Wednesday, February 1, 2012

Day 18 GMC Fitness to Practice hearing for Andrew Wakefield



Wednesday 8 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


Cross-examination by MR HOPKINS 13
Re-examination by MS SMITH 21
Questions by THE PANEL 26
Further cross-examination by MR MILLER 38


Examination by MS SMITH 40
Cross-examination by MR COONAN 54
Cross-examination by MR MILLER 57
Further re-examination by MS SMITH 59
Questions by THE PANEL 60
Further re-examined by MS SMITH 62

THE CHAIRMAN: Good morning, everyone.

Cross-examined by MR MILLER

Q Forget about conflicts of interest, we have no more questions about conflict of interest as far as I am concerned. The 1998 paper was sent to The Lancet by Dr Wakefield.
A Correct.

Q As you told us, he had submitted a number of papers previously which had been published by The Lancet.
A Correct.

Q Were you aware, at the time, that he had done research on the possible link benefit measles and bowel disease.
A I know that he, in the 1990s, had been looking at the epidemiological association between measles and inflammatory bowel disease, yes. What I was not aware of was this specific new syndrome that he had described in this paper.

Q We will come back to that. The thread of your evidence, both your evidence to the Panel and also in what you have written in The Lancet, is that is, in fact, the most interesting aspect of the paper that the new syndrome.
A There is actually a continuous thread of thought, from the paper published in the very early 1990s, about the possible origin of Crohn’s disease to the point of the 1998 paper.

Q Having received the draft you look at it first and decide whether it is worth sending out for peer review. One of the reviewers in this case was Professor Candy, a consultant paediatric gastroenterologist.
A Correct.

Q But you cannot now remember who the other two would have been.
A Correct.

Q There would also have been an epidemiologist or a statistician.
A That is right.

Q We will be hearing from Professor Candy that he approved the paper with limited, if any alterations to it. It came back from peer review with a tick rather than a cross this particular paper.
A Yes. I cannot remember if it was him or one of his fellow reviewers. There was also the issue of concern raised about how we contextualised the testimony regarding the MMR temporal link?

Q You took the view certainly, as the editor, that the central argument of the paper was not about MMR vaccine; it was a description of the new syndrome.
A That is exactly right. If you go back and look at the log book entry, the fact that we described it as a new GI syndrome in children, that verifies that point.

Q You felt that was something that was definitely worth publishing.
A Certainly.

Q You give it the sub-title Early Report to reflect that the work is at an early stage and it is not the finished article on the subject because of the way in which it was being reported, 12 cases?
A You put your finger on it exactly. In the world of thinking about evidence, there is a hierarchy of evidence from a case report or case series all the way through to a randomised trial. In terms of the strength of evidence, the randomised trial has the greatest strength and the case series the least strength. On those terms, it was appropriate to publish it as an Early Report.

Q The paper itself made clear, first, that there was no proof of an association between MMR and the syndrome described.
A Correct.

Q Secondly, there could be no basis, from the paper anyway, for arguing that MMR vaccination policy should be affected by their findings?
A Exactly right.

Q In your judgment, the testimony of the parents, which is described in the paper about the possible events leading up to their child’s illness, was an important part of the process towards understanding the new syndrome or disease?
A Yes, it was. A lot of debate has reflected around this issue but I think one’s first stance should be to respect the views of the parents and report them accurately in any scientific paper. Whether they turn out to be correct or not, the passage of time and further investigation will tell. One’s first impulse as a physician should be to respect the views of the parents at that time.

Q As you made it clear, you considered it inappropriate for The Lancet to suppress that information in this Early Report for reasons which you gave yesterday.
A That is right. It would be an act of censorship to do so and that would be inappropriate.

Q Obviously there was a question mark about the possible environmental triggers, the terms used. Did you, at the time - and this is a very important “at the time” - that that could be properly addressed, first, by the statement in the paper itself that no causal link had been established; secondly, by labelling the study as preliminary or Early Report; and, thirdly, by commissioning the commentary, which you did, by Chairman Stefano to put the whole paper in context?
A Correct, and fourthly by not ourselves drawing attention to it ourselves in the weekly Lancet press release that we issued. We were trying not to put, so to speak, our own spin on the story.

Q Again, in February 1998 did you believe that taking these steps would prevent any misunderstanding about the message from the paper?
A That was the intention.

Q That was your hope and belief as well presumably.
A Precisely put.

Q Again, it is terribly important, because it is looking forward and not knowing what happened around the publication, did you believe, in any event, that the paper alone in its published form, in fact, did not have any major public health implications, the paper itself?
A My view was that it did not have any major public health implications. I can tell you that there have been many occasions of papers we have published before then and since then where I thought that they could easily have had adverse public health implications and yet did not. It is very hard to predict which will and which will not. My view was we had put enough safeguards in place that it would not.

Q We had a little trouble a few days ago about using the term “state of mind”. It is not in any way pejorative, and anyway we are talking about The Lancet. That was the thinking of The Lancet at the time of publication. Underpinning it all, as far as you were concerned as the editor, is that the fact that they were reporting the possible link between bowel disease and autism as a new syndrome. A serious scientific point was being made.
A A serious scientific point was being made. You rightly use the word autism. The actual paper talks about a pervasive developmental disorder. I do not want to get into semantics but the debate around the diagnosis is quite important because these labels matter in the way they are discussed in the media.

Q Exactly, because they can have undertones or overtones which people attach more significance to than the authors, if they use that word, may have thought.
A It can over-interpreted or simplistically interpreted and be quite misleading and promote a scare rather than diminish one.

Q Was your view about the scientific value of the paper shared by others at the time?
A Others within the editorial group, certainly, amongst the peer reviewers, certainly, then subsequently, when the Medical Research Council held a review meeting, at which I was not present but subsequently heard reports of, my understanding was that while they deplored the public statements as regards the vaccine they recognised that there was scientific value which required further investigation in the new syndrome.

Q In fact, fast forwarding to 2004, even with what had gone on between 1998 and 2004 you wrote something in your commentary, the lessons of MMR. Do you have FTP 3, page 1208? This is at the time of the partial retraction, the right-hand column, the penultimate main paragraph in that right-hand column:

“The reason that today’s retraction is partial and not total is that the discovery of a possible link between bowel disease and autism is a serious scientific idea as recognised by the MRC and one that deserves further investigation. Although dismissing the entire 1998 Lancet paper as poor science gives a clear and correct message to the public about the status of any claim regarding the safety of MMR, in scientific and clinical terms it is both wrong and damaging. The autism-bowel disease link was considered part of a series of physiological observations judged by the MRC to be interesting and in principle worth investigating.”

That is the point you have just made.
A That is certainly what I wrote in 2004 and I still believe that today.

Q Can I deal quite briefly with Dr Rouse’s letter again to see where we get to? That is in 1998. We have been through this twice already so we will not look at the documents but I will put to you what I would like you to comment on. He wrote a letter published in The Lancet on May 2, 1998 raising the possibility of recall bias. In the same issue Dr Wakefield wrote and disclosed that only one author, A J W, has agreed to help evaluate a small number of these children on behalf of the Legal Aid Board.
A Correct.

Q You did not take the matter any further at that stage apart from publishing the correspondence. You have explained that you took the view that the phrase “one author A J W has agreed” as being something that had happened after publication of The Lancet paper.
A Particularly in conjunction with the additional statement in his reply saying that there was no conflict of interest. I had no reason to disbelieve that statement.

Q It lay there until it was revisited in 2004.
A That is correct.

Q Chronologically, if you could just turn. In the same bundle, to the documents that I asked you to read yesterday, 1140B and C. Have the Committee had an opportunity to read these?

THE CHAIRMAN: Yes, right at the end we went into camera.

MR MILLER: It saves me the time of going through them. You had an opportunity as well.
A Certainly.

Q The first is 1140B, a letter from Professor Walker-Smith to The Lancet and he makes a number of points, does he not?
A He does.

Q He says, first of all, that he had remained silent except for one letter very early on where he said the Chief Medical Officer had misunderstood something about the his logical findings, but that was purely from a doctor’s point of view, otherwise he had not been involved in correspondence but was saying that it is a shame what has happened since we published the paper. Although he declared that he was a supporter of the government policy on MMR and his grandchildren had had MMR, nonetheless he thought it was worth objective study to see whether or not there was a link. I am summarising probably rather badly.
A No, that is right. In fact, I believe that together with Dr Murch, as he then was, he made similar points in the immediate aftermath of the publication of the 1998 paper and correspondence too.

Q He says let us cut the personalities out of this and, in view of what were then being described as work from other centres, it is worth having an objective look at this again, an independent look, to see whether there was anything there in fairness to the parents, or the families of the children who had that disorder?
A In fairness to the children themselves.

Q That was the message, what he was saying, was it not?
A Exactly right, and one of the difficulties had been that in the storm of public debate and recrimination after the publication of the 1998 paper, in large degree those children and families had been forgotten.

Q The storm started with the press conference?
A I am obviously somewhat partial in this, am I not, so what I say has to be seen through a particular lens. Obviously, we were trying to manage the way this paper landed in the public domain. We thought we had put in place a number of procedures, that you have correctly outlined, to protect that management but, clearly, the press conference, from where I sat, blew that whole plan apart.

Q You wrote quite a long editorial, you wrote directly responding to it?
A Is this in response to Professor Walker Smith?

Q Yes.
A Yes.

Q I am leaving the press conference. I realise that was not part of your strategy or the way in which you were putting this paper into the scientific debate. What we have at 1140(c), the next page, is your response in quite a long editorial, in which you say:

“Is the measles, mumps and rubella (MMR) vaccine safe? Yes, acceptably so, is the only conclusion possible to reach in the face of the totality of the epidemiological evidence.”

We have used this phrase, this word, any number of times in this hearing. Your understanding would be helpful, some of the Panel are not
A Epidemiological?

Q Yes, when the word epidemiology, epidemiological evidence is used, what do you mean by that?
A In its most simplest way, I would describe it as the study of disease in populations.

Q It can in some ways be quite sophisticated and far reaching, in other ways it can be quite simple and crude?
A It goes all the way from a single case report to a randomised trial of 50,000 or more individuals. That would encompass the broad bands of epidemiology.

Q Indeed, in a letter which Professor Walker Smith had written, he was saying epidemiological is a pretty blunt tool – I think a quotation from somebody else – and what was required was the looking at the gut tissue properly rather than just listening to what people said or looking at statistics?
A It is a vital part of it, that is exactly right.

Q You made in the right hand column, bottom of the left hand column:

“The debate also needs to move beyond the safety of MMR. What of autism and the burden it brings to children and parents? As Walker Smith highlights, these children are ill served by the current fear that MMR causes autism. The UK Department of Health announced last week that £2.5 million was to be given to the MRC to support autism research.”

A If I may say, may I?

Q Yes, do.
A That is a critical point because, at the time the paper was published and through the 1990s, the conventional view was that autism spectrum disorder maybe accounted for four to five cases per 10,000 of the population. We know now, yes, a long time since, but from a paper that The Lancet published last year by Gillian Baird, that the prevalence is 116 per 10,000 of population. When The Lancet paper was published in 1998, the view was that autism spectrum disorder was a pretty small group in the population. In reality it is one per cent of the school age population, it is a huge under recognised problem. Here you have a paper coming out, reporting a link or a syndrome and a potential association with a vaccine that then gets escalated in a press conference. You can see how, if there is one per cent of the school age population with slightly odd behavioural symptoms undiagnosed, how you could get this huge parental reaction of concern which was not anticipated in 1998 because we did not know how prevalent autism spectrum disorder was. I think that is one of the lessons to be learned from this. I totally understand the public health authority response to bolster vaccination, but in doing so, to some degree, they were denying the fact that there was this vast unknown quantity of children with autism spectrum disorder and you ended up having the two forces hitting one another straight on leading to a disaster.

Q That is as you end up this editorial, is it not. At the bottom right hand paragraph:

“In 1998 in The Lancet, calling for an effective pharmacovigilance system for detecting vaccine associated adverse events, Chen and DeStefano said, ‘Without such a system, vaccine safety concerns such as that reported by Wakefield and colleagues may snowball into societal tragedies when the media and the public confuse association with causality and shun immunisation’. Unfortunately this is exactly what has happened with MMR. In addition to such a system, a clear research agenda into the causes, developmental abnormalities, and treatments of the autism spectrum disorders is needed.”

A Yes that is the second lesson of this, that when we are bringing any device, drug or vaccine into the public domain for use, we have to be very sure that we have the systems in place to protect its usage. I think the situation we had here was that, while many people were convinced of MMR safety and that the evidence was around confirming its safety in epidemiological terms, it had not been brought together so that if there was a signal of anxiety it could be rapidly deployed to assure the public. There was a lot of catching up that took place in the aftermath of February 1998 which took too long to bring that evidence base to the public attention.

Q Can we move to 2004, which is the last topic I would like to ask you about. As we have heard, you received an approach from Mr Deer, a free lance journalist who made a number of serious allegations, which, as we have seen, are summarised in The Lancet on 6 March 2004 in the same bundle at page 1211. Again, I want to put a timetable on this. I hope my timetable is correct, I appreciate it is some time ago. Following the approach from Mr Deer on Wednesday 18 February, you met with Dr Wakefield, Professor Walker Smith, Dr Murch and, incidentally, Dr Harvey
A Correct.

Q to obtain their responses, initial responses. I think that meeting was at The Lancet offices?
A That is right, at my office at The Lancet.

Q At on that occasion Dr Wakefield confirmed that three to four, of the children whose results were published in the 1998 paper, had been involved in a study commissioned by the Legal Aid Board?
A Or four to five, yes.

Q It was left that he had to confirm?
A He had to confirm with Richard Barr.

Q As you have confirmed, you understood that to have been a different study from the twelve patient in The Lancet?
A That is right.

Q We can see your understanding of this in the statement which is at the bottom of page 1211. It is the last three lines on the right hand column:

“We believe our conflict of interest guidelines at the time should have triggered such a disclosure, including the fact that a significant minority of the children described in the Lancet paper were also part of the Legal Aid Board funded pilot project.”

A That is what we believed, yes.

Q You go on to say, just a bit further down, the last part of that paragraph in the left hand column of page 1212:

“Finally, although the Legal Aid Board funding referred to a different aspect of Dr Wakefield’s work from that reported in The Lancet, the perception of a conflict of interest nevertheless remains.”

That was the position, as you understood it, having had the discussion on the Wednesday?
A That is right.

Q You described yesterday how you reacted to Mr Deer’s allegations. There were to be no sound bites for the Sunday Times or attributable quotations from you as the editor of The Lancet. In other words you were not prepared to give something which could be published at the weekend in the Sunday Times. You wanted something for more formal to decide what had happened?
A It was a bizarre meeting because, as I think I says yesterday or the day before, we do not often have Members of Parliament pitching up to The Lancet’s offices to take part in what was a very serious discussion about research misconduct of a paper. The whole circumstances of the meeting was extraordinary and somewhat disconcerting because statements were made in that meeting about the motivation behind what was going to be coming, which I found very disturbing and which made me and my colleagues cleave to the side of taking this process very formally and very cautiously to try and establish as many of the facts as possible.

Q As you said, since there was not in place in 1998 any sort of body that you could go to, which there might be in the United States at a second stage, the most important thing was to go to the institution, in this case the Royal Free Medical School?
A Correct.

Q And to conduct your inquiries there with somebody sufficiently senior at the medical school to assist and to involve themselves with that institution?
A To supervise that investigation, precisely.

Q Professor Hodgson was, I think, the top. At that stage, I think, Professor Zuckerman had retired and Professor Hodgson was the top man?
A Indeed, he was, I think the term is, the Vice Dean.

Q Because of the
A Because there is University College, the Royal Free which had combined, but he was the Vice Dean for the Royal Free campus.

Q That visit, that part of your investigation, took place on the following day on 19 February, the Thursday?
A Correct.

Q You met there with Professor Hodgson and discussed, presumably, what the allegations were with him?
A That is right.

Q At the Royal Free there was Professor Walker Smith, Dr Murch as well as Professor Hodgson, and, I suggest, Dr Mike Thomson, one of the consultant paediatrics, one of the co authors of the paper?
A Yes, you are jogging my memory now. I do remember him being involved at some stage.

Q Dr Wakefield was not there.
A Right. That is what I could not quite remember yesterday because he had left the Royal Free by then.

Q I do not know, I know I was not there – well, I do not know that, I think Professor Hodgson told us he was not there. The three clinicians were there, the third being Dr Mike Thomson. He played quite an important role, I suggest, because the case notes for the twelve children were produced and he and Professor Walker Smith went through the case notes on the individual children to identify the mode of referral in each case for the twelve children?
A From what I can remember, what happened was that we met in Professor Hodgson’s office, we reviewed the allegations, we decided on a course of action to try and investigate those allegations, we all went up to the Department of Paediatric Gastroenterology, sat in one of the offices there and Professor Walker Smith, Dr Murch and, as you rightly remind me, Dr Thomson then went off and gathered the notes, investigated them. Professor Hodgson was there some of the time, went off for part of the time and came back. Professor Walker Smith went to look at the biopsy book to establish questions about referral patterns and then a view was formed about the evidence in support of, or not, the allegations.

Q I think there were the documents there and there was also discussion, or supplemented by discussion, if it was required, about individual cases and the biopsy book as to what it showed?
A Amongst the team yes, exactly.

Q It was a lengthy meeting.
A It went on long into the evening as I recall.

Q Starting about 2 o’clock in the afternoon and going on until late in the evening?
A Yes.

Q At the end of that quite detailed process, you felt able to reach the conclusions which are to be found in your statement in The Lancet which is actually printed or published on 6 March 2004, which is this document.
A What I then did was, we discussed the findings. I discussed those with Professor Hodgson, I then took a summary of that back to my colleagues at The Lancet, we discussed that as an editorial group and with a bit more toing and froing ended up with the statement you see.

Q Just before we get to it, I think you also knew when you left the Royal Free, in outline anyway, what Dr Murch and Professor Walker Smith were going to say in their letters to The Lancet about these events?
A Exactly, because if you look at the order of the allegations on page 1211, they begin with issues surrounding ethics committee, so it was agreed that Dr Murch would deal largely with those, and then the issues about referral, allegation 3, that was dealt with largely by Professor Walker Smith, and on the question of Legal Aid Board Funding, Dr Walker would conclude, and then the Royal Free would finish with a general statement.

Q In broad terms you knew what was going to be said having discussed it.
A Correct.

Q And you knew what Professor Hodgson was going to say on behalf of the Royal Free?
A Correct.

Q This statement actually first saw the light of day on the internet rather than, as we see it here, published in The Lancet. I think you put out that statement on the Friday, so it all happened within a three day span.
A That is right.

Q We end up with the printed text of the next available Lancet issue?
A Exactly.

Q You told us about, let us not forget, Mr Deer, that there was some threat of legal action that was taken by the Sunday Times at some stage. Was that in relation to the press statement?
A There were several things that happened at that time. First of all, Mr Deer called me on Friday afternoon to express his horror and anger about the fact that The Lancet was going to issue this statement. Second, Evan Harris called me because he was all ready to give many, many press statements himself about this whole issue. I think he had been lined up to be the chief political spokesperson about this whole debate somehow, in a way that I am not privy to, but he was certainly going to be in the media limelight over this. Nevertheless, we then went ahead and released that statement. After that, I made some statements to the media which then triggered various threats of one sort or another.

Q But by the time we get to close of play on the Friday, this statement, the statement itself rather than what Dr Murch, Professor Walker Smith and Dr Wakefield had written, the statement, in other words The Lancet statement, had been disclosed on the Friday?
A Correct.

Q Can we just then go to page 1211, bundle 3, and I am only going to deal with a couple of points. You set out the allegation that had been made by the journalist, the first part of it, on the left hand side, and then your conclusions about it on the right hand column on page 1211, and the first allegation was that ethics approval had not been given.
A Correct.

Q And you answered that in the second column under the heading “Allegation 1”.

“The evidence we have seen indicates that ethics committee approval was given for data collection from clinically indicated investigations in the children with an initially undiagnosed illness... This illness was at first believed to be enteritis” which is the bowel component “combined with a disintegrative disorder. Subsequent detailed clinical investigations eventually showed this to be the syndrome finally reported in The Lancet.”

A Correct.

Q Now, that would be in no way unusual, would it, that one might start off looking for one condition but find that you are encountering something slightly different as the investigation continued and you see more patients, and at the end of it you would write about what you found rather than what you thought you had found at the beginning.
A Entirely usual, and also the other aspect that would be entirely usual which we considered was when does a research study begin or not, so in this particular case the allegation was that these investigations had taken place without ethics committee approval, but the way we saw the thinking evolve was that these children had been referred into the Royal Free through various routes and investigations had been conducted. Again, I would underline the point that Professor Walker Smith’s unit was an internationally recognised and respected paediatric gastroenterology unit; it would be entirely normal for him to be seeing complex cases and to have a mechanism for investigating those cases, often with quite invasive tests, to rule out rare causes of conditions or to give clues as to what the origins of those conditions might be. Our understanding was that, as these children were being referred in, his unit did indeed investigate these children extremely thoroughly. As time went on he and his colleagues formed a more detailed view about the nature of their complaints, some of the investigations were downgraded in importance, others were regarded as crucial, and also there was a view that there was a possibility that they were seeing something truly original here that required a more systematic investigative effort which would constitute research, so what began as a very careful specialist clinical investigation evolved into research.

Q The second allegation is that the study reported in The Lancet was completed under the cover of ethics approval for an entirely different study of 25 children with the heading as “A new paediatric syndrome; enteritis and disintegrative disorder following measles/rubella vaccination”, which of course was the original title of the project which, as you say there, became 172 96. You say in the right hand column.

“as described under Allegation 1, detailed clinically appropriate investigations led to a re evaluation of the initial diagnosis of these children, as set out in protocol 172/96” ---

for which we are to read, presumably, disintegrative disorder as what became known as the developmental disorder described in the paper?
A That is right. We read that protocol extremely innocently because the allegation was that somehow this protocol the allegation was that children were cherry picked. That this potential syndrome with autism, that is a key word here, and MMR vaccine, those children with that linkage were then cherry picked to be put in this Lancet paper. The way we read the protocol was that the beginning of this was not at all about looking at MMR autism; it was about looking at some connection between measles and a behavioural complaint which was at that time undiagnosed. It began with childhood disintegrative disorder, which is within a category, if my understanding is correct, of pervasive developmental disorder, and in the end it was the pervasive developmental disorder, the broader category that was reported in The Lancet paper. So again, that tended to support our view, as we looked at the evidence, and the Royal Free’s view, that this was a perfectly normal approach to gathering information, synthesising ideas and ultimately recognising they had something original which eventually got reported.

Q And the end product is the case reports of twelve children, and the suggestion that this syndrome, the new syndrome, had been recognised?
A That is right, and so in my mind there was no fabrication or falsification, no dishonesty, no attempt to mislead, no deception of any sort.

Q You would, of course, have seen from the original ethics committee application that the possible link with MMR, MR, was going to be considered?
A “MR” - that is quite important though, that difference, isn’t it, because correct me if I am wrong but I do not think MMR is mentioned in that original application. MR is, measles/rubella, but that seemed to me from an intentional point of view quite important, the allegation that somehow this was all about nailing MMR vaccine was not substantiated by looking at the protocol.

Q Because the reference is to MR rather than MMR?
A Exactly.

Q And in the end, if we go back to where we started with you, or I started with you, Dr Horton, the paper makes it clear, MR or MMR, in neither of them has a causative link been found.
A Correct.

Q In passing, the allegation in relation to referral which you deal with, saying the pattern was unusual, page 1211, “direct contact by patients with Dr Wakefield leading to referral for the Royal Free”, that comes from the case notes, presumably, which would show how the children had got to the Royal Free?
A That is how it was reported to us, yes, indeed.

Q And the children who were, indeed, consecutively referred would come from the biopsy book, I think, which was obtained as well?
A Correct.

Q “[Professor Walker Smith] reports to the best of his recollection he did not invite any children to participate in the study. Thus, as far as the facts can be ascertained by a review of the case notes and from memory, children reported in the 1998 Lancet paper were consecutively referred to the Royal Free and were not deliberately sought by the authors for inclusion in their study based on parents’ beliefs about an association between their child’s illness and the MMR vaccine.”

Those are the only three allegations that relate to Professor Walker Smith. Four and six relate to Dr Wakefield.
A I understand.

Q Just turning over the page to “Summary”,

“The first three allegations of alleged research and misconduct have been answered by clarifications provided by the senior authors of this work”.

Could I pause there, and again it is just for clarification. How does somebody become a senior author of a paper? What is the qualification for it?
A That is an extremely good question and one I cannot give you a precise answer for, because in this particular case you have, what, twelve or thirteen authors. We have three people here. Who is senior, who is responsible, who is not responsible seems to me somewhat random. In this particular case you go back to the protocol and you look at the named investigators and you see that Dr Wakefield, Professor Walker Smith and Dr Murch, as he then was, are named but there are a couple of other names as well. Traditionally the first author might carry greater responsibility, the last author might, but every study is different, I think is the answer.

Q Thank you for that.
A Not very helpful.

Q “The wording in the published paper regarding Ethical Practice Committee approval and patient referral was accurate, yet at the same time summarised obviously lengthy and complex institutional and clinical review and referral procedures. In the light of the public controversy surrounding this work and the allegations made to us one could argue that more explanation could and should have been provided in the original paper. Although, with hindsight, this seems a reasonable criticism, all research papers published by all journals are inevitably concise accounts of often complicated research protocols. We do not judge that there was any intention to conceal information or deceive readers about the ethical justification for this work and the nature of patient referral. We are pleased to have had the opportunity to clarify the scientific record over the matters raised by these serious allegations”.

A And I might add - might I?

Q Yes?
A That if one went and looked at the documentation that lay behind every statement in any medical journal about ethics approval being given I am sure one would see those kinds of lengthy and complex negotiations between an ethics committee and investigators. There is nothing unusual in that.

Q Just finally, because it happened at the same time, the retraction of interpretation, which has a formality of its own, by the sound of it. Retraction of a paper is a pretty dire thing for the authors of the paper because it implies that there is something wrong with the research, but the retraction of the interpretation is the interpretation that might have been put on the paper, and if it was put it should not have been put?
A Correct.

Q All of the authors except Doctors Wakefield, Harvey, and Linell published that retraction on page 1210, and indeed they stress the point which again we started with in the second paragraph:

“The main thrust of this paper” that is The Lancet 1998 “was the first description of an unexpected intestinal lesion in the children reported. Further evidence has been forthcoming in studies from the Royal Free Centre for Paediatric Gastroenterology and other groups to support and extend these findings. While much uncertainty remains about the nature of these changes, we believe it important that such work continues, as autistic children can potentially be helped by recognition and treatment of gastrointestinal problems”.

So that is the first part?
A Yes.

Q Keep alive the findings because it may benefit those with these conditions by, if possible, finding treatment for those conditions?
A And that is terribly important because again, in all of this debate, even to today, that central fact is often forgotten, and if I was a parent of a child - and you think 1 per cent of the school age population, how many children might we be talking about - and I heard people arguing sometimes quite offensively against the validity of those observations, I think I would be, to put it at its very least, dismayed at the lack of respect being given to me as a parent of a child who had a serious medical condition.

MR MILLER: Thank you, Dr Horton.

Cross examined by MR HOPKINS

Q Good morning, Dr Horton.
A Good morning.

Q I want to go back to the issue of authorship and senior authorship because the role of Professor Murch in the authorship of the February 1998 article is in issue here. Can we therefore, first of all, consider that concept of senior author again, please? I take it from what you have told this Panel there is no definition of what a senior author is in any of The Lancet guidances issued to authors, would that be correct?
A That is correct.

Q If we just look, please, at what was issued in 1997, if you go back to bundle 2 and turn up page 616, we are on the second page of the guidance that the Panel has been looking at before, and if we go to the left hand column the Panel has already looked at the section halfway down on conflict of interest but it is the section entitled “Authorship”:

“Disputes over authorship, and unacceptable multi authorship especially, usually arise late in the publication process. These matters are far better resolved early on, preferably before the study begins. An author must have made significant contributions to the design and execution and analysis and writing up of the study, and he or she must share responsibility for what is published” ---

and then you say this:

“We now ask authors to specify their individual contributions and we publish this information” ---

I will come back to that in a moment.

“‘Gift authorship’ is unacceptable. The provision of samples or the recruitment of patients, for example, are vital to research but they do not by themselves constitute authorship; an acknowledgement suffices for such contributions. In complex studies group authorship may be the only answer, and a clearly identified writing committee is essential here.”

A Yes.

Q Now, it may be that last sentence and the middle sentence are particularly important to the article that this Panel has to consider. You say in the middle:

“We now ask authors to specify their individual contributions and we publish this information.”

That presumably means it is published within or at the end of the article that you are printing, is that right?
A Yes. Would you like me to expand on this notion of contributorship, because it is quite important to the way journals, certainly the way The Lancet works now, and then in 1998. To be quite honest we had all become a little bit sceptical about the whole value of authorship and the reason was that, going back to the 1990s, there had been various serious episodes of frank fabrication and falsification; work that had been entirely made up. Often on the by-line of the paper, the traditional authors, there had been some very senior people, famous cardiologists and so on, largely in the United States. As soon as the fraud was discovered they ran a million miles away from taking any responsibility for the study at all and left the person who had done the fabrication to take his or her punishment. Well, that is fine, except it was a system that did not work because the assumption, if you truly believed in authorship, was that every member on the team of the by-line of a paper would take equal responsibility, but clearly that was a system that was not working. It is not like if I write a novel you know who the author is, I hope, but on a research paper you did not really know who did what and who was going to take responsibility for what. So in the mid late 1990s we were coming to a view that we needed to abandon the whole idea of authorship and, instead, adopt a policy of contributorship, where we would certainly allow people to be on the by-line of a paper, named underneath the title, but we wanted to know exactly what individuals had done, so if there was a problem later you could say: “Well, he or she was responsible for that part of the study, so if that part of the study went wrong he or she has to take” - I do not want to use the word “blame” but has to take responsibility for that. Then you can see that somebody else might not have taken responsibility for that. That is especially important when you are doing complex interdisciplinary or research across different geographies to know who did what and when. In 1998 we were publishing contributorship statements.

Q Thank you for that, and we will look at the relevant passage in the 1998 paper dealing with that very point. Going back to the last sentence in this passage on page 616:

“In complex studies group authorship may be the only answer, and a clearly identified writing committee is essential.”

A Yes.

Q We know from this paper there were 13 co-authors?
A Yes.

Q Would that be something that would fall within this last sentence?
A Having a writing committee?

Q Yes.
A Usually writing committees are for large clinical trials where they are multi-centre. In this particular case you would expect there would be one person who would draft the paper, circulate it to his or her colleagues for their comments and additions, and then be the person who would take the paper through all the negotiations with the journal.

Q That is something I want to explore with you on the evidence that we have. Going back to the concept of senior authorship, it does not, of itself, mean the person is professionally senior?
A No, absolutely not.

Q It may have some bearing on what role they played in the study.
A Yes. In fact, the whole idea of senior authorship, to me, is rather meaningless. What I am interested in is who did what and who will take responsibility for what is in the study.

Q Let us explore what evidence there is about that. If we go to look at the article, page 783 of the same bundle, towards the top of the page, you see the list and remind ourselves of the list of authors. It starts with Dr Wakefield, then mention of Professor Murch, Anthony Linnell, et cetera, and then ending with Professor Walker-Smith. Clearly in the title no mention of what each was doing or their rank or importance in the study, not that you would expect that to happen.
A I would only make one comment. The corresponding author is usually the person who takes the responsibility to manage any subsequent discussion or debate around the paper. The corresponding author, although not necessarily the senior author, whatever that might mean, is the person who, in a sense, is the external representative for the group.

Q If we go to the bottom of this page, bottom left-hand corner, we see there is a description of the groups and departments involved in this study. At the very bottom it says “correspondence to Dr Wakefield”. Is that the label that means he is the corresponding author?
A Correct.

Q Just as a matter of fact, stepping aside from this article, did you have any dealings with Dr Murch, as he then was, concerning this paper prior to its publication in February 1998?
A No, I did not. I did not know Dr Murch at this time.

Q He was neither treated as nor named as the corresponding author, was he?
A To my knowledge, no.

Q Just in terms of the positioning of names, we have heard mention by another witness in this case that there may be some significance in names being at the beginning of the list of co-authors and some significance of the name being at the end.
A Correct.

Q Do The Lancet adopt that approach?
A We leave it entirely up to the individual research teams to make their own minds up; we have no rules about that ourselves.

Q Presumably the same applies for those authors who find themselves sandwiched in between the first and the last names?
A Yes. Somehow they have to work out who is going to take precedence in the order of authors. This can often be a source of conflict which is why we try and stay out of it.

Q From the face of this paper there is no indication, is there, as to what role Professor Murch played in the writing of this paper other than the section on contribution, which I will come to?
A No, there is not.

Q Can we then turn to that part and go on to page 787? We then see, towards the bottom left-hand column, the penultimate paragraph in fine print, Contributors. We then see that Dr Wakefield’s name is mentioned as the senior scientific investigator and then it says Dr Murch and Thompson did the colonoscopies.
A Correct.

Q It may be obvious from what you already have said but can we spell it out. What was this information telling you about Dr Murch’s role in the authorship of this document?
A This specified absolutely precisely his contribution to this overall study: no more, no less.

Q Did you take this to mean that he was one of two technicians who was carrying out the colonoscopies on the children reported?
A Yes. The way a clinical team works is you have a leader of the team, and Professor Walker-Smith, as the Professor and head of department, was the leader of that team. He would have had a group of people around him (consultants, senior lectures and other doctors in training) who he would have had overall responsibility for and, to some degree, directed. I would have seen that Dr Murch and Dr Thompson were two of his - I am not entirely sure what their precise positions were at the time - colleagues in his unit who were carrying out these colonoscopies.

Q We can leave the paper there. Can I move on to what happened in its immediate aftermath after publication. If we turn on to page 818, we there see the beginning of correspondence that was published at The Lancet about this paper, is that right?
A That is right.

Q If we move on to page 821, do we there see replies, the first one by Dr Wakefield titled Author’s Reply?
A Yes.

Q Then in the middle column, again under Author’s Reply but this time three of them, Dr Murch, as he then was, Dr Thompson and Professor Walker-Smith replying about issues raised in a letter from Keith Lindley and Peter Mills.
A That is right.

Q Did you see this letter, the letter from the three clinicians, as setting out their stall as to what they saw was the value in the information they had obtained from this study from a clinical point of view?
A Yes. It is highly unusual, to be frank, to have the authorship divide in this way. You publish a paper and there will be letters quite commonly and the authors will reply as one group. Here there had been a split and Dr Wakefield was replying to one aspect of that. Dr Murch and colleagues were replying to their colleagues in the paediatric gastroenterology community and to other paediatricians who were expressing concern about the potential damage to MMR vaccination. This reflected the division that had taken place following the press conference.

Q If we look, in the middle column, you see, about half-way down that page, the statement:

“We emphatically endorse current vaccination policy until further data are available.”

A Yes, that has always been their position.

Q That was their position maintained by Dr Murch throughout his dealings with you and The Lancet, is that right?
A That is right.

Q Put that on one side. Can I deal with some duties relating to authorship and see where we go with that? You have explained that in a paper like this there would be one lead author who would draft the paper and that, in this case, then Dr Wakefield act as the corresponding author?
A Yes. I would expect him to share the draft with all of his co-authors, co-contributors, to seek their comments but then to be the person handling negotiations with the Journal.

Q Can we look at it from the position of the co-authors not the person drafting it? You would expect each of them obviously to read through the draft.
A Prior to submission, certainly.

Q You would expect them to point out any errors to that lead author?
A Correct.

Q From a co-author’s point of view, he or she could not guarantee, could they, the accuracy of everything that would be written in that paper?
A Which is exactly the reason why we have contributor’s statements so that you can see who would be taking responsibility for which parts of the manuscript.

Q Indeed. Can I slice it in this way, in a multi-authored paper such as this it is a coalescence of people with different areas of expertise?
A That is right.

Q Therefore, each co-author cannot guarantee the accuracy of what is being said by an expert outside his or her field?
A That is correct.

Q Similarly, a co-author cannot guarantee the accuracy of an event or statement of fact that is outside his or her experience in that study?
A That is correct. You use the word “guarantee” which is a very precise word that we, in the medical journal community, often talk about ourselves: who can guarantee the credibility of particular parts of the work.

Q When it comes to division of responsibility amongst co-authors, would this be fair: it, in part, depends on the role they play in the study?
A Yes.

Q It, in part depends, on the expertise that they have and bring to bear on that study?
A Indeed.

Q It, in part, bears on the knowledge they have of the events that are being reported in the study?
A Correct.

Q Can we look, in practical terms, at the mechanisms in place for the co-authors to play that part? As I understand it, the process of The Lancet is for a manuscript to be submitted by the lead corresponding author but having run that manuscript past the
co-authors, is that correct?
A Yes.

Q Do you know when that actually occurred on this case? Are you able to put a date on the first time The Lancet received the first manuscript of this paper?
A I do not know the precise first date of when the paper was submitted to the Journal, no.

Q Would it be fair to say that the paper trail relating to that, nine or ten years down the line, has now gone by and large?
A It has. What we have are the log book entries where you see the dates on which the paper was discussed which we have already discussed.

Q After submission of the paper you then told us what the process is: it is considered by editors, it goes out for review and there may be revisions to be suggested.
A In every case that I am aware of, yes.

Q Those suggestions for revisions are then sent directly to the corresponding author, is that correct?
A Yes.

Q Not to any of the co-authors?
A No.

Q Therefore, would this be fair, that you rely on the corresponding author to liaise with the co-authors before coming back with a revised document?
A Exactly.

Q I think it follows from what you have said there is a large element of trust in this process.
A There is indeed.

Q There is trust in relying on the corresponding author to correct the manuscript but in accordance with whatever the co-authors have said?
A Correct.

Q To report back to The Lancet with their suggested revisions and to liaise with the editors.
A Correct.

Q And to be rely on the corresponding author to make any appropriate amendments and proof read.
A That is right. In the last 12 to 18 months, in fact, we have had that policy of trust run until very recently. It is only now we are beginning to question that ourselves because we have had another episode of outright fraud where a corresponding author did not share information with his colleagues - this was a study from Norway - and completely invented an entire data set, did not tell any of his colleagues and we did not communicate with any of his colleagues. We are now thinking about instituting a practice where we do share all information with co-authors but certainly in 1998 and to this date we do not.

Q Would it be right to say that from The Lancet’s point of view, and certainly within your knowledge, you do not know what role, if any, the co-authors took after the submission of the first manuscript of The Lance?
A That is exactly right.

Q Prior to the publication of the paper in February 1998, did you have any verbal oral discussions, firstly, with Dr Wakefield about the paper?
A No, I did not.

Q Or with any co-author?
A No, I did not.

Q Can I move on to a separate topic, and I take it fairly shortly. We are going ahead now to 2004 when allegations were being made by Mr Deer. Mr Miller has covered much of the ground with you on that. I want to deal with the meeting at the Royal Free on the 19 February, just a few points in that relation to that. I think now your memory has been jogged that Dr Thompson was there. I think you accept that Dr Wakefield was not present at that meeting.
A Yes.

Q Do you recall that he was contacted by telephone however?
A To be entirely honest with you, I do not know how he was contacted.

Q Do you recall that there was initially some delay in obtaining the patient’s records that afternoon partly because there was a problem in identifying patient names because in The Lancet they had been anonymous?
A I do recall that.

Q Indeed, it was necessary to contact Dr Wakefield to ascertain that list of names I suggest?
A Right. I cannot recall that part of it but I do remember the delay.

Q The records, in fact, did not became available until around about five o’clock that afternoon.
A I certainly remember it took a long time to complete the investigation. The exact timings I do not recollect, I am afraid.

Q Once those records were available, they were looked at by Dr Thompson, is that right?
A Yes.

Q Professor Walker-Smith?
A Correct.

Q And Dr Murch?
A That is right. I think Professor Hodgson was coming in at various occasions. I am not quite sure what records he saw or did not see but he was certainly around for some of the time.

Q Was it later that evening, some time between 7:00 or 9:00 - Dr Murch is unable to be precise about that - that Professor Hodgson then asked him to respond to the allegations about the ethics point?
A I do not recall it being Professor Hodgson asking Dr Murch, or anyone else, to do specific aspects of the responses. I do remember us all discussing how we would divide things up and coming to a view about who would take responsibility for different allegations.

Q Can you remember when that division occurred?
A That would have been on that evening.

Q We have looked several times now at the statement that Professor Murch wrote. Just for the Panel’s reference, there is no need to turn it up, it is page 1212, bundle 3. I want to deal with the context for that. Professor Murch was, in effect, replying to Mr Deer’s allegations that in part ethical approval had been obtained for a fake study, is that right?
A Exactly.

Q Also in part that ethical approval had been obtained in 1998 and then backdated.
A Exactly.

Q We have to bear in mind, do we not, the context in which Professor Murch was being asked to respond to allegations when he writes that statement?
A You mean in relation to those allegations? Yes, of course he was addressing those.

Q Is it right that he prepared that statement overnight and made it available to you early on the next day?
A Correct.

Q You have told us that was then subsequently published on the internet before going in print in The Lancet.
A Exactly.

Q Finally, in relation to the retraction of an interpretation, would it be fair to say that Professor Murch played a central role in getting the retraction together?
A He was the first person I contacted to discuss this, yes.

Re-examined by MS SMITH

MS SMITH: At this stage in the proceedings I will be skipping about a bit and I apologise for that but it is just asking you to clarify some of the matters that have been covered by all three counsel. I will start backwards in the hope that our memories will be fresher.

First of all, in relation to the questions that Mr Hopkins asked you on behalf of Professor Murch, I want to touch on this question of the concept of senior author and what you said about that. You were asked whether the actual order of the authors on the paper was of significance and you said that it was to some degree but it was up to the research teams to determine, is that correct?
A It is different for every research group, yes.

Q You said that it can be the subject of some dispute. What are the prime positions as far as authorship are concerned?
A First and last are absolutely key. There is often a debate about who comes second and third.

Q Although you rejected for yourself the word “blame” and used the word “responsibility” and of course it is perhaps not surprising in the context of the General Medical Council that that is what you are thinking about, do those positions also carry with them the positive side, in other words the scientific glory if the paper should happen to be a particularly interesting one?
A That is very interesting. There are two aspects to publication from an author’s point of view: credit and responsibility. Prior to introducing contributorship, the emphasis was also on glory, the credit, and, when something went wrong, as I have mentioned, everybody runs a million miles away from it. Authors often only want to take the credit and not the responsibility. The whole point of contributorship is that it says, here precisely is the detail of who should take responsibility for which parts of this study, which is totally unambiguous whereas, when you just look at the by-line of authors, it is utterly ambiguous.

Q When papers are talked about in scientific circles, are they frequently identified by the first author with et al added on?
A Yes, absolutely.

Q That is all I want to ask you about in relation to Mr Hopkins’s questions. As far as Mr Miller is concerned, sitting in the middle and representing Professor Walker-Smith, I have one or two matters. You said when you published this paper that you had done your best, in effect, to put into place what you described as safeguards.
A That is correct.

Q When you published the paper, what was the reason in your mind why you needed safeguards?
A Because of the potential misinterpretation of the parental testimony in one of the tables in the paper and the discussion within the paper of the possible temporal link as a trigger for the syndrome.

Q The temporal link being the MMR?
A Exactly.

Q The commentary that was one of the safeguards, as I understand it, that you were referring to actually refers to the need to avoid societal tragedy and that is the very phrase that you subsequently picked up in your lessons of MMR.
A That is exactly right.

Q Presumably you saw and considered the commentary before it was put in with the papers?
A Yes.

Q Did you feel that the commentary did an effective job or a hopefully effective job of redressing any difficulties that might arise as a result of the paper?
A The goal was to leave the reader without any doubt in his or her mind that measles vaccination had been a safe and vastly effective means to save literally millions of lives.

Q If you had not put in those safeguards, would you have regarded it as being responsible to publish this paper?
A Reckless I would have called it.

Q At the time without those safeguards?
A Yes.

Q The other matter that I wanted to ask you about that Mr Miller talked about was the 2004 investigation. Would you go back to volume 3 at page 1212. Mr Miller asked you about the first three allegations relating to issues of referral and the position as far as the ethics committee was concerned and I want to look at the summary with you. You say,

“The first three allegations of alleged research misconduct have been answered by clarifications provided by the senior authors of this work.”

A Yes.

Q To whom were you referring when you used the “senior authors” phrase there?
A I was referring to Dr Wakefield, Professor Walker-Smith and Dr Murch.

Q Looking at the referral process, did you actually see these referral letters yourself?
A No.

Q As far as we know, you saw the ethics committee ---
A I did. I saw a lot of documents relating to the ethics committee approval process: correspondence between the Chair of the ethics committee and various members of the research team and other letters I believe involving the Dean.

Q We see ranged behind me the clinical records relating to these children; did you have any opportunity to study those yourself?
A No, certainly not. I might add that this is one of the reasons for going to the institution. The journal is not set up by its very structure and staffing to be able to conduct investigations on its own and that is why we would go to an institution and say, “Here are some concerns. Please, can you take up an investigation.” We of course want to have a very close involvement in that, so we take responsibility for our involvement in that, but we do not have the resources to create our own inquiry team to do that kind of investigation.

Q As far as specialisms are concerned, we know that you are a qualified doctor of course, but would you feel remotely able to challenge anything that was said to you by the team of gastroenterologists as to whether these tests were clinically indicated or not?
A I believe that I could have a robust discussion about the appropriateness of those tests or not. Could I enter into a detailed discussion of the immunopathology of bowel disease? The answer would be “no”.

Q Turning to the questions that you were asked yesterday by Mr Coonan, but actually a propos also of the same issue of the 2004 investigations, he put to you questions on the basis that any funding from the Legal Aid Board had been indirect as far as this study was concerned and that it applied to another part of the study than the one written up in The Lancet paper.
A That is correct.

Q You will appreciate that that is Dr Wakefield’s account and it is obviously going to be a matter for the Panel ultimately to determine if it is a correct account. What I wanted to ask you was, so far as you were concerned, did you have any information about the precise nature of the funding and what it was spent on other than what Dr Wakefield told you?
A No, I did not and, to be quite honest, I thought that irrelevant to the issue of whether there was a conflict of interest or not.

Q You were asked about The Lancet’s conflict of interest test at considerable length and I am certainly not going to take you through all that again but there are a couple of matters that I wanted to look at with you. Would you go back to volume 2 and page 615. This is the 1997 “Writing for The Lancet” which you have been through before and we looked at the conflict of interest test there but what I wanted to look at is at the top in the box “Writing for The Lancet” in 1997 where you make the very point that you made to Mr Coonan yesterday,

“The Lancet is a signatory journal to the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, a document issued by the International Committee of Medical Journal Editors”

and you say where it can be found on the website, and you say,

“‘Writing for The Lancet’ enlarges upon or emphasises what is in that document and in other pronouncements from the editor group. Not all the answers you seek will be found on these pages and the journal’s editorial staff in London and New York will be pleased to help.”

A That is correct.

Q Is that, at that time and presumably now, a fact, Dr Horton? In other words, was that just some vague observation or do you regard yourselves as being approachable for individual inquiries?
A We pride ourselves on being approachable for individual inquiries.

Q You highlighted, when you were answering Mr Coonan’s questions, the importance of the conscience and judgment of the author and you said that, in the end, that is what it has to be down to. In circumstances where a situation which might be thought to be a conflict of interest but is an unusual one or a novel one arises, what kind of role do you then think that conscience and judgment plays?
A In the first instance, to contact one of the editors at the journal and to discuss the matter in an open and frank way, to take advice, to take wise counsel on the understanding that that advice and consultation will be confidential and will be based, I hope, on the great deal of experience that the editorial team will have in dealing with these matters over many years.

Q Mr Coonan put to you that, in 1997, frequently conflicts were not disclosed and you made the general point that that was no excuse for not doing so, but I want to ask you whether, in the specific circumstances of this paper given the sensitive nature of this paper, does that affect at all your view as to the strength of the obligation of the authors?
A Yes. May I come back to your first point. What I was trying to draw a distinction between yesterday and may have failed was that there are two parts to disclosure: disclosure to the editors confidentially in order that there can be a private discussion about the significance of that possible conflict/competing interest; second, a decision about whether that should be published. What has changed over time is less the disclosure to the editor and more the disclosure in the public domain. So, the step-change that we spoke about yesterday was saying that this information should be in the public domain for readers to see and to make their own judgment about. Prior to that, editors had taken a rather paternalistic role saying, “Tell us what your possible conflict of interest is – tell us – and we will decide with you.” What has changed with time is that that paternalism by people such as myself has been stripped out and we now move towards total transparency.

Q As far as the second half of my question – I am sorry that it was certainly a twofold question – is concerned, do you regard the obligations on the authors as being any different depending on the nature of the paper that is being submitted or do you regard it as a uniform obligation whether the paper is an important one or a sensitive one or is a more run-of-the-mill one?
A Uniform although obviously the author will … This is where conscience and judgment comes in and this is a terribly subjective issue. If the author is thinking, this paper might have quite an impact in certain ways, then I would hope that their conscience and judgment would make them think, I really need to seek advice about this particular matter, and there will be instances where that is more or less important. I know that seems a terrible imprecise reply but that is simply because these issues are so subjective on a case-by-case basis.

Q This may or may not be of significance later, doctor, and I am sorry if it is just a question of semantics but, during the interchange between you and Mr Coonan yesterday afternoon, there was use of both the terms “perception of a conflict of interest” and “potential conflict of interest”. Can those phrases be used interchangeably in your view or do you see any distinction between them, between a perception of a conflict of interest and a potential conflict of interest?
A They are words that we do not spend a lot of time about at the journal distinguishing between. I can see that semantically they do refer to slightly different aspects of a conflict of interest, one being utterly in the reader’s imagination or belief or perception, the other being perhaps more material. Again, this is why it is so difficult to legislate in guidance.

Q If we could talk in terms, just for a moment, of a potential conflict of interest, if there is any difference, would your view remain the same as you have already expressed in relation to Dr Wakefield’s obligation to disclose his involvement in the litigation to you?
A Yes especially the extent of the involvement. That is why I was trying yesterday to bring us back to the actual case rather than the abstract discussion because it was the extent of that involvement that struck me in 2004 as so obviously requiring some kind of disclosure.

Q You were taken to a bird’s eye tour of the development and the way in which you have regarded conflicts of interest over the past 15 years. I want to look back, very briefly, at two documents. Would you turn to volume 7 at page 202? That is the Vancouver Group’s 1997 observations about conflict. We read through them yesterday and I am certainly not going to do so again. I want to look at one phrase in that paragraph on the right hand side. It refers to conflicts existing where there are ties to activities that could inappropriately influence judgment. It says:

“Financial relationships with industry – for example through employment, consultancies, stock ownership, honoraria, expert testimony...”

which may be relevant:

“...either directly or through immediate family are usually considered to be the most important conflicts of interest. However, conflicts can occur for other reasons, such as personal relationships, academic competition, and intellectual passion.”

A Yes.

Q If you could put that away and turn to the file that Dr Wakefield has produced, the blue file.
A I do not have that with me, but I think I can remember from yesterday afternoon. I have the documents, but I thought we had moved on.

Q We will give you one so you are in the same page as me. Tab 2 page 155 in the internal document, which is The Lancet in 2001, left hand side. Halfway down the first paragraph:

“The potential for conflict of interest can exist whether or not an individual believes that the relationship affects his or her scientific judgment. Financial relationships (such as employment, consultancies, stock ownership, honoraria, paid expert testimony) are the most easily identifiable conflicts of interest and the most likely to undermine the credibility of the journal, the authors and of science itself. Conflicts can occur for other reasons, however, such as personal and family relationships, academic competition and intellectual passion.”

So is it your view, Dr Horton, that the fundamentals in regard to this issue have changed at all over the period?
A The fundamentals have not changed. The fundamentals have been in place since the early/mid 1990s, which is why I came back to those statements in the ICMJE guidelines in 1997. The issue about whether people do or do not adhere to those guidelines seems to me immaterial to the fact that those guidelines exist and on the basis of our instructions to authors they should be adhered to.

MS SMITH: Thank you very much.

THE CHAIRMAN: It is very close to quarter past eleven. I think what we would prefer to do is, first, we will say it is time for the mid morning break, even more important for Dr Horton and ourselves but I think we all need that break. Secondly, I think we will need to spend about twenty minutes going through our own notes of the evidence Dr Horton has given before we are in a position to ask him some questions.

It is now 11.15 am and that will take us to about 11.55 am. We will spend about twenty minutes or so in camera first looking at our notes and then have coffee. Dr Horton, once again, I have to remind you that you are under oath and still giving the evidence. I do apologise for the long time you have been sitting in that chair, but these are important matters and we have to look at them very, very carefully. We will go into camera and then adjourn.


(The Panel adjourned for a short while)


Questioned by THE PANEL

THE CHAIRMAN: Dr Horton, as I said before, it is now for the Panel members to ask any questions. If they have any questions, I will introduce them individually to you. Ms Golding is the lay member.

MS GOLDING: Good morning. When you started investigating the whole situations did you
A In 2004?

Q Is this when you spoke with all the doctors and you went to the Royal Free?
A That is right, yes.

Q Did you have a look at the application to the ethics committee for the original study, and did you have a look at the application for the second study which Dr Wakefield said he was carrying out?
A I certainly remember looking at the application for the first study. I cannot recall now, unless you have the documents here in the folders, whether I saw a second one or not.

Q In FTP1, I believe page 104 is the second study. Perhaps someone will correct me if I am wrong, this is the application that went to the Legal Aid?
A This is the Legal Aid Board application. No, I did not see the Legal Aid Board application. When we met in my office on that afternoon, I think the Wednesday afternoon, I did ask Dr Wakefield if it was possible not to see the application but to see the final report submitted to the Legal Aid Board. That document was, I believe, confidential and so, understandably, he was not in a position to share that with me at that time and I have not seen it subsequently I might say.

Q You were told then that it was the same research group?
A The patients – the children?

Q No, the scientists and the clinicians who were carrying it out?
A No, not at all. The only thing that was common.... To be honest, I did not know who exactly was the research group for the Legal Aid Board funded study. The only person in common to my knowledge was Dr Wakefield.

Q Were all the statements from the doctors prepared at the same time?
A Yes, from in between the time that we met in my office to the time of publication.

Q Did you feel that all the statements answered the allegations adequately?
A The allegations as put to us that at that time, yes, indeed.

Q Did The Lancet actually get involved in assisting in the press briefings for any other type of paper?
A Not related to the 1998 paper?

Q No.
A At the time in 1998 we really did not get involved in any press briefing activity at all apart from a weekly press release that we sent out. One of the lessons of the February 1998 paper and subsequent press conference was very much that we, as editors, should be much more actively engaged in working with authors and institutions over the public dissemination of our findings should they choose to have a press conference. Our policy now is that, if the authors or institutions are going to hold a press conference, we request, at the very least, to have a meeting with the authors and the press officer – we have our own press officer – put the two in contact, so that we know exactly what is going to be said. We look at the press materials that are going to be distributed. If, and there often is not, but if there was going to be a video news release we would see that beforehand, and if the press briefing was going to be held in the United Kingdom then one of the editors, ideally myself, would actually be a panel member, possibly chairing the press conference.

Q This was before the 1998
A No, no, this was one of the lessons of the 1998 experience. What I now see as errors of the 1998 experience, was that I was not sufficiently sensitive to the dislocation between the messages that might come out of a press conference and the messages in the paper. It seemed to me – it did not cross my mind that there was going to be a different set of messages coming out of the press conference to what was in the paper. Clearly there was, and one of the lessons is that I have a responsibility to make sure that any dissemination of research findings in whatever way, including a press conference, is actively managed by The Lancet.

MS GOLDING: Are you able to give us a run down as to what happened at the press briefing?

THE CHAIRMAN: Miss Smith, are you able to hear what Ms Golding is asking?

MS SMITH: Yes, I can.
A The account that I would give you would be second hand.

MR COONAN: He was not present at the press conference.
A I can describe the materials, the press release and the video news release which I did see and which were publicly available.

MS GOLDING: What is the difference between a scientific and clinical study because in some of the papers here or the statements, scientific and clinical are used, but Dr Wakefield said that the 1998 paper was not a scientific paper. Would The Lancet make a difference between the two of them?
A No, we would regard – I mean the section of the journal in which his paper was published would by any ordinary reader be seen as research, so the definition of “research”, if you ask me that, would be any kind of systematic investigation to increase the sum of our knowledge. In that sense, his study was certainly research and I do not make a particular distinction between clinical or scientific.

Q It appears to me that he makes a distinction and I wondered whether that would have made a difference in what is allowed?
A What is the basis of his distinction?

Q Page 1216, in bundle 3. This is page 1216 in responding to the retraction on the right hand side, second paragraph, halfway down:

“We emphasise that this was not a scientific paper but a clinical report.”

Is there a difference?
A I do not accept there is a material difference there. This is research in the sense that the paper was describing a set of systematic investigations of twelve children with the aim of trying to draw some general implications, facts, out of those and making some interpretations on the basis of those facts. That would be a research study in my definition. It is a clinical study, it is a scientific study, it is all of those things.

Q On 1214, on the left hand side, the fifth paragraph where it says that there is a written statement by the parents of the children.
A In the fifth paragraph from the top on the left hand side?

Q It says “A statement by Dr Andrew Wakefield” and further down it says:

“In support of this and in view of these allegations...”

Were you able to check the statements or question any of these people?
A The parents, no. I was not aware of the names of the children identified 1 through to 12. I heard some names banded about, but I did not know which names related to the number of the child, 1 to 12, and I did not know any of the parents either so, no, I did not verify precisely what the parents had told Dr Wakefield.

Q What about the solicitor, Richard Barr?
A Richard Barr, no, he seemed to have disappeared off the face of the earth.

MS GOLDING: Thank you very much.

THE CHAIRMAN: Dr Moodley has a question. Dr Moodley is a medical member.

DR MOODLEY: You explained in some detail the safeguards you had put in place to ensure that the paper was judged on the scientific merit and that the findings were not misinterpreted.
A Correct.

Q I just want look at the actual paper and the structure of the paper. Am I right in thinking that, as editors of journals, you look at the readability and impact factor and the way a paper would actually be structured for the message?
A Yes. The impact factor is an impact factor of the journal, so it is not related to an individual paper, but the paper has a very particular format. We call it the IMRAD format – an introduction, methods, results and discussion. That structure is a highly formalised standard, as you know, in research reports.

Q In the actual paper on page 787 of bundle 2.
A The final page.

Q There is a very firm assertion that there is no proven association between measles, mumps etc?
A Indeed.

Q But, the paper actually ends with:

“We have identified [this syndrome]... In most cases, the onset of symptoms was after measles, mumps and rubella immunisation. Further investigations are needed to examine this syndrome and its possible relation to this vaccine.”

What is the impact of presenting this as the final line of the paper?
A I do not think the two statements are contradictory. We did not prove an association is a fact, but at the same time what they are saying at the end, in my reading, was eight out of twelve parents had reported this temporal link and they are inviting readers to take that as an indication that further investigation is worthwhile. But, at the same time, they are qualifying that in the earlier paragraph by saying there is no proven association. I would add that, in the paragraph immediately after, we did not prove an association. They reinforce that by saying:

“Published evidence is inadequate to show whether there is a change in incidence or a link with the measles, mumps and rubella vaccine”.

I think what they are trying to do is evenly balance the cautious statement with the fact that they have this testimony which exists and they want to be taken seriously.

Q On another issue, what is meant by “consecutive”, because in the referrals we talk about consecutive referrals. How do we understand, or what is normally understood, if we see “consecutive referrals” in a paper?
A The ordinary meaning of consecutive referral, to my mind, would literally mean a sequence of children referred one after the other to a specialist, individual or a clinic or unit. That is certainly the way it was presented in this paper. What we found out in 2004, both from what Brian Deer presented to us and also from what Professor Walker Smith discovered and reported to us, was that that consecutive referral, while it was to the letter correct, behind that was actually a much more complex set of relationships. So yes, parents or children had been referred from in most cases general practitioners and I think in two cases consultant paediatricians, but that followed in some instances - and I do not know which - direct contact between the parents and Dr Wakefield. I think there was one instance where there had been a conversation between Professor Walker Smith and one of the consultant paediatricians as well, and those children had been referred into the clinic and then been examined what appeared to be consecutively when one looked at the biopsy book, and I think there is a reference made in the paper to this actually. Yes. On page 639, in the first paragraph of the discussion, page 785 in your numbering system, there is a statement where the authors say in the second sentence:

“Intestinal and behavioural pathologies may have occurred together by chance reflecting a selection bias in a self referred group”,

so there is a part of the paper in a sense discussing a limitation of the study where the aspect of self referral might have led to bias. So I think behind the statement “consecutive series” there is a much more complex set of relationships which, again with that word “hindsight”, it would have been good to have drawn greater attention to.

Q Thank you. You said in terms of the conflict of interest that it seemed at the time that people were not paying sufficient attention to this issue of conflict of interest and may not have always been disclosing. Do you have any idea why people may not disclose if they had some concerns or doubts?
A No. It is very hard for me to put my mind in the mind of an investigator to know why they would not disclose. I think probably, from what we can understand about the motivation behind disclosing, there was an honest view that conflicts of interest may not have made any material difference to an interpretation of the study; not that it was a dishonest withholding of information, merely that it was not understood back in the early 1990s that conflicts of interest were actually associated with methodological and interpretative biases, and it was only through a series of papers, many of which we have referred to in the past day and a half, during the 1990s where it became clear that those associations actually were related to outcomes, and then that was the trigger for a great deal of alarm; that these things were not just “It would be nice to know them”; they are absolutely vital to interpret the meaning of a study.

Q You had a meeting in 2004 with Dr Wakefield and others and then a subsequent meeting with Professor Murch and so on. At either of those meetings was there any discussion of a patent application?
A No, there was not.

Q Lastly, is it customary for an investigation of possible serious research misconduct to be carried out by the people who have been so accused of the misconduct?
A It is customary for the institution to lead an investigation and to gather the data which will inevitably involve those who took part in the investigation. It is then the responsibility of the institution to make sure that there is some kind of separation between its interpretation of those findings and those who are involved in the investigation who are being in some sense accused of a set of allegations, and once that interpretation by the institution has taken place and has been conveyed to whoever has brought the allegations to them then we can go forward. So there certainly should be some separation, which is why in the first instance I wanted to get the reaction from Dr Wakefield, Professor Walker Smith and Dr Murch, but after that my duty was to go to the head of the institution, the Vice Dean, in this case Professor Hodgson.

DR MOODLEY: Thank you.

MRS DEAN: I want to ask you a follow up question to something that you spoke to my colleague, Dr Moodley about, just a few moments ago about this issue of consecutive referrals. Forgive me, I think you were explaining something and then you went off to talk about the reference to “self referred” which appears in the paper, so if I can get to the point where my interest was, you said that Professor Walker Smith went off and got the biopsy record and that the biopsies appeared consecutively.
A Correct.

Q And you said just before that that children appeared in the clinic and so on after referrals. Was the case ever put that these children literally appeared in clinic consecutively?
A Well, I think that is one of the ordinary meanings of “consecutive referral”, so anybody innocently reading the paper might well have thought that was the case. What became clear on further direct questioning was that that certainly was not the case, that there had been direct contact partly between Dr Wakefield and some of the parents so that when these children were referred into the Royal Free it was certainly not a random process of referral.

Q Indeed. To state the obvious, the children were literally not seen in clinic one after another?
A Quite right. My understanding was that they were not seen in clinic literally one afternoon, 1 12, one after the other.

Q So there were children in between, clearly, seen in clinic?
A Exactly.

Q Did the fact that the biopsies all appeared consecutively make you question in your own mind whether those biopsies were clinically necessarily?
A No, because the issue about clinical indication we had tried to take account of in assessing the first two allegations on ethics committee approval, so just to go back to that, one of the allegations was that some of the investigations, such as colonoscopy and lumbar puncture, were not clinically indicated and were not covered by ethics committee approval. My understanding, by looking at the documents asking about the nature of the process by Dr Wakefield, Professor Walker Smith and Dr Murch, was that the process began with one or two children being referred into the Royal Free with a behavioural disorder of some uncertain type, but broadly a disintegrative disorder, associated with bowel symptoms, hence the referral to a paediatric gastroenterology unit. At that point, again a highly specialist unit, it would not be surprising that there would be some quite serious investigations taking place to ascertain either a treatable cause or maybe give some clues as to what a cause might be of those conditions. Those investigations took place on the first few children. Uncertain diagnosis. At that point there began to be some collection of ideas to narrow down what might be going on here. Then what started off as clinical investigations on chronic conditions of an uncertain kind evolved into formulating some kind of research question. A protocol was then written up, the research protocol, which then went to the ethics committee, and during all of this time there were investigations taking place but the nature of the clinical problem was changing with time such that some investigations were downgraded in importance. I think at one stage Dr Murch felt that there was no need to pursue up a gastrointestinal endoscopy but other investigations continued, and the way it was described to Professor Hodgson and myself, looking through the documentation, that seemed to be an entirely routine and normal process in the way one would evaluate any series of patients being referred into a tertiary centre such as the Royal Free. I think if one went back and looked at variant CJD or HIV or any other case series, one might see a very similar pattern.

MRS DEAN: Thank you very much.

THE CHAIRMAN: Dr Horton, I have questions for you. Can I first ask you, I think it might seem a long time ago that you were asked a question about what happens when the paper is submitted to you, and I think you said there were three options available to you, that is either to accept, reject or to seek further opinion and, if possible, elucidation.
A Yes, we would never accept a paper without some kind of external peer review.

Q Of course, but after that external peer review these are the three options open to you?
A That is right.

Q In this particular paper you had already sought the external peer review from at least Professor Candy and maybe a couple of other authorities.
A Yes.

Q Was, then, this paper accepted without any further questions?
A No, no, there would have been negotiations that took place and that is why you saw in the log book the paper came to the meeting on two separate occasions, so the first occasion we opened negotiations to put points to the authors, then the paper came back in a revised form, and at that point the paper was accepted, which is entirely usual.

Q Thank you. When you send a paper for peer review I expect you ask for a written report from external peers?
A Yes, we do.

Q Did you have any external peer review reports on this paper?
A Yes, we certainly did.

Q Maybe you have not been able to get your hands on those? They are not available.
A Yes, I am afraid, and also we have been asked at various stages for earlier drafts of the paper which might have been submitted or revised, and I am afraid I do not have copies of those either.

Q Thank you. We have at least seen one draft, but obviously there are bound to be more drafts than that.
A Yes, and I might say there would have been galley proofs as well which might have had small amendments on them at a late stage in the process of drafting prior to publication.

Q And I think you have been asked a question about this press conference, press briefings, or whatever you want to call it, and you said they were not very common in 1998 although they are much more common now.
A That is right.

Q Do you have any theories about that? Why was it the case that they were not common in 1998 and are now?
A Well, the pressures on institutions now are so much greater. Institutions are expected to be much more concerned with revenue than they were perhaps in the late 1990s, so publicity, getting research grants, press interest, is now seen as a major role of any chief executive of any institution. I get letters now from heads of institutions often quite angry that a paper will have been reported in the media and their institution has not been mentioned. The authors are mentioned, the journals are mentioned, the results are mentioned but nobody says what the institution is. I had one only a month or so ago. There is much more concern with publicity now than there was in the late 1990s.

Q But nothing to do with the publicity of the contents of the research? Is it only for the publicity, the authors, the institution?
A No. I think it would be unfair to say it is only for the publicity for the institution. It depends on what the research is. There have been instances where the research has been of such serious public health importance that people do want to have a press conference so that the message is very clearly laid out. For example, when we have published work about the safety of hormone replacement therapy, that is a very difficult message about risk to transmit to a readership if you have just sent out a press release, so to get the risk message right we would hold a press conference, the data would be presented so you could literally say to the journalist: “This is the absolute risk, this is the relative risk, be careful not to exaggerate here”. So the press conference can be a very useful tool to make sure that the study results land, so to speak, in the right way in the media.

Q We have talked a lot about the conflict of interest and the possibility and the potential and all these sorts of things. I think these guidelines that we have actually seen that you sent writing in The Lancet at the top, that was published in 1997.
A Indeed, yes.

Q And similarly in 1997 there was also that one of that very eminent American journal. I think they also published their guidelines in the conflict of interest.
A Now we are talking about the guidelines that were specifically “Writing for The Lancet” which were meant to be supplemental to the statements of the International Committee of Medical Journal Editors. The document we saw giving the ICMJE statement happened to be published in JEMA, but that document was also available on our website and is drawn attention to in the box at the top of “Writing for The Lancet”.

Q But the one at the top of page 615
A Yes. 615 is the one that was in The Lancet.

Q Yes, and that was published in 1997.
A Correct.

Q Was there any procedure in place that, if any paper was submitted to you, you would individually send them these, saying: This is the new process, procedure we are now operating?
A No, we did not. We took submissions to the journal on trust that authors would have read these guidelines and put the guidance that we asked for into practice. As we went through the documents with Dr Wakefield’s counsel yesterday, you saw how the, shall we say, rigour with which we required authors to sign off on certain aspects of these guidelines has increased in the past decade, so now we do send an explicit statement to the authors saying: “Check off this on conflict of interest, on informed consent, on ethics committee approval, so we are absolutely clear that we have got the documentation for that at the journal”. In 1998 we did not do that to such a rigorous degree. We have learnt over time and cases unfortunately like this have taught us that to rely entirely on trust in the publication process might work 95 per cent of the time but that 5 per cent is a very important 5 per cent when it does not work.

Q Now, you also wrote your web address on this “Writing for The Lancet”, page 615?
A Yes. We are talking about the top, indeed, yes. That is right.

Q And there is a web address so at least even in 1997 these were available on the Internet?
A Perfectly available for free on the internet. That is right.

Q For someone who was a regular contributor to your journal, what would have been your expectation about the knowledge of this, as you later on called it, supplement to the guidelines?
A I can even speak as somebody who used to submit papers to The Lancet before joining the journal. You would look at the guidance provided for authors and you would, in an effort to maximise your chance for publication, adhere to every single suggestion, rule, guidance note, that was in the instructions for authors, because your feeling as an author would be that if you did not that might increase the risk that your paper would be rejected, so by following every rule or guidance note you would improve your opportunities for publication, and I would have expected any author submitting a paper to the journal to have done that.

Q Coming to the meeting that you had with the three authors who are here, I think you mentioned, which I made a note of, that you told Dr Wakefield that he should have disclosed Legal Aid Board funding?
A Correct.

Q What was Dr Wakefield’s response?
A Surprise. He genuinely took the position that he did not see that as a conflict of interest, for the reasons that we have heard, that the Legal Aid Board funding was funding a different study to the one reported in The Lancet, and that he had not considered that something to be worth disclosing to us.

(End of B4 turn)

I explained further why I thought the several areas of competing interest would have merited disclosure. We had a general discussion about that which included Professor Walker-Smith, Dr Murch and Dr Harvey. Again, from my recollection, Dr Harvey very much shared, as I recall, Dr Wakefield’s view but Dr Murch and Professor Walker-Smith expressed surprise and concern that that information had not been shared and discussed with them. Again, my understanding, from our conversation, was they felt that is something that should not only have been shared with them but also should have been shared with the Journal. When I took that information to Professor Hodgson, that was also a view that he took as well.

Q But Dr Wakefield was quite open about it, he did not try to hide it?
A Certainly not. His position throughout has been that that was an interest that he did not feel was necessary to disclose to The Lancet.

Q That was your genuine understanding of the state of the knowledge that was in Dr Wakefield’s mind at that particular stage?
A That is right. I disagreed with him, and so did others, but that was a view he expressed that afternoon and has been consistent about since.

Q Bundle 3, page 1211, that is the statement by the editors of The Lancet.
A Yes.

Q On page 1211, on the left-hand side, you have actually listed the allegations 1 to 6.
A Correct.

Q On the right-hand side of the page you have then started giving your decision after having looked at all the things, the meeting, seeing all the authors, and all that, which allegations are proved and which are not.
A Correct.

Q Allegation 1 you have said:

“In sum, the evidence does not support this allegation.”

A That is right.

Q Allegation 2, you have said at the end:

“In sum, the evidence does not support this allegation.”

A Correct.

Q Allegation 3, I think I have actually understood what you are saying but you have not mentioned whether the evidence is there, whether it does or does not support the allegation. Can I ask your outright view on that? I have understood what you mean from that but what is your decision on that allegation 3?
A The way the allegations were put was that there was a deliberate attempt to mislead. There was an accusation of deception, falsification, even fabrication, within the paper that we published. That is the allegation of research misconduct. Our view was that there had been no deception, no fabrication and no falsification. What there had been was a compression of a complex process of referral and, with hindsight, that compression could mislead and, again with hindsight, it would have been better to have provided a fuller description of the way in which those children had been referred into the Royal Free. Specifically against the allegation of fabrication, falsification or deliberate deception there was not one shred of evidence that was presented to me to support that allegation.

Q That is very clear. Allegation 3 you felt it was not proved. Then you have gone on to allegation 4 to 6. They go on for three or four paragraphs. I think I can make my summarisation of what you are saying but, if you do not mind, would you be able to tell me whether you find allegations 4, 5 and 6 proved or not?
A Let me just take them to make sure I am as precise as possible. For allegation 4, the allegation there was concerning whether the children reported in The Lancet study were also part of the Legal Aid Board-funded pilot project. The answer was that some of the children, an indeterminate number (somewhere between three, four and five), were indeed part of the same two studies so, to that extent, the allegation was partly correct.

Q Partly proved.
A Allegation 5:

“That the results eventually reported in the 1998 Lancet paper were passed to lawyers and used to justify the multi-party legal action prior to publication, a fact that was not disclosed to the editors of The Lancet.”

Dr Wakefield’s response to that, as I understand it, was that there was nothing hidden about these data because they had already been partly published in an abstract presented to us at conferences. I cannot remember how many abstracts but at least one. If that information had got into the hands of lawyers to justify any legal action, that was not relevant to this allegation because the information was out there prior to February 1998. To that extent, I think that allegation is not proven because there was no written record that I saw, something like “Dear Lawyer, here is the information from the February 1998 Lancet paper. Kind regards, Dr Wakefield.” I never saw anything like that. There was no paper trail proving that.

Allegation 6, that Dr Wakefield received £55,000 from the Legal Aid Board, he was very open in saying he did receive money from the Legal Aid Board. My recollection was that he had a different figure for the amount devoted to this separate study. £25,000 sticks in my mind for some reason.

Q That was supposed to be part-payment, the first instalment.
A OK. There was a sum of money from the Legal Aid Board to conduct this pilot project.

“Since there was substantial overlap of children both Legal Aid Board funded pilot project and The Lancet paper, this was a final conflict of interest that should have been declared .”

From my perspective and the Royal Free’s, that was an allegation proven.

Q I am looking at my questions because the next question you have already answered. The reference in the study you actually did say was meant for either measles or MR but not MMR.
A Correct.

Q On The Lancet paper, which you would have seen, bundle 2, page 785, is this table 2, neuropsychiatric diagnosis. In the second column, the child number first, then the behavioural diagnosis and exposure identified by parent or doctor. It says MMR, MMR, MMR virtually in every case apart from one or two number. For example 10 is measles, previously vaccinated with MMR. In one or two the trigger factor is not mentioned.
A Yes.

Q What was your view that this was actually much more a study conducted on MMR children rather than measles or measles/rubella?
A Are you asking what I thought in 1998 or 2004?

Q 1998, because that would be much more appropriate to consider at that stage.
A In 1998 I had not seen the protocol so I was not aware of what the original intention was. At the time The Lancet did not routinely look at protocols for studies. Even now we would not routinely look at a protocol for a case series, although for clinical trials we require protocols to be submitted at the same time as the paper. At the time I did not know what the original intention was behind this work. I must say that is not a common practice at journals to go back and look at protocols in any detail.

Q In 2004, when you had the opportunity to have a look at the protocols, what was your view then?
A The allegation had been that in some way these children had been cherry picked to prove an association between MMR vaccination and this syndrome. When I looked at the protocol it seemed to suggest entirely the opposite, that the protocol did not mention MMR vaccine at all and that the protocol was referring to a neuropsychiatric condition which was not specifically autism; it was talking about a disintegrative order, as I remember. It seemed to me that the intention, amongst the totality of the research team, was they had these children who were being referred in whatever way with a mysterious diagnosis and this reported parental history. They were struggling to try and put these jigsaw pieces together in some coherent way to understand what was going on as a pathological process. I did not see any evidence in the totality of the research team, not one shred of evidence, to suggest that they began with a pre-formed view that they were setting out tooth and nail to prove that MMR vaccination was linked to this syndrome. Indeed, if they had it is not very convincing, is it? First of all, it is a case series only. Second of all, four of the families do not report any temporal association at all. They did not do a very good job of cherry picking if that was the allegation.

Q That is very clear once again. In the same paper, on page 787, there is mention of an addendum which actually mentions a further 40 patients having been assessed, 39 of them with the syndrome.
A Yes.

Q You have said before that you do not have any drafts with you at the moment so you will not know at what stage that was added.
A The fact it is an addendum suggests it was added some time after submission of the paper. Between submission of the first draft and publication, I suspect - this is only a guess but a fairly logical guess - that was added in some way.

Q That is how I would take it. We have talked about this retraction of interpretation. Was there ever any consideration given to the retraction of the paper?
A Yes. There was a long discussion amongst the editors about whether the whole paper should be retracted or not. In some ways there was a lot of merit to that from the Journal’s point of view. It is pretty obvious that The Lancet, and I, have come under a lot of criticism for publishing this paper in the first place. In some sense it would have been an easy option to say let us try and erase this entire paper from the research record and wash our hands of it. When we sat down and looked at this we felt that would be completely the wrong line to take. The only aspect of this paper which had been discredited was this supposed association with MMR vaccination, for all the reasons we have discussed and I will not repeat. The essential documentation of these children, the fact of their existence, the reality of their symptoms, the reality of the findings on clinical examination and investigation, the observations on lymphoid hyperplasia, nobody was questioning those facts so to have retracted the entire paper would have been absolutely wrong. It might have made life a lot easier for editors, and perhaps even for some of the authors, but it would have been entirely the wrong thing to do clinically and scientifically, hence the focus on the interpretation.

Q Thank you very much indeed. This is now the final opportunity for the counsel to come back to you for any questions if they have any.

MS SMITH: I have no questions.

MR COONAN: No, thank you.

Further cross-examined by MR MILLER

MR MILLER: I have two short points. I was slightly concerned about a question from Ms Golding asking this witness about the research, or this research group. That is the introduction to the question. It will be some time before you hear any further evidence about what happened at the Royal Free. All I would like to say is you heard evidence from Professor Zuckerman at Day 16G, to Day 17D, in which he explained the inter-relationship between two separate parts of the Royal Free Medical School. I leave it at that. It is only because it is some time before we can have that explored by any other witness and this witness does not know anyway what this situation is.

THE CHAIRMAN: I am sure we have made a note of it.

THE LEGAL ASSESSOR: Do you have a page reference?

MR MILLER: Day 16, starting at the bottom of page 23, letter G, and over the page to page 24D. I wanted to identify it in the transcript. This witness has no idea anyway.

The second point arises out of questions you were asked about consecutive referral. You took the Committee to the reference in the paper to a largely self-referred group.
A Correct.

Q I think in answer to whether or not they were consecutively referred, the question was would a reader, bearing in mind it is a medical reader of the paper, have understood “consecutively referred” to be 12 patients that came in to this tertiary referral unit over a period of 24 hours or 48 hours?
A No, I do not think anybody would think it was over 12 or 24 hours. Anybody reading this paper would see that it was coming from a highly specialist centre in paediatric gastroenterology so the likelihood was these patients were being referred from many centres having already been investigated.

Q What would you have understood “self-referred” to mean? It says “this largely self-referred group”.
A The way I would have read that would have been that here we had parents of children who had already been evaluated by one or more doctors. There had been remaining uncertainty about diagnosis and treatment and, therefore, they had asked if there could be some further referral to a tertiary specialist centre for more in-depth investigation.

MR HOPKINS: I have nothing.

THE CHAIRMAN: Dr Horton, at last I am very pleased to confirm you are now released. Thank you once again for coming and giving us the benefit of your evidence. You are now released.

THE WITNESS: May I thank the Panel and all counsel for the clarity and courtesy with which these proceedings have been conducted. The past nine years have been very tempestuous for many people and I am very grateful for the calm reason with which these proceedings, for my part, have been conducted. I am very grateful for that. Thank you.

(The witness withdrew)

THE CHAIRMAN: Ms Smith, I am looking at the time now. I think it is obviously the lunch break. I am saying this for the information of all counsel. It seems quite clear that we have fallen behind considerably from the timetable. The panellists are going to have a diary meeting to see if we can find some availability of future timings. We are going to compare our diaries and give that information to the Panel Secretary who will pass on that information to all of you at some stage today.

The other matter I will need to confirm from you, Mr Coonan, because I know that Mr Sheldon has been away, is that you were going to confirm whether the recording of all the admitted allegations list is correct or not.

MR COONAN: His initial view was that they were correct but I have not had a great deal of time to talk to him this morning.

THE CHAIRMAN: There is no rush. Perhaps some time today you could let us know and the Panel Secretary can then publish the new list.

MR COONAN: We will address that today.

THE CHAIRMAN: It is now 1.10. The diary meeting will take us to 1.20, ten minutes or so. We will then adjourn and resume at 2.20.

(Luncheon adjournment)

MS SMITH: Sir, I will call the next witness who is Professor Sir David Hull.

Examined by MS SMITH

(Following introductions by the Chairman)

Q Would you begin by telling us your full name and address and your professional qualifications.
A My name is David Hull; I live in XXX. I retired from clinical practice 11 years ago. I was employed as a hospital doctor with responsibilities for looking after sick children.

Q I think it is right that, until your retirement in 1996, you were the Professor of Child Health at the Medical School at Nottingham University; is that correct?
A Yes and that gave me responsibilities for research and teaching and administration. I was asked to give a list of these and those appear in my statement as Appendix DH/1 or something.

Q Do not worry about that because all the numbering has changed in fact since you gave your statement. Your CV is a bundle and I would like to take you to it for a moment. The bundles are called FTP bundles and it is FTP7, page 22 behind tab 3. Looking down that, we see your appointments listed: 1966 to 1972, consultant physician at Great Ormond Street and then, 1972 to 1996, your last appointment as Professor of Child Health to which I have just alluded. You set out your numerous committees for the Department of Health over very many years including, we see three from the bottom, 1995 to 1999, Chair of the Joint Committee on Vaccination and Immunisation; is that correct?
A That is correct.

Q Further down, your national committees and professional bodies, the British Paediatric Association; you were President from 1991 to 1994 and, in that capacity, sat on numerous committees including the ethics committee.
A Yes, that is correct.

Q If we turn on, professor, I do not take you through a long CV but we will see that you have given numerous lectures, edited numerous books and produced a large number of research papers and they are set out between pages 25 and 32 of that document. You can put that volume away because you will not be needing it again and I am going to be asking you to refer to others later.

I want to ask you about your post between 1991 and 1994 as President of the British Paediatric Association. As the President of that organisation, were you an ex officio member of the ethics committee?
A I am not absolutely sure of that. I know that is in my statement. I think I was; I certainly attended the ethics committee on a number of occasions.

Q Were you at least to some degree involved in the production of the 1992 British Paediatric Associations guidelines on research on children?
A I was involved insofar as the guidelines went to the Executive Committee for approval and then on to Council and I was chairing the Executive Committee of Council and they had to go back to the ethics committee, so I was involved in that way.

Q Were they in fact the first guidelines that were produced by the British Paediatric Association about research in children?
A The guidelines were produced in 1982, I think, and this was a review of those first guidelines, so in a sense they were the first guidelines.

Q Were they regarded at the time, are you able to tell us, as an important guide?
A They were useful, yes.

Q Was there a particular reason why they were produced in the form that they were at that time relating to whether children were or were not being subject to research?
A There was a concern among paediatricians that many of the treatments that we were giving had not been fully evaluated on children and that was partly because of the difficulty of doing research involving children partly because of legal restraints, whether you could get informed consent to do so sort of things. So, there was an attempt to try and get a set of guidelines that would enable paediatricians to evaluate the treatments that they were giving on children to show that they were effective.

Q Could we turn to those guidelines which are in FPT4 which is a volume entitled “Ethics Guidelines” and they are at page 176 in FPT4. They are dated August 1992. If we look at the first page, page 178, we see a commentary on the guidelines which was in fact drafted by you; is that correct?
A That is correct, yes.

Q Before I look at that, I want to look very quickly at the guidelines themselves just to remind the Panel of the matters that were included at that time. I am not going to go through them in great detail but, if you would turn to page 182, we see the principles on which the guidelines were based.

“1. Research involving children is important for the benefit of all children and
should be supported, encouraged and conducted in an ethical manner.

2. Children are not small adults; they have an additional, unique set of interests.

3. Research should only be done on children if comparable research on adults could not answer the same question.

4. A research procedure which is not intended directly to benefit the child subject is not necessarily either unethical or illegal.

5. All proposals involving medical research on children should be submitted to the local research ethics committee.

6. Legally valid consent should be obtained from the child, parent or guardian as appropriate.”

If we turn on to page 184, we see at the top of the page,

“Children are unique as a research group for many reasons”

and then the matter you have alluded to in relation to consent,

“They are the only people … on whose behalf other individuals may consent to medical procedures. Many children are vulnerable, easily bewildered and frightened and unable to express their needs or defend their interests. Potentially with many decades ahead of them, they are likely to experience, in their development and education, the most lasting benefits or harms from research”

and then again – and this is a matter that I want to ask you about because you allude to it in your commentary – on page 188, we see there assessment of risk with respect to children, and just going down to the paragraph which starts “After the high risk procedures”, we see:

“It would be unethical to submit child subjects to more than minimal risk when the procedure offers no benefit to them, or only a slight or very uncertain one. Higher risks in research and novel treatments are accepted when children are enduring very harmful disease. Illness and anxiety alone may put pressure on families to assent to heroic experimental procedures. In cases of severe or chronic disease, therefore, the harms to the child of the condition, of the medical treatment, and of the stress through taking part in research need to be assessed, so that all avoidable distress may be relieved”.

And we see “minimal risks” defined as “(the least possible)” which is procedures such as questioning, observing and measuring children, provided it is done in a sensitive way with consent, and procedures with minimal risk include collecting a single urine sample (but not by aspiration), or using blood from a sample that has been taken as part of treatment. Low risk is procedures that cause brief pain or tenderness and small bruises or scars.

“Many children fear needles and for them low rather than minimal risks are often incurred by injections and venepuncture. High risk procedures such as lung or liver biopsy, arterial puncture, and cardiac catheterisation are not justified for research purposes alone. They should be carried out only when research is combined with diagnosis or treatment intended to benefit the child concerned”.

As far as the high risks procedures, there are examples there given, Professor, but, broadly speaking, are they intended to cover invasive investigations?
A Yes.

Q I think it is right that there was some questioning of the categorisation there which is what led to your commentary at page 178?
A Yes.

Q And you said there, if I can just run through it,

“After the Guidelines for the Ethical Conduct of Research Involving Children were published and distributed, the British Paediatric Association received a number of helpful comments”,

and then going to the bottom of that paragraph,

“The particular issue concerns taking blood from children and whether this can be regarded as a minimal risk procedure or a low risk procedure”.

Can I ask you first, and tell me if you do not feel able to answer this, but if you were talking about adults, would taking a blood sample for research purposes be regarded as being a minimal risk for adults?
A Generally, yes.

Q You say,

“The purpose of the document is to encourage good, ethically sound research in childhood. It is of great importance that research should be conducted with children to evaluate properly their medical management, but the risk of doing harm to a child must always be considered beforehand. Some people have been concerned that, by including taking a sample of blood from a vein as a low rather than a minimal risk, the guidelines might discourage important research which could benefit children.

“It is clear that, except possibly in the case of small infants, there is only a minimal risk of physical harm when blood is taken from a child by an experienced venesector. The problem is that children do not always see it like that. The use of needles to take blood upsets many children and a few are very frightened indeed by the prospect of blood sampling or an injection. Children who are admitted to hospital often perceive needles as more unpleasant than an operation.

“It is essential to recognise this problem when undertaking research. As the document states, every effort must be made to reduce the amount of pain suffered by children by performing procedures skilfully and by considering the use of local anaesthetic agents. A research worker must recognise when a child is very upset by a procedure and accept this as genuine dissent from being involved. In this sense, the issue is no different from an adult’s refusal to join a research project because of an extreme dislike of venepuncture.

“The sentence on low risk that ‘Many children fear needles and to them low rather than minimal risks are often incurred by injection and venepuncture’ is intended to encourage research workers to recognise the distress of these children.”

Now, you were obviously supporting, in effect, in that your decision to categorise as low risk the taking of blood from children, is that correct?
A No. There was a tension between two interested groups. The paediatricians who regularly took blood samples from children as far as therapy was concerned and were keen to evaluate therapy took the general view that taking blood from children, just as pricking their finger when they pick blackberries, was of minimal risk. Those who were advising the BPA on the ethics committee who were non medical took a rather more severe view of sticking a needle in a child and giving them pain, so there was a bit of a tension between the two that had to be resolved in some sort of way. This was my attempt to do that. It was not a small point because if the research on the child, if the control group or the comparison group had to have a test that was said to be of low risk, then it would not pass the ethics committee and would not get funding, so it was a major break on doing evaluations of therapies for children if, in certain situations, blood could not be taken from the child for the purposes of investigation and evaluation.

I accept that is not a very clear distinction but I was moving between two fairly strong positions, and that is my personal position. You will notice in the Ethics Report itself it puts it down as a low risk. This was to try and deal with the possibility that it could be a minimal risk in a good number of situations.

Q And you seem, tell me if I am interpreting it correctly, to be associating the physical risks as minimal but accepting that other risks might be described as more than that.
A It was acknowledging the fact that we were not just talking about the pain of the prick or the seeing the red blood but the whole frightening experience that some people have. Just as some adults occasionally have some horror of needles so it is possible for children to be the same, and therefore if blood samples were being taken in a research programme it was important that that sampling was done sensitively, painlessly and as happy as possible. Some children were very happy to put their arms out.

Q To whom would lie the evaluation of whether it is being appropriately handled in a research context?
A Well, it would be written clearly within the research protocol, the application to the ethics committee. It would be for the ethics committee to see that there were sufficient securities in place to protect the interests of the children.

Q When you say the ethics committee, remembering we have lay members on the Panel, you mean not your ethics committee but the ethics committee for the hospital in which research was taking place?
A Yes.

Q Now, I am going to come back obviously to this whole issue, Professor, but I want to turn on to matters relating to another of the hats that you wore during this period, because we then have the context. You were between 1995 and 1999 the Chairman of what we have heard called the JCVI, the Joint Committee for Vaccination and Immunisation, is that correct?
A Yes.

Q And I think if we can begin the chronology of the evidence you have to give, it was in that capacity that you were invited by Dr Wakefield to a presentation with regard to his research?
A Correct.

Q And did you think that that was an invitation that it was appropriate for you to accept as Chairman of the JCVI?
A A letter was written to me as Chairman of the JCVI and I thought it was proper, if there were anxieties about vaccines, to go and listen to those.

Q And I think it is right that you went to a meeting at the Royal Free Hospital in February 1997.
A Correct.

Q Can you tell us who attended that meeting from the JCVI?
A Professor Keith Cartwright was on the JCVI; I think Professor Michael Langman was on the Committee of Safety of Medicines but came because he was knowledgeable about gastroenterological disorders, and Dr David Salisbury, who is the head of the immunisation division of the Department of Health were there.

Q And who was there from the Royal Free Hospital?
A Well, I guess you should know better than I. My memory is not what it was, but I seem to think

Q Who do you remember being there?
A I remember Dr Wakefield because he had invited us and greeted us. I think Professor Pounder was there, and I think the Dean, Professor Zuckerman was also there. I think there were others but you would know better than I.

Q Well, they are the ones you allude to in your statement and the ones I wanted you to tell us about. Following that meeting I think you wrote to Professor Zuckerman. If you turn to another volume, FTP1, page 367, that was a letter you sent firstly thanking Professor Zuckerman for his hospitality and you said it was helpful to hear evidence from Professor Pounder and Dr Wakefield about their work and how they interpret their findings, and you say:

“The JCVI have to consider whether the increase in any disease of unknown aetiology might be due to the changing experience of infection or the consequence of the vaccination strategy, so it is important that we listen to Mr Wakefield, Prof Pounder and their colleagues when they raise the possibility that IBD is due to measles virus”,

and you then set out your views at that stage in relation to the findings of the group, and if we go on to the paragraph on page 368,

“I was a little troubled when I heard that Mr Wakefield was investigating many children with autism. I think I must have misunderstood what he was saying. I see from the submission to the House of Commons Select Committee by Dawbarns solicitors that they ‘are working with Mr Wakefield of the Royal Free Hospital London. He is investigating this condition (Crohn’s)’. It is possible he is also advising Dawbarns about the association of vaccination with autism and is not, in fact, investing the children or advising about their care, and that this explains his statement that he was looking at hundreds of cast notes”.

and you then end up with your thanks.

First of all, doctor, that letter indicated that you felt it was important for the JCVI to listen to the views of Dr Wakefield, and we can assume from that, can we, that you believe that to be the case, that you should listen to what was being raised as a possibility of a problem?
A Yes.

Q If they were, in fact, raising the possibility of a link between a vaccine and a disease without a known aetiology, were you concerned about the reaction of the public to that being raised as a possibility?
A Yes. Actually the discussion was that measles virus as well as the vaccine could be a latent cause of disease, so if an infection was causing a late result then that was important in the vaccination strategy to eradicate the disease. It is not just the vaccine. There is concern if there is the possibility raised that either the virus or the vaccine was causing damage that it would have impact on the public, yes.

Q Can I ask you, before we leave that letter, about what you said in the paragraph about the investigation of numbers of children? You mention there a connection with Dawbarns, the solicitors. Can you recall where you got that information from, that there was some connection with Dawbarns, solicitors?
A Well, I cannot remember now, I cannot remember quite a few things now, it is a long time ago, but I wrote down then, when I wrote that letter, that I had got that information from the many documents that were sent in to the Select Committee of the House of Commons that was looking into child health services, and as I have written that there I presume that is where I got it from. I would have got Dawbarns’ statements coming to me as Chairman of the JCVI, but I think that was at a later date.

Q You say.

“I was a little troubled when I heard Mr Wakefield was investigating many children with autism”.

What was it in particular that was troubling you about that, if it was correct?
A Well, it was the notion that a vaccine could cause acute brain damage leaving a child with the features of autism. It is that notion that is very similar to a previous notion 25 or 30 years ago that was that the whooping cough vaccine could cause brain damage and leave a child permanently damaged. When that notion was brought to public attention it was based largely on chronological association then. It took many, many years to establish that that association was by chance, and during those many years whooping cough outbreaks returned, many children came into hospital, some of them died and some of them were left with brain damage, so even the notion that an association is present on the basis of chronological evidence alone can cause quite a lot of harm.

Q And what about the actual role that Mr Wakefield was playing? You are saying.

“I was a little troubled when I heard that Mr Wakefield was investigating many children with autism”,

and you then quote the reference to Dawbarns, and you say,

“[possibly] he is advising Dawbarns about the association of vaccination with autism and is not, in fact, investigating the children or advising about their care”.

What was it that worried you about him, if he was, investigating children or advising in their care?
A The possibility that he was pursuing the vaccine area there. I did not know enough about it really to say more than I have said there.

Q Mr Zuckerman replied to you, and we have his letter at page 369. We have already read this letter to the Panel but just to remind you this letter is 18 February 1997. He thanks you for your letter and alludes to findings made by the IBD study group and says,

“I am rather alarmed by the extension of the investigation to children with autism, and more so by the involvement of lawyers”,

and then he quotes the phrase that you quoted and says:

“I am also aware that the Legal Aid Board has offered financial support for work on IBD which the School has not accepted”,

and he was seeking advice from the Ethics Committee and he refers to the arguments for academic freedom and how that is balanced against the reputation of the Medical School. He then said:

“I would welcome the exchange in confidence of any information which may help to prevent a major public relations issue and potentially the impact on public health”.

Can you recall whether there was, in fact, an exchange in confidence after that?
A No.

Q I think it is right that the whole meeting with the presentation by Professor Pounder and Dr Wakefield was subsequently discussed at a meeting of the JCVI in May of 1997.
A Yes.

Q And after that discussion I think it is correct that it was agreed that the JCVI would continue to recommend the MMR programme, as they had until then?
A Yes.

Q The following year, after the publication of The Lancet study, were you present, Professor Hull, at a meeting at the Medical Research Council which was convened to champion the evidence relating measles and measles vaccine to chronic gastrointestinal inflammation?
A I was.

Q Do you recall being at that meeting?
A Yes, I do.

Q At that that meeting, did Dr Wakefield allude to the investigation of further children than those in The Lancet paper?
A He did.

Q Did that cause you concern?
A Yes, it did.

MS SMITH: I would like to take you through the transcript of the Medical Research Council meeting.

THE CHAIRMAN: One request, Professor Hull, would you put the microphone closer to you so that your voice can be heard by everybody in this chamber.

MS SMITH: It is in volume 7. I do not expect you to remember and I am sure you do not remember, Professor, the precise wording, but you told us that you were concerned about an illusion to the investigation of further children. Would you look at page 152. You will see a heading “Mr Andrew Wakefield” and this was a presentation given in the course of that meeting by Mr Wakefield. If we look at the third paragraph down, we see:

“We originally reported, in a paper that came out recently, 12 children. We have now the results of a paper that was presented at the British Society of Gastroenterology two weeks a go and we have now looked at 51 of these children to date. So I report here on the 30 consecutively referred children with a mean age of 6 years.”

If you go on to page 154, at the bottom of the page – this is in the context of Dr Wakefield talking to a slide about the aetiology of the syndrome – we see:

“We now have some 500 of these children who have been referred, or who are in the process of referral. We do not know what their guts show yet. But none of them – not one – is associated with monovalent vaccine. They have all been associated with MMR.”

Those are two references I found, but in broad terms was that the sort of information that was given that caused you some concern?
A Yes.

Q Can you tell us in broad terms – and I will take you to the letter you wrote to Professor Zuckerman about this – what was it that was worrying you?
A The concept of a new syndrome, which variously used Heller’s Syndrome, of an encephalopathy plus a significant bowel disorder, plus autism, must be pretty rare. They had possibly ten or such twelve such children and investigated them, as I understood it, identifying a syndrome in The Lancet paper. Having identified the character of the syndrome, I did not think it necessarily appropriate to investigate every child that could be diagnosed with the condition from the clinical features alone. It seemed a pretty intrusive set of investigations.

Secondly, an encephalopathic reaction is not usually described at the beginning of autism in children as my understanding of that is. From the studies they had done in the first twelve children, the LP MRI scans and the electroencephalogram were all normal, so there is no evidence, even in their syndrome group if all of them had the syndrome, of an encephalopathy, at least no persisting evidence of it and no evidence of residual brain damage. It is difficult to see on the clinical protocol why it was necessary to continue doing those investigations on other children with autism. It had been my experience that chronic significant bowel disorders were not common in autistic children, but I had not seen many, but it was not consistent with my reading about the condition either. At the MRC meeting there was a number of papers saying that Crohn’s disease or ulcerative colitis were very rare within the context, or no commoner within the context of people with autism than anyone else. It seemed to me to be unlikely that the bulk of children with autism would have significant bowel disorders justifying doing biopsies. That was the level of my concern, what was the clinical protocol for doing these studies on all the children.

Q So you wrote to Professor Zuckerman, I think that is correct, with your concerns?
A I did, yes.

Q That is in volume 3, FTP3, page 928. That is a letter dated 6 July 1998 and you say:

“I would welcome your help on a matter of personal concern. In February 1998 Mr Wakefield and his colleagues reported the findings of their search for the cause of bowel disorder in children with autism. At the MRC meeting they said that many more children had been similarly investigated and still more were on the waiting list. The studies include: admission to hospital, sedation, lumbar puncture, biopsies of the bowel, MRI imaging and radiography.

In the light of the initial findings and the evidence that as a group the children do not suffer long term bowel disorder, it would seem difficult to justify such invasive studies on clinical grounds. It may be that there are arguments to perform further investigation to elucidate the nature of the brain disorder and the bowel findings. As I cannot see what those might be, the thought of autistic children being subject to such investigations continues to trouble me, and thus my request to you.

I see that the investigations were approved by the Ethical Practices Committee of Royal Free Hospital NHS Trust. If the studies are continuing I would be grateful if I could see the Ethics Committee position on the investigations, especially if they have reviewed their position in the light of the reported findings. If you thought it helpful the Ethics Committee of the Royal College of Paediatrics and Child Health could give an independent view.”

I am going to ask you about the context of that letter. You say “on a matter of personal concern”, in what capacity did you write that letter to Professor Zuckerman?
A It just worried me.

Q Was it unprompted by anybody?
A It was unprompted, I was troubled.

Q Did you have concerns that the letter might be perceived as you having some sort of vested interest?
A Yes, that was a difficulty with me because, as the Chairman of the JCVI, I might have been thought to be pro vaccinations. I tried to keep an independent position. Mr Wakefield and his colleagues were asking two very important questions: did latent viral infections, whether by attenuated viruses or not, cause chronic disease and, particularly, whether autism followed an acute encephalopathy earlier in childhood. Obviously, if there was a possibility of either of those happening, it was important to investigate them thoroughly and properly with sound research which is ethically proper. It was very important questions they were trying to answer.

Q Did you have in your own mind any thought of trying to constrain any investigations if they were being properly carried out?
A I would certainly wish proper investigations to be done, rather the reverse.

Q Turning to the letter itself, you say:

“I see that the investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust.”

Where did you get that information?
A It was in The Lancet article.

Q When you were talking about those investigations, were you talking about “The Lancet 12”, if I can call them that?
A In The Lancet it said the investigations were approved by the ethics committee.

Q You say:

“In the light of the initial findings and the evidence that as a group the children do not suffer long term bowel disorder, it would seem difficult to justify such invasive studies on clinical grounds.”

Were you intending to make a distinction between the twelve who had ethics committee approval for research, and continuing investigation on clinical grounds?
A No.

Q Explain to us exactly what you were trying to say?
A If you are exploring a new syndrome, there is an argument to investigate the first few that you see thoroughly to define it and to work out what the proper recognition and management is. Once those have been done, you can then rely on the clinical presentations to define it and apply treatment. In this instance they find non specific changes in the large bowel and, possibly, with a non specific therapy it might be eased or helped. It seems to me to be reasonable in that situation to try the therapy before subjecting the child – bringing them into hospital and subjecting them – to an invasive procedure.

Q As far as the first twelve were concerned, when you saw the observation that the investigations had been approved by the ethics committee of the Royal Free, what conclusions did you draw from that as to whether this was a research programme or clinical treatment?
A I do not think I knew.

Q You saw that the investigations were approved by the ethics committee because that, as you say, what is said in The Lancet paper. Did you have any reason, having seen that in The Lancet paper, to question any further the nature of the treatment in relation to the original twelve?
A The thorough investigation of children with a new syndrome is a proper clinical responsibility. Does that answer your question?

Q It answers half of it, certainly?
A Could you put the other half to me.

Q What I asked was, you have quoted that part of The Lancet article which says that the investigations were approved by the ethics committee of the Royal Free?
A Yes.

Q When you that in The Lancet article that the investigations were approved by the ethics committee, did you have any reason to feel any more concern in relation to the nature of the investigations of the original twelve, were you reassured by seeing that?
A Yes, I suppose I was in that sense.

THE CHAIRMAN: Professor Hull you will need to keep your voice a little up.
A It is a bit aggressive, sir.

MS SMITH: As far as the investigations you were now enquiring about, I think it is right that you were not in a position to comment on the nature of those investigations on clinical grounds?
A No, I did not. I knew very little about the clinical features. That is for the clinicians at the time and who were there to judge. It was not for me to comment on that, I did not know.

Q I think it is also right that you would not have expected ethical approval for lumbar punctures solely for research purposes?
A No.

Q On children?
A No.

Q The reason for that being?
A If you need to do clinical studies, you need to do clinical studies. It is not an ethical matter as to doing it on someone who would not benefit from the procedure.

Q But if it is a research matter, you would not expect leave to be given?
A That is leading me a tad further than I would finally go. There may, indeed, be – I could not think of it now – but there may be an extreme scenario when it is very important to know something for the sake of a lot of people that you might do a procedure like that. But, on the whole, it had to be very special pleading and the ethics committee would need quite a lot of convincing.

Q You were asked whether you could see the ethics position on the ensuing investigations. Why did you ask to see that?
A I thought, having given ethical permission for the original twelve that were published, it would be timely for the ethics committee to review its decision as to whether its permission was needed for the further studies.

Q You suggested the possibility of an independent view from the ethics committee of the Royal College of Paediatrics if that was required. Can you tell us what your thinking was behind that suggestion?
A I think when research is making waves, as this was, which was as important as this was, it is essential that the research is scientifically sound and ethically proper and to be quite sure about that because, certainly, it was going to be criticised round the world if it was to establish its point. The more security you have with opinions of others to make sure it is scientifically sound and ethically proper, the better.

Q Professor Zuckerman replied to you. His letter is on page 955. That letter which we looked at before gives you information both as to the original study and as to the ongoing investigation. It says:

“Dear Sir David,

I am now able to respond to your letter.

The Original protocol was approved by the Ethics Committee...”

and he gives a date:

“... The Committee was very conscious of the requirement to avoid non-therapeutic research of more than minimal risk in young Assurance was therefore sought and obtained that the investigations that were to be carried out during this study were indicated clinically and were not being carried out just for research. The study was undertaken with parental consent.

Subsequently, children have been seen by clinicians and are investigated by clinical need. The tests which are usually carried out include a range of blood tests, plain X-ray of the abdomen and ileo-colonoscopy with appropriate biopsies. A review by a child psychiatrist is also undertaken.

As an outcome most of the children have been found to have non-specific colitis with lymphoid hyperplasia and have been started on treatment with Melasazine or related drugs, generally with a favourable clinical response.
The results will be analysed in due course.

I referred your letter to the Ethics Committee, and the senior clinician responsible for the care of these children wrote formally to the Chairman of the Ethics Committee requesting approval by the Committee for clinical research analysis of the children with this syndrome who are seen by clinical need. The Chairman of the Ethics Committee wrote to me that the study was reviewed again. Reassurance was given that only investigations which were indicated clinically would be carried out. Again, the Committee approved the study on the understanding that all that was being approved was data collection.

The Chairman of the Ethics Committee also wrote to me pointing out that your comment that: ‘I see that the investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust’ was incorrect. He adds that the Committee did not approve the investigations. The Committee approved data collection from investigations that were indicated clinically and that is not the role of an Ethics Committee to question clinicians’ judgment as to what are and what are not clinically indicated investigations. The Chairman of the Committee added that the Committee seeks expert review of all applications, and in the case of this particular investigation the opinion of a senior gastroenterologist was sought and a review of the project was provided with strong support of the study.”

Q Could you understand, Professor Hull, how the information given in that letter tallied with the representations as to ethical approval that had been made in The Lancet article?
A Could you ask me that question again?

Q Could you understand how the information that Professor Zuckerman gave you, namely that the chairman of the Ethics Committee said that the investigations were not approved by the Ethics Committee, tallied with the information that you had seen in The Lancet article?
A They did not easily fit together.

Q Did your concerns remain?
A I think the Ethics Committee gave its permission after some of the studies had been done. It was clear that the permission was being granted to scrutinise the notes presumably. That was consistent. What was actually written in The Lancet article did not give me that impression that that is what the Ethics Committee had actually granted. I accept it might be a way of reading it.

Q If we look on to your reply, at page 958, in September 1998:

“Thank you for your letter in response to my concerns ... I see that many in authority know what is happening and presumably do not share my unease.

In the February Lancet article it is stated that ‘the investigations were approved by the Ethical Practices Committee of the Royal Free and yet the Chairman of that Committee wrote to tell you that that was not so. He also told you that the Committee had sought the view of a senior gastroenterologist, not perhaps the best person to advise on the ethics of intrusive investigation of children with autism.

As you gather, I am still troubled but obviously others are not so I accept that there I must let it rest.

Thank you for exploring the issues for me.”

Did you feel able to take the matter any further than that or feel the wish to?
A I could have taken it further. I did not think I should.

Q What was it that made you feel that was where you, at least, should leave it?
A Perhaps Professor Zuckerman had discussed it with a good number of people. A lot of the people involved, certainly those in authority, knew about my concerns. There were a lot of other important people at the MRC meeting who knew, and presumably all the people who read The Lancet article so I thought maybe it was me who got it mixed up.

Q With regard to the JCVI, of which you were still the chairman, would the ethics of these studies have been of any concern to that committee?
A Only in so far as they were informed individuals. The JCVI has a duty to look at the facts and the evidence. If the evidence came through unethical routes, it would still have to look at the evidence.

Q If it did come through an unethical route in some way, if there was some concern about the ethics of the study, whose responsibility is that?
A We all have to be stand up and be counted for our own consciences. It was not the responsibility of the committee to hold an ethical brief.

THE CHAIRMAN: It is 3.25 pm. I wonder whether Professor Hull and all of us should take a break at this time. We will adjourn and resume at 3.45 pm.

Professor Hull, I have to remind you that you are still under oath and still in the middle of giving the evidence so please do not discuss this case with anyone during this break. I am sure will someone will look after you.

(Short break at 3.25 pm until 3.50 pm)

Cross-examined by MR COONAN

MR COONAN: There is just one topic I would like to seek your assistance on, if I may. Just to set the scene, it may be helpful if you have bundle 4, page 178. This was the commentary you wrote back in 1992. Your attention was directed to it earlier this afternoon and you made various comments upon it. One of the observations you made, to the assistance of the Panel, was that the general view of paediatricians within this discussion in the BPA was that the taking of blood from children was of minimal risk.
A Usually.

Q That, of course, presupposes obviously a compliant and willing child, a child who was not distressed and obviously full consent principally by the parent as well as the child?
A As well as the child, yes.

Q There are, in a sense, a number of fairly obvious requirements before a doctor would embark on the taking of blood from children.
A For research purposes, yes.

Q That was the commentary in 1992 and I think that those guidelines were amended, were they not, later on? I am going to show you a document and it represents the amendment to the guidance issued by the College, as it became. I will show you so you can refresh your memory.
A You may be telling me for the first time. I have been retired for a long time.

Q It is no surprise because it is written by you.
A I might remember it. (Document handed out)

THE CHAIRMAN: This document, “Guidelines for the ethical conduct of medical research involving children”, will be in tab 8 of D2.

MR COONAN: Just to get your bearings with the document, you will see that your name appears at the end of the commentary, the last page, is that right?
A Yes.

Q If we turn to the second page, there is quite a bit of small print above the references and we will see that we get a date there that the guidelines were modified and updated by the College in 1999. It is terribly small print but you see whether I mean, the penultimate page.
A Yes.

Q This document, as we can see, is dealing with updated guidelines. Would you forgive me if I take you to a number of passages and just read them out and then we can invite you to comment, if you may. Would that be helpful?
A If you wish.

Q Looking, first of all, at the first page, in the left-hand margin at the top:

“These guidelines are written for everyone involved in the planning review and conduct of research with children. The Royal College of Paediatrics and Child Health’s first guidelines (then the British Paediatric Association) were published in 1980. Since then there has been significant progress in the understanding of children’s interests, in legal requirements and in the proper regulation of research. The revised guidelines take account of such developments.”

The body of the document deals with a host of matters relating to research generally. I am going to take you to the topics which you were invited to look at in the 1992 guidelines just to see the extent to which there has been a change. If you turn to page 179, at the top, the third page in, it follows the same format, does it not, on the left-hand side, “Risks may be limited, low or high”. Then you deal with the categories: minimal, we can see the definition there; low; and high. It is the next paragraph that I would like to take your attention to:

“We believe that research in which children are submitted to more than minimal risk with only slight, uncertain or no benefit to themselves deserve serious ethical consideration. The most common example of such research involves blood sampling. Where children are unable to give consent by reason of insufficient maturity or understanding, their parents or guardians may consent to the taking of blood for non-therapeutic purposes provided that they have been given and understand a full explanation of the reasons for blood sampling and have balanced its risk to their child. Many children fear needles but with careful explanation of the reason for venepuncture and an understanding of the effectiveness of local anaesthetic cream they often show altruism and allow a blood sample to be taken. We believe this has to be the child’s decision. We believe that it is completely inappropriate to insist on the taking of blood for non-therapeutic reasons if a child indicates either significant unwillingness before the start or significant stress during the procedure.”

Pausing there, that was the distillation of the view by the College in 1999.
A Yes.

Q Then I take you on to the penultimate page to the commentary. Do I take it that simply because your name is at the bottom that you drafted the commentary, is that correct?
A It would be fair to conclude that, yes.

Q As I just read parts of this, we can have in mind the earlier Commentary drafted by yourself which we see on page 178 of bundle 4. I am not asking you to read both at once but the Panel will have page 178 in mind. This is the 1999 draft. Under the heading Commentary can I read it:

“The Ethics Committee of the BPA, now the Royal College of Paediatrics and Child Health, has prepared guidelines on the planning, conduct, and review of research on children. Two of the basic principles are that ‘research involving children is important for the benefit of all children’ and that ‘the research procedure not intended directly to benefit the child’s subject is not necessarily either unethical or illegal’. Research is necessary to ensure that children receive fully informed care. ...

Taking blood is often painful, it sometimes leaves a worrying bruise and the experience can be distressing. Debate both in and out of the Councils of the BPA/RCPCH have centered on whether taking blood from children poses a minimal or a low risk. Procedures that have a low risk are usually inappropriate if the child involved is unlikely to benefit from the experience.

Blood taken by a skilled person poses only a minimal risk of physical harm except possibly the taking of a separate sample of blood from a very immature infant. It is the pain and distress and the memory of it that might cause more than minimal harm.

Taking blood from children can be a positive experience. Children, like adults, are capable of being generous and doing something worthwhile even if it means they experience discomfort. Parents when they are fully informed usually consent to their babies experiencing the brief pain of blood taking if the investigation might be to the benefit of other infants. It seems to me that the blood taking to be of minimal risk it is important that all concerned know what is happening, that the moment when the blood is taken is appropriate, that the procedure is skilfully performed and that all steps are taken to reduce the amount of pain the child experiences - for example, by using local anaesthetic creams.

Some children, however, like some adults are frightened of needles and the site of blood. The guidance originally stated ...”

That presumably is harking back to the 1992 version.

“... stated that ‘Many children fear needles and to them low rather than minimal risks are often incurred by injection and venepuncture’. It now says ‘Many children fear needles but with careful explanation of the reason for the venepuncture and an understanding of the effectiveness of anaesthetic cream they often show altruism, and allow a blood sample to be taken.’ I welcome the move to a more positive position. It is in the common interests of children. But it makes it more, rather than less, necessary for research workers to be able to recognise” [your emphasis] “when a child is very upset whether by the thought of the procedure or at the time of the procedure and to accept” [your emphasis] “this distress as genuine dissent from being involved. The child’s feelings are not to be sacrificed.”

Two possible observations from that, Professor Hull, is that the general tension of view that you described back in 1992 has, as it were, perhaps you would agree with this, swung a little more to the paediatric view which was being expressed in 1992 that blood taking in children, provided you have a compliant and willing child, was really of a minimal risk?
A Yes. I should add that the first statement I wrote was as president of the BPA trying to balance the impossible and the second was my feelings about the matter.

Q Absolutely. We can see how the wording of the guidance and guidelines in the 1999 version has shifted somewhat to a more liberal view.
A The Ethical Committee had moved a little, for which I was grateful.

Q Again, it is perhaps an obvious point but your observations in the commentary in 1999 were less of a need to balance these tensions which were to the fore in 1992, is that fair?
A Yes.

Cross-examined by MR MILLER

Q I have only a few questions to ask you and the first of those questions starts in the same sort of area, the guidelines that were published by the British Paediatric Association. That Association was the forerunner of the Royal College of Paediatrics and Child Health which now fulfils the same function as the BPA did before.
A And a few more things as well.

Q It is a Royal College now. The BPA felt it was appropriate to put out guidelines quite early on and then to re-work them during the time of your presidency between 1991 and 1994.
A Yes.

Q You have told us that the motivation was that there was a risk that children would be denied research activity because they were not in a position to consent to procedures being carried out.
A Yes, that is a bit simplistic but it was an issue. There was legal restraint that children were not in a position to consent or not consent. It was thought the age at which they could do so was not known. Every time it went to the MRC or to the Department of Health for research applications it was turned down on the grounds that you could not do research on children non-specifically, which was not helpful.

Q The point I was going to go on to is that is not necessarily a problem in respect of clinical care because parents could provide appropriate consent for investigation and/or treatment if it was in the best interests of the child to have it and it was properly explained.
A I think clinical care it is the duty of the doctor to do what is in the best interests of the child.

Q That was the point I make. The difference is there that provided it is in the best interests of the child, and importantly it is explained to the parents for them to give consent, then different considerations apply in clinical care.
A Yes.

Q You were asked to look at the guidelines and you are not to know it but the Chairman of the Royal Free Local Ethics Committee sent an extract from the guidelines to Professor Walker-Smith in October 1996 and I would like you to turn up page 265C which is in FTP1. It is green in colour. Do you have that?
A I have a green paper 265C which is an extract from the BDA guidelines.

Q It deals with the point you have been discussing with Mr Coonan about risk estimates of middle, low or high and it identifies, as Ms Smith went through, in the middle of the page examples anyway of high risk procedures and cautions against them being carried out unless research is combined with diagnosis or treatment intended to benefit the child concerned.
A Yes.

Q That is specific guidance for those proposing to carry out investigations as part of research where it is proposed that children will be subjects.
A Yes, they are research protocols.

Q And that guidance in that form would have been available in 1996?
A Yes.

Q That is the end of that. The only other topic that I want to ask you about is the meeting at the Royal Free in February 1997. Had you become familiar in whatever role with the research that had been carried on by Dr Wakefield and, amongst others, Professor Pounder which was published in the early 1990s?
A I certainly saw a lot of papers that were published by Professor Pounder and Dr Wakefield because they were all presented through the JCVI for the Committee to read in preparation of its guidance but I cannot remember them.

Q I am not going to ask you about anything. I want to look at what the position was in 1997 when, as Chairman of the JCVI, you were invited to the meeting that you went to at the Royal Free.
A Yes.

Q It was not a blank canvas; you knew at that stage the background.
A No, I did my homework. I have forgotten it but I did it.

Q I am not going to jog your memory on it except to say that it related in general terms to the suggested relationship between measles, not MMR, and inflammatory bowel disease.
A Yes.

Q So, that is what you were being asked to come to hear the presentation on.
A That is correct.

Q You made the point that it was talking about wild measles as well as vaccinations, so it was not limited to vaccination, but you went with people who had a particular interest in vaccination: Professor Cartwright?
A Professor Cartwright was a microbiologist who was interested in infections and organisms. Professor Langman was a physician of adults, a gastroenterologist. David Salisbury was the head of department and he would be the one who would know most about vaccination strategies.

Q Yes, he is the thread. He deals with vaccination and may deal with vaccination in this case.
A Yes.

Q It was not simply vaccination that was being discussed, it was wild measles as well.
A The main concept was whether latent viral infection could lead to subsequent diseases. That was the idea. As I understand it – and I am open to correction – there was not the ability then to distinguish whether the viral particles that were in the cells were wild virus or vaccine virus.

Q Present from the Royal Free – there may have been other people there as well – were Dr Wakefield and Professor Pounder who were presenting the material.
A Yes.

Q And Professor Zuckerman, the Dean, was there as well and you subsequently corresponded with him.
A I am not sure whether he was there for all of it.

Q As far as others are concerned, there were other people there but Professor Walker-Smith was not there.
A No, he was not.

Q What you were being addressed on or discussing issues with was what was known as the inflammatory bowel disease study group.
A Yes.

Q The IBD study group at the Royal Free.
A Yes.

Q As a result of that meeting, presentation, whatever it was, you went back and discussed things with your colleagues and I think you told us that the JCVI continued to support MMR vaccination after that meeting.
A There was no evidence for us not to continue our current policy.

MR MILLER: Thank you, Professor.

MR HOPKINS: I have no questions.

Further re-examined by MS SMITH

Q Professor Hull, I want to ask you a few questions arising out of the guidelines that Mr Coonan produced for you to look at. Is it correct that this was in 2000?
A The date on the top is 2000; I wrote it before 2000.

Q I am sorry, I simply do not recall: did you give evidence as to exactly when before? Did you say 1999?
A No. It was actually brought to my attention in the fine print in font 7, “and has been modified and updated by the Royal College of Paediatrics, Child Health and Ethics Advisory Committee in 1999” long after I had left.

Q You quoted again the six basic principles to which I referred you when I was first asking you questions on the first page.
A That is the ethics committee’s report; I had nothing to do with rephrasing it.

Q One of those principles is that all proposals involving medical research – I am looking at number 5 – on children should be submitted to a research ethics committee.
A Yes.

Q Were the views that you were expressing and the guidelines set out there all in the context of research, a formal research study taking place with ethical committee approval?
A Yes.

Q Is that ethical committee approval always a fundamental requirement to ethical research on children?
A If it involves research, asking a research question, yes.

Q May we go on to the ethics committee situation under the heading, “Research ethics committees” on page 179 on the internal paging. Do you see where I am in the right-hand column?
A Yes.

Q We see,

“As assessment of benefit and harm is complex, children are best protected if projects are reviewed at many levels, by researchers, funding and scientific bodies, research ethics committees …”

and then, going down to the next paragraph,

“Ethics is about good practice, and each research ethics committee considering a project involving children should be advised by people with a close, practical knowledge …”

Going on to the next page, if you would, the top left-hand paragraph, where we see,

“The duties of LRECs have been clearly described …”

and they are set out in a number of bullet points and then, after that,

“… LRECS may also wish to know how researchers plan to monitor and respond to any signs of distress in child subjects.”

Would that framework of safeguards be there in relation to the assessment of risk and benefit for a child in taking blood, whether that child responds in a positive or negative way, whether the research is appropriate? Would that be the framework in which it would take place?
A I think any research involving children doing a battery of studies and bringing them into hospital ought to do some sort of appraisal as well as to the effect of that experience on the children, but that is research.

MS SMITH: Thank you very much, Professor Hull. If you stay there, the Panel may have some questions for you.

Questioned by THE PANEL

MS GOLDING: Professor, when you offered the assistance of the ethics committee of the Royal College of Paediatrics and Child Health for an independent view, was that to look at the ongoing investigations which may have been still going on or the ones that had been carried out already?
A The ones that were going on, not the ones that had been … The ones that had been carried out I understood had been done as part of a clinical protocol to investigate a rare syndrome. The future ongoing of fifties or hundreds of children, whatever the figures were, was what I wanted a research appraisal of, if it was for research.

THE CHAIRMAN: Professor Hull, I have two small questions of you. First of all, regarding this meeting which took place at the Royal Free to which you were invited as Chairman of the JCVI. Who made the presentations in that meeting?
A Who made what …?

Q The presentations, as far as you can recollect.
A There was a whole day of it. I remember Michael Rutter presenting something on autism. There were others who presented statistics on all sorts of subjects. There is a list of them somewhere but certainly I think it was Mr Wakefield presenting on behalf of his team at that meeting.

Q Had the invitation come to you from Dr Wakefield?
A No, no, no, it was an MRC.

MR MILLER: I think there is a crossed wire. There are two meetings. There is the 1997 meeting at the Royal Free and the MRC meeting which Professor Hull was asked to consider when he gave his evidence.

THE CHAIRMAN: I was asking about the 1997 meeting.

MR MILLER: Yes, but I think that the first answer related to the MRC meeting.

THE WITNESS: I am sorry I misunderstood. The first meeting was at the invitation of Mr Wakefield. He was concerned about the information he had and he wanted to make sure that we knew about it.

THE CHAIRMAN: Was that meeting a whole day meeting or a half-day meeting?
A I think it was a half-day meeting.

Q Were the presentations made by anybody else apart from Dr Wakefield in that meeting?
A I think that Professor Pounder presented one part of it but precisely what section he presented I am not sure. I think that Professor Pounder and Dr Wakefield both presented.

Q My next question is, you have been taken through the guidelines, the previous ones and the newer ones that you drafted in 1999, but on two occasions you said, “Yes, if it was research”. My question to you is, do the same guidelines apply if it is a full and proper research or if it is a case studies report?
A I see the point you are making. The application for research permission in this instance was permission to look at the notes, collate them and present them. You will be aware that doctors often look at a series of case notes and present them in the literature without getting ethical permission for doing so. Increasingly, people are now asking ethical permission to look at other people’s personal information. So if it went to the ethical committee, as the Chairman of the Ethics Committee indicated, just for permission to review the notes that could be one selective activity, but the data was collected according to a clinical protocol. So this was for analysis and publication of the data.

THE CHAIRMAN: Thank you. That is very helpful. Counsel do have the opportunity to come back to you for any further questions, if they wish to. Ms Smith?

Further re examined by MS SMITH

Q Thank you, sir. Just arising out of the question that the Chairman has asked you, so we are all clear, Professor Hull, one of the things we are all conscious of is the passage of time in relation to this case. The answer that you have just given in relation to your understanding of what the clinicians asked permission for from the Research Ethics Committee at the Royal Free, does that relate back to the letter that Professor Zuckerman wrote to you at the time telling you what the Chairman of the Ethics Committee said was the position?
A Yes. I was confused because of what The Lancet said. I read it as I imagine most other people would read it, that they in some way had given ethics permission for the investigations, which was difficult to understand. If, in fact, it was ethical permission to scrutinise the notes to present it as a publication, then that is a different matter.

Q And that is what you were told by Professor Zuckerman was what Dr Pegg, the Chairman of the Ethics Committee said, when you wrote and inquired?
A That is what Dr Pegg said, we were only asked to approve the investigations, which I think even at that time would have been a bit unusual.

MS SMITH: Thank you.

THE CHAIRMAN: Any other questions?




THE CHAIRMAN: Professor Hull, you will be very pleased to know that we have finished with your evidence. Can I thank you on behalf of this Panel for coming this afternoon. You are now released.

The witness withdrew

THE CHAIRMAN: Ms Smith, it is 4.25 pm so are we going to go on to tomorrow morning now?

MS SMITH: Yes, sir. The next witness I think will be Mr Martin Else, who is the chief executive dealing with financial matters. I do not think you would want to embark on those at twenty five past four!

THE CHAIRMAN: That is very helpful. We will adjourn and resume at 9.30 tomorrow morning. Thank you.

(The Panel adjourned until 9.30 on Thursday morning.)

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