GENERAL MEDICAL COUNCIL
FITNESS TO PRACTISE PANEL (MISCONDUCT)
Friday 12 October 2007
Regents Place, 350 Euston Road, London NW1 3JN
Chairman: Dr Surendra Kumar, MB BS FRCGP
Panel Members: Mrs Sylvia Dean
Ms Wendy Golding
Dr Parimala Moodley
Dr Stephen Webster
Legal Assessor: Mr Nigel Seed QC
WAKEFIELD, Dr Andrew Jeremy
WALKER-SMITH, Professor John Angus
MURCH, Professor Simon Harry
(Transcript of the shorthand notes of T. A. Reed & Co.
Tel No: 01992 465900)
A P P E A R A N C E S
MS SALLY SMITH QC and MR CHRIS MELLOR and MR OWAIN THOMAS of counsel, instructed by Messrs Field Fisher Waterhouse, solicitors, appeared on behalf of the General Medical Council.
MR KIERAN COONAN QC and MR NEIL SHELDON of counsel, instructed by Messrs RadcliffesLeBrasseur, Solicitors, appeared on behalf of Dr Wakefield, who was present.
MR STEPHEN MILLER QC and MS ANDREA LINDSAY-STRUGO of counsel, instructed by Messrs Eastwoods, Solicitors, appeared on behalf of Professor Walker-Smith, who was present.
MR ADRIAN HOPKINS QC and MR RICHARD PARTRIDGE of counsel, instructed by Messrs Berrymans, Solicitors, appeared on behalf of Professor Murch, who was present.
I N D E X
PROFESSOR IAN WESTERBY BOOTH, continued
Examined by MS SMITH, continued 1
STATEMENT OF DR MARY STUART read 28
STATEMENT MS DEBORAH DAVIES read 29
STATEMENT OF MS FRANCES WHARTON 29
THE CHAIRMAN: Good morning everyone. Ms Smith.
PROFESSOR IAN WESTERBY BOOTH, continued
Examined by MS SMITH, continued
Q Good morning Professor Booth.
A Good morning.
Q I want to deal with one very short matter and then I am going to go on to ask you about some of your general conclusions about the patient records that we have looked at. So far as the short matter is concerned, for you it is page 60 of your report, and if I could everyone to go to FTP7 at page 235/divider 16 – and perhaps I could say, because I am not going to go through all of them – and there are similar documents behind every divider thereafter until divider 25, ending on page 387 of this bundle. These are documents that you have seen I think and to which we have already looked very briefly in this hearing with Dr Davies, the histopathologist, and they are reports, and the one on page 235 is on child 2. They are all undated but they are plainly prepared, as one sees from the contents of them, for the purposes of the litigation, and they are reports into the investigation into the possible link between viral exposure and developmental disorder in children. We have those reports available for children 2, 8, 3, 12, 10, 6, 1, 4, 5 and JS.
I have only got one question arising out of them but if we quickly look so we know what we are talking about: it is a document setting out the entire details of the investigation of the child. We will see the birth history on page 236. On page 237 are all the developmental details and the milestones achieved: 238, the initial behavioural abnormality where it was initially diagnosed what the diagnosis was, by whom, current diagnosis and then on page 239 the investigations carried out in previous hospitals, and infection and vaccination history, which goes on to the next page, 240. Page 241 is the current gastrointestinal symptoms; then the colonoscopy carried out in 1996, on page 242, which is the colonoscopy we have looked at; the histology, and that goes on to page 243: immunohistochemistry on page 244 and the virological studies. Page 245 shows the testing for measles and rubella: 247 is the testing on the cerebrospinal fluid, and again we see the ‘96 dates relating to this admission. On the next page, 248, the urea, electrolytes and endocrine studies, also all ’96 dates. Page 249, September 1996 follow up in this child, Child 2, with, as we will remember, the enteral feeding. Page 251 is the details of the staining for measles and page 252 is the summary of the view reached on the child after the 1996 admission, and as I say it is apparent it is for the purposes of litigation by the observations at page 253, where the opinion is expressed that the autism and the inflammatory bowel disease were caused by MMR.
As I say, there is one of those documents in respect of each of the children whose numbers I have read out, but it is fair to say that some of the documents are not as complete as others (this happens to be one that is filled in completely).
Professor Booth, I think it is right that you have been through these and that broadly speaking the histological descriptions, where they are available in these proformas conform with the descriptions which were given in The Lancet paper of these children?
A Yes, that is correct.
Q That is all I want to ask you although we may have to look at these again with the doctors later.
I want to revert, if I may, to the views that you have expressed as a general overview on The Lancet patients, and for your purposes if you would turn to page 34 of your report: these are the general conclusions that you reached, I think, having looked through all the patient records. We have dealt with it to some degree before we looked at the patient records but I want now to ask you overall what you have to say about the nature of the investigations in the context of these children’s conditions.
A I think, firstly, it is clear that a lot of these parents were quite vulnerable; they had clearly not been able to satisfy themselves about the cause of their child’s symptoms previously, and they had I think been put in a very vulnerable position by taking part in this research study, where, as we have discussed, the nature of their symptoms would not in general lead one to think that a colonoscopy, and these other intensive investigations, was going to be in their bests interests.
Q You say the parents themselves were vulnerable: does that apply to the children?
A I think the other issue is that normally when embarking on any investigation in a child you would want to discuss it not only with the parents but with the child if they were of sufficient age and intelligence to be able to understand it. I think one of the recurrent issues here was that these children would normally in general have been of an age where you would be able to try and explain to them what the investigations were all about and what was involved, but because of the major learning difficulties that these children had as part of their neuropsychiatric diagnosis that would not be possible.
Q Given the nature of the investigations, which you described as “intensive”, and the vulnerability of the children, and the understandable vulnerability of their parents, was the ethical background to what was being undertaken an important consideration for these clinicians?
A Yes, particularly important I think.
Q Is it your view that from their point of view, you said you think there were some deficiencies in the ethical review of the issue, but from the point of the clinicians, do you think that they appropriately dealt with the ethical background and the ethical requirements? When I say “clinicians” I should say the responsible consultants.
A I think one of the themes that emerges by reviewing the patient records is that referral of these patients often appeared to have been solicited, which is very unusual, and it is particularly unusual, and I think worrying with this vulnerable group of patients.
Q You have referred to a research study and we have looked exhaustively at the records relating to that particular issue in this case and I have asked your view individually on each one, but overall is it your view that that is what these doctors were undertaking?
A Yes. I think the clinical notes are littered with references to research studies. Often the patient’s records contain statements like “the patient has been admitted for a study of disintegrative disorder”. There are references in the correspondence to the intensive programme and therefore needing to confirm ethical committee permission. There are references to “beginning the programme”; references to the investigation having been performed because of disintegrative disorder variant of autism; references to the protocol having to be worked out; beginning the programme. So I would find it a difficult concept to accept that these patients were not being investigated as part of the research protocol that has already been looked at by this hearing.
Q Looking at it clinically, again, we have been through the individual children, and with the exception of child 6 and child 7 in whom you expressed a contrary view on the symptoms, were the symptoms such that any of them would lead one to think that they needed an immediate colonoscopy without prior screening investigation?
A With those caveats, I would not have thought that these children needed an immediate colonoscopy.
Q What is your impression as to the timing of the colonoscopies? Do you think they were for clinical medicine appropriately considered?
A Part of the diagnostic process involves an evaluation of all the information that is available from the referral letter, from the history from the patients, and cones down on a differential diagnosis. Under some circumstances, in a patient who has, for example, got bloody diarrhoea it is fairly clear that the patient needs a colonoscopy but generally speaking, if that is not the case you would come up with a differential diagnosis in many cases and you would, in the patient’s interests, start with some non-invasive investigations, in general, before embarking on invasive tests like colonoscopy. As I have said, there are exceptions to that, so going straight in and doing a colonoscopy on these patients would be clinically very unusual indeed.
Q Just turning on to page 35, as far as Dr Wakefield’s role was concerned – again we have dealt with this as we have gone through the individual patients – I would like you to summarise overall the concerns that you have already expressed in relation to the apparent role that he was playing in the clinical care of the patients.
A In the application to the research ethical committee he was clearly identified as one of the lead investigators. I think in fact in the video of the press conference that took place at the Royal Free Hospital he was specifically identified as the research team leader, so he was clearly involved in the research. Notwithstanding that, there are a number of references in the clinical notes to Dr Wakefield ordering clinical investigations, and curiously suggesting clinical interventions to Professor Walker Smith, which I find very difficult to understand, that Professor Walker Smith would need advice from Dr Wakefield on patient management. I have seen a document that we have discussed here which expressly said that Dr Wakefield should not have clinical involvement. Moreover, even if he were to have clinical involvement, without any identifiable training in paediatrics, it would not be appropriate for him to have any clinical responsibility in the management of children.
Q As far as training in paediatrics is concerned, would you expect those who are trained in paediatrics, or indeed who are not trained but become involved in research in paediatrics, to be aware of the special ethical rules that apply to researching on children?
A Yes, absolutely.
Q Just turning on to page 40 of your report, which is the other place at which you make general comments, I want to ask you in particular about the issue which is at the bottom of the page and over on to the next page. We know that a lot of these children were put on to anti-inflammatories. What would be your expectation if this was indeed the research study that it is your view it clearly was as to the way in which any novel treatment arising out of that research study would be handled?
A I think if you were using agents for a novel indication, you would expect that there would be an application to the research ethical committee for using agents in that way, and it would be framed in the context of a clinical trial. It would not necessarily be appropriate to start a clinical trial before you treated any patient, but if you were treating patients as a way of getting some pilot information that could go into a clinical trial, you would expect them to be treated with the same agent in the same way by the same team for the same duration, and that during that treatment they would have very careful follow up so that you could be absolutely crystal clear about whether, even in an uncontrolled situation like that, there was evidence of clinical benefit, and I did not find that in the clinical records.
Q You have said that the situation might arise, as you investigated the patients. If part of the research aim had been to look the effect of anti-inflammatory agents in these circumstances – if it had from the beginning – would you then expect that to be included in the original application to the ethics committee?
A If that had been the aim, yes, but I think when the original research ethical committee application was submitted, it was not necessarily clear that one of the outcomes of that work would be a therapeutic intervention.
Q Absolutely, and that is one of the reasons I am simply reminding the panel that when you gave your views before and we looked at the patients, you said in its initial stages this was non-therapeutic research?
Q As far as the indications for prescribing the anti-inflammatories in those cases, which is the vast majority where they were prescribed, Professor Booth, were those indications conventional indications?
A In the sense that they were prescribed to patients who had, it was perceived, evidence of inflammation in the colon, then that would be a conventional indication. I think the issue is that in some of the patients, going through the records, there was a view that the gastrointestinal symptoms were not severe, the inflammation was not severe, and there was a view that this may in some way alter their behaviour. I think that the other issue with prescribing anti-inflammatory agents in these patients was that alternative explanations for the inflammation did not appear to have been considered.
Q As far as any idea that it might have an effect on behaviour, would that indeed be a novel indication for giving anti-inflammatory treatment?
A Very novel.
Q As far as the behaviour of these patients generally, do you think any account was taken of the apparent improvements in some after the clearout for the bowel was concerned?
A There are references in some of the clinical records to the improvements possibly having been related to the bowel preparation. I think there was one patient; there may have been more. So there was possibly some recognition of that but the first three patients that were studied all had pretty severe constipation, by which I mean that it would have been obvious early on in the study rather than later in the study of the 12 patients that constipation was going to be possibly quite a major issue that needed to be considered in the differential diagnosis of any improvement following a colonoscopy, because almost by definition you have at least transiently improved their constipation.
Q But if you were of the view that the problem is constipation, would that ever be a justification for doing a colonoscopy?
A If you thought constipation was present in the patient as part of your differential diagnosis of their symptoms, it would be a contra-indication to doing a colonoscopy.
Q So the clearout of the bowel would be achieved by a different means?
A You may use the same agents but you would have a different aim in view.
Q Absolutely. As far as the investigations which were carried out on these children, again I have asked you this question as we have gone through them individually, but is it your view that on the whole they do indeed conform with the timetable of investigations, not necessarily the timing of them but the timetable of the investigations, that were envisaged in the ethics committee application?
A Yes, these children had lumbar punctures, MRI scans, EEGs, for example, which were part of the original research ethical committee application and they are investigations that you would not normally carry out in children with the symptoms that these children had unless it was part of some research study. It would not be clinically indicated.
Q If it was part of a research study, should it have had ethical approval for all the investigations
A I think that would depend on whether there was a clinical indication for carrying out the colonoscopy. If you said, “First of all, we are going to investigate children who have disintegrative disorder”, and therefore you are only investigating children who have disintegrative disorder and they subsequently, after we have seen them, have a valid clinical indication for a colonoscopy, then the colonoscopy could be done outside the research ethical committee permission, but if you have not got a valid clinical indication, then it has to be considered as part of the research application.
Q As far as the other investigations are concerned, would they have to be part of the research application?
A You mean ---
Q The other investigations, save for the colonoscopy – the MRI, EEG, lumbar puncture?
A They would have to be, yes.
Q You have dealt in each individual case with your views as to the clinical indications for the colonoscopy.
A Yes. I think that the clinical indications for colonoscopy were present only in a minority of these patients, and colonoscopy took place, for example, in patients where I think quite appropriately the preliminary diagnosis was, for example, toddler diarrhoea. You would not then go on and do a colonoscopy in a patient with toddler diarrhoea unless there was some major change in the symptomatology.
Q When you say “quite appropriate”, you mean the diagnosis?
A I think the diagnosis, the clinical diagnosis of toddler diarrhoea in that particular patient, for example, was entirely appropriate. Without new clinical information apparently having come in, a decision was then made to do a colonoscopy, for reasons I just cannot understand. Other patients were felt initially not to have any evidence for example of Crohn’s disease but still had a colonoscopy.
Q In those cases where there was thought to be no evidence of Crohn’s disease or indeed of inflammatory bowel disease and Dr Wakefield’s theories as to the possibility of some subtle form of inflammation being present were taken into account in the treatment which was subsequently given, what does that say to you about whether it was a research or clinical treatment?
A Sorry, could you just repeat the first part of your question?
Q Sorry, it was a long question. In those cases which we have looked at where we know that a conclusion was reached by Professor Walker-Smith that there were not apparently signs of inflammatory bowel disease and the decision to undertake a colonoscopy then appears, on his own letters, to have been motivated by Dr Wakefield’s view that there might be some other kind of subtle form of inflammation, what does that say to you about whether the investigation was clinical or a research investigation?
A Well, it would clearly be a research-driven indication for doing the colonoscopy, having established clearly that there was no clinical reason for doing it.
Q One last question just generally, Professor Booth. When you wrote your reports, describing as you have to the panel your view that this was a research study and not clinical investigations, had you any knowledge of the views that Professor Rutter, who is the other expert as you know who has dealt with the neuropsychiatry side of the case, was expressing as to whether this was a research or clinical investigation?
A No, I do not have any knowledge of Professor Rutter’s views – full stop.
Q I now want to turn on, if I may, to a completely different topic, which is Dr Wakefield’s involvement in the MMR litigation and the funding issues related to that. First of all, that involves going to the documentation. Can I just remind you first of all: as you know, the ethics committee application was signed off by Professor Pounder in August 1996 and submitted in September 1996. As you know, Child 2, who is apparently envisaged as being the first child in the study according to the correspondence, was seen by Professor Walker-Smith at the Royal Free Hospital in June 1996. I just want to look at the documentation to remind the panel, but more importantly to remind you before you express your views, which shows when Dr Wakefield’s role in the litigation is first documented. Could we turn to FTP1, page 90. That is a newsletter, Professor Booth, from Dawbarns the solicitors. It is dated, as you see from page 91, February 1996. I am not going to read it all out but just briefly remind you.
“As you may have read in the Sunday Times of 17 December 1995 Dr Andrew Wakefield has published some very disturbing material which indicates a clear link between the measles element of the vaccine and Crohn’s disease…. He has deeply depressing views about the effects of vaccines on the nation’s children. He is also anxious to arrange for tests to be carried out on any children vaccinated with MR or MMR who are showing symptoms of possible Crohn’s disease.”
Then it sets out the symptoms and says that if a child is suffering from any of those, it might be appropriate to put them in touch with Dr Wakefield. That, as I say, is the first documentary indication that we have, which is in February ’96. Then in June ’96, if you go on in the same volume to page 103, we have a letter from the solicitor at Dawbarns, Mr Barr, to a lady at the Legal Aid Board and the second paragraph says:
“To give you further information on the costing proposals I enclose a copy of a draft (not entirely finished yet) of Dr Wakefield’s proposed protocol for the study and his costing proposals).
It has an attachment to it at page 104, a document which I think there is no argument is almost identical to that subsequently submitted to the ethics committee. You see at page 108 the introduction in identical terms and the explanation of disintegrative disorder is in identical terms. At page 113, the tests indeed conform with some extra detail in relation to the virological studies: full clinical examination, full blood count, measles and rubella immunoreactivity, colonoscopy, histology and immunohistochemistry for measles, analysis of the biopsies and virology in relation to the measles and, on the next page, MRI, EEG, evoked potentials and lumbar puncture. Then at page 115, a description of what was to be involved. Again, I will not read it all out, but it sets out the aims of the study and the implications for public health and it says that referrals will be co-ordinated by Professor Walker-Smith, Dr Wakefield and Professor Murch. It also sets out the timetable we have already looked at. Then at page 121, the costing proposal which was attached. It says:
“A protocol giving the detailed technical specification is attached.”
That is the document we have just looked at. It says the costing proposal is for testing a selected number of MR and MMR vaccinated children and the objective is stated as:
“ … to seek evidence which will be acceptable in a court of law of the causative connection between either the MMR or [MR] vaccine and certain conditions reported … by families of children who are seeking compensation.
It is hoped that using the testing protocol attached it will be possible to establish the causal link between the administration of the vaccines and the conditions outlined I this proposed protocol … ”
Then the costings and I know you are familiar with this. There are the setting-up costs and then it says that some patients are to be tested for inflammatory bowel disease and then the ones with which we are concerned: enteritis/disintegrative disorder cases. It says:
“In contrast with the IBD cases, which have a prima face gastrointestinal pathology, children with enteritis/disintegrative disorder form part of a new syndrome. Nonetheless the evidence is undeniably in favour of a specific vaccine induced pathology. Many more tests have to be carried out for investigating these conditions and accordingly the costs of investigation are considerably higher.
The children will come into the Paediatric Gastrointestinal Ward under the care of Professor John Walker-Smith. Costs for four nights stay for the child and the parent plus colonoscopy will be £1,750.
The MRI plus evoked potential studies will cost £1,000 and the combination of the molecular, immunohistochemical …. Studies will cost a further £1,000.
The medical reports … from the individual experts, including Dr Harvey, Dr Berelowitz, Professor Walker-Smith … and Dr Wakefield will cost £1,400. The total cost per child will therefore be £5,150.”
Then the sums add up and we see the second category, which of course is the enteritis and disintegrative disorder cases, are £25,750, with an estimated total of £57,750. It then refers to the fact that if more children are to be tested under the protocol, then the sum of £5,150 would be added on each occasion. It concludes:
“It is not of course possible to anticipate the conclusions that will be reached but the indicators are that it should be possible to establish a clear causative link between the vaccines and the two sets of conditions mentioned above.”
After that, we reach August 1996. That is at page 183, which is the authority to do the work from the Legal Aid Board. Paragraph 2:
“To facilitate the setting up of the clinical and scientific study proposed by Dr A. J. Wakefield in respect of 10 assisted persons at a maximum cost of £55,000 and to cover the work necessary by the solicitors …. ”
Then if you could go to page 189, this is the next newsletter in September 1996. On page 190, we see what is being said about the pilot study and Dr Wakefield’s role in it on the right-hand side:
“If we can prove a clear link between the vaccines and autism/inflammatory bowel disease this will be exceedingly useful not only for cases involving those conditions, but also for other types of damage such as epilepsy.
To obtain the evidence to do this, we will be running a pilot study. Around 10 children with symptoms which are closely linked to the vaccine will be extensively tested by a team of doctors headed by Dr Wakefield at the Royal Free Hospital in London.
We will be selecting children to take part in the study from details and medical notes we already have. The investigations will involve a whole battery of tests to be carried out by a number of leading experts in their fields. We will of course be liaising closely with the families concerned; and the doctors will be giving very full details of what will be involved.”
Then lastly, page 317, please. We see the continuing involvement of Dr Wakefield in November 1996. This is a letter to Mrs Cowie, who is the lady who had taken over the Legal Aid area office at that time, again from the solicitors. It asks for extra costs in relation to Dr Wakefield’s fee personally in the first paragraph. Then it says in paragraph 2:
“We have seen an absolute explosion in the number of autism cases. Autism claims are far and away the greatest number of cases now and it is very important to try and establish a level of proof that the autism is connected with the vaccines. Dr Wakefield has suggested that one way of producing quite convincing evidence is to do a survey of the autism cases.”
Then going to page 318, the penultimate paragraph:
That is, Mr Barr –
“ … would like to try to establish that there is a fairly consistent time link between the administration of the vaccine ... and the onset of autistic features. To achieve this we have prepared a survey questionnaire … which has been approved by Dr Wakefield. The aim is to send it out to all 170 families ….
We would then collate the data and in the Committee we would be looking very closely at the date of onset of the beginning of the autistic condition … Dr Wakefield feels that if we can show a clear time link between the vaccination and the onset of symptoms we should be able to dispose of the suggestion that it is simply a chance encounter. The reason for this is that there is quite a wide range of ages between which the vaccination is administered.”
Then it sets out how they are going to collate the data in this questionnaire and on page 319, in the second main paragraph down:
“After that analysis and collation of the report by Kirsten Limb and myself … ”
Both of whom are at Dawbarns –
“ … plus discussions with Dr Wakefield (along with his fee for examining the data and possibly writing up the report himself) … ”
So that was the work relating to the questionnaire which Dr Wakefield had suggested.
Around that time, you also know – I should briefly remind you – that concerns were being raised by Professor Zuckerman, who is the Dean at the Royal Free and the British Medical Association had been consulted. I just want to look at the correspondence passing between Professor Zuckerman and Dr Wakefield. Before I do that, Professor Zuckerman, who has given evidence, has told us, Professor Booth, that he had never previously encountered the provision of funds for research by the Legal Aid Board. Have you, or had you at that time?
Q Is that no to both? Neither then or now?
A That is correct, yes.
Q The letters which passed between Dr Wakefield and Professor Zuckerman on this issue are in FTP2, page 393. This is a letter from Dr Wakefield to Professor Zuckerman of 10 March 1997. There had obviously been a telephone conversation between them when Professor Zuckerman had raised this issue of Dr Wakefield’s link with the solicitors, Dawbarns. If we just go to the last paragraph on that page:
“You mentioned a conflict of interest when we spoke. This is something which has exercised my mind greatly in the interim. I feel I must go on record as stating that I do not see how any conflict of interest exists. It is, as I am sure you would agree, our joint and several responsibility as members of the medical profession to use our training and expertise appropriately. In the context of the current measles vaccine safety/consequences debate, I am providing independent expert guidance based on facts available to me. I do this in common with colleagues worldwide. The fair legal assessment of potential claims relies on high-calibre expert advice. The GMC and the Royal Colleges have long accepted this premise.
In the particular circumstances with which I am dealing, there is, I believe, an even higher moral obligation to act as an expert adviser. We are faced with a situation where the most vulnerable category of patients, ie children, may be put at risk. It is right and proper therefore to review the facts, assess them, and offer guidance.”
He then says:
“Please do feel free to contact me if you wish to discuss my role further.”
Professor Zuckerman did and his letter is on page 397. He says there have been two misunderstandings and he asks for clarification and an indication by the solicitors that they were working with Dr Wakefield. Then in the last paragraph, he says:
“I do not think that there is any conflict between duty of care to patients or the provision of independent expert advice to lawyers. However, it is a different matter when lawyers fund particular piece of research where a specific action is contemplated. This surely suggests that some preliminary legal discussions have taken place and that a specific action is contemplated. If so, then the interpretation must surely be that a conflict of interest may well exist. The School must, therefore, seek expert advice, but in the meantime you should know of my concern.”
If you then go on to the last letter at page 401 from Dr Wakefield to Professor Zuckerman of 24 March:
“Further to our exchanges regarding the investigation of children with enterocolitis and autism, and especially the involvement of Dawbarns Solicitors and the Legal Aid Board, please find enclosed all documentation relating to this matter. This includes a letter to Dawbarns from the Legal Aid Board specifying the conditions for making the award. These conditions were based upon the enclosed protocol which has been approved by the Ethics Committee at the Royal Free Hospital. I got the impression from Roy … ”
That is, Professor Pounder, who is the head of his department –
“ … that you were concerned that we were being contracted to provide a specific answer – that is, that the measles vaccine or the MMR vaccine was the cause of this disease. That is absolutely not the case. We are being funded to conduct a piece of scientific research to establish or refute the link between MMR vaccine and the disease. There are absolutely no preconditions concerning the outcome. If this were the case, you may rest assured that I would never have been involved in the first instance. The science must lead and everything else follows. As with medical experts opinion elsewhere, I am being asked to provide my opinion, whether that opinion is positive or negative. It is on this basis and only on this basis, that I have agreed to assist interest his matter. I hope that this issue can be resolved as quickly as possible and my group are working to achieve this end.”
That letter did not allay the fears which Professor Zuckerman had already expressed and ultimately, as you know, the medical school refused to accept the money and Professor Zuckerman has said that was his decision on the basis of his concerns about conflict of interest. It was paid, instead, into a research account held by the special trustees at the NHS Trust. I want to ask you this, Professor Booth – and you of course are now the dean of a medical school – how usual an occurrence is it for a medical school to refuse research funds in your experience?
A It is very unusual. I think there are probably examples of schools refusing to accept money for funding research from tobacco companies in the past. Other than that, I cannot think of an example.
Q In those circumstances, would you expect a researcher to regard it as a pretty significant matter, if the dean of his medical school refused to accept the money?
A Absolutely, yes.
Q With regard to the items claims in the costing proposal, if we could just turn back to that, please, in FTP1. I do apologise; there is one more document I would like to go to in FTP2. I should have referred to it before. At page 420, this is the last letter in the Legal Aid Board sequence which I should have taken you to. It is a typewritten account of a meeting that the representative from the Legal Aid Board had with Dr Wakefield. It is in April 1997 and there are references in it which will be relevant later. In the second paragraph down:
“Dr Wakefield was enthusiastic about his investigation. He is a gastroenterologist and didn’t enter these investigations on a crusade and in fact ha been completely convinced by his subsequent studies and tests of a link between the vaccine (MMR) and the gastroenterological effects showing as various bowel disorders … identified in all but one child in the protocol study. The children in the study are autistic and have bowel problems. Are probably on the way to developing Crohn's disease.”
Then he refers to the fact that they are in the process of having specimens studied in Japan of the children with controls. He says in the next paragraph:
“All three … ”
That is, the doctors who she met –
“ … were keen to stress that they had to get the science right first before launching into new steps. They feel confident that they can now show a temporal association at work at least.”
So now you can put away FTP2, please, Professor Booth, and go to FTP1. If it assists you, in your report you deal with these matters at pages 17 and 35, but I think page 35 sets out your main views. In FTP1, if you could go to page 121, please, which is the costing proposal, and then turn to page 122, which sets out the costs in relation to the enteritis/disintegrative disorder cases. We see there that the cost is being claimed for colonoscopies, MRIs and EP and biological studies. I want to ask you this, first of all. If any of those tests and investigations were clinically required, would there be any question of needing funds from any source outside the NHS?
Q In broad terms, if an investigation is clinically indicated, who do you expect it to be funded?
A In the mid 1990s, it would have been paid for either by the hospital in which it was being undertaken or paid for. If it was outside their contract, in other words, the patient was coming from some way off usually from the investigations, it would be funded by an extra contractual referral, which means that the hospital referring the patient would pay the cost.
Q I said to you if the tests were clinically indicated. I perhaps should have said if they were represented as being clinically indicated, because I want to ask you, whose responsibility is it to make and convey that decision that the test is required clinically?
A That would be the consultant in charge of the patient’s management.
Q If, on the other hand, you developed a protocol for research purposes and you want to fund the same investigations under that protocol, and if we take the colonoscopies as an example, how do you go about funding that research protocol and the investigations included in it if they are for research purposes?
A Normally you would write a grant application and get a grant to fund it. I think in the past in the NHS – things have changed substantially now but in the mid-1990s – if you were admitting a patient for a research investigation, it would vary from trust to trust on how assiduous they were in tracking the money through the system, but often patients would have come in for essentially research tests without, in a sense, any money changing hands, but in some trusts then a charge would be made. The situation is a lot clearer now in that with the availability of clinical research facilities, for example, those costs are very clearly identified in a grant application and the trust makes a charge to the grant for those investigations, but it was less clear in the 1990s.
Q In this case it would appear that funding was being sought for research purposes, if we look at the costing proposal. You have told us that this particular source, the Legal Aid Board, is outside your experience, but I want to ask you about the specificity of grant expenditure in your experience, and that is something you deal with at page 36 of your report. If you are applying for research funds to any kind of fund-giving organisation do you generally, as a research doctor, have to specify what you want the money for?
A Yes, it is normally expressed in very specific terms because grant-giving bodies want to be absolutely clear what it is they are providing money for, and, as part of the peer review process, a peer reviewer is asked specifically to comment on the appropriateness of the money that is being requested, so it is looked at very carefully.
Q If you then decide that you want to use the money for something else, as a research doctor, what would you do?
A You would have to go back to the grant-giving body and say that you want to reallocate that sum of money, but in general it is not done very often because grant-giving bodies are not very keen on reallocating money, it rather puts the researcher in a bad light to have to make that sort of admission to the grant-giving body that they got it wrong first time round.
Q Would it ever be appropriate to divert funding received for one purpose into another without first indicating to the grant-giving body that you intended to do that?
A No, it would not be appropriate, and I would hope in most institutions the financial controls would be such that it could not happen. Our finance department is very clear about what research expenditure should be spent on within the terms of a grant, and if people were to start spending it on other things it would be identified.
Q With regard to the proposals submitted to the Legal Aid Board, can you understand why in all the circumstances the costs connected with these investigations would be claimed?
A Do you mean for the colonoscopy and the MRI and so on?
Q Yes, for all the investigations, the details of which are set out in that report. First of all, what does it suggest to you as to the basis upon which the testing was being done, the investigations were being done?
A To have funding for these investigations makes it very explicit that this is a research study, otherwise there would be no need to get funding from outside the NHS. If these were part of the clinical management of the patient you would not have to go outside the NHS for funding.
Q With regard to the claim for the medical reports on the children at the end of that, in the last section, do you have any view as to that? Again I am on page 36 of your report.
A If these were clinical investigations then charging for a medical report would be absolutely contra-indicated. It would be part of their clinical management and these doctors would be working within the NHS. It would be part of their routine job to provide reports on these patients, but as it is not part of their NHS management it is unusual to express the cost of the involved people in this way. What does happen is that in part of a grant application people may say, “I am going to be spending two hours, six hours, 10 hours a week” and that goes into the cost of the grant, but to put a specific sum against providing medical reports is outside my experience because normally research would not generate medical reports for which a charge would be made; research would generate research publications that would go into the research literature.
Q Turning on to page 37 in your report, Professor Booth, with regard to project 172-96, the ethics committee study, we know that Dr Wakefield was a responsibility consultant and coordinating investigator in that study. What would that mean with regard to the overall design of the study?
A You mean against the background that we have reviewed with the Legal Aid Board involvement?
Q Yes. First of all, as a coordinating investigator does he have a responsibility for the overall design of the study – and I think you have already told us that he does?
A Yes, if he is the coordinating investigator, yes.
MS SMITH: In general terms I want to ask you, as you set out at page 37, about the impact of the Legal Aid Board funding on the design of the study, and I should preface this by saying, of course, the precise factual background is going to be a matter for the Panel ultimately but I want to ask you what concerns you as an expert have in relation to that?
MR COONAN: Just before Professor Booth answers, and I am sure the learned Legal Assessor can see the content of the second paragraph on page 37, I invite my learned friend to be extremely careful, and that introductory caveat is, in my submission, not sufficient as a warning to Professor Booth not to trespass on the facts. He is not here to find the facts, that is a matter for the Panel, and I rather raise this concern that I wonder, we wonder, the extent to which in reality Professor Booth is being asked to express an expert opinion as opposed to an opinion from a commentator, which is an opinion which could in fact be expressed by a significant number of people outside Professor Booth’s actual expertise. We have reached a point where there is a grave danger of trespassing the boundaries which define the limits within expert evidence, opinion evidence can be given?
I have kept very quiet so far because my learned friend has kept on the proper side of those boundaries but at this stage there is a real danger of trespass. I have risen in an anticipatory way. I do not want to be bobbing up and down after Professor Booth has started to give his evidence.
THE CHAIRMAN: The Panel obviously do not have the report. Legal Assessor, do you have any views on the objection raised by Mr Coonan?
MS SMITH: I do not think there has been an objection.
THE LEGAL ASSESSOR: He has not raised an objection yet: I am monitoring what is going on.
MS SMITH: Yes, and if may also respectfully say, Mr Coonan has made lengthy and threatening observations which boil down to exactly what I prefaced these questions with, which is that in the end the factual background is a matter for the Panel. But, nonetheless, I propose – and Mr Coonan can of course keep jumping up and objecting if he thinks I am going to – to elicit from this witness, who is here as an expert – the concerns that he has which are directly relevant to the issue of conflict of interest, which must be plain to everyone that I am going on to ask him about, that are set out in that paragraph.
Mr Coonan knows exactly what Professor Booth is going to say because it is written down and he has got it in front of him, and that is the evidence I propose to adduce, so if he is objecting he had better say so now.
MR COONAN: I have made my position abundantly clear. What I say is in no way a threat; it is the sort of thing that one, as responsible counsel, indicates just to let one’s opponent know that there are boundaries even though one has an expert here. The question is an expert in what? That is the sort of issue that, as I say, I am inviting the learned Legal Assessor at this stage simply to monitor.
THE CHAIRMAN: I think the Legal Assessor has already indicated that he is monitoring things. Ms Smith, would you continue.
MS SMITH: (To the witness) Professor Booth, you know the paragraph I am asking you to talk to us about, and I repeat the question, which is in general terms I want to ask you about the impact of the Legal Aid Board funding in your view on the design of the study. You set out some concerns there and perhaps you would tell us what they are.
A The concerns relate to the funding by the Legal Aid Board, but also the apparent link between Dr Wakefield and a firm of solicitors who appear to be referring patients to Dr Wakefield for further study. My concerns are that if that link, and if the requirement for Legal Aid Board funding has not been present, or not undertaken, the way in which the study was designed might have been different. It might never have arisen, and also, having designed the study, the background of legal aid funding may well have influenced the selection of patients that were going to be included in the study, both in terms of the route that they arrived at the Royal Free Hospital but also by the people that were enrolling them into the study.
Q As far as that last observation is concerned, I think that is the third of the concerns that you express: what is your feeling about the group of patients and the way in which they came to be in the study, what is your concern about that?
A There is the possibility that they entered the study by a route that involved selection by a firm of solicitors and it may also, given that their motivation for contacting the solicitors was issues related to perceived damage to their child from MMR, have influenced their decisions with respect to giving consent for invasive investigations.
Q If there was an element of selection about these patients, does that impact on the nature of the group? I think you say in your report that it represents a highly biased group of patients: is that a further concern?
A Yes, if they have come from a source other than normal channels – and one would expect them to be normally referred spontaneously either by their general practitioner or by the local paediatrician. If they do not come through that normal route then they are an unusual and selective group of patients.
Q As far as the receipt of funding from the Legal Aid Board is concerned, what is your view as to whether that should have been declared to the ethics committee?
A I think ethics committees are more concerned now than they were in the 1990s about sources of funding. My recollection of how things were in 1996 was not that the source of funding was routinely asked for. It is not so much the source of funding but the reasons why the funding was requested which are relevant. In other words, it was requested in order to provide evidence to the courts, as far as I understand it.
Q Arising out of that, and in rather more specific terms, if there was funding provided by the Legal Aid Board and that funding was for the study which was the subject of the ethics committee application, should it in your view have been declared? Before you answer that, I think we need to look at what the terms of the request from the ethics committee was in terms of the information they required, so if you would go to FPT1, page 200 which is the ethics committee application. Would you turn to page 209, the question under paragraph 10, “Substances to be given to subjects”:
“How are the substances for this study being provided, and how is the study being funded?
Answer: Clinical research at the Royal Free Hospital [extra-contractual referral].”
I am sure you have forgotten the question in the rather specific terms I asked it so I will ask it again: given that, if there was funding provided by the Legal Aid Board and that funding was for the study which is the subject of the ethics committee application, should it in your view have been declared?
A Yes, there is a very specific question there that the applicants are asked to complete, so the Legal Aid Board funding should have gone in there. Moreover, the suggestion in the answer given is that the funding for the investigations that were included in the application to the Legal Aid Board were actually going to be funded by the NHS.
Q That is because of the reference to extra-contractual referral?
A ECR stands for extra-contractual referral, yes.
Q In slightly more general though connected terms, in 1996 when you were formulating a research project and subsequent when it is submitted for publication – and I underline in 1996 – would conflict of interest be a subject to which you would expect a researcher to give consideration?
Q In broad terms, firstly can you tell us, I know it is a big question, what is its relevance to scientific research? Why does the possibility of a conflict of interest matter?
A Because when the readers look at a publication they need to see whether the authors, either singly or in concert, for example, have received funding from a body – often it is a pharmaceutical company – so that the conclusions that they reach in their publication can be judged against that particular background. There is evidence that when people review the literature on a particular topic, for example, they come to a different conclusion about that particular drug, for example, if they have received funding during the course of their work from the pharmaceutical company that manufactures that drug, compared with, on the other hand, people that review the use of the drug who do not have any history of a commercial link with a company manufacturing that drug or that class of drug, so it does influence people’s views. I do not think it is necessarily bad. It is just a state that someone is in but it needs to be declared so that people can be absolutely clear about why they are doing it. Different journals have different levels of request about – had in the 1990s – different levels of requirement specifically about expressing conflicts of interest.
Q Before we go on to the journal: still on the subject of the application to the ethics committee, at the time it was submitted, September 1996, you have told us that it is your view that Dr Wakefield should have declared the Legal Aid Board funding, but generally speaking, having looked at the documentation prior to that date, what is your view as to whether he should have indicated to the ethics committee his involvement in the litigation regardless of whether or not he had at that time actually received the money?
A It is clear that he should have declared the funding in response to a very specific question there, and I think following out of that, if I was chairing the ethics committee I would have, I think, wanted to know what the terms of that funding involved. You would hope that in the interests of transparency, previous involvement in litigation around the topic of this research study would be made known. There is no specific question asking for it: difficult. As I say, in the interests of transparency you would anticipate that Dr Wakefield would make that known. You would also expect him to make it known to his colleagues as well.
Q The fact, as you have told us and as we have heard previously, of the novelty of the funding which was envisaged, where does that place the responsibility do you think in terms of ethical decisions as to whether to declare a possibility of a conflict? Whose responsibility would it be to assess that matter? I mean assess whether it should be disclosed, not assess whether it exists?
A It is very much the responsibly of the individual who has that conflict of interest to declare it, yes.
Q With regard to The Lancet, can we first of all just remind ourselves of the test formulated in respect of conflicts of interest, which is in FTP2 at page 616. This is a copy of the notes which are put in The Lancet in relation to writing to The Lancet and appear on a regular basis. The conflicts of interest and funding heading is in the middle of the first column on the left hand side:
“The conflict of interest test is a simple one. Is there anything – e.g. a shareholding in or receipt of a grant or consultancy fees from a pharmaceutical company or a contract from a medical devices manufacturer – that would embarrass you if it were to emerge after publication and you had not declared it? The Editor needs to be informed and will discuss with you whether or not disclosure in the journal is necessary. All sources of funding must be disclosed, as an acknowledgement in the text.”
You have a significant expertise in the submitting of research papers to medical journals, including, you have told us, The Lancet. From the point of view of someone submitting a paper, would you regard that test as one which should have triggered disclosure by Dr Wakefield in relation to his involvement in the litigation?
A Yes. It is very clear that he should have done.
Q Would you regard that test as triggering disclosure in relation to monies received from the Legal Aid Board in respect of the research project which was the subject of The Lancet paper?
A Yes, that is the basis for my saying that it should have been declared.
Q Just in broad terms, tell us why you apparently unhesitatingly say “Yes, it should have been declared” ?
A Because the funding from the Legal Aid Board falls into the type of funding that is referred to here. It is not mentioned specifically. It gives some examples, but I think the examples are such that you would not have any difficulty in recognising that you needed to declare that source of funding. In general, people do not have any difficulty in declaring their source of funding. It is not an issue. The funding is clear. It is sometimes more difficult if people, as it says here, hold shares, that sort of thing, but with sources of funding it is automatically disclosed.
Q If you are dealing, as we were, with a novel source of funding and the kind of involvement in the litigation which we have looked at on the documents, when you say it should have been declared, you mean the Editor should have been informed. Is that correct?
A Well, no, it should have gone into the manuscript. It says “All sources of funding must be disclosed as an acknowledgement” in the text.
Q As I say, if it is a novel situation, would you expect some sort of consultation with the Editor as to whether indeed it did constitute a conflict of interest?
A No. If you had received funding, it has got to be declared.
THE CHAIRMAN: We will take the break now and resume at 11.20. Professor Booth, I give my usual warning about not discussing this case.
(The Panel adjourned for a short time)
MS SMITH: Professor Booth, I just wanted to ask you one more question before I left this subject and went on to the related subject of the patents. You said just prior to the coffee break, when you were talking about the Legal Aid Board funding, “It is not so much the source as the reason for the funding. That was to provide evidence to the court.” I wondered whether you could just clarify for us why you regard that reason as constituting a conflict of interest.
A Because if the study in a sense had been commissioned by the Legal Aid Board in that they were funding and had an interest in the outcome, that may well have influenced the selection of patients that went into the study and therefore may have had an impact on any scientifically valid conclusion that you might arrive at as a result of the study.
Q Now, turning on, as I say, to the related subject of the patents, we know that in June 1997 Dr Wakefield instructed patent agents in relation to the patenting of an idea as to the proposed use of transfer factor. Could I just remind you as to the documentation that you have seen on that and also tell you that the view that you have expressed about that is on page 73 of your report. Could we all go to FTP2, page 479. This is the first of the letters, which is a letter from the patent agents involved, the filing receipt from the Patent Office on 6 June 1997. Could we go on to page 480, which is the description of the patent. At the top of the page:
“The present invention relates to a new vaccine for the elimination of MMR and measles virus and to a pharmaceutical or therapeutic composition for the treatment of IBD… particularly Crohn’s Disease and Ulcerative Colitis and regressive behavioural disease.”
He then refers to an earlier patent application. Going on down to line 23:
“At present vaccination is used for the prophylactic prevention of measles virus and as a public health measure has proved to be generally effective.”
Then to line 28:
“Unfortunately, as I have shown previously in the above mentioned patent application”
– and we know there had been a previous one in relation to IBD –
“the use of this vaccine has been shown to be instrumental in development of Crohn’s Disease and other forms of IBD over the ensuing 30 to 40 years and…. a substantial increase in Crohn’s Disease in children.…
The Physician is therefore confronted with a difficulty at the individual level in that whereas as a public health measure measles vaccination is called for, it can have unwanted effects in those subjects who are unable to immunologically eliminate the virus so introduced.”
Going on to line 8:
“What is needed therefore is a safer vaccine which does not give rise to these problems, and a treatment for those with existing IBD. I have now discovered a combined vaccine/therapeutic agent which is not only most probably safer to administer to neonates and others by way of vaccination, but which also can be used to treat IBD whether as a complete cure or to alleviate symptoms.”
Then going on to 488, we see clear reference to The Lancet children at the bottom of the page.
“The results of Examples 1 and 2 show anecdotally that [transfer factor] is an effective agent for the treatment of IBD and as a vaccine for measles virus.
In order to investigate a consecutive series of children for a new syndrome comprising chronic enterocolitis and regressive behaviour disorder (RBD) 12 children with a mean age of 6 years, range 3 to 10, all but one of whom were male, were referred with a history of achievement of normal developmental milestones followed by loss of acquired skills including language along with bowel symptoms, diarrhoea, abdominal pain and in some cases food intolerance all associated with the presence of MMR viruses in the gut.”
Then it sets out gastroenterological, neurological and developmental assessment, ileo-colonoscopy, MRI, EEG and lumbar puncture were performed. Barium follow through …. where possible. Chemistry, haematology and immunology profiles were examined. It says at line 13:
“All 12 children had significant intestinal pathology ranging from lymphoid nodular hyperplasia to aphthoid ulceration.”
Then furthermore it sets out the detail of the study. Going on to the claims, they are three-fold. He sets out the pharmaceutical composition for the treatment first of all and then he says:
“The composition according to Claim 1 adapted for use as a vaccine for the prophylaxis of measles virus”.
“A composition according to Claim 1 adapted for use as therapy for IBD and/or RBD”.
That is inflammatory bowel disease and the regressive behavioural disorder he identifies. There we have the claim of the patenting of a substance for use both as a vaccine and as a treatment or therapy. As I say, I am at page 73 of your report, Professor Booth, and the question is a simple one arising out of that document. What is your view as to whether the existence of that patent, again given The Lancet test, should have been disclosed to The Lancet when this paper was submitted?
A Yes, I think if a researcher is fulfilling the role of an investigator on the one hand and on the other hand has a financial interest in the outcome of the research, as would appear to be the case from looking at this document, that should undoubtedly be declared.
Q That is all I want to ask you about that specifically. I want to turn on to a separate related topic which arises in more general terms out of the eventual writing up of the 12 of the children in this study in The Lancet. First, could you turn back to The Lancet paper which is in the same volume, FTP2, at 783. Can we remind ourselves that on page 783 we see the patients and methods in the right hand column, Professor Booth, with the history of the children. Then the clinical investigations, which are listed. Histories, including details of immunisations and exposure to infectious diseases, assessment of the children, obtaining of the history, neurological and psychiatric assessments and then ileocolonoscopy and, at the bottom of that paragraph, MMR, EEG, including evoked potentials and lumbar puncture. That is the clinical investigations and it goes on and sets out the laboratory investigations. I want to ask your views about the observation made on page 784 where we see under “Ethical approval and consent”, it states:
“Investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust, and parents gave informed consent.”
I want to ask you this. What would an informed reader of this scientific paper understand “Investigations were approved by the Ethical Practices Committee” to be referring to?
A That statement under ethical approval would refer to the investigations outlined on the previous page under “Clinical Investigations”.
Q In the light of what you have already said to us with regard to the ethics committee application, do you regard that statement as made in The Lancet paper as correct?
A I have not found any evidence that parents gave informed consent in that I have not seen any printed information in the clinical notes, as was in fact requested to be placed there, for parents’ use, nor have I seen any signed consent forms for research investigations.
Q As far as the ethics committee had approved all the investigations set out in the clinical investigations, is it your understanding that the ethics committee had in fact done that?
A My recollection was that they had not been requested to approve some of the clinical investigations because they were being portrayed as being clinically indicated.
Q I am sorry to hammer the point home if you have made it, but in those circumstances do you regard that statement as a correct one in The Lancet paper?
A It does not comply in those terms with the application which was made to the ethics committee.
Q The paper was also about children under the heading, as we know, on page 783, of pervasive developmental disorder. The diagnosis, the behavioural diagnosis, is set out on page 785. You will see there it is mainly autism, with one query disintegrative disorder, two post viral encephalitis and an autism spectrum disorder. Leaving aside for a moment whether the investigations were clinically indicated or not, given the inclusion criteria for the ethics committee application, is it your view that ethical approval was given for this study as it was written up?
A No, because the ethical committee application form was very clear that children with disintegrative disorder were going to be studied and what is listed here under the behavioural diagnoses, apart from one query disintegrative disorder, does not conform to that key inclusion criterion.
Q Just going on to the end of the document, at page 787, in the acknowledgements at the very bottom of the page, we see that the study was supported by the special trustees of the Royal Free Hampstead NHS Trust and the Children’s Medical Charity. If all these tests were indeed clinically indicated, as appears to be being contended, can you see any reason for funding from the special trustees?
A Well, one possibility is that some of the special laboratory investigations fell outside normally available investigations on the NHS. That might be one explanation. But if it is being claimed that all of the investigations, both clinical and laboratory, were clinically indicated and done within the NHS, it is difficult to see what that funding would be needed for.
Q Turning on to the circumstances of referral, Professor Booth – this is page 32 in your report – first of all, if it were the case, as appears to be so, that the doctors at the Royal Free received spontaneous requests from parents of children with autism to be seen, given that there had been media interest in their interest in those matters, is that in itself particularly surprising or unusual?
A That they should have been contacted spontaneously by parents?
A No, I think particularly with this group of parents, in other words, of children with autism, that would not be at all unusual.
Q How would you expect that situation to be dealt with if parents spontaneously contacted either Dr Wakefield or Professor Walker-Smith?
A I think under those circumstances – and it happens on a regular basis that parents do make contact with specialty departments and say, “I’d like you to see my child”, although perhaps not in this volume – what would normally happen is that you would ask the parents to arrange for a referral; you would refer them back to their general practitioner or to the local paediatrician to discuss a referral and, if they felt that it was appropriate, to then make the referral on the patient’s behalf.
Q We have looked at the individual cases and in respect of some of them, I have asked you specifically whether you regarded the way in which the referral came about as usual or unusual and you have said that it was unusual. I now want to ask you about how the referral is described in The Lancet paper. Could you turn to page 783, please? The background summary on the left-hand side:
“We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder.”
Then under Patients and Methods:
“12 children, consecutively referred to the department of paediatric gastroenterology with a history of a pervasive developmental disorder with loss of acquired skills and intestinal symptoms …. were investigated.”
As far as those descriptions are concerned, firstly with regard to the description “consecutively referred”, is it your view that that fairly represents the process of referral of these children?
A It is difficult to comment, because we just have case notes from 12 children, so I do not know whether children were referred to the unit in between the children whose notes we have had access to on the basis of their having been in The Lancet publication. So it is difficult to know if they were consecutively referred or not.
Q What would you take it as intending to convey, that particular way of describing these children?
A That the series begins with patient 1 and every subsequent patient up to the twelfth patient that was referred is included, without any patient having been excluded or included within the 12 retrospectively, in other words, someone who had already been seen, but put into the series.
Q Do you think that description accurately gets over the unusual circumstances of those children in which you have expressed that view, that the method of referral has been unusual?
A It is unusual for so many children in a study to have apparently initiated the referral. That is not made clear here. Nor is the involvement of a firm of solicitors who in their documentation said that they have referred children for investigation. If those children that they describe were any of the 12, that should be made absolutely crystal clear.
Q What about those cases where it would appear that the initial contact has come from either Professor Walker-Smith or Dr Wakefield to the general practitioner? In each of the cases you have described, that is unusual. Do you think the way that The Lancet paper was written up conveys that?
A No. I think if the referrals were initiated by the investigating doctors, that is not really covered by just saying they were consecutively referred. The nature of the referral should have been made clear, because it is a key factor in being able to interpret the observations that they subsequently describe.
Q That is the next thing I was going to ask you. Why do you say it is a key factor? Why is the description of the patient population important?
A Because, for example, the symptoms which may have been elicited may have been influenced by the reason for the parents seeking the referral. They may have had a dual purpose: one, to try and get further information about their child’s symptoms, but secondly, if they have been involved in potential litigation on the basis of a perceived claim against MMR vaccine, they are not then really reliable witnesses; they have a conflict of interest.
Q The same paragraph which I have referred you to goes on to say, having said the children were consecutively referred, that they had, amongst other things, a history of intestinal symptoms. Again, we have looked at all of the individual cases and in respect of some of them we have discussed at some length the lack of an indication of any gastrointestinal symptoms in the referring letter and an indication in the referring letters of the principal reason for referral as indeed being investigation into whether damage has been caused by the MMR vaccine. Again, in those circumstances, do you think that this description is an appropriate one in a scientific paper?
A No. I think it is substantially less than transparent about these particular subjects which were being studied.
Q Overall, as you know, Professor Booth, the main part of this report refers to the gastrointestinal findings in these children, but it also reports on page 787 the reporting of the temporal link which the parents have made between MMR and the symptoms that their children had. I want to ask you this. Is the overall description of the study and the reference to the temporal link reported by the parents a fair and accurate one, given what you have seen of the purposes of the research study and the way the children came into it?
A Sorry, could you just define which part of page 787 you are referring to?
Q I was just trying to summarise what the paper included, which is first of all the gastrointestinal findings in these children, but then at the top of page 787, there is an examination, if you like, of the association with measles, mumps and rubella and an indication that it has not been proved, that there are virological studies under way, but that if there is a causal link, then that is something which may indicate a rising incidence. Then if you look back to page 783, under Findings:
“Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children.”
So that is one of the summary findings. The question I asked you was this. That overall description of the study and the reference to the temporal link reported by the parents, do you think that is a fair and accurate one, given what you have been able to ascertain as to the way in which the children came into this research study?
A I think, given the background whereby these children appeared to enter the study, their description of the temporal association between the onset of symptoms and MMR vaccine must be regarded as unreliable.
Q Thank you very much. Would you put FTP2 away now because we are going on to another subject and that relates to a presentation given by Dr Wakefield to the MIND Institute on 20 March 1999 in which he describes the taking of blood from normal children for comparison purposes for his research (that is control purposes). That is at page 66 of your report. You have seen I think the video of that presentation given by Dr Wakefield, and indeed, read a transcript of it.
A Yes, I have.
Q Before going to the particular circumstances, I want to ask you some general questions relevant to it: first of all, if you want to obtain blood for comparison reasons in normal children who are not patients, how do you categorise that with regard to whether it is research or not, first of all, if you want to obtain normal blood for control purposes?
A Then it would be a research study because you would have to submit the proposal to take the blood to the research ethical committee and they would come to a decision about whether it was appropriate or not, so taking blood for control children (or normal children) would be part of a research study.
Q Would it be something that there are any circumstances in which you could do it without research ethics committee approval?
A I think today I think the answer to that would be no, not under any circumstances. I think in the mid-1990s if you were taking blood from a child … Actually, no, I am just thinking of a study, at about the same time – no, we had research ethical committee permission to take an additional volume of blood from a child who was being bled anyway. These were patients who were undergoing elective surgery so they were having blood taken – they were having a needle in the vein while they were anaesthetised anyway, but the taking of the additional blood was part of an application and parents gave consent before it was done.
Q But that, of course, is in the context of a patient, as you say, who is having a procedure, and you might be adding something on for research purposes.
Q If you wanted to take blood from a normal child who was not having a procedure and did not have any reason to be having blood taken from them, and you needed it for research purposes, would that always require research ethics committee approval?
A Yes, absolutely, because actually taking blood from normal children as opposed to children who are probably normal is very difficult.
Q Is it your experience as a researcher in paediatric practice, you said it is difficult, is it difficult to get approval for that risk to be taken, albeit a very small risk, of taking blood if there is no benefit, in other words if it is just for a child who does not have anything wrong with them?
A I think it is difficult to justify taking blood from normal children, although I think opinion has probably shifted somewhat over the last 10 years and I think that is largely as a result of being able to make blood-taking pretty painless. Before local anaesthetic preparations were available it was inevitably painful. Now that such preparations are available I think it is possible and ethically acceptable to take blood from normal children, under very carefully defined circumstances.
Q Would those carefully defined circumstances always involve an application to an ethics committee?
A Yes, that would be essential.
Q Could we just quickly remind ourselves of one guideline, which is in the British Paediatric Association guidelines for 1992, which is in FTP4 at page 178. That is the commentary by Professor Hull, dealing with the particular section in relation to what constituted minimal risk and low risk. He explained to us the circumstances in which that commentary came about. Halfway down it says:
“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 those children.”
Does that accord with the views you have just expressed that it has to be done under very careful circumstances and with the consideration of an ethics committee?
Q With regard to payment to research volunteers, is that a matter that would be appropriate with respect to a child, the payment of …
A No, it would be reasonable to – if the family had incurred expenses, but normally one would not consider reimbursing patients, children, for taking part in a study.
Q We can see that on page 192, which is at the top of the page, it says:
“… the assent or agreement of school age children to their involvement in the research …”
“… and should always ensure that the child does not object.
Legally valid consent is both freely given and informed. For consent to be given, researchers:
- Offer families no financial inducement, although expenses should be paid.
- Exert no pressure on families …”
Turning to the circumstances of the episode that was described by Dr Wakefield in the video that you have seen, first of all, what was your overall view of it when you heard it?
A I found the description of the activities that he had undertaken with the children deeply disturbing and utterly repellent on a number of levels.
Q Can you tell us what in particular were your concerns?
A I suppose when you first hear about it you have concerns as a paediatrician responsible for care and welfare of children. The events took place at a birthday party so as a parent you are very concerned that such things should be happening in that context. As a researcher Dr Wakefield was transgressing very many well recognised research ethics but I think just generally we all have a responsibility to protect the dignity of children and I think these children were just, many of them, being humiliated.
Q It was being told, and I think there will be no argument, as an amusing story: what was your view of that as an attitude to the telling of this event subsequently?
A I think the humorous nature of the description was one of the factors that makes it so deeply unpleasant and the use of irony in describing that the parents had given informed consent was given in such a way that the audience, certainly in this country, if you have got a sense of irony you would realise that it was implying it had not been given.
Q Do you think that was appropriate?
A No, not at all.
MS SMITH: Would you excuse me for a moment, I am just making sure I have covered everything I should have? (Pause) Thank you very much Professor Booth. Sir, I have no further questions. I have finished rather earlier than I anticipated. Mr Thomas wants me to point out to you that he was right. I am sorry, I had slightly over-estimated the time things were going to take, but those are all the questions I have for Professor Booth.
THE CHAIRMAN: Thank you. That is the advantage of having a good junior.
MS SMITH: Two good juniors, or it will cause trouble.
THE CHAIRMAN: It is now 12 o'clock. How are we going to proceed from here? Mr Coonan, have you got any views?
MR COONAN: Sir, yes. The position that I outlined to you last night remains the same. In fact, I have been advised that Dr Wakefield has not, for various technical reasons and also because of his professional commitments, been able to see the transcript from Tuesday yet, so I am not in a position to cross-examine today, regrettably, because I do need to obtain instructions, as I am sure members of the Panel will appreciate. I cannot cross-examine without instructions. So, as far as my role is concerned, I would ask you please to let me take instructions over the weekend and therefore I can, in so far as I need to, cross-examine on Tuesday. Sir, that is my request for those particular reasons.
THE CHAIRMAN: Thank you. Mr Miller?
MR MILLER: Sir, we have just heard for three and a half days from the Council’s main expert, certainly so far as clinical matters are concerned. He has also dealt in great detail with Dr Wakefield’s position, not only in relation to the care of the children but also on the various ethical issues, some of which do not concern Professor Walker-Smith; some do. We consider that in this instance, because that evidence is important evidence, it would not only be appropriate but also necessary for counsel for Dr Wakefield to conduct his cross-examination first because the alternative would be that I would have to start and deal with matters not knowing whether or not they are going to be covered by counsel by Dr Wakefield and that puts me in a difficult position and may put Dr Wakefield in a difficult position as well. So, I do not feel it would be right for me to deal with them before they are dealt with by Mr Coonan, if he chooses to do so. We have ranged over quite a few of them this morning, and, as I say, although some of them are peripheral to my case they do impact on Professor Walker-Smith’s position and I would be unhappy about pre-empting any cross-examination that may take place by Dr Wakefield’s counsel and found that I have to some extent muddied the water. Unusual though my application is, I would invite you to break off now and start cross-examination by Mr Coonan on Tuesday morning.
THE CHAIRMAN: Mr Hopkins?
MR HOPKINS: Sir, it is anticipated by all that I am third in the pecking order, and I support the application you have just heard. I have nothing to add.
MR MILLER: Sir, perhaps I should make the point, it does not make any difference to the timetable. We are not putting the timetable back. I am still very confident that we will finish Professor Booth’s evidence in two days with all cross-examination.
THE CHAIRMAN: Thank you. Ms Smith?
MS SMITH: I do not think it is a matter for me. There is a somewhat bewildering change in order in which defence counsel seem to think they are going to be examining witnesses, but, as I say, I do not think it is a matter for me. The representations have been made and I think it is a matter for the Panel.
The only thing I would say: I am comforted, and I know Professor Booth will be, by the observation Mr Miller has made that it will not affect the timetable, and I noticed that Mr Coonan was nodding his head as well on that, so if I can just say that so that Professor Booth is reassured by it.
The other thing is, if you were minded to take that course, it does occur to me that there are two or three short statements which, if I am given five minutes to put them together and if the defence did not object to having them interposed, I could deal with now with the Panel because that will save half an hour next week when we may be anxious for half an hour.
THE CHAIRMAN: I think when Mr Coonan I think he also said, although it may have been in a very quiet voice, that he agrees with it.
What about the suggestion Ms Smith has made about using this time to read some statements?
MR MILLER: I think it is an excellent suggestion. I would just like to identify – with Ms Smith rather than in open forum – which statements she has in mind. If we could have five minutes, genuinely five minutes rather than 25 minutes, so we know what we are talking about, I am sure we can come back and deal with those without any problem.
MS SMITH: It is pointed out to me that we will need to do some photocopying, as I have rather sprung this on my instructing solicitor, but, as I say, I do not think there is any problem with the statements, and they are a line long most of them, so if you were prepared to rise until, say, 12.30, in other words 20 minutes, we could have a quick discussion amongst us and photocopy anything that needs photocopying. You would still be through by the luncheon adjournment.
THE CHAIRMAN: I am just going to ask the Legal Assessor about the application to postpone the cross-examination until Tuesday morning.
THE LEGAL ASSESSOR: Dr Wakefield is first in the charge list and the convention is that he is entitled, and would normally be expected, to cross-examine first. The fact that Mr Miller has gone first with some of the witnesses is more because those witnesses concerned Professor Walker-Smith more than Dr Wakefield. It is obvious that this witness concerns Dr Wakefield more than the others, and therefore it is not only procedurally correct but it would also be more convenient, and probably, as Mr Miller has pointed out, will minimise repetitious cross-examination. Therefore I advise that it would be entirely proper, until Mr Coonan is fully instructed, to postpone the matter until Tuesday morning.
Also, it will give the Panel an opportunity, because Monday is officially a sitting day and the Panel have heard, as Mr Miller has said, three and a half days of – he did not use the word “dense” but I use the word dense, about the evidence not of course about Professor Booth! – very dense evidence and it may help if the Panel were to spend Monday looking at their notes, deciding which questions they may wish to ask and then when they hear questions from defence counsel it may be that a lot of the Panel’s questions will be eliminated because the issues will have been dealt with, so it seems very proper use of the time and not wasting Monday.
THE CHAIRMAN: Thank you. Because of the very clear advice from the Legal Assessor, I am going to look towards the Panel members to see if they agree to the application or if they want to go into camera to make a decision on this. There is a nod of approval from all Panel members, without going into camera, so as far as that particular question is concerned, the application for cross-examination to begin on Tuesday morning, it is agreed that Mr Coonan should go first on behalf of Dr Wakefield, if he chooses to do so, so the application has now been agreed by the Panel.
The second point which has been made is that we rise, and I think that is appropriate, until about 12.30 and then hear some statements read.
Thank you we will rise and come back when you are ready.
THE CHAIRMAN: I forgot to mention before we rose just now that someone should remind Professor Booth that he remains under oath until Tuesday morning. Please pass on that message to him. I am sure he has remembered because I have repeated this warning on every occasion.
MS SMITH: I am sure he will recall, sir, and indeed he will have been made aware of it from the fact that I did not speak to him when he left.
THE CHAIRMAN: I am grateful for that.
MS SMITH: I am going to read three statements, sir. You are not going to get a copy of the first because it is just an additional paragraph from a witness statement of a witness from whom you have heard, and that is Dr Mary Stuart, who was the general practitioner to Child 12. As I say, she has already given evidence but there was one paragraph of her evidence which was the subject of some objection, which is now no longer an objection and so I am going to read it out on to the transcript. This is included in the evidence of Dr Mary Stuart. It is in her witness statement which she made on 23 March 2006. She says this:
“I was not aware at the time that Child 12 was one of the children who featured in The Lancet paper published in 1998. I had not known about the paper when it was published because I do not regularly read The Lancet. However, the alleged link between the MMR and autism/bowel disease claim that was made by Dr Wakefield greatly affected the surgery. It is still affecting the surgery to this day. Parents started coming in asking for single vaccines but they were not supplied in the UK. Therefore, some of the parents decided to pay for the single vaccines. This greatly concerned me because there was no guarantee as to where these vaccines were being imported from and whether they even worked.”
Sir, you should of course when you are reading that put that back into the context of the rest of Dr Stuart’s evidence as she gave it to you. That is the first matter.
The second matter is a statement and I am going to hand round copies of that. It is a statement of Deborah Davies. It is the third statement that she has made. The other two have been previously read to you.
(C14 marked and circulated)
As I say, this is the third statement of Deborah Davies signed by her on 20 September 2007.
“I, Deborah Davies, will say as follows:
1. I have already signed two witness statements in relation to this matter dated 23 November 2006 and 10 July 2007.”
As I say, you have already had both those statement read to you.
“2. On behalf of the Trust I have disclosed to the GMC to the best of my knowledge and belief all of the original clinical records in the Trust’s possession relating to the children reported in the Lancet paper in February 1998.
3. I understand that my statement may be used in evidence for the purposes of a hearing before the General Medical Council’s Fitness to Practise Panel and for the purposes of any appeal, including any appeal by the Council for the Healthcare Regulatory Excellence.
I believe the facts stated in this witness statement are true.”
The last one is in fact two statements by Frances Wharton. Perhaps those could both be handed to you, one of each. In order to make sense of this, you will need the Royal Free Hospital records of Child 2.
(C15, both statements, marked and circulated)
MS SMITH: This is the statement of Frances Wharton and it is signed and dated 31 August 2007. It says:
“I, Frances Wharton, will say as follows:
1. I have been assistant secretary to Dr Robert Surtees for a period of 2 years.
2. Dr Robert Surtees was a Consultant in Paediatric Neurology at Great Ormond Street Hospital until his death very recently.
3. I have been shown a fax dated 2 September 1996 from Dr Surtees to Dr Mike Thompson, and a letter dated 23 August 1996 from Dr Surtees to Dr Hilary Cass in relation to Child 2.”
That is in the Royal Free Hospital records at page 152, with a letter to Dr Cass attached after it at pages 153 and 154. Reverting to the statement, she says:
“I can confirm that the handwriting on the fax which reads ‘CSF: protein electrophoresis measles Ab [antibodies], cytokines, lactate, pyruvate, glucose’ is not the handwriting of Dr Surtees.”
Then she makes the usual statement:
“I understand that my statement may be used in evidence for the purposes of a hearing before the General Medical Council’s Fitness to Practise Panel….”
There is a second statement from her, which is dated 6 September 2007 and signed by her.
“I, Frances Wharton, will say as follows:
1. I have already made a statement in connection with this matter dated 31 August 2007. In that statement I have confirmed that the handwriting on a fax I have seen dated 2 September 1996 is not that of Dr Surtees.
2. I attach as exhibit ‘FW1’ copies of letters and notes containing Dr Surtees’ handwriting. These documents cover the period 1996-2005. It is clear from these documents that Dr Surtees’ handwriting does not appear on the fax dated 2 September 1996.”
“I understand that my statement may be used in evidence for the purposes of a hearing before the General Medical Council’s Fitness to Practise Panel…..
I believe the facts stated in this witness statement are true.”
Attached to that are indeed some letters signed by Dr Surtees, as you will see, and some notes written by him. You can look at those at your leisure, sir. It is obviously not the contents but simply an example of his handwriting.
Those are all the matters that I have to read. I think that concludes all the evidence that we can deal with today.
THE CHAIRMAN: Thank you, Ms Smith. We will start at 9.30 on Tuesday morning with Professor Booth’s cross-examination. I have already said that I am sure the Panel Secretary will pass on a message to Professor Booth in the meantime that we are resuming at 9.30 on Tuesday morning and that he is not supposed to discuss this case with anyone during this period.
(The Panel adjourned until 9.30 on Tuesday 16 October 2007)