GENERAL MEDICAL COUNCIL
FITNESS TO PRACTISE PANEL (MISCONDUCT)
Friday 28 March 2008
Regents Place, 350 Euston Road, London NW1 3JN
Chairman: Dr Surendra Kumar, MB BS FRCGP
Panel Members: Mrs Sylvia Dean
Ms Wendy Golding
Dr Parimala Moodley
Dr Stephen Webster
Legal Assessor: Mr Nigel Seed QC
CASE OF:
WAKEFIELD, Dr Andrew Jeremy
WALKER-SMITH, Professor John Angus
MURCH, Professor Simon Harry
(DAY FORTY-NINE)
(Transcript of the shorthand notes of T. A. Reed & Co.
Tel No: 01992 465900)
A P P E A R A N C E S
MS SALLY SMITH QC and MR CHRIS MELLOR and MR OWAIN THOMAS of counsel, instructed by Messrs Field Fisher Waterhouse, solicitors, appeared on behalf of the General Medical Council.
MR KIERAN COONAN QC and MR NEIL SHELDON of counsel, instructed by Messrs RadcliffesLeBrasseur, Solicitors, appeared on behalf of Dr Wakefield, who was not present.
MR STEPHEN MILLER QC and MS ANDREA LINDSAY-STRUGO of counsel, instructed by Messrs Eastwoods, Solicitors, appeared on behalf of Professor Walker-Smith, who was present.
MR ADRIAN HOPKINS QC and MR RICHARD PARTRIDGE of counsel, instructed by Messrs Berrymans, Solicitors, appeared on behalf of Professor Murch, who was present.
I N D E X
Page No
ANDREW JEREMY WAKEFIELD, Recalled
Examined by MR COONAN, Continued 1
THE CHAIRMAN: Good morning, everyone.
MR MILLER: Sir, Professor Walker Smith has had to see his doctor this morning to have a blood test. He is going to come as soon as that is completed and will probably be here within the next hour.
THE CHAIRMAN: Have you his permission for us to proceed in his absence?
MR MILLER: Yes.
THE CHAIRMAN: In that case, I do not see any difficulty. Mr Coonan, you were in the middle of your examination in chief.
ANDREW JEREMY WAKEFIELD, Recalled
Examined by MR COONAN, Continued
Q I was midway through section 5 of the index. Dr Wakefield, there is one matter I want to complete. If you turn back to your Panel bundle, volume 1, please, and turn to the pages running from 200 to 235. On page 202, you were dealing yesterday with the source material for the series of paragraphs set out there under the heading of “Disintegrative Disorder (Heller’s disease)” and you indicated that that came from Professor Sir Michael Rutter’s textbook, which you had read.
A Correct.
Q For completeness, I am going to ask that that extract be produced, please, so the Panel can see that source material.
MS SMITH: The entire chapter is in fact already before the Panel.
MR COONAN: I would like it to be part of the defence bundle. It should be inserted as tab 11 of D2. (Same distributed)
THE LEGAL ASSESSOR: Mr Coonan, it might be helpful to have a cross-reference if it is elsewhere, in case the Panel has made notes on their copies.
MR COONAN: That is very sensible. Perhaps Ms Smith could tell me the reference.
MS SMITH: It is FTP5 ---
MR COONAN: It is FTP6, tab 41. Mr Sheldon supplied me with the reference.
MS SMITH: I am told by Mr Thomas it is tab 40, page 460A.
MR COONAN: It is tab 41 in our bundle.
MS SMITH: It is page 460A in FTP6 and in my bundle, like Mr Sheldon’s, it is at tab 41, but I have to say in my junior’s bundle it is at tab 40. So that is a confusion. I apologise for it, but if you have FTP6 at page 460A, you will be able to find it.
THE CHAIRMAN: Thank you.
MR COONAN: Might the extract which Dr Wakefield has produced go into tab 11, please? (To the witness) Dr Wakefield, can I just take you to the extract which you have produced and ask you to turn to page 581? There is a heading halfway down the right-hand column “Disintegrative disorder”. Can I take this very quickly? Is that the section which was the source basis of the material in volume 1, page 202?
A Yes. Certainly for the majority of it, yes, it was. You will see further references at the bottom for a great majority.
Q You can put that extract to one side now, please. I want to turn to a different topic within the application itself. At page 201, under the heading “Design of the Study”, there are two aspects to this which I would like your assistance with, please. The first is part of the wording in the first five lines under paragraph 4 and the second topic, which is rather a larger one, concerns the nature of the investigations set out. Can I deal with the first point first? You will see in the text on the fourth line of paragraph 4, it says:
“With fully informed parental consent, children will undergo the following investigations in an attempt to characterise the intestinal and cerebral pathologies that potentially underly this condition.”
If you bear in mind that specific text, “children will undergo”, together with the structured series of investigations laid out on the grid on page 231, the question I want to ask you is this. So far as you are concerned, did this document indicate that these children would undergo all the investigations in this document inevitably? In other words, willy-nilly?
A No, it did not.
Q What did it mean?
A It meant that there were a series of clinically indicated investigations and a series of research investigations which would be explained by Professor Walker-Smith to the parents. The parents would then provide or not their fully informed consent for those respective investigations and then they would be conducted according to the clinical indication in that particular patient.
Q When you say “according to the clinical indications”, what does that mean as far as you are concerned?
A It meant that according to the judgment of the clinicians as to whether a child needed a particular investigation or not, then that would be the advice given to the parent.
Q Let us move on to the investigations. On page 201, there are in bullet point form a series of investigations, somewhat compressed in linguistic terms. Do you accept that?
A Yes.
Q Keep a finger in that page and turn to pages 221, 222 and the top of 223. Again, quite apart from anything else, which we will turn to for another reason later, that sets out a series of investigations.
A Yes.
Q What is the relationship between page 201 on the one hand and pages 221, 222 and 223 on the other?
A As you have pointed out, the description is rather compressed, necessarily, on page 201 and this is expanded upon to some extent in the three pages in the full protocol.
Q To complete the pagination relevant to this topic, could you turn to page 209? Under paragraph 11 on that page, the heading deals with “Procedures or Samples to be taken from Subjects”. The subheading is:
“Would the procedure(s) or sample(s) to be taken, especially for this investigation, or as part of normal patient care.”
Then this piece of text. Dr Wakefield, are these your words, as drafted initially at least?
A This will be a consensus statement from the senior investigators, including myself, yes.
Q Let us look at the terms. The answer to the question is:
“Yes: in view of the symptoms and signs manifested by these patients, all of the procedures and the majority of samples are clinically indicated. Additional intestinal biopsies (5 per patient) will be taken for viral analysis. DNA for genotyping will use blood cells isolated from the routine blood sample, and will not require an additional sample.”
In general terms, before we look at the detail of the investigations themselves, can you deconstruct that linguistically for us?
A What it is seeking to clarify for the lay members in particular of the ethics committee, but all members in general, is that these tests, these clinical tests, are being undertaken for clinical purposes in the individual child and that the research will require extra biopsies to be taken during the clinical procedure of colonoscopy for the purposes of laboratory investigation. In addition, blood cells from the routine sample will be processed further as part of the research programme. So setting out very clearly that all of the investigations are being done as part of the clinical investigation of the child and that research is an adjunct to that.
Q The exercise that I want you to do, please, to assist the Panel, is based upon pages 201 and 221 and 223. I think you have prepared for our assistance, to elucidate and illustrate your evidence, a schedule setting out each of these investigations with the comment that you seek to make to the Panel about them. Is that right?
A Correct.
Q It is yourself who has prepared this document?
A It is.
MR COONAN: Sir, I invite you to receive this document and Dr Wakefield can speak to it.
THE CHAIRMAN: Is this going to go into the bundle?
MR COONAN: Yes, it is. It will be D2, tab 12. (Same handed) Can we just look at the structure of the document for the moment, and in the interests of speed and efficiency, perhaps I can just comment and you agree or disagree with it, looking at the first page, have you listed in the left-hand column each of the investigations which have been listed in the EC application document?
A I have.
Q In the extreme right-hand column have you put the page reference number ---
A I have.
Q --- where you can find the investigation set out?
A Yes.
Q In the right-hand column you can see there are page references either to page 201 or to page 222 or to page 223, if you look over the page, and sometimes the investigation is set out on both pages, is that right?
A Yes.
Q The first page deals with what you describe as “clinical tests” and on the second page – and we will hear your evidence about this – what you say are the research tests, underneath the black line halfway down the page, is that right?
A Yes.
Q In looking at the document on the first page, apart from the nature of the test you raise the question whether in your opinion EC approval was required, and you give an answer; you raise the question whether in fact the test was ultimately performed, is that right?
A Yes.
Q In the middle column you describe the methodology involved in the test; in the next column on the right you set out the purpose of the test, and as I say, then you deal with the reference: is that the general structure of the form?
A Correct.
Q To save time, I am not laboriously going to turn up the corresponding entry on the page, I am going to take them as a subject as the individual examination or investigation and ask you to comment. The first matter concerns a full history and clinical examination, and there is a reference to that on pages 201 and 221. In relation to this study, which was submitted to the ethical committee was ethical approval for that required?
A No.
Q Tell the Panel, please, about the methodology?
A This is, as I am sure many members of the Panel are well aware, the starting point for clinical assessment of any patient, and that is a full history and examination, and is entirely a clinical matter.
Q The next test, colonoscopy, ileoscopy and biopsy. Can we just break those down again, it is a long time since we looked at these in detail? Colonoscopy and ileoscopy, remind us of those two techniques, please?
A This is, in effect, a telescopic technique for looking at the lower bowel, including visualisation and biopsy of the last part of the small intestine just as it enters into the large intestine.
Q Then that would be placed in formalin and frozen for the purposes of examination under the microscope?
A Correct.
Q So far as that investigation is concerned, was EC approval required in your view?
A You will see that the text that is used is taken directly from the protocol itself, and the routine conduct of colonoscopy, ileoscopy and biopsy does not require ethical approval.
Q As a matter of fact, were those investigations performed on the children that we are going to look at later on?
A Yes.
Q The purpose of carrying out these investigations, as you understand it from a clinical standpoint, is what?
A It was to identify the origin of the child’s symptoms, and particularly to exclude the presence of inflammation or inflammatory bowel disease such as Crohn’s or colitis.
Q The next investigation was the upper gastrointestinal endoscopy and a small bowel biopsy: the first is this, it may be obvious but I want to be absolute clear about it, to what extent does that differ from the one in the previous box?
A This is a similar technique but it is used to visualise and biopsy the upper gastrointestinal tract, including the oesophagus, the stomach, the duodenum and sometimes the first part of jejunum.
Q Again, if that is carried out for clinical purposes, does that require EC approval?
A No.
Q Histology: just remind us, please, what histology is?
A This is the examination of tissues taken from patients under the microscope for the purpose, in this case, of diagnosing disease.
Q Again, is EC approval required for that?
A No.
Q A barium follow through: again, we can ask the clinicians about this but from your standpoint what do you understand that to involve?
A This is an X-ray technique where the patient swallows a contrast medium that outlines the anatomy, if you like, of the small intestine, and particularly that which is not visible, not accessible by the colonoscope or the upper gastrointestinal endoscopy.
Q Again, is EC approval required for that?
A No.
Q The modified Schilling test: can you explain what that is?
A This is a method using a radio isotope for determining the ability of the small intestine to absorb vitamin B12.
Q Was EC approval required to carry that test out?
A No.
Q You have noted that it was performed but only on Child 2, is that right?
A Correct, yes.
Q We will look at Child 2 in due course. Lumbar puncture: a lumbar puncture is carried out, is it, to obtain cerebrospinal fluid?
A That is correct.
Q There are three aspects of this I want to ask you about: first, the biochemical analysis for protein, sugar and lactate, what is that designed to discover?
A It is not an area of my particular expertise at all but there is a routine process for analysing cerebrospinal fluid in order to detect, for example, the presence of inflammation related to the brain or the spinal cord and the possibility of infection in the brain or spinal cord or the cerebrospinal fluid. Lactate, as I mentioned yesterday, is a test which was introduced from the Birmingham Children’s Hospital protocol by Dr Mike Thomson for the purpose of detecting or excluding a mitochondrial cytopathy in the central nervous system.
Q As you understood it, if carried out for that purpose would that require EC approval?
A No.
Q What about the next purpose that you have listed there under the heading of lumbar puncture?
A This is the microscopic analysis of the cerebrospinal fluid, that is looking under a microscope at a preparation of cerebrospinal fluid and again this assists in the diagnosis in particular of infection, and an abnormality in the number of immune or inflammatory cells that might be present.
Q If, as you understood it, a lumbar puncture is carried out for that purpose, would that require EC approval?
A No.
Q Finally, under this category, antibody analysis of the CSF, can you help us about that?
A Yes, if the antecedent history of the child indicates that they underwent neurological deterioration following a viral exposure, for example, then it is pertinent to examine the spinal fluid for the presence of viral antibodies, and this is referenced again in the Birmingham Children’s Hospital protocol, and other references can be provided as necessary, and the two viruses that one was particularly concerned with because of their propensity to infect and cause problems in the central nervous system were measles and rubella.
Q As you understood it, if that were being carried out for clinical purposes would that require EC approval?
A No.
Q MRI, help us about the purpose for that?
A Again, it is not an area of my expertise but in essence this is used in order to detect structural abnormalities of the brain and spinal cord – particularly in the brain in this instance – by using high resolution imaging technology.
Q Did you understand EC approval to be required for that?
A No.
Q Finally under this section, the EEG and also visual, somato-sensory and brainstem auditory evoked potentials, and we will see reference to that as we go through things later, you set out the purpose there in the right-hand column: was that a clinical test as you understood it?
A Yes.
Q That being the case, would EC approval be required?
A No.
Q Dealing with the blood tests, there is a series of biochemical tests that can be carried out. I am just going to take them for the moment compendiously, what was the purpose of carrying out those blood tests on samples?
A As I understand it, there is a series of routine biochemical and haematological blood tests which are used as a general screen for a patient’s wellbeing, the presence of inflammation, disturbances in the biochemical and metabolic balance of the body, reasons for possible developmental regression in a child, such as abnormalities of thyroid function, and those are part of the routine clinical screening.
Q Would ethical committee approval be required for those to be carried out?
A No.
Q Haematology: detection of blood cell abnormalities and inflammation, just help us about that in so far as it is necessary, please?
A Similarly, and as the Panel will have heard before, there are blood tests which help in the detection and screening for possible inflammatory conditions such as Crohn’s disease, ulcerative colitis and others and that can often, although not invariably, be picked up in the blood.
Q Over the page, you deal with the reference to viral studies. That is a reference we can see on pages 201 and 221, which you have captured in the right-hand column. You will have to help us, please, with these terms. What do you mean by “viral studies”?
A These are studies determined to detect either the presence of the virus, or, in this instance, the host’s immune response to the presence of the virus, looking for evidence of abnormalities of that response which might indicate the continued presence of the virus or a pathological response to it.
Q Those studies, as you understood it that is, were they being carried out on an individual patient for clinical purposes?
A Yes.
Q That being the case, would ethical committee approval be required?
A No.
Q Immune profiling: just help us with that as an umbrella term, please?
A Yes, this is an examination of the blood for any abnormalities of immune cells or antibody levels generally.
Q It was included, as we can see on pages 201 and 221: was that a reflection of a clinical test as you understood it?
A Yes, it was, it is something in which the paediatric gastroenterologists were particularly familiar and expert and it was included as part of the routine profiling of their children with suspected inflammatory bowel disease.
Q Then urine tests: you have described it as a spot sample and urinary MMA excretion: can you help us about that?
A Again, this is not an area in which I have any expertise at all but methyl myelonic acid is a metabolite associated with vitamin B12 and abnormalities particularly detectible in a spot urine sample, that is a single random urine sample, from a patient can assist in the diagnosis of the presence or absence of an abnormality of vitamin B12 metabolism and it is a valuable clinical test in the screening of a child who has undergone neuro-developmental regression.
Q And then stool tests.
A Yes, in children or adults presenting with gastrointestinal symptoms, prior to conducting further studies, often the history is indicative, a stool test for screening for pathogens, amoeba, for example, by microscopy or other tests, is routine.
Q Again, in relation to that and the previous matter, I do not think I formally asked you, would EC approval be required for those?
A No.
Q I want to come on now to what you, in anticipation, describe as “Research tests”, and we see that under the heading of “intestinal biopsy research” there are references in the right-hand column on page 221 to histology, and we see that on the first page of this document, in the fourth column down, there was also a reference to histology. Why is histology captured under this heading of “Research tests” with the source reference at page 221? What is the difference between the two?
A Standard routine histopathology is involved in the clinical diagnosis of disease in these children. Dr Paul Dhillon as part of his contribution to this decided at a relatively early stage that, in light of the findings in these children, in light of the apparent novelty and subtlety of some of the changes, a pro forma driven analysis would be necessary in order to provide a semi quantitative estimate of what was going on in their intestine, and to this end he designed a histology pro forma which could be scored as, for example, zero for no inflammation; one for mild inflammation; two for moderate inflammation, and three for severe inflammation, and he took the various categories of changes in the intestine and set them out under those numbers, normal, mild, moderate and severe. And that was used in a detailed histopathological review by Dr Dhillon and Dr Anthony, principally, with me looking over their shoulders to learn, and that formed the basis of the research histopathology.
Q So we have, is this right, Dr Wakefield, a strata of clinical histopathology but also a strata of research histopathology?
A Correct.
Q And, in respect of the strata of research histopathology, would that require EC approval?
A Yes.
Q I shall return to this later, but let’s move down the columns. Immunohistochemistry for measles virus protein, N protein and rubella virus. Just help us about that.
A Immunohistochemistry is a term we will return to again and, therefore, it merits explanation. This is a technique which uses a section, just like a histological section of a tissue, cut from a biopsy, and applied to it is a re agent, a chemical, which is specific for a protein that may be within that tissue, for example, a measles virus protein, or a rubella protein, or a host protein associated with a particular cell type, and those re agents are now referred to as polyclonal or monoclonal antibodies. A polyclonal antibody binds to more than one protein; a monoclonal antibody binds to a single protein, and those re agents, those chemicals, are applied to the tissue and the reaction is developed so it develops, for example, a colour, brown or red, that when visualised under the microscope can tell the pathologist whether that protein, for example, measles, is present or absent.
Q Was the immunohistochemistry from your standpoint to be treated or considered as a routine clinical test?
A No. In this context it was a research test.
Q The next one is RNA extraction from frozen biopsies and amplification of measles and rubella RNAs. Now, again, this is the prose taken from the page reference. Can you deconstruct that for us?
A Yes, I will try. Immunohistochemistry looks for, for example, viral protein. This technique goes one stage further and looks not for the protein but for the gene of the virus, in this case, or various host genes, but let us stick with measles to save confusion. What this technique requires is that you extract from the biopsy the genetic material and then, using a highly sophisticated piece of molecular technology, you amplify that specific gene to levels where it becomes detectable and you can characterise it to say for sure whether it is the target gene, such as measles, or not.
Q And what is the reference to “PCR” in this context?
A “PCR” is the acronym for this technique, the polymerase chain reaction. It is, if you like, a photocopying reaction that amplifies in an exponential way a very small amount of, for example, measles, to a large detectable amount of measles.
Q Is that a routine clinical investigation?
A At that time, no, it was not.
Q And, insofar as it was included in this document, was it intended to be there for clinical purposes or for research purposes?
A For research.
Q Coming to the next one, which is also concerned with immunohistochemistry, you will see it has the same page reference, page 221. On a preliminary basis what is the difference between the two entries, as you have broken them down?
A The essential difference is that the immunohistochemistry here is not looking for the presence of virus but for the changes in the tissues associated with the disease process. It is looking, for example, at different cell subsets or evidence of tissue injury, so it is asking a distinct question from the viral immunohistochemistry.
Q Is that a routine clinical investigation?
A No.
Q And would EC approval be required?
A Yes.
Q Now we move on to ultrastructural analysis of mucosal biopsies, and the methodology involved electronmicroscopy and immunogold studies. Can you help us about the technology and the purpose there?
A Yes. The principle here is identical to histology but does so with a microscope that looks with very much higher power so one can see cellular and subcellular damage, or the presence perhaps of virus within cells themselves.
Q Now, we move away from laboratory based interventions to neuropsychiatric studies, referring to Dr Mark Berelowitz, and the source reference for that is page 201 and 221 in the right hand column. We can look at the source reference, if necessary, but can we just stick, first, to looking at this document? What were neuropsychiatric studies intended to constitute?
A Again, this is not an area in which I have any expertise but when we consulted with Dr Mark Berelowitz and he agreed to join the collaboration, he referred us to several standardised assessments for childhood developmental disorders developed by, in large part, his mentor, Professor Sir Michael Rutter at King’s and the Maudsley, and those included the autism diagnostic interview, a standardised structured assessment of the child based upon interview with the parents for the purpose of diagnosis and characterisation of the developmental disorder in the child.
Q I do not want to go into the fine detail of those investigations or intended investigations but I just want to stay with the principle. Would that on any basis have been considered to have been a routine clinical investigation?
A For the purposes of this study, no, it was not. It was intended as a research investigation, although it is used widely now in particular in a clinical context.
Q But at that time, when this was drafted, that was for research purposes?
A It was for research purposes.
Q Again, I take this globally, in respect of all those matters that we have just been looking at, the six elements in column form, do you say that EC approval would have been required for those to be carried out?
A Yes.
Q Moving on to blood tests, the first one is complement studies. Now, you referred to complement studies yesterday but did not go into any detail. I think now is the time to tell the Panel, as short as may be, what you are talking about here.
A Complement is a sequence of proteins in the blood essentially that, when activated by an infection or an immune response, operate in a synergistic way to, for example, bind a protein to an infectious agent which then facilitates the immune systems attack and clearance of that infection, so they are part of the host’s response to, for example, an infectious insult, and in this instance, based upon the published literature that genetic abnormalities in complement regulation are associated with autism in some children, this was something we wished to look at in this preliminary way.
Q And on that basis, and again on the basis of an intention to look at it, to employ this technique or this investigation, for that purpose would that require EC approval?
A Yes.
Q The next element in the blood test category is a reference to plasma total homocysteine. Just help us about that.
A This is a chemical in the body that is an intermediary of vitamin B12 metabolism.
Q And, again, the purpose of investigating that?
A The presence of abnormal levels of this in the blood might be an indication of abnormal vitamin B12 metabolism.
Q And, if you were to carry out that sort of investigation for that sort of purpose, would you require EC approval?
A Yes.
Q Finally, under the Blood Tests, cobalamin co enzymes, again, in the far right column, detection of abnormal B12 metabolism, the same purpose as the previous element?
A Yes.
Q And would you require EC approval for that, if you intended to carry it out for that purpose?
A Yes.
Q If we come back to the CSF, obviously you cannot get CSF other than via lumbar puncture.
A Correct.
Q On the previous page you had dealt with lumbar puncture and you have given evidence about the three elements which you described as “clinically based”.
A My apologies. Just a correction about the “only” way in which it can be obtained. It may be obtained also by what is called cisternal puncture, an unusual procedure, but in essence, yes.
Q I stand corrected. But in relation to this element of lumbar puncture and analysis of CSF we come back to this concept of the cytokine measurements. Again, can you go back, please, and bring in full circle as to the purpose of looking and measuring cytokines?
A Yes. This was a relatively novel approach at that time but cytokines, as I mentioned yesterday, are chemical messengers that convey messages from one cell to another in the body that turn on or turn off inflammation, and if there were the presence of inflammation within the central nervous system this might be reflected in abnormal levels of cytokines in the cerebral spinal fluid, and that is what we were intending to look at in this instance.
Q Finally, back to urine. Under the clinical section the text of the document refers to “Urinary MMA excretion” and a reference to spot sample. Now it is a somewhat different type, and I think there you describe it as being on a 24 hour basis?
A Correct.
Q How does that work, as it were, clinically, as far as you are able tell us, and if you do not know, tell us?
A Again, it is not my area of expertise. A spot sample perhaps will give an indication on a screen of an abnormality. A much more detailed assessment of methylmalonic acid excretion would be obtained from a 24-hour urine sample, clearly a much more arduous procedure, both for clinician and child, but would give potentially further information. But considered in these circumstances it is my belief it was a research investigation.
Q And, that being the case, that would require EC approval?
A Correct.
Q Let’s stand back for a minute and look at the summary of your evidence captured in this document. Those tests which you have, as you understood it, categorised as clinical and not requiring EC approval you have dealt with. Those tests which you say are, in your opinion, research tests which would require EC approval you have listed, and I want now to look, please, at the time the document was sent into the EC committee, at the state of approvals that you may or may not have had? Can you just go through it, please? Looking at page 2, the histology, did you, in fact, have EC approval for the carrying out of that for those purposes?
A Yes.
Q And what was the source of that approval?
A 162 95.
Q Immunohistochemistry. Did you have EC approval at the time that this document was sent in?
A Yes.
Q And the basis for that?
A Similarly under Professor Walker Smith’s existing 162 95.
Q RNA extraction. I will not read the whole lot out, but did you have EC approval by the time this document was sent in, or not?
A Yes.
Q From?
A Similarly under 162 95.
Q Immunohistochemistry?
A Yes.
Q And where did you have that from?
A Under 162 95.
Q Ultrastructural analysis. Did you have approval?
A Yes.
Q Same source, or different source?
A Same source.
Q Neuropsychiatric studies? Did you have EC approval?
A No.
Q And so, therefore, would you need to seek EC approval above and beyond 162 95 in order to be able to carry out those studies?
A Yes.
Q Blood tests, and we will break them down. The complement studies purpose. Did you have EC approval already?
A No.
Q Did you therefore need to seek EC approval in order to carry out complement studies?
A Yes.
Q Plasma total homocysteine. Again, did you have EC approval already?
A No.
Q Did you need, therefore, to seek it?
A Yes.
Q Cobalamin co enzymes. Did you have EC approval already?
A No.
Q Did you, therefore, need to seek it in order to carry out that investigation?
A Yes.
Q CSF, for the purposes of cytokine measurement. Did you have already EC approval?
A No.
Q Did you therefore need to apply for it in order to carry out cytokine measurements?
A Yes.
Q Finally, urinary MMA excretion on a 24-hour sample basis. Did you have EC approval for that already?
A No.
Q Would you need to seek EC approval for that?
A Yes.
Q If it were to be carried out as described on the children?
A Correct.
Q So there were a number of elements in the study as described and as submitted to the EC committee which, on any view, required EC approval for research purposes?
A Yes.
Q Just so that the Panel understand it, from your standpoint as a researcher, were you seeking EC approval for those elements?
A Yes.
Q I am jumping slightly ahead, but perhaps we could simply, without further comment, note this. If we look at this document again, in the third column in, you have written down the answer “Yes” or “No”, as the case may be, in relation to the question “Was the test performed?” Rather than taking you through it laboriously, could you just cast your eye down that third column and tell the Panel whether the answers to the question posed are accurate?
A Yes, they are accurate.
Q Dr Wakefield, can you just put that to one side, please? I just want to ask you a couple of further questions about this document. You spoke yesterday about the objectives of the study as it was put together and on the basis that it was intended to be carried out at some stage. Can you help the Panel with any of its limitations, inherent or otherwise?
A Any study of this nature, dealing with what is a novel and highly complex situation, can only be speculative. One seeks to refine that speculation based upon rigorous adherence to the clues evident in the parents’ history of what happened to their child and the findings on clinical examination. Nonetheless, beyond that point and the clinical investigations, the research elements are inherently speculative. One is testing a hypothesis and the hypothesis may turn out to be right or wrong; elements of those hypotheses may turn out to be right or wrong. So it is by definition, if you like, limited to that extent. Nonetheless, it was a valid attempt based upon our state of knowledge at the time and the availability of the relevant technology to answer the question which the parents had posed to the clinicians, to me effectively, and we had articulated into the hypothesis itself.
Q What might have been the next step, on the assumption that this study had been carried out?
A The next step operates on two levels: a clinical level and a research level. On a clinical level, one can refine the investigations to continue with those that have been helpful and have provided clinical information which have influenced the child’s management and treatment and to remove those that have not yielded any important information. An example of that would be, for example, the removal of the neurological investigations: the EEG, the MMR and cerebrospinal fluid analysis, lumbar puncture, because those did not yield any evidence of abnormality in the children and they did not lead to a change, as I understand it, in the clinical management. On the research side, the next step would be to likewise pursue those elements that had yielded positive information, such as the detection of bowel inflammation. The characteristics of the bowel inflammation would be pursued further, the presence or absence of a virus would be pursued further and to remove or modify those elements of the research programme that had not been productive.
Q In overall terms, this document, when it was submitted to the ethical committee – and this is just coming full circle – in overall terms, from your standpoint, can you describe, as it were, its essential nature?
A If I understand you correctly, what I was seeking to obtain by submitting this document in its form was to get permission from the ethics committee to conduct a series of scientific investigations, as an adjunct to a clinical programme, to correlate the findings from that research with the clinical findings for the purpose of peer review publication.
Q If you look at page 210, there is just one expression I would like your help with. Under paragraph 13 there is the assertion “Clinical Research at the Royal Free Hospital and School of Medicine”. What was to be intended to be conveyed by the use of that expression?
A It was my understanding that there was an insurance policy held by the medical school, possibly jointly with the Trust, but certainly by the medical school which covered clinical research in the event of a patient having an adverse outcome or adverse reaction from any research procedure.
Q It is more the potential linguistic significance of the term “Clinical Research”. What did you intend that to convey when you used the expression?
A This is research effectively involving patients.
Q Can I move to Dr Epstein’s role? We see a reference to him in two places. At the top of page 208:
“Who has verified the scientific validity of merit of this study?”
And his name has been typed in. If you keep a finger in there and move to page 236, there is an undated letter from Dr Epstein:
“Dear Andy
I have reviewed your proposal to study enteritis and disintegrative disorder following measles rubella vaccination. The outline of the study is clear and the methodology testing the hypothesis is appropriate. This is a very important and original study which should be strongly supported on scientific grounds.”
What did you ask Dr Epstein to do?
A I asked him, as a senior gastroenterologist and someone who had been involved in clinical research for many years, to provide an objective, independent opinion of the scientific merits of this project.
Q Was it normal at that time to seek someone’s opinion who was in the same or adjoining department?
A This was the first such application that I had made. Before this, applications had been made by my line manager, my boss, Professor Roy Pounder, and I had contributed to those. This is the first one that I had been involved in. I felt, as did Dr Epstein, as did Dr Pegg, that this was an appropriate choice of reviewer.
Q Can I look, please, with you at the involvement of others in this document and in the application? The first page is page 200, if you could keep your finger in that, and then also look at pages 213 and 214. The investigators with their departments are summarised together with the responsibilities. Have you had an opportunity of reviewing this text?
A Yes.
Q Primarily, who drafted the responsibilities going forward of the individual investigators?
A I was responsible for drafting and co-ordinating this document.
Q If we look at the responsibilities where you feature in paragraph 1.2 on page 213:
“Department of Histopathology & Medicine and Department of Molecular Chemistry, University of Greenwich”
You are mentioned, together with Drs Dhillon and Linnell, Professor Bruce, Dr Subhabi and Mr Chadwick. Then over the page, under “Responsibilities”:
• “Evaluation and description of histopathological changes
• RNA studies for identification of measles and rubella viruses
• Cobalamin studies”
Were those three elements research elements?
A Yes.
Q Were they therefore part of your responsibility?
A Correct.
Q Then under paragraph 1.3 is the name of Dr Berelowitz of the Department of Child Psychiatry and:
“Confirmation and characterisation of features of disintegrative disorder.”
Was that a research aim, activity?
A Involving the ADI and the structured studies.
Q Then under paragraph 1.4:
“Department of Neurology
Dr P. Harvey …
Responsibilities
Full neurological assessment and investigation”
What as you understood it was his role? Clinical or research?
A Essentially he had a clinical role in assessment of the children.
Q Finally, if I can take you back to page 213, Professor Walker-Smith, Dr Simon Murch, Dr Casson and Dr Phillips. Those responsibilities we can see set out: referral and co-ordination of patient admission for investigation, clinical evaluation, procurement of blood, urine and serum samples, colonoscopy and tissue procurement and processing. Do you understand that to be clinical or research?
A It is clinical.
Q If you look, please, at page 200, yesterday you told us that Professor Pounder’s writing appears in relation to the date. I think we have some evidence about the signature as well. What is you view about that?
A That is Professor Pounder’s signature.
Q As you understood it, what was Professor Pounder’s role in signing and dating this document?
A He was my head of department and it was essential that this had been scrutinised and approved by my head of department, even though he was not a participating investigator. It was part of the due diligence applied to it.
Q On the same page, you will see the names of Professor Walker-Smith, Dr Murch and yourself are set out under the heading of “Responsible Consultants”. What do you understand that term to mean?
A That we took overall charge and responsibility for the respective clinical and research aspects of this programme.
Q We have Dr Subhani’s name and then Dr Casson. We see that in specific particulars, Dr Harvey and Dr Berelowitz have signed as heads of collaborating departments denoting approval. What did you understand those two signatures to mean?
A That they had been involved in the design of this project, that they had approved it, that they had seen the final draft of these documents and signed up to them.
Q You mentioned earlier in respect of one aspect at least of the document that it was a consensus piece of text, I think you said. What about the whole document? To what extent was that a consensus document?
A It must by definition be a consensus, to the extent that it is agreed upon by all those who sign up to that document.
Q Were there earlier drafts?
A Yes.
Q Were they circulated?
A Yes.
Q Did they come back with any amendments, suggestions, deletions, additions and so on?
A Yes, absolutely. Every investigator had the opportunity to make such changes.
Q One of the matters which the Panel are invited to consider is the proposition that you had a duty to ensure – that is the word which is used – the accuracy of information or material – those are my words – within the document. What do you say about the use of that term?
A I think it is to a large extent unrealistic, since I have no expertise in the respective areas of child psychiatry or neurology, it is too much to assume that I can ensure the accuracy of what is said about those in this document. Similarly, for my colleagues in paediatric gastroenterology, who have to ensure that what is said in the context of childhood developmental disorders is accurate, that is too onerous. We do have a duty to the best of our ability to ensure that those aspects which fall under our specific expertise are as accurate as possible.
Q The document was eventually signed by you and we can see that at page 233 and was submitted on 16 September 1996 (page 233).
A Yes.
Q When that was submitted had you in fact used your best ability to ensure that the details were accurate and correct and honest?
A Yes. As the Panel are now aware, drafts of this document were prepared as early as October 1995, and a great deal of time and effort went into ensuring that what went into it was not only appropriate but accurate, so, yes is the answer.
Q After the document was submitted – if you would take the schedule of children, D8 – the date of submission falls just between Child 3 being investigated and Child 12 being referred, do you see that?
A Yes.
Q As far as you were concerned, the researcher, did you continue to carry out research on these children after the application was submitted?
A Yes.
Q When you were carrying out that research did you have ethical committee approval for what you did?
A Yes.
Q On what basis did you have EC approval?
A On the basis of Professor Walker-Smith’s existing approval for analysis of biopsies, 162/95.
Q I shall take you through these children in due course but does your answer apply from the point that I have just identified, right down the page of D8 in respect of all those children?
A Yes.
MR COONAN: Thank you very much, that is all I ask you about section 5.
THE CHAIRMAN: Thank you. This is probably the right moment to have a short break, I am sure Dr Wakefield needs a break. We will now adjourn and resume at 11.15. Dr Wakefield, can I remind you again, please do not discuss the case during the adjournment because you are still under oath.
(Short adjournment)
THE CHAIRMAN: I see Professor Walker-Smith is back. I hope you are feeling much better. Yes, Mr Coonan?
MR COONAN: (To the witness) I am going now to turn to the next section, which concerns the ethical committee approval and in order to set the scene for this, Dr Wakefield, can I just ask you to re-cap two or three points before we look at the unfolding chronology? When the application was submitted in September of 1996 by yourself, you told the Panel that from your standpoint – others may have to speak for themselves but from your standpoint – you assumed that you were seeking ethical approval, first of all, for those for which you did not have ethical approval already, those elements: is that correct?
A Correct.
Q For the neuropsychiatric element that you have identified?
A Correct.
Q In respect of the matters already covered by 162/95, did they form part of the application in any event or not?
A I suppose you could refer to it as a “belt and braces” exercise, this was a circumscribed project and therefore they were covered, effectively, under both once the approval was obtained.
Q What about writing up results? Let me just break this down. In so far as one can rely on 162/95 for the grant of ethical approval for one particular purpose, what was your understanding at that time about the ability of writing up results in connection with a product flowing from 162/95?
A Implicit in any approval is the ability to submit the analysis, the results and analysis and write-up of the data deriving from that approved study for the purposes of publication, indeed it would be unethical not to ---
THE CHAIRMAN: Would you go a little slower? Some of us are trying to take notes and this is an important point.
MR COONAN: Would you begin again?
A Let me recap. Implicit in any ethical approval is the ability of the researcher or research group to analyse the data and to write those data up in the form of a peer review publication. Moreover, it would be unethical not to at least attempt to do so, having put patients through a research protocol, not to then communicate the results of that protocol to the broader medical and scientific audience.
Q Therefore, in your own words, tell the Panel what were the elements as you saw it back in September 1996, based on your recollection now, of the elements for which you were seeking approval?
A Based upon my recollection now, and specifically following the introduction of documents by Professor Walker-Smith’s team which clarified this issue, permission was being sought to … Sorry, for 172-96 we are talking about?
Q Yes.
A Yes, to take those research elements, which I have identified, to correlate them with the clinical data derived from the investigations of Professor Walker-Smith and his team and put them into a publication for the purposes of dissemination of the information.
Q Were you, from your standpoint, at any stage seeking ethical approval in respect of what you have described as “the clinical elements”?
A No because that is not necessary.
Q Against that background, let us look at the unfolding chronology. You will need Panel bundle 1. I have already drawn your attention to page 233, which was the date of submission document, and we turn on to page 239. I can take these letters quite shortly. It is a letter to you from Maureen Carroll. Is there any significance or otherwise in the fact that Maureen Carroll wrote to you as opposed to anybody else at this stage?
A No, that was perfectly appropriate. I was the one who submitted the documents to her.
Q She writes:
“I acknowledge receipt of your application for ethical approval of your research project”.
She sets out the title, again, they are her words but I just wanted to cover linguistic possibilities: have you any comment to make about the use of her term “research project”?
A No, it is perfectly appropriate. As secretary to the ethics committee she receives only research projects, and this was one such document.
Q Would you move on, please, to page 265A? This is a letter from Dr Pegg to Professor Walker-Smith, dated 15 October 1996, and we can tell from the green colour that this was put into the bundle by Mr Miller at an earlier stage of these proceedings on behalf of Professor Walker-Smith: do you remember that?
A Correct.
Q When did you first see that document?
A I do not remember but I must have seen it, and I suspect that it was when it was copied to me, with other documents in the sheath, and sent from Professor Walker-Smith.
Q Before looking at the body of the letter, if we can just remind ourselves that there were two internal documents, at pages 241 and 244 which pre-dated that letter at page 265A – I say that simply to assist the Panel in the chronology.
A Correct.
Q Nobody is suggesting you would have seen those documents, but, as I say, they are internal documents and therefore I just ask you about page 265A. I will leave aside the reference to the ARSAC licence, and Dr Pegg writes:
“It is a very intensive regime involving some unpleasant investigations – LP, endoscopy, MRI, etc., some of which may require a general anaesthetic. I would consider the risk of such procedures to be “high” (BPA guidelines classification).”
There is a clip of that at page 265C:
“The guidelines state: ‘It would be unethical to submit child subjects to more than minimal risk when the procedure offers no benefit to them, or only a slight or very uncertain one’.
Your submission indicates that all these tests would be carried out (apart from 5 extra biopsies and some extra blood) in the normal care of the child. I would therefore like you to:
(a) Confirm that the child would undergo this regimen even if it was not in a trial.
(b) Indicate what benefit the child will receive from having been investigated I this way. Will the benefit be more than ‘slight or uncertain’.
I enclose sections of the guidelines …”
Then there is a reference to the consent form.
Again, do you have a memory now of receiving that letter from Professor Walker-Smith, or a copy of it?
A Only a memory provoked by the disclosure of these documents, not prior to that.
Q Again, if you find this question unfair please do say but on the assumption that you would have seen it copied to you by Professor Walker-Smith, what do you think would have been your response to him if you had seen this document?
A Firstly, I think that it is an entirely appropriate letter in line with Dr Pegg’s responsibility as the head of the ethics committee, someone who has clearly raised an issue and he has sought clarification from Professor Walker-Smith and that is his duty and responsibility and Professor Walker-Smith was in a position to provide a comprehensive answer to that.
Q Would you have taken the view that it was a matter for Professor Walker-Smith to deal with as opposed to yourself?
A Yes, very much. It was an issue relating to the clinical indications for the tests that were part of the protocol.
Q Would you turn to page 291, Professor Walker-Smith replied to that letter on 11 November 1996, and if we turn to page 292 you will see that that letter was copied both to yourself and to Dr Murch. We have looked at this letter now quite a number of times. First of all, do you accept that you saw this letter at or about the time, 11 November 1996?
A Yes.
Q Do you have any observation to make about the content of that letter, particularly paragraph 2?
A I think it is an entirely accurate representation of the situation as I think we all saw it at the time, particularly in relation to the devastating condition from which the children suffered, and, indeed, what appeared to be (and sadly has turned out to be) the rather hopeless prognosis of many of these children.
Q Professor Walker-Smith says at the bottom of that paragraph:
“This whole study is parent/patient driven, as every case referred has been initiated by the GP by the parents of the child.”
As far as you were concerned when you would have seen that assertion, was that in your view an accurate assertion for Professor Walker-Smith to have made?
A Absolutely. Every referral had been initiated by the parents.
Q He goes on:
“I can confirm that children would have these investigations even if there were no trial … we would not be investigating children without gastrointestinal symptoms.”
Again, have you any observation about that?
A No, that is something with which I would agree entirely.
Q He says in that letter:
“We agree that consent always involves discussion and signature of the researcher. We will change the protocol.”
Have you any memory of any changes to the protocol being effected?
A Yes, what was changed was the rather imperfect consent form that was previously prepared in late 1995.
Q Just turn back to page 211: is that the document you were just referring to?
A Yes.
Q Can you turn on now, please, to page 313, where Maureen Carroll writes to you again on 14 November 1996:
“I refer to your recent application to the ethics committee regarding the above project and I am pleased to inform you that this was approved at the meeting on 3 November 1996”,
and she goes on to deal with other details.
Do you remember receiving this letter?
A Yes.
Q And did you take it, at least initially, as an approval letter?
A Yes, I took it at face value.
Q Did you subsequently, and we will come to it, come to understand that that was not, in fact, the approval letter?
A Correct.
Q Turning to the chronology there is just one issue I need your comment on, page 235, part of the EC application form signed by Dr Pegg dated 18 December 1996, and there is a reference to “meeting with Dr Wakefield”. Now I am not going to trouble you with rehearsing what Dr Pegg said in his evidence about that: I just want your view. Do you remember meeting Dr Pegg to discuss any of these matters at all?
A I do not remember meeting him. I am perfectly willing to accept that a meeting may have taken place, but I have no memory of it.
Q We move on now to January 1997, page 358, please. This letter is from Dr Pegg to Professor Walker Smith and not, in fact, formally copied to you, as we can see from page 359. However, do you accept that you came to know about the content of this letter?
A Yes, I did.
Q Do you think you would have come to know about it shortly after Professor Walker Smith received it?
A Yes.
Q In fact, we can just get your bearings by moving on to page 362, where Professor Walker Smith replies to Dr Pegg:
“Many thanks for your letter. I accept its contents and we will modify our protocol ...give an annual report ... we will place a copy of the patient consent form and information sheet in the clinical notes”,
and that document is copied to you?
A Correct.
Q So we just take the two of those together, 7 January at page 358 and the reply at page 362, 9 January, and I shall proceed on the basis, therefore, that you round about that time did come to know of the contents of the letter of 7 January. What was your understanding as a result of seeing the content of that letter, and take your time to refresh your memory by its contents, please.
A Firstly, I imagine there was some enduring confusion as to why Maureen Carroll might have written to me earlier, but nonetheless clearly this letter superseded that. I have no problems with any aspect of the letter: I am still slightly confused about the Schilling test. This is a clinical matter, the Schilling test was in there for clinical reasons, and yet the Ethics Committee seemed to have arbitrated that it should be removed. It is my memory that it was performed clinically in Child 2 and it was normal, and I think that, even though we did not know what an ARSAC licence was at that time, Dr Hillson was of the opinion that the volume of paperwork that would be required was prohibitive for him, and it may then have been decided by the clinicians that they would get far more information from colonoscopy and ileoscopy from doing this test, and they will speak to that. But other than that I have no problem with this letter at all.
Q One matter I would none the less like to ask about is the first item in the second paragraph where the Ethics Committee, Dr Pegg, says: “Only patients enrolled after the date of the December meeting will be considered to be in the trial”. Did you understand that to say on its face what it did say?
A Absolutely.
Q Again, I do not want to leap ahead too much but, Dr Wakefield, when we come and look at The Lancet material, were you at any stage in breach of that stricture?
A No.
Q Therefore, leaving aside the oddity of the Schilling test that you describe, what did you understand this letter to have given approval for?
A It meant that from this point forward the research elements that I had set out in the application that were over and above the biopsy analysis could now be started on patients admitted after this point.
Q Now, we had a lot of evidence from Dr Pegg as to what he believed that permission had been given for, and I am not going to trouble you to comment on any aspect of his evidence, in due course those submissions will be made, of course, but there was at one stage a position taken by Dr Pegg about the extent of the approval that I just want your comment on, and you will find that in volume 3 of the Panel bundle at page 951. It is a letter from Dr Pegg to Professor Zuckerman, 24 July 1998, and this is now some four months after The Lancet paper was published, just to get our bearings. Now the first part of the letter I am not interested in for present purposes: I am going to take you to the second page, and at the beginning of the last paragraph, following an extract from The Lancet paper - and Dr Wakefield I shall be asking you about that later - I want you to comment on Dr Pegg’s position at that time.
“We did not approve the investigations: we approved data collection from clinically indicated investigations”.
Would you like to comment on that?
A In the context of clinical investigations, no, Dr Pegg’s committee did not approve them because there was no need to approve them. In the context of research investigations, Dr Pegg is wrong because his committee did approve the additional research investigations that I have described earlier, and so to that extent his memory was at fault.
Q As I say, the position was further elucidated in the course of his evidence. Let’s get back to the unfolding chronology, back to 1997, please. Having got approval in the letter we have looked at can I now ask you, please, to turn to page 366aa and bb, a letter dated 3 February 1997.
THE CHAIRMAN: Just to clarify, originally this document was written as 366a and then it was added as 366aa, and similarly the second one, 366b, was added as 366bb, but they are the same documents.
MR COONAN: Thank you, sir. Dr Wakefield, we all have it. This is a letter written by you to Dr Pegg in February 1997, and the first question is this. Quite apart from the time when, of course, you wrote it to him back in 1997, when was the first time next, as far as you can remember, that you saw this letter?
A When it was introduced by Professor Walker Smith’s team some time early in the course of the last session of this hearing.
Q Now, I am going to ask you a number of questions about this but, rather than adopt the format that I have done so far of myself reading out the material, I am going to ask you to read it, please, and to pause at each of the points in it where, as I anticipate, you would need to make some comment. So if you could break it up in that way, could we do that? Just begin, please, if you can, with the first paragraph.
A Just by way of background, Professor Walker Smith convened a meeting of several of us to discuss the contents of Dr Pegg’s letter and this is the letter that arose out of that meeting, and as the co ordinating investigator it was my responsibility to write back to the Committee.
“Dear Dr Pegg, further to your recent letter and our response regarding the granting of Ethics Committee approval for our study, A new paediatric syndrome: enteritis and disintegrative disorder ref 172 96 on enterocolitis and disintegrative disorder following MMR vaccination, we would request that the following amendments be made”.
I will stop there to say Dr Pegg in his letter giving approval had required that any changes in the ethics application should be communicated to his committee, and this was an effort to do that.
“The pilot study has demonstrated that MRI and EEG studies are all normal and therefore we feel that there is no need to continue these unless specifically indicated”.
This is crucial because this letter was one of the final pieces of the jigsaw that allowed me personally to reconstruct the events of all those years ago. Firstly, I refer to the pilot study, not to 172 96; and this is not to be confused with the LLB pilot study in any way. The pilot study, that is the clinical investigation of the first 12 children in this case, has been undertaken and has demonstrated that the neurological investigations and here I have included MRI and EEG but this was also later to include the lumbar puncture, I think, soon after this had not revealed to the clinicians any valuable clinical information which had caused them to change their management of the child, and therefore in the interests of the children they were removed. There was no research emphasis to this at all.
“Eight out of the 9 children examined so far have an indeterminate inflammatory bowel disease...”
And I will stop there. What this means, “indeterminate”, is that it is neither Crohn’s disease nor ulcerative colitis, but it is nonetheless an inflammatory bowel disease.
“...is clearly present both histologically” - that is down the microscope - “and endoscopically” - that is via the telescope - “Therefore, we feel that gastrointestinal inflammation may be, in part, the source of the underlying problem in these children and we would like to investigate this in more detail by studying intestinal permeability”.
One of the consequences of inflammation in the small bowel in particular is that it becomes leaky and components, elements, of the gastrointestinal lumen through which the food passes that should not normally get into the bloodstream can do so, and there are tests of permeability which can give an indication that there is underlying inflammation in the bowel, and this is what we proposed. These are routine clinical tests but we intended to examine them in a research setting.
“This involves an overnight fast by the children followed by a voiding of the bladder, and taking a harmless sugar solution. The urine is then collected over the next five hours. This urine sample is then analysed to look at the ratio of the sugars in order to determine the degree of intestinal permeability”.
So I pause again - this is a non invasive test that simply involves taking a sugary drink and collecting urine.
“Not only is this test a non invasive screening method for detecting intestinal abnormality but it may also be useful for examining therapeutic efficacy in the future. Please find enclosed a copy of the explanatory letter to the parents. It is anticipated that, for the most part, the patents will be able to conduct this study at home and send the urine sample to us or, alternatively, bring it up to their inpatient or outpatient appointment, depending upon the timing of the investigation.”
We are seeking changes in 172 96 prior to its enactment, that is the removal of the neurological test, so we are not seeking that, we are informing him of that, and asking for an additional research test to be put in. I continue,
“I look forward to hearing from you at your earliest convenience.”
Q You mentioned you were seeking, applying, for amendments to 172 96 prior to its enactment?
A Correct.
Q We can see that this is 3 February 1997, and if we now turn to the schedule of children and look down at the bottom of the page, 3 February 1997 is very shortly before the admission and investigation of Child 10. In other words, that was the last of what was to become The Lancet 12 to be investigated, is that right?
A Correct.
Q Plus Child JS being admitted and investigated. Did 172 96, either in its unamended or amended form, operate as far as you were concerned in relation to those 12 children?
A No.
Q In seeking the amendment as you did, what was the intention going forward in relation to 172-96?
A To include a further research study, that is intestinal impermeability in the protocol, as a way of assessing a non-invasive marker of bowel inflammation.
Q That is all I am asking you about this aspect of the matter in this section. We now need to round matters off by looking at the heads of charge together in relation to both these sections, that is, section 5 and section 6, and for these purposes you need to have a copy of the charges and look, please, at heads 5 and part of head 6. I am going to take this slowly and you can comment, Dr Wakefield, making sure that you read the terms of the individual charge or subcharge as we go through. The stem of 5 and (a) have been admitted. In (b), that remains unadmitted. Do you have an observation to make about that charge as it is drafted?
A The project was described as a clinical and scientific study involving 25 children.
Q The person who has drafted this has used the description “research study”.
A I felt that point needed clarification to the Panel, in that what was put before the Committee was a clinical and scientific study and, although the clinical aspects could not require the EC committee’s approval, that required clarification.
Q Let us look at (c). Looking at the stem first:
“Describing a study which entailed a programme of investigations, including invasive gastrointestinal and neurological tests, to be carried out on children …”
Sometimes to take the stem without reference to the subparts is rather meaningless, but looking at the stem on its own merits, do you have any observation to make about the linguistics there?
A I am very sorry about this. Can I just go back to that last point, because there is one thing that I missed in (b).
Q Yes, of course.
A In the last line, it says, “disorder following measles/rubella vaccination” and the protocol itself says “measles and measles/rubella vaccination”. That was another reason for not admitting this.
Q What about the stem of (c)?
A The stem as far as I can see is straightforward.
Q Look at the subparts:
“who had,
(i) been vaccinated with the measles or measles/rubella vaccine;”
Do you have an observation to make about that as a particular reference to the word “vaccinated” and the reference to measles or the measles/rubella vaccine?
A Yes. This is incorrect and has misunderstood what the protocol actually said. It was following measles and that, as I said yesterday, refers to natural measles infection, because of its established association with disintegrative disorder, or measles/rubella vaccination, again referring to the component viruses of these vaccines, the various vaccines which have been linked historically to autism.
Q Do you have any other comment about (i)?
A The study did not require any exposure, any particular exposure at all. In other words, the entry criteria for the study did not require exposure to anything in particular, including vaccines. So just an added point to be made.
Q I think you said that yesterday.
A Correct.
Q Let us look at (ii). Obviously you have to consider (ii) against the background of the stem, as you must do with all of these.
A Again, the term “disintegrative disorder” is clarified more precisely in the body of the application as children manifesting signs and symptoms, or disintegrative signs and symptoms. That is just a further clarification which was not evident within this particular subsection.
Q And (iii)?
A I may have missed it, but (iii) at the moment, unless it is with reference to the stem, I do not see any particular problem at all.
Q If there is no particular problem, I will move on.
A May I ask, is it necessary to refer back to the head of charge to interpret these various subsections?
Q You comment as you feel fit, Dr Wakefield. I think that is the wisest thing to do.
A My comment would be that if the word “study” refers back to “research study” in (b), then it does not clarify that this was a clinical and scientific investigation and therefore carries the connotation that these investigations were done, these clinical investigations were done for research reasons, which they were not.
Q Then (d)?
A This is clearly an error. “Indicating that all the procedures you proposed to undertake …” I did not propose to undertake any clinical procedures at all.
Q If the focus on the word “you” is removed, what comment would you make?
A Then I think that would be acceptable. “All the procedures”. Clearly not all the procedures were going to be clinical. There were going to be research procedures which were under my control. So no, not all.
Q (e). I want you to break this down into its constituent parts. “Indicating that you would be responsible for arranging a number of those procedures …” relating back no doubt to (d), “including MRI”. What do you say about that?
A As set out in the document, I was going to be responsible where necessary for arranging, not ordering, but arranging the MRI. This applied also to the EEG. It did not, however, apply to the lumbar puncture. I had no role in arranging that or in its conduct.
Q (f) and (g) of 5 are admitted as fact. We move on therefore to 6. 6(a) is admitted. 6(b)?
A The concerns of the Chairman of the Ethics Committee were raised with Professor Walker-Smith directly. He did not raise them with me.
Q Save as to that, do you have any difficulty with 6(b)?
A I think the emphasis that this was an intensive regime – no, I think other than that ---
Q Simply on the words as drafted?
A Yes. I think as long as “the study” is taken to mean the clinical and scientific investigation, I do not have a problem.
Q Then (c). Do you now have a problem with 6(c)? This is a direct reference to the letter we have already looked at.
A No, that is correct. I have no problem.
Q And (d)? There is a stem to (d). Again, do you now have any problem with (d) as drafted?
A No. That is also correct.
Q And (e)? Again, a letter we have looked at. Do you have a problem with that?
A No problem.
Q And (f)? Do you have a problem with that? It has been amended from the previous draft, as the Panel will remember. Do you have a problem now following the amendment?
A Only to the extent that my letter of January 1997 did include amendments to the application.
Q Do you have the amended version there, doctor?
A Mine says:
“Between 16 September 1996 and 15 July 1998, no further applications were made to the ethics committee for approval in connection with project 172-96.”
Q Is that all it says?
A That is what it says.
Q You have not been given the amended version.
A I am sorry. Going on, it says at the end:
“ … save as set out in Dr Wakefield’s letter to the Chairman of the Ethics Committee dated 3 February …”
So as it reads, no.
Q You do not have a problem with that as amended?
A No, that is fine.
THE CHAIRMAN: There is also another bit in the middle:
“ .. for approval in connection with Project 172-96 nor was the Committee informed of any amendments to your initial application save as set out in Dr Wakefield’s letter to the Chairman of the Ethics Committee dated 3 February 1997.”
A That is correct. That is fine.
MR COONAN: Let us look at (g). “As a named Responsible Consultant you had a duty to ensure”. I want you to focus on that. Can you comment first on (i) in respect of that?
A The difficulty here, as I have discussed with the Panel earlier, is the burden of a duty to ensure. As I have said, it is impossible to ensure beyond one’s own expertise. You can consult with colleagues and in the end one has to rely upon their expertise in helping you do your due diligence in this respect. In respect of all of these points, starting with (i), the duty to ensure is overly onerous.
Q (ii), again bearing in mind the stem containing the word “ensure”, can you consider the wording of that?
A Certainly. “Only children who met the stated inclusion criteria”. One of the inclusion criteria was a disintegrative disorder or the manifestation of signs and symptoms of a disintegrative disorder. This was beyond my expertise and lay within the realms of Dr Mark Berelowitz and therefore for that reason I could not undertake a duty or did not have a duty to ensure that these children had such a diagnosis.
Q What about the reference to the research study?
A Again, this was a clinical and scientific investigation. The emphasis here is that it was a research study, which it was not. There was research contained within it, for which I was responsible.
Q Then (iii). What do you say about that assertion?
A In light of the documents which have come forward, I think again the duty to ensure is overly emphatic and that applies to all of these. Now that we have all the documents from the ethics committee and the responses to the ethics committee, that is less problematic.
Q Then I will move smartly to (iv), a duty, it is said, to ensure that the children admitted under the protocol were treated in accordance with the terms of the approval. What do you say about that?
A I did not admit any child and therefore that is in fact wrong.
Q What about an alleged duty to ensure however they were admitted that they were treated in accordance with the terms of the approval given by the EC committee?
A Again, I had no role in the treatment of any child, no executive decision in the management of children, and therefore this does not properly apply to me. It could be said of (iii) as well, just going back to it, that I was aware of and complied with the conditions outwith my own expertise. I am not in a position necessarily to comply with the clinical conditions or elements outside my own sphere of work.
MR COONAN: I shall leave head of charge 6(g)(v) until later on. Dr Wakefield, that is all I am going to ask you about that section, thank you very much.
Sir, I am now going to commence with Dr Wakefield’s assistance a lengthy section, section 7, which concerns the position of legal aid in terms of the application and the ultimate expenditure, and, as I say it will be quite lengthy.
THE CHAIRMAN: Dr Wakefield, obviously you have heard Mr Coonan saying it is a lengthy subject and you have been giving evidence for a while now. Would you prefer to have a lunch break at this stage and then commence your evidence so there is no break in the continuity, as Mr Coonan is implying, but I am entirely in your hands. We can continue for a little longer, but if you want to break now that will be absolutely fine with the Panel as well.
THE WITNESS: I will be advised by counsel. I am happy to continue or happy to stop.
THE CHAIRMAN: In that case, it comes to me now what to do so I suggest we do have a break at this stage, and take it as a lunch break. We will resume at 1.20. Once again, Dr Wakefield, you are under oath and in the middle of giving evidence. Someone will look after you so that you get lunch here or there is no problem if you go out provided you do not discuss the case.
(Luncheon adjournment)
THE CHAIRMAN: Good afternoon, everyone. Before you start, Mr Coonan, can I raise that issue I raised yesterday morning about a couple of corrections to the heads of charge against Professor Walker-Smith and Professor Murch. I know they were very minor, but I think for the purpose of the transcript I think it is better that they are corrected.
MR HOPKINS: Sir, thank you for that. In respect of Professor Murch you drew our attention to page 88 of the heads of charge and we were looking at 18(c)(vi). The allegation is:
“Child 12 was admitted to hospital on 5 January 1997, under Professor Walker-Smith’s clinical care”.
Then the sentence you were drawing our attention to is:
“Admitted and found proved only to the words “January 1999”.
As you rightly point out, that should read January 1997.
THE CHAIRMAN: So you accept that?
MR HOPKINS: Yes.
THE CHAIRMAN: Thank you. Mr Miller have you had time to look at it, or we can deal with it next week if you have not?
MR MILLER: Sir, I have had time to look at it and I discussed it with the prosecution this morning, it is not admitted as it stands on page 58. It relates to Child 8 and it is 20(a)(i) and (ii). The position is that we accept that that is what the general practitioner Dr Jelley wrote to Dr Wakefield, and if that is all that is intended by that head of charge then it will be admitted but I have asked Mr Mellor about this morning and he just wanted to discuss it with Ms Smith to see whether there was anything underlying that, so again if we can perhaps resolve that later this afternoon and come back to you on that.
THE CHAIRMAN: Yes, thank you. My only question was that on your document D1 there was nothing mentioned about this.
MR MILLER: That is what was puzzling us.
THE CHAIRMAN: You had been very meticulous in mentioning against every charge either “admitted” or “not admitted.”
MR MILLER: I have nothing to hide on this; that is the only issue.
THE CHAIRMAN: Very well. We will leave it on the sidelines for the time being.
Mr Coonan?
MR COONAN: Thank you sir. As I indicated before we broke off, I am going to start section 7, which concerns the legal aid issues, and just for your note and points of reference, we are dealing with heads of charge 3 and 4, although the content of those I will not take you to at this stage.
(To the witness) Dr Wakefield, we are going to be looking at a large number of documents so would you have to hand bundle 1?
A Yes.
Q When did you first have contact with Dawbarns, a firm of solicitors?
A My first memory of contact was in the January of 1996, when I met with Richard Barr and his assistant Kirsten Limb in my office at the Royal Free.
Q Before we go into any evidence about discussions and so forth, can you remind us, please, immediately prior, if you like, to that meeting, what was the state of your scientific thinking by the end of December/beginning of January? I know this is a recap, but it is important to have this backdrop before we start these discussions with Richard Barr?
A It was, firstly, in the context of ulcerative colitis and Crohn’s disease, particularly Crohn’s disease, and association, or a possible associated between exposure to the measles vaccine and that disease in children, and in the context of regressive autism or disintegrative disorder that this was possibly occurring in a group of susceptible children following exposure to either measles or a measles-containing vaccine, particularly MMR.
Q How was the first contact made between you and Richard Barr?
A To my memory, it was a phone call from Kirsten Limb to set up that meeting.
Q Who did you understand Kirsten Limb to be?
A She will have introduced herself as the medical investigator. She had a BSc, she was a scientist by qualification and she was working for Dawbarns researching into possible adverse vaccine reactions.
Q Had you heard of Dawbarns before this first contact?
A I have no memory of having heard of them before that at this time.
Q Let us turn to the meeting in your office: there was yourself, Kirsten Limb and Richard Barr. What was the purpose of the meeting as you understood it?
A It started as a general discussion about my work and about their interests, and I think they had come to learn of my work through the publication of the 1995 Lancet paper, raising the possibility of an association between measles vaccination and Crohn’s disease, and there was discussion about that and about vaccine safety studies in general, which was a subject that I had been researching for some time and the overlapping interests that we had in as much that they had children who were presenting as clients or potential clients who had developed Crohn’s disease, in particular following the MR campaign, which I believe took place in the autumn of 1994, that is the measles/rubella “catch up” campaign.
Q During the course of the meeting did any proposal emerge?
A I think towards the end of the meeting they asked me if I would be prepared to act as an expert. I do not think there was any litigation under way at that time but they were exploring the possibility of whether such litigation had merit and a reasonable prospect of success and they asked me if I would help them in a scientific context to establish whether that was the case.
Q In exploring the idea of you acting as an expert, to act as an expert in what sort of litigation?
A At that stage it was more an exploratory procedure determining whether there was merit in such litigation, and that would be a litigation aimed – the defendants in such litigation would be the manufacturers of these vaccines.
Q Which vaccines in particular?
A Their particular interests were in the measles/mumps/rubella vaccine and the measles/rubella vaccine.
Q Were they interested in any particular form of any particular injury or outcome following the vaccines?
A They had a very broad interest in not only Crohn’s disease but also regressive autism, but more broadly in Guillain-Barre syndrome, in multiple sclerosis, in diabetes, in juvenile arthritis and a whole range of conditions beyond certainly my scope and expertise.
Q Did you agree in principle to act as an expert at that stage?
A No, I agreed that I would consider it and get back to them.
Q Quite apart from acting as an expert in eventual proceedings, was there any other proposal or suggestion which was made either at that time or perhaps later?
A Yes, there were two elements to this: one was that we both had an interest in vaccine safety, what vaccine safety studies had been conducted; how thorough were they; how long had they lasted for; what were the outcomes; did they provide any clues – sorry, I am rushing – as to the sorts of disorders that we were seeing, and one of the questions was would I be prepared to assimilate my researches on vaccine safety studies into a report for them? That was the first aspect. The second aspect was by way of scientific inquiry and the question put to me was, “How would you now approach this problem in seeking to determine whether or not there is indeed a causal association between these vaccines and, in the first instance, Crohn’s disease, and my response to that was in line with the way that my group had been examining this for many years, was to see if there was evidence of the measles virus in the hallmark lesions of Crohn’s disease, that is those granulomas, granular matter that were destroying blood vessels.
Q So you have spoken now in effect about three strands to the discussions and I asked you about whether you agreed in respect of the first one, which was to act as an expert, what about the other two elements: did you agree in principle with the proposals straightaway in the first meeting you had with them?
A No, again, these were left in abeyance and I was going to give consideration to the considerable implications for becoming involved in this and would get back to them on that.
Q Did you take time to consider these issues?
A Yes, I did.
Q Was there a further meeting or further contact between you and Dawbarns?
A There was certainly further contact at some stage when I agreed in principle to act as an expert.
Q What about the other two elements?
A Yes, I agreed to assimilate a safety report and I agreed to the proposal that I should design and study to answer the question “Is there evidence of the virus in the tissues, the diseased tissues in these children”?
Q In general terms, what would be involved in such a scientific inquiry to determine the presence or otherwise of measles virus in the diseased tissues of Crohn’s disease suffers?
A The first question is, is there evidence of the viral protein, the antigen, in the hallmark lesion, granulomas of Crohn’s disease. The second question is is there presence or absence of measles virus protein just generally in the diseased tissues of Crohn’s, for example, in the base of an ulcer. If that were the case that may make it just a non-specific reaction, the virus present in inflammation, so is it specific to the hallmark lesion?
Q No. 2, or the next question would be, is there evidence of measles virus in the tissues of children with other bowel diseases that have not been linked in a similar way to exposure? Control tissues for example. And then, if that is the case, is there evidence of other viruses, if we look for other common childhood viral infections are they present in the tissues? In other words, is this just something about the child that means such viruses hang around and persist for years? If that were the case it would suggest that it is a non-specific thing and perhaps the measles virus does not have a causal role and then beyond that, and that is a great deal of work, can it be replicated in different populations? Can it be replicated using different techniques of viral detection, and so on and so forth?
Q In terms of that scientific inquiry that you have been describing, was that an investigation which was laboratory-based essentially or was it wider than that?
A It was a laboratory-based analysis.
Q Did you discuss these proposals with anybody?
A Yes I did, the question that I was asked by Richard Barr was, “Acting as an expert, what would your professional fee be?” and I had no idea, I had never done any medico-legal work before, and so I consulted Professor Pounder – he was not able to help because he did not involve himself in medical litigation. I asked Dr Harvey, and I do not remember his precise response, and I asked the BMA’s professional services committee and they indicated that such a fee would be in the range of £150-£200 an hour and I opted for the former figure.
Q Having made these inquiries did you go back to Dawbarns or did they come back to you, and was an agreement – these are my words – sealed, or come to, at a subsequent occasion?
A Yes, I think there was a meeting with Augustus Ullstein at his chambers, who was the QC who was looking at this issue, and by that stage an agreement by me to act had been reached.
Q When you saw Mr Ullstein QC in his chambers, was that with Richard Barr and Kirsten Limb?
A Yes, I believe it was.
Q When, roughly, was the meeting at which the agreement was reached about these matters?
A I think it was probably in February 1996.
Q There are two documents I want to ask you to look at, the first one is at page 104 of volume 1, and keep your finger in that and turn to page 212. You told us that page 212 was the version of this submitted to the ethical committee is that right?
A Correct.
Q Going back to page 104, was it at this stage a completed document?
A No, this was a draft.
Q Would you look at page 105, just before halfway down, is there anything there which suggests unfinished drafting?
A Yes, particularly under the telephone number for AP, that is, Amar Dhillon, Dr Dhillon, there is no extension number.
Q Then page 106, about five lines down?
A Again, similarly, no number for Dr Dhillon.
Q Page 107?
A There are information details missing on Dr Law at the MRC Immunochemistry Unit in Oxford.
Q What about the bottom, reference to complements studies?
A Yes, clearly this is just a draft because there is a reference to “details to follow”.
Q Page 111?
A Again, there is an annotation by me
Q I think it is 112, is it?
A At the bottom of 111, you will see a subscript.
Q Sorry, my fault, yes. Then over to 112?
A Yes, another annotation by me.
Q And then 115?
A Here, once again, to be completed are the complement studies at point number 5.
Q And finally 118?
A There is a reference, 10, which is missing.
Q Now, on the basis that this was a draft, as we see, going back to page 104 of a proposed clinical and scientific study, did you give that to Richard Barr?
A Yes, I did. By this stage the scope of the work had extended beyond Crohn’s to a proposal, or at least their bringing to my attention, that they were seeing many children with regressive autism, and I said we were aware, although we had not investigated any children, of similar problems, particularly with gastrointestinal symptoms, and that we were planning to conduct a clinical and scientific investigation of these children, and this was provided to him by way of information in the first instance.
Q And, just help the Panel, why did he need to know about what was going on or going to be going on at the Royal Free?
A He had asked me how I would go about designing a study that sought to answer the question of possible causation between these vaccines and Crohn’s disease in the first instance, latterly autism, and this was an example of that. I provided him with that information.
Q When you gave this document to Richard Barr, did you intend at that stage that he would send it to the Legal Aid Board?
A No. This was given to him some time before any submission to the Legal Aid Board, and was by way of information. I think it was far too complex for anything that the Legal Aid Board may subsequently have required, and I have no problem with such a protocol being sent to them at the right time but this was a draft and was clearly in the process of being produced, so it looks a little sloppy, at the very least, to be sending a draft protocol in.
Q The second document, page 121, is headed “Proposed protocol and costing proposals for testing a selected number of MR and MMR vaccinated children”. Now there are a number of questions I need to ask you about this document. First, who, in fact, drafted it?
A This was drafted by Richard Barr, with input from me.
Q Take this slowly, please, because it is an important area. How did it come about that you provided input to him and for what reason?
A When I had outlined the study for looking at autism and for looking at children with Crohn’s disease he asked me if we might put this together into a protocol to be submitted to the Legal Aid Board, and I said I was happy to do that, and what he needed from me was an estimate of the costings for the study that was proposed, and that was in the first instance fairly straightforward because what it required, based upon our experience of examining Crohnism colitis tissues historically was the salary of a technician for a defined period with expertise in the procedure of immunohistochemistry, who could examine these tissues, the cost for the associated re agents she or he would require for examining those tissues, the commercial re agents, for example, and the cost of the laboratory equipment, if any were necessary, to complete that study.
Q And when you are talking about, in this context, that study, which study are you referring to?
A I am now talking about the proposed Legal Aid Board study.
Q You told the Panel that the question of potential costs had arisen. In what sense might such costs arise?
A Once I had furnished Richard Barr with the initial costs for the laboratory work he said to me: “Please make sure you have included all possible costs that might arise in respect of this project”, and I asked him for guidance on what he meant by that and he said: “Well, if, for example, you require one of your colleagues to produce a report on the child, a psychiatric report, a neurological report, for example, then that is the sort of cost you should include. If, for example, clinical tests are required for the child’s admission that were not covered by an ECR or the doctor refused to admit such a child despite the clinical merits of their investigation, then that might be another area that needed to be covered - for example, the cost of an MRI or an overnight stay in a hospital, and we went back and forth on this because it was extremely unlikely that general practitioners or paediatricians were not going to be forthcoming in terms of making the referral, because these children were being investigated on clinical grounds for the clinical indication. Nonetheless, based upon his instruction, those potential costs were included in the submission that was being prepared for the Legal Aid Board.
Q And where do the figures that we see in the document and I will ask you to look at them in a minute come from?
A The costs of the technician and the re agents were something I was well aware of. I had been costing those for years in other research projects. I had no idea what the clinical costs were so I went to, I believe it was, David Lee(?), who was quite senior in the division of women and children’s health at the Royal Free, to seek his guidance and he was able to give me an estimate of the costs of a colonoscopy, or an overnight stay, an MRI, et cetera.
Q At this stage had you any reason to think that it would be inevitable that there would be no such costs arising?
A Absolutely. Since these were clinical referrals these costs, in essence, should not have arisen, but it was possible that if an ECR were refused but the child merited clinical investigation then funds would be available in that instance.
Q So it is to reflect the possibility that an ECR might be refused?
A Correct.
Q Looking at the structure of the document, and I appreciate you were not the drafter of it, did you see it before it was sent off, the final version?
A I do not remember seeing it in its final version.
Q If we look at the first page and look at the title, is that title a correct description of the exercise contemplated? In other words, it appears to be confined to vaccination?
A Yes, it is. I think it is a very reasonable title. What it does is to reflect the fact that the attached document was not appropriately attached, in other words, the attached document, the protocol that we were evolving, referred to measles infection and MR vaccination, and clearly Richard Barr was not interested in investigation of children who had had natural measles. That was not his remit. He did identify the potential ambiguity of using measles rubella vaccine, and this was because there had been an MR campaign in the October or November of 1994, and therefore he reconciled that ambiguity by referring specifically to MR and MMR vaccination.
Q Can you draw your attention to the second paragraph, where he says using the “testing” protocol attached. What do you say about that?
A Again, he is making reference to the draft protocol that he sent in with this document.
Q Is that a correct way of approaching matters? That using that protocol it will be possible to establish the causal link between the administration of the vaccine and the conditions outlined in this proposed protocol and costing proposals?
A Yes. This is his document and these are his words, and they are crafted in a legal way. In other words, they are not necessarily what a scientist might say. For example, it would be possible to establish “the causal link”. Now, it is more accurate to say that it would be possible to establish an association, for example, or a possible causal association, that would be scientifically more accurate, but the difference with this document is that one was dealing with a balance of probability argument, which is a legal argument and something with which I had no familiarity at all. I was used to dealing with scientific levels of proof and not balance of evidence arguments, so, as I say, these are his words, his interpretation, and it is framed in a way that would be understandable to presumably colleagues at the Legal Aid Board.
Q The first section that deals with costings refers to setting up costs. Insofar as you had input into that material could I ask for your observation, please, upon his assertion that it is anticipated that this sum will need to be paid once only, even if the trial lasts more than a year?
A Yes. This was my input. I had given him this advice and it was my feeling, based upon experience, that given the limited scope of the question that we were asking it would be possible to resolve this within a one year timeframe, and I was wrong. The reason, and this may require just a little explanation, is that the document that had to be produced at the end of this had to be scientifically credible, that means it had to be able to withstand peer review and be published, and I think Richard Horton of The Lancet has said himself: “If it is not published, it does not exist”. In other words, if evidence were to be produced that was to stand up in court then it had to, prior to that, have stood up to scientific scrutiny and be published.
The situation there is that you may complete work at the end of one year and you may feel that it is worthy of publication but the reviewers do not, and they require further work, and in this instance my estimate of one year to complete the work was, in fact, wrong and it required more than that.
Q You spoke about two separate groups, the inflammatory bowel disease cases and the enteritis disintegrative disorder cases, and on page 123 the document says that the costings are based on a proposal that in each category five children should be tested. Was it your idea that the scientific investigation should be limited to five children in each category?
A It seemed a reasonable number in the first instance. I will say two things: one is that this is another example of how this protocol, the Legal Aid Board protocol, is clearly different from the protocol that was attached to it which was the autism or disintegrative disorder study, because in this we see reference to five children with Crohn’s disease. Clearly they do not find mention in that larger protocol.
Secondly, science is an iterative process. If in five children with Crohn’s and/or five children with autism nothing were found, well, that might be a point under which to draw a line under it. However, if evidence of the virus was present in either or both of these groups then it would be worth pursuing, and for that reason, as a Legal Aid Board pilot, five in each group seems a reasonable number
Q When you supplied Richard Barr with the costing information, and the details can be seen on page 122, Dr Wakefield, did you supply that to him in good faith?
A Yes, absolutely.
Q Did you anticipate that Richard Barr may send these costings to the Legal Aid Board?
A That was my anticipation, yes.
Q And did you think that the Legal Aid Board might rely on that costings document?
A Very much so.
Q And did you anticipate that the Legal Aid Board may grant some money for the purposes of the Legal Aid Board pilot that you had described on pages 121 123, based on that document?
A I think it is fair to say that, given the novelty of this approach to the Legal Aid Board, or this scientific approach by the Legal Aid Board, it was something of a long shot, but nonetheless it was well worth trying.
Q Can I put it again: did you think that the Legal Aid Board may rely on that document and pay over a grant pursuant to an application made to it?
A Yes.
Q Had you had any dealings with the Legal Aid Board before?
A No. None at all.
Q Who was going to make the application?
A Richard Barr.
Q As matters stood in the early part of 1996, if an award were to be made, did you think that such an award might, therefore, in fact reflect the possibility of clinical costs to be incurred in the future?
A The possibility? Yes. The likelihood? No.
Q If, as it were to turn out, and we will look at it, clinical costs were not to be incurred, going forward, how would you prospectively deal with that point?
A The grant effectively was in two parts. The first, as I have set out at the bottom of page 121, was the setting up cost. This was clearly identifiable; it was the laboratory costs, the technicians costs, et cetera. The second part was to be incurred only as necessary and there was no pot of money at the Royal Free to pay for that.
My understanding from Richard Barr at the time was that during the process of awarding legal aid each child was awarded a sum I think in the order of £10,000, and that was to pay for legal costs and all associated costs for that child in the preliminary prosecution of their case and, again, it is a long time ago, but this is my memory. The situation was that, in the unlikely event that clinical costs were incurred, since there was no pot of money to cover those at the Royal Free, these would be invoiced on a per patient basis via Richard Barr who would then submit it for reimbursement to the Legal Aid Board. So in that way the Legal Aid Board, Richard Barr, would be aware of costs incurred for any clinical tests, if you like, on an ongoing basis. As the cost of the test arose, so the invoice would be paid. What I did not know at the time, which has emerged during this evidence, is that that is the agreement which had been arrived at by Richard Barr and Joanne Cowie, or the Legal Aid Board. But it was nonetheless my understanding, purely as a pragmatic exercise, that if these costs arose, that is how they would be dealt with.
Q Conversely, if the costs did not arise, what then?
A Then it would be evident to Richard Barr and the Legal Aid Board that they had paid nothing out.
Q At all times, Dr Wakefield, was there any legal relationship between yourself and the Legal Aid Board?
A No. No legal relationship at all as far as I am aware.
Q Who was your relationship with?
A With Richard Barr.
Q Could we turn to the unfolding correspondence, please, for some comment where appropriate? Turn to page 101, please, of volume 1. This is a letter from Richard Barr to a Mrs Simpson dealing with Legal Aid matters. This letter is not copied to you, but did you ever see it?
A No.
Q Can I ask you, please, to look at the first page, the third paragraph? It is dated 21 May:
“Dr Andrew Wakefield (who has been mentioned to you in Counsel’s Opinion and by me several times) is actually quite astonished at the evidence that he is uncovering and feels that objective tests may well establish conclusively that the measles vaccine is causing a wide range of these injuries.”
I appreciate these are Richard Barr’s words, not yours. Would you like to comment on how he puts those matters?
A I think it is written enthusiastically. As you say, this is his document, these are his words and therefore I am not able to put myself in his particular mindset. Nonetheless, my interpretation of this must be that, because as of 22 May 1996 we had certainly not seen or evaluated any children with autism, what he is referring to here is the other aspect of my work and that is the assimilation of the report on vaccine safety. In that respect, he is correct. I was somewhat astonished, alarmed, in reading the many hundreds of papers that had been published on this matter that the safety studies seemed, at least to my mind, to be wholly inadequate.
Q The next paragraph:
“I am waiting for his protocol proposals but a significant part of the costing will be in a proposal for testing a selected number of children to try and establish the link.”
Would you like to make any comment about the way he puts it there?
A Yes. I think that again, this is enthusiastic legal language possibly. In scientific terms, what one is trying to do is to adduce evidence for or against a link and that is how I would have put it.
Q Turn to page 103, please. This is again to Mrs Simpson from Richard Barr. Did you ever see this letter?
A No.
Q It is dated 6 June. You see the title. Do you have any observation about that? Is that a correct title?
A I think that is largely what it is referring to, yes.
Q The second paragraph:
“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.”
A Again, it cannot be correct, simply by virtue of the fact that the proposed legal Aid Board pilot study was five children with autism, five children with Crohn’s. The protocol that he appears to refer to is exclusively for the evaluation of children with autism. So I think Mr Barr has become confused on this point.
Q At page 124 is a letter to Mr Barr from Ms Cowie dated 27 June 1996. Did you ever see this letter?
A No.
Q I take you to page 125, just over halfway down, the end of the penultimate paragraph:
“I also note the kind offer made by Dr Wakefield to your goodselves to meet with representatives of the Legal Aid Board if required.”
Did you make that offer?
A Yes, I would have done.
Q Did you ever meet with the Legal Aid Board?
A I believe I met with Joanne Cowie in Sunderland on the back of an autism meeting there at some stage.
Q She referred to the meeting in Sunderland during the course of her evidence. Is that the same meeting?
A That is the one, yes.
Q Can I take you to page 155? Did you ever see this letter from Richard Barr to Mrs Cowie?
A No.
Q Just one small point. You may have already answered it, but on page 156, just over halfway down:
“To ensure that your concerns are dealt with comprehensively and to ensure that there is no more delay I suggest we have a full meeting with you to include Mr Augustus Ullstein, Dr Andrew Wakefield, Paul Balen …”
He was another solicitor, was he not, from another firm?
A Correct.
Q
“ … and Kirsten Limb and myself.”
Again, did that meeting ever take place?
A I do not remember it.
Q Then we go to page 183. Perhaps we can keep a finger in that and look at the same time at page 185. In fact, I will deal with page 185 first. This is a letter from Richard Barr to yourself dated 23 August 1996. Is that your writing on the top right-hand corner?
A Yes, that is my writing.
Q Do you accept that you received this letter?
A Yes, indeed.
Q That says:
“Dear Andy
I refer to the telephone message left on your answering machine on 22 August 1996 …”
Just pausing there, can you remember where you were at that time?
A I was on annual leave. I believe we had been away for two or three weeks on the continent.
Q
“ … and I am writing to confirm that at long last the Legal Aid Board has now given authorisation for the pilot study.”
What did you understand that phrase to mean, “pilot study”?
A This refers specifically and exclusively to the Legal Aid Board pilot study. That is, the investigation of five children with Crohn’s disease and five children with regressive autism and gastrointestinal symptoms.
Q He goes on:
“The limit is £55,000 which does include the setting up costs.
I think we need to have a meeting about the mechanics of running the study …
As I mentioned on the telephone the only slight cloud is that the Legal Aid Board rather hoped that within the £55,000 you would be able to include preparing us a written over-view in relation to vaccine damage.”
Just pausing there for a moment, I do not want to waste time by going back to the document, but had you informed Richard Barr to include in the costings document a fee element for writing an overview in relation to vaccine damage?
A No. This was a separate issue and another point of confusion. The £55,000, the up to £55,000, was for the scientific investigation. Writing the report was something quite different. In fact, I made no charge whatsoever for my time in the Legal Aid Board pilot study.
Q
“We have discussed this and I don’t know whether it is impertinent to suggest that you should do it within that funding bracket.
We also need to make sure that cases are properly selected for the pilot study. Obviously only legally aided children can be included (we have details of cases where legal aid has either not been granted or has not been applied for) …
I assume that for the purposes of the pilot study you would like us to supply a full set of medical records …”
And so forth. Just pausing there for a minute, Richard Barr is talking about the selection of cases. For what purpose did you understand children would be selected?
A Let me tell the Panel what it was and what it was not, because there has been some confusion. Richard Barr’s role in selection was exclusively to identify that a child who might be eligible for inclusion had in fact got Legal Aid Board funding, had a Legal Aid Board certificate and was a client of theirs. That was his only role in selection. He has absolutely no role whatsoever in deciding which children should be investigated clinically.
Q As we go forward, did it in fact come to pass that Richard Barr did select the children for the Legal Aid pilot?
A Yes, he did. The mechanism of this was that parents would make it known to him, as his clients, or parents of his clients, that their children were at some stage also undergoing investigation or had undergone investigation at the Royal Free or elsewhere. When he was made aware of that information, he would then be in a position to pass it on to me with the parents’ permission and then I could deem whether that child was suitable from a scientific perspective to be so included.
Q We see the authority that had referred to at page 183. Did you see this document itself at some stage?
A Yes, I did. I think this was provided to me by him.
Q On that basis, did you read the content of paragraph 2?
A Yes, I did.
Q
“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 …”
These are not your words, but there are three elements to that. The Legal Aid Board have used the phrase “the setting up of the clinical and scientific study proposed by Dr Wakefield”. Was that what you had in fact proposed to the Legal Aid Board?
A “Facilitate” is probably – sorry, let me deal with your point first. The study that had been proposed to them, the viral detection study, which was the important thing, and the possibility that clinical tests may be required suggest that that is an accurate term, but nonetheless it may refer to the document, the clinical and scientific investigation. That would be a mistake, if it were taken that that was a reference to the clinical and scientific investigation.
Q To deal with your point, “facilitation”.
A Yes. This clearly allows a degree of flexibility on my part as the investigating scientist to determine how best to approach this problem from the laboratory perspective and that was my understanding. They were facilitating my role in that.
Q Quite apart from the precise words that were used, was it correct that the study which was being proposed by you was in relation to ten assisted persons?
A Correct, yes.
Q Finally on this run of correspondence, would you look at page 187, please? This is a letter dated 27 August 1996 from Joanne Cowie to Dawbarns. She encloses a copy of the amended authority and then says:
“When the 10 children have been chosen for Dr Wakefield’s study please let me know so that their individual certificates can be properly amended.”
It may be, I do not know – you tell us – did you ever see this letter?
A No.
Q Were those comments she makes to Richard Barr consistent or inconsistent with your general understanding of how the system worked?
A Yes, I think so. The children would be chosen over perhaps a somewhat protracted period, because it required, as I say, the parent to make it known to Richard Barr that they were being seen at the Royal Free or elsewhere, had tissues taken elsewhere, and then that information to be passed on to me. Clearly I could not tell him, nor would I, who was being seen at the Royal Free. So the information had to come from the parent to Richard Barr and then to me.
Q Dr Wakefield, I want you to just stand back for the moment and address these questions: as of August 1996 you had been told that the Legal Aid Board was going to make an award to the solicitors to be dispersed up to a maximum of £55,000 in respect of the study that you were proposing, which you have described as “The legal aid pilot study”, all right?
A Correct.
Q What did you think might be included in the overall limit of £55,000?
A The laboratory costs and, if necessary, the clinical costs of the child coming in to be assessed.
Q Did it include possible funding in that regard for both groups of patients?
A Yes.
Q The IBD and the other group?
A That is a very good question actually, certainly the autistic children – and I cannot answer in the context of the Crohn’s children, I do not know. I would have to do the sums to tell you.
Q Do not worry about the sums for the minute, it may become the subject of discussion later, but the authority related to ten assisted persons, not five, ten: what do you understand to be derived from that?
A That it would cover those costs for the ten.
Q For both groups?
A For both groups.
Q Did you understand the award in principle for up to £55,000 to include the full setting-up costs?
A Absolutely. That was the only definite cost that might be incurred. The other costs were to be incurred as necessary.
Q At this stage, of course, you did not have the money, you just had the notification of the money.
A No.
MR COONAN: I want to move on to the period that saw the receipt of the first payment, and, Dr Wakefield, so we all have our bearings here: I am going to be looking at the period between September 1996 and December 1996.
THE CHAIRMAN: Sorry to interrupt, Mr Coonan, I am just wondering whether Dr Wakefield needs a short break.
MR COONAN: We all might need a short break, I do not know.
THE CHAIRMAN: This might be an appropriate time.
MR COONAN: I am more than happy to have a break now.
THE WITNESS: I am happy to carry on, I am fine.
THE CHAIRMAN: Are you sure, because I could see the reaction.
THE WITNESS: You have more experience than I do.
THE CHAIRMAN: If you are happy, Mr Coonan, and Dr Wakefield is happy, then we will continue.
THE WITNESS: I am happy to continue.
MR COONAN: (To the witness) Can we start looking at that period of time by looking at a document at page 192? The Chief Executive, Mr Else wrote to you on 4 September 1996, and there are a number of matters in this I would like your assistance with. He writes in relation to, and you see the heading of the letter:
“I am writing to confirm that the Special Trustees will fund the salary of Ms Rosslyn Sim to support the above project for a period of two years.”
Pause there a moment: first of all, what does the title refer to?
A This refers to the clinical and scientific investigation of the children with autism.
Q Is that the same title of the document that was submitted as we know in September 1996?
A In essence, yes.
Q He writes to the effect that he is writing to confirm, had you been in touch with him prior to that?
A Yes, I had, I had requested that the special trustees give consideration to awarding a grant to conduct some of the scientific aspects of this work.
Q When you say “this work”, can you in this territory please be very specific about what you are referring to?
A I am referring here specifically to biopsy analysis for the detection, on the one hand, of viruses and on the other hand with the characterisation of the disease process in the intestine of the children.
Q In terms of your contact with Martin Else at that time, were you referring in any way to the LAB pilot?
A No.
Q In so far as you were engaged in a conversation or discussion with him about funding, at that stage was her work covered by ethical committee approval?
A Yes.
Q Which was?
A 162/95.
Q Why did you approach the special trustees?
A Since the publication of our paper raising the possibility of a link between measles vaccine and Crohn’s disease, funding had become more and more difficult to obtain in this area and I was aware that the special trustees did not routinely fund projects. They acted as a charity which handled funding from other sources, but, nonetheless, given what was becoming a rather desperate state of affairs in a compelling area for research I approached Martin Else to see if he would help.
Q I may do this more than once later on but at this stage, please, so that we have no confusion, would you remember articulate the difference between the work that Rosslyn Sim was doing, or about to do, in relation to that study compared with the laboratory work which was anticipated under the LAB pilot study?
A Yes. Rosslyn Sim’s remit as an expert in immunohistochemistry was very much broader than the very narrow focus of the Legal Aid Board pilot study, in particular, and the greater part of her work was to be the characterisation of the disease process in the intestine, the cell types, the subsets, the numbers of cells, characterising the tissue damage in the intestine, and this was a very large part of her work. The second part was to be viral detection work. The Legal Aid Board pilot study involved only viral detection work in a limited number of cases initially.
Q Did you have any idea as matters stood at the beginning of September 1996 as to who would do the Legal Aid Board laboratory work in conformity with the Legal Aid pilot study, when you could start it; who was going to do it?
A Yes, I had been approached by a post-doctoral student from Germany, Dr Silke Schepelmann, who had a variety of techniques in which she was expert, and I was going to put Dr Schepelmann on to the Legal Aid Board pilot study (at least initially) as part of her introduction to my group.
Q Would you turn to page 199A? This is Dave Wilson writing to you on 13 September 1996, do you have that letter?
A Yes.
Q Mr Wilson writes:
“… Dr Schepelmann has been appointed as post-doctoral Research Fellow for a period of two years from 1 October 1996 to 30 September 1998”.
There is reference to the appointment letter, “the appointment is supported by a grant held by Dr Wakefield” and he raises a question.
Can we also turn on to page 237B, and keep your finger in both documents, please, 199A and 237B, is that your reply to Mr Wilson’s letter?
A Yes, it is.
Q We can all see what the letter at 237B says. Could you put this correspondence in proper context for us?
A He is asking me to identify the funding and seems to be trying to identify that it would be adequate for the tenure of her appointment. I point out to him that we have Legal Aid Board funding and an amount and an account number into which it should be paid.
Q You say in that letter:
“This is a most unusual source of funding but one cannot complain.”
A Correct.
Q Had you had such a source of funding before?
A Never.
Q You say you have written seeking the first £25,000. Why did you choose £25,000 as opposed to any sum of money in the light of the fact that the award was up to £55,000?
A The only definite cost was going to be that of the salary and reagents for the laboratory scientist. The other funds would be applied for as necessary as the costs were incurred, for example for any clinical tests.
Q If you look at page 237 you will see in effect what you had written about on 237B, the letter to the solicitors. Would you look at the content of this letter which was written to Richard Barr:
“We are now in a position to start work on this study on behalf of affected children identified by ourselves and approved by the Legal Aid Board.”
Which study are you referring to?
A Specifically to the Legal Aid Board pilot study of five children with Crohn’s and five with regressive autism.
Q “I would be grateful if the initial sum of £25,000 could be transferred …” and you have set out a named account – “for the purposes of initiating and carrying out the initial phase of this analysis … Naturally, we will keep you appraised of progress …”
When you said that you were “now in a position to start work on the study” what did you mean by that?
A I would imagine that by this stage Dr Schepelmann had been given her appointment – I cannot remember the precise date of that – and we were in a position to start the investigation as and when the tissues became available.
Q To what extent was the commencement of the Legal Aid Board pilot dependent upon the receipt of Legal Aid Board money?
A By definition, the Legal Aid Board pilot study, any work done under that grant could not start until that funding was available to be spent, by definition.
Q As of this date, September 1996, was that funding available to you?
A No.
Q Would you turn on to page 268? On 23 October 1996 Richard Barr wrote to Mrs Cowie, did you ever see this letter?
A No.
Q Perhaps you could have in mind the last letter I asked you to comment on, and I take you to the penultimate paragraph on page 268:
“Dr Wakefield is about ready to get up and running with his testing of the clients …”
Pausing there: would you like to comment on that?
A This is his interpretation of the letter that I have just sent to him saying that we are ready to begin.
“… I enclose a copy of his preliminary account to cover the setting up charges.
I am not sure that we have this document, but what do you think that would have referred to?
A The preliminary account will presumably be the sum contained within the letter.
Q It is possible, I do not know, might page 237 be a preliminary account?
A Yes, there is a specific sum referred to there.
Q At the end of the last paragraph on page 268 he says this:
“ … I should be grateful if you arrange for £25,000 to be issued to us so that we can pass it on to him. In view of the substantial size of this sum is there any additional documentation that the Legal Aid Board would like before the money is released to the Royal Free?”
And then this:
“We have, of course, already emphasised to him that the work must be done in accordance with the pilot study already submitted to you.”
Do you accept that that took place?
A Correct.
Q Moving on to page 292A, we are now in November 1996, and Dave Wilson was again writing to you. He says:
“… I had thought it might be of some use to provide you with a projection of her salary costs over the two year period.
…
Funding received or committed by the Legal Aid Board does not cover the full costs of the appointment …”
Did you have any observations to make about that letter?
A Yes, and it is entirely reasonable, the school had given her a two year appointment and were legally committed to that, but the funding thus far was for one year only and what he is in effect saying is “you have got to go and find funding for the second year”, which is exactly what I did.
Q At page 317 is Richard Barr writing to Mrs Cowie: did you ever see this letter?
A No.
Q Nonetheless, I would like you to comment on a number of parts of it. The first paragraph:
“You might be interested to know that they have already started testing some of the children.”
Pausing there: had you started testing some of the children pursuant to the Legal Aid Board pilot?
A No.
Q And he goes on:
“And so far every single child tested has come out positive with positive staining for measles virus in the inflamed area. They will now need to do very much more detailed testing to confirm that it is the measles vaccine virus that is causing the damage.”
Can you shed light on how it might come about that he makes that assertion, or those assertions, in that paragraph?
A Yes. Certainly. As part of the preliminary studies under the clinical and scientific investigation, Ros Sim had been conducting viral immunohistochemistry, and this had nothing to do with the Legal Aid Board pilot study but was part of our pilot study on the first 12 children, and he is correct, some of those tissues were undoubtedly positive for what looked like measles virus, and he is communicating that to Mrs Cowie. It appears he has become confused possibly, that is not evident from this letter, between our pilot study and his Legal Aid Board pilot study.
Q And then in the penultimate paragraph he reverts back to the question of the fee for the overview report and asks for a provision of £5,000 to be set aside. I am not concerned about that and I want to move on to another topic in the letter.
In the middle of number 2 paragraph, he says this:
“Dr Wakefield has suggested that one way of producing quite convincing evidence is to do a survey of the autism cases”
and the theme is picked up again on page 318, the penultimate paragraph.
“I would like to try to establish that there is a fairly consistent time link between the administration of the vaccine (MMR) and the onset of autistic features. To achieve this we have prepared a survey questionnaire (enclosed). This has been approved by Dr Wakefield. The aim is to send it out to all 170 families who are now on our database and invite them to fill it in as accurately as they can”,
and the details of that are set out at the paragraph that follows. I just pick up the last five lines:
“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”.
Now, survey, Dr Wakefield. What is all this about?
A I suggested to them, again quite outwith the Legal Aid Board pilot study I was conducting, or intended to conduct, that they might examine their population of children, which was now quite considerable, to ask the question or questions about the relationship between the timing of exposure to vaccine and onset of symptoms, and this would be particularly interesting in children who had been exposed to more than one dose, a phenomenon called “rechallenge”. If I, for example, give you a drug and you develop a rash - well, that is coincidence. But if, some years later, I give you the same drug and you develop exactly the same rash that is causation until proven otherwise, and rechallenge is a fundamental aspect of pharmaco vigilance of drug safety. So among their group were some children who had been rechallenged, and there was suggestion that, following the second exposure, there was anecdotally further, rather rapid dramatic deterioration. That sort of information is very powerful in the context of causation. Indeed, the Institute of Medicine in America accepted just one case as causation in a rechallenge instance. That is the kind of information that they could use or could have used the database to examine.
Q Can I just take you back to the first paragraph on 317? You spoke about the work that Rosslyn Sim had done. Again, we are now in November. Was that work covered at that stage by Ethical Committee approval?
A Yes, it was.
Q And what Ethical Committee approval was it that she was covered by?
A 162 95.
Q I want to move into December which is the endpoint of this period, and there are two letters I would like you to look at. The first one is at 337 from Richard Barr to you, 6 December, “Dear Andrew”, and sets out the subject matter.
“Further to our discussion on Thursday, I enclose a cheque for £25,000 made out to the [Royal Free Hospital School of Medicine] in respect of the setting up costs and first year’s costs of the MMR investigation”.
Just pausing there, what investigation do you understand him to be referring to?
A Here he is referring specifically to the £25,000 for the laboratory costs, the technician’s salary and the re agents.
Q Is that, to be absolutely clear, a reference to the Legal Aid Board pilot?
A Absolutely.
Q “I shall be grateful if you could arrange to let me have an official receipt and also for the enclosed receipt to be signed. This funding has been provided directly by the Legal Aid Board and the payment should go exclusively for the furtherance of investigation into the side effects of MMR/MR vaccine”.
Pausing there and jumping ahead for a minute, was that funding used exclusively in the furtherance of the investigation for the effects of MMR and MR vaccine?
A Yes.
Q Now, on the subject matter of receipts we had some evidence which was given about this, and I just ask you to deal with it. Page 338 is a document pro forma receipt. Right at the end it says:
“The Royal Free Hospital School of Medicine acknowledges receipt from Dawbarns of a cheque for the sum of £25,000”,
et cetera, et cetera, in other words, reflecting the wording in the letter. Did you or anybody else to your knowledge sign that document and send it back to Dawbarns?
A I imagine if I was asked to I would have signed it and sent it back, yes.
Q We have a blank copy in our bundle. Can you shed any light on that?
A No.
Q Look at pages 338a and 339, page 339 first. Here there is a receipt addressed to Dawbarns on 9 December signed by you not in the form that we have looked at on page 338. Did you construct the receipt?
A Yes.
Q And sign it?
A Yes.
Q And send it to Dawbarns?
A Correct.
Q Again, insofar as it is necessary to deal with this, can you shed any light as to why you did that and you did not send, or may not have sent in, a completed version at 338?
A I was seeking to comply with Mr Barr’s request. I appear to have transgressed Mr Tarhan’s rules and I apologise to him in his absence for that but
Q As you remember, the finance department was not particularly happy about the arrangements?
A No. Indeed.
Q Is there anything of significance to be attached to that, Dr Wakefield?
A None at all. I was over enthusiastic.
Q If we now look at 338a it has not been photocopied fully and it is a composite of the cheque and the letter, and the cheque is drawn on Dawbarns’ account and made out to the Royal Free Hospital School of Medicine, is that right?
A That is correct.
Q And not made out to you?
A No.
Q And the letter which you signed sends over the cheque to the finance officer, Dave Wilson, and I want you to look, please, at the terms of the letter. The heading is:
“Silke Schepelmann - Funding by the Legal Aid Board. Enclosed herewith is a cheque for £25,000 from the Legal Aid Board for the funding of Silke Schepelmann’s salary”.
Stopping there, was that still the understanding going forward that the Legal Aid Board money would be expended upon?
A At that stage, yes.
Q “This is the first payment received from the Legal Aid Board. I shall advise you of any other grants we receive to support her salary”.
Was that an honest account of your understanding at that stage, Dr Wakefield?
A Yes. I had agreed to seek further funds to cover the protracted period of her employment, and I had gone out and done that.
Q Now, that money was received by the School in December, the award having been made in principle in August. Had the Legal Aid pilot study started even by December of 1996?
A No. Once again by definition it could not start until the funds from the Legal Aid Board were available to be spent.
Q Now, Dr Wakefield, we heard from Professor Zuckerman and also from other evidence that the money that you had caused to be sent in cheque form to the school in the way we have just been looking at was not in effect accepted but paid into what was called a suspense account, and there is a number of pieces of correspondence relating to that which in the interests of completeness I am just going to ask you to go through.
Sir, I am just wondering, in fact, if it might be a good idea to have a break now.
THE CHAIRMAN: It might be a good idea; I think we are all starting to feel a little bit tired at this stage. We will adjourn and resume at twenty past three.
(Short break)
THE CHAIRMAN: Yes, Mr Coonan?
MR COONAN: Dr Wakefield, can we just start the next series of correspondence, beginning in January 1997? We have to look at the period from January 1997 until September 1997. We are not going to finish the whole of that period tonight, but I would like to start on it. We start on page 362A, which is a letter from you to Dave Wilson, again of the Royal Free Hospital School. This follows the sending of the cheque, as we saw 20 minutes ago, to the finance officer. In the first paragraph you say that you would like to establish an account to pay for Dr Silke Schepelmann and for the next two months Dr Andrew Anthony. Again, can you just comment about the various roles of people as matters stood in January 1997?
A Yes. Dr Schepelmann was a molecular biologist who had been designated to work on the Legal Aid Board pilot study as and when the funding became available to be spent. Dr Andrew Anthony was a histopathologist, or experimental histopathologist, working in the department of histopathology who had previously been paid from an account held in the name of Professor Roy Pounder.
Q You then in the second paragraph deal with a number of other sources of funding and you say in the sixth line:
“This grant will also receive funds from the Legal Aid Board in respect of studies conducted on children who suffered intestinal injury following MMR vaccination. The funds raised for this will be coming in over the next 3 years and will more than cover the salaries of Dr Schepelmann and, for the next 2 months, Dr Andrew Anthony.”
I may have taken that slightly out of context, because I have not read what preceded it. However, can you just help, please, about the language you use there in relation to the receipt of funds from the Legal Aid Board and the timeframe of three years?
A Yes. Let me take you back just a few lines. I had fulfilled, or was in the process of fulfilling, my obligation to Dave Wilson to generate funds from other sources to cover the salary of Dr Silke Schepelmann for the duration of her contract. There was an account and “the funds raised for this would be coming in over the next three years” refers to the account itself.
Q Does it refer – this is really the point of my question – does that sentence refer to funds from the Legal Aid Board?
A No. There was no agreement at any stage for funds for three years to come from the Legal Aid Board.
Q Then we move to page 366A, which is a note from Dave Wilson to Bryan Blatch. Did you ever see this?
A No.
Q I just want to pick up a comment made by Dave Wilson:
“We already hold on a suspense a/c £25,000 to potentially cover part of Dr Schepelmann’s salary costs. Dr Wakefield has earmarked further funding from the LAB over the next three years.
Has a decision yet been reached as to whether the funding can, or will be administered by the School?”
Just pausing there for two reasons. Firstly, did you know that the money had been put into a suspense account at that stage?
A No, I had not been advised of that.
Q He makes an assertion that you appear to have earmarked further funding from the LAB over the next three years. If you go back to page 362A, which was addressed to Dave Wilson, is his understanding correct?
A No, and I can understand his confusion, but, no.
Q Did you ever see the document at page 366?
A No.
Q I am not going to take you through it but in so far as it deals with issues relating to whether or not the department should accept the money or not, were you aware of those background discussions and so on?
A I do not think so, no, absolutely not.
Q At any rate, on 21 February, you wrote again to Dave Wilson, at page 370A:
“Thank you very much for your letter …”
Unless I have missed it I am not sure we have that letter:
“Thank you very much for your letter regarding the new account BXDXA. I would like Dr Schepelmann’s salary to come form this account as of 1 October 1996. I would, however, be very grateful if the Legal Aid funding could be paid into this account since it was principally given to us to investigate this new syndrome under Dr Schepelmann’s guidance.”
Again, just help us about that?
A It sounds by this stage that I am aware that this funding has not been paid into the account that is to pay her salary; that I have gone out and raised funds to cover her salary from elsewhere, but for some reason (that I am clearly not certain of at this stage) that Legal Aid Board funding has not been placed in this account.
Q Then at page 371 there is an internal memo and it would appear that Mr Blatch is asking or telling Mr Wilson that the money should remain on the suspense account: did you ever see these internal memos?
A No.
Q We have got to turn to bundle 2, starting at page 401. In March 1997 you wrote a letter to Professor Zuckerman and this is now nearly four months after the receipt of the money by the school from the Legal Aid Board. In the first three lines in the letter you indicate that you are enclosing all documentation relating to the involvement of Dawbarns and the Legal Aid Board:
“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 of the Royal Free Hospital.”
Pausing there: why did you send Professor Zuckerman documentation relating to the Legal Aid Board?
A When I was made aware that the funding had not been paid into the account as I had requested, I got the information that Professor Zuckerman, the Dean, had requested that it been placed in a suspense account and I will have made contact with him to try and establish why, and during those discussions he will have given – or at least I refer here in this letter to some of the reasons that he has alluded to but has not been very specific about, but what I wanted to do in sending this letter and attaching the documents was to fully appraise him of the terms and conditions under which this grant had been awarded so that he could satisfy himself that it was indeed for the conduct of a legitimate piece of scientific investigation.
Q Keep a finger in 401: did you enclose pages 402, 403 and 404, documents we have looked at already, for the assistance of Professor Zuckerman?
A Yes.
Q The rest of the letter – and, again, I am not going to waste time by reading it all out – is directed, is it not, to your endeavour, as you saw it, to establish or refute the link between MMR vaccine and the disease, and in the context of the Legal Aid Board pilot, is that an accurate summary?
A Correct.
Q As far as you can recall, what had been Professor Zuckerman’s concern prior to that?
A Do you mean the telephone conversation we had had?
Q Yes.
A He referred to a conflict of interest but he did not specify at the time what that conflict of interest was.
Q Was this letter, or part of it, you dealing with the issue of the conflict of interest?
A Yes. I could not see quite what the problem was. Here was a grant, the source of which was unusual but nonetheless was awarded for the conduct of a legitimate piece of science and I failed to see how that was in conflict with my duties as an investigator.
Q In fact, I do not want to get bogged down into issues of conflict of interest for the moment, but if you just go back to pages 393 and 397, are those documents passing between you and Professor Zuckerman which touch on an issue of conflict of interest?
A Yes, particularly in the third paragraph I refer to that conflict that he had mentioned.
Q On page 393?
A Yes.
Q I am going to come back to the whole question of conflict of interest later, but I want to keep on my path of dealing with the legal aid monies. Go back, please, to page 401, and please look at the fourth, fifth and sixth lines, the sentence beginning:
“These conditions were based upon the enclosed protocol which has been approved by the ethics committee of the Royal Free Hospital.”
What are you referring to in that sentence?
A I think what included in the documents are the combined protocol, the clinical and scientific investigation plus Legal Aid Board protocol, most certainly the latter, but including, clearly, the investigation of children with developmental disorder that had been approved by 172-96 at that stage.
Q If we move on to 428a, you are writing to Dave Wilson and it is now 28 April 1997. Had you got access to the funds by this date?
A Clearly by this stage I felt that my exchanges with Professor Zuckerman may have resolved the problem and that his reading of the documents, having enlightened him, may have made him feel willing to accept the money, and I suppose this was an assumption that that had taken place and that the money was now available to be spent.
Q In fact, did that turn out to be the case?
A No.
Q And when you asked Dave Wilson to extend Dr Anthony’s contract to be paid “from the funds available to us from the Legal Aid Board”, can you just help the Panel, please, how does it come about that Dr Anthony may be ending up being paid, as it would appear, from money from the Legal Aid Board, assuming the money is available?
A Dr Anthony’s job was in the interpretation of the histopathologies. Ros Sim’s job was to conduct the immunohistochemistry sorry, let’s go back. Silke Schepelmann’s job was to have been to conduct the immunohistochemistry: Andrew Anthony’s job was to have interpreted that down the microscope, and therefore his contribution was essential to the conduct of the Legal Aid Board pilot study. Ultimately it was part of it but not charged for.
Q But at any rate had the Legal Aid Board pilot started by 28 April?
A No. Again, by definition, it could not have done because the funds were not available to be spent.
Q Turn on, please, to 469, a memo from Mr Tarhan to Professor Zuckerman and Mr Blatch on 20 May 1997. Did you see this document?
A No.
Q Let’s look and see what it records, nonetheless.
“Mr Wakefield is unhappy with the fact that the School has not formally accepted the research funding and has asked that the funds be returned to the Solicitors”.
Was that an accurate reflection of the position at that time?
A Yes, I felt the only honest course at this stage, if we were not going to be allowed to conduct this Legal Aid Board pilot study, was to send the money back in total.
Q Did you speak to anybody else about that problem?
A I will have discussed it with my line manager, Professor Roy Pounder, at some stage, yes.
Q On page 470, on another copy of this memo, Professor Zuckerman has written in effect that the funds be transferred to the Special Trustees at the Hospital. Were you aware of the timing of any such decision?
A No. This is rather confusing and has always rather confused me. When I discussed this issue with Professor Roy Pounder he said: “Why don’t you administer or have the funds administered through the Special Trustees as an alternative if the Dean is not happy?” Then we explored that possibility and that ultimately came to happen, but the timing is somewhat confusing, particularly in light of Professor Zuckerman’s testimony, and so having not seen this document and not being aware of it the timing is difficult to interpret.
Q Now, the next document I want to ask you about is an important document, and I may need to spend a little time on it. I see the time and, sir, I do not know whether you might think that is a convenient moment to pause, because I am going to spend about 15 or more minutes on this document.
THE CHAIRMAN: Yes. I think in that case it will probably be better that we conclude for the day now.
We will now adjourn and resume at 9.30 on Monday morning. Dr Wakefield, I should tell you that you are under oath, you are in the middle of giving evidence, and it is not always easy for practical reasons but please make sure that you do not discuss this case with anyone.
MS SMITH: Sir, can I raise quickly one administrative matter? The Secretary has told me that one or two members of the Panel have asked whether they can have an electronic version of the list of the principal medical records which we are inviting you to read before the experts are called. It is just a list of page numbers. You all have that in paper form but I understand you would like to have it electronically, and what we will do is e mail it to the Secretary and she can e mail it on to the individual members. I understand it would be helpful for you to have it by the time Mr Coonan is asking about the individual children.
THE CHAIRMAN: Obviously I do not have any problem with that but, Mr Coonan, have you any objection to that?
MR COONAN: No, sir. Very helpful.
THE CHAIRMAN: Mr Miller?
MR MILLER: No problem, sir.
THE CHAIRMAN: Mr Hopkins?
MR HOPKINS: I have no problem, but could I be included in the e mail, please?
MS SMITH: Certainly.
THE CHAIRMAN: Thank you for raising that particular issue, and now that it has been resolved can I wish you all a good weekend and see you on Monday morning at 9.30.
(The Panel adjourned until 9.30 a.m. on Monday 31 March 2008.)
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