this is back to the draft document and so we know somewhere in the early part of 1996. We see there a clear reference to the duties which you envisaged Dr Harvey to take and which are then echoed in the ethics committee application and in the final protocol. Dr Harvey: full clinical examination, MRI, lumbar puncture, CSF antibody profile, cytokine measurements, EEGs, evoked potentials. So right from the very outset, I suggest to you, Dr Harvey’s role was perfectly clear with regard to these children and their lumbar punctures, there is no reference to Professor Walker-Smith playing any individual part in the assessment of whether a child should see Dr Harvey or not.
A Dr Harvey’s role was largely in the interpretation of these tests once they had been conducted, that was the intention.
Q What do you mean “interpretation”, it starts off “full clinical examination” – what does that mean? That does not mean you are interpreting tests, that means you are seeing the child.
A That is correct. It was his intention to see the children and to conduct a full clinical examination. That was my understanding.
Q In order to do what, decide whether they would have a lumbar puncture or not?
A That is a question that I am unable to answer, it is a question for Dr Harvey although of course he is not here. The decision for a lumbar puncture was a clinical decision and I am really unable to offer any further insight into that matter.
Q Cytokine measurements for a start in this early document were part of your research protocol, were they not?
A Yes, they were, but that is not the lumbar puncture but the cerebrospinal fluid taken at the clinically indicated lumbar puncture for a research test. I thought that further information might be gathered from that but in fact it was not undertaken in any child.
Q If we go on and look at the ethics committee application or the protocol attached to it, page 214, we see at the bottom of the page “Dr Harvey: full neurological assessment and investigation.”
A These are clinical questions and they are best directed to the clinicians. I am really unable to offer any further insights into this.
Q Dr Wakefield, you have told us that the lumbar punctures were clinical decisions that were made when these children were admitted by Professor Walker-Smith or a member of his team, that is what you have told us, and I am asking you to explain why it is in those circumstances that in none of these documents do we see any reference to Professor Walker-Smith and his team being responsible for the lumbar punctures and instead we see that they were to be under the auspices of Dr Harvey. You were the one who told us that they were assessed by Professor Walker-Smith and I am asking you to explain that discrepancy in relation to the documents which you submitted to the Royal Free ethics committee.
A I did not make the decision to include lumbar puncture in the protocol and I played absolutely no role in the performance of the lumbar puncture in any child whatsoever, and I am unable to offer you any further insight into the mechanism by which this occurred and most certainly one finds absolutely no reference to me being involved in a lumbar puncture in any child at any stage.
Q Dr Wakefield, we understand that that is your position and I think you probably understand the question that I am putting you which is that you were the coordinating investigator and the responsible consultant, with a role to play in the design of this study. You have told us that in fact those investigations were decided upon, as was your understanding, when these children were admitted for clinical reasons by the clinicians who saw them then. I am asking you why it is, in that case, in a study which you accept you played a part in designing, we see no reference to that whatsoever and instead we see a clear reference to those investigations – including research investigations, the cytokine from the CSF – by Dr Harvey. It is not a question of asking you to take a view as to the clinical judgment, I am asking you why the study was designed in this way and if you say that in fact on the ground it operated in a completely different way I am asking you why.
A I am not saying that. I am saying that the clinical decisions, the decision to include lumbar puncture and the mechanism by which the lumbar punctures were conducted, were entirely down to the clinicians and nothing to do with me and I can offer no further insights into them.
Q Except, you say, that you did play a role because you took it upon yourself to telephone their secretaries, and to that extent you admit, you accept, that you played a role in the roles played by Dr Harvey and Dr Berelowitz?
A No. I merely contacted their secretary to let them know the child would be coming to the ward on several occasions. That was the limit of my role. It is not in any way a clinical role. It is a clerking role. One would never suggest that a ward clerk had something to play in the conduct of a lumbar puncture in a child in similar circumstances.
Q Perhaps you can explain to us first of all this. Why do either of them need you to phone their secretaries? There are junior staff, we know. We have seen letters from Dr Casson indicating that he had a role to play in the investigations that were to be carried out. Why did you need to phone their secretaries?
A In the end, I did not. I did it on several occasions but I think it petered out very quickly since the clinicians, Dr Casson in particular, just assumed that role, and I made contact on a couple of occasions as per the original plan, as I had agreed to enter into it, and beyond that point my administrative role became redundant. It was merely an offer that I made in order to help out with the workload by making that call, and in the end it was deemed unnecessary.
Q Why, if these were ordinary clinical referrals, in other words as I understand it you are saying Professor Walker-Smith, or one of his team, saw a child and said, “Dr Berelowitz and Dr Harvey need to see this child”, and that was a clinical decision, why did you need any input from you at all? Why do you have to be the one who telephones people’s secretaries?
A Simply, when this was being set up, it represented a considerable additional burden to what was already the busiest paediatric gastroenterology unit in the country. For that reason, and that reason alone, I offered to help out.
Q If we look at the Royal Free records of JS, this is an undated later document of a ward protocol which appears to have been developed simply dealing with the pragmatics of the study. We see at number 4:
and I imagine that is a reference, is it, to Jill Thomas, your research nurse –
“will inform Dr Berelowitz of admission.”
Do you see where I am? It is top of the page, paragraph 4.
A I do.
Q That is a reference to Jill Thomas, is it not?
A I imagine it is, yes.
Q Why could she or her equivalent, if it were a time when she was not there, not take on this role?
A I am not entirely sure when she started, but it seems from this document at point 4 she did assume that role at some stage.
Q Yes, but you tell us that on this timetable you were assuming the role of arranging from an entirely administrative basis that instead of someone on the ward ringing up Dr Berelowitz’s secretary and saying, “We have a child who Professor Walker-Smith needs seeing,” you are saying that for some reason you chose to go through a process which involved them ringing you, and you ringing Dr Berelowitz or Dr Harvey’s secretary?
A It depends entirely upon when Jill became part of this process. It may well be that when that document – the original document – was designed, and I believe it is the case, she was not part of the team. She was not employed.
Q I accept that. I accept that. That is why I said to you “her equivalent”. The point I am now asking ---
A There was no equivalent.
Q All right. Then the point I am asking ---
A She had a unique position.
Q The point I am now asking you is a slightly different one, doctor, which is why it is that if these were straightforward clinical referrals from this ward, to ask another doctor in a straightforward clinical way, to come and see a child they needed your role at all, whatever you were doing?
A Again, I reiterate. It was merely an effort to alleviate some of the administrative burden from a very, very busy unit in the early days of this work. That was my role. It was as simple as making a phone call to a secretary and letting her know that a patient would be coming to the word. That was it.
Q I suggest that your role in this protocol, doctor, and its carrying out means that you were in fact responsible for these children having routine lumbar punctures because they were arranged by you when they came into the ward as a routine research investigation under the protocol.
A Again, this is a somewhat bizarre suggestion on the basis that the lumbar punctures did not need arranging by anyone. They were conducted following on from the colonoscopy under the same sedation by the clinicians at the behest of Professor Walker-Smith, where he deemed it clinically necessary.
Q Would you plan ---
A It was nothing whatsoever to do with me at any stage.
Q Would you turn on to page 370aa in FTP 2. Do you have the letter? It is on blue paper?
A Yes, I do.
Q This is a letter that was written a considerable time after The Lancet children work concluded, from Professor Walker-Smith to you, and he says at the bottom of the letter – which is the only bit I want to ask you about at this point:
“I also feel that Dr Harvey’s contribution to the study should now be concluded and Dr Andrew Lloyd-Evans asked to join us. Do you agree with this?”
Would you explain to us first of all, what was Dr Harvey’s contribution, as you understood it referred to in that letter?
A Dr Harvey was the collaborating neurologist.
Q And why, if he had a clinical involvement determined by the clinicians, is Professor Walker-Smith writing to you, asking if you agree to curtail his role?
A It is not my letter and I do not know, and I find no evidence of a response from me in the documents. Professor Walker-Smith is the best person to answer this.
Q It is a letter that was written to you, Dr Wakefield, and it says that Professor Walker-Smith felt that Dr Harvey’s contribution to the study should now be concluded, and he asked whether you agreed with that. There is only one interpretation that one can put on that, is there not, which is that for some reason he felt that it was necessary or polite or appropriate, or whatever word you like to use, to consult you as to whether Dr Harvey’s role should be curtailed, and I am asking you why he should write to you in those terms if, as you say, Dr Harvey’s role had nothing to do with you at all but was determined by the clinicians?
A I reiterate that Dr Harvey’s role had nothing to do with me at all, whether he continued to participate in the project or not was not a decision for me. It was a decision for Dr Harvey. There is no response from me to this particular question, and to try and understand the provenance of this question, Professor Walker-Smith is the appropriate person to ask.
Q If Professor Walker-Smith were under the impression that Dr Harvey’s contribution to the study was in some way something that you had arranged and which you had to agree to curtail, he would have misunderstood the situation, would he?
A When the original protocol was put together as the coordinating investigator, it was my job to try and bring together a group of people who might shed some light upon this disorder. Dr Harvey, in the absence of a paediatric neurologist, was one such person. Beyond asking him if he would help, I have no input whatsoever into Dr Harvey’s role so, again, I am unable to offer any insight into why it was felt by Professor Walker-Smith or others that this role had come to an end, or might be curtailed. I am sure that Professor Walker-Smith can talk to that.
MS SMITH: Sir, I see it is five past three. I do not know what you would like me to do now – stop for a few minutes?
THE CHAIRMAN: Yes. I think we will now have a short break. It is five past three, so shall we say until twenty-five past three? We will then resume. First of all, Dr Wakefield, are you happy to continue for a little bit longer after the break?
DR WAKEFIELD: Yes.
THE CHAIRMAN: Or would you feel you have had enough?
DR WAKEFIELD: No, I will let you know.
THE CHAIRMAN: So we will continue at twenty-five past three.
(The Panel adjourned for a short time)
THE CHAIRMAN: Good afternoon. Ms Smith?
MS SMITH: Thank you, sir. Dr Wakefield, just apropos of where we reached before the tea break, could I ask you to look at Child 6, please, GP records? It is page 245. This is a letter from Dr Peter Harvey a considerable time later, in May 2001 to Dr N, who was Child 6’s GP, in relation to him then having headaches. The only part I want to ask you about is the first paragraph.
“Many thanks for your kind referral of this young man, who I have actually met before, when I was on the staff of the Royal Free Hospital and I examined him neurologically at the request of my colleague Dr Andrew Wakefield, who was investigating children with autism and the relationship with chronic inflammatory bowel disease.”
That account by Dr Harvey these years later reflects, does it not, the role that the ethics committee said that you were going to carry out, namely that you were the one who was requesting the neurological examination from Dr Harvey?
A Firstly, it is not my document. Secondly, we are now some years down the line and, thirdly, it is incorrect. It is not consistent with my role, which was to inform Dr Harvey’s secretary that a child would be coming to the ward and in this instance Dr Harvey’s memory is in error.
Q Like many others, it is not your document, and the person who has written it is in error as to their understanding of your role in this study, Dr Wakefield?
A Other than what I have said, I can offer no further insights into this letter.
Q Can we go to FTP1, please at page 209. At the bottom of the page, doctor, is a paragraph that we have looked at on a number of previous occasions and in this, the indication is that the procedures that were to be carried out on these children in response to a question in relation to procedures and samples was that they were part of normal clinical care, clinically indicated. Is that correct?
A I am sorry, Ms Smith, I am losing part of what you said.
Q I am sorry. I said it is a paragraph we have looked at a number of times before and we see at the bottom of the page an indication in answer to the question:
“Would the procedure(s) or sample(s) be taken, especially for this investigation, or as part of normal patient care?”
We see an indication that the procedures were clinically indicated?
A That is correct, yes.
Q That, I suggest to you, is the first time in the ethics committee application that that is said. The protocol does not say anywhere that the tests are clinically indicated, nor does the patient information sheet which we have looked at. They, as I think we agreed, are in the language of research.
A Yes. The document itself, the full protocol, Dr Pegg has said it is not uncommon for clinical investigations and the research elements to be included in the same document. I will give you an example. If you said you were going to analyse the cerebrospinal fluid for cytokine levels without mentioning the fact that a child was going to undergo lumbar puncture, there would be a certain lack of logic to it and that is the reason why clinical investigations are included, to give the ethics committee a full picture.
Q I am sorry, Dr Wakefield. You quote Dr Pegg, but the fact is that you have told us already that you had not filled in a form before this form. That is correct, is it not?
A No. What I am saying is that my perception of this is entirely in accordance with that of Dr Pegg, that providing a comprehensive list of the investigations that a patient is to undergo is by way of providing a coherent picture to those who are reviewing the document and the purpose of this specific pro forma is to establish by virtue precisely of that question whether these are clinical investigations or not. That is what it seeks to establish and that is the answer that is given in this case. These are clinical investigations and there are additional research elements to it to be undertaken on the samples taken during the clinical investigation. Therefore at that point it is entirely the prerogative of the ethics committee to ask for further and better particulars if they require it.
Q Dr Wakefield, we are going to be here an awful long time if you do not address your answer to the question which you are asked. I think maybe you did not on that occasion, so can I just go through it again with you? I am not going to engage with you on what Dr Pegg may or may not have said and, if I may say so, that is not what you are here to give evidence about. I have directed you to that paragraph which indicates that the procedures were clinically indicated, part of normal patient care, and I am asking you whether it is correct that that representation that the procedures were clinically indicated, that was the first time, I suggest, that that had been said. What I said to you was, it is not in the protocol and we looked at the terms of what the aim of the protocol was yesterday, if you remember, and I am also suggesting to you that it is not in the patient information sheet. In other words, this paragraph is the first time that you say that the procedures were clinically indicated.
A It is the first time it is said that the procedures are clinically indicated and that is the opinion of the clinicians. It is not my decision to take, but it is the first time the question is specifically asked and it is asked appropriately in this document.
Q I do not know, in the light of your answers to questions about your knowledge of research ethics, whether this is a question you will feel able to answer or not, but were you aware when you filled this form in – when I say “you”, I mean collectively you – that ethics committee approval would be, to say the very least, highly problematical if these invasive investigations were in fact being carried out for research purposes?
A It is an entirely speculative question and I am unable to answer it. From the outset, it was determined by the clinicians that these investigations were indicated.
Q Dr Wakefield, it is not a speculative question and I am going to press you for an answer. What I said to you was, were you aware that it was highly problematic that any ethics committee would give you permission to do colonoscopies and lumbar punctures on children for research purposes? Was that something which you considered?
A It did not even cross my mind.
Q When you say it did not cross your mind, it did not cross your mind whether you would get permission for it, are you saying?
A It did not cross my mind that there was any intention on anyone’s part to conduct investigations, clinical investigations, under the guise of clinical indication but for the purposes explicitly of research.
Q I think you would accept that the younger children are, the more problematical it is that you would get consent for investigations upon them of whatever kind. It becomes more difficult, the younger the child is.
A I have no experience of that at all, I am afraid.
Q If we can look, please, at page 211 – we have looked at this briefly before – this is just to remind ourselves. This is the October 1995 document and I think you agreed with me that that is framed in the language entirely of research. Then if we go on to the one which you asked me to go to before, which is page 232, this is a far fuller version of information to be given to the parents. Again, we see in the first two paragraphs that doctors have been alerted to the possible existence of a new disease, that they have looked into the background medical and scientific literature, they have formulated the hypothesis and what the hypothesis is. It then says:
“We would like to carry out a series of tests which, we believe, will help us to establish the features of this possible disease. Our aim is to characterise the problem so that, for the future, we may be able to treat affected children and improve their wellbeing.”
I have suggested to you that every line of that clearly indicates that this study was a research study down to that point, the improvement of their well-being, and I think as a general proposition you would accept that, would you not, because you told me on Friday that that was related to the research investigations that you wished to carry out?
A I think if the interpretation is confined specifically to the adjunct research investigations, then this was in part a research study. The document at page 211, imperfect as it is, was drawn up by me because I felt that it was relevant to the research aspects of any study and therefore it does not concern itself with the clinical aspects.
Q I think you would agree with me that these documents were hugely important, because they explained to the parents what was going to be done and why.
A No. As I pointed out yesterday, in a clinical setting it is not necessary to have a hand-out which is given to parents to describe why their child, symptomatic child, might undergo colonoscopy. That is not necessary. A hand-out, an information sheet, to parents is required as a necessity, a specific part of the ethics committee application, to describe the background to the study.
Q I think we would all agree on that and I think we are also agreed that the differentiation from the parents’ point of view between clinical and research is extremely important; it is important from the parents’ point of view that they understand it.
A That is correct and that is something which will have been explained in detail to the parents by Professor Walker-Smith during their first encounter.
Q You see, can you explain to us on that basis, Dr Wakefield, why the entirety of the rest of that document sets out the precise nature of the investigations that the child is to undergo?
A Because that is a specific requirement of the ethical practices committee.
Q Not if it applies, as you have just told us, to clinical medicine, because, as you have rightly said, you do not have parent information sheets in relation to standard clinical medicine; it will be explained to them by the clinician. You started off by saying that and I accepted that. Then why, in the rest of this document, do we have, if you look down at the rest of it, past “improve their wellbeing”, which we are all agreed relates to the research investigations, it just goes straight on to say, “You and your child will be admitted” and then a very detailed explanation of precisely the investigations they are going to undergo, which you say were clinical?
A That my colleagues, my clinical colleagues, deemed to be clinically merited. It was our duty as part of the completion of this ethical application to provide a comprehensive background to the parents on that. In the absence of any research study at all, there would be no such explanatory document and it would be done entirely by the clinician in the outpatient appointment.
Q Doctor, this is information for the parents. That is what it says at the top. That is right, is it not? A hand-out to the parents. Is that correct?
Q You then start off by telling them all about your research – you accept that – for the first two paragraphs. The possible existence of a new disease, the background medical and scientific literature, the formulation of the hypothesis and then you set out the hypothesis and you say:
“We would like to carry out a series of tests which, we believe, will help us to establish the features of this possible disease. Our aim is to characterise the problem so that, for the future, we may be able to treat affected children and improve their wellbeing.”
A The background is really a summary of the interim clinical findings. So not research, no. It is a background to how we came to this position at that particular time.
Q Doctor, five minutes ago you told the Panel – and I entirely accept you were correct in what you said – that parents whose children are undergoing clinical investigations do not need to be told all the details in a parent information sheet, because the clinicians will have explained it to them.
A I think there is a misunderstanding. In order to make this document as comprehensive as possible and understandable to the parents, it is necessary to provide a description of the origins of where this came from. That is, the clinical background which led to the formulation of the research hypotheses which then led to the science. To start, for example, at paragraph 3 would make no sense at all. So it is simply an effort to be as comprehensive as possible for the benefit of the parent.
Q Doctor, what matters, really matters, when we get down to brass tacks, is that these parents understand what is being done for their child, because their child needs it clinically, like any other child, has gone along with symptoms and the doctor is doing something to make it better. That is the first thing. What is being done for research purposes, where, however laudable the aim, they have to consent, knowing all the risks, to research on their child. Would you accept that? Those are the two things they have to understand.
A To understand how the clinician might go about addressing their concerns, their symptomatic concerns, in their child through routine clinical investigation on the one hand and as far as the research elements to this particular protocol, then the risks and benefits or potential benefits of that and what it is seeking to find.
Q This document, when we get to the part which sets out all the investigations and their risks, does not say “Now we have told you about the research, these are the things that you would be having anyway”, how is any parent to know from that what is research and what is clinical medicine, how do they tell from that handout?
A What happens routinely – and this is a clinical matter – is that having explained the background and the procedures, the modus operandi in the clinical context of what a child might undergo, and what the benefits of that and the expected findings might be – for example if there is inflammation then there is potential for treatment – then the parent is given a handout at the end of the outpatient appointment to go away and to assimilate in their own time and to come back if there are any questions. Again, this is not something that is within my remit, it is not something in which I was involved directly in terms of the outpatient explanation or distribution of any documentary information at that outpatient appointment. Again, that is a question best directed to the clinicians.
Q Who drafted this, Dr Wakefield? Who drafted the parental handout?
A It would have been a consensus document drawn together by the team.
Q Sorry, someone would have done the draft though, was that you?
A I will have done the typing or my secretary will have done the typing.
Q Yes, but a document as long as this, someone has to come up with a first draft. Who came up with that, do you recall?
A I do not recall.
Q Because that document, I suggest to you, would leave a parent under the impression that the child was being asked to undergo research investigations, all of them, and that would be correct, that is what they were being asked to undergo.
A No, I am afraid that is completely and utterly wrong; what it takes out of the equation is the essential interaction between the clinician and the patient in the outpatient appointment where that process is described in some detail.
Q But we have agreed, have we not, that in normal clinical medicine you do not give patients handouts like this explaining the precise nature and the risks of the procedure that they are to undergo. You do not do that in normal clinical medicine because the clinician sits down with the parent or the patient and discusses it with them and makes a note of what he says.
A Again, this is an issue for Professor Walker-Smith but I am sure what he will say and at least from my experience of the clinical encounter sitting there as an observer is that there is a very detailed description given to the parents of what the clinical investigations will be, and it is very clear to the parents that that is what they are, they are clinical investigations undertaken to elucidate the origin of the child’s symptoms which the parent has sought referral for.
Q You are telling the Panel that a parent, who does not have necessarily sophisticated knowledge of the distinctions between clinical and research medicine, would be able to understand from this document that some of these things were clinically indicated in their child and some were research for which they could volunteer or not?
A No, that is not what I said; again, let me reiterate. This document should be taken in combination with the explanation provided orally to the patient at the outpatient appointment.
Q Can we go on to page 234? This is the actual consent form:
“I have read and understood the aims and nature of this study [a reference to the information sheet that they will be given] and I have discussed, in detail, the implications of the study with the Doctors concerned. I hereby agree to let my child take part in the study. I understand that I can withdraw my child from the study at any stage without prejudicing his/her management or treatment in any way.”
Those last words “I understand that I can withdraw my child” is again the pure language of research, is it not, and I will suggest to you why, Dr Wakefield, so you can understand what I am saying. If the child needs this treatment, it is clinically indicated, the parent cannot withdraw him without prejudicing his treatment, obviously. If he needs a clinical colonoscopy and the parent says “I do not want him to have one” then that is going to prejudice his treatment and that is clinical medicine. I suggest to you that this is research medicine because the whole point about research is that you can withdraw your child without prejudicing his normal clinical treatment.
A This statement is a standard statement required by the ethical practices committee to be included in the consent document and it refers to, specifically, those elements of the protocol for which it is necessary to obtain ethical practices committee approval and those would therefore be research. So if, for example, a parent said “I do not wish my biopsies to be examined in any way for evidence of measles virus or to be used for the purposes of elucidating the characteristics of this disease and I do not want them to appear in any peer reviewed publication”, that is entirely their prerogative, and what this is doing is offering the parent that option. If they so choose it will not in any way prejudice Professor Walker-Smith or his team’s approach to the care that he would give to that child.
Q So what you are envisaging, when the parent gets this consent form, accompanied as we see by the parent information sheet – and that is why it says “I have read and understood the aims and nature of the study …” – you expect them to be able to understand from these two documents that some of the investigations are going to be clinically indicated, and so if they withdraw their child they will prejudice their treatment, and some are not clinically indicated and they can withdraw their child without prejudicing their treatment. Are you seriously suggesting, doctor, that these documents are saying that?
A Again,, Ms Smith has omitted the fact of the discussion, the detailed discussion, that would have taken place between Professor Walker-Smith and the parent in the outpatients which will have categorised what was clinical and what research investigations would or could be conducted in addition. That is a fundamental part of it, these documents really only serve to clarify and they give the parent the opportunity to come back and seek further and better particulars. There is also an ongoing dialogue, as I understand it, and as was my experience when I was clinically involved back in 1981, that the ongoing dialogue takes place between doctors and parents during the week that the parent is present with their child on the ward. There is an opportunity at any stage for the parent to raise queries with the doctor and have the position clarified.
Q If we look back in FTP1 at 86b, this is a consent form that Professor Walker-Smith comes with on which you rely and at which we will be looking again later, but just for the purposes of the wording:
Your child has been referred for diagnostic colonoscopy [i.e. it is clinically indicated]. Several small pieces of tissue are taken during the procedure for diagnostic purposes ... It is therefore of great value for laboratory research to have such biopsies available to study … Your permission is asked to agree for two extra biopsies to be taken for these purposes.
Whether or not you agree to this will in no way influence your assessment or treatment.”
That is perfectly clear information to a parent, is it not, that is all you need to say about the colonoscopy, it is a diagnostic colonoscopy. You do not need all these pages of information about risks because they are having it anyway because they need it, but what you do need is a piece of information which says “We want to take a couple of extra bits while we are in their anyway and do you mind, for research purposes”.
A Again, Professor Walker-Smith will speak to this, but this is I imagine a template that came with him from St Bartholomew’s Hospital where this protocol operated. It is a consent form and not a patient information document. What the ethical practices committee at the Royal Free required were two separate documents, one a patient explanation document and the consent form, and it required some considerable detail to be given in the information document, and that was entirely appropriate.
Q Turning on, doctor, we know that the nature of this application elicited further inquiries and whether you discussed them directly with Dr Pegg or not you knew, I think you accept, that inquiries had been sent to Professor Walker-Smith and you accept that you would have seen the letter asking about the nature of the intensive regime.
MS SMITH: Dr Pegg’s request for clarification elicited a response from Professor Walker-Smith which was copied to you, and that is at page 291.
Sir, I see it is five to four; I am quite happy to go on but I would tell you that if you were planning to finish at four we would end in the middle of the questions I have to ask about this letter.
THE CHAIRMAN: In that case it would be better that we adjourn. It is getting very close to four o’clock, so we will now adjourn and resume at 9.30 tomorrow morning. Dr Wakefield, you are still going to remain under oath overnight as has happened over the past few weeks now, so please make sure that you do not discuss this case with anyone. We will resume at 9.30 tomorrow morning.
(The Panel adjourned until 9.30 am on Tuesday, 15 April 2008)