Wednesday, February 1, 2012

Day 22 GMC Fitness to Practice hearing for Andrew Wakefield



Tuesday 14 August 2007

Regents Place, 350 Euston Road, London NW1 3JN

Chairman: Dr Surendra Kumar, MB BS FRCGP

Panel Members: Mrs Sylvia Dean
Ms Wendy Golding
Dr Parimala Moodley
Dr Stephen Webster

Legal Assessor: Mr Nigel Seed QC


WAKEFIELD, Dr Andrew Jeremy
WALKER-SMITH, Professor John Angus
MURCH, Professor Simon Harry


(Transcript of the shorthand notes of T. A. Reed & Co.
Tel No: 01992 465900)


MS SALLY SMITH QC and MR CHRIS MELLOR and MR OWAIN THOMAS of counsel, instructed by Messrs Field Fisher Waterhouse, solicitors, appeared on behalf of the General Medical Council.

MR KIERAN COONAN QC and MR NEIL SHELDON of counsel, instructed by Messrs RadcliffesLeBrasseur, Solicitors, appeared on behalf of Dr Wakefield who was present.

MR STEPHEN MILLER QC and MS ANDREA LINDSAY-STRUGO of counsel, instructed by Messrs Eastwoods, Solicitors, appeared on behalf of Professor Walker-Smith who was present.

MR ADRIAN HOPKINS QC and MR RICHARD PARTRIDGE of counsel, instructed by Messrs Berrymans, Solicitors, appeared on behalf of Professor Murch who was present.


Page No


Examined by MS SMITH 1
Cross-examined by MR MILLER 18
Cross-examined by MR HOPKINS 28
Re-examined by MS SMITH 30
Questioned by THE PANEL 31
Further cross-examination by MR MILLER 35


Examined by MS SMITH 35
Cross-examined by MR COONAN 43
Cross-examined by MR MILLER 46
Re-examined by MS SMITH 47
Questioned by THE PANEL 48

THE CHAIRMAN: Good morning to you all. Ms Smith, do you have a new witness?

MS SMITH: Yes, I will call Professor Revell.

Examined by MS SMITH

(After introductions by the Chairman)

Q Professor Revell, would you first of all give your full name, address and your qualifications?
A Professor Peter Alan Revell, and I now live at XXX, and my qualifications are BSc, MB BS, PhD, FRC Path and FPSC.

Q Thank you very much. I think it is right that you are now professor emeritus, in other words retired, at the University College London, and you were formally professor of histopathology there?
A Yes, that is right, at the Royal Free, yes.

Q You were appointed, is it correct, as the academic head of the department of histopathology at the Royal Free in May 1992.
A That is correct, yes.

Q You began your post at the beginning of 1993?
A Yes.

Q Ultimately you retired in September 2003?
A Yes.

Q Can you tell us what that post involved?
A Yes, I was academic head of department, so responsible for the undergraduate teaching, postgraduate affairs, like PhD students and research, and also responsible for the NHS side of the department, the diagnostic biopsy service, the autopsy service, and all sorts of things like that.

Q Can you explain, remembering that there are lay members on the Panel, the difference between research histopathology and clinic histopathology, in broad terms?
A Yes, indeed. Clinical histopathology is the looking at biopsies to tell if somebody, for example, has a bit of a liver problem, they might take a liver biopsy, send it to us and we would look at it and say “they have such and such a disease” and then they would work out how to treat it. A breast biopsy would be another example, a frozen section of the breast. It also involves looking involves looking at specimens after they have been excised to make sure, for example, that a cancer had been properly removed. Although people think that pathology is mostly cutting up dead bodies, that is a very, very small part of the work actually, but it is also the autopsy service, so that is the diagnostic side. Then in research one is always being asked to look at things that are going on in terms of experimental work. It might be experimental animal work or it might be material coming from human cases. We have to have ethical approval for both of those things, both animal work and for human research work.

Q Just so we are all clear, because I think these are terms that you may be using later during your evidence, what does the term “clinical research” actually mean?
A By that I mean research that is based on clinical material, material that is obtained from patients. It might only be blood tests; it might not involve any tests at all; it might be having two groups of patients and putting one on one treatment and one on placebo, or another treatment, and comparing them, so it is really human case-based – not necessarily case-based, human clinical patient-based research.

Q So, research involving patients?
A Yes.

Q In your role as academic head of department, did you have responsibility for directly supervising your own research group?
A Yes, yes, indeed. I took four people with me to the Royal Free. We were interested in bone and joint disease, particularly artificial joints and things like that, but there were other people doing research in the department in hepatology and inflammatory bowel disease, neurology and so on.

Q As far as your own research is concerned, was that clinical research, in other words related to the care of patients at all? Did it involve patients?
A No, it did not. We were doing two sorts of things, one was experimental studies in animals and in cell culture, looking at new materials for implantation in man for artificial joints and things like that, and then we were looking at tissue from people whose joints had failed and tried to work out why they had failed, obviously with ethical committee approval, but it was not directly related to patient care, it was ongoing, what is going on in this condition?

Q You have mentioned that there were others in the department who were pursuing their own research, would those other specialisms who were also researching in your department, would some of them also be doing pure research and some of them doing clinical research, in other words research involving patients?
A I think it would be fair to say that all the rest of the department, or as far as I can think, everybody was doing case-based clinical research in the way that we have defined it already. I think we were the only ones doing fundamental experimental research.

Q What knowledge did you have in relation to the research which was being undertaken in your department? Did you have a responsibility overall for it?
A Yes. There are questions about academic freedom and so on, but I felt I was responsible for what was going on in the department in terms of the ethical background; whether proper ethical permission had been obtained. Things changed while I was in the Chair with the Alder Hey and all these other things, but at the time we are talking about all that had not happened, but, yes, I had that responsibility. Then I also had ultimate responsibility for the funding and the budgetary sides of the department.

Q You have mentioned academic freedom, would you have regarded it as part of your role to have any control over the actual subject matter of the research?
A No, not so long as it was ethical. I think that senior colleagues should be allowed to pursue their things without a big stick attitude from the professor.

Q You have mentioned various specialisms. I think you mentioned hepatology and urology in relation to research projects going on in the department. What was the research that was being conducted in gastroenterology? What was the group that was doing it?
A When I first went there, there was Dr Andy Wakefield’s group, the inflammatory bowel disease group, which had Paul Dhillon … I am trying to think who else – but there was a group of people within the department, Professor Pounder and others, but Dr Wakefield had a joint appointment and they used lab space in our department. Dr Wakefield had an office, but basically they were doing a lot of things in medicine. But they were mostly working on inflammatory bowel disease I understood that to be two different aspects. I mean, I did know what was going on to some extent.

MR MILLER: I am sorry, I did not hear the answer, inflammatory …

THE WITNESS: Inflammatory bowel disease.

MR MILLER: I thought you said joint.

THE WITNESS: They called themselves the IBD group, inflammatory bowel disease.

MS SMITH: (To the witness) I think it follows from what you said before about the other specialisms, researchers other than yourself … Was the inflammatory bowel disease group, as far as you were aware, engaged on clinical research, in other words research involving patients?
A Predominantly. They had done some work on animal … Andrew Anthony had done some work on models of inflammatory bowel disease in relation to non-steroidal anti-inflammatory drugs in animals as well. I was always interested in that because I had done some human stuff in a previous incarnation, before I took that job at the Royal Free.

Q You have mentioned the role of Dr Wakefield: when you took up your post as head of the department of histopathology in January 1993 – I do not think there is any dispute about this – it is right that Dr Wakefield had just been made a senior lecturer across the departments of medicine and histopathology.
A That is right, yes.

Q Is it a usual situation, or was it for you at that time, to have an appointment across two departments in this way?
A No, I found it very unusual. I had never met it before.

Q You were Dr Wakefield’s joint head of department, is that correct?
A That is correct.

Q With whoever was the head of department in medicine?
A Yes. There were two professors of medicine at the time.

Q Was he ultimately promoted to a reader in the medicine department only at some point in 1997?
A That is right, yes.

Q Did he then have anything further to do with your department after that?
A Not directly, in so far as Dr Andrew Anthony was continuing to work in the department and was being paid through, towards the end of his appointment, was being paid through an account which had a department number, but from memory that was about 2000 or something like that.

Q Dr Anthony may arise again a little later. Is it right that he had a research post in your department under Dr Wakefield?
A That is right, yes.

Q At the time when you were joint head of Dr Wakefield’s department, what was your understanding of his position? What did you understand him to be doing?
A I understood him to be somebody who had qualified as a surgeon but was no longer practising clinically and had devoted his life to doing full-time research.

Q So when you say no longer practising clinically, did you understand him to have any involvement in seeing patients or treating them or indeed with surgery?
A I was not aware that he had any association with doing any surgery. I do not recall knowing for sure whether he was seeing patients or not. I assumed he was not seeing patients. It is too long ago for me to know but that was my impression.

Q Were you in any applications in which Dr Wakefield made for funding with regard to his research or was that organised through the Department of Medicine?
A I cannot recall a single occasion when I was given a proposal to look at with a view to, say, getting ethical committee approval or the sorts of things that a head of department would have done. I may be wrong but I cannot recall that. I had assumed that all that was going through the other head of department, namely the Department of Medicine. Certainly none of the grants or none of the things were attributed to us in terms of a department; they were all attributed to medicine.

Q I want to ask you about a particular matter which involves looking at a document in FTP2. At page 506 is a letter dated 8 August 1997 addressed to you from Mr Tarhan, who was a finance officer.
A That is right.

Q “Dear Peter,

Freemedic – Scientific Advice

You may be aware that Andy Wakefield has put forward a proposal to Freemedic to fund his research work which we understand may identify a treatment (not cure) for Crohn’s disease. The procedure has been patented. The problem I have is understanding the science involved.

Are you able to assist in reviewing the attached documents and making any scientific comments in confidence to the directors of Freemedic to assist with their deliberations.

I realise the documents are substantial, for which I apologise. Unfortunately that is the way Andy gave them to me.

If you are not able to assist, please return the documents and I will pass them on to someone else.”

Can I ask you a few questions about that letter, Professor. Did you know anything about it other that what is contained in the face of that letter? Were you aware that there was a new treatment for Crohn’s disease being identified?
A Not at all.

Q Did you know anything about the fact that there had been a patent taken out in relation to it?
A Not at all.

Q Can you tell us what Freemedic was?
A Freemedic was a company formed by the Royal Free, hence Freemedic, to exploit the intellectual property of academics within the Royal Free so if you had some research which was patentable they would help towards the cost of the patent and they would look for people who might help to exploit that invention and they would have a small amount of money to give to research. I used them myself. I had a patent and they gave us a small amount of money to do some further research as well.

Q When you talk about intellectual property, you mean the ownership of the invention, in effect; the ownership of the idea?
A Yes, that is right.

Q Was it a common practice for a researcher in the hospital to put forward a business case in this way for a particular idea or project that they had in mind?
A There was a channel for small amounts of money from Freemedic to take things a bit further if you had a patent or you had something which looked good for the institution, yes. I do not know how much people used it. I used it myself.

Q Was there anything unusual to you in you being asked to assess a proposal?
A No, I did not think so. I had no interest in terms of exploiting intellectual property, or in fact no knowledge of it. I was also a very experienced appraiser of research proposals for the medical research, EPSRC, lots of charities, NIH in the States, European Commission and so on. I have had a lot of experience of looking at grant proposals so it seemed a natural thing that he would ask me.

Q Under cover of that letter from Mr Tarhan, if we turn to page 507 we see the proposal that was attached to it. This is Measles Virus and Crohn’s Disease, A Clinical Strategy, including a preliminary study of the effect of oral measles virus-specific dialyzable lymphocyte extract Transfer Factor in Crohn’s disease, dated May 1997. I want to take you to one or two parts of this document because it is relevant to matters that the Panel are going to have to consider. We have seen a transfer factor ethics committee application in respect of children but this is another proposal. This time it is the use of Transfer Factor in Crohn’s disease with regard to adults. Was it your understanding, Professor, that it involved a proposal for funding in respect of two trials about the effect of Transfer Factor?
A Yes. I have not been through this word for word in the last day or so but I have read my own summary of it. Basically there is one main trial and tucked in at the end there is another brief thing asking for small – from memory there were about 30-odd patients in each group in the main thing and then there was a small thing at the end asking for somebody to do I think 10 Crohn’s disease patients.

Q I will take you through the relevant pages just so the Panel can see it. Going to page 549 we will see that is the index setting out the trial and giving the title. Going to page 553 ---
A I have to say that this is set out in exactly the sort of way one would expect a well prepared document of this sort to be set out.

Q Going to page 553, I am not going to take you into the substance of this, just so we know what the trial was about, that is all. This is the patient selection and we see the patient population – 50 patients with a documented history of Crohn’s disease. Looking at page 554, we will see the point that I have just underlined for the Panel that this is a trial for adults 18-65 years of age, is that correct?
A Yes.

Q Going to page 577 we see the reference at paragraph 12.6:

“Patient compensation for adverse effects on health.
This trial constitutes clinical research, and as such is covered by appropriate insurance held by the Royal Free Hospital School of medicine.”

Is that the kind of provision you would expect?
A Absolutely, yes. We would all have been covered by virtue of our posts in the medical school for those sorts of things, including the animal research.

Q Going on to page 579, it appears also to be intended to do a small open label study. Is this the second project that you referred to as being tucked in at the end?
A Yes.

Q It says:

“A small pilot study will be conducted in an identical manner to that described above, excluding the placebo arm, to assess the efficacy of the drug in up to 10 patients with active Crohn’s disease. As above, patients should be receiving no immunosuppressive medication. The drug will be given on a named patient basis …”

That is a pilot study, Professor Revell, but was it also a research study still, part of the research as you understood it?
A I do not quite know how to answer that. What do you mean by a study? One assumes that there were, even with only 10 patients, the methods present in terms of statistical approach and so on to get a meaningful answer. It is called a study. It is clearly not like the big study where there are all the protocols and so on. Maybe it is just taken as a given that all those protocols exist for these 10 cases. I got the feeling it was an afterthought; not necessarily an afterthought in terms of their research, but that it was something that was put in and say we want to do 10 more at the end.

Q Would all the requirements as far as compensation and ethics committee approval be the same for a small study as they would for the larger study?
A I would have thought so, yes.

Q Going to page 593, this is the patient information sheet. I will take us to a few paragraphs so the Panel can see them. The fourth paragraph:

“A possible new treatment called Transfer Factor, which has been developed by NeuroImmunoTherapeutics Research Foundation, an American-based research charity, in collaboration with workers at the IBD Study Group at the Royal Free Hospital.

This is the first study of a measles-virus specific transfer factor in patients with Crohn’s disease. To date, Transfer Factor against other viruses, bacteria and tumours has been given and has been extremely well tolerated without any adverse effects.”

On page 594, at the bottom of the page we see:

“The procedures in this study have been approved by the hospital’s ethics review committee.

Are there any risks involved?

Along with the possible desired effects, any medication may cause unwanted effects. Measles specific TF is a new drug and its possible side effects are not known.

If you feel unwell or have any unusual discomfort during the study, it is important that you tell the doctor as soon as possible. Your doctor can withdraw you from the study at any time if he/she feels it appropriate.

You may experience temporary discomfort …”

Are there any benefits?

It is hoped that you will benefit from the study drug but it is not known how long this benefit could last. Because the effects of Transfer Factor have to be thoroughly studied, it will not be available for general use for several years and cannot at this time be given to you after you complete the study.”

At the bottom of the page:

“What if something goes wrong?

The Investigators will adhere to the ABPI Clinical Trial Compensation Guidelines … A copy can be obtained from your doctor.”

That was the information that was to be given to patients who were in that trial, is that correct?
A Yes, indeed. That, I think, is entirely reasonable and what one would have expected.

Q Absolutely. You may not feel able to answer this but there is a reference to the fact that, because the drug is being given as part of a study, it will not be in general use for several years and cannot be given after the patient completes the study. Is that in fact an ethical issue for doctors that they have to underline to patients in a research trial that they may not be able to go on having whatever it is when the study is over?
A Yes, it can be an issue, not just a treatment but a new investigation. Is this investigation affordable? All sorts of things come in as to whether it might or might not be available. I do not think it is relevant to what we are talking about. We then get into postcodes and all those sorts of things perhaps.

Q Would you go back in the document to page 575 where we see the references to the ethical conduct of the study and to ethics committee approval.
A Yes.

Q At the top of page 558, the provisions as to patient consent,

“Patients who may be eligible will be informed about the study, provided with a patient information sheet approved by the local Ethics Committee (…) and given time to read and answer the questions.”

A Yes.

Q That was the proposal that you were sent, Professor Revell, and I think it is right, although we need not trouble you to go into the detail of this, that you indeed wrote a report detailing your views on the proposal.
A Yes. I do not know whether you have that in this bundle or not.

Q We do not have it because, with the greatest of respect to your views on it, it is not relevant to the matters that the Panel has to consider.
A Okay. It was, as Mr Tarhan had asked me, a two or three page fairly detailed criticism – and I mean that in the best sense – of what I was being asked to do of the proposal giving details in lay terms because Mr Tarhan is an accountant and he was trying to advise people funding who were not scientists. I do not know what the outcome was, whether it was funded or not, and I took the ethical signs as given. I do not know whether there were ethical issues around this or not. I was not looking at that, I was looking at the science.

Q Absolutely. I have asked you about your involvement with Dr Wakefield or the involvement of your department. Did you come across Professor Walker-Smith in the course of your work at the Royal Free Hospital School of Medicine?
A Yes. I could not give you an exact date or year but there was a time when Professor Walker-Smith and Dr Murch, as he was then, and the team were recruited or came over or were attracted to the Royal Free to set up a department of paediatric gastroenterology.

Q Did that apply to Professor Murch as well?
A I believe that Andrew Murch came across with John Walker-Smith, yes, from Bart’s. I think that the three of them came across together.

Q What was the role of the histopathology department as far as the paediatric gastroenterology department was concerned? Did you offer them a biopsy service?
A They were provided with the biopsy service they needed, yes, in order to do that and we set up with them regular clinico-pathological meetings which is common in all modern teaching hospital level hospitals if not general hospitals now. The clinicians and the pathologists often meet once a week or once a fortnight to discuss cases in detail.

Q I will ask you about those meetings in a moment, Professor. Would you explain to us in the context of what you told us earlier: you were providing a biopsy service in the normal way to look at tissue which had been removed from patients to help in diagnosis; is that correct?
A Yes.

Q In addition to that, were there histopathologists in your department who were undertaking research in collaboration with the inflammatory bowel disease group, in other words looking at biopsies for research purposes?
A Not that I knew of in a … It depends what we mean by research. If you mean were then involved in a defined clinical trial, as far as I knew they were not. They were looking at biopsies as they came through from the patients on the basis of clinical need. That is what I was told and that is what I believed.

Q I will ask you about that in more detail in a moment. You mentioned the meetings that had taken place. Those meetings were between whom?
A They were between the paediatric gastroenterology team and at least one pathologist who was delegated to sort of look after them, as it were, to look out the cases and prepare a discussion of them and talk about cases on an individual case management basis. Susan Davies was the one who took most of it but it might have been that if she was away or very busy, a registrar would have done it. On the whole, somebody from the department looked after the paediatric gastroenterologist meeting.

Q What exactly was that meeting to do? What was it to discuss/look it?
A I never attended it but I assumed that it was the same as the sort of meeting that I ran with the rheumatologist and other people ran with the hepatologist and so on, which was a day-by-day case management, what is happening? Let us see what is happening down the microscope, and we would show things on a screen projecting what the findings were in order that they would see what the pathology was and they would understand what was going on and we could understand their side and it was basically an extremely good way of communicating with your clinical colleagues in a way which you cannot get with just bits of paper. It was very important for laboratory scientists.

Q What was the ultimate aim of it?
A The ultimate aim was the day-to-day superb care, I think, across the board of patients.

Q Did there come a time when you were aware that there were biopsies being taken from the small intestine of children with autism?
A Yes. I should explain that I had antennae because I was head of department and I was always looking out for things like this where you might suddenly find that a series of biopsies were coming through and you would wonder whether they were really part of a trial – this sort of thing was happening occasionally – and one would then wonder where the funding was coming from. That was the reason for doing it and occasionally things would come through in which it might say autism or small intestinal … I cannot remember the details but something made me aware of the fact that there were biopsies going on.

Q You say that you had your antennae out and that you would sometimes wonder if something was part of a trial.
A Yes.

Q Do you mean by that a research trial?
A A clinical study, yes.

Q You said that if that were the case, then you had to start wondering about the funding.
A Yes.

Q Would you elaborate. Funding is not an issue for the normal diagnostic analysis of samples in the histopathology department, is it?
A Absolutely … Well, apart from the general lack of funding for everybody. Yes, in general, it was not an issue. Every now and again, somebody – and I do not want to say that it was these colleagues here – a gynaecologist, for example – I do not want you to think that gynaecologists were doing it either – would slip one or two things through and the NHS were paying for it and a drug company was paying for it as well and that is not appropriate and I thought it was my job to sort that out. That is what I mean by my antennae going out. I regarded it as part of my job.

Q When you became aware that there were biopsies from children with autism coming into the department to be analysed, what was your reaction to that? What was your concern?
A I went to see my colleagues who were linked with paediatric gastroenterology and asked them what was going on. Is there a trial going on? Is there a study going on? Although I have not mentioned it in there, I seem to remember having a conversation with Professor Roy Pounder who was involved in the inflammatory bowel disease group and I did everything that I could to satisfy myself that there was not a study of that sort going on and that these were on the basis of clinical need, which is what I was told and what I believed. I had no reason to not believe my colleagues.

Q As far as you were concerned, Professor, you have told us the difficulties about the funding and how that was an issue. Did you have any other concerns as well in relation to this particular … I do not want to use the word “study” because you have just told us that it was but in relation to this phenomenon that you noticed, that biopsies were coming in from autistic children? Did you have concerns in relation to that ---
A No because ultimately a clinician is responsible for what he does and the biopsies he takes and it is for him to decide whether that is part of the clinical need or not and it is the pathologist’s job to take that specimen and interpret it in the best way that he can putting together the best team that he can to do so and that was why we had specialists/people who liaised closely with Professor Walker-Smith and the paediatric gastroenterologists in terms of understanding their particular needs. That is what experts are for.

Q Of course. You say that you asked Professor Pounder. Did you also talk to anyone in your own department?
A No. Yes. That is what you have in my statement and the people I was most concerned with were people in my own department and I spoke to Susan Davies and to Professor Paul Dhillon and they both reassured me at the time that that was what was going on. I thought that this is what was happening. Perhaps I should add that subsequently when The Lancet paper was published, I then went back to them again and said, “How did it fall out?” and so on – and you have it in the statement anyway – that this phenomenon of the lymphoid nodular hyperplasia was noted in patients … The biopsies were sent through the ordinary department. That was the other thing. They were not being sent straight to Susan Davies or Paul Dhillon, they were going through the ordinary run of the mill and then being looked at, presumably at the meeting, by the specialist and that was our policy for the department in general. We have to do that for the sake of training. If you have young pathologists, you cannot have the expert creaming off all the good stuff, all the expert stuff. You cannot have the renal pathologist, for example, taking all the renal pathology and just doing that on his own because all the registrars do not get any chance to look at renal pathology. So, everything goes through the main thing (sic) and is looked at by whoever is on rota and then they are split out to be looked at and checked by the expert.

Q I will come on to The Lancet paper and matters of that kind in a moment, Professor Revell, if I may. Before I do that, you say that you asked your staff – and you have mentioned Dr Davies and Professor Dhillon – and you were informed by them that there was no study taking place and that the samples were coming through what you have described as being the normal process.
A On the basis of clinical need, yes.

Q I do not want to complicate matters but I do want to ask you about one particular issue. Are there what are known as retrospective studies which sometimes take place?
A Yes.

Q Would you just explain as clearly as you can to the Panel what they involve and whether they were relevant at all to your consideration?
A Yes. This is what I believe happened in this case, but I can give you another completely different example, and that was many years ago I was reader at the Royal London Hospital and a colleague of mine noticed the presence of some material called amyloid in the thyroids of a particular patient, or was it … Anyway, it does not matter, he made an observation and he thought, “That’s very interesting, I wonder if that happens and nobody’s ever noticed it before?” so he went back and looked at another one, and lo and behold there was this amyloid in this particular organ, and so retrospectively they went back through five or six or seven cases and described the presence of amyloid in a particular type of – I cannot remember whether it was thyroid or parathyroid disease. They were the first to describe that entity, and that is how things happen sometimes. Sometimes the penny drops that has never dropped before and people go – I have done it myself over changes of ankylosing spondylitis in the hip, accumulated a whole load of things from other colleagues all round the place and looked at them carefully and written a paper which defines that – it was not ankylosing spondylitis but … That is what I mean by retrospective study, so that if you had a series of things then you would look at them in hindsight, that is what we mean, but, again, I personally would set them up in a rigorous way so that I would deliberately dig out some controls, normals or a different condition and look at them all blind with a view to saying “Can we tell a difference?”

Q But that would be, as you said, when you stumble on something and then you look back to see whether you can see a pattern, if you like, emerging from previous cases, that you at the time had in a normal clinical way, is that correct?
A Yes, I think you would probably have seen the pattern already and be looking for confirmation, otherwise it is a bit like stamp collecting or just looking for a needle in a haystack, and that does not work as a research strategy.

Q Reverting to this particular matter, you discussed it with Dr Davies and Dr Dhillon and they told you that the intestinal biopsies from the autistic children had come in the normal way to the histopathology department. What was your understanding as to who would have been looking at them? If they had come in the normal way are they assigned to a particular histopathologist or are they just seen by anybody in the histopathology department?
A We had a system whereby two consultants were in charge of the biopsy service for, say, a week and then two others would take over. They would work as a team with, from memory, three or four senior registrars, or registrars, and all the material would come into that reporting room. We all sat together in a reporting room. I did it myself along with other people, took my share doing it, so everything would come in there. Most of the time you would be able to deal with those yourself but very occasionally you would be out of your depth and need to go and talk to the renal man yourself, but what one tended to do was to send the registrar to go away to do that because then that was part of their learning experience, as it were. So, yes, everything would come through, we called it “the routine service”, and then it might have been collected up and looked at by the specialists afterwards. If people had problems about being out of their depth, which even as a senior consultant happens all the time, then you want to make sure – why have an expert liver pathologist in the department and not use him, so there was a lot of discussion and to’ing and fro’ing going on all the time.

Q In relation to the samples which, as you know, came from children who were subsequently reported in The Lancet article, was it your understanding that they had been reviewed? You have told us they came in in the normal clinical way, as far as you understand, and we know later that histopathological findings were reported in The Lancet article. Did you become aware through your staff that there had been a retrospective reviewing of those samples?
A Not until just before The Lancet article. I mean, they had clearly been involved in the review. They had not particularly come along to me and said, “Oh, by the way, Prof, we’re doing this”, it was – everybody in the department was – I mean, you cannot have your hands absolutely on everybody all the time.

Q Of course not, no. You have told us that retrospective studies are done. Was there anything unusual about going back to look at these samples?
A Not as far as I know, they had noticed a nodular lymphoid hyperplasia, which I had been shown, in the odd case maybe. We also had a department meeting on a Monday morning where we showed each other things as well so I was aware of the possibility of there being an entity, I was not aware of any possible associations or anything like that, or any study, until the fact that a retrospective study came up.

Q When The Lancet paper was ultimately published, by that time were you aware that some sort of research study had taken place of the tissues?
A Just before the publication. I would not know how long before but – whether it was weeks or a month or so – it certainly was not six months or a year.

Q Did you know that there had been an ethics committee application in respect of the project written up in The Lancet?
A No, I do not think so.

Q We know from The Lancet paper that ---
A I mean, I assumed there had been but I was not – the head of department was through the department of medicine, I assume it had all been channelled that way.

Q When you say you assume that there had been, why was that? If the original samples had come to your department through the normal channels ---
A Oh, I see what you mean.

Q --- what was your understanding of the reason why there would be an ethics committee application? If you do not know please tell us?
A What I cannot remember is where we are in relation to Alder Hey and the animal – all these other things. I have absolutely no idea where all this fits in.

Q You were ---
A And we ---

Q --- for it?
A Well in that case it would not necessarily have needed an ethics committee to write a retrospective case-based study, as far as I remember.

Q Of the examination of tissue you mean?
A Exactly. Indeed, that is the sort of thing we did all the time in the 80s and in the early 90s.

Q I think it follows from what you said, but as far as you were concerned did you ever see or become aware of any sort of ethics committee application in relation to this project, at the time?
A No, but I am not sure whether it was relevant to have one.

Q I am going to take you on to ask you about a related but different topic. That is the issue of where there is a divergence between the clinical histopathology findings, in other words the findings that were made when a member of your department looks at tissue that comes through in the normal clinical way and then when someone looks at it again, in what you have described for research purposes, if there is a divergence in the findings, is that a situation that sometimes arises that the research finding will be different from the clinical finding?
A I am not sure it would be different. It might enhance the clinical finding. Yes, okay.

Q I think it is important, Professor, you are the one who is giving evidence, I do not mean to do it for you: can you tell us how usual or unusual it would be for there to be a significant difference between a clinical and a research analysis of the tissue. Is it something you have come across or not?
A Right, okay. For some research the analysis of the tissue would be confirming that something was there or not and it would not be any different. Sometimes you might be applying a new staining method or a new immuno histo chemical method or some new technique to the tissue, giving you more information. That is what I meant by “enhancing” it, but I do not personally believe that that results of that research should go into peer review, as it were, before it becomes part of the body of knowledge of how to treat that particular disease or patient. Do you see what I mean? I think there is a …

Q I do, Professor, but you said, “I do not personally believe”, do you mean that or do you mean you do personally believe?
A I personally believe that if you make a stunning new finding you need to get that peer review and at least present it at a scientific meeting in a peer reviewed way, and probably have a paper somewhere showing that so it is there for everybody else to challenge and look at before that becomes your recommendation as to why the treatment of the patient should be altered. Is that clearer?

Q It is very clear, yes, thank you very much.
A I mean, that is what NICE is doing for us all the time now.

Q I think you have answered the next question I was going to ask you, which is, as far as the treatment of the patient is concerned, what should that be based on?
A I think it should be based on the currently best accepted practice nationally or internationally agreed for that disease, and the availability of resources. Clearly, you cannot do a heart transplant in a district general hospital.

Q In the context of what we were just discussing, if you get a situation where you have a clinical biopsy analysis and then you have a research one which may alter it slightly, enhance it or change it, upon which should you base your treatment of the patient?
A I think, on balance, one should treat it on the accepted body of knowledge. It might be that your research finding is completely wrong, that is the risk, no matter how sure we are. That is why I think peer review is so important.

Q Also in relation to this, if you have a position where a biopsy is reported by the clinical histopathologist in your department, a normal clinical biopsy, reported at one of the normal clinical meetings that you have told us about and for some reason that discussion results in a change of view about the report, or I should say a change of view about the findings in the biopsy report, what should be done about that?
A The common politeness and courtesy between professional colleagues would be for whoever was wanting to change it to do so in consultation with the person that had written and generated the original report so that they should go back to … If I had said so and so was cancer and somebody said they thought it was benign, then I would expect them to come to me, argue their case and we would sort it out between us and write any report.

Q When you say “someone came to you”, is it the case that there is a great deal of reliance and consultation between the clinician who is treating the patient and the histopathologist who is analysing the tissue?
A There should be, yes. There usually is.

Q At these meetings, where you have the clinicians and you have the histopathologists who have looked at the tissue, the clinician in charge of the patient might, in some circumstances, have a different view from the histopathologist who has looked at the tissue, or might want to talk it through with them.
A Okay, yes.

Q If that occurs, and you are saying as a matter of courtesy that should occur …
A Yes.

Q Would you expect a new histopathology report to be issued?
A Only if the histopathologist was convinced that he had made a mistake and if he had gone back to his colleagues and probably shown that to other colleagues, and may be sent it off to other people elsewhere in the country or even abroad – histopathologists are sending tissue on sections in difficult cases all over the place to get people’s opinions. So, no, if a clinician came along and said, “You have diagnosed this as membranous gloneronephritis” – I am deliberately sticking in a completely different area – “and we think it is proliferative gloneronephritis” then the pathologist is the expert and he says, “No, I’m very sorry but this is membranous gloneronephritis, I will check it with colleagues in the department. I will send it to Fred who is the expert in renal pathology in Nottingham and to so and so in the States if you like, but I believe that is what it is”.

Q As far as the patient is concerned, if there had been some change of view, or, indeed, dispute in the circumstances that you set out, would you expect to see that reflected in the records? Would you expect to be able to see the basis upon which treatment was being given?
A Yes. If there is a need to change a report you would expect that to appear in the record. For example, what used to happen when I – my particular interest is in bone and joint disease – when I went away on holiday the department would report the bone and joint things, but they would often write a report which had a caveat saying, “this will be shown to Professor Revell on his return and a further report sent if there is any change” and in fact I used to, even if there was not a change, I used to follow up by saying, “I’ve looked at this and I agree absolutely with this diagnosis.”

Q You would follow up by writing that, would you?
A Yes, I would personally, yes.

Q So would you expect it to be clear, on the face of the medical records, exactly what had happened, the process of thought?
A Yes, I would, yes. The process should be clear either within the notes or within the department of histopathology. In fact, there was a thing put in place whereby, even before a report is written, if there are ideas about then they might be put for internal purposes on that particular file so that people would know what the thinking was.

Q I think it is right, Professor, by the time of The Lancet publication, which was in February 1998, that you were no longer head of the NHS service provisions in the histopathology department?
A That is right.

Q Indeed, Dr Wakefield no longer had a joint appointment, as we have discussed, he had by then ---
A No, that is right he got his readership in March 1997 I think it was.

Q Did that put him firmly in the department of medicine?
A Yes, but he did not actually move office to the department of medicine until about 1998, but, yes.

Q If we go back to FPT2/page 638, this is a document entitled “A New Syndrome: Regressive Developmental Disorder associated with Ileo-colonic Lymphonodular Hyperplasia, non-specific Colitis and Immunodeficiency, Proposed Collaborative Clinico-Pathological Study” and the short tile is “Autistic Enteropathy” with the lead investigator as Dr Wakefield.
Do you recall that you received this document?
A Yes.

Q Can you tell us how it came about that you did? Do you remember how you got it?
A What I believe happened was it was delivered to the department possibly by hand. It came to my hand and I was told it was from Dr Wakefield. As to the exact date, there should be another ---

Q I will take you on to that correspondence that we have in a moment, Professor. I am not going to take you through the document.
A I did not understand why I had been sent it because I was not his head of department any more, or what it was for.

Q We will be looking at it later this morning just so that we can identify what it is about. Turning to page 639, it sets out the summary and describes the first 12 children studied at the top of the page.
A Yes.

Q We see the background to it and a short summary about autistic spectrum and then reference to two studies, one a clinical study which was in press at The Lancet at that time in 1998 and the second one on page 640, a laboratory study, which had been submitted (as opposed to in press) to The Lancet in 1998, is that correct?
A Yes.

Q Turning to page 674 we will see the memo that you wrote to Dr Wakefield about it dated 21 January 1998.

“Dear Andrew,

Thank you for sending me the document A New Syndrome: Regressive Developmental Disorder; short title Autistic enteropathy.

I have read this with some interest. I should be glad to know whether this is the project for which you have recently received funding. May I remind you also that the correct title for your post conferred during last year was Reader in Experimental Gastroenterology. The Dean has recently confirmed that you are not a reader in medicine and histopathology.”

Can you tell us what you were referring to when you say, “I should be glad to know whether this is a project for which you have recently received funding”? Do you remember?
A I do not remember, no. At the time there must have been some hint or some information around that there was some funding but I do not remember. All I know is what is in that letter.

Q At that time were you involved in reviewing funding proposals in relation to Dr Wakefield at all?
A Not at all, but there was a question, as you will see later on, about whether it was funding for a Dr Anthony.

Q I will take you on to that to refresh your memory. Going to page 755, please, this is February 1998 now.

“I wrote to you on 21 January 1998 asking whether the document you sent me … was the basis for the funding and do not seem to have had a reply.”

I think it is right that you have very recently produced two letters that you have found in relation to this issue?
A In going through the papers for this hearing I found two letters which I do not remember ever seeing before which were in a file which were related to Dr Anthony and I suddenly thought: wait a minute, I said that I never got a reply from Andrew Wakefield and in fact there was a letter which you have there and which I have not got here but I know what he says in it.

Q We will hand it round so that everyone can insert it in their bundles. There are two letters, sir, going in at 755a and 797a. (Documents circulated)

THE CHAIRMAN: We do not have page 797. After page 796 our next page is 817.

MS SMITH: If you put it in at the appropriate point, sir, we will deal with that later. Page 755a, a letter dated 23 February 1998, from Dr Wakefield thanking you for your reminder.

“In answer to your question, yes, the protocol refers to the grant obtained for Andrew Anthony.”

He then deals with the accommodation issue. At page 797a we have a letter from you dated 4 March 1998:

“Dear Andrew,

Thank you for your reply confirming that the autism document is the grant supporting Andrew Anthony. I was interested to see the article in The Lancet and hear all the publicity that went on around it. The issues have started to be aired and your observations on nodular lymphoid hyperplasia certainly deserve careful observation and further study to see whether there is any evidence of the links that you are suggesting.”

Again, you refer to the accommodation issue.

Can you help us at all, having refreshed your memory from that correspondence, Professor Revell, who was Andrew Anthony first of all?
A Andrew Anthony had been training as a histopathologist and when I went to the Royal Free he was part of the inflammatory bowel disease group. He had given up his training and had decided to become a full-time researcher, so he was working in the department with funding which was through the Department of Medicine but he occupied part of an office in the department and worked between the Department of Histopathology and Medicine.

Q We know from The Lancet article on which he is a co-author that he played a part in the review of the histopathological samples. Were you aware that he was engaged in work relating to the analysis of tissue from children with autism at the time?
A No.

Q The correspondence that you found does not assist in jogging your memory as to the nature of the funding that you were referring to there?
A No. This was new to me yesterday. I found this yesterday and it was my honest belief that I had never got a reply from Andrew Wakefield and that there was no follow-up to that document 755. I do not have access to all these files – I have been retired for four years – but I have kept some things with a view to all this happening in due course. Those two letters came up. We have had a series of meetings with solicitors and various people and I do not remember ever seeing them before and I do not remember what the details are either.

MS SMITH: Thank you very much indeed, Professor. Sir, you may feel it is appropriate to break?

THE CHAIRMAN: That is exactly what I am thinking. It is ten to eleven now. We will now adjourn for the mid morning break and resume at 11.10 am. (The usual warning was given to the witness)

(The Panel adjourned for a short time)

THE CHAIRMAN: Ms Smith, I think you had completed your examination-in-chief?

MS SMITH: Sir, I had.

MR COONAN: I have no questions, thank you.

Cross-examined by MR MILLER

Q Professor Walker-Smith and his paediatric gastroenterology team came to the Royal Free from Barts I think in September 1995. Do you remember that?
A I remember them coming but I would not know exactly the date.

Q It sounds as though you came from somewhere as well.
A I was at the London until 1993.

Q At that time was the London separate?
A We were merging. I was involved in committees and things, yes.

Q You did not come across Professor Walker-Smith then?
A Not at all, no.

Q You were at the time with which the committee is concerned professor of histopathology and head of the department which had two separate elements to it, one research, the other clinical care providing a service for NHS patients.
A Yes, that is right. There was an academic department which concerns itself with research and teaching undergraduates, training doctors and with postgraduate training, training pathologists and higher university degrees and the other half was the diagnostic NHS work.

Q That was a vital adjunct to the clinical care provided by the clinicians.
A Yes, absolutely.

Q It had been recognised, I think, that paediatric gastroenterology would require substantial histopathological back-up if it was to properly fulfil its clinical role.
A Yes.

Q I think you took the lead in persuading the director of operations at the trust to provide further resources. Do you remember that?
A Yes, indeed.

Q Would you look at a small clip of documents from the time. (Documents circulated) Sir, these are three green letters which will go in at the appropriate parts of FTP1 and FTP2. The first one is a letter from 23 November 1995 which I am going to show to this witness which starts at page 89a.

THE CHAIRMAN: Mr Miller, we already have a 605a in the bundle so this will be 605aa.

MR MILLER: Sir, yes. The first document, Professor, at 89a is a letter from you to Mr Shields dated 23 November 1995. It looks as though you are trying to get an additional senior lecturer/consultant appointed:

“At our meeting on 8 November 1995 we discussed the document I had produced requesting that further resources be made available for the appointment of a senior lecturer in histopathology. This would partly be required to address the question of the increased workload from such activities as dermatology and the arrival of new consultants and partly to put us in the position of being able to provide the pathology services which were promised by the Royal Free Hospital to Professor Walker-Smith and paediatric gastroenterology.”

It is true, is it not, that Professor Walker-Smith had been promised a consultant to lead in particular the proposed weekly clinico-pathological meetings which he considered to be essential for providing service?
A Apparently so, yes.

Q You are pitching, if you like, for some more resources.
A I was not party to those promises. They were made without my knowledge.

Q You were clearly aware of them.
A I was aware of them and I was fighting my corner trying to make sure that we got some resource because we were overstretched.

Q You were also saying there is no point me providing more pie charts because I have shown you all the figures and they clearly demonstrate the need for more resources.
A Absolutely. They even called the National Audit Office in to see whether what I was saying was true and they proved that it was a year later.

Q Exactly. It took rather a long time to get the whole thing ---
A Absolutely.

Q I think as a stopgap a lecturer, Dr Paul Kitching, took this role but in fact he left in 1996 and then in due course we will see at the end that Dr Davies became the person who was nominated as the head.
A Yes.

Q It rumbled on for quite some time.
A Yes, Paul Kitching was a very able senior registrar who, from memory, had pretty well qualified, if not got his qualifications, for moving on to consultant level and he moved on, but he was entirely appropriate, I thought, in the lack of a dedicated consultant.

Q Looking at 89c, this is a letter from Ron Shields. He is the person who is dealing with it on behalf of the trust, is he not?
A Yes, he was my line manager and director of operations.

Q 28 December 1995:

“I write further to your letter of 12 December 1995.

Peter Revell has provided all the information necessary for a statement of case to be put to the trust executive for another consultant histopathologist. I will be pursuing this during January and, in particular, whether the next appointment would have a specialist interest in paediatric gastroenterology which is Peter’s preference.

Whether or not the post has paediatric gastroenterology as a declared special interest, it is expected that the histopathology department should provide you with consultant level support. I had understood that this was to be provided to you by Susan Davies, who has now taken up post. I will review these arrangements with Peter Revell when I return to work on 8 January. I will then arrange to discuss the situation with you.”

You knew that what was being proposed was that Dr Davies would take the consultant lead?
A Absolutely, yes, and Ron Shields and I were colleagues at different sides of the story but we had regular discussions. There was a good relationship.

Q Looking back to 89A, we can see that at that stage in November 1995 Dr Davies is not on the letter-heading as presumably one of the consultants on the left-hand side.
A That is right.

Q She was appointed at about that time on later letters which we saw in relation to your correspondence.
A Yes, she would be on the letterheads, without checking, yes.

Q It may be that she was somewhere else in between. I do not know whether you can remember whether she came from St Bartholomew’s or from somewhere else.
A She came from, from memory, XXX; she came from the south coast.

Q When she gives evidence, we can ask her about what her background was.
A I believe that she was from XXX.

Q In fact, it is not until August 1997, I think, that Dr Davies was finally confirmed as the identified histopathologist to provide a lead for the paediatric gastroenterology service. Would you look at the second bundle, FTP2, and you may still have the green copy there. While you are, would you put pages 89A to C in that bundle to ensure that it does not get lost. (Pause) If that bundle is not there, do not worry.
A I am not sure it goes back that far.

Q Do not worry, somebody else can do it later on. We can do it later. Do you have page 605AA, the green copy.
A Yes, I have it.

Q Would you stick that in the bundle after page 605A. It is a letter written by Ron Shields dated 15 August 1997 to Professor Walker-Smith copied to Dr McLaughlin and, by then, Dr McLaughlin had taken over the running of the NHS aspect of your job, the supervision of the NHS side, had he not?
A That is right. I was still head of department. Jim McLaughlin was head of service and he took over the whole of the NHS side for me. By this time, I was involved at international level; I was President of European Societies and director of all sorts of things and basically full up doing too much.

Q You said that you delegated the NHS side to Dr McLaughlin who was the next senior to you, I think, in the department.
A Jim McLaughlin had looked after the department in the six months between me being appointed and actually taking the post; he was a very senior safe pair of hands and an obvious person to do it.

Q So, it would be logical that this letter would be copied to him as well as to Dr Davies obviously who was mentioned in the body of the letter.
A Absolutely.

Q Again, it is a letter to Professor Walker-Smith,

“Dear John,

I write further to our discussion of a couple of weeks ago which was preceded by discussions that I had with both Susan Davies and Jim McLaughlin.

I am happy to confirm that Susan Davies is the identified Histopathologist to provide a lead for the Paediatric Gastroenterology service and it was pleasing to hear your acknowledgement of the service that she and the Histopathology Team have provided. Obviously, for the sake of continuity of service it is important that there is more than one person providing the service but Susan is happy to be identified as the Lead Histopathologist.”

I want to come back to this because I want to discuss with you or ask you some questions about the relationship between the histopathologists and the clinicians because it is quite an important part of the case and quite an important part of the service, so bear with me for a moment and we will come back to it and deal with it in more general terms. I would like to ask you about your department. It is the department of histopathology which, as you say, involved supervision certainly initially until 1997 of the research side and the NHS clinical side and then, as you say, you delegated the latter to Dr McLaughlin in March 1997.
A Yes.

Q In your witness statement at paragraph 7, I will tell you what you said and see whether I have understood it correctly.

“There were various clinical research projects taking place in the department including hepatology, gynaecology, urology, neuropathology in collaboration with other clinical departments. There was also gastroenterological research under the umbrella of the inflammatory bowel disease group. All of this work was clinically related and care based involving collaboration with various clinical colleagues. It arose out of the service provision of the hospital.” (Document not available to the shorthand writer)

Do I understand that to mean that research which involved your department in the areas you have identified arose out of patient care provided by the various clinical departments at the hospital?
A Yes, for the most part. For example, in the gynaecological work, there were projects on ovarian cancer; there were projects on breast cancer, prostate cancer and things like that going on.

Q All of which would originally derive from patients presumably who had provided tissue samples.
A Yes and the discussions between colleagues in their clinical meetings, “That is a very interesting idea, let’s look at this” and so on and so on, yes.

Q The second point that I want to ask you about is the inflammatory bowel disease group which we can see from that letter heading was part of your department within the department of histopathology.
A Yes.

Q As far as Dr Wakefield was concerned, until he became Reader in Experimental Gastroenterology and nominally in the department of medicine after that ---
A Well, he could not have been nominally anyway because he was a member of the university and had to have a line of management.

Q Cut out “nominally”, in the department of medicine after being promoted to readership.
A Yes.

Q But, up to 1997, he was senior lecturer in both your department and the department of medicine which you said was an unusual appointment.
A Yes.

Q For the period from when you arrived at the Royal Free in 1993 until 1997, you were one of his heads of department.
A Yes.

Q And I think you said there were two professors in the department of medicine, one Professor Pounder?
A Professor Pounder and Professor McIntyre.

Q As far as the inflammatory bowel disease group is concerned, that was not in the paediatric gastroenterology department which came over from Bart’s, that had been there for a number of years before 1995.
A Yes.

Q In fact, I think it had been in place some years before you joined.
A Yes. It was an established thing (sic) when I got there as there were other groups that I was head of until such time as we changed things.

Q It was not involved in the clinical care of patients, was it? It was a research …
A That is right. Yes, as far as I remember.

Q There were quite a number of people within that group, were there not?
A Probably four or five. If I scratched my head and worked hard, I could probably give you some names.

Q Do not worry about scratching your head and working hard! It was not simply Dr Wakefield, it was a number of doctors as well,.
A No, not at all.

Q But he headed it up.
A Yes, I think with Roy Pounder. I think the two of them were … I saw them as working together, being close colleagues.

Q Anyway, a distinct entity when you came and therefore obviously when Professor Walker-Smith and Dr Murch came. As far as Professor Walker-Smith and Dr Murch are concerned, you obviously came into contact with them in connection with the biopsy service which your department provided to the paediatric gastroenterology department.
A Yes.

Q As part of the clinical care of their patients.
A Absolutely and my only relationship with John Walker-Smith and with the two of them or any of the rest of the paediatric gastroenterology department was when there was a problem. In other words, the buck stopped here. If there was a complaint about a delay on a biopsy coming or something like that, they would quite rightly come and jump up and down in my office. I do not remember that either of them did because I think we were all right but this is the sort of thing that would happen.

Q You will be relieved to know that I am not going to suggest that there was any problem.
A No but that was the sort of relationship. I did not have a direct relationship with either of them.

Q No but I think you recognised and recognise that his department could not have operated without a skilled histopathologist ---
A No, absolutely not.

Q And it was for that reason – and we have seen it in the correspondence – that, when they transferred from Bart’s, they rightly expected that support and anticipated having weekly clinico-pathology meetings.
A Yes.

Q I say on a weekly basis which I think is what happened, and you see that as a vital part of the service being provided, do you not?
A Absolutely, yes.

Q The importance is that you cannot have the pathologists locked away in a room somewhere looking down microscopes and sending reports because they have to discuss individual cases face to face with the clinicians.
A Yes.

Q Because it may be that joint decisions are made as to the management of patients arising out of those discussions.
A Yes.

Q We will take colonoscopy as an example. Colonoscopy would identify or might identify some sort of pathology in the bowel which would be seen by the person who is operating the colonoscope but he would not know necessarily the significance of what he was seeing; nonetheless he would be able to say whether it looked abnormal at any particular point. During the course of the colonoscopy, biopsies would be taken which would then be handed over to the histopathologists for them to produce slides and analyse what, if anything, could be seen and that is the routine.
A Yes.

Q Your approach as head of the department was that it would not be in the interests of your department in terms of training people within the department if the most experienced people picked all the plums.
A That is absolutely right.

Q So that those in training would never get ---
A They only saw acute appendicitis.

Q Yes. So, your idea was that it had to be routine within the department that whoever was available would be dealing with it rather than a particular dedicated histopathologist looking at each case that was coming in.
A Yes, but the backstop for that situation was if you have a clinical meeting on a regular basis, then the slides for that particular … We used to have a whole load of places in the reporting room so that all the slides for the gastro meeting would go in there and all the things for the liver meeting would go in here and so on and then the senior pathologist would collect those slides and have them available to discuss in detail.

Q That was a vital point, was it not? It was not a question simply of saying, “Here is the report, do what you will with it”. Each week there was a meeting, latterly I think mostly organised, from your department’s point of view, by Dr Davies, in which the slides of individual patients would be put up and then there would be a general discussion about what the slides showed.
A Yes.

Q Obviously with some input from the clinicians as to what had been seen at colonoscopy or any other investigations there might be.
A Yes.

Q It was a free discussion on a patient-by-patient basis with the slides being shown and a discussion of the outcome and the purpose of these meetings was to get to a consensus of what had been found from the various different sources with a view to planning treatment of the patient. That was the purpose of the meeting, was it not?
A That is a primary purpose. There are other purposes in the sense that trainee doctors both from the clinical side and from the pathology side and anybody else could go along and would be party to that discussion. So, there was a large educational basis to all those meetings, not just in this area, but that was the point of them.

Q That was the interface between your department and the other clinical department.
A Yes, absolutely.

Q I think you said that it is part of the provision of superb care. I think that “superb” as the word you used.
A I hope so. We try.

Q It was not related only to this department but it was certainly the way in which it would operate with at least two purposes: teaching and instruction being one of them but care of the patients and treatment of the patients ---
A That is the first one, obviously. The medical students might come along but we would have to be careful not to have them … If you spent time discussing things at a medical student level, you are not doing the patient care discussion, so that was always, I have to say, a priority.

Q One of the advantages was that there had not been a dedicated paediatric gastroenterology department before 1995 but you actually acquired one that was up and running.
A Yes.

Q With considerable experience and reputation.
A Yes and then we had to raise our game to provide them with what they needed.

Q Yes. As far as the clinicians are concerned, we have two of them here but I think that there was another consultant, Dr Thomson, and a lot of trainees as well within the department involved in dedicated gastroenterology rather than just general paediatrics, so it was quite a prestigious unit.
A Yes.

Q I do not think that you attended any of the weekly meetings. That was not your particular area and you had other things to do.
A Absolutely.

Q The purpose certainly once the system was up and running was that they would primarily be in the hands of Dr Davis.
A Yes. My job was to facilitate whatever was needed.

MR MILLER: I would like to ask you about what happens in the meeting. The slides go up and there is discussion and clearly the clinicians themselves may have had views because they were experienced in looking at these slides over a period of time but it would be a general discussion and it may be that there would have been changes as a result of discussion at those meetings to what ---

MS SMITH: I am sorry to interrupt Mr Miller but it does seem to me that these questions to a witness who has just said that he never attended a meeting are not going to take us a great deal further.

MR MILLER: I shall deal with it with Dr Davies. Dr Davies is the best person to deal with this if you did not attend the meeting and she can tell us what happened at the meetings.
A You would be better talking to Dr Davies. I can tell you what would happen in general in those sorts of meetings and what happened with me with the rheumatologists but that is not relevant to what you are talking about and I have no information whatsoever, so I would have to sit here and tell you “I do not know”.

Q Dr Davies is going to be giving evidence, so we can ask her what happened.
A I think that would be entirely appropriate.

Q And what the dynamic of these meetings was.
A Yes.

Q You were asked at the end of your evidence about what would happen if slides subsequently came to be looked at from the point of view of research, in other words somebody coming back to the slides and maybe enhancing them and looking at them and making a decision about them or passing on their views about what was found; do you remember that part of your evidence?
A Yes.

Q What we have been talking about up to now is what would happen at the time the patient was there or around the time the patient was there when the people doing the reporting would be involved in the general clinical care of the patient.
A Yes.

Q So, nothing to do with research, it is simply reporting to the clinicians on what the findings were.
A Yes.

Q You also contemplated a different situation which was when somebody much later or some time later looked at them for a different purpose and may revisit what the findings were and, in those circumstances, you say that if the interpretation of the slides was significantly different from the earlier interpretation, you would not expect the treatment to change as a result of that simple reinterpretation of the slides; is that right?
A What you are saying is quite complicated and needs to be broken down. If, on the general running of how do we treat this patient within a meeting there was a change, then that would be within that meeting. If, six months later having thought that there might be an entity nodular hyperplasia and this might be related to measles or autism or whatever, then what has gone has gone in terms of treatment of the patient but this is, if you like, a scientific interest question. If we look at these, have we been missing something? Is there an entity? If there is an entity, then what I would do and have always done is to set up a blind study. So, I would get the seven or eight or however many patients there were, ten patients, that might have that diagnosis and another ten who were from something else and so on and mix them all up together and get two or three people to look at them blind and see whether they fell out as an entity. That would be the proper scientific way to do it.

Q Yes, that is where you think, “Hang on, I think I’ve spotted something on this slide which did not cross my mind before when it was looked at” or it did not apparently cross somebody else’s mind when they looked at it in the clinical context, “and I think I would rather like to see whether or not I can replicate that in other situations”, and that is your example of ---
A Yes, new knowledge.

Q And the example from the London, somebody thinks, “I will go back and see if ---
A It was – I have had time to think – it was amyloid in parathyroid tumours.

Q So that is a completely different discovery really about anything that was thought to be there when you looked at the slides in the first place?
A Yes.

Q And as you say, that is some way away from the clinical context because the patient is long gone and that may be something ---
A Yes. You can get an intermediate position. We had – again in my own field – a position where a particular sort of – I thought I was looking at a particular sort of bone tumour, of which there were only seven cases ever described, all by one chap in Brazil, so in the ongoing treatment of that patient, I said to the clinicians, “Hang on a minute, let me send this” – and another case we had – “to this chap in Brazil and see whether he agrees that that is what it is”, and that is what it was and we wrote up the eighth and ninth cases in the literature on that tumour, so that was ongoing, so there is an intermediate position as well.

Q So it was capable of affecting ---
A Exactly.

Q --- in a rather rare situation where you found something that might tie in with something else that somebody else discovered?
A Yes, but then you would consult the person that had described it or the – in the same way that people might start sending lymphoid nodular hyperplasia to people here.

Q Because having described it, you think, “Well, somebody else has described it, can you tell me whether what you are seeing is ---
A Does this agree?

Q --- my slide that you have been describing?”
A Absolutely, yes.

Q So the findings would be there, and it might or might not have an effect on treatment depending upon where you were?
A Yes.

Q And the basis of your decision to treat, But as I understand it, you can see two different, completely separate processes, the first is linked into the care of the patient at the time that the biopsy is taken, within a short time reporting on the findings, and then the pathologist and the clinician discussing how to interpret the combination of features and the alternative may be something which is pulling out slides.
A The whole situation has changed now anyway since all this because now one – to do that sort of retrospective study on tissue you would need, I think, to go back to the patients and ask their permission, but that is in the last four/five years, that is the Human Tissue Act and so on.

Q That is a matter which, again, we will have to deal with with other witnesses I think but there has been quite a sea change since 1996 and now?
A Yes, absolutely.

Q Can I ask you, in terms of documentation, in an ideal situation, if the situation works properly, if there is any change in diagnosis, or significant change in diagnosis or interpretation – I am sorry, I am talking about the histopathology – then you would expect, or at least hope, that the documentation to cover that change in interpretation would be amongst the patients’ notes?
A Yes. If it was a research finding then it would not necessarily be in the notes but it might be something that one communicates to the clinicians involved, saying, “This might fit into the situation. It is a research finding: it has yet to be established. You need to do a proper study and whatever”.

Q So, it is, “Hang on, you might find this interesting.”
A Exactly, exactly, but it would not be appropriate to change the patient’s care on that basis.

Q Can I ask you about The Lancet paper: you were sent a copy before it was published, and I think in fairness you found it an interesting observation that had been made. It was quite short, a small number of patients, which required further work before any serious claims could be made about it, but it was an interesting observation.
A Yes.

Q So, in other words 12 cases could support a preliminary observation but there would need to be a larger study producing the same results, with sufficient safeguards to say, “Well I think that is a reasonable conclusion to draw from a larger study”?
A Yes, as a non-expert in that field, of course. I mean, I was … Yes.

Q No, but interesting observations is how I put it.
A Absolutely, yes.

MR MILLER: Thank you, professor.

Cross-examined by MR HOPKINS

Q Just a few questions and they relate to the circumstances surrounding The Lancet paper which, as we know, was published in February 1998. If I understand your evidence correctly, on reading that paper you regarded that as a retrospective case-based study, is that right?
A Yes. I was particularly interested about the histopathology side, clearly. I was not really in a position to comment on the epidemiological aspects or other things. I mean, I read those at face value because I would have needed to discuss those with an epidemiologist.

Q Let us just focus on the histopathology: is it right that you understood at around that time that two members of your department, Dr Sue Davies and Dr Dhillon, as he then was, had carried out a retrospective review of the slides that were being reported in that paper?
A Yes.

Q Did you understand that the purpose of that retrospective review was to verify the description of the histopathology for that paper?
A Yes, “is there an entity of nodular-type lymphoid hyperplasia in the bowel?” Yes, “Is this the real thing or are we making it up?” basically.

Q And your understanding was that at the initial clinical diagnostic evaluation of those slides, lymphoid nodular hyperplasia had been identified and the retrospective review was to confirm that finding?
A No, I would not know one way or the other about that.

Q Are you able ---
A I was not party to what they were thinking or doing at the time they were making the diagnosis, and the diagnosis was being made by everybody in the department to start with.

Q It might have been explained?
A It might have been that they described lots of lymphocytes in nodules and it had not got a name.

Q As you explained, initially the slides would be reviewed in a routine way by potentially someone junior and then some ---
A Always with consultant supervision, and then being looked at by a consultant, Sue Davies or Paul Dhillon or whoever.

Q Just so we understand the process: it may well be someone relatively junior in the department would have first look but they would be under the supervision of a consultant, is that right?
A Yes.

Q And then, as we have heard, there would be the weekly meetings with a consultant, and in this case usually Dr Sue Davies would attend those meetings and discuss those findings?
A Yes. You could not make a diagnosis of lymphoid nodular hyperplasia if it had not been described, and if it had not been described at the time they were looking at it they could not make the diagnosis, but that is theoretical.

Q Can you tell us how you came to be aware that this retrospective review of the slides had been carried out by Dr Sue Davies and Dr Dhillon?
A They told me that there was a paper coming out in The Lancet that they were involved in and they had done the review, as far as I remember. I do not have any documentation but my memory is it was word of mouth between colleagues.

MR HOPKINS: Thank you very much. I do not have any further questions.

THE CHAIRMAN: Ms Smith, do you have any re-examination?

Re-examined by MS SMITH

Q Just for the sake of clarification: could I ask you to look at FPT2 page 783, which is The Lancet paper.
A Yes, I have that.

Q In the authors at the top – I am only doing this so we are all clear, I want to identify the initials, that is all: we see AP Dhillon, that is Professor Dhillon, is that correct?
A Yes.

Q We see SE Davies, is that Susan Davies?
A That is Susan Davies, yes.

Q If you go to page 784, the “Histology” paragraph on the left-hand side:

“Formalin-fixed biopsy samples of ileum and colon were assessed and reported by a pathologist …”

– that is Dr Davies, is that correct?
A That is what it says, yes.

“Five ileocolonic biopsy series from age-matched and site-matched controls whose reports showed histologically normal mucosa were obtained for comparison. All tissues were assessed by three other clinical and experimental pathologists”.

We then get APD, and that is Professor Dhillon, is that correct?
A Yes.

Q Is AA Andrew Anthony?
A Yes.

Q And AJW we know to be Dr Wakefield’s initials?
A Yes.

Q As I say, I do not want there to be confusion in the Panel’s minds, you have talked about, in answer to the last questions you were asked, a review which you knew was being done by Professor Dhillon and Dr Davies.
A Yes.

Q Was that independent of The Lancet article, the review that you ---
A No, I thought that the three people reviewing were Sue Davies, Paul Dhillon and Andrew Anthony. I am sorry, obviously when I read that that passed me by.

Q So in fact when you were talking just now in answer to Mr Miller and Mr Hopkins about the retrospective review that was done, were you in fact talking about the review that was spoken about in that paragraph in The Lancet article, in other words the one done by Professor Dhillon, Andrew Anthony and Dr Wakefield, or were you talking about your understanding of some check, if you like, that had been done by Professor Dhillon and Dr Davies independently of The Lancet paper, or can you not clarify one way or the other?
A No, I really cannot clarify. My understanding was that the cases had been reviewed retrospectively by three pathologists and I assumed I knew who the three were, that was Paul Dhillon, Sue Davies and Andrew Anthony.

Q When you say you “assumed” it, can you recall whether that is what you were told by them at the time or that you made a note about in a reading of the paper or how?
A I did not speak to – I spoke to Sue Davies and Paul Dhillon and they confirmed that they had been concerned with this as a review, and that the results of their review went into The Lancet paper. That was why I asked, “Why are you authors?” and they said, “Well we did the histopathology as a review, that is why I am an author.”

Q It was your understanding as far as Dr Davies was concerned that she had done a review rather well as doing ---
A As well as because she was the target pathologist for the ongoing reporting in terms of the clinical case meetings and so on.

MS SMITH: We will have to ask Dr Davies to clarify, thank you very much. Thank you professor, it is now up to the Panel to ask you any questions they may have.

THE CHAIRMAN: Ms Golding is a lay member.

Questioned by THE PANEL

MS GOLDING: You said there came a time when you noticed that there were several biopsies from children with autism coming in: did you have an idea of how many?
A No.

Q Was it an unusual pattern of biopsies coming in?
A No. The biopsies were coming in and I noticed one that said “autism” and I did not quite know why, apart from one – I would not know how many it was. I had no idea how many it was, and having checked with my department members to see if they were not involved in a formal study. It would not have mattered if they were so long as it was properly set up, but I wanted to know where the parameters were.

Q Why did you decide to check on that if it was just the one?
A Because that is what I did all the time, it was part of my job to see if the NHS resource was being used appropriately.

Q Was it unusual for a child with autism, a child with a problem such as this to come in?
A I am not an expert gastroenterologist.

Q I am looking at page 89A, the page with all the people in the department. You are named as the head of department, and then it says “department administrator”: tell me, what would that person do?
A The department administrator was my personal secretary/PA and she looked after monitoring budgets, did all sorts of other things. There was not a formal administrator provided within the set-up and Lynette Bannister acted in that capacity. She was my secretary and PA and we chose to give her that title.

Q Then you have got the laboratory manager histology, Mrs Boxer, what would that person do?
A She was in charge of the – if I can say, if a sample comes into the department, a piece of biopsy, that arrives and it is looked at by a doctor but with the technician … and then it is handed over to a technician and it is processed through paraffin wax and stained and put on the slide and then delivered back to the pathologist, and Linda Boxer was the head person in charge of running that for the whole department.

Q Would there be a record of everything that came in to the department or to that section?
A Absolutely, yes.

Q Who would keep those records? Who would deal with them?
A You mean, if you wanted to know about them who would you consult?

Q If you wanted to check how many ---
A You would go probably to Lynette Bannister in the first instance, the administrator, because she looked after those things for the NHS side, but she is acting, she is a facilitator really. There are written records all over the place but for everything that came in, and all the pieces of tissue that came in would all be monitored and tracked, and could be tracked, but after a while, you cannot keep everything, you have to start throwing things away but Linda Boxer would be the one that threw them away, in consultation with the consultants.

MS GOLDING: Thank you.

THE CHAIRMAN: Mrs Dean is a lay member.

MRS DEAN: I apologise if I am about to ask you a silly question. Can you explain to me what nodular lymphoid hyperplasia is?
A As a non-specialist, my understanding was that you can get cells in the gut wall and you see them all the time, lymphocytes and so on, but if you get enough they are formed into clumps, into nodules, so that is what the “nodular” bit means, that there are enough of these lymphocytes present for them to be accumulated into nodules. The word “hyperplasia” means an increased number of cells in response to some stimulus, so … Well, if your body needs to respond in a particular way, you might produce more cells. Your liver might produce more liver cells in response to certain challenges, so that is what we mean by hyperplasia. So what it means is there is an increase in lymphocytes in the bowel wall and these are collected together in nodules and the histopathologist looking down a microscope might recognise it and say, “Ah, that’s what it is.”

Q Would that be relatively simple to spot for a histopathologist?
A The answer I think is no. If it had been described and was in the textbooks then you would expect any competent histopathologist to recognise it, but if it had not been described in the literature then he might notice that there are a lot of lymphocytes there forming these nodules but he might not know what it means. He might write a descriptive report, literally saying, “This is what I see” and not put a bottom line on it giving it a name.

MRS DEAN: Thank you.

THE CHAIRMAN: Dr Moodley is a medical member.

DR MOODLEY: I think you have answered this question but I want to check that I have understood your answer: if one of the pathologists, junior or senior, makes a diagnosis at a routine level and then goes to a clinical pathological meeting and discussions happen at that meeting which may then revise the diagnosis or firm up the diagnosis, where would that be documented, because this is a clinical diagnosis on a patient and who would have responsibility for documenting it in the appropriate place?
A First of all, a junior pathologist would make the diagnosis but would not actually issue the report, so the junior pathologist would then, sitting with a senior colleague, the senior colleague would check what had been written. If it was okay then they would add their initials or say “that is fine” and let it go. If there were things to change then the pathologist, the senior pathologist, might say, “Let’s change this wording slightly because it is a bit misleading or …” – that is part of the training process. What would happen if it was changed? First of all, we have established that the report would not go out under the junior’s name, then it would go out under the senior’s name who was responsible that week for the biopsy service, and then if there was a need to change the diagnosis then a new report would be issued after appropriate discussions between colleagues in terms of what the diagnosis was.

Q Even if that discussion took place at the clinical pathological meeting?
A Even if what, sorry?

Q The discussion and the review of the histology took place at the clinical pathological meeting?
A I would have hoped that any change in diagnosis from what was written on the report would have been discussed with the person that wrote that report and the change would have only been done with their full awareness and their full consent. It has happened to me the other way round, that something was referred to another hospital where a report was changed and I was not consulted, and it is not nice.

DR MOODLEY: Thank you.

THE CHAIRMAN: Professor Revell, I think you said earlier, in examination in chief, that in 1998 you would not necessarily need ethics committee approval if you were writing the case studies, is that correct?
A I cannot remember. The whole thing has changed so much over the last few years; I cannot tell you where the changes were occurring. I cannot remember at which stage we were just writing up case reports or retrospective studies without.

Q Yes, but ---
A Now you would be required to do it.

Q Yes, I accept that, but I think we are obviously looking at the situation as it was in 1998 or 1997.
A Yes. I was always concerned that whatever was done in my department was done as ethically as it could be, but that was my own personal standard, not what the law was.

Q But that is a different thing, is it not, doing it ethically or needing an ethical committee’s approval, these are two different things?
A Yes.

Q But your understanding, and again if you cannot recollect it say so but if you can tell us your understanding in 1998, was it that you did need or you did not need an ethical committee’s approval if you were writing retrospective case studies?
A It is too long ago for me, you are asking me to remember something and that … The whole thing has been such a quagmire over the last few years. My feeling was that a clinical study would need – a trial or a clinical study would need ethical committee approval.

Q But is that true ---
A But if you were doing a retrospective look back, I honestly cannot remember.

Q I think in answer to a question that Mr Hopkins asked you said, “They told me that the paper is going to be put out”, who was that, was it Dr Davies?
A It might have been Paul Dhillon but my communication with Paul Dhillon were better than with Sue – I mean, you know, it is just that he and I talked more often.

Q Finally, in re-examination you were asked by Ms Smith, regarding the review by Professor Dhillon and Dr Susan Davies, at what time it was done or at what stage it was done, or was it said to you that that review would be done? Again, if you do not remember it say so.
A My memory is they certainly did not come along and discuss with me, “We are thinking of doing this review and we are letting you know”, they did it, but that would have been true of most of the other senior members of the department. I had to trust them to get on with the job and do it properly. You can be hands on but you cannot be completely hands on all the time. The fact that they had been involved and had reviewed the case is something that came up, say, weeks before, before a month or so before the paper was accepted in The Lancet.

Q I was going to ask you, was that before or after The Lancet article?
A It was before.

Q Was it before it was published?
A Yes, they said that, “you need to know about this because there is a paper coming out in The Lancet.”

Q Yes but was it actually already submitted to The Lancet?
A Oh yes.

Q But before it was published?
A Yes.

Q The study that was published in The Lancet in February 1998, in your understanding was it actually a retrospective case study report or was it in your view a proper clinical study? What was your view about it?
A I was not expecting this question. I would need to look at it and read it through in detail, it is so long after, but my feeling was that the bit that concerned me was the pathology, and my colleagues had been asked to review the pathology retrospectively and that is what they had done, and that is what was important to me. Whether or not it was prospective or not, etc., was not what concerned me basically, I was concerned about my own department and my own people.

THE CHAIRMAN: Thank you. I do not think the Panel members have any more questions but the Council might. Ms Smith?

MS SMITH: I have no further questions.

MR COONAN: No, thank you.

Further cross-examined by MR MILLER

Q As far as the histopathologist is concerned, you are dependent upon the biopsies which are provided by the clinicians. In a case which starts with a colonoscopy, you get material which has been obtained by the clinician during colonoscopy and then you have to work on that bit of tissue.
A Yes.

Q The clinician has targeted a small number of places within the whole of the bowel, produced a small amount of tissue then for you to work on to see whether there is any pathology there.
A Yes.

Q You are not in fact doing histology of the whole bowel; it is just a tiny little bit.
A Good clinicians will actually biopsy a large number of sites because within that they will be giving us a spectrum of changes so we can say this is more advanced than that, that is normal and so on, so a report would perhaps have six biopsies and they would all be carefully detailed – this was from so many centimetres and so on – and each of those reports would say normal bowel, or mild changes of so and so, this one is worse than that one and so on.

Q If you are doing a colonoscopy and you have gone throughout the whole bowel, then you would expect to find biopsies taken ---
A Increasingly so.

MR MILLER: Thank you.

THE CHAIRMAN: Thank you, Professor Revell, for coming this morning and giving us your evidence.

(The witness withdrew)

Examined by MS SMITH

(Following introductions by the Chairman):

Q Professor Candy, could you begin by giving us your full name and address, please, and your medical qualifications?
A My name is David Candy. My address is XXX. My qualifications are MB BS, MSc, MD, FRCP, FRCPCH.

Q I think it is right that you have held the post of consultant in paediatric gastroenterology and nutrition at St Richard’s Hospital, the Royal West Sussex Trust, since 1998, is that correct?
A Yes, February 1998.

Q You have been a visiting senior lecturer at the University of Southampton since June 2000?
A Yes.

Q And a visiting professor at University College Chichester since September 2001.
A Yes.

Q As you know, Professor, we are interested in the role you played as a peer reviewer for a particular article in The Lancet. I want to ask you first of all had you acted as a peer reviewer for more journals than The Lancet?
A Yes, I have been a peer reviewer for I suppose the last 20 or more years of my career and continue to receive about four articles a year from various journals, mainly paediatric for peer review.

Q We have heard from Dr Haughton, the Editor of The Lancet, about the peer review system in general. Could you tell us from the viewpoint of a peer reviewer, remembering there are lay members on the Panel, how does it come about? Do articles simply come out of the blue for you to review or are you on some panel for each of the journals for whom you review or how is it arranged?
A It is usually arranged by the authors nominating peer reviewers, perhaps about five in number, for the editor’s information. Sometimes the editor will make their own choice because they are aware through their contacts of people with particular interests and specialities in the subject of the article, and sometimes I think they will actually pick up on the suggestion made by the authors and send the article to them.

Q As far as you are concerned is it just on an ad hoc basis? Do you know how many papers a year from one particular journal you are going to receive or do you just get them as they come?
A No. I think if you form a satisfactory peer review, return a timely detailed review, then you are likely to end up on the editor’s list of people who he or she would look to again.

Q As you know, we are talking about a time in November 1997. At that time can you recall how many papers you peer-reviewed for The Lancet roughly?
A I think that was the first one. The Lancet is a general medical journal and would only publish a limited number of paediatric articles, particularly in paediatric gastroenterology.

Q I would like you to turn in FTP2 to page 626. Before going to the contents, one thing I did not ask you about the general system is do you know who the other reviewers who have been asked to look at a particular paper as well as you are?
A No, that was so then and continues to be so that the process is confidential. I suppose how it has changed since that time is you are given the option of revealing your name to the authors or indeed concealing it. My practice now is to invariably ask that my name be transmitted to the authors which makes it much more of a transparent process.

Q The letter is dated 14 November 1997. At that time you were in the academic department of child health at King’s College London:

“Dear Professor Candy,

We would be most grateful to you for your expert opinion on these two papers.

The implications of publication are self-evident so we need to be quite sure that the findings are watertight.

Information about these papers has already leaked in the UK press: accordingly, could I ask for a fairly speedy response so that we can make a decision.”

That was from John Bignall, one of the senior editors at The Lancet. Did you know Dr Bignall?
A No.

Q He states that there were two papers enclosed, is that correct?
A Yes, that is correct.

Q Do you have a recollection in broad terms of those two papers?
A Yes, I do.

Q Were they both from the same authors?
A Yes.

Q Who were the senior authors on the papers to your recollection?
A Dr Wakefield and Professor Walker-Smith were the senior authors. Any observations that I present on the second of the two papers, the one that was not published, are entirely based on recollections of events nearly 10 years ago.

Q We do understand that and I have a few questions to ask you about that second paper. Of course you will tell the Panel if you simply cannot remember the answer to the question that I am asking.
A Yes.

Q It follows on from that, Professor Candy, the answer to my next question which is did you to this day retain copies of those two documents as they were sent to you at that time?
A No, one of the conditions of peer review is that these documents, because they have not been published, are privileged information and in keeping with the confidentiality they have to be destroyed once you have submitted your review.

Q Did you know why it was that you had been asked to peer review these papers? In other words, whether you had been nominated as you have told us was sometimes the case by the authors or whether the editor for some reason had decided to ask you?
A No, one is never party to that information as a peer reviewer, but I counted several of the authors and collaborators as colleagues and friends. I am a paediatric gastroenterologist so it was really no surprise that the papers ended up on my desk. I suppose I had a special research interest at the time on the nature of damage caused by infections to the gut which would perhaps have given me additional qualifications to make an opinion on the papers.

Q Looking at the second paragraph of the letter – “The implications of publication are self-evident, so we need to be quite sure that the findings are watertight” – were the implications of publication self-evident to you? Did you understand what that was an allusion to?
A Yes, I understood it as an allusion to the fact that any reports of adverse reactions to vaccines are likely to be picked up by the mass media and reported widely and the vaccine under consideration was a very important public health tool.

Q When he said we need to be quite sure that the findings are watertight, what was the implication of that as far as what your task was?
A The responsibility lay in the fact that if I had given these papers a favourable peer review and they were accordingly published, then mass media attention would have been very strong, very powerful, not only about the vaccine aspects but also of course the condition of autism as well.

Q The third paragraph – do you recall being aware that there had already been some information about the papers leaked in the press?
A I had not seen that myself.

Q Was the request for a fairly speedy response unusual in any way?
A In the days of electronic communication nowadays a speedy response is expected and easy to deliver. I concluded that the editors of The Lancet would be concerned that if there was not a definitive publication then the mass media speculation might continue but be ill-informed.

Q In Lancet editor terms, what did “speedy response” mean in terms of time as far as you were concerned?
A I would have thought within a week or two.

Q Do you have a recollection as to whether you did in fact complete the review speedily?
A Yes, I did complete it speedily in that sort of timeframe.

Q You have told us this was the first time you had reviewed for this journal but you had had experience of reviewing for other journals. Were there guidelines for reviewers at that time as to what they were supposed to put into the contents of their review?
A No. Many journals still leave it up to the peer reviewer, although others do actually give broad-based guidelines of what aspects they want reported on, but these are fairly self-explanatory – statistical power and relevance of statistical test – the things that one would do anyway really.

Q Casting your mind back as well as you can as to your practice at that time, how would you have conducted your review process? What would you have been looking for and commented upon?
A I look at the experimental design, the relevance of controlled material and statistical methods where used and also general expression – English and use of language. Scientific literature uses different conventions to writing for non-specialist journals. For example, the use of the passive voice and one looks for that sort of thing in the paper as well.

Q I am sorry?
A The use of the passive voice. It is frowned upon in writing in general but it is accepted form in scientific writing.

Q Can you explain to the Panel what you mean by that?
A You do not say “I did this experiment and found this …” You say, “The experiment was done and it was found that …”

Q That is linguistic.
A Yes.

Q Because you had been asked to make sure it was watertight, would your threshold for a criticism be lower as a result of that?
A I was not so much influenced by the editor’s comment because that would be almost self-evident. You either do the job properly or not at all. I was more influenced, I suppose, by the origin of these papers from Professor Walker-Smith’s unit. I had known him since 1976. He was an important mentor in my career as well as many other paediatric gastroenterologist from around the world and I knew him as a person of enormous integrity. In fact, the other review I did for The Lancet later was to review his autobiography. In a way I knew it was going to be a good paper, I knew it was going to be well written and I knew it was going to be data that could be believed in because of inside knowledge, if you like, of the environment in which he worked.

Q Did you know Dr Wakefield at all?
A Less well.

Q You said when you began to give your evidence to me, Professor Candy, when I asked you why you had been asked to review this paper you referred to the fact that some of the senior authors were friends.
A Yes.

Q Does Professor Walker-Smith fall into that category?
A I hope so, yes.

Q Can you recollect whether you did in fact recommend any amendments as far as any significant amendments to the text were concerned?
A No, I thought it was well written, as expected, and I would have been very surprised to have had to made major amendments to an article with Professor Walker-Smith as a senior author. He had written textbooks which are models of being extremely lucid and which are referred to by all paediatric gastroenterologists, so this paper came up to that sort of mark.

Q We know there were two papers. I would like you to tell us in broad terms what each paper was about and how they tied in with each other?
A The first paper was, in broad terms, a clinical observation on a limited number of children mainly with autism who were investigated for gastrointestinal pathology. What was found was in the lymphatic tissue in the gut there was marked enlargement. I think one of the areas where controversy has come in, and I was aware of the controversy at the time, is that this enlargement can be seen in healthy children who are investigated for other reasons, children without autism, but I was also aware that the endoscopists who performed the examination on these children, Dr Mike Thomson and Professor Simon Murch, were leaders in their field of paediatric endoscopy, particularly Dr Thomson who now works in Sheffield. He is probably regarded as the best paediatric endoscopist in the UK. If they had seen something which to other paediatric gastroenterologists would be seen as normal, that the lymphatic tissue that defends the gut was enlarged and abnormal, having performed the same investigation on other children then to me that meant something. The paper in its own right was an important example of where clinical observation can lead to important discoveries but it was subject to the same flaws that had been pointed out repeatedly in the medical literature – that is recalled bias – that when something awful happens to a child the parent looks around to think what could this be due to and can latch on to something which is not relevant to the child’s problem. For example, if a child can be brought to hospital vomiting and they have hit their head the day before and that is the thing the parent links with the vomiting. That is an example of recalled bias. It was really the second paper that led to my endorsement of the papers and the two in a way are indivisible. You cannot make sense of the first paper without being aware of the second and the results contained in that paper.

Q What was the second one about?
A The second paper was a basic science paper which demonstrated the presence of measles virus protein in the part of the bowel that had been seen to be abnormal; in other words, the lymph tissue, and this paper had been very carefully controlled by using biopsies from children without autism from the same area of the gut and, as I recall, they had also gone to the trouble of obtaining gut biopsies from African children with HIV Aids infection and using a different stain this protein from that virus was identified in samples from children with HIV. So they had disease controls, they had negative controls, children without the disease ---

Q Was it your view that the information in the second paper was significant to the account in the first paper?
A In retrospect, the first paper was probably written in a very confident and outspoken way implicating particularly the measles component of MMR because the authors knew what was in the second paper. It was almost, to choose a common phrase, like a double whammy. You had the clinical observation backed up by good basic science and that is what makes for excellent clinical research.

Q If you could look at page 783, you will recognise that paper. That is the paper that was printed in The Lancet. Was that the first paper to which you are referring?
A That is correct, yes.

Q When you completed your review of that paper did you review the second paper at the same time?
A Yes. My expectation was that had the other peer reviewers come to similar conclusions the two would be published back to back.

Q Was it your understanding that there was an overlap between the children reported in the first paper and those reported in the second?
A I am not able to answer that question definitely because of my limited recollection of the second paper but one might assume that that would be the case because these were the children that were being evaluated in this way and the samples from the patients in the first paper would be very reasonably subjected to the special testing for the measles virus.

Q Turning to page 638, this is a document that has been produced by the previous witness, Professor Revell, a professor of histopathology at the Royal Free at the relevant time and it was produced to him to assess for funding purposes.
A Yes.

Q You see the title on page 638: “A new syndrome: regressive developmental disorder associated with ileo-colonic lymphonodular hyperplasia”. Looking at page 639, you will see a summary at the top about a novel chronic inflammatory bowel disease identified in children. In the middle of the page,

“Below we describe the first 12 studied. We have now examined 35, 34 of whom have the identical syndrome. This proposal is based on the detailed investigation of a further 75 and we are aware of a further 520 with a similar history either referred or in the process of referral for investigation.”

There is then a hypothesis about how the condition is caused. In the background section you see:

“(1) Clinical study (Lancet 1998; in press)

In a pilot study we examined 12 children between the ages of 3 and 10 who developed autistic spectrum disorders and gastrointestinal symptoms, many soon after MMR …”

I am not going to read it all out but if you run your eye down it, does that seem to you to be the first paper that was indeed published in The Lancet paper?
A Yes, absolutely.

Q “In press” means it has been accepted and it is going to be published, is that correct?
A Yes.

Q Going over to page 640, we see:

“(ii) Laboratory studies (Lancet 1998; submitted for publication)”

I know you have seen this document before but could I ask you to read it through to yourself very quickly and tell me whether the description in that paper accords with your recollection of the second paper?
A I think in part it certainly does and it was reassuring to see this document because I do not think the original version of this paper that was submitted at the same time as the clinical paper has come to light. In fact, my recollection of the paper that I was sent to review relied on different techniques to detect the measles virus. What this document is saying is perhaps when that was rejected the authors went back and did further detailed studies using different techniques to try and confirm or refute their initial observation. The techniques where it refers to PCR – this is not an immunological technique; this is a molecular technique and would have added and contributed to the initial observation. My recollection of the paper I looked at was purely based on a different immunological technique to detect not the genome of the virus but the protein produced by it.

Q You are saying that this description that I have just taken you to is going on a step further into the virological testing than the paper that you recollect.
A Yes.

Q In that case I will not ask you any more about it. We know in fact from Dr Horton that the second paper that was submitted with the first paper was not ultimately published, it was rejected. Do you know why it was rejected?
A No, I do not. It is interesting that the editorial that was published in the February Lancet which was highly critical of the clinical paper had one of its major criticisms as the lack of evidence of chronic viral infection in the gut and the subsequent editorial in the BMJ made the same point. So what was missing from the equation/jigsaw was the confirmation of chronic virus infection in the gut that was there in a paper that was rejected.

Q You told us that you gave a positive review with respect to the first paper; did you give a positive review in respect of the second?
A Yes, I did because, in work that I had done previously myself in animals, in mice, to detect the presence of a virus in the gut namely rotavirus, I would use the same technique with colleagues and demonstrate where the virus was infecting the gut and where it was not. So, I had faith in that technique. I suppose that any technique is only as good as the reagents you are using and I can only postulate that perhaps the reagents that we used were not as specific as they could be. On the other hand, the controls were there. If there was a non-specific binding of the reagent to the gut, why were they not binding to the children without autism? There must have been some flaw that an expert who was another peer reviewer who perhaps had more interest and expertise in that area had picked up on that paper which I had missed.

Q You of course do not know what the content of the other reviews in relation to ---
A No, that is another practice which has changed between then and now. Nowadays, the peer reviewers’ comments are exchanged between peer reviewers anonymously. That is a useful educational process for the reviewer. They can at least see what they have missed and perhaps what the other reviewer has missed as well. In those days, no such exchange took place.

Q Were you ever notified by The Lancet as to what was going to be accepted and what was going to be rejected?
A No. The next I knew is that the clinical paper appeared and I was not pleased with that result and I had a telephone conversation with Dr Horton about it. I suppose from The Lancet’s point of view there was that tremendous pressure to try and get something out into press and that would be perhaps the reason why they had not come back to the peer reviewers and said, “Do you want to have another think about this?” If just the clinical paper was going to be published on its own which is what happened, then my opinion could well have been very different because it was standing on the observations of 12 families rather than being underpinned by the basic science confirming the clinical observation.

Q We know the nature of the funding that is referred to in the first paper as it is published in The Lancet, Professor Candy, but I want to ask you this. With regard to the second paper, do you have any recollection of any reference to Legal Aid Board funding being acknowledged in that paper?
A No. That was not there.

Q Had it been there, would it have been something that meant anything to you?
A Yes. Again, I keep harping back to this but it is important to put the papers we are discussing into their context and nowadays the requirement to declare conflicts of interest is still voluntary but is taken very seriously and sometimes the number of conflicts that are listed almost goes to ridiculous length, some of which can even be semi-humorous. Like when the editor of a journal writes an article and says, “Well, this was what pays my salary”, it is self-obvious. In those days again, acknowledgement of conflicts of interest were not requested.

Q May I take you back to the question I asked you. You said you were sure that there was not a reference to the Legal Aid Board funding in the second paper and what I asked you was, if there had been such a reference, would that have meant anything to you?
A It would have raised the question of conflict of interest, yes.

Q It would in your mind?
A Yes.

Q What would you have done about it?
A I would have put that in my review.

MS SMITH: Thank you very much, Professor. Sir, I see it is 12.50; I do not know whether you want to go straight on or whether you want a break.

THE CHAIRMAN: Looking at the time, it is 12.50 and we will now adjourn. (To the witness) Professor Candy, I have to remind you that you are still under oath and you are still in the middle of giving your evidence. I am sure that someone will look after you over lunch and supply you with a sandwich. Please, do not discuss this case with anyone including any lawyers during this break. We will now adjourn and resume at 1.50.

(Luncheon adjournment)

THE CHAIRMAN: Ms Smith, I think you had finished your examination-in-chief.

MS SMITH: I have.

THE CHAIRMAN: Professor Candy, as I intimated earlier, if the counsel representing the three doctors have any cross-examination to conduct, then this will the time for them to do it. Mr Coonan?

Cross-examined by MR COONAN

Q Professor Candy, would you turn up volume 2 which I think is in front of you and open it up at page 626. This is the letter of instruction from Dr Bignall and we can see that it is dated 14 November 1997. We have heard from Dr Horton something of the stepwise procedure which operated at that time and it looks as if, by the time these two papers got to you, they had both survived the first stage of the editorial process; is that fair?
A Yes. It is referred to by words like the Star Chamber or the Hanging Council whereby, in high-impact rapid turnover journals like the BMJ and The Lancet, something like 90 per cent of submissions are rejected at that stage without going out to peer review.

Q As high as 90 per cent do not survive?
A I think that is correct, yes. It is true because these journals receive so many submissions every year and can only publish a very tiny fraction of those and therefore most of them are rejected by the editorial panel.

Q You saw both these two papers and scrutinised them and the end result was that you sent back an opinion to the editor that both papers should be published.
A That is correct.

Q Is it right that you saw both these two papers together as a package.
A Yes. I think they were indivisible.

Q One was the clinical observation paper; is that right?
A Yes.

Q Which was the one that was actually published.
A That is true.

Q With a degree of anecdotal evidence with it.
A That is correct.

Q And the second one, as you have described it, the basic science paper. Would it be right to say that your view is that the observations in the clinical observation paper, that is the paper that was published, were strengthened and confirmed by the science paper?
A Yes, immeasurably.

Q In the science paper – and again I hope I summarise this accurately – there was described the finding in the laboratory of evidence of chronic measles infection in the gut of autistic children.
A Yes, that is right. That is exactly why the strongest criticisms of the clinical paper would have been answered had the second paper survived the peer review process.

Q As you were able to read the science paper, it was obvious there that – and again I am not going to go into fine detail – a staining technique was used with which you were familiar.
A Yes.

Q As you have said, both well written, articulate and did not require any, or at least any significant, amendment by you.
A That is true.

Q When you reported back to the editor, presumably Dr Bignall, did you actually write to Dr Bignall?
A Yes. The typewritten report would have been sent to him as the commissioning editor.

Q When you sent off your report in effect saying that both should be published together, did you anticipate that both would be published together?
A Yes.

Q Did you anticipate that both would be published together without any additional balancing commentary by anybody else?
A Yes. Clearly, I had no insight or control over the other unknown peer reviewers, unknown to me, but, yes, as far as I was concerned, that is what should have happened.

Q As far as you were concerned, when you judged both papers together as an indivisible whole, were you of the view – going back now to page 626 – that the findings were, in your opinion therefore, watertight?
A Yes. I supposed I was influenced by the information that was going around at the time about chronic measles infection being involved in inflammatory conditions of the gut from the same group and, to actually demonstrate persisting antigen in the bowel weeks, months and years after exposure to that antigen to me was a very revolutionary finding and one which deserved publication in this sort of journal.

Q So, publication of the clinical observation paper without the basic science paper being published was and I think you described it really as publication with an important piece of the jigsaw missing.
A Yes.

Q If you had known that The Lancet was not going to publish the science paper, would your view have been that therefore it would have been better not to publish at all?
A Yes, largely because, as the letter suggests, this was going to be a publication with enormous interest and impact and therefore to just publish the 12 case histories with their relevant clinical investigations without the backup of positive identification of a chronic virus infection would not have been worthy of a paper for The Lancet.

Q Again, it must be your words, not mine, but the publication of The Lancet paper as we have called it without the accompanying basic science paper on the face of it looks like an error, does it not?
A I think it was an error not to consult the peer reviewers before making that decision. We may not have been able to have any influence over that decision because that rests with the editor, but perhaps, as I say, you get the impression from page 626 of the pressure the editors were under and perhaps that is why they short circuited going back to the peer reviewers again.

Q If they had gone back to you, by the sound of it, your view, if you were asked, would have been – and I am summarising – that it was better not to publish either of them.
A Certainly extremely caution.

Q You only discovered subsequently that only one of the papers had been published, that is after obviously February 1998; is that right?
A Yes.

Q And I think you have described to the Panel that you were annoyed about that. Let me separate out two factors. Were you annoyed out of pique that you were not told or annoyed or concerned because only one was published?
A I think that the real basis of my feelings was that, when the paper was published and there was such a strength of negative opinion about the paper and about The Lancet and about the authors and thereby, by assumption, the peer reviewers as well, the peer review system had seriously failed with this paper by allowing it through, because I was bound to secrecy, I was unable to reply on behalf of the peer reviewers and show that in fact the peer review system did not fall down here as a result of poor peer reviewing on the part of the peer reviewers. I was angry because of the situation I was in, feeling a personal responsibility for the result of the paper, the way in which my abilities as a peer reviewer were compromised, albeit anonymously, and now, ten years later, this is the first chance I have had to speak about those feelings publicly.

Q By the sound of it – is this right? – your feeling would be that perhaps a great deal of this concern being expressed by third parties following publication may well have been avoided if the science paper had been published.
A Yes. There would have still have been discussion, doubt and criticism which is just the nature of the hurly-burly of academic medicine, being judged by your peers, but I think that the level of adverse comment would be lower if these two papers had been published together because everyone who read The Lancet would have seen the pictures that I saw. I suppose the other departure was that when there is a difference between two peer reviewers, as occurred in this case, the usual practice would be to go back to the authors with those results and ask for their comment and then for the peer reviewers to have another look in the light of those comments, but of course that did not happen either.

MR COONAN: Professor Candy, thank you very much, indeed.

Cross-examined by MR MILLER

Q Professor Candy, I only want to ask about one point which you made earlier in your evidence about recall bias. As I understand it and, if I am wrong, please, tell me, that involves wittingly or unwittingly attributing an event to the causation of another event.
A Yes.

Q In the context of this case, it might be in relation to the time of onset of symptoms where a parent might say that symptoms followed a particular event.
A Yes. I gave the example of head injury and subsequently symptoms occurring in the next period of time.

Q Obviously, it could affect that, the timing of the onset of symptoms, but, as far as the clinical findings at endoscopy are concerned, they obviously would not be so affected. In other words, if clinicians are simply reporting what they see on colonoscopy, their findings on colonoscopy, recall bias has nothing to do with that.
A Endoscopic findings are obviously more objective, but I suppose one has to say that what was being dealt with here by myself as a peer reviewer was a new disease, something that had not been recorded before, and therefore it was difficult to say very much about what the natural history was going to be or the time course of events simply because what was unfolding here was something that had never really been identified before in such a detailed way.

Q Certainly in the paper that was published, the new syndrome was the combination of the endoscopic findings and the pervasive development disorder.
A Yes.

Q And again, as far as that was concerned, that may have been less within your area of expertise. Your real expert area of expertise was paediatric gastroenterology, was it not?
A Yes, that is true, although, as a paediatrician, I was still aware of some of the things that the measles virus could do to the brain, albeit naturally occurring measles virus or attenuated virus. The other criticism that has been laid at the feet of the peer reviewers is the biological implausibility of the condition that was being described but, of course, when I was reading the paper, it did seem unlikely but not implausible that the measles virus could both damage the bowel and damage the brain, either directly or indirectly.

Q As far as the former was concerned, that was something with which you had experience and with which you had been involved in research.
A The techniques, yes. What was published were not really research techniques, what was published was the clinical techniques which all paediatric gastroenterologists would have experience of but, by that, I was referring to the techniques used in the basic science paper that was ---

Q The other paper that was not published?
A Yes.

Q And that would be research techniques involving …?
A Special stains and so on.

MR MILLER: Thank you, Professor.

MR HOPKINS: I have no questions.

Re-examined by MS SMITH

Q I have a couple of matters that I want to ask you, Professor Candy, in fact arising out of the questions that Mr Coonan asked you on behalf of Dr Wakefield. In relation to this issue of what you have described as the basic science paper, first of all, just in order that the Panel is clear, of course we all know what basic science means in general terms but can you explain to us what doctors mean when they talk about a basic science paper as opposed to a clinical observations paper.
A The clinical observation paper is very well exemplified by the paper which is part of the evidence: you talk to patients, they inform you about their disease and response to treatment and sometimes that can trigger off an observation which can lead to important advances in the treatment of that disease. That is a fairly inexact science. That is a science which is subjected to the recall bias we have been talking about this afternoon and it can lead you up the wrong path, as has happened before, not infrequently with autism. With basic science, you are using techniques that give you objective numbers which are not subject to those influences of clinical medicine and which gives you a “yes/no” answer, something you can measure and something which you can also control for. You can put in experiments which make sure that what you are seeing is specific for what you are looking for and not an error or a mistake or a non-specific effect. So, basic science is underpinned by histochemistry and immunology and molecular biology and all the sciences that underpin the practice of clinical medicine but which not all doctors are involved in or have deep knowledge of.

Q You have told us that you cannot insist on the identity of the other reviewers but, looking at the nature of the two papers which you were asked to review and which you felt able to review, would you have anticipated that they included people who would have an expertise in the basic science as well as the clinical side of the papers?
A Yes, because of the nature of the second paper. That is the sort of paper you would send to somebody who knew a lot about virology or immunology or histopathology, but those are conjectures. When a doctor undertakes extra scientific training, these are the sort of disciplines that they at least have a grounding in. So, equally a paper that had been submitted to someone with a similar career background to myself.

Q I do not mean this remotely as a criticism, I hasten to add, but you have talked rather in terms of as though you were representing the peer reviewers in the sense of saying, “It was an error not to consult us if a decision was being made to publish one paper and not the other”, but, if the basic science paper had had negative reviews elsewhere, which you have told us that it must have done, then would it be the case that other peer reviewers might not necessarily share the views that you are expressing?
A That is obviously the strength of the peer review system. That is why at least two or three people are involved in the peer review, each bringing their own expertise and knowledge to bear on that paper. It would obviously be inappropriate if just one person were to judge a paper simply because each person who reads the paper sees it in a different way, sees it in a different light and takes away different messages, and certainly this comes out now that peer reviews are shared between the reviewers, you can say, “Gosh, why didn’t I spot that?” or “That person missed this completely”. I suppose that the sum total of the peer review is greater than its parts.

Q As I understand it, you are accepting that it may have been the case that others did not share your view that the second paper should be published.
A That is correct. I am sure if others had shared my view, it would have been published. It must be perhaps people with more expertise in that particular area who were able to form a different judgment to my own.

Q One last matter on a slightly separate subject. Mr Coonan asked you, “Did you anticipate that both these papers, on the basis of your review, would be published without” what he described as “any balancing commentary?” I think you are aware that in fact The Lancet paper was published with a commentary.
A Yes.

Q Would that be a matter for the editors to consider rather than you as a reviewer?
A Yes although I must admit that I was surprised to see such a negative commentary or editorial on a paper that they had accepted for publication. Perhaps they were surprised as well. One of the major criticisms of that editorial was the lack of virological backing for the observation which, as far as I was concerned, was there, was available but not published.

MS SMITH: Thank you very much. I have no other questions but the Panel may have some.

Questioned by THE PANEL

THE CHAIRMAN: Professor Candy, as I said earlier, if there are any questions from the Panel members, then I will introduce them individually to you. Ms Golding is a lay member.

MS GOLDING: What did you receive from The Lancet?
A Two typewritten manuscripts, one of which was very similar to that which eventually appeared in the pages of The Lancet. The other containing glossy photographs which would have been published in the same way as the photographs were published in the article that did get through showing microscopic appearances of the gut and the staining and those sorts of things.

Q Did either paper refer to the other one?
A That I cannot remember, but they came in the same envelope, and from the same place. You see before you the paper that was published and there are no claims in there to there being a biological diagnosis or explanation for the abnormal findings in these children’s bowels, so whether that was amended at the last minute I do not know but I just – because they arrived together and from the same group then I just made the assumption that they were to go together, that one underpinned the other.

Q Were you surprised that none of the statements from the authors mentioned this other study which would have clarified anything that was criticised?
A The trouble is I cannot remember the detailed text of the second paper but you can see how elsewhere in the evidence both papers are cited by the authors to support their wish to do deep research in that area.

MS GOLDING: Thank you.

THE CHAIRMAN: I think I have understood it but I just want to be sure, you were one of the peer reviewers for these two papers; are you given the list of the other peer reviewers of the same paper?
A No, this is still the case, even though you are shown the conclusions of the other reviewer you still do not know their identity, it is part of the system for peer review.

Q The instruction letter from The Lancet, the letter of 14 November 1997, page 626, asked you to be quite sure that the findings were watertight and I think your response was that you felt they were watertight.
A Yes.

Q Is it your opinion that they were watertight because you knew the quality of the author, who was Professor Walker-Smith, and that you had a lot of respect for him and you knew him well?
A Yes. Sometimes you are asked to judge pieces of scientific work with the author removed, so that it is completely blind but when you are given – abstracts for meetings, for example – then you judge it entirely on its merits but when you are given a manuscript you cannot help but be influenced by who has written it.

Q So coming back to this particular paper, you knew who the author was?
A Yes.

Q I know it is probably a difficult question for you to answer and if you cannot answer please say so, did you feel they were watertight because you knew the quality of the author: were your views subjective or in some way objective?
A I suppose it was both. It is not as if it had an easy ride because of who the author was but by the same token I had every confidence that the findings outlined would have been carefully checked and validated because of the reputation of the institution from which they came. I have to say, as a human being I had to be influenced by that, but then if the paper had been seriously … Well, if both papers together had been seriously flawed then I would have had to have said that as well, regardless of who it was who had written them.

Q So you still would have had some kind of criteria in your own mind as to how to look at that paper and check that paper and whether the implications and the findings were reasonably derived?
A Yes, although I must say in my experience people who are at the top of their game produce good papers, and reliable papers, so reputation I suppose does play a part, yes. I cannot actually think of an example where someone who was an outstanding figure in the field produced a paper that was total rubbish and would be rejected out of hand.

THE CHAIRMAN: Thank you very much. Those are all the questions from the Panel. Do counsel have any questions following Panel questions?

MS SMITH: No, thank you.

MR COONAN: No, thank you.


MR MILLER: I understood Ms Golding to be asking, when she talked about the statements of the authors, to the correspondence with The Lancet in subsequent years after the publication of the paper, if I am wrong about that I will not go on. Obviously this witness cannot deal with it.

THE CHAIRMAN: Ms Golding, was that your question?


MR MILLER: Just for Ms Golding’s reference, bundle FPT3 page 925 is correspondence from Professor Walker-Smith, dated 2 May 1998 to The Lancet. It is the continuation of a letter written to The Lancet and Professor Walker-Smith will be able to deal with it in evidence, but plainly this witness cannot deal with it.

THE CHAIRMAN: Thank you. Mr Hopkins?

MR HOPKINS: Nothing, thank you.

THE CHAIRMAN: In that case, Professor Candy, thank you for giving evidence today, the Panel is obviously very grateful to you. You are now released.

(The witness withdrew)


MS SMITH: Sir, that concludes the witnesses that I have for this afternoon. That is just the way the timing has worked out, but I hope it also is helpful to you because you indicated to me at the outset that it would be helpful to you to have an hour now and again to keep up with the papers, and I am conscious of the fact that you did not have that opportunity at an earlier stage, so we are trying to allow for it when the opportunity arises. As I say, that concludes any evidence I wish to call this afternoon.

Can I also tell you, sir, the position tomorrow is that we do not have any live witnesses tomorrow. We are anticipating there being some discussion first thing with the Legal Assessor and then there may or may not be an application that we wish you to consider, and so we have built in time to allow for that and to allow for any deliberations as a result of the applications that are made before you, but I cannot tell you anything more useful about it than that today but we will tell you exactly what is happening tomorrow morning and what time it is happening.

THE CHAIRMAN: Thank you. I am sure the Panel will use this time in an appropriate way. I can see the Legal Assessor’s finger going on the microphone.

THE LEGAL ASSESSOR: Does that mean that you would like me to see the legal representatives at 9.30 tomorrow and the Panel to arrive a little later?

MR MILLER: I think that might be sensible.

MS SMITH: I think that would be a good idea.

THE CHAIRMAN: Do you wish the Panel to be here at 10 o'clock?

MS SMITH: Yes, if you would not mind being here by 10 o'clock, sir, and then perhaps you will bear with us and do a little more reading if we need a little longer than that but I think that will probably be sufficient time, thank you.

THE CHAIRMAN: That is helpful, so we will now adjourn until 10 o'clock tomorrow morning and we will leave it to the learned lawyers in this Chamber to tell us how they wish us to proceed. Thank you, we will now adjourn.

(The Panel adjourned until 10 o'clock on Wednesday 15 August 2007)

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