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IN THE HIGH COURT OF JUSTICE

QUEEN'S BENCH DIVISION

ADMINISTRATIVE COURT



MR JUSTICE MITTING :

Procedural history

Undisputed facts

" Clearly this is an intensive regime with procedures that could be regarded as "high" risk although they are particularly used for the investigation of children with chronic inflammatory bowel disease. These children suffer from a disease with a "hopeless prognosis" in relation to their cerebral disintegrative disorder. They have often not had the level of investigation which we would regard as adequate for a child presenting with such a devastating condition. In relation to their gastrointestinal symptoms which will be present in all the children we investigate, these have often been under-investigated. We have so far investigated five such children on a clinical need basis, all in fact have proved to have evidence of chronic bowel inflammation. One child has already had a significant response to enteral feeding. Certainly there is a measurable benefit to the child:

i) establishing a diagnosis and excluding metabolic and other causes.

ii) commencing on a therapeutic regime.

This whole study is parent/patient driven as every case referred has been initiated by the GP by the parents of the child.

I can confirm that children would have these investigations even if there were no trial. I must make clear that we would not be investigating children without gastrointestinal symptoms."

On 13th November 1996, the Ethics Committee discussed Project 172-96. The minutes record that it was not approved: "improvements required on patient information sheet and clarification as to whether this is a study or normal patient investigation". Confusingly, the secretary to the Ethics Committee wrote to Dr. Wakefield on 14th November 1996 to tell him that Project 172-96 was approved at the meeting. That did not happen until the next meeting, held on 18th December 1996, at which it was approved, "subject to modification of patient consent form and removal of Schilling test". On 7th January 1997 Dr. Pegg wrote to Professor Walker-Smith notifying him of that approval, subject to three conditions: only patients enrolled after the date of the December meeting would be considered to be in the trial; the Schilling test was to be removed from the protocol; and the consent form was to be modified so that possible complications of lumbar puncture were explained. He also required the patient consent form and information sheet to be lodged with the clinical notes. Professor Walker-Smith acknowledged Dr. Pegg's letter on 9th January 1997. On the same date, he sent his clinical team and Dr. Wakefield a copy of the Ethics Committee's recommendations "for our study" and said "we need to implement this now". On 3rd February 1997, Dr. Wakefield wrote to Dr. Pegg telling him that "the pilot study" had demonstrated that MRI and EEG studies were all normal so that there was no need to continue them unless specifically indicated. He requested an amendment to authorise overnight fasting and an analysis of a urine sample to investigate intestinal permeability. On the same date, Dr. Wakefield wrote to Professor Walker-Smith to explain why he thought it right to become involved in what he described as "the legal aspect of these cases"  i.e. the litigation then being proposed by Dawbarns, pursuant to which the Legal Aid Board had provided £25,000 in December 1996 towards the costs of the "MMR investigation". Professor Walker-Smith responded on 20th February 1997:

"My position as with measles, MMR and Crohn's disease is that the link with MMR is so far unproven. It is clear that the legal involvement by nearly all the parents will have an effect on the study as they have a vested interest. I myself simply will not appear in court on this issue.

I would have been less concerned by legal involvement if our work were complete and we had a firm view. Never before in my career have I been confronted by litigant parents of research work in progress. I think this makes our work difficult, especially publication and presentation.

I am very excited by this work and it is very worthwhile. Simon Murch and I met today and have drawn up a draft for patient selection for your comment please."

That document set out primary and secondary criteria for "patient selection for study of enterocolitis and regressive autism". It is dated February 1997.

"On the issue of autism, I am completely astounded by the clinical features of these children with autism and bowel inflammation. Very often the gastrointestinal symptoms have been ignored by a succession of the doctors and the findings on ileo-colonoscopy appear to be quite distinctive. This seems to me a whole new syndrome which is in urgent need of clarification".

That was the conclusion of the published paper.

A fundamental issue: the distinction between medical practice and research

"What constitutes research in patients?

2.2 When an activity is undertaken solely with the intention of benefitting an individual patient, and where there is a reasonable chance of success, the activity may be considered to be part of "medical practice". The progressive modification of methods of investigation and treatment in the light of experience is a normal feature of medical practice and is not to be considered as research.

2.3 In contrast, where an activity involving a patient is undertaken with the prime purpose of testing a hypothesis and permitting conclusions to be drawn in the hope of contributing to general knowledge, this is "research". The fact that some benefit expected or unexpected, may result from the activity does not alter its status as research".

"The distinction between "medical practice" and "research" is often less clear than is suggested above because both are practised simultaneously".

Its own guidance hovers between an objective and a subjective test. The concluding sentence of paragraph 2.4 states,

"Any activity which affects the patient in any way which is additional to ordinary medical practice is to be regarded as research".

Yet in paragraph 3.1 of a report published at the same time, "Guidelines on the practice of Ethics Committees in medical research involving human subjects", the Royal College restated the importance of intention:

"The definition of research continues to present difficulties, particularly with regard to the distinction between medical practice and medical research. The distinction derives from the intent. In medical practice the sole intention is to benefit the individual patient consulting the clinician, not to gain knowledge of general benefit, though such knowledge may incidentally emerge from the clinical experience gained. In medical research the primary intention is to advance knowledge so that patients in general may benefit; the individual patient may or may not benefit directly".

Again, in the opening sentence of paragraph 3.2 of the same report,

"Thus, when a clinician departs in a significant way from standard or accepted practice entirely for the benefit of a particular individual patient, and with consent, the innovation need not constitute research, though it may be described as an experiment in the sense that it is novel and un-validated".

"Whether or not the individual doctor's intention at the time is relevant is a significant issue in dispute between the parties and you have their respective submissions on that and the relevant guidelines. If you are sure that the GMC is right when it submits that the intention of the individual doctor is not relevant you do not have to go on to consider the individual intentions. If, however, you think that the doctor's submissions are right or might be right  that the intention at the time is a relevant consideration  then you must consider the intention of each doctor separately".

Thus, if the panel accepted that the GMC's interpretation of the guidance was correct, it would have decided that if what was being undertaken by Professor Walker-Smith was, objectively viewed, research, he would have been undertaking research even if his sole intention was to benefit his patients. Given the absence of any finding about Professor Walker-Smith's state of mind (as to which see more below), that is a conclusion which the panel may well have reached. If it did, it would not have been a sustainable finding.

Professor Walker-Smith's intention

Facts supporting the proposition

a) It was Dr. Wakefield who first perceived a link between behavioural and gastrointestinal disorders and between both and measles/measles vaccines. As a researcher, he was, throughout, principally interested in testing his hypotheses. Dr. Wakefield played an unusual role for a researcher in the referral of many of the Lancet children to the clinical team for investigation. b) Between April and September 1996 (a period spanning the admission of the first three children, beginning with child 1 on 21st July 1996) Professor Walker-Smith wrote to Dr. Wakefield, to the parents of children 2 and 6 and to other medical practitioners referring to a "plan" or "programme" for investigation, to a "proposed" or "forthcoming" study and to "our study of autism and bowel disorder". He also suggested sending a copy of Project 172-96 to the mother of child 2 and did send a copy of it to the local Consultant Paediatrician for child 9. c) There was no complete written clinical protocol separate from Project 172-96. d) The investigations carried out on the Lancet children substantially replicated those set out in Project 172-96 and did so irrespective of the detailed clinical history and presentation of each child. e) The Lancet paper contained a statement that investigations had been approved by the Ethics Committee. No other investigations apart from Project 172-96 and the general permission to take two additional biopsies given to Professor Walker-Smith had been so approved. (I will deal with the cases of the individual children, the expert evidence relating to them and with the Lancet paper in detail below.) Facts negating the proposition i) None of the five clinicians involved in the investigation of the Lancet children who gave evidence to the panel considered that they were following Project 172-96. ii) None of the children fitted the hypothesis to be tested under Project 172-96, in that none of them had both received a single or double vaccine and had developed disintegrative disorder. The great majority had received MMR vaccine and been diagnosed with autism. iii) No parent was required to sign either the consent form in the proposals submitted to the Ethics Committee or in the revised form approved by it. With one exception (child 2  see paragraph 34 below) the only consent forms signed were for diagnostic colonoscopy and the additional research biopsies approved in September 1995. iv) In every case investigations were followed by a discharge letter prepared by Dr. Casson which set out a diagnosis of the child's condition and by a recommendation for treatment. In some cases, the treatment produced an apparent marked improvement in gastrointestinal symptoms and behaviour. v) Dr. Pegg was not the only responsible person to whom Professor Walker-Smith stated that the investigations were clinically indicated; he told Mr. Else, Chief Executive of the Royal Free NHS Trust that they were, as Mr. Else confirmed to Dr. Wakefield on 4th September 1996; he gave a lecture at the Wellcome Trust on 20th December 1996 in which he spoke of the investigations and gastrointestinal diagnoses of the first seven Lancet children; on 6th February 1997, he wrote to Dr. O'Connor, a Consultant in Public Health Medicine responsible for funding the referrals of children 6 and 7 to him, enclosing a five page explanation of the rationale, aims and potential therapeutic implications of the investigations, in which he and Dr. Wakefield set out the clinical justification for them. Although the latter document was described by the GMC as "defensive" it was never suggested to Professor Walker-Smith that he deliberately misled his interlocutors about his intention. vi) Professor Walker-Smith had no rational motive to begin research before it was authorised, carry it out in breach of the requirements of the Ethics Committee after it was authorised or deliberately to mislead the Ethics Committee and others about his intention. Unlike Dr. Wakefield, he was agnostic or cautious about the claimed link between MMR and autism and gastrointestinal disorders. On 29th and 31st July 1997 he wrote privately to Dr. Wakefield to express his and Dr. Murch's concern that their professional reputation would be damaged by association with work prematurely leaked to the media. vii) As Miss Glynn accepts, a clinical protocol can, in principle, prescribe multiple identical investigations into patients with complex and intractable problems in an attempt to diagnose their condition.

(Again, I deal with the cases of individual children and the Lancet paper below).

"The panel has heard that ethical approval had been sought and granted for other trials and it has been specifically suggested that Project 172-96 was never undertaken and that in fact, the Lancet twelve children's investigations were clinically indicated and the research parts of those clinically justified investigations were covered by Project 162-95 [the general permission given to Professor Walker-Smith in September 1995]. In the light of all the available evidence the panel rejected this proposition."

In its decision on the second issues, it reiterated that conclusion, without explaining its reasons for doing so further. It hinted at lack of probity on the part of Professor Walker-Smith, without expressly finding that he had acted without probity and/or explaining its reasons for doing so:

"The conditions for approval for Project 172-96 and the inclusion criteria for it were not complied with and thus the expectation of the Ethics Committee and their reliance on the probity of Professor Walker-Smith as a responsible consultant were not met".

Its conclusion that Professor Walker-Smith was guilty of serious professional misconduct in relation to the Lancet children was in part founded upon its conclusion that the investigations into them were carried out pursuant to Project 172-96. The only explanation given for that conclusion is that it was reached "in the light of all the available evidence". On any view, that was an inadequate explanation of the finding. As it may also have been reached upon the basis of two fundamental errors  that Professor Walker-Smith's intention was irrelevant and that it was not necessary to determine whether he had lied to the Ethics Committee, it is a determination which cannot stand unless it is justified by the detailed findings made in relation to the eleven relevant Lancet children.

The Lancet children

i) In relation to all eleven children, that Professor Walker-Smith subjected them to a programme of investigation for research purposes without Ethics Committee approval (either because the investigations were carried out before approval was given or because the childrens' condition did not meet the selection criteria or because they were carried out in breach of the conditions of approval).

ii) In relation to all but two of the children (6 and 7) he caused them to undergo colonoscopy although it was not clinically indicated.

iii) In relation to seven of the children (all but 4, 6, 7 and 10) he caused them to undergo barium meal and follow through although not clinically indicated.

iv) In relation to three of the children (3, 9 and 10) he caused them to undergo a lumbar puncture which was not clinically indicated.

v) In relation to all eleven children, his conduct was contrary to their clinical interests.

Allegations (ii) and (iii) stood or fell together: if colonoscopy was not clinically indicated, barium meal and follow through  a procedure designed to investigate part of the bowel which colonoscopy and endoscopy could not reach  would also not have been clinically indicated. It was not suggested that if colonoscopy was clinically indicated, barium meal and follow through would not be.

Child 2

"I think it would be very helpful if I saw (child 2) again. I have had discussions about (child 2) with Dr. Wakefield. We have a plan for investigation but I think if it were convenient for you, it would be helpful for me to see (child 2) first in the outpatients and discuss and plan what we have in mind "

A slightly postponed outpatient appointment was fixed for 21st June 1996, at which child 2 was examined by Professor Walker-Smith.

" CSF

Protein electrophoresis

Measles Ab

Cytokines

Lactate, pyruvate, glucose".

The irresistible inference is that Dr. Thomson discussed the reasons for obtaining cerebrospinal fluid by a lumbar puncture with Dr. Surtees and agreed with him that one of the purposes would be to exclude metabolic disorder  hence, "lactate, pyruvate, glucose". Dr. Thomson and Dr. Casson also made handwritten notes on a typed protocol for investigations of possible degenerative disorders of the CNS, which Dr. Thomson had brought with him from the Birmingham Children's Hospital where he practised before his move to the Royal Free Hospital.

"Referred for Ix [investigation] of ? assoc between GI [gastrointestinal] disease/autism/measles"

A lengthy and detailed clinical history is then set out. Towards the end, Dr. Casson noted that child 2 had "started going down hill again" and had been to the B12 Unit at Chelsea and Westminster. He described his current condition as follows:

" Presently ? has "episodes" about every 18 months. Last in April. Last up to 3/52.

? Association jaundice and pale stools.

Poor sleep, increased diarrhoea, screaming."

He then noted that he had been prescribed an exclusion diet and bacteria by Dr. Hunter at Addenbrooke's which seemed to have eased abdominal pain.

"It is, I think, a responsibility of such a doctor to investigate that child as fully and comprehensively as he can, to try and determine what is wrong with him".

"5a. You subjected child 2 to a programme of investigations for research purposes without having Ethics Committee approval for such research,

Found proved

The panel were satisfied that you admitted the child under your care after discussion with Dr. Wakefield, and reassessing the child on 21st June 1996. You also sent the child's mother a copy of the protocol for investigations and arranged the investigations. You wrote to child 2's GP on 28th June 1996 stating "I think Crohn's disease is unlikely. Dr. Wakefield has the view that there may be some kind of other inflammation which may be a relevant factor in child 2's illness and we now have a programme for investigating children who have autism and a possible reaction to immunisation." The panel has concluded, on the basis of the medical records, that the programme of investigations that child 2 underwent was for research purposes for which there was no ethical approval.

b. The programme of investigations carried out on child 2 was part of the project referred to at paragraphs 2b and 2c above (i.e. Project 172-96)

Found proved

The panel found that the programme of investigations carried out on child 2, and the reasons for the investigations, follow closely the project protocol referred to at paragraphs 2b and 2c. In coming to that view, the panel had regard to the letter signed by you on 28th June 1996 to Dr. Wakefield where you state that child 2 is "the most appropriate child to begin our programme". The medical records further indicate that at least four paired biopsies were taken at colonoscopy, which the panel concludes was in accordance with the investigations described in the project.

e. You caused child 2 to undergo a,

i. colonoscopy

Found proved

ii. barium meal and follow through,

Found proved

Which was not clinically indicated,

Found proved

The panel accepted your own evidence that the child's condition was improving at this stage and therefore these investigations were not clinically indicated.

i. your conduct as set out above was contrary to the clinical interests of child 2,

Found proved in the light of the panel's findings above."

Child 1

"Has problems with eating  picky eater. Has undigested food in stools, has no control. Has had blood occasionally in stools."

He arranged for routine blood tests to be performed. On 21st June 1996, he wrote to Dr. Barrow stating that it was difficult to associate a clear historical link with MMR vaccine and,

"As part of Dr. Wakefield's and mine interest in the relationship between immunisation and chronic inflammatory bowel disease, I have arranged for a routine blood test to be done for screening for C-reactive protein etc. The diarrhoea which (child 1) currently has does have the features of toddler's diarrhoea. His mother is concerned by the diarrhoea

My plan would be to see him again in 3 month's time and then if (child 1's mother) feels that it is appropriate we could consider performing endoscopy and a further assessment neurologically and psychologically of his autism to explore the possible link between measles immunisation, bowel inflammation and autism."

On the same day, he wrote to Dr. Wakefield telling him that he had seen child 1. The blood test results revealed that haemoglobin was below normal range, at 10.8  which Professor Walker-Smith said in evidence was a mild but significant degree of anaemia and in accord with the history of passing rectal blood. He accordingly reconsidered his diagnosis of toddler's diarrhoea and arranged for child 1 to be admitted for investigations.

"7a. You subjected child 1 to a programme of investigations for research purposes without having Ethics Committee approval for such research,

Found proved

The panel was satisfied that you saw this patient, that you expedited his admission and that there was no Ethics Committee approval for these investigations in July or October 1996. Child 1 underwent a colonoscopy, MRI scan of his brain, an EEG and a variety of blood and urine tests. These were some of the investigations listed in the programme of the project. He was again admitted in October 1996 for further investigations regarding the "aetiology of the autism" again for no obvious clinical gastro-intestinal reasons. During this admission child 1 underwent a barium meal and follow through and a lumbar puncture which were also investigations listed in the project. The panel concluded that child 1 underwent these for research purposes for which there was no Ethics Committee approval.

b. The programme of investigations carried out on child 1 was part of the project referred to at paragraphs 2b and 2c above,

Found proved

The panel had regard to the letter dated 21st June 1996 from you to child 1's GP which states "As part of Dr. Wakefield's and mine interest in the relationship between immunisation and chronic inflammatory bowel disease, I have arranged for routine blood tests to be done for screening for C-reactive protein etc." The panel also took into account the discharge summary dated 9 August 1996 that states "Child 1 was admitted for further investigations into his autism and specifically to look into a possible association between his neurological condition and any gastro-intestinal disorders." On the basis of the investigations carried out, the panel has concluded these were part of the project.

e. You caused child 1 to undergo an attempt at colonoscopy when such an investigation was not clinically indicated,

Found proved

The panel was satisfied that you considered the child had the features of toddler's diarrhoea and therefore a colonoscopy would not be clinically indicated.

f. You caused child 1 to undergo a colonoscopy and a barium meal and follow through although

ii. such investigations were not clinically indicated,

Found proved, for the reasons set out above.

i. Your reliance on the views of child 1's mother in making the decision to undertake a colonoscopy was inappropriate,

Found proved

The panel was satisfied on the basis of your letter to his GP dated 21 June 1996, where you stated " if (child 1's mother) feels that is appropriate we could consider performing endoscopy and further assessment " The panel concluded that your reliance on her views that there was a link between autism and immunisation and bowel inflammation was inappropriate.

j. Your conduct as set out above was contrary to the clinical interests of child 1,

Found proved in the light of the panel's findings above".

Child 3

"Thank you for asking to see this young boy who developed behavioural problems of autistic nature, severe constipation and learning difficulties after MMR vaccination .His severe constipation is requiring frequent enemas and oral medication. The parents are very convinced that the difficulties in his behaviour etc. started only after vaccination. I am extremely grateful for you to have taken on (child 3) for case study."

The GMC did not suggest that Professor Walker-Smith had asked to see child 3. Dr. Wakefield said in evidence that it was very likely that he had had contact with the parents before the referral was made. Professor Walker-Smith replied on 22nd February 1996, saying that he had arranged for an outpatient appointment to be sent. On 27th February 1996, in a letter to Dr. Shantha, Dr. Balachandran noted a history of constipation and blood in stools, for which the parents had used lactulose and micro enemas on the advice of the specialist nurse.

"Whether this is causally related I simply don't know at present. (Child 3's mother) is keen that we pursue this avenue. In the first instance I have screened (child 3) with routine blood tests etc. and we will consider in due course whether it is appropriate to go ahead and perform a colonoscopy. A colonoscopy offers the opportunity to demonstrate if there is any ongoing infection in the gastro-intestinal tract which could in some way be causally related to his present problems".

On 23rd April 1996, Dr. Rosenbloom provided child 3's notes to Professor Walker-Smith and asked for references available for the link between MMR vaccine, autistic behaviour and Crohn's disease. Professor Walker-Smith replied on 16th May 1996, saying that he had passed on his letter to Dr. Wakefield "who is the inspiration of our work linking MMR, autistic behaviour and Crohn's disease and I am asking him to write to you to fill you in on our proposed study."

"No abdominal pain  no joint pain. No rash. Suffers from constipation from the age of six months. Rectal bleeding with hard stools  not mucosy

No gastro symptoms"

The endoscopy clerking sheet gives the reason for the procedure as,

"? CROHN'S DISEASE. (Severe constipation intermittent PR bleeding from 8/12  4 ½ years)."

Dr Thomson's colonoscopy report notes an increase in the number of lymphoid follicles in the terminal ileum. There is no explanation in the transcribed clinical notes supplied to me for the decision, which must have been made after 23rd August 1996, to undertake procedures other than colonoscopy. There was, apparently, a handwritten note by Dr. Thomson on his colonoscopy report of 9th September 1996, "Plan: other Ix [investigations] as per protocol". A barium meal and follow through was planned for 11th September 1996, but cancelled. An MRI scan, and EEG and lumbar puncture were performed on 12th September 1996. The EEG was requested by Dr. Harvey for "disintegrative disorder + possible enteritis". A barium meal and follow through was performed on 13th September 1996, which revealed no evidence of (?) [possibly inflammation]. Dr. Dhillon's histology report of 13th September 1996 noted mild inflammatory and reactive changes in the small bowel samples of uncertain significance. The discharge notification of the same date diagnosed Crohn's Disease with autistic behaviour and prescribed lactulose and sytron for the bowel condition. Dr. Casson's discharge notes dated 4th October 1996 set out the procedures undertaken and their outcome and concluded that he did not appear to have significant bowel disease.

"9a. You subjected child 3 to a programme of investigations for research purposes without having Ethics Committee approval for such research,

Found proved

In reaching its decision that you subjected this child to the programme of investigations, the panel is persuaded by child 3's Royal Free Hospital records, in particular the letter dated 4 April 1996 from you to Dr. Wakefield in which you state that you have not yet booked child 3 for a colonoscopy as you were waiting for the "full details of the investigative protocol" to be worked out. It also noted your letter dated 18 July 1996 to Dr. Wakefield which states, "We are arranging for (child 3's) admission for colonoscopy on Sunday 8 September, followed by you intensive investigations". The panel concluded on this basis that the programme of investigations that child 3 underwent was for research purposes and that there was no Ethics Committee approval for such research.

b. The programme of investigations carried out on child 3 was part of the project referred to at paragraphs 2b and 2c above,

Found proved

The panel is satisfied that the programme of investigations carried out on child 3, and the reasons recorded in the clinical notes for those investigations, followed closely the project protocol referred to at paragraph 2b and 2c. In addition, the panel took into account the letter dated 16 May 1996 from you to the Paediatric Neurologist which states, "I am actually passing on (your) letter to my colleague, Dr. Andy Wakefield, who is the inspiration of our work linking MMR, autistic behaviour and Crohn's disease and I am asking him to write to you to fill you in on our proposed study "

e. You caused child 3 to undergo a,

i. colonoscopy,

Found proved.

The panel notes the handwritten note on the letter of 18 July 1996 where Dr. Casson records he has discussed the undertaking of a colonoscopy with you and Dr. Murch.

ii. Barium meal and follow through,

Found proved

The letter dated 18 July 1996 from you to Dr. Wakefield where you state child 3 will undergo colonoscopy "followed by your intensive investigations", together with the clinical notes of this child persuaded the panel that he had undergone barium meal and follow through and because he was under your clinical care, you had caused it.

Which was not clinically indicated,

Found proved

Experts on both sides, Professor Booth and Dr. Miller, agreed that a colonoscopy (and therefore the barium meal and follow through) would not be clinically indicated at this stage.

f. You caused child 3 to undergo a lumbar puncture,

Found proved.

The panel is satisfied that the clinical notes including the discharge summary show that this procedure was undertaken and that you caused it to be done

iii. Which was not clinically indicated,

Found proved

The panel has taken into account that there is no evidence in child 3's clinical notes to indicate that a lumbar puncture was required. Professor Rutter and Dr. Thomas, experts on both sides, considered that such a test was not clinically indicated

i. Your conduct as set out above was contrary to the clinical interests of child 3,

Found proved.

The panel had regard to its findings above".

Child 6

"13a. You subjected child 6 to a programme of investigations for research purposes without having Ethics Committee approval for such research,

Found proved.

In reaching its decision that you subjected child 6 to a programme of investigations, the panel is satisfied by the evidence of the medical records, in particular the letter from you to the child's GP dated 4 October 1996 wherein you state, "I am arranging for him to come in to have a colonoscopy and entering our programme of investigation of children with autistic problems." The panel has concluded that the programme of investigations that this child underwent was for research purposes for which there was no ethical approval.

e. Your conduct as set out above was contrary to the clinical interests of child 6,

Found not proved.

The panel found that despite this child being subject to a programme of investigations rather than specific ones tailored to his needs, there was insufficient evidence to make a finding that the investigations were contrary to his clinical interests."

Child 9

"You may remember that at the project meeting last Tuesday, this child was briefly discussed and it was agreed he should if possible be included in our first ten cases. I have since spoken to the mother and it appears that she received a discharge letter from the Chelsea and Westminster last October, recommending that child 9 be referred to you! Since I gather you know 'Clifford Spratt (child 9's Consultant Paediatrician in Jersey), I wonder if you would be able to telephone him and activate the referral?"

On 11th September 1996 Professor Walker-Smith wrote to Dr. Spratt:

"We recently have become aware of a syndrome of enteritis and disintegrative disorder or autism. We have in fact investigated two children so far and during treatment they both had evidence of bowel inflammation. Whether this relates to Crohn's disease or whether it is related to measles immunisation or measles itself is quite unclear. However, I have heard from Dr. Wakefield that there is a child called child 9 who is resident in Jersey whose parents would be quite keen for us to investigate the child in our protocol. I am just wondering whether you think this is at all appropriate. If you felt it appropriate I would be happy to see the child.

Just in case you would be interested I am enclosing a copy of Dr. Wakefield's detailed proposal."

The proposal was Project 172-96. On 25th September 1996 Dr. Spratt wrote two letters to Professor Walker-Smith: the first, a formal request for his opinion, addressed to the Royal Free Hospital; and the second, much longer letter, to Professor Walker-Smith's home address. He said that child 9 had been a vexed case for him since September 1992, that he distrusted Dr. Bhatt's diagnosis and proposed treatment and was not aware of "any convincing bowel symptoms in his history".

"We have now seen several children with autism and gastrointestinal symptoms, all of whom on gastrointestinal investigation have proved to have some kind of bowel inflammation. It is quite difficult to relate this directly to autism. Dr. Wakefield as you know, believes that immunisation may play some part, although I remain neutral on this issue for the moment. However the parents are keen that we should endeavour to investigate child 9, and I have therefore arranged for him to come in to have a colonoscopy and barium meal and follow through and a repeat lumbar puncture".

"15a. You subjected child 9 to a programme of investigations for research purposes without having Ethics Committee approval for such research

Found proved

In reaching this decision that you subjected the child to the programme of investigations, the panel is persuaded by the evidence, in particular your letter dated 11 September 1996 to the local Consultant Paediatrician, Dr. Spratt, in which you enclosed, "Dr. Wakefield's detailed proposal" and state that child 9's parents are keen "for us to investigate the child in our protocol" and that if Dr. Spratt felt it appropriate, you would be happy to see child 9. Having seen the child in outpatients, you wrote to Dr. Spratt on 8 November 1996, stating, "we have now seen several children with autism and gastrointestinal symptoms I have arranged for him to have a colonoscopy we will then endeavour to follow this with barium meal and follow through and repeat lumbar puncture." The panel is satisfied that the programme of investigations that child 9 underwent was for research purposes, for which there was no Ethics Committee approval.

b. The programme of investigations carried out on child 9 was part of the project referred to at paragraphs 2b and 2c above,

Found proved

The panel concluded that the programme of investigations carried out on child 9, and the reasons recorded for those investigations, followed closely the project protocol referred to at paragraphs 2b and 2c. The panel has also taken into account the letter dated 9 September 1996 from a research colleague, John Linnell to you, which states " It was agreed that he should, if possible, be included in our first ten cases." In addition the panel has noted that child 9, having been discharged from the Royal Free in November 1996 with normal results on the investigations to date, was readmitted on 9 December 1996 for completion of the programme of investigations.

e. You caused child 9 to undergo a,

i. colonoscopy,

Found proved

ii. barium meal and follow through,

Found proved

Which was not clinically indicated

Found proved. The panel is persuaded by the evidence in the clinical notes and also accepted the evidence of both experts called by the GMC and defence, who agreed they would not have undertaken these procedures and therefore they were not clinically indicated at this stage.

f. You caused child 9 to undergo a lumbar puncture,

Found proved on the basis of your letter dated 8 November 1996 to the local Consultant Paediatrician, informing him that your plan included a repeat lumbar puncture.

ii. Which was not clinically indicated,

Found proved.

The panel is satisfied that there had been no evidence of recent further neurological deterioration to warrant a repeat lumbar puncture.

k. Your conduct as set out above was contrary to the clinical interests of child 9,

Found proved on the basis of above findings."

Child 5

"In relation to the research that is being done concerning this group of children I suggest that you or (child 5's mother) should be directly in touch with Dr. Andy Wakefield who is directing the research aspect of this study. If you have any further queries please do not hesitate to contact me."

"17a. You subjected child 5 to a programme of investigations for research purposes without having Ethics Committee approval for such research,

Found proved. In reaching its decision that you subjected child 5 to a programme of investigations, the panel is persuaded by the letter dated 1st October 1996 to you, from his GP, stating "This child's parents have been in contact with Dr. Wakefield and have asked me to refer him to yourself regarding your current study into association between autism and childhood bowel problems" and your decision to admit, copied to Dr. Wakefield as detailed in your response dated 12 November 1996, " I saw him in the clinic I am arranging for him to come in for a colonoscopy." The panel has concluded that the programme of investigations that child 5 underwent was for research purposes, for which there was no Ethics Committee approval.

e. You caused child 5 to undergo a,

i. colonoscopy,

Found proved

ii. barium meal and follow through,

Found proved

Which was not clinically indicated,

Found proved. The panel concluded that there were not significant GI signs and symptoms to justify colonoscopy and BMFT at that time

i. Your conduct as set out above was contrary to the clinical interests of child 5,

Found proved on the basis of the above findings."

Child 12

"Soils  not had diarrhoea

Has variable abdominal pain  occurs every week. Stops him eating".

He arranged for blood tests to be performed.

"We do feel that (child 12) does have a problem in that most children his age do not soil themselves a number of times a day. As well as being pale in colour and foul smelling (as are his motions in general), this soiling is always very loose which makes plain why he is not always aware that he has done anything. Although I would not say it was diarrhoea exactly.

Obviously I do not wish to put my son through any procedures unnecessarily but there must be reason why he has these problems. Also as I mentioned to you at our meeting, Matthew is not growing our putting on weight like my other two children.

I keenly await the results of the blood tests and if you feel they warrant further investigations my husband and I are happy for him to be referred onto Dr. Wakefield's study project. As you pointed out it might not help Matthew, but if not hopefully it will be of benefit to others. There is also the chance that Matthew has a problem that can be detected and helped."

The mother of child 12 was the only parent to be called by the GMC. She said that she did not remember the conversation described in her letter. Professor Walker-Smith gave evidence that he remembered it in somewhat different terms. He explained to her what colonoscopy involved and its possible outcomes, including that nothing would be found. He told her that autistic children had not been studied to any degree and that their bowel problems had been rather dismissed as features accompanying a psychiatric illness  and that a normal result would be of interest as well as an abnormal result. In her letter to Dr. Wakefield, child 12's mother repeated her description of his soiling, but also spoke about her appointment with Professor Walker-Smith, who "took some blood from Matthew for analysis but did not feel sure that Matthew would need referring to yourself for further investigations. His main reasons were the absence of blood in the faeces and the lack of diarrhoea". She said that she did not think that she had stressed his symptoms sufficiently to Professor Walker-Smith.

"Some of the previous children I have had referred to me with autism have had clear cut gastrointestinal symptoms with quite severe abdominal pain and intermittent bleeding and we have gone ahead with our programme of colonoscopy and intensive investigation. However in (child 12's) case there is relatively minor gastrointestinal symptoms, I felt it right to perform a full blood count ESR, CRP".

To Dr. Wakefield, he wrote,

"It is interesting to see this child who really has the features of autism but rather minimal gastrointestinal symptoms. I did not feel it right in fact to proceed with our intensive programme at the moment until we have had ethical committee approval and it is clear that the parents wish us to proceed".

"I have now got back the blood tests. One was slightly abnormal. As I see that you are keen for us to proceed with investigation I think it would be appropriate for us to arrange for (child 12) to come in for a colonoscopy .The children are usually admitted for the course of a week and various other aspects of the protocol are undertaken".

A handwritten note on the letter states:

"'Go ahead and arrange colonoscopy for New Year".

Child 12's mother responded on 28th November 1996 confirming her agreement to the investigations going ahead and asking for an explanation of the blood test abnormality. Professor Walker-Smith responded on 27th December 1996, explaining that one of the markers of information was "just slightly above the normal range, it just means that we should go ahead".

"19a. You subjected child 12 to a programme of investigations as part of the project referred to at paragraphs 2b and 2c above,

Found proved. In reaching its decision that you subjected this child to a programme of investigations, the panel is satisfied with the evidence contained within the letter from (child 12's mother) to you of 20 October 1996, where she makes it plain that she had seen the "Proposed clinical and scientific study" and that she is "happy for (child 12) to be referred onto Dr. Wakefield's study project", and your response to her dated 25 November 1996, in which you state that as she is keen to proceed with investigation, you will arrange it, and the children are usually admitted for the course of a week and various other aspects of the protocol are undertaken. The panel also noted your letter dated 21 October 1996 to Dr. Wakefield in which you state "I did not feel it right in fact to proceed with our intensive programme at the moment until we have had Ethical Committee approval and it is clear that the parents wish us to proceed"

d. You caused child 12 to undergo a

i. colonoscopy,

Found proved

ii. barium meal and follow through,

Found proved

Which was not clinically indicated,

Found proved. The panel is satisfied that the slightly raised CRP, in conjunction with the overall clinical picture, did not warrant a colonoscopy or barium meal and follow through.

j. Your conduct as set out above was contrary to the clinical interests of child 12,

Found proved on the basis of the above findings."

Child 8

"21a. You subjected child 8 to a programme of investigations as part of the project referred to at paragraphs 2b and 2c above,

Found proved. In reaching its decision that you subjected this child to the programme of investigations, the panel noted that no clinician at the Royal Free had seen the child at outpatients prior to her admission. Your letter to child 8's mother, dated 3 December 1996 stated, "I have had documentation concerning child 8 and I have heard that you would like us to go ahead with the investigations I have arranged for her to be admitted the colonoscopy will be the next day other investigations will be arranged during the week.

d. You caused child 8 to undergo a,

i. colonoscopy,

Found proved

iii. barium meal and follow through,

Found proved

Which was not clinically indicated,

Found proved. The panel considered that there were minimal GI symptoms to warrant a colonoscopy at that stage. It also noted your own evidence (Day 94 B32) that if a colonoscopy was not clinically indicated, "then the barium meal and follow through is not.

j. Your conduct as set out above was contrary to the clinical interests of child 8,

Found proved on the basis of the above findings."

Child 7

"You subjected child 7 to a programme of investigations as part of the project referred to a paragraphs 2b and 2c above,

Found proved. The panel is persuaded by the evidence, in particular your letter dated 17 January 1997 to the child's GP, and copied to Dr. Wakefield, which states "he will be having other investigations as part of the protocol", together with the admission clerking notes in the Royal Free Hospital notes, which record that the child is undergoing "colonoscopy and investigations as part of the disintegrative disorder/colitis study" and under the heading "Plan" it states "Autism Protocol"."

The panel went on to find that the investigations were undertaken without the approval of the Ethics Committee because he did not meet the inclusion criteria  that he had been given MMR vaccine not measles or measles/rubella vaccine and had not been diagnosed with disintegrative disorder.

Child 10

"This colonoscopy was definitely abnormal, in probably a more striking example of the pattern seen in the cohort of the autistic children. The rectum showed definite mild abnormality, with a slightly granular mucosa and abnormal vascular pattern. Prominent lymphoid follicles could be seen throughout colon, with no other mucosal abnormality. The caecum showed an erythematous, granular mucosa around a swollen ileo-caecal valve, while the terminal ileum showed minor inflammatory change and striking lymphoid hyperplasia distally.

I suspect that the biopsies will show unequivocal abnormality!"

Perhaps surprisingly, the first undated histology report did not. A second report dated 19th February 1997 found minor abnormalities: confluent lymphoid aggregates in the biopsy of the ileum and a very subtle scattering of chronic inflammatory cells within the lamina propria in the large bowel. A lumbar puncture was performed on the 17th February 1997. Child 10 was seen by Dr. Berelowitz on 18th February 1997, who diagnosed an encephalitic episode which led to some low grade generalised brain damage. Dr. Casson's discharge summary dated 17th March 1997 recited the procedures and their results and recommended anti-inflammatory medication.

Conclusions to be drawn from the panel's findings in the Lancet children's cases

"The children described in the Lancet paper were admitted for research purposes under a programme of investigations for Project 172-96, the purpose of which was to investigate a postulated new syndrome following vaccination. The Panel rejected Professor Walker-Smith's contention that Project 172-96 was never undertaken. It found that Professor Walker-Smith, in an application for Project 172-96, to the Royal Free Hospital Ethics Committee, was named as a Responsible Consultant and thereby took on the shared responsibility for the research governance of the application; for ensuring that only children meeting the inclusion criteria would be admitted; that conditions attached to the Ethics Committee approval would be complied with; and that the children would be treated in accordance with the terms of the approval given. The Panel also concluded in accordance with expert evidence that Responsible Consultants who sign up to research are individually responsible and have a duty to ensure such research governance."

In respect of Child 2, 1, 3, 6, 9, 5, 12, 8, 7 and 10, the Panel found that Professor Walker-Smith subjected them to investigations as part of Project 172-96, a research project, without Ethics Committee approval, thus without the ethical constraints which safeguard research. The Panel further found that the investigations carried out on Child 2, 1, 3, 9, 5, 12 and 8 were contrary to his representations to the Ethics Committee that they were clinically indicated.

Ethical considerations are there to protect research subjects, to reassure the public and they are crucial to the public's trust in research medicine. The conditions for approval for Project 172-96 and the inclusion criteria for it were not complied with and thus the expectations of the Ethics Committee and their reliance on the probity of Professor Walker-Smith as a Responsible Consultant were not met.

In respect of the clinical care of the children, Professor Walker-Smith assessed nine of the Lancet children in the outpatients' clinic, prior to admission and all eleven children were admitted to hospital under his clinical care. The public is entitled to expect that patients entrusted to the clinical care of a doctor will be treated in accordance with their best clinical interests.

With regard to Child 2, 1, 3, 9, 5, 12 and 8, Professor Walker-Smith caused all seven of them to undergo colonoscopies that were not clinically indicated.

In respect of Child 2, 1, 3, 9, 5, 12 and 8 Professor Walker-Smith caused all seven to undergo barium meals and follow throughs which were not clinically indicated.

In respect of child 3 and 9, Professor Walker-Smith caused these two children to undergo lumbar punctures which were not clinically indicated.

In respect of Child 4, 9, 12 and 8, Professor Walker-Smith failed to record in the medical records the basis upon which their histological diagnoses were changed. He also failed to record the reason for a prescription in respect of Child 8, when the clinical histology report did not indicate a need for this medication. Good Medical Practice emphasises the need to record accurate and contemporaneous clinical findings and keep other colleagues well informed when sharing the care of patients. The Panel considered that this was a failing on Professor Walker-Smith's part which could lead to confusion in respect of the children's subsequent treatment.

In respect of seven of the Lancet children, 2, 1, 3, 9, 5, 12 and 8, Professor Walker-Smith's conduct was contrary to their clinical interests. The Panel is concerned that Professor Walker-Smith repeatedly breached the fundamental principles of research and clinical medicine. It concluded that his actions in these areas were sufficient to amount to serious professional misconduct."

The Lancet paper

"Conclusions of clinical study: we have identified significant gastrointestinal pathology in association with developmental regression in a selected group of previously, apparently normal children. In the majority there was a clear temporal association with possible environmental triggers. Anecdotally, children who were subsequently treated with standard therapy for inflammatory bowel disease had a mild marked improvement in both behavioural and intestinal symptoms."

"Conclusion the data are not proof of a causal association between measles virus and this syndrome: however, they are significantly provocative to merit further detailed study, in particular, to either establish or refute the possible association with MMR vaccine".

"Ethical approval: approval for these studies has been granted by the Ethical Practices Committee of the Royal Free Hampstead NHS Trust."

Dr. Berelowitz's comments appear to have been reflected in all subsequent drafts and in the final published article. The next draft was headed "Ileal-lymphoid-nodular hyperplasia, non-specific colitis and developmental disorder in children: a new syndrome?" A passage which dealt with the possible causal link with MMR vaccine stated

"It is important to note that the present study does constitute proof of an association between MMR and the syndrome described: detailed viralogical studies are underway that may help to resolve this issue .If there is a causal link with the MMR then a rising incidence might be anticipated following its introduction in 1988. Despite an impression of a rise in autistic spectrum disorders, published data are inadequate to determine whether there is a rising incidence or a link with MMR. The diagnosis of autism is usually made on symptoms starting in the first year of life, when children receive MMR. Despite the striking temporal association with MMR in many of these children, this factor must be taken into consideration when examining the apparent association described."

This draft contained a revised form of words about ethical approval:

"This clinical investigation has been approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust."

"Ethical approval and consent

Investigations were approved by the Ethical Practices Committee of the Royal Free Hospital NHS Trust, and parents gave informed consent."

This statement was untrue and should not have been included in the paper.

"In eight cases the onset of behavioural problems had been linked, temporally, with MMR vaccination, either by the parents or by the child's physician. Five of these eight had suffered an early adverse event, including rash, fever, delirium and, in three cases, convulsions. In those children in whom a precipitating event was reported by the parents, the average interval from exposure to first behavioural symptom was 6.3 days (range 1-14 days). Parents were either less clear or unclear about the timing of onset of intestinal features firstly, because children had not achieved toilet training at the time that symptoms first appeared, and secondly, because behavioural features indicative of, for example, abdominal pain only became evident to parents with time, since children were unable to communicate symptoms directly."

The published paper stated,

"In eight children, the onset of behavioural problems had been linked, either by the parents or by the child's physician, with measles, mumps, and rubella vaccination. Five had had an early adverse reaction to immunisation (rash, fever, delirium; and, in three cases, convulsions). In these eight children the average interval from exposure to first behavioural symptoms was 6.3 days (range 1-14). Parents were less clear about the timing of onset of abdominal symptoms because children were not toilet trained at the time or because behavioural features made children unable to communicate symptoms."

The charges accurately summarised that passage as follows:

"The Lancet paper purported to identify associated gastrointestinal disease and developmental regression in a group of previously normal children which was generally associated in time with possible environmental triggers which were identified by their parents in eight cases with the child's MMR vaccination."

This paraphrase was admitted and found proved.

"29 .

c in the circumstances set out at paragraph 29b above, [i.e. the public health implications of the paper] and as one of the senior authors of the Lancet paper, you

i. knew or ought to have known of the importance of accurately and honestly describing the patient population,

Found proved

30a. You failed to state in the Lancet paper that the children whose referral and histories you described were part of a project, the purpose of which was to investigate a postulated new syndrome comprising gastrointestinal symptoms and disintegrative disorder following vaccination,

Found proved on the basis that the children who were described in the paper were admitted under a programme of investigations under Project 172-96 for research purposes.

b. Your conduct as set out at paragraph 30a was,

i. dishonest,

Found not proved. The panel concluded that your actions were not premeditated and you did not intend to be deliberately dishonest. It noted that you did not write or see the final draft of the paper and considered that you had been naïve in your lack of thoroughness regarding the paper submitted to the Lancet. [Both sides accept that the reference to naivety was a reference to the conclusion of the panel and not to any evidence given by Professor Walker-Smith].

ii. Irresponsible,

Found proved. The panel considered that you as a senior author should have checked the validity or otherwise of the paper. You said you were given the second draft but did not see the final one. The panel concluded that your conduct as a senior clinician and senior author was irresponsible.

iii. Resulted in a misleading description of the patient population in the Lancet paper;

Found proved

31a. The Lancet paper stated that the children who were the subject of the paper were "consecutively referred to the department of Paediatric Gastroenterology with a history of a pervasive developmental disorder with loss of acquired skills and intestinal symptoms (diarrhoea, abdominal pain, bloating and food intolerance)" and subsequently described them as a "self-referred group",

Admitted and found proved.

b. You knew or ought to have know that such a description, implied,

i. A routine referral to the Gastroenterology Department in relation to symptoms which included gastrointestinal symptoms,

Found proved

ii. A routine process in which the investigators had placed no active part,

Found proved

The panel took into account the article in the Lancet (Volume 350 October 4 1997) "Writing for the Lancet"  "It is a general reader whom you are trying to reach". The panel is satisfied that a general reader would interpret the wording in 30a [in fact 31a] to mean that children were referred to the Gastroenterology Department with gastrointestinal symptoms and that the investigators had played no active part in that referral.

32a. Contrary to paragraph 31b(i) the referrals of,

i. Child 1 as set out at paragraph 6a and 6b

Found proved

ii. Child 9 as set out at paragraphs 14a  14c

Found proved

iii. Child 5 as set out at paragraphs 16a-16b

Found proved

iv. Child 10 as set out at paragraphs 24a and 24b

Found proved

Did not constitute routine referrals to the Gastroenterology Department in relation to intestinal symptoms as the referring doctors referred the children for investigation of the role played by the measles vaccination or the MMR vaccination into their developmental disorders and did not report any history of gastrointestinal symptoms,

Having regard to its findings in relation to child 1, 9, 5 and 10 namely that these children were admitted to undergo a programme of investigations for research purposes, and that they all lacked a history of gastrointestinal symptoms, the panel is satisfied that these referrals did not constitute routine referrals to the Gastroenterology Department.

b. Contrary to paragraph 31b(ii), the referrals, of,

i. Child 2, as set out at paragraph 4e,

Found not proved. At the end of the first assessment of the child, you said you would be happy to see the child again should the need arise. The panel accepted that you wrote to child 2's mother on 16 May 1996, offering to see child 2 again, in response to her telephone call saying that her child's symptoms had worsened.

ii. Child 9, as set out at paragraph 14a,

Found proved. The panel is satisfied that your letter to Dr. Spratt the paediatrician, asking if it was appropriate to investigate child 9 in the protocol, was tantamount to an express invitation for the child to be seen by you.

Involved your express invitation for the child to be seen by you

c. The description of the referral process in the Lancet paper was therefore,

i. Irresponsible

Found proved

ii. Misleading

Found proved

iii. Contrary to your duty to ensure that the information in the paper was accurate,

Found proved

In reaching its decision the panel concluded that your description of the referral process as "routine" when it was not, was irresponsible and misleading and contrary to your duty as a senior author."

"We describe a pattern of colitis and ileal-lymphoid-nodular hyperplasia in children with developmental disorders. Intestinal and behavioural pathologies may have occurred together by chance, reflecting a selection bias in a self-referred group; however the uniformity of the intestinal pathological changes and the fact that previous studies have found intestinal dysfunction in children with autistic-spectrum disorders, suggests that the connection is real and reflects a unique disease process."

The general reader of that paragraph would note the author's caution about the possibility of selection bias in the self-referred group. Taken together with the comments already cited made about the temporal coincidence of the onset of symptoms and MMR vaccination in the case of eight children, the author has made it clear that this was not a routine referral. It was a referral generated by the concerns of parents about a possible link. The statement made by the panel in paragraph 32c that it was Professor Walker-Smith who had described the referral process in the Lancet paper as "routine" was wrong. It put its stretched meaning of the wording of part of the paper into his mouth and then found that it was irresponsible and misleading. This was not a legitimate finding.

Transfer Factor and child 10

"After due consideration we would like to start (child 10) on measles-specific Transfer Factor and we are prepared to take full responsibility for the outcome of this treatment.

The supplies of the drug are presently in our hands (Dr. Wakefield) and will be deposited with pharmacy later this week when he returns from Birmingham."

Nothing further happened until on 9th September 1997 Dr. Wakefield wrote to Dr. Geoffrey Lloyd, Chairman of the Medical Advisory Committee, a letter which has not been preserved. Dr. Lloyd replied:

"I am prepared to give you chairman's approval for the use of Transfer Factor for the patient you referred to in your letter of 23 July, namely, (child 10). This should be used on "a named patient basis."

"Over Christmas + New Year we felt very optimistic about the apparent effect of Transfer Factor  there seemed to be such a noticeable change in child 10 but this week we feel pessimistic."

From this answer, the panel drew the justifiable conclusion that child 10 had taken Transfer Factor over Christmas and the New Year 1997/8.

"26a. In or about December 1997 you started child 10 on a substance called Transfer Factor,

Found not proved.

The panel accepted your evidence that you did not, and has seen no evidence to support this allegation."

(Paragraphs 26b  e dealt with the admitted approval of the application made in 1998).

"27a. You inappropriately caused child 10 to be administered Transfer Factor,

Found proved. The panel is persuaded that child 10 was administered Transfer Factor by the weekly diary card completed by his mother, submitted to the Royal Free Hospital in January 1998 which states, "Over Christmas and New Year we felt very optimistic about the apparent effect of Transfer Factor is it possible that the dose now needs to be increased?" The panel concluded that you caused the child to be administered with Transfer Factor on the basis of the letter of 23 July 1997 that you and Dr. Wakefield wrote to the dispensary manager. You informed her "that we would like to start child 10 on measles-specific Transfer Factor and we are prepared to take full responsibility for the outcome of this treatment. The supplies of the drug are presently in our hands (Dr. Wakefield)." Further, Dr. Wakefield sought permission from the Medical Advisory Committee by a letter dated 9 September 1997 for child 10 to be administered Transfer Factor on a named patient basis as is evidenced by the approval letter dated 15 September 1997 sent to him and copied to you, by its Chairman, Dr. Lloyd.

i. For experimental reasons,

Found proved. The panel is persuaded that this was experimental treatment and not given for clinical reasons, because you had not seen or assessed the child before causing him to be administered with the unlicensed drug and you stated "We do not know whether the treatment will work" in your letter to the dispensary manager of the pharmacy, dated 23 July 1997, jointly signed by you and Dr. Wakefield. You also state within the letter, "We are prepared to take full responsibility for the outcome of the treatment".

ii. Prior to obtaining information as to the safety of prescribing Transfer Factor to children,

Found not proved. The panel has noted the letter dated 23 July 1997 to the dispensary manager from you and Dr. Wakefield, in which you refer to about 300 peer-reviewed scientific publications on the use TF and state that this substance was safe.

iii. Prior to obtaining ethical approval for a clinical trial of Transfer Factor,

Found not proved. The panel has taken into account the letter dated 15 September 1997 from Dr. Lloyd to Dr. Wakefield and copied to you, giving chairman's approval for the use of Transfer Factor to child 10 on a named patient basis. The panel is therefore satisfied that obtaining ethical approval for a clinical trial for this child was not relevant in December 1997.

iv. Without,

a. Recording the fact of or dose of prescription in child 10's medical records,

Found proved. Despite the application form to the Ethics Committee signed by you on 30 January 1998, stating "Anecdotally we have started one child on an approved compassionate basis he has tolerated therapy for one month so far", the panel noted that there is no evidence of any notes nor a recording of this child being seen

b. Informing child 10's general practitioner that child 10 had been prescribed it,

Found proved. The panel concluded an essential requirement of a doctor is to share information with colleagues in the ways the best serves patients' interests. The child's GP did not have knowledge of any prescription of TF other than that contained in a letter from a Consultant Community Paediatrician. You did not inform the GP nor did you arrange for someone else to do so.

c. Recording in child 10's medical records the fact and nature of any discussion as to the risks and benefits of the prescription with child 10's parents,

Found not proved. The panel noted your evidence that after this child was discharged from hospital on 19 February 1997, you did not see the child again and therefore had no opportunity for discussion with the parents of child 10 concerning the prescription and could not have recorded it.

b. Your actions as set out above were,

i. Irresponsible,

Found proved

ii. Contrary to the clinical interests of child 10

Found proved [on the basis of the findings at 27a(i), 27a(iv)a and b]."

Child JS

"Through Dr. Wakefield we have been looking at a group of children with autistic symptoms related to MMR vaccine and have found that a significant number of children have had gastrointestinal symptoms. When these have been present we have so far found endoscopic abnormalities in all five children we have investigated. I would be quite happy to see (child JS's parents) and to discuss the situation with them and to indicate what investigations might be appropriate and then get your advice as to the right for us to proceed ".

Dr. Mills replied on 15th November 1996, stating that he did not consider that child JS was appropriate for the investigation schedule recommended by Dr. Wakefield and that he did not think that "your research programme is appropriate for him at present". He concluded,

"I am beginning to wonder whether you and your department are rather pressurising this family and I would request this to stop".

Professor Walker-Smith replied on 22nd November 1996,

" I can quite understand you feeling that it may not be appropriate for us to see (child JS) at the moment. However I would be happy to hear from you again should the position change.

In relation to your last comments, I am certainly doing nothing to pressure the family to see us. In fact my department is somewhat overwhelmed by the response of parents who believe that their children have autistic and gastrointestinal symptoms following MMR. I personally had no idea that there were such large numbers of patients in the community across the country where the parents had made this association "

On 8th January 1997, Dr. Wakefield wrote to Dr. Mills, copied to Professor Walker-Smith, expressing his indignation at the suggestion that the family were being pressurised. Dr. Mills replied on 12th February 1997, reiterating his view that the programme of investigations would not benefit child JS at present.

"We have begun to have some quite remarkable success in treating children with autism and evidence of bowel inflammation with sulphasalazine [an anti-inflammatory] and related drugs. I do believe it really would be helpful for us to do these investigations in [child JS] or for me to at least see the child to assess the situation. I enclose a copy of our protocol and would be grateful if you would reconsider this issue once more."

The "protocol" was that sent to Dr. O'Connor on 6th February 1997 (to which reference is made under the heading "Facts negating the proposition paragraph (v)), not Project 172-96. As its title indicates, it was concerned with "The rationale, aims and potential therapeutic implications of the investigation of children with classic autism or the autistic spectrum disorder who have gastrointestinal symptoms". Its text set out what the study hoped to achieve:

"The purpose of this preliminary clinical study is, firstly, to adequately and appropriately investigate the gastrointestinal signs and symptoms manifested by these children: investigation is merited on clinical grounds. It is our experience that these clinical features often have been ascribed to the inevitable consequence of behavioural abnormalities upon bowel function, and as a consequence the children have not necessarily been investigated adequately. It should be stressed, therefore, that the investigations are clinically indicated in all cases that are admitted for evaluation. The validity of this approach is borne out by the fact that most children investigated so far has significant and consistent intestinal pathology (lymphoid-nodular hyperplasia and microscopic colitis). Secondly, the purpose of the study is to seek the presence, and characterize the nature, of any intestinal and cerebral pathologies in affected children. In view of the coincident changes in both behaviour and intestinal symptoms we believe that this form of regressive autism, and perhaps other behavioural problems within the autistic spectrum, may be linked to chronic intestinal inflammation.

It is our aim to investigate and institute appropriate therapeutic measures aimed at controlling the intestinal inflammation and correcting any nutritional deficiencies that may be present. The impact of these measures on behaviour will be monitored. Preliminary experience has shown that mesalazine or enteral nutrition may have significant benefit in some cases.

Finally, we hope that the possible role of MMR will be elucidated and that further insights into the pathogenesis of regressive and classical autism will be provided."

"The success that we have had with treating autistic children is an unexpected secondary aspect of our study, we had expected improvement with the gastro-intestinal symptoms with use of 5 ASA derivatives and salazopyrine, but we had not expected the parents to tell us that there had been such an improvement in behaviour. We are in fact with the help of Dr. Mark Berelowitz, planning a further study to analyse the successes but our work at the moment has been to provide a diagnostic service to determine the gastro-enterological manifestations of these children .

My own position in this work is entirely responsive, when I transferred from Barts to the Royal Free I was quite sceptical about the research work of Dr. Andy Wakefield, but since I came here it is absolutely obvious to me that there is a large unmet need of children with autism who have a variety of GI symptoms ranging from quite mild symptoms to quite major ones. The unexpected outcome of this research has led us to being very interested in the treatment of these drugs

I am myself not soliciting for patients to be referred to us, but I am reacting to the parent's requests."

"I think it is essential that this child does have a colonoscopy. This kind of service is just not available elsewhere for children with autism and for the special investigations which Dr. Wakefield can offer."

"Elective admission for colonoscopy

Probs

1. Autism

2. Intermittent diarrhoea

Without blood, but with occasional mucous."

The endoscopy report, misheaded "Endoscopy clerking sheet" dated 13th November 1997, records the reason for the procedure as: "Autistic" and Dr. Thomson's findings as

"an ? vascularity in recto-sigmoid area to SPL. Flexure

? ? granularity around caecum, +/- ? vascularity

Lympho-nodular hyperplasia of TI".

The histology report, added on 21st November 1997, noted no active inflammation in the ileum, but patchy changes in the colon, lymphoid aggregates in the caecum and active cryptitis in the transverse and sigmoid colonoscopy, characterized in the histology report itself as "of a mild patchy non-specific acute colitis". At his ward round on 14th November 1997, Dr. Thomson suggested anti-inflammatory treatment. The discharge summary dated 27th November 1997, set out the findings noted above. A handwritten amendment in Professor Walker-Smith's writing stated:

"Histology revealed active inflammation of the distal colon with patchy active cryptitis (with eosinophils neutrophils) and crypt abscesses formation. There was lymphoid-nodular hyperplasia of the terminal ileum."

"36a. You subjected child JS to a colonoscopy,

Found proved. The panel noted the letter to the Deputy Contracts Manager of the Royal Free Hospital on 10 November 1997 where you stated that "It is essential that this child has a colonoscopy".

i. In reaction to parental pressure,

Found not proved. There was insufficient evidence to find that the colonoscopy was undertaken as a direct consequence of parental pressure and it accepts you evidence that it was not.

ii. Without any proper consideration to your duty to treat him in accordance with his best interests,

Found proved. The panel noted that the parent's concern was regarding the child's presenting with behavioural difficulties rather than GI symptoms because the child was at the time well-nourished and had improved bowel motions. A colonoscopy was undertaken without proper consideration of his current clinical presentation.

iii. For the purposes of yours and Dr. Wakefield's research into a purported association between gastrointestinal symptoms, autistic symptoms and the MMR vaccine,

Found proved. The panel noted the letter dated 6th November 1996 from Dr. Wakefield to you stating that "This is a child I would like to be included in our study " together with the letter dated 7 November 1996 from you to the Community Paediatrician stating, "Through Dr. Wakefield we have been looking at a group of children with autistic symptoms related to MMR vaccine and have found that a significant number of children have had gastrointestinal symptoms." You wrote to the Deputy Contracts Manager of the Royal Free Hospital on 10 November 1997, saying "I think it is essential that this child does have a colonoscopy. This kind of service is just not available elsewhere for children with autism and for the special investigations which Dr. Wakefield can offer" and the panel also noted the admission note dated 13 November 1997 which notes an "elective admission for colonoscopy".

v. Which was not clinically indicated,

Found proved. The panel concluded that subjecting the child to a colonoscopy was not clinically indicated as his main presentation was behavioural difficulties and you accepted his GI symptoms were "rather minor" in your letter to the Community Paediatrician on 31 July 1997. In your evidence to the panel you accepted that you did "lower the threshold" in relation to this child. (Day 96 p15)

b. Your conduct as set out above was contrary to the clinical interests of child JS,

Found proved on the basis of the above findings."

Conclusion