GENERAL MEDICAL COUNCIL
FITNESS TO PRACTISE PANEL (MISCONDUCT)
Monday 8 October 2007
Regents Place, 350 Euston Road, London NW1 3JN
Chairman: Dr Surendra Kumar, MB BS FRCGP
Panel Members: Mrs Sylvia Dean
Ms Wendy Golding
Dr Parimala Moodley
Dr Stephen Webster
Legal Assessor: Mr Nigel Seed QC
WAKEFIELD, Dr Andrew Jeremy
WALKER-SMITH, Professor John Angus
MURCH, Professor Simon Harry
(Transcript of the shorthand notes of T. A. Reed & Co.
Tel No: 01992 465900)
A P P E A R A N C E S
MS SALLY SMITH QC and MR CHRIS MELLOR and MR OWAIN THOMAS of counsel, instructed by Messrs Field Fisher Waterhouse, solicitors, appeared on behalf of the General Medical Council.
MR KIERAN COONAN QC and MR NEIL SHELDON of counsel, instructed by Messrs RadcliffesLeBrasseur, Solicitors, appeared on behalf of Dr Wakefield, who was present.
MR STEPHEN MILLER QC and MS ANDREA LINDSAY-STRUGO of counsel, instructed by Messrs Eastwoods, Solicitors, appeared on behalf of Professor Walker-Smith, who was present.
MR ADRIAN HOPKINS QC and MR RICHARD PARTRIDGE of counsel, instructed by Messrs Berrymans, Solicitors, appeared on behalf of Professor Murch, who was present.
I N D E X
PROFESSOR IAN WESTERBY BOOTH, Sworn
Examined by MS SMITH 1
THE CHAIRMAN: Good morning. Ms Smith, I think you were going to introduce a new witness. Is that going to be the start of the proceedings this morning, or is there any other matter?
MS SMITH: Yes, sir. I am going to call Professor Ian Booth.
IAN WESTERBY BOOTH, Sworn
Examined by MS SMITH
(Following introductions by the Chairman)
Q Professor Booth, could I ask you first of all to give us your full name and address, please, and your medical qualifications?
A Ian Westerby Booth. My home address is XXX. My qualifications are BSc in Physiology, MSc in Biochemistry, a doctorate in medicine: Bachelor of Medicine, Bachelor of Surgery, Fellow of the Royal College of Physicians, Fellow of the Royal College of Paediatrics and Child Health.
Q I want to begin, if I may, by asking your about your own personal experience which qualifies you to express views in this case. You have produced a CV for us. If you go to the bundles in front of you, you should find one which has FTP7 on its spine. If you go to page 33 in that file, please, that is the beginning of your CV. If we go on to page 35, does that give your present appointment, which is Professor of Paediatrics and Child Health at the University of Birmingham Institute of Child Health?
A That is correct, yes.
Q I think it is right that you held a professorship firstly as a personal chair and then in your present position since 1992 at the University of Birmingham Institute of Child Health.
A That is correct.
Q Since 1993 you have been the Director of the Institute of Child Health at the Medical School at the University of Birmingham.
Q Your CV refers to you from 2000 as being the Deputy Dean of the Medical School, but that is in fact out of date and you have recently been appointed as Dean.
A That is correct.
Q Just to remind the Panel, that is the position which Professor Zuckerman held at the Royal Free during the period with which we are concerned, in other words, the head of the Medical School. Is that correct?
Q In addition, do you hold an honorary consultant position at the Diana Princess of Wales Children’s Hospital in Birmingham?
A Yes, I do.
Q With regard first of all to your academic appointments – a rather obvious question, I am afraid – has that meant a very considerable involvement in medical research?
A Yes, it has.
Q Has that been both clinical research, in other words, involving patients, and laboratory based research?
Q For how long would you say that you have been involved in research medicine?
A Probably since the late 1970s.
Q In addition to that research medicine, are you a clinician because of your honorary clinical appointment, seeing patients in the normal way?
A Yes, I do.
Q In broad terms, insofar as you are able to say, does your work cover the same sort of set-up as that of Professor Walker-Smith and Professor Murch?
A I think there might be some differences in emphasis. My impression is that the work at the Royal Free dealt mainly with inflammatory bowel disease. We have a more extended repertoire perhaps, in that we provide input into the regional neonatal intensive care unit for gastroenterology problems and the regional neonatal surgical unit, which is a major source of referral of patients to us with intestinal failure. We also have a major input into the small bowel transplantation programme at the Children’s Hospital in Birmingham, which is the only one of its kind in the UK. So we practise across quite a broad range of paediatric gastroenterology and nutrition.
Q Does your work also cover the inflammatory bowel disease work?
A Yes. I cannot be absolutely certain, but I have been told by my colleagues that our referrals to the European Registry of IBD in children is the highest in Europe at the moment. So we see a lot of patients with IBD.
Q As far as you personally are concerned, you have told us you have a Chair in the University, are you any more or less academic or clinical, or do you span the two?
A These days, all people who have NHS consultant contracts, whether it is a substantive NHS contract or, in my case, an honorary NHS contract, have to have a very carefully defined job plan which gets reviewed annually. All clinical academics have to have at least five programmed activities out of a total of ten or more per week and I have five clinical programmed activities in my job plan, which, because of pressure from the NHS, are quite difficult to relinquish.
Q Just look at the rest of your CV, if we turn on to page 40, please, we see the committees and working groups with which you have been involved, both for the Department of Health and for the Health Education Authority at the Royal College of Paediatrics and Child Health, which was formerly the British Paediatric Association. Is that correct?
A Sorry, did you say page 40 or 41?
Q Could we go to page 40 for the moment? That is the offices within medical societies. You have been President of the British Society of Paediatric Gastroenterology and Nutrition, Chairman of the Paediatric Committee of the British Society of Gastroenterology and Council Member of the Paediatric Research Society, amongst others.
Q Then, as you rightly point out, I have already referred to the committees and working parties on page 41. Then coming on to page 44, we see you have been an external examiner for numerous universities which are listed there and you have had both editorial responsibilities and the refereeing of scientific manuscripts and we can see that you have been on the editorial board of a number of scientific journals as well as refereeing manuscripts for a number of journals, including The Lancet, The British Medical Journal and Gut. Is that correct?
A That is correct, yes.
Q Turning on to page 47, I am not going to go through all those, but those are the start of your publications and they run to some 250 scientific papers, chapters, reviews and articles.
Q As a result of all those publications, Professor Booth, involving medical research, have you experience of submitting applications to research ethics committees?
A Yes, I have.
Q And submitting papers to scientific journals for publication?
A Yes, I have.
Q In both those respects, you say you have experience. Is that very extensive experience?
A I think so, yes.
Q With regard to your own clinical practice, do you regularly see children as patients?
A Yes, I do.
Q Does that include, amongst of course many other children, children with autism?
Q Do you yourself personally carry out colonoscopies?
A Yes, I do.
Q When did you last do a colonoscopy?
A Last week.
Q Do you have out-patients clinics every week with children?
Q You told us a little bit about your own unit in Birmingham. You said you believe it to be one of the biggest centres as far as referrals are concerned for paediatric gastroenterology. Can you just help us as to how many other centres – I do not expect you to be able to enumerate them all – but how many centres in the UK there are for specialist paediatric gastroenterology and IBD in particular?
A The number has grown consistently over the last 20 years. Most old NHS regions have a centre now, so I suppose it is 12 or 15; something like that.
Q Turning to the circumstances of this particular case, before we go into them, I want to deal with some general principles and terminology that we are going to be using consistently throughout. You can put away your FTP7 if it gives you a little more room. I want to ask you first of all, Professor Booth, in basic terms, and remembering we have some medical members and some lay members on the Committee, inflammatory bowel disease – what exactly is it?
A It can be interpreted in a number of ways, but conventionally, certainly in this country, we use it to describe a group of patients who either have inflammation in the gut due to Crohn's disease or ulcerative colitis or, in some cases where the differentiation in the colitis is not possible, at least initially we talk about an “indeterminate colitis”. Those are the major groups, but there are patients who have inflammation in the gut that falls outside those definitions. In general, when people are talking about inflammatory bowel disease it is those three disorders that we are referring to.
Q So that is Crohn's disease, ulcerative colitis and then, as far as indeterminate colitis, is concerned, you say there are uncertainties about it, but as to what categories? Just those two categories?
A Sorry, I do not quite understand.
Q I am sorry. When you talk about indeterminate colitis, you said that is because there are uncertainties about categorising it?
A Yes. They have inflammation that is confined to the colon, which has perhaps some features of ulcerative colitis, some features of Crohn's involving the colon – Crohn's colitis – and even after looking at all the available information it is not possible to say for sure whether it is Crohn's or ulcerative colitis. So under those circumstances, you follow the patient up and wait and see what evolves.
Q Colitis – you better just tell us what colitis is?
A Colitis literally means an increased in inflammatory cells in the lining of the colon. That would be one definition. If you are seeking a clinical definition, then it would imply that this is a patient who has bloody diarrhoea.
Q As far as inflammatory cells are concerned, if you were to look at the colon – I appreciate the circumstances are difficult to imagine – but if you were to look at the colon of somebody who has no symptoms of any kind, would you still expect to see some inflammatory cells?
A Yes. It is never free of inflammatory cells. There are always some inflammatory cells there, yes.
Q Are there any other types? You have now told us about Crohn's disease, ulcerative colitis and indeterminate colitis which might be one or the other, are there any other types of colitis which are generally recognised?
A Yes, there are.
Q Can you tell us?
A Some patients have a colitis due to an infection, like Shigella or certain types of salmonella or various types of e-coli. Some patients have colitis as a result of graft versus host disease; Hirschprung’s entercolitis, Bechet’s. There are a number of other, much less common causes.
Q And as far as children are concerned, is inflammatory bowel disease of the conventional kinds, if I can use that term, the most common kinds, ulcerative colitis and Crohn's disease, is that a common or an uncommon condition to find?
A I think it depends which population you were sampling. If you sampled the population that a general practitioner were seeing, for example, it would still be relatively uncommon in children. If you were sampling the population in a tertiary level gastroenterology centre, it would be very common. The jury is still out whether there has been a true increase in, particularly, Crohn's disease over the last 30 years or not but certainly, for one reason or another, paediatric gastroenterologists are seeing a lot of patients with inflammatory bowel disease now.
Q In general terms, is the cause known for inflammatory bowel disease?
Q How is it diagnosed?
A It starts, as most diagnoses do, with taking a full history from the patient or, in this case perhaps, the parents as well, examining the patient and on that basis formulating a differential diagnosis. If within that differential diagnosis you think inflammatory bowel disease should be included, depending on the symptoms that the patients had, you would either arrange for some preliminary investigations or in a patient who had severe bloody diarrhoea where it was clinically fairly obvious that they had a form of colitis, once you had excluded infective causes you would proceed to a colonoscopy. Generally it is not always clear-cut in that way, so some preliminary investigations are often needed.
Q You have mentioned bloody diarrhoea. In so far as the clinical picture is concerned again, in broad terms I am talking at the moment, what are the symptoms? Is that the only symptom, or are there others?
A In a patient with colitis?
A Normally they would have bloody diarrhoea, abdominal pain. They often have a symptom called tenesmus, where they open their bowels and there is a subsequent feeling of needing to return to open their bowels. It is a feeling of incomplete evacuation. Often patients are systemically unwell. They may have a fever, for example. They are often off their food.
Q And as far as children are concerned, does being off their food have a knock-on effect as far as their general overall ---
A Yes. If it is sustained, then obviously they lose weight. If that continues they undergo a process of reductive adaptation and stop growing.
Q I want you to explain exactly what happens at a colonoscopy, if it is decided that it is appropriate to carry out that investigation. Before I do so, perhaps I can hand around to you two diagrams that Professor Booth has produced for us. One is an anatomical diagram, and is referred to as a “Road Map”. I think they could probably have one exhibit number between them, which will be C13.
THE CHAIRMAN: The larger diagram, “The Digestive System”, we will call C13. What do you want to do with the other one?
MS SMITH: I was going to suggest you had them both with one number.
THE CHAIRMAN: We wills staple them together and make them as C13. (Exhibit marked and circulated)
MS SMITH: Now you have them, Professor Booth, do feel free to refer to them when you think it might help in anything that you are explaining. What I would like you to tell us first of all, endoscopy is the general umbrella term. Is that correct?
A Yes. It means looking into a hollow organ with an instrument.
Q Can you explain to us, by reference to which diagram is the most helpful, exactly what happens? If you decide a child patient has to have a colonoscopy, what do you have to do?
A In the outpatient clinic, once you have decided to recommend a colonoscopy, you would have a discussion with the parents and if the child was old enough explain to them what was going to be involved. Then, quite often, if they have not had a colonoscopy before, one of the specialist nurses would see them and go through it in more detail, and also give them a further opportunity to ask questions about the procedure. Two days before the colonoscopy takes place, the child goes onto a liquid diet, which is to remove as much residue in the diet as possible, so that there is less stool in the colon. One of the problems with colonoscopy sometimes is visibility. On the day before the investigation, children are given strong laxatives so that they have quite bad diarrhoea to flush all the stool out, otherwise you would not see anything when you put the colonoscope in.
The child then comes in. If it is just for a colonoscopy they would come in as a day case first thing in the morning, to the day unit. These days the procedure is done under general anaesthetic because it is much more – one hesitates to say “pleasant” – but a lot more acceptable to the patient to be anaesthetised for a colonoscopy. We use to use intravenous sedation and analgesia.
Q Can I just stop you there, just to ask you: in 1996, which is the time, you know, with which we are concerned, generally speaking what was the procedure as far as anaesthetic was concerned? Would it be local?
A Intravenous sedation and intravenous analgesia. The patient comes to the endoscopy unit and either they are intravenously sedated or anaesthetised. The endoscope is introduced at the anus, which is No. 1 on the blue diagram. Then it is insinuated round the colon, round to the caecum, which is on the other side, No. 10 and then, if possible, into the terminal ileum, which is No. 13, but which is missing on here, but which is next to No. 11.
Q You say it is insinuated in. It is a catheter, is it, a tube?
A It is a plastic-coated instrument that is a metre or so long. I suppose it is about the thickness of that pen (demonstrating). They vary. For older children, bigger children, we would use a somewhat thicker endoscope than for small children, so there are a variety of sizes. It has a means of illuminating the inside of the colon, a means of blowing air in, a means of washing the lens, and a means of taking biopsies, and a means of sucking out as well.
Q Is part of the procedure to blow air in to expand the area you are looking at?
A So you can see where you are going, yes – if necessary.
Q And it is then possible – it is not relevant in the circumstances of this case because these doctors were looking to see what they could see and to take pictures of it – to undertake various procedures, is that correct, when you have actually got in there?
A Yes. Almost invariably you would take biopsies which involve putting a long, metal pair of forceps down the scope, and snipping off little pieces of mucosa. The other procedure that is commonly undertaken is to remove polyps, so where there is a polyp in the colon, you can put a wire round it and pass an electrical current through the wire which severs the polyp, and you can remove it.
Q There were indeed biopsies taken in the cases with which we are concerned. We can see on the colon roadmap diagram actually photographs in the circles. Are they taken during the procedure?
A Yes, yes.
Q And is that part of the procedure, to take pictures so you can study them afterwards?
A Often, but not invariably. It would depend on the particular circumstances. We have a particularly low threshold for taking photographs, because one of my colleagues has just co-authored a big atlas of paediatric GI endoscopy so he was very keen to have plenty of pictures.
Q If you are just doing that exercise, Professor Booth, of inserting the colonoscope, taking pictures if you were taking biopsies, how long does the whole procedure take?
A From when you introduce the endoscope into the patient?
A It is quite variable. In some patients it might be over in 15 minutes; sometimes it takes an hour, sometimes longer. It just depends on what the question is that you are trying to address. The last colonoscopy list that I did, one of my colleagues was particularly keen for me to, because it was a patient who had had a small bowel transplant. They were very keen to get round into the bit of small intestine that was the transplanted bit, and take some biopsies. That took a very long time.
Q This is a terribly general question, I do appreciate that, and like any other patient, they do differ from each other, but generally speaking it is a procedure children tolerate well?
A I think they tolerate it a lot better now that we do it under general anaesthesia. I think that is an important consideration when a lot of patients, either because they have inflammatory bowel disease or because they have a syndrome where they get a lot of colonic polyps, so they need repeated colonoscopy. It is much more acceptable, particularly to those patients, to have the investigation under general anaesthetic. In the old days the intravenous sedation and analgesia was reasonable, but a lot of children found it an upsetting experience. One of the sedatives had the effect of tending to make them forget the procedure, which was often quite fortunate.
Q You have produced some literature for this. I am not going to take you to a great deal of it but I want to look at one or two of the extracts from contemporaneous or earlier literature in relation to this. Would you go to FTP5, page 15, please. This is a chapter from a textbook in 1992 on gastrointestinal endoscopy by Professor Mougenot.
A That is right.
Q Is this a fairly standard textbook for 1992?
A Yes, it is a French textbook translated into English.
Q If we could look at the left-hand column:
Perhaps I could just stop myself there, because we have seen this raised in other parts of the literature I am taking you to. That is just a broad term for any endoscopic procedure going to different bits of the anatomy that are set out on that map, is that correct?
A No, the oesophagogastroduodenoscopy refers to endoscopy from the top end of the gastrointestinal tract, so the endoscope is introduced through the mouth, passed down the oesophagus into the stomach and then into the duodenum.
Q The text continues:
“… and colonoscopy” –
which, as you have explained, is from the rectum –
“have only recently been introduced into paediatrics. These exploratory procedures, at first limited by the inadequacy of available materials, have developed rapidly during the past few years, which explains the appearance of fibroscopes of slender diameter and the formation of experienced paediatric teams.”
That is in 1992, so by 1996 it had become a relatively widespread investigation.
A Yes, that is right.
Q If we turn on to page 17, the right-hand column, under the heading “Preparation of the colon” – and you have explained this to us, we see that it says, :
“There is no point in dietetic measures. Evacuant enemas and laxatives are often included in the preparation.”
It gives the laxatives and then continues:
“It will still be necessary to give several large warm enemas 2 to 4h before the examination and these must be repeated if they produce any solid material.”
Is that your experience, that children frequently require enemas as well as laxatives?
Q Is that an early ----
A No, I think that just reflects the preferences of these particular people. In the UK, right from the early days, when we started doing colonoscopies in children in the late 1970s, we used very much the sort of laxative regimen that we still tend to use.
Q And that you find enables a sufficient clearance.
A Yes. Children find it particularly unpleasant to have enemas.
Q Turning on to the next page, the left-hand column, under the heading “Features of colonoscopy”, reads:
“Unlike rectosigmoidoscopy, which can be done without premedication, total colonoscopy is sometimes a painful procedure. The pain that indicates colonic distension or excessive stretching of the sigmoid loop or the transverse colon is a valuable alarm signal as he fibroscope advances. Nevertheless the unpredictable character and the intensity of the abdominal colic have led most paediatricians to perform total colonoscopy under general anaesthesia. After 10-12 years some prefer neuroleptic analgesia.”
That would be heavy sedation, is that correct?
“In some children it is still possible to perform total colonoscopy under a simply premedication.”
But, generally speaking, even at that stage, general anaesthesia, given the degree of pain, was apparently thought to be preferable.
A Yes, that was their particular preference and probably it would have been most people’s preference. In the UK, in the NHS, it was largely, I think, an issue of resource.
Q At page 19 are the complications of endoscopy. ON page 20: “Colonoscopy”:
“Perforation is a major but rare complication of colonoscopy. It is brought about in two ways:
(1) direct trauma to the mucosa by the colonoscope ….
(2) a punctiform wound made by the end of the colonoscope …
These complications are often due to inexperience of the operator, particularly if an attempt is made to advance ‘blind’ … More rarely, perforation of the colon and even of the ileum complicates exaggerated insufflation.” –
In other words, as you have told us, the introduction of air.
Q Then they mention the risk of abdominal distension, of infectious complications, going on to the next paragraph; in other words, infection caused by the procedure. Generally speaking, are they the major, albeit everyone accepts, very small risks of the procedure.
A Yes. The risks of perforation are small.
Q Turning on to page 23, the indications for the procedure, at the bottom right-hand column:
“The symptoms that lead to a request for proctocolonoscopy in children may be summed up as follows:
(1) recurring rectal bleeding with no anal lesions.
(2) signs indicative of colitis; that is mucousy and/or blood diarrhoea, abdominal pain which may or may not be combined with emaciation, and a febrile state.”
That is in 1992. Would you agree that in broad terms those are the indications?
A Yes. They had not really changed. When we published the first description of colonoscopy in children ten years earlier, those were essentially the same indications.
Q Thank you. Is constipation, as a general proposition, ever an indication to undertake a colonoscopy?
A I cannot think of an indication. Expressly, it would be a contra-indication because you would find it hard going to see anything.
Q If there is a problem which involves constipation as a symptom, is it sometimes the case that it is assisted by the preparation for the colonoscopy; in other words, the clearing out of the colon?
A Yes, the preparation for colonoscopy is a very effective treatment for constipation.
Q When you say you cannot think of a situation where constipation would be an indication, do you sometimes have a situation arising where there is an overflow problem?
A Yes, one of the problems sometimes with making the diagnosis of constipation is that it can present with what is loose stools, which parents interpret as diarrhoea. Not surprisingly, often there is abdominal pain because the colon is full of stool and the colonic muscles are trying to empty the colon against an obstruction. In patients who have severe constipation, eventually the colon reaches its capacity for the amount of stool that it is possible to hold and stool starts leaking out from the anus, often uncontrollably. It is called “spurious diarrhoea” and in fact the patient is constipated but the parents come along and say, “My child’s got diarrhoea.”
Q For a paediatric gastroenterologist, as opposed to a parent, how do you make the distinction between spurious diarrhoea and true diarrhoea?
A Often there is an earlier history of constipation. If you take a careful history about bowel opening and the nature of stools, it often begins early on with constipation and then subsequently they develop this spurious diarrhoea. Sometimes the situation has been compounded because they have sought medical advice – someone has said, “You’ve got diarrhoea, we will give you something to stop the diarrhoea” so they get a medication that makes the constipation even worse. Sometimes when you examine the patient and do a rectal examination you find that there is a lot of stool all the way down that you can feel with your finger, so that the rectum is full of often quite firm stool and when you examine the patient and put your hand on the abdomen you can often feel a lot of stool retained within the abdomen. Sometimes, if it is not entirely clear and often as a means of convincing the parents that their child actually does have constipation and not diarrhoea, because this is a concept that they find difficult to understand, an abdominal X ray is very helpful. Our practice is to give little pieces of white plastic which show up on the X ray over several days, and then, after a further two days, to take an abdominal X-ray and the parents can see that all the markers are still inside the patient even though they have had loose stool, so it is a very graphic way of demonstrating that the patient has constipation.
Q I want to turn on a little bit later to 1994, so a couple of years before the time with which we are concerned. Would you turn to page 27 in volume 5, please. The first paragraph reads:
“Colonoscopy is an established procedure for the investigation of large bowel and terminal ileal diseases in infants and children. There are specific indications that vary with the age of the patient, including unexplained rectal bleeding, chronic diarrhea, evaluation of an abnormality visualized on barium enema, family history of polyposis syndrome [polyps], diagnosis and management of inflammatory bowel disease, and therapeutic intervention. The preparation and sedation of the child and the technique of colonoscopy must be tailored to the age and physical stature of the patient. Familiarity with these issues is essential for the endoscopist performing paediatric colonoscopy.
Adequate bowel cleansing may be achieved by several different methods.”
Those methods are set out. On page 32, the complications.
“The safety of colonoscopy in childhood has been documented with more than 1100 reported examinations ... Bleeding has been reported, but no paediatric patients have required transfusion … Bacteremia has not been found to be significant in paediatric patients, even if the procedure is accompanied by [other procedures] …”
At the bottom of the page:
“Perforation of the colon has been reported in at least four children wand has usually been associated with polypectomy.”
That is the removal of the polyp.
“Delayed perforation has been reported several hours after the colonoscopy and was thought to be related to [a particular polyp pathology] …”
“INDICATIONS FOR COLONOSCOPIC EXAMINATION
Rectal bleeding represents the most common indication for colonoscopic examination in paediatric patients and is usually indicated if rectal bleeding is persistent, severe, or associated with anemia.”
Could I take you back to a particular matter you quote in your report, Professor Booth, at page 4 of the same bundle. In the right-hand column, under “Colonoscopy” – and this is again a Mougenot paper and again a 1992 paper – in the second paragraph it says:
“Total colonoscopy in children involves real stress. The colon must be thoroughly prepared, since only a clean colon can be examined; neuroleptanalgesia or general anaesthesia is necessary, since stretching of the sigmoid loop, which cannot always be avoided, often gives rise to intense abdominal pain.”
Obviously, if it is a procedure that is needed, it has to be done, but, in your view, is it a procedure that should be undertaken lightly with young children?
A No. If it needs to be done, it needs to be done, but, as is pointed out here, it is an investigation that is invasive and children find unpleasant.
Q In the context of children, who, as you know we are particularly concerned with, namely those who had a variety of in some cases quite severe behavioural disorders, does that affect your view as to how lightly the procedure should be undertaken?
A I think there is always a concern where .. Inevitably, in paediatrics, because of the age range that we see, a lot of our patients we cannot explain things to adequately, but wherever possible one likes to explain to a child what is happening, as I was mentioning earlier, from the outpatient clinic through seeing the gastroenterology nurse to the time that they are admitted. In children with learning disorders, behavioural problems, that is an added concern. They are never going to be in a position to give consent and certainly children do withdraw their consent to colonoscopy. Not often, but two or three times a years, I think, in my practice, children say, “No, I don’t want the colonoscopy” so you say, “Okay, we will continue to see you and we will see what happens” and often their symptoms get worse and they say, “Yes, okay, I’ll come and have the colonoscopy.” I think the other issue is that if you have a child who has a major disorder associated with learning difficulties, major behavioural problems, poor quality of life for the child and the parents, parents are sometimes robbed of a certain sense of objectivity when they are consenting to investigations.
Q We will return to that particular subject in some detail when we are looking at the individual cases. You have touched on this already, but if you have a child who presents with symptoms which might indicate that a colonoscopy is needed but are not conclusive of that being the appropriate course, are there less invasive steps which paediatric gastroenterologists can take first?
A Yes. When you are evaluating the need for particularly invasive investigations you want to be fairly clear about why you are doing it and under certain circumstances, if the patient has blood diarrhoea or blood in the stool for whatever reason and then clearly they need a colonoscopy, sometimes the clinical presentation is so much like Crohn’s disease that you know when you first see them that they are going to need a colonoscopy, so they may not have blood diarrhoea but they may have diarrhoea, abdominal pain, mouth ulcers, weight loss, growth failure and so on, and under those circumstances they are going to need an endoscopy, you would combine it with other investigations as well, But sometimes there are patients who have much less, what you might call, “first rank symptoms”. We see a lot of patients like that and you would say, “I think it is appropriate to do some screening investigations first before we embark on unpleasant invasive investigations.”
Q What is a screening investigation?
A It is an investigation which, in general, provides less discomfort or invasion to the patient, which provides you perhaps with a pointer towards whether or not they are likely to need an investigation. By definition, screening investigations are never absolutely 100 per cent reliable. They are never 100 per cent sensitive or specific. If they were, they would not be a screening investigation, they would be the definitive investigation, so they are never completely reliable. Medicine is about making difficult decisions with inadequate information. You want to get as much information as you can before you embark on a particularly course of action. An example of a screening investigation that we use quite often would be to detect patients with coeliac disease. There is a variety of blood tests that one can use which would help you to make a decision about whether the patient needed an endoscopy in order to carry out a duodenal biopsy.
Q As far as inflammatory bowel disease is concerned, are there screening investigations which can help?
A The series of investigations that is very commonly carried out is to detect inflammation. The investigations do not tell you that there is inflammation in the gut, they will tell you that there is inflammation somewhere, but, in a patient who has bowel symptoms, you are particularly interested to know whether they have any evidence of inflammation. There is a series of blood tests that are requested to give you a bit more information, so you would look at haemoglobin and check if it is low; white count to see if it is raised, platelet count to see if it is raised. There is a test called the ESR (erythrocyte sedimentation rate) which is raised in inflammation. There is a test called C reactive protein, and also measuring albumin. So there is a panel of investigations that one requests under those circumstances, yes.
Q And they all arise from taking one blood sample from a child.
Q This is a method of investigation which has been written up by, indeed, Professors Walker-Smith and Murch and you refer to that paper in your report. Would you turn to that, please, at page 45 of FTP5. This is a paper that was published in the Archives of Disease in Childhood in 1995. We see the authors at the top. The abstract on the left-hand side of page 45 summarises what it is all about. It says:
“Simple routine blood tests …” –
and then it sets out the very ones you have referred to: full blood count, platelet count, ESR, C reactive protein (CRP) and serum albumin, and it continues:
“may select children with chronic gastrointestinal symptoms who require endoscopic assessment and are thus an important aid in the prediction of endoscopic status. When all of the results are normal then chronic inflammatory bowel disease is an unlikely diagnosis.”
That is the summary. If we look down at the paper:
“Colonoscopy is indicated in children with chronic gastrointestinal symptoms in order to diagnose chronic inflammatory bowel diseases, polyps, and less common conditions. Many children who undergo endoscopy are, however, found to have no organic disease. Additionally in Crohn's disease, the commonest inflammatory bowel disease, diagnosis is often delayed, and despite the availability of paediatric colonoscopy the median time to diagnose from onset of symptoms is still around 15 months. As the early symptoms of Crohn’s disease are often non-specific, diagnosis is often dependent upon investigations, in particular contrast radiology … “
That is barium meals –
“ … endoscopy and histology. Although abdominal pain is an important symptom of Crohn’s disease, it is also a common children complaint.”
Can I just pause to ask you, is that your experience of abdominal pain being a common childhood complaint?
A Yes. The epidemiological studies suggest that ten per cent of children at some point during childhood will get recurrent abdominal pain lasting for at least three months and sufficiently severe to interrupt their normal activities.
Q If we go on:
“The selection of whom to refer for endoscopy may therefore be difficult: use of screening blood tests to aid in patient selection is therefore likely to be of benefit.
We have audited all tertiary referrals to our unit for diagnostic colonoscopy over an 18 month period …. and correlated the endoscopic diagnosis with the results of easily available screening investigations.”
Before I go any further, Professor Booth, because it may become relevant later, is this a kind of research, an audit kind of research, where these children had colonoscopies anyway, they had blood tests anyway and then they look at a lot of them to see whether they can glean anything as to whether in fact they could have relied on the blood tests rather than the colonoscopy, rather than being a prospective study?
A That is correct. It is retrospective study, yes.
Q We can see that, because when we look under “Patients, methods and results”, we see:
“One hundred and twenty four patients were referred for endoscopic assessment by consultant paediatricians over an 18 month period. In 93 children the diagnosis was uncertain. All patients reported two or more of the following symptoms; abdominal pain, diarrhoea, rectal bleeding, weight loss, or mouth ulceration for greater than three months.”
Then in the next column we see:
“All patients underwent endoscopy and barium follow through at initial assessment. Endoscopic assessment included total colonoscopy and ileoscopy with biopsy.”
Then we see:
“Screening variables assessed … ”
Then they are set out. Then in the last paragraph in that section:
“The results of the screening investigations are shown in the table. Overall no child with Crohn’s disease had fully normal screening investigations … “
If we go to the Discussion, we see:
“Our results show that simple routine blood tests may be valuable in the selection of children with gastrointestinal symptoms who require endoscopic assessment.”
Then going down to the middle of the page:
“The diagnosis of Crohn's disease is unlikely if screening investigations are normal, but should be strongly considered if these indices are abnormal. The diagnosis of ulcerative colitis is unlikely if the indices are all normal and rectal bleeding is not present.
The role of blood tests in the assessment of known chronic inflammatory bowel disease is well established.”
And it sets out the authorities who say that. Going on to the next page:
“The use of inflammatory markers to aid the approach to diagnosis has been investigated in adults.”
It sets out the papers which have established that. Then in the last column:
“We suggest that these simple tests should be performed early in all children with chronic gastrointestinal symptoms. Abnormalities suggest the need for early referral, whereas normal investigations and no history of rectal bleeding make chronic inflammatory bowel disease unlikely. This policy should lead to swifter diagnosis in children with inflammatory bowel disease and may spare many others invasive investigations.”
First of all, Professor Booth, that report, as I say, comes from two of the doctors who are the subject of these proceedings. Has it in fact become a recognised approach?
Q Have others also written about it as an approach to diagnosis of inflammatory bowel disease?
A Yes, indeed, they have, including some of my own colleagues.
Q Overall, how would you summarise it? Are you suggesting that first of all it is always definitive of the position with regard to the diagnosis?
A No, because it is a screening test.
Q Broadly speaking, how reliable a screening test is it?
A I think it is pretty reliable. It is very unusual to find a patient with gastrointestinal inflammation who does not have some abnormality, but it is not absolutely infallible. As I said, no screening test ever would be, but I think one particular useful application of these observations, as the authors point out, is, as they say, total colonoscopy in patients with abdominal pain and, as I say, it is particularly important in children.
Q The last paragraph says the possibility is that it will spare other children from invasive investigations. Do you think that is desirable, when balanced against the respective invasiveness of taking a blood test or a colonoscopy?
A I think one would always want to avoid unnecessary invasive investigations in anybody, but particularly children.
Q Turning on to the other gastrointestinal investigation which we are going to be looking at, barium meal follow through, all the children with which we are concerned, or almost all, had that procedure after the colonoscopy. Can you just explain to the Panel what a barium meal and follow through is and the reason for it and what it entails?
A Yes. Of the two major type of inflammatory bowel disease that we were discussing earlier, ulcerative colitis and Crohn's disease, ulcerative colitis is confined to the colon, but Crohn's disease can and frequently does affect any part of the gastrointestinal tract from the mouth down to the anus. So just carrying out a colonoscopy would not be an adequate assessment of the entire gastrointestinal tract. One can, in addition to doing an endoscopy through the rectum and looking up at the colon, as I was mentioning, one can do an endoscopy through the mouth and look at the oesophagus, stomach and duodenum. A substantial minority of patients who have Crohn's disease have abnormalities there, but the problem is that there is still a large length of small intestine between the two ends that you can approach with your endoscope which you would otherwise have no information about unless you did a barium follow through. A barium follow through involves the patient drinking some barium and having X-rays taken perhaps every 15, 30 minutes as the barium goes down through the gastrointestinal tract. Then, when it gets to the part of the small intestine where it is about to go into the colon, usually the radiologist will actually look at the patient and the barium in the abdomen in real time and put a hand on the abdomen and screen it and try and spread out any overlying loops of bowel. So there is a sort of passive phase while it is just allowed to go down, but then an active phase when the radiologist screens the last part of the small intestine before it goes into the colon.
Q How long does that whole procedure take?
A Most patients are up in the X-ray department for half a day while that is done.
Q What is the downside of the procedure as far as the patient is concerned?
A They have to fast, but not for very long. Some children do not like drinking the barium, but most do. It is exposure to radiation which is the issue. There are newer methods now for examining the small intestine which are used relatively infrequently and were not available in the mid 1990s anyway.
Q Does it have gastrointestinal consequences on occasion in itself?
A Some patients say that they get constipated after it. That is about all I think.
Q Again, I have asked you this question in relation to colonoscopy, but given the presence of behavioural problems in a child, does that have implications as far as the investigation is concerned?
A Yes. Getting children to drink the barium when they do not want to is fraught with difficulty.
Q Just one last matter arising out of the questions about the actual procedures I have been asking you, just so that we are absolutely clear as to those. You said that screening tests should be undertaken if there are no what you describe as first rank symptoms. Can you just run through again for the Panel, Professor Booth, what you would regard as first rank symptoms for inflammatory bowel disease in a child?
A First of all, a child who has bloody diarrhoea, particularly if it has been going on for more than a week or two, which would make an infection unlikely, demands investigation. Then they can present usually with a constellation of symptoms of pain and diarrhoea, loss of appetite, weight loss, mouth ulcers, joint pain, sometimes skin rashes on the legs, growth failure. The assessment of the patient is, I suppose, where clinical acumen comes in and the experience. You would not immediately think of inflammatory bowel disease automatically in a patient with, for example, growth failure, but certainly Crohn's disease can present with growth failure and not much, if any, in the way of gastrointestinal symptoms. So it is very difficult to be absolutely dogmatic, but you look at the whole constellation of symptoms and also obviously you want to examine the patient carefully as well.
MS SMITH: Sir, it is now 11.15. I am now turning on to a completely different general issue: the distinction between clinical and research medicine. I do not know whether this would be a convenient moment to take a break.
THE CHAIRMAN: Yes, I think that would be appropriate. We will now take our mid morning break. Professor Booth, can I just remind you that you are under oath and in the middle of giving your evidence, so please make sure you do not discuss this case with anyone. We will resume at 11.35.
MS SMITH: Perhaps I could just tell you, Professor Booth, if you wish to have a look, I am turning to the matter which you deal with on page 203 of your report.
(The Panel adjourned for a short time)
THE CHAIRMAN: Yes, Ms Smith?
MS SMITH: Professor Booth, I want to turn to another general issue to ask you about clinical medicine and research medicine and, first of all, how they differ. I realise that is a big question, but can you start off first of all by telling us what you understand clinical medicine to mean and how it interconnects with research medicine?
A Clinical medicine is involved with treating patients who are referred with disorders or, rather, usually referred with symptoms and signs for a diagnosis and institution of the appropriate treatment. So they are referred because they and often their general practitioner think there may be something wrong with them.
Q What is research arising out of clinical medicine: clinical research? What is that involved with in general terms?
A Clinical research normally, or good clinical research, normally arises from an unanswered clinical observation. So that might be on an individual patient or it might be on a group of patients. The sort of questions which patients generate vary, as I think I have pointed out. Sometimes it is a therapeutic question which they generate: we do not know whether drug A or treatment A is better than treatment B. Sometimes we are confronted with a novel, apparently novel, disorder in a group of patients which has not been reported before and you seek to determine the physiological or biochemical or, in many cases these days, genetic basis of that disorder. Sometimes it is related to defining the epidemiology of a particular disorder: how common is treatment A? Is it getting more common? Often, when disorders become apparently more common, that in itself gives rise to a further series of questions: why is it becoming more common? Increasingly, a lot of questions are related to what is the most appropriate way of distributing scarce resource within the health service. A lot of questions relate to the management of the health service and what is the most effective way of using money to help patients with asthma or diabetes, that sort of thing.
Q Are all those examples that would come into the category of clinical research, in other words, research involving patients who are there for clinical reasons?
A Yes. It relates to patients, yes.
Q I think you have in part answered this, but are you asking a single, definitive question in a research project, or may it be a series of questions?
A It could be either.
Q You mentioned one in particular which may be pertinent to the case we are looking at of novel disorders. If you are studying a disorder, how does that generally begin? Before you get to the stage of research, what will have happened?
A It usually starts with referral of the patient or patients with a constellation of symptoms and signs which you have not seen before and which you cannot fit into any existing diagnostic framework. It may well be that you raise that question because when you investigate them, you find a series of abnormalities which have not previously been reported.
Q In practice, Professor – we have heard a number of doctors explaining to us the distinction – but in practice when a patient comes to see you with something wrong with them, is that distinction between treating them clinically and embarking on research involving them a difficult distinction to draw?
Q If you decide that you are going to conduct a research project – if it helps you, I am on page 3 of your report, which the Panel do not have – can you just run through how that becomes formulated? How do you go about formulating a research project?
A Normally, as I say, it begins with a clinical observation. So you might have a particular group of patients and you are not quite sure what the best way is of treating them; you have an observation. Within my own experience, infants who have iron deficiency anaemia and you want to know why do they have iron deficiency anaemia and what is the best way of treating it. So you formulate a research question. I think for good research, it is important that you address important issues. Issues are important because they are very common, so it may be that you are addressing an issue relating to asthma or diabetes, which are extraordinarily common, or it may be you are addressing, at the other end of the spectrum, something which will, although it is rare, you feel will led to a much better understanding of normal physiology or biochemistry, and that is very often the case with rare inherited genetic disorders where defining what the genetic abnormality is not only explains the disease, but also adds an enormous amount of information to our understanding of normal functioning. Those would be two extreme examples, but it is important to have an important question. Then you think about what is going to be the most appropriate way of addressing the question and the methods that you will use will obviously depend very much on the nature of the question. If it is a question, “Is Drug A better than Drug B?” you would obviously be moving towards a clinical trial. If it is a group of patients whom you have not seen before, in other words they have an unrecognised disorder, then you would think about drawing up a series of investigations to research what actually is going on in that group of patients. You would quite often need people working with you who are outside one’s own team and, increasingly, research teams are getting bigger and bigger and bigger. That is a reflection of the greater sophistication of questions that are being asked now, and often involve people collaborating across teams within the institution and often between institutions as well.
Q Is there anything unusual about a situation where you have academic researchers and clinicians collaborating on a research project?
A That would be very common indeed, and I think is to be commended. The clinicians know what the good questions are. They know what the unanswered problems are. Laboratory scientists often have the means of addressing those questions whether it is in the laboratory or maybe in the epidemiological laboratory or the clinical trials unit. So there is often the need to bring together different types of expertise to address the question, yes.
Q Having got your group of people in the appropriate specialisms, then what happens next?
A You would agree a protocol that you were going to follow that defined pretty carefully how you were going to address the question. In a lot of research it is particularly important to define very carefully indeed the characteristics of the group of patients that you are going to be studying, so that when you come to interpret your findings you can make some sense of them. If you were interested in investigating patients with diabetes it would not be appropriate to include patients with other diagnoses within that group. Otherwise you would not be able to interpret your findings. So the protocol needs to very rigidly define who it is that you are going to be investigating. It also needs to define how you are going to investigate the patients, what samples you are going to take and often what laboratory tests you would then undertake on those samples.
Q So have --- Sorry.
A If we are talking about research involving investigation on patients or using material from patients, you would submit your protocol in an appropriate format to the research ethical committee.
Q Would you generally expect the protocol to include matters? You have talked about the patient selection.
Q And you have talked about laboratory testing. Would you expect it to include the nature of the investigations that would be undertaken?
Q And the time-tabling of the matter?
A Yes. You expect it to include the nature of the investigations and also, I think importantly, to define very carefully what the nature of the control patients was going to be. Again, this is something that could render your observations uninterpretable if you did not have a control group of patients. So in the context, say, of a clinical trial, if you were administering a drug to a group of patients with a disorder, you could not interpret your observations unless you could compare them with what happened if you gave a placebo drug to an equivalent group of patients who were matched for the same disorder, age, sex, sometimes social class, smoking history – that sort of thing. So a very detailed match. If you do not have appropriate controls, you can never interpret your observations.
Q At some point during all this, Professor Booth, is funding an issue?
A Is – ?
Q Is funding an issue?
A Funding? Yes, usually, almost invariably. So at some point, usually at the stage where you are bringing the protocol together, you would start to think very seriously about where you get funding from, yes.
Q I think there is no issue on this, but apart from the research and development funds in a hospital which are provided by the NHS, is the NHS going to be a source for the funding of research, or do you have to find some external body?
A In general you have to find some external body. The issue of NHS-funded research has changed just in the last few years and NHS research funding is used in way which is much more like application to an external body. But in the mid-1990s hospital received a budget to support research and development.
Q If that did not cover some or all of a research project that you wanted to do, did you then have to go to some outside charitable or research organisation?
A Generally speaking, you would almost invariably have to go for outside funding, yes.
Q Going back to the sequence of events, you said you would be submitting the protocol to a research ethics committee. At that stage might you be at a relatively preliminary stage in respect of the first stage of the research that you were going to do? In other words, planning something preliminary before going on to a more formal study?
A I think the research ethical committee would want to know that the protocol had been carefully formulated and thought about, and that you were in a position to generate interpretable data. It might be the precursor to a bigger study, but I think each application to the research ethical committee would need to hold water in its own right.
Q If it is the precursor to a bigger study, does it still need ethics committee approval in the same way as a bigger, more formalised study would?
A Yes, yes. You may use the results from your precursor study to convince the Medical Research Council, for example, that your observations were worthy of further funding, but the preliminary study that might have been just a relatively small study, relatively few patients, a kind of “proof of concept” study, would both need to be funded from somewhere, but it is easier to get small amounts of money rather than large amounts, but equally well, it would need to be ethically sound as well in its own right.
Q We have heard used a number of phrases, amongst them the phrase “pilot study”. Is that what you are referring to when you talk about a precursor, or is that something --- ?
A Yes, essentially. Yes.
Q Could you ever be doing a pilot study and it not be research requiring ethical committee approval?
A I cannot think within the terms that we have been discussing of an example of that.
Q And then obviously, assuming that you get ethics committee approval, that you will go on and do the study and funding, you will do the study in the way that you would envisage, is the ultimate intention from that the presentation and publication of results?
Q I want to turn very briefly to the ethical framework with regard to research. I say “very briefly” because the Panel re going to be only too familiar with the guidelines now which we have been through on a number of occasions. I have to refer to just the basic principles both in relation to the matters I want to ask you about on project 172-96 and also the charges relating to the birthday party. Could I ask you to take out volume FTP4. Although you refer to all the ones we have been through, Professor Booth, rest assured the Panel are now familiar with them. I am only going to take you to two, which are the British Paediatric Association Guidelines and the Medical Research Guidelines. Firstly, the British Paediatric Association guidelines which are at page 176. Would you go straight away to page 183, please. This just sets out the very basic position in the second paragraph.
“Research with children is worthwhile, if each project:
- has an identifiable prospect of benefit to children;
- is well designed and well conducted;
- does not simply duplicate earlier work;
- is not undertaken primarily for financial or professional advantage;
- involves a statistically appropriate number of subjects;
- and eventually is to be properly reported.”
Then on to page 184:
“Children are unique as a research group of many reasons. They are the only people in British law, on whose behalf other individuals may consent to medical procedures. Many children are vulnerable, easily bewildered and frightened, and unable to express their needs or defend their interests. Potentially with many decades ahead of them, they are likely to experience, in their development and education, the most lasting benefits or harms from research.”
Are these the basic principles that paediatricians are expected to abide by?
Q Page 188, just the central proposition that we all now know in the middle of the page:
“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.”
Then page 191, at the bottom of the page:
“Parental consent will probably not be valid if it is given against the child’s interests. This means that parents can consent to research procedures which are intended directly to benefit the child, but that research that does not come into this category can only be validly consented to if the risks are sufficiently small to mean that the research can be reasonable said not to go against the child’s interests. Even when it is not legally required, researchers should obtain the assent or agreement of school age children … and should always ensure that the child does not object.
Legally valid consent is both freely given and informed. For consent to be given, researchers:”
And then I am only going to the first two:
“- offer families no financial inducement, although expenses should be paid;
- exert no pressure on families;”
Then, could we go on, please, Professor Booth, to the Medical Research Council guidelines at page 154. This is for 1993, and if you go to page 161, just for the definition of “therapeutic” and “non-therapeutic”. In the middle of page 161, paragraph 3.3.1:
“The primary intention of all medical research is to acquire knowledge that will be of benefit to humanity as a whole – to all who are or may become ill. Therapeutic research is directly concerned with treatment and thus offers the possibility of immediate benefit to participants. Direct benefit to participants in non-therapeutic research is either unlikely or long delayed.”
On page 167:
“6.1.1 There is thus a broad consensus …. that a principled case can be made on ethical grounds for research on children.
6.1.2 At the same time, there is agreement on the need for strict safeguards for such research. In particular … all projects must be approved by the appropriate LREC(s)” –
the Local Research Ethics Committee(s).
At page 168 we see the Medical Research Council’s take on therapeutic and non-therapeutic research.
6.2.1 We believe that subject to the safeguards listed at 6.1.2 above there is a strong ethical case for including children who cannot consent in therapeutic research; indeed we would argue that in circumstances where participation would be in their best interests their exclusion would be unethical.
6.2.2 When a child lacks sufficient understanding to consent, his inclusion in therapeutic research should be subject to his parents’ or guardians’ judgment that the benefits likely to accrue to him outweigh the possible risks of harm, and that participation is therefore in his best interests.
6.3 Non-therapeutic research
6.3.1 Because it might infringe the rights of a group which society should take particular care to protect, the participation of children in non-therapeutic research raises more complex ethical issues. We do not seek to argue that a child’s participation in non-therapeutic research is in his best interest. But we recognise that there are circumstances in which it is important to gain knowledge which may be of benefit to children in general and which can only be acquired as a result of research which involves children.
6.3.2 We therefore believe that there is a strong case for including children unable to consent in such research, but it is essential that the safeguards listed at 6.1.2 are observed, and that those included are placed at no more than negligible risk of harm.”
Then, in particular:
“6.3.3 The degree of risk involved in a particular project should be given particularly careful scrutiny by the LREC when children are to be included.”
With that background, Professor Booth, I wanted to turn to some of the specifics in the case with which we are concerned. Before I do so, can I preface it by saying that I am going to ask you to give some general examples, then I am going to take you to individual cases, and then I am going to revert to the more detailed explanation of your general views. First of all, perhaps we could remind ourselves of the scientific protocol and how that ties in with the ethics committee application. Its earliest version was in June 1996. Would you turn to FTP1, page 153 – which is just to date it. That, as you know, is a letter from the solicitors in the MMR litigation to the Legal Aid Board. It says 6 June 1996 at the top, and the second paragraph reads:
“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.”
We will revert to the proposals at a much later date, but perhaps we could look at the proposed protocol, please, starting at page 104. On the first page, we see that the coordinating investigator is Dr Wakefield, and on pages 105 to 107 the investigators are set out: for the Department of Paediatric Gastroenterology, Professor Walker-Smith, Dr Murch, Dr Philips and Dr Casson and their responsibilities. Then, for the Department of Histopathology, Dr Wakefield, Dr Dhillon and Dr Linnell; on the next page, for the Department of Child Psychiatry, Dr Berelowitz; on the next page, for the Department of Neurology, Dr Harvey; and their respective responsibilities are set out. Would that document, in your view, Professor Booth, necessarily have involved Dr Wakefield’s discussion of these matters with all the people whom he was envisaging investigating?
Q I am not going through it all, but, could we turn to page 115, please.
(i) firstly, and significantly, this is a demanding protocol both for the children, and for those clinicians carrying out invasive procedures in particular. Due consideration should be given to this when planning the details of admission (for example, should colonoscopy be performed under GA). However, it is essential that we characterise as comprehensively as possible, the pathogenesis of this condition – control of any underlying intestinal immunopathology may open up new therapeutic avenues for the treatment of affected children. Our ability to confirm or exclude a role of measles or measles/rubella vaccine also has major implications for public health.
(ii) Referrals will be coordinated …” –
and we see the names of the doctors. They will be admitted on a Sunday; remain in hospital for one week; have 24-hour urine collection, blood tests performed on the Monday, followed by colonoscopy, psychiatric and neurological assessments, and an outpatient follow-up arranged for one month. Knowing what you do, Professor Booth, of the ultimate protocol that was submitted to the ethics committee, which I will turn to in a moment, does this document seem to you to describe the same or a different study?
A This is the same study.
Q Could you turn to the application to the ethics committee, which is in the same volume at page 200. We see the responsible consultants set out at the top of the page and the collaborating departments underneath. The date the application was signed off by Professor Roy Pounder (who we are told was the head of Dr Wakefield’s department) was in August 1996. There is the title, the objective and design of the study, and investigations which it was planned to carry out, including virology, with a full protocol to be attached. Page 208 sets out the science of the study, which I do not have to read through again. The subjects are set out, with the selection criteria being the presence of disintegrative disorder; symptoms and signs of intestinal dysfunction; and a parental request for investigation to be undertaken. Twenty-five subjects, all to be under the age of 16, who manifest disintegrative symptoms and signs to differing extents; to be accompanied by a parent, with a designated nurse in attendance throughout the week; and then there are the procedures that will be undertaken. It notes that the parents will be aware that they can withdraw their child from the study at any stage. At the bottom of the page:
“…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.”
At page 211 is the information to be given, setting out an explanation of what is intended. At page 212 we have another copy of the proposed clinical and scientific study in the terms I have already taken you to. Attached to that, at page 226, is the virology detection. At page 231 is the timetable, setting out an arrangement that Dr Wakefield was arranging the neuropsychiatric tests and the rest were the paediatric gastroenterology tests. At page 232 is a handout for the parents and at page 234 is the formal consent form. At page 236, as you know, is a supporting view from Dr Epstein, the consultant gastroenterologist in the Department of Medicine at the Royal Free Hospital. In your experience of submitting applications of this kind, Professor Booth, is that set out in a relatively standard way for an application to a research ethics committee?
A Yes, I think so. Yes.
Q I have not gone through all the details of the science as it is set out, because I know you are familiar with it and so are the Panel, but what, as you understand it, is the overall aim of that application?
A To study a group of children with disintegrative disorder is the first stage and to define some of the pathophysiology of that disorder that might lead to an understanding of what is causing it.
Q You have already touched on this, but are the selection criteria a crucial element of that application or of any application for ethics committee approval for a research project?
A Yes, I think this is a good example of what I was saying earlier. There is a very full description of disintegrative disorder as part of their application.
Q Does this go to the fundamental consideration of the ethical side of things as well as whether or not it is accurate? Is it an ethical consideration that the study should be done in a way that makes meaningful research arise out of it?
A Yes. It should be done in a meaningful way. I am not quite sure I understand your question. The nature and severity of the disorder that is being investigated and its prognosis has implications for some of the investigations that you might want to or not want to sanction as part of the ethical committee process.
Q If some of the aim were to have been to try out a treatment, not necessarily a new treatment, but a treatment for particular symptoms, would you expect that to be reflected somewhere in this application?
A Yes. I think if you were anticipating a therapeutic intervention subsequently and it might be the subject of a further application to the research ethical committee, you would anticipate seeing it in this document. Certainly you would also expect to see a separate application being made for a novel treatment, yes.
Q If we can just go back to page 232, please. This is the handout which was envisaged would be given to the parents, as you know. We see in the second paragraph:
“We would like to carry out a series of tests which, we believe, will help us to establish the features of this possible disease. Our aim is to characterise the problem so that, for the future, we may be able to treat affected children and improve their wellbeing.”
If at that stage there had been some plan as to the nature of the treatment which might be given, would you expect to see that reflected somewhere in the ethics committee application, if there had been a plan at that stage?
A If there had been a definite plan, yes.
Q I am going to revert to these questions when we have looked at the individual children, but from this application and bearing in mind the guidelines we have looked at, would you characterise this research project as therapeutic or non therapeutic research?
A At this stage, non therapeutic.
Q If it held out some prospect of a treatment in the future, in other words, going on to a more formalised plan as to giving these children treatment, would that in any way affect the view that you are expressing that at this stage it is non therapeutic?
A At this stage, it is non therapeutic, yes. There is no defined therapeutic intervention.
Q If there were some undefined hope that treatment might emerge out of it, would that affect its essential non therapeutic nature?
A No, not if it was a sort of ill-defined concept at some future possible date.
Q Can you just – I am at page 52 of your report, if it helps you – explain to us exactly what it is, what your understanding is of what constitutes therapeutic or non therapeutic research?
A I think therapeutic research is one where there is a very clearly expressed view in the ethical committee application, which would of course embody the protocol, and in the information to parents and carers and to children that there is a component within the research which is probably going to involve a clinical trial, which is how therapy is evaluated. Alternatively, it might say, “We have a novel treatment and we are wanting to try it out because we feel your child has a very poor prognosis and it is very experimental. We just do not know how your child is going to react.” That would be another way in which a very novel treatments are introduced. But the fact that there was therapy would be very clearly expressed in the various documents associated with the research. Non therapeutic research would be characterised by an absence of that documentation
Q What is the ultimate aim of non therapeutic research?
A The ultimate aim of all research is patient benefit. Non therapeutic research may be several steps away from that. So non therapeutic research is important for understanding about the causes, the pathogenesis of disease, for example, which may then allow you to formulate a separate proposal for therapeutic research. Sometimes, unless you know what the nature of the disorder is, you do not have any clues about what an appropriate therapeutic intervention might be.
Q Obviously you would not use those words, but is it important for the parents to understand the nature of the research, what its aims are, when they are considering whether to submit their children for it or not?
A Yes, particularly with respect to whether there is going to be a possible positive therapeutic outcome for the child.
Q If it is non therapeutic research, as we have seen from the guidelines which we have looked at, the risks have to be small ones. Is that correct?
Q Because there is not any benefit to put on the other side of the scales.
A That is correct, yes.
Q If – and we will revert to this obviously – colonoscopies and indeed lumbar punctures were being carried out on these children for non therapeutic research purposes, would the risks ever in your view fall into the category of small ones?
Q With regard to the issue of parental consent for a research project, if it involves children with very severe disorders of whatever kind, does that have ethical implications as far as the clinician is concerned? In other words, he obviously makes an assumption to begin with that every parent has its child’s best interests at heart. Are there other matters which he has to consider when he is consenting the parents for a research project of this sort?
A I think it is important to consider parental objectivity. Parents may be so overcome by the nature of their child’s disorder that it is difficult for them to retain some objectivity. For example, in paediatric oncology there have been a number of high profile cases where parents have been in conflict with the doctors about whether or not their child should have a particular novel treatment and parents sometimes will loose that sense of objectivity. That is also true of parents of children in my experience with severe autism, which is a very unpleasant disorder to manage as a parent and where they will be keen toe explore any possible avenue with respect of their particular child. So they can loose objectivity and I think that places an additional responsibility on the shoulders of the clinicians caring for that child.
Q In your expert view, Professor Booth, is that a well-known consideration for doctors who have to deal with the parents of very sick children?
Q How do you grapple with it? Here you have parents who love the child and who you assume have the child’s best interests at heart. You have said there may be circumstances where they may lose objectivity as to what is in the child’s best interests. How does the clinician deal with that?
A If it is at the level of an individual sick patient, it is normally dealt with by discussion with the parents, so that you are clear they have all the necessary information available. If the child is very ill, it is very difficult for them to assimilate that information and it may need repeated discussions with them. It is also important under those circumstances for clinical care to involve colleagues from other disciplines. So nursing staff are often very relevant and other therapists quite often too. Then it is often helpful to get the opinion or make available to the parents the opinion of other consultant colleagues who are not involved in the management of that child. Sometimes there are very difficult issues about whether to initiate treatment in patients where the prognosis would appear to be particularly poor and, as clinicians, one sometimes goes to a within hospital group of senior experienced clinicians and asks them for advice about what to do, so that you are retaining as much objectivity as possible through a number of other sort of prisms. It is often quite difficult to engage parents in that if they are very committed to whatever the particular course of action might be. It might be a form of treatment, it might be continuing with treatment, it might be that they are very keen to withdraw treatment sometimes and the doctors do not feel that it is appropriate; they feel it is too early to be thinking about that. So it occurs in a number of different contexts clinically if managing one particular child. I am not sure if I have answered your question.
Q Yes, you have answered it. In the circumstances of this particular situation as far as you can ascertain it from the papers, this research project, if this research project is envisaged in children with varying degrees of serious behavioural disorders, is that an instance where the responsibility of the clinician may be greater?
A Yes. In my experience, the parents of children with severe autism are very, very keen to explore every conceivable avenue, even those avenues where there is no evidence base to support it; they are prepared to get involved in investigations and treatment for which there is very, very little convincing evidence base and sometimes they need to be steered away from that, because apart from doing harm to the child, they often can be potentially very expensive.
Q In the end, Professor Booth, however much you may obviously be listening to and consulting with the parents, in the end, who is your patient?
A The child.
Q Is that a basic consideration which all paediatricians have to bear in mind?
A Yes. It is invariable.
Q Can we just turn back to the beginning of the ethics committee application, please, page 200? The responsible consultants are listed at the top of the page: Professor Walker-Smith, Dr (as he then was) Murch and Dr Wakefield. If we go on to page 231, we see their respective roles set out there. Can you just tell us first of all what does being named on the ethics committee application as a responsible consultant mean with regard to that application?
A I think it means that you are taking responsibility for making sure that the protocol is followed as defined in the application.
Q With regard to the general design of the study, what is going to be done, the nature of the investigations which are going to be undertaken, the order of what happens, the timetabling of those investigations, whose responsibility is that?
A I think that is the team overall, because there are a number of investigations here which involve, for example, endoscopy. Often endoscopy lists are on fixed days of the week and are very difficult to change, so there would need to be a discussion between the investigators just so that they agree between themselves what an appropriate order would be for investigating these patients. As I say, a fixed point around which everything else might have to be arranged is the endoscopy.
Q With regard to the timing of the neuropsychiatric assessment and the lumbar punctures, which we can see take place at the end of the time of these children’s admission on the Wednesday and the Thursday, with the colonoscopy, MRI, EEG, barium meal and follow through and all the blood tests all taking place before then, do you regard that plan of investigation as a satisfactory one?
Q Can you just tell us in broad terms why not?
A The protocol or the application to the research ethical committee makes it very clear, and there is a very detailed description of it, that the study is about investigating children with disintegrative disorder, which is a pretty rare disorder. You would, before wanting to expose children to these investigations, particularly as some of them are unpleasant and invasive, want to be absolutely certain, both for ethical reasons and for scientific reasons, that the population of children you were discussing fulfilled the diagnostic criteria for disintegrative disorder and, if they did not, they should not be part of the study. What you see here is that the invasive investigations are taking place before that check, that important check, has been made.
Q Arising out of that, Professor Booth, can I ask you this? Are there any gastroenterological reasons in your view which would justify carrying out lumbar punctures on these children?
A No, I cannot think of one.
Q We have heard reference made to mitochondrial disorders. You may be asked more about this, but I want to ask you just in general terms, would a mitochondrial disorder which impacted on the gastrointestinal system be an indicator for doing a lumbar puncture?
A No. These children did not have the clinical characteristics of a mitochondrial disorder. Some children with mitochondrial disorders have a raised level of lactate, lactic acid, in their cerebrospinal fluid, for which you would need to do a lumbar puncture. Before going straight to a lumbar puncture, you would do a number of other, less invasive tests which you would carry out in this group of children first: blood tests, for example, to see if you could find any supportive evidence for this being a mitochondrial disorder.
Q When children come to a specialist unit like yours with inflammatory bowel disease, or with a suspicion of inflammatory bowel disease, how far down your list of things you would consider would mitochondrial disorders be in normal circumstances?
A Very small indeed.
Q So that takes us just back to the order of the investigations. The purpose, as you are envisaging of the lumbar puncture, is to see whether there is any symptom or sign of disintegrative disorder. Is that correct?
Q And that is why you criticise the doing of the lumbar puncture after the children have anyway had the colonoscopy?
A I think the tests that were going to be done on the CSF were not relevant, in the research ethical committee application, to the diagnosis of the mitochondrial disorder anyway. I cannot just find the page, but I think the paper was looking for CSF antibody and cytokine profiles, which would not be relevant to a mitochondrial disorder.
Q You said in broad terms that this overall design and time-tabling would be part of the responsibility of what you described as the team when I asked you about responsible consultants. I want to ask you a few more questions about your understanding of the role of these three doctors. As far as Professor Walker-Smith is concerned he, as we know, was the most senior clinician. Can you assist us as to whether, if patients are being admitted to a gastrointestinal department. Do they have to be admitted under a name, as opposed to a department?
A Almost invariably. One department in the Children’s Hospital I know managed patients as a team, but that is quite unusual and certainly in my own department we have, and keep, our own patients.
Q As the senior clinician, what would you regard Professor Walker-Smith’s responsibility to be towards the children in this study?
A I think firstly, in making sure that the patients fulfilled the inclusion and any exclusion criteria in the study. As, as one of the clinicians involved, you would anticipate that he would be enrolling patients with disintegrative disorder but from the point of view of the scientific integrity of the study, you would anticipate that everyone involved in the study would want to reassure themselves that the patients who are being entered in the study did actually fulfil the inclusion criteria.
Q With regard to Dr Wakefield, you have seen his CV, but I think it would be helpful if we just had a look at it because you base your views on it. It is in FTP3
At page 940a. It is in my bundle. I do apologise. It is being pointed out to be it actually starts at page 940b.
THE CHAIRMAN: We only have 941. Then we have 942, so we do not have 941a either.
MS SMITH: Please can you insert it after 940, sir. I am sorry the numbering is a little strange, but it is then 940b to 940y. (Pages 940b-940y distributed) Just so everyone is clear, and I have checked this statement with Mr Coonan, it is his CV as of July 1998. That sets out, in the normal way of CVs, a great many scientific papers with which Dr Wakefield has been involved, presentations and his general qualifications are set out at 940c, with his present appointment as at that time in 1998 at the Royal Free. It sets out his previous appointments at page 940d and e. I think it is right that you have perused this document, Professor Booth. From your perusal could you see that Dr Wakefield had any paediatric qualifications at all?
A No, I could not.
Q And in those circumstances, would you expect him to have any involvement with the clinical management of paediatric patients, with children?
A No, I would not.
Q Could you see in his CV any indications of any recent clinical experience, i.e. working with patients, as opposed to laboratory based worked?
A No. There is no direct reference to any clinical work. His appointment in experimental gastroenterology in the Department of Medicine and Histopathology would suggest otherwise – that he was not engaged in any clinical work.
Q In addition to that deduction that you have made, that he had no paediatric qualifications, I think you are also aware of his specific job description at the Royal Free Hospital and I just remind you of the terms of that. It is in FTP1 at page 40. I am certainly not going to read the whole of it out, but if we look at the end of the paragraph setting out his job description, we see:
“The overall aim of the job is to provide leadership and strategic research initiatives that will make the Royal Free Hampstead NHS Trust and Royal Free Hospital School of Medicine the World Leader in inflammatory bowel disease research. His research involves the laboratory investigation of resected human tissues, but he will not be involved either in the clinical management of patients with inflammatory bowel disease or the routine histopathological reporting of tissues from these patients. He will not be involved in the out-patient or in-patient management of patients in the Royal Free Hampstead NHS Trust. He will not practise as Consultant Surgeon , Physician or Gastroenterologist as part of this appointment.”
We see set out his daily time-table which is wholly research-based.
I will go to the individual patient records with you shortly, Professor Booth, but when you look at them, what was your impression as to whether Dr Wakefield kept within his qualifications and his job description?
A I think I have rarely seen a more explicit list of negatives in a job description, and the impression that I gained from going through the patient records, that he was not complying with this.
Q If this was a research study, would you expect him to be clinically involved in it?
A No, not clinically.
Q If, as the defendants seem to be suggesting, these children were being seen clinically for these investigations, and not as part of a research study, is there any basis that you can understand for involving Dr Wakefield in their admissions?
Q Lastly, with regard to Professor Murch, Professor Booth, he too was a responsible consultant. Do you regard him in general terms, in other words with regards to the design of the research study, as having the same responsibilities?
A Yes. He was a co-applicant, so I would not differentiate between the co-applicants.
Q As far as his role generally in the research, having said that, did you form a view as to its nature?
A Professor Murch’s role, subsequent to the submission of the research ethical committee application, seemed to be in carrying out some of the colonoscopies. He did not, as far as I can remember, play a role in selecting patients for the study. He did, in some instances, see the patients subsequently for follow-up but essentially, as far as the study goes, after the submission he carried out some of the colonoscopies.
Q As far as the colonoscopies which he actually carried out, what are the duties of the person carrying them out in circumstances where the initial ordering of that procedure was not theirs? In other words, if Professor Walker-Smith requests a colonoscopy, and we are told he did not undertake colonoscopies himself, what is Professor Murch’s responsibility if he is carrying it out?
A It is always difficult, if you are requesting investigations on your patients to be carried out by someone else, for the person who is carrying out the investigation to say, “Well, I do not think you should be doing this,” or, “I would do it differently”. It puts that person in a rather difficult position clinically, I think.
Q Broadly speaking accepting that that is a difficult position, does he still have personal responsibility as to whether it is an appropriate investigation?
A I think so, yes. If you are doing an endoscopy on your, or someone else’s patient, you have to be sure in your own mind that it is clinically appropriate, yes.
Q And how do you do that? You have not seen the patient in outpatients, have you? How do you make sure that you are happy in your own mind that the investigation is appropriate?
A I am not sure what happened at the Royal Free, but from time to time my colleagues and I do endoscope one another’s patients, for a variety of reasons, and what happens under those circumstances is the patients are discussed at the weekly clinical meeting on the Monday. That includes patients coming in for endoscopy, so the reasons for the endoscopy and any other investigations that are going to need to be done are discussed and/or you go and see the patient when they come into the day unit, and talk to the parents and satisfied yourself that the investigation is needed. Sometimes patients just get better.
MS SMITH: Thank you. Sir, that concludes what I wanted to ask about the roles played in the original application. I am now going on to the subsequent correspondence with the ethics committee. It will take longer than ten minutes. I do not know whether it might be appropriate to finish now and start again at ten to two, if you were happy with that, rather than for me to start the correspondence and then not finish the chain of it.
THE CHAIRMAN: No. I think it would be better, also to keep the continuity properly flowing. When you start with that particular subject, you had better go through it fully. We will now adjourn for the lunch break. It is ten to one, and we will resume at ten to two.
Professor Booth, I have to remind you that you are still under oath, still in the middle of giving evidence. I hope you will forgive me, because I will keep giving you these reminders all the time while you are giving evidence. That is the process that we have to follow. Thank you again. We will now resume at ten to two.
THE CHAIRMAN: Ms Smith.
MS SMITH: Thank you, sir. Professor Booth, I want to ask you now about some of the correspondence with the ethics committee subsequent to the application. I wonder if I could ask you to turn to FTP1, please, at page 265a. It should be a piece on green paper.
A Yes, I have it.
Q This is a letter which I know you have seen subsequent to these proceedings starting, which Professor Walker-Smith produced. It is a letter which was missing from the papers originally, and which was the forerunner to the letter with which you are familiar, which was Professor Walker-Smith’s reply. It is dated 16 October 1996. It sets out some of the queries of the committee via Dr Pegg to Professor Walker-Smith. If you look under “Comments”, it is inviting Professor Walker-Smith’s comments:
“2) 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).”
Then he quotes:
“’It would be unethical to submit child subject 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 in this way. Will the benefit be more than ‘slight or uncertain’.”
He encloses with that letter the BPA guidelines which I have already taken you to at page 265c. Would you turn on to the reply, please, which is at page 291. This is Professor Walker-Smith’s reply, and we can now see the paragraph numbering echoes Dr Pegg’s. He says at paragraph 2:
“2. Clearly this is an intensive regime with procedures that could be regarded as ‘high’ risk although they are particularly used for the investigation of children with chronic inflammatory bowel disease. These children suffer from a disease with a ‘hopeless prognosis’ in relation to their cerebral disintegrative disorder. They have often not had the level of investigation which we would regard as adequate for a child presenting with such a devastating condition. In relation to their gastrointestinal symptoms which will be present in all the children we investigate, these have often been under-investigated. We have so far investigated 5 such children on a clinical need basis, all in fact have proved to have evidence of chronic bowel inflammat8ion. One child has already had a significant response to enteral feeding. Certainly there is a measurable benefit to the child:
a) Establishing a diagnostic and excluding metabolic and other causes
b) Commencing on a therapeutic regime
This study is parent/patient driven as every case referred has been initiated by the GP by the parents of the child.”
Then he says:
“I can confirm that children would have these investigations even if there were no trial. I must make clear that we would not be investigating children without gastrointestinal symptoms.”
I want to ask you this: what do you understand the phrase “would have these investigations even if there were no trial” to mean, vis a vis whether this is clinical medicine or research?
A I think I would interpret that as meaning that the symptoms, signs and other investigations suggested a strong possibility of inflammatory bowel disease and that they needed to be investigated from that point of view.
Q That, of course, accords with what I have already taken you to, which was the section of the actual application form, with the ethics committee indicating that the investigations were clinically indicated. How important are those particular representations to the ethics committee, that the investigations are clinically indicated?
A I think they are very important because the application indicated that the GI investigations were going to be clinically indicated. I think this letter also confirms that the investigators were in fact dealing with cerebral disintegrative disorder as their inclusion criterion.
Q Is it in your experience relatively usual for there to be interchanges between the chairman of the ethics committee and research investigators?
Q And to clarify aspects of the study?
A Absolutely, yes.
Q Whose responsibility is it to ensure that the committee is clear about what is proposed?
A I suppose there is a dual responsibility. It is important that the chairman accurately reflects the view of his committee members to the investigators and that the lead investigator consults with his colleagues, and sends a response which they all feel comfortable with.
Q As far as indications as to clinical indications, are the committee to be expected to be in a position to go behind what is said by the responsible consultants involved in the application?
A Yes. I think in circumstances where one is considering invasive investigations, you would want to get an outside independent view on the appropriateness of that, particularly if you are investigating children with major neurological and behavioural problems who are not going to be able to take part in the discussion with regard to consent.
Q As far as the information that was presented by Professor Walker-Smith in this letter to the ethics committee, we will re-visit this, but with the knowledge that you have of the cases which we are going to look at and which formed the children who were ultimately written up in The Lancet, do you think that the ethics committee were given sufficient information to enable them to judge the ethical status of this project?
A It is difficult for me, as a gastroenterologist, to comment on the relationship between phrases like “hopeless prognosis and devastating condition” and the neurological disorder of disintegrative disorder, but to use those terms for the gastrointestinal symptoms, and subsequent diagnoses, that these children had would be highly inaccurate and therefore would put the ethical committee in quite a difficult position.
Q Generally speaking, although there are one or two exceptions, and we will be looking at the individual cases, the indication to the ethics committee that these investigations were clinically indicated – do you think that was a proper one?
A It is not a view that in general I have shared.
Q As far as the ethics committee is concerned, you said that they would normally seek some sort of independent review and, of course, we know that they did in the shape of the letter from Dr Epstein.
Q But as far as the actual knowledge on the Committee is concerned, are they in a position to question the views that are expressed by the clinicians as to whether a test is clinically indicated? Whatever specialism it is. Or do they have to accept and ask the clinicians?
A I think a member of the committee did question the invasive nature of the investigations.
A What one would anticipate would be that there would be someone from the relevant discipline, but outside the research team available to the ethical committee, either as a member or co-opted to give advice on that particular issue to inform their decision. I think under the circumstances of this application, Professor Murch was indeed a member of the research ethical committee but, quite appropriately, was required to withdraw while this matter was being discussed, which denuded the committee of any paediatric advice.
Q In this context, I think it is right to say that your view is that the handling by the ethics committee left something to be desired?
A I think the expertise available to the ethics committee in coming to a decision about what I think must have been a very difficult application for them to assess, because it involved a lot of highly invasive investigations, I think their decision must have been particularly difficult, and you would therefore not want to make any decision without getting some independent paediatric advice, of which plenty would be available .
Q Having said that, in so far as the responsible consultants are concerned, is it your view that that criticism absolves them from the responsibility for the information that they give?
A I think that the responsibility rested with the ethical committee to get independent advice.
A But it does not absolve the responsible consultants for providing them with the most accurate information possible with regard to the patients who are being investigated. I commented that “hopeless prognosis” and “devastating condition” could not, in my view, be applied to the gastrointestinal problems that these children had.
Q With regard to the representation in the application and, indeed, in the letter at which we have just looked that all the children had disintegrative disorder, would that, in your view, have had an effect on the way in which the application was regarded by the ethics committee?
A Often, if you are being asked as an ethics committee to comment on an application that involves a very serious disorder that leads to, for example, a drastic shortening in life expectancy and you are presented with something that may possibly do the patient some good, then I suspect – although I have not sat on an ethics committee – that most people would say, “Well, this patient has a very poor prognosis, let’s give them the benefit of this novel treatment,” for example, or an investigation that might then lead to some novel therapy, compared with, say, making a request to do highly invasive investigations on a disorder that might be troublesome but does not lead to a reduction in life expectancy.
Q As you rightly say, you have not sat on an ethics committee, but you have made a great many applications to ethics committees for research studies. Wearing that hat, would you expect the severity of the disorder which you are researching into to be something that you would need to tell the ethics committee about? – I mean, with regard to balancing the risk and benefit that they have to do.
A Yes, I think that would be an important component of the application and perhaps the topic of a subsequent discussion if the original application had not made it absolutely clear what was being intended and why.
Q We know the ethics committee ultimately granted permission for this study and attached conditions. At page 358 is a letter from Dr Pegg to Professor Walker-Smith dated 7 January.
“I refer to the recent application to the Ethics Committee regarding the above project and I am pleased to inform you that the project was approved at the meeting on 18 December 1996” –
so two years from the date of this letter.
“As you may be aware this application was discussed at length at two committee meetings and the approval is conditional on the following:
(1) Only patients enrolled after the date of the December meeting will be considered to be in the trial
(2) The Shilling test to be removed from the protocol
(3) The consent form to be modified so that the possible complications of lumbar puncture are explained.”
He asks for a report of any adverse events and then goes on:
“The ethics committee must also be informed of, and approve, any proposed amendmenet to your initial application which has a bearing on the treatment or investigation of patients or volunteers.
A copy of the patient consent form and information sheet must be lodged in the clinical notes.”
Then he talks about confidentiality. The reply to that letter is at page 362. This is Professor Walker-Smith’s reply and it was copied to Dr Wakefield, dated 9 January.
“Many thanks for your letter. I accept its contents and we will modify our protocol as you recommend and give an annual report of the progress of the study.
We will place a copy of the patient consent form and information sheet in the clinical notes.”
First of all, whose responsibility, Professor Booth, do you regard it to ensure that a study complies with the conditions imposed by the ethics committee?
A It is the joint responsibility of all the investigators. In this case there were three main investigators, and on the application, as I recall, they were not differentiated, so I think the responsibility would rest jointly. In some circumstances, a study has a PI (principal investigator) and under those circumstances you would anticipate that they would make sure that the requirements of the ethics committee were complied with. I do not have a sense in this study that there was an obvious PI.
Q Is the reply the same with regard to any modifications to the protocol? My question is the same: whose responsibility is it to ensure that modifications which are prescribed by the ethics committee are carried into effect?
A It would be the joint responsibility of the applicants, not all of whom seem to have been copied in on this correspondence.
Q As far as making sure that the correspondence is known about and any conditions or modifications are known about by the principal investigators, whose responsibility is that?
A I think you would hope that the ethics committee chair would circulate them, but, if they happen to have written to one of the team, you would hope that the ruling and the requirements from the ethical committee would be circulated by that person to their colleagues.
Q I want to ask you about two of the conditions. With regard to the requirement that the consent forms and the patient information sheet which is appended to the ethics committee is included in the records of the children, did any of the 11 children whose records you looked at in fact have that information in their clinical records?
Q Given that it is all of them rather than one or two having been inadvertently mislaid, do you regard that as an important omission?
A It is certainly a breach of the requirements of the ethics committee.
Q Yes. As far as the condition with regard to the start date of 18 December, I think it is an agreed fact that Child 1, 2, 3, 4, 6, 9 and 5, were all investigated prior to 18 December. Was that acceptable in your view?
A I think if you are planning a research study that requires ethical committee permission, it is not appropriate to begin the study until you have received that permission.
Q The conditions imposed by an ethics committee, Professor Booth, in respect of a proposed research study on young children, are they a formality or are they something which you regard as being of importance as far as the researchers are concerned?
A I think they are both a formality and a matter of great importance. I think that the wishes of the research ethics committee carry enormous weight, not least because they can bring your research to an end.
Q I want to ask you to summarise your overall view of the nature of this programme of research and the information provided to it, and then I am going to revert back to it when we have looked at the individual children. I am at page 18 of your report, if that assists.
A I think the research ethics committee could have done more to have satisfied themselves about the appropriateness of these investigations in children with disintegrative disorder. I do not think that requesting information from someone in the same institution who is not a paediatrician was an appropriate thing to be doing. If I had sought, as chairman of the ethics committee, the opinion of a paediatrician who was well-informed about these matters from outside the institution and they had sent back a three-line answer, I would have got another opinion. It was completely inadequate for the purposes of the committee. As I have said, I think the information supplied to the committee with respect to the gastrointestinal problems that these children had, in that they were described as “devastating” and “hopeless” – that was the meaning of the letter – would also be inaccurate. So I think they sought inadequately and were supplied with inappropriate information.
Q Would the inadequacy of that information impact upon their ability to measure up the risks and benefits of this study?
A Yes, substantially.
Q As far as the criteria which were to be used and which were set out in the ethics committee application for performing these invasive tests, do you think they were adequately defined?
A I think it is something that would have been important to get an independent expert to clarify with the researchers. These were invasive investigations. They were justified in the application as being clinically indicated. I think it is the job of the research ethics committee to be absolutely certain that clinicians are going to be acting appropriately. The chairman of the research ethics committee said: “Well, these were senior clinicians and one has to go with what they say.” I think it is the job of the ethics committee to challenge those assertions.
Q Do you regard the making of the assertions as acceptable in this case?
A It may have been. I think one would want to look at the individual cases before coming to a conclusion about whether the investigations were or were not clinically indicated.
Q We will of course be going on to that. Perhaps I can ask you, generally speaking – and I know the answer is dependent upon the individual cases, Professor Booth – did you come to the conclusion that these investigations were in fact clinically indicated, as was represented, or were undertaken as part of a research project?
A In overview, the clinical records are peppered with references to this research study, the need to get it approved, agreeing the protocol and so on, and so I came to a consideration of the patient records against the background that they were taking part in a research study.
Q If they were being done for research purposes, what do you think about the ratio of risk to benefit of these particular investigations?
A I think the nature of the invasive investigations, particularly the colonoscopy, was not justified by the degree of gastrointestinal symptoms that they had for a research study.
Q No one can obviously predict what the ethics committee would have done had they been given full information, but would this particular issue of risk benefit in the context of non-therapeutic research have required a very careful consideration before it was undertaken?
A Yes. I think doing a research colonoscopy would need very, very careful consideration indeed.
Q As I say, no one is asking you to predict what the ethics committee would have done, but if an experienced clinician is thinking about wanting to do colonoscopy for a research investigation, would you expect him to regard that as being a difficult thing to get permission to do?
A Yes. I think a lot of people probably would not get that far. I cannot think of a scenario where I would want to make that application just for a research study.
A Because, if it was just for a research study, the ratio of risk and benefit to the patient could not be justified by something as unpleasant and invasive as a colonoscopy.
Q You say you would not go so far as making the application ----
A But if I did, I would anticipate it would be very difficult to convince an ethical committee of the need to do it purely for research.
Q I would like to ask you on one other matter, Professor Booth, before we look at the individual children – and then, as I say, we will come back to all these issues – and that is the role played by the subsequent histology on the biopsies in these children’s cases. First of all, we have heard about the situation at the Royal Free Hospital – and I know you are aware of it from the transcripts – that there were weekly meetings between the histopathologists and the clinicians to discuss histopathology reports. Is that something that happens in your own unit?
A Yes. I would be very surprised if it did not happen in every major GI unit.
Q It is not special in any way to the Royal Free.
Q Can you tell us what the respective roles of gastroenterologists and histopathologists are?
A In my experience, in such meetings one of the clinicians presents the clinical story fairly briefly and the endoscopist presents the macroscopic findings at endoscopy; there may be results of other investigations that are relevant; and then the histopathologist takes the meeting through a review of the histology using a projecting microscope so that everyone can see what they are talking about and they can point out relevant features and people can ask them questions as well.
Q How knowledgeable is the clinician, an experienced gastroenterologist, in the reading of histopathology slides?
A I think most of us go to these meetings weekly or fortnightly and have done so for very many years, so within a limited area of gastrointestinal pathology one becomes reasonably expert, yes.
Q Firstly, with regard to the documentation – and I am at page 26 of your report if that helps you – if there has been a clinically relevant histopathology report, do you expect that to be filed in the clinical records?
A All the histopathology reports are relevant and so yes, everyone’s histopathology should be filed in their records.
Q If an alternative view has been reached of an original interpretation of the histology by either the histopathologists or the clinicians in consultation with the histopathologists, would you expect that to be in the clinical records?
A Yes. Sometimes if it is a major departure – and by major, I mean something which is going to have an impact on the patient’s subsequent clinical management – the histopathologist would often – not that this happens all that often, but when it does – they would submit – publish, rather – a supplementary histopathology report which has an updated opinion and that would go into the notes.
Q We know that on the face of it, there are some discrepancies between the clinical histopathology as reported in the histopathology reports in the children’s records and the histopathology findings ultimately reported in The Lancet paper. Dr Davies has told us that for routine diagnostic purposes, the level of minute detail published in The Lancet would not have been necessary in the vast majority of cases. That was the evidence she gave. If those subtle research findings were relevant to the child’s treatment, then would you expect that to filter through to the clinical records?
A Yes. I think the definition of a relevant change is probably one which leads to a change in the child’s management. As I am sure the Panel has heard, histopathology is a very subjective occupation and so opinions differ from time to time. I think if the clinician in charge, who is the person who carries ultimate responsibility for the child’s management, feels that some change in the histopathology is appropriate, then it is relevant when it changes treatment.
Q How common is that, Professor Booth? Would it be usual for subtle research findings to drive clinical treatment decisions?
A No. I think the presentation of the results at the histopathology meeting and the discussion that takes place in relation to them at the time are the main usual drivers for determining treatment.
Q If for some reason a subsequent research finding did result in decisions being made which influenced treatment, then again, would you expect that to be ascertainable from the clinical records of the child?
A Yes. Everything relevant to the clinical management of the child should be available in the clinical records.
Q Lastly, I want to ask you about lymphoid nodular hyperplasia itself. You deal with this on page 16 of your overview report at paragraph 8. Is there a consensus about the significance of findings of lymphoid nodular hyperplasia in children?
A I think most people would agree that it is common that it has been recognised for a long time. I think most people would agree that in patients with various immuno deficiencies you see it more frequently. There is some evidence that it may be related to abdominal pain and rectal bleeding, although my view is that the evidence is not particularly strong. When people see it at endoscopy, they note it and it does not usually lead to changes in management or a sort of diagnosis as such.
Q Whether this is a significant finding or not, can the finding of a characteristic justify making the clinical decision to look for it?
A I am not quite sure that I understand the question. Do you mean if you note something is present frequently in otherwise normal children as an endoscopic finding, would determining its frequency in a separate population of children be appropriate?
Q Yes. Is it retrospectively justified in looking for it, if you find it?
A By retrospectively, do you mean retrospectively in the records of children who you have already ----
Q No. If you colonoscope a child and you find a particular histopathological manifestation in that child, can you use that as a reason for having done the colonoscopy, the fact that you found something?
A You do not know before you do the colonoscopy what you are going to find.
A So the justification for doing the colonoscopy has to be on information which is available before you do the colonoscopy.
Q In general, clinical medicine, that will be what?
A That is history, examination, results of other investigations.
Q With those background facts and, as I say, Professor Booth, with the proviso that we will have to return to them all, I want to turn to look at some of the individual patients. Before I do so, I want one thing to be clear about the records. What we are looking at of course is what the Royal Free Hospital would have had to look at when they saw these children in 1996. I just want to be clear as to what they would have expected to have. Obviously they would have the GP or consultant referral letter and they would have anything that they were sent by way of records by the referring doctor. Would they have anything else, generally speaking, except what they elicit from the patient or the parents themselves?
Q It is for that reason I am not going to take you to all the early general practice records which we looked at with the GPs. I am going to look at the children, as you know, in the order that they were referred to the Royal Free Hospital. That means starting with Child 2. If you could turn up your individual report on Child 2, please. As far as the Panel are concerned, they will need the Royal Free records and the GP records. At the outset, Professor Booth, at page 201 of the Royal Free records, just so we are clear, there is an allusion in a letter of January 1995 to the desirability from the Chelsea & Westminster Hospital to of this child being referred to you. You can see it in the third paragraph down. There is no other mention of you seeing this child. Do you have any recollection to your knowledge that you have ever done so?
Q I should have said before I embarked on this, I hope you have a plastic sheet in front of you so that you can look at the names.
A Yes, I have.
Q Do you have the appropriate individual records which you have done?
A Yes, I have.
Q I am going to have to take you, I am afraid, through the records which we are all becoming familiar with, but I hope I can be reasonably selective in what we refer to. Dealing first of all with the circumstances of the referral, this case starts early on, as you know, in 1995, when Professor Walker-Smith was still at St Bartholomew’s. If you go to page 197, please, of the Royal Free records, you will see a letter dated 29 June 1995 from Dr Wozencroft, who is a consultant psychiatrist:
“Dear Professor Walker-Smith
I write to ask you to see [Child 2] and to express an opinion upon him. I know that his parents have contacted you and your colleague, Andrew Wakefield. The family doctor, Dr Cartmel also wants the benefit of your opinion.
[Child 2] is a boy who has been seen by a great many doctors over the years. I have become involved only recently. My tasks are to take an overview of the situation; to follow [Child 2’s] development and to discuss it with the parents … ”
Then he gives his condition as autistic spectrum disorder.
“[Mr and Mrs 2] feel there is a strong physical component to [Child 2’s] difficulties and I must say I agree with them. At the moment, [Child 2’s] physical, medical and emotional states are all deteriorating. In the past, just such a deterioration has been nipped in the bud by B12 injections …
For my part, I am not familiar with the research evidence which connected immunisation with difficulties like [Child 2’s]. Naturally I am trying to educate myself in that area. [Child 2’s] condition, however is going down hill again and his parents, his GP and I would all be grateful for an urgent opinion from you.”
That, as I say, is while Professor Walker-Smith was still at St Bartholomew’s. If we go on, please, to page 196, Professor Walker-Smith writes back, thanking him for his referral. He says:
“I am left somewhat confused as to what the evidence is of B12 deficiency in this child.
On examination there is no evidence of Crohn's disease which concerned he mother, in view of the possible association between measles and Crohn's disease. Apparently there has been a gastrointestinal problem in the past and I am writing to the various professionals to try and find what has been done in the past and I plan to see [Child 2] again in 2 months’ time.”
And again, he refers to the involvement of a local paediatrician. He concludes by saying:
“However, I plan to see him again in 2 months’ time when I have more information available. I have done some routine blood tests.”
That initial view by Professor Walker-Smith that there was no evidence of Crohn's disease, but that there had been gastrointestinal problems and he had undertaken routine blood tests, would you regard that as being a fairly standard reaction to the problems?
A Yes, absolutely.
Q If you could then go to page 193, Professor Walker-Smith does indeed make inquiries, as he said he was going to, and he writes to Dr Cavanagh, who is a paediatric neurologist at the Chelsea and Westminster:
“This child was referred to me by … a child psychiatrist from Peterborough … I am very puzzled by this child and am interested in your letter where you consider the diagnosis of Vitamin B12 malabsorption.”
He asks about the investigations. Then he says:
“This child was referred to me via Andy Wakefield at the Royal Free because of mum’s perception of the child’s really began with MMR and in view of the possible link of measles with Crohn's disease.
On examination there is absolutely nothing to suggest the diagnosis of Crohn's disease. His weight and height re both close to the 50th centile.”
Does that mean a normal weight and height?
A Yes, that is normal.
“The gastrointestinal story sounds very much like multiple food allergy/irritable bowel syndrome rather than inflammatory bowel disease or indeed coeliac disease. However I have done routine blood markers, CRP, endomysial antibodies etc, and I plan to review him again at the Royal Free in 2 months’ time.”
Those routine blood markers with particular reference to CRP, would that be testing for inflammatory indices which you have discussed with us?
A Yes. The endomysial antibodies are a screening test for another disorder called coeliac disease.
Q Then Professor Walker-Smith writes to Professor Warner, who is a general paediatrican. That is page 195. That appears to be asking for a general paediatric view, rather than specialist gastrointestinal.
“I would be very grateful if you could give me your opinion on this child whom is diagnosed as having autistic syndrome and has had evidence in the past of multiple food allergy …
Obviously this is a very complicated problem and I would be grateful for any assessment that you may have made concerning him.”
Professor Warner writes back at page 186, enclosing with that a previous report, which is at page 188. That was a much earlier report in 1992 from Professor Warner himself. As far as the gastrointestinal symptoms are concerned, he says he has Asperger’s syndrome:
“Whether or not this can ever be established to be associated with any food intolerance remains to be seen.”
Going down to the bottom of the first page:
“His stools were very loose though they had been since early infancy and tended to be rather pale and offensive.”
“I pointed out that there are many ways in which one might interpret or misinterpret an apparent reaction to food and we would need to consider doing appropriate challenges and also consider whether a small bowel biopsy was required to exclude Coeliac disease as a diagnosis.”
As I say, this was back in 1992. Then at the bottom of the page:
“I did in passing discuss with [Mr and Mrs 2] the question of whether [Child 2] did have a gut overgrowth of organisms, particularly because of his very loose offensive stools. With his very abnormal diet it is of course possible that he might have odd gut colonisation with organisms though this extends way beyond the consideration of candida. If there is any possibility that he might have Giardiasis or any other gut overgrowth then it weld be reasonable to give him a short course of Metronidazole.”
So that was the letter which was sent to Professor Walker-Smith from three years previously. Then Dr Cavanagh also responds at page 184. That letter sets out the details of the B12 investigations which had been carried out. He says at the end of that letter:
“… it seemed to me sensible that [Child 2] had some B12 absorption studies and I suggested a referral to a Paediatric gastrointestinal nearer home.”
He enclosed with that letter the letter at page 190, which was a letter from August 1994. Looking to the bottom of that page:
“… he seemed to be wasting away and very miserable and then responded to Vitamin B12 injections.
The present situation is as follows:
His stools have been firmer since September and his mother is beginning to be able to include some foods into his diet which had previously upset him. Even now there are some foods that make him hyperactive …. He is not potty trained.”
Then it sets out his behavioural history. Then at the bottom of the page:
“Examination of [Child 2] does not reveal any focal or formal abnormal neurological signs. Clearly, he is hyperactive …
The history points strongly to an underlying dietary sensitivity, and I note that he has never been on a oligo-anti-genic diet.”
And the desire to test him for B12 deficiency first of all. That again is the letter that informed Professor Walker-Smith. As we know at the start of that correspondence, he reaches the conclusion that there is no evidence of Crohn's disease. I want to ask you first of all, Professor Booth, in regard to that 1995 correspondence, is that, with a series of inquiries with other clinicians, consistent in your view at that stage with appropriate clinical care?
A Yes, absolutely.
Q And having concluded, as he did, that there was no evidence at all of inflammatory bowel disease, would you have expected any invasive investigations to be undertaken?
A No, I do not think I would.
Q He writes confirming his conclusions, and he says he has not arranged to see Child 2 again. If we go to page 178, 13 September 1995:
“Dear Dr Cartmel
I have now reviewed [Child 2]and I think inflammatory bowel disease is extremely unlikely and I have had a copy of the letter which Dr Bhatt wrote to you and I do believe that the best way forward is for a Schillings Test. This is a test which is best done by experts and I would recommend that this is done in the Chelsea & Westminster.”
He suggests the involvement of a local paediatrician, and he says:
“I have not arranged to see [Child 2] again but I would be happy to do so should the need arise.”
The plan not to see the child again or to review him, is that consistent with the conclusions that he had reached?
A Yes. I think that if you are not planning any further investigations, particularly if you are aware that other paediatricians are closely involved, then not arranged to see the patient again would be quite appropriate.
Q If we go to page 179 just for completeness, he writes to Dr Wozencroft in the same terms.
“After reviewing [Child 2], I don’t really believe there is any evidence of chronic inflammatory bowel disease….”
Then the next to last paragraph:
“I have not made an appointment to see [Child 2] again, but I should be happy to do so again in the future and I have left the line of communication open with [Mrs 2].”
He then suggests the involvement of a consultant paediatrician. Page 180 is another letter to Dr Cavanagh.
“I have spoken a number of times on the telephone to [Mrs 2] and I don’t really believe [Child 2] has any features of chronic inflammatory bowel disease.”
Then, at the bottom of the letter:
“I would be very interested to hear what turns up but I have not made an appointment to see the child again.”
The next thing that happens is some ten months later when we have a letter from Professor Walker-Smith to [Mrs 2] and that is at page 165, dated 16 May 1996.
“Dear [Mrs 2]
I think it would be very helpful if I saw [Child 2] again. I have had discussions about [Child 2] with Dr Wakefield. We have a plan for investigation but I think if it were convenient for you, it would be helpful for me to see [Child 2] in outpatients and discuss and plan what we have in mind. I have arranged an outpatient appointment …”
and he gives the date. I have some questions to ask about that letter, but just before I do so, can we go to page 28. We see he is in fact seen on that day by Dr Murch, and the details of his exclusion diet. I am sorry – it is Professor Walker-Smith’s handwriting.
Q But it is Dr Murch’s clinic stamp. There are details of his exclusion diet, and at the bottom of the page, “Arrange admission with Dr Wakefield”. Then at page 162 we see the culminating letter between Professor Walker-Smith and Dr Wakefield of 24 June 1996.
I at last saw [Child 2]. I think he is now the most appropriate child to begin our programme. Can we discuss together the most appropriate date? I think September might suit [Mrs 2] best. She has some apprehension about colonoscopy and she was concerned that last time [Child 2] had a general anaesthetic he reacted with a transient fall of blood pressure. In fact we will not be using a general anaesthetic but it is difficult to judge whether he might in any way react to pethidine. I think she would like a copy of the protocol that we are using. I don’t know whether you think it is appropriate for you to send her that, or whether I should.”
As far as those two letters are concerned – the letter from Professor Walker-Smith to [Mrs 2], Professor Booth, and then the arrangement of the admission with Dr Wakefield, and the letter from Professor Walker-Smith to Dr Wakefield – do they seem to you to be consistent with ordinary clinical practice, or the beginning of a research study?
A They are not consistent with ordinary clinical practice. Professor Walker-Smith had already come to a conclusion with regard to the clinical management and this is indicating that the reason for admitting him is a research study.
Q If this were a clinical plan, would you expect Professor Walker-Smith to be evolving a clinical plan for investigations with Dr Wakefield?
Q The use of the phrase “to begin our programme” – “I think he is the most appropriate child to begin our programme” – is that consistent with a clinical plan?
A No. It indicates that these investigations were being planned as part of a programme; in other words, a research programme. That would be my interpretation of that wording.
Q The suggestion that the mother might like a copy of the protocol, would you expect a protocol in respect of investigation of one child to be send a parent?
A Not if it was just a routine clinical admission. It would be unlikely that there would be a written protocol outlining a routine clinical admission. We know that there was a research protocol and that, combined with the information in Professor Walker-Smith’s letter to Dr Wakefield, would suggest it was the research protocol that was being referred to in that letter.
Q Let us then go on to see how things panned out, would you go on to page 130, please. This was the letter that Professor Walker-Smith sent to the general practitioner dated 28 June 1996.
“Dear Dr Cartmel
I duly saw [Child 2] in the clinic. As you know I first met [Mrs 2] via Dr Andy Wakefield who is concerned with measles immunisation and possible Crohn's disease. I think Crohn's disease is unlikely. Dr Wakefield has the view that there may be some kind of other inflammation which may be a relevant factor in [Child 2]’s illness and we now have a programme for investigating children who have an association with autism and a possible reaction to immunisation. I am arranging for [Child 2] to come in for investigation at the end of August.”
Again, if this was a clinical admission, Professor Booth, would you expect Professor Walker-Smith to be writing to the general practitioner in terms which suggest that Dr Wakefield has had an involvement in the theory, at least, of might be wrong with this child?
A No, you would not.
Q I am sorry to drum the point home, but is that the letter to your mind suggestive of research or clinical investigation?
A This implies very strongly that the investigations are research investigations. It refers to a programme for investigating children, and so on.
Q We know that Professor Walker-Smith had come to the view that this child did not have Crohn's disease and, indeed, he has repeated here, perhaps in a little less strong terms, that it is unlikely. Would you expect a change of heart on his part as a result of any view of Dr Wakefield’s in relation to the possibility of a connection with Crohn's disease and measles immunisation?
A It is difficult to answer that question. I would not expect Professor Walker-Smith to change his mind in the light of any clinical information that Dr Wakefield could add to Professor Walker-Smith’s original assessments on Child 2, no. If Professor Walker-Smith changed his mind about admitting this patient, as he appears to have done, it could not have been for clinical reasons and must presumably have been for research reasons.
Q Can we now turn to the admissions and investigations that were carried out on this child, and then I want to ask you about the appropriateness of those investigations. The first admission was between the 1 September 1996 and 6 September 1996. Can we just turn to the Royal Free records at page 4, please. Can you just tell us? You see at the bottom where it says “Patient Episode Summary”, and we see the dates for inpatient and outpatient appointments, and the consultant on the right hand side – what do you understand that reference to the consultant to be?
A That would be the consultant under whose care the patient was being admitted to hospital or seen in the outpatient clinic, or whatever the clinical activity was.
Q On 1 September – so the day of admission – a consent form was signed, and that is at page 340. We see the investigations signed by Mrs 2 and the investigations at the top: “Colonoscopy and biopsy; Schilling test; lumbar puncture; MRI scan.” Is that a standard clinical consent form?
A Yes, it is.
Q Can we then go to page 15. We see at the top of that it looks like the 20th. You can tell from the context of the rest of the notes that it is, in fact, 2 September. We see,
“Referred for investigation of ? association between gi disease/autism/measles.”
Then a detailed history is taken, which makes it clear that this child did indeed have gastrointestinal symptoms, including a long history of diarrhoea. There was a colonoscopy and would you look at page 247, please. This took place on 2 September, so the day after admission. We see:
“This colonoscopy was performed in the further investigation of disintegrative disorder, and was in fact abnormal.”
Is that a surprising indication for the performance of a colonoscopy, Professor Booth?
A A surprising what? I am sorry.
Q Indication that, apparently, was performed in the further investigation of disintegrative disorder?
A I think one issue about performing this colonoscopy was that disintegrative disorder had not at this point been confirmed. That diagnosis had not been made.
A I am not sure if that answers your question or not.
Q Yes, it does. That, of course, is a procedure that was performed by Dr Murch, and I will come back to the role that he plays. The next thing we have on the same date is the request form for an EEG and evoked potentials. That is page 257. It is signed by Dr Wakefield and the reason for the request is given as disintegrative disorder, regression of milestones and social skills, vitamin B12 deficiency and then “? abnormal myelination”. I want to ask you this: if that was a standard clinical investigation would you expect Dr Wakefield to be requesting it?
Q What is the effect of signing a request for an investigation in a child?
A It means that you have some clinical responsibility for the patient. It does not necessarily mean that you are the consultant in charge because other people on the clinical team will very often sign request forms. It means that you are one of the people sharing clinical responsibility for the patient; that you have evaluated the need for the investigation and that you agree with it being done, and you will take responsibility for the result.
Q In view of what we have already established in general terms, of Dr Wakefield’s lack of paediatric qualifications and the terms of his job description, are you critical of his role in signing that investigation?
A Yes. I think it is inappropriate for a non-clinician, non-paediatrician, to be requesting clinical investigations on children. By clinical investigations I mean that are done directly on the patient.
Q Just turning on through the chronology to the rest of the investigations that were carried out, there was a Schilling test and we can see that from page 18, so that was the next day, 3 September. There was an EEG as per Dr Wakefield’s request, and that is on page 245.
“The patient was alert, very restless – he had to be held still throughout.”
He ultimately fell asleep. The conclusion is that the recording was within normal limits. There was a barium meal and follow through, and we see from page 336 that the date of the examination was the same day, 3 September. On 4 September there was an MRI and a lumbar puncture, and we can see that from the top of page 9. Against “MRI” there is a tick, and then:
“LP [lumbar puncture] for CSF for protein electrophoresis
measles AB [antibodies]”
and for a note to be sent Dr Chadwick. We know that the CSF from the lumbar puncture was tested for measles because the result is at page 22. At the top of the page:
“CSF measles Abs [antibodies]: -ve [negative].”
That set of investigations, Professor Booth – the colonoscopy, EEG, EP, barium meal and follow through, MRI and lumbar puncture – does that accord with the protocol that was submitted to the ethics committee?
A Yes, it does.
Q Could we then go to the histopathology report to see what it ultimately showed? That is page 264, please. At page 265:
“Fragments of small bowel mucosa with mild chronic inflammation within the lamina propria. No granulomas identified. Fragments of large bowel mucosa with a moderate chronic inflammatory infiltrate within the lamina propria. No granulomas identified.”
For the next three specimens:
“All these specimens show fragments of large bowel mucosa with patchy increase of chronic inflammatory cells within the lamina propria and occasional prominent lymphoid follicles with a germinal centre within the ascending and transverse colon biopsies. An occasional focus of acute cryptitis is present within the ascending colon specimen and there is mild crypt distortion. No granulomas are identified.”
For the next specimen:
“A fragment of large bowel mucosa with mild chronic inflammation of the lamina propria and very focal cryptitis.”
The comment is:
“The mild patchy generalised increase in inflammatory cells with lymphoid aggregates and follicles is not very specific but could be in keeping with low grade or quiescent inflammatory bowel disease.”
That is the report that was obtained. The child is then seen by Dr Berelowitz and we have the note of that at page 143. We can see that Dr Berelowitz saw the child on 5 September 1996, three days after the colonoscopy on 2 September, and then ultimately the child is discharged home and later is readmitted and seen by Dr Harvey. That is on page 13. He is the neurologist who was involved. He sets out a brief history and says at the bottom:
“I await the CSF studies with interest.”
On the next page, page 14, there is a ward round with Professor Walker-Smith in the middle of the page. We can see:
“Provisional diagnosis: Crohn’s disease” –
and a plan CT3211. Is that the enteral feeding, liquid diet plan?
A I think it is, yes.
Q Is that a standard treatment for Crohn’s disease?
A Yes, it would be.
Q There is a discharge summary sent and we can go to that at page 145.
“Diagnosis: 1. Apparent neurogenic degenerative disorder
2. Provisional diagnosis of Crohn’s disease.
[Child 2] was admitted to our ward on the 2nd September 1996 for further investigation of several problems. The main problems are of developmental regression from 20 months of age, diarrhoea from 20 months of age and abdominal pain from the same period.”
Then it sets out his behavioural problems and then:
“The diarrhoea started at this time, occurring 10 times a day and contained mucous. There was only one episode where it contained blood ...”
“At 3 years of age he had sudden onset of weight loss associated with increased frequency of diarrhoea, general lethargy and pallor. There did not appear to be any precipitating events causing this and the episode as a whole lasted for 3 months.”
We can see that he lost several of his skills and it is important to note:
“… 3 such episodes of acute exacerbation with subsequent loss of developmental skills have characterised [Child 2’s] illness.”
He had another episode at 4 with increased diarrhoea, lethargy, weight loss and loss of skills. There is a diagnosis of language and possibly Asperger’s, details of the family neurologist and details of his family history. If we turn to the top of the next page, it reads:
“He was extensively investigated. A full panel of blood tests was performed with regard to his developmental regression. He had a colonoscopy. He had an MRI. He had a sleep EEG and evoked responses. A Schilling test was performed.”
The details of the colonoscopy are set out.
“The rectum showed very minor abnormalities of vascular pattern without any frank ulceration or friability of the mucosa. Overall appearances were normal until the ascending colon. Here one definite apthoid ulcer was seen … multiple prominent lymphoid follicles …. Histology possibly demonstrates mild chronic inflammation within the lamina propria of the terminal ileum. It should be noted that it is difficult to estimate whether or not this is within normal limits. No granulomas were seen.”
It goes on to say that the Schilling test was normal and that the MRI did not show any structural abnormalities. The EEG was normal and evoked responses were normal. The blood tests are set out and the CSF results. On the barium meal and follow through there are still several results awaited:
“There was a significant finding of patchy inflammation within the colon.”
“With regard to [Child 2’s] neurological problems an opinion of a neurologist and a child psychiatrist have also been sought. I am sure that they will forward further information to you.
We will review [Child 2] in clinic in 2 weeks time.”
That was the discharge summary.
Sir, I am conscious that people might like a break, but I have three or four more records to refer to and that will only take a minute.
THE CHAIRMAN: Yes.
MS SMITH: There is the letter from Dr Berelowitz to Dr Murch on page 143 which I have already mentioned. He says that it was not intended that he should have clinical responsibility but he saw the child. It sets out the history, and at the bottom of page 144 he says that he thought the presentation:
“…. looked like autism, whatever it actually turned out to be. I must say I thought the presentation was indeed very typical and await the next patient with considerable interest.”
As far as that letter is concerned, Professor Booth, with its references to not intending to have clinical responsibility and the awaiting of the next patient, does that seem to you to be suggestive of clinical or research medicine?
A Can I just find the reference to clinical responsibility.
Q It is in the first paragraph, the last sentence:
“I saw him at the request of yourself and Andy Wakefield, for the purposes of learning more about possible links between his presentation and measles vaccination and bowel disease …”
A This I interpret to be Dr Berelowitz’s assessment, as part of the research protocol that we have already looked at, to see if this patient fulfilled the diagnostic criteria of disintegrative disorder.
Q The child is readmitted to the Royal Free on 10 November until 12 November – so just for two days. That was so he could undergo a repeat colonoscopy because he had been tried on enteral feeding. Would that be a course of action that you would expect if the child had been on enteral feeding?
A No, not automatically. He may have been in a research study of that particular enteral feed, so the repeat colonoscopy may have been for research purposes.
Q The last letter – and then I have some questions to ask you about the clinical implications for all this – is on page 140. The letter is to Dr Cavanagh, Consultant Paediatric Neurologist at the Chelsea and Westminster, dated 13 November 1996.
“Further to my earlier letter in which I just mentioned [Child 2]. In more detail, we have investigated [Child 2] for evidence of Crohn’s disease. I had been, as you may remember, somewhat reluctant to do this in 1995 but more recently, in view of [Mrs 2’s ] concern with his gastrointestinal symptoms and his general symptoms may be related to MMR, we went ahead and did a colonoscopy. This in fact did show evidence of bowel inflammation with involvement of the ileum and the colon and we commenced him on enteral nutrition with CT3211. In fact, rather surprisingly there has been quite a considerable improvement in his general behaviour and the repeat colonoscopy which was undertaken this week showed return to endoscopic normality although at the time of writing I have not had the histology report. I will ask my Registrar to send you a full discharge summary after his current admission.”
Sir, that is the end of the records. As I say, I am going on to ask Professor Booth his view as to various aspects of that. If you felt it was appropriate to have a break now, it would suit the course of the case.
THE CHAIRMAN: In view of you taking Professor Booth through questions relating to the documents, I am wondering, unless Professor Booth objects, whether it may be perfectly in order for us to complete this.
MS SMITH: I have to say, it might be helpful, but I did not want to overload you without a break. I do warn you it will be a little while.
THE CHAIRMAN: Thank you for warning us. In that case, we will take a break. It is now 20 past three, so we will resume at 20 to four.
Professor Booth, please do not discuss this case because you are in the middle of giving the evidence.
(The Panel adjourned for a short time)
THE CHAIRMAN: Good afternoon everybody again. Ms Smith.
MS SMITH: Thank you, sir.
Professor Booth, I have various questions to ask you about the views you have in relation to the treatment of this child. I think we are going to have to remind ourselves as we go along, because the history is an exceptionally complicated one on this child. Going back to the first admission, he is referred in 1995, when Professor Walker-Smith is still at St Bartholomew’s, and he sees Professor Walker-Smith in outpatients. He is having diarrhoea three or four times a day. In September 1995, Professor Walker-Smith writes to Dr Cartmel that he has reviewed Child 2 and he thinks that inflammatory bowel disease is very unlikely. Then, as we know, he asks to see the little boy again in 1996. He writes to the mother and he subsequently sees him in outpatients. We have been to that note, but perhaps we could just go back to it for a moment. This the outpatient records for June 1996, at page 28 of the Royal Free records. The note is from Professor Walker-Smith. We see in the second paragraph that he was seeing Dr Hunter and that he was on an exclusion diet at that time, June 1996, which was yeast free and additive free. We know that on that occasion blood tests were taken and inflammatory markers were tested, because we have the results of those blood tests at page 326. We see the first column shows the results shows the results for 21 June 1996. Can you tell us what they indicate?
A The first is haemoglobin, HB, which is normal. Anaemia can be a sign of chronic inflammation. The white count is normal and you are looking for a raised white count in inflammation. The ESR is normal and not raised. The platelet count is normal. Again, you would be seeking a raised level there. The next is the CRP, about three-quarters of the way down, which is 1, which is normal. The albumen was not measured, but the inflammatory indices there are normal.
Q So in June 1996, when he re-sees him as a result of discussing the matter with Dr Wakefield, we get the normal inflammatory markers again. Following that out- patient consultation, when he records the details of the consultation with Dr Hunter, who was in the department of gastroenterology at Addenbrooke’s, he writes to Dr Hunter and we have his letter at page 163. It is dated 24 June 1996:
I would be very interested to hear your view concerning [Child 2]. I understand that you are seeing him and that he has had a good response to food elimination … I would be most grateful if you could let me know what regime he has and your thoughts about him. Via Andy Wakefield I have been asked to see him to consider doing a colonoscopy and a general assessment as to consider whether bowel inflammation of some kind might be playing a role in his illness and also performing Schilling Test which has not been performed as there had been some concern about B12 metabolism.”
Dr Hunter writes back in July 1996 at page 155. I will not read the whole letter, but it says:
“[Child 2] was referred to me by his paediatrician … because we have had some success in treating children with behavioural problems with the exclusion diet which we use routinely in adult patients with irritable bowel syndrome.”
Then he sets out the details. He says at the end of it:
“I have understood from [Mrs 2] that [Child 2’s] guts are greatly improved when he sticks to his diet and his bacteria and I personally would be reluctant to do a colonoscopy.”
Then he gives blood test results – they predate of course the ones which Professor Walker-Smith did – and he says:
“Please let me know if there is anything I can send you.”
So that was Dr Hunter’s information. Then, as we know, we have been through the admission on 1 September 1996, but we should just re-look at the clinical notes at page 15. This is when he was admitted as an out-patient as the first child in the study. I took you only to the first line which referred to the investigation and the association between gastrointestinal disease, autism and measles. If we go on to page 17, please, we see reference at the bottom of the page to Dr Hunter at Addenbrooke’s and the fact that he is on an exclusion diet. At the bottom of the page:
“Started April ’96. Seems to have eased abdominal pain.”
That was the situation when he was admitted on 2 September 1996. He says he has had normal inflammatory markers when they were tested at the out-patients appointment in June 1996, the details of Dr Hunter’s exclusion diet are known to Professor Walker-Smith and they seem to have helped a bit. The real overall question I have to ask you is whether, in the light of all that, a colonoscopy was clinically indicated in this case on this child?
A His symptoms were long-standing. He did not, as Professor Walker-Smith concluded originally, have anything to suggest that he had chronic inflammatory bowel disease, particularly Crohn's disease, and Dr Hunter was quite clear in his correspondence that this patient was much improved on diet and probiotics. So I cannot understand the need for doing a colonoscopy.
Q You say you cannot understand the need for it, Professor Booth, but what does your overall reading of the records suggest to you the reason for it was?
A Professor Walker-Smith seems to have changed his mind about investigating Child 2 following consultation with Dr Wakefield and that seems to have changed his mind and to be driving the investigations.
Q In those circumstances, would you call this a clinical admission or a research admission?
A A research admission.
Q Insofar as that colonoscopy is concerned, it was performed by Professor Murch. You have told us in broad terms what the person who actually undertakes the colonoscopy has a responsibility to do. Would that apply to this case, that you are of the view that he had a responsibility himself to be satisfied that it was appropriate to undertake an investigation?
A Yes. I think that applies universally, whoever is doing the investigation and whatever the context, whether it is a research study or a clinically driven study.
Q As far as the barium meal and follow through, which came after the colonoscopy, what is your view as to whether that was clinically indicated?
A I think I would not have done a follow through. Not clinically indicated.
Q For the same reasons that you have already given in relation to the colonoscopy?
A Yes. The index of suspicion of inflammatory bowel disease in this patient was very low indeed clinically, or should have been.
Q As far as the follow up on this child is concerned, it is extensive and I am not going to go through it all, although you may be taken to it in more detail by defence counsel. In fairness, however, we should complete the history and in fact this child was seen by the Royal Free on and off until 2004. If we just go to page 138, that is a review undertaken by Professor Walker-Smith which resulted in a letter to the school doctor in December 1996. He says:
“ … it was clear that his behaviour had altered quite significantly with a series of food re-introductions … Certainly he seems to be altogether better when he is on … form of enteral feeding, although our colleague Dr Mark Berelowitz [the psychiatrist] did not detect any objective measure of improvement … ”
And he said he seemed more hyperactive and he suggests a review in two months’ time. Then at page 125, in February 1997, he reviews Child 2 in the inflammatory bowel disease clinic, says he is tolerating an increasing range of foods and that his progress has been satisfactory at school with an improvement in behaviour. Then in the last paragraph:
“As other children with a similar problem to [Child 2] have had some response to Sulphasalazine or Mesalazine, I have commenced him on Sulphasalazine suspension 250mgs twice a day to observe particularly any beneficial effect it may have on his behaviour. I would like to review him again in a month’s time.”
Is that an anti-inflammatory?
A Yes, it is.
Q Is it normally given for gastrointestinal reasons rather than behavioural reasons?
Q Then at page 124, in March 1997, we see Professor Walker-Smith saying:
“I was very pleased to see [Child 2] again in the out patients clinic. When I saw him his behaviour seems to have significantly improved …
This change is confirmed by his mother … Interestingly, he could not tolerate Sulphasalazine suspension when colouring and flavouring was added but he is tolerating Sulphasalazine in suspension … It would seem that this regime together with dietary regime has led to considerable improvement.”
And he says he plans to go on reviewing him. Then at page 121 we see a letter asking the school for some objective assessment:
“As you know we have found an unusual type of colitis in this child and have treated him not only with a special enteral feeding but also with Sulphasalazine. This seems to have led to a significant improvement in his behaviour.”
He says he seemed calmer and he asked for an independent assessment. Then the reply to that is on page 106 of the GP records, if you could turn to that. This is from the head of the school:
“Thank you for your letter concerning [Child 2]. You are asking me for an objective assessment as to whether I think his behaviour is improving. At school [Child 2] has never shown hyperactivity and has not suffered from diarrhoea. There was only one occasion of diarrhoea which lasted a day and would not have been considered anything out of the ordinary in a young child.
We have not seen [Child 2] behave in a destructive way at school, although he is a very lively little boy with autism.”
She says he shows a lack of awareness of his environment rather than excessive activity.
“It appears that [Child 2] is a very different little boy in his home environment as his mother report problems with diarrhoea and hyperactivity.”
She says they are continuing with treatment that he has been given. Then at page 111 of the Royal Free records – this is in June 1997 by now:
“ … [Mum says] his behaviour in her estimation was appreciably worse. He was hyperactive. Since he has been home he ha calmed down and continues to [have the liquid diet] … We are working closely with [Mrs 2] to determine which foods he can tolerate. As you know, we made a diagnosis of unusual type inflammatory bowel disease which responded very well to [enteral feeding] and we are endeavouring to return him to normal diet.”
Then page 92, Professor Walker-Smith to the GP in September 1997:
“I reviewed [Child 2] in the out patient clinic with Dr Wakefield. Unfortunately [he] reacted dramatically as far as behaviour is concerned … Also there was hyperactivity …
Plain xray of the abdomen showed generalised faecal loading and I am sure that constipation with overflow diarrhoea is contributing to his current diarrhoea.”
That is the situation you described to us earlier. Is that correct?
Q He goes on:
“The situation seems fairly stable … He is having a dietary supplement … However I have stopped Salazopyrine therapy whilst it had initial therapeutic benefits, but now has no therapeutic advantage.”
And he says he is going to review in seven weeks’ time. Then – and I do underline that I have been very selective, simply in the interests of some clarity – page 69. He is still under the care of Professor Walker-Smith, but this time he is seen by Dr Murch. He says:
“I was very pleased to see [Child 2] again today. He has not really shown significant improvement …. Apart from a brief period when this was first commenced … However, I suspect the underlying problem has been constipation … ”
And he gives the reasons why he thinks that:
“ … clearly passing overflow stools.
His abdominal x-ray was grossly loaded with mega rectum.”
What does mega rectum mean?
A It means that the rectum is very markedly distended with retained stool; it gets very large.
“I do think it will be most important for [Child 2] to tackle this effectively.
On a broader front, I am concerned that he has lost weight and I think, on balance, he would be better to return to the … formula … but enriched anti-inflammatory molecules.
The clearance of his constipation is likely to be important in increasing his appetite in addition.
It is very clear that [he] does not have a fixed level of functioning, and sorting out his bowel optimises things for him.
I have suggested that we review him … ”
Then at page 55, this time again he is being seen again by Dr Murch and by now we are in 2001:
“He has unfortunately slipped back a little in the last few weeks and I think there is little doubt that this reflects recurrent constipation. In his case this is often manifest by behavioural disturbance … He has been quite labile in the past in relation to extent of constipation, and he was undoubtedly loaded on palpation today.”
Then he suggests that he stays on picolax and liquid paraffin. Are they treatments for constipation?
A Yes, they are.
Q As I say, he continued and the last records of referral to the Royal Free or of being seen at the Royal Free for any review were in 2004. That extensive follow-up appears to have been in relation to a series of problems and attempts to sort them out, Professor Booth. Does that influence in any way your view that the initial investigations undertaken at the Royal Free were for research reasons rather than for clinical reasons?
A No, it does not.
Q Turning to the nature of the research investigations, as we have seen in this case, Dr Berelowitz carried out a behavioural assessment on 5 September 1996 and he reported in his conclusions that the presentation was very typical of autism. That behavioural assessment was obviously undertaken after the colonoscopy and the other investigations which we know were performed between 2 and 4 September. Bearing in mind the contents of the research protocol, were those investigations appropriate as part of that protocol?
A The protocol indicated that the inclusion criterion was patients who had proven disintegrative disorder. So the research investigations were initiated before that diagnosis was confirmed or excluded. I think the other issue is that carrying out behavioural assessments on children on an inpatient ward is likely to be misleading. Carrying out investigations on behaviourally disturbed children after they had been exposed to a battery of investigations is also likely to be misleading. So the timing of that assessment by Dr Berelowitz in the context of the protocol was inappropriate.
Q As far as Dr Wakefield’s involvement is concerned, I have already asked you about, and you have been critical of, his signing of the request for the EEG and evoked potentials, there is just a final matter that you also question in your report. If we look at page 36 where we see outpatient clinic notes under the Wakefield clinic stamp on those notes. Can you just tell us: what in general terms does a consultant’s name on a clinic stamp indicate?
A That means that they carry ultimate responsibility for everything that is transacted within that clinic, whether it is patients seen by them or their colleagues.
Q Given what we have already discussed in relation to Dr Wakefield’s apparent lack of paediatric qualifications and given the particular restrictions contained in his job description, are you surprised to see that?
A Yes, I am. It is not consistent with a job description of someone who was not meant to be carrying out clinical activity, nor having clinical responsibility.
Q Again, leaving aside the propriety or otherwise of it, given his job description, if this were the ordinary clinical admissions of this child, would you expect to see Dr Wakefield playing a role ---
Q --- which was apparently that central?
MS SMITH: Would you just excuse me for a moment, please? Sir, that concludes Child 2. I am in your hands as to whether you want to commence another one or not. I can tell you that you are up to where I hoped to be up to by the end of today, but I am very happy to start on another child. I will not finish tonight.
THE CHAIRMAN: We will be happy to do it as you would want to continue, but the only thing is, as long as you can finish by about 4.30, or thereabouts. I am just wondering if it is appropriate to start a new child today or in the morning.
MS SMITH: If I am being given the choice, sir, all of us have had a long and intense day. I would be quite content to start Child 1 tomorrow morning – Child 1 being the second, you will appreciate. We could perhaps take a view. At the end of tomorrow I will know how many more I have to do; in other words, how long it is taking because Child 2 is one of the longest.
THE CHAIRMAN: Yes, indeed.
MS SMITH: So we can take a view and if there is any risk of us falling behind, we might perhaps be able to start a little early and/or a little later.
THE CHAIRMAN: I am sure that is an appropriate thing to do. In that case we will now adjourn and resume at 9.30 tomorrow morning. Is that acceptable to you, Ms Smith?
MS SMITH: Yes, certainly.
THE CHAIRMAN: Professor Booth, you are going to remain under oath overnight so please make sure you do not discuss this case. We will resume at 9.30 in the morning.
(The Panel adjourned until Tuesday 9 October 2007 at 9.30 a.m.)