Monday, February 6, 2012

Day 45 GMC Fitness to Practice hearing for Andrew Wakefield

GENERAL MEDICAL COUNCIL

FITNESS TO PRACTISE PANEL (MISCONDUCT)



Wednesday 17 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




CASE OF:

WAKEFIELD, Dr Andrew Jeremy
WALKER-SMITH, Professor John Angus
MURCH, Professor Simon Harry



(DAY FORTY-FIVE)










(Transcript of the shorthand notes of T. A. Reed & Co.
Tel No: 01992 465900)



A P P E A R A N C E S


MS SALLY SMITH QC and MR CHRIS MELLOR and MR OWAIN THOMAS of counsel, instructed by Messrs Field Fisher Waterhouse, solicitors, appeared on behalf of the General Medical Council.

MR KIERAN COONAN QC and MR NEIL SHELDON of counsel, instructed by Messrs RadcliffesLeBrasseur, Solicitors, appeared on behalf of Dr Wakefield, who was not present.

MR STEPHEN MILLER QC and MS ANDREA LINDSAY-STRUGO of counsel, instructed by Messrs Eastwoods, Solicitors, appeared on behalf of Professor Walker-Smith, who was present.

MR ADRIAN HOPKINS QC and MR RICHARD PARTRIDGE of counsel, instructed by Messrs Berrymans, Solicitors, appeared on behalf of Professor Murch, who was present.








I N D E X

Page No


PROFESSOR IAN WESTERBY BOOTH, recalled

Cross-examined by MR MILLER, continued 1

Cross-examined by MR HOPKINS 47




THE CHAIRMAN: Good morning, everyone. Mr Miller, you were in the middle of your cross-examination and I believe that you wanted us to get out the files for Child 1.

MR MILLER: Child 1, Royal Free Hospital notes.

THE CHAIRMAN: As these are going to be short cases, would it be better for us to get two or three files together?

MR MILLER: Not quite that short!

THE CHAIRMAN: I should not be too optimistic then.

MR MILLER: Sadly not. I was feeling more optimistic last night. Some will take longer than others.

THE CHAIRMAN: It was just a light-hearted comment.

MR MILLER: I am very much in the witness’s hands as well; it depends how he answers the questions.

IAN WESTERBY BOOTH, continued
Cross-examined by MR MILLER, continued

Q Professor Booth, Child 1 was referred by Dr Barrow following what we have seen was his mother’s intervention at the general practice surgery leaving a note about a referral to or proposed referral to London and, as we have been through the notes before on a number of occasions, we know that enclosed with the referral letter was a letter from a consultant psychiatrist, Dr Hauck, which is at page 58 in the Royal Free notes from March 1996.

“[The mother] is much exercised about [Child 1’s] eating; he is a choosy and slow eater and she feels he is not adequately nourished. He suffers from loose stools on most days …”

and you made the point in evidence that, in the referral letter itself, there is nothing about the gastrointestinal symptoms, a point you have made in relation to other cases. True, on the face of it, there is nothing in the letter. This accompanied it. Unlike the previous case at which we were looking where, in Dr Wozencroft’s first referral letter, there is no reference at all to any bowel symptoms.
A Yes, that is correct.

Q At Professor Walker-Smith’s outpatient clinic on 20 June, which is at page 13 in the bundle, there seems to be some suggestion at the bottom of the page about five lines up,

“Dr Sue Burrow referred her [and] the Autistic Society referred here”

and then he talks about the problems with eating, that he was picky eater; has undigested food in his stools; has no control; has had blood occasionally in the stools which, as I understood you when you first gave your evidence, in some circumstances may be an indication to go straight to colonoscopy.
A Under some circumstances, yes.

Q In this case, Professor Walker-Smith arranged for blood tests to be carried out and the results were normal save for the haemoglobin which was slightly low; is that right?
A Yes, 10.8.

Q I think you said that that can be consistent with bleeding.
A I am not aware that I did. It is above the published cut-off that Professor
Walker-Smith uses for abnormality in the use of these tests.

Q A low haemoglobin can be consistent with bleeding, can it not?
A Yes.

Q This was, although slightly low, above the cut-off.
A Yes, that is correct.

Q We have already seen in the literature and do see in some of these cases that these screening tests are not diagnostic of either the presence or absence of inflammatory bowel disease.
A As we have said, no screening test is 100 per cent specific, that is correct, but it is an investigation, as we have discussed, that Professor Walker-Smith has recommended both in his 1995 original publication and in a number of reviews published before 1995 and since 1995 in which he makes that recommendation.

Q Thank you for reminding us of that. Is that the Beattie paper to which you are referring, the 1995 publication?
A The original paper is at tab 16 which is the original 1995 one.

Q Is that the Beattie paper?
A Yes and then there are others in Professor Walker-Smith’s bundle as well.

Q The child was however admitted on 21 July 1996 and the clerking note is on page 9 from Dr Casson. Is “G.I.T” gastrointestinal tract?
A Yes.

Q
“Diarrhoea – started [18 months] = [5 times a day]. Watery, [no] blood, [no] mucous.
Since then undigested food.
Now [seven times a day]. No bowel control.
[No] blood. ? occasional mucous.
Not offensive
… pale.”

Then “UGS” which is urinogenital …?
A Yes, that is correct.

Q
“[passes urine] – OK. [No] pain. [No] offensive stool.
[One episode] of bleeding. Fresh red blood → resolved.”

We know from the colonoscopy that this child had faecal loading which made the first attempt at colonoscopy impossible.
A That is correct.

Q My understanding of your evidence on this is, that is the answer to the whole thing because this child had constipation and that should have been what was considered at the time.
A It is certainly a diagnosis.

Q Bowel preparation was more successful three days later to the extent that a colonoscope was passed to the caecum by Dr Murch. Would you look at page 99,

“Some evidence of scoppe trauma in the descending colon. Terminal ileum obscured by food debris and not entered. No obvious pathology.”

Would you turn to the histology report from Dr Rees and Dr Davies at page 103 where, under the microscopic description … Putting it in context, there is no small bowel biopsy because they did not get into the small bowel.
A Yes, that is correct.

Q So, it is only large bowel.

“I. Sections show large bowel mucosa with a somewhat distorted lymphoglandular lesion with no histological abnormality.

II. Large bowel mucosa with preserved architecture. There is a patchy chronic
inflammatory infiltrate. There is a focus of transepithelial neutrophil migration. (cryptitis) with incipient crypt abscess formation. No granulomas, ova or parasites are seen”

and the comment is

“Colonic serial biopsies with focal active chronic inflammation in the caecum."

That is the outcome of the colonic biopsy, none having been taken from the ileum. I understand your point, Professor Booth, that this child did not require a colonoscope because his inflammatory markers were normal and he had constipation.
A I think the other issue is that Professor Walker-Smith had made a diagnosis of toddler diarrhoea.

Q How do you account for the findings in the colon at colonoscopy?
A This was a severely constipated patient and there are a number of references in the literature before 1996 to lymphoid nodular hyperplasia with inflammatory changing including cryptitis in patients including children with colonic stasis and stagnation.

Q In the colon?
A Yes.

Q So, you are saying in fact that this is evidence of the effects of the chronic constipation that has caused cryptitis and incipient crypt abscess formation.
A I am saying that it is one possibility. Carrying out colonoscopy in children with gross faecal loading is not commonly undertaken.

Q There are two points there. The first is that therefore the evidence of what you are likely to find is not readily available; is that right?
A I am saying that it was well recognised in 1996 that, in patients who had colonic stagnation, these sorts of changes were well recognised.

Q Could you give me the references?
A I would need a minute to be able to do that, if I may.

Q Would you just provide them for me. You do not have to do it on the hoof. If you have them before you …
A The one I have in mind is 1992, the first author is Drut, and it is Paediatric Pathology 1992,

“Hyperplasia of lymphoglandular complexes in colon segments in Hirschprung’s disease.

Q In Hirschprung’s disease?
A Yes.

Q Is that what this child had?
A No. I am saying that, as they point out in their paper, stagnation of colonic contents can lead to changes of lymphoid nodular hyperplasia and inflammatory change.

Q As I understood it, you say the tentative diagnosis put forward by Professor Walker-Smith was that of toddler diarrhoea rather that chronic constipation?
A His diagnosis before the colonoscopy was toddler diarrhoea. As soon as the colonoscopy first time round was start, I imagine it became immediately clear that this patient had gross constipation.

Q At the time, anybody who had looked at this before would not have considered it appropriate or would not have seen it as a constipation case or an overflow case because you say it was perfectly reasonable to treat this as toddler diarrhoea whereas, in fact, the colonoscopy produced the evidence not only that the child was constipated but also that there was pathology in the bowel?
A No. I am saying that this patient’s working diagnosis was toddler diarrhoea and that would not be an indication for colonoscopy. As it turns out, the diagnosis of constipation was made by a rather strange route. One would not normally carry out a colonoscopy in order to make a diagnosis of constipation.

Q Do toddler diarrhoea, properly described, and chronic constipation usually go hand in hand?
A Not usually, no.

Q So here was a case where you say that although on the evidence before him it was perfectly reasonable to consider toddler diarrhoea, in fact it turned out that the child had something completely different, which was discovered on colonoscopy?
A I am saying that toddler diarrhoea would not be an indication for doing a colonoscopy and that there are other ways of making a diagnosis of constipation. Yes; if the patient had not had a colonoscopy, the diagnosis of constipation may have been delayed. That is perfectly true but to carry out a colonoscopy to diagnose constipation would be a very unusual way of doing so.

Q I do not think there is any suggestion that was the case, but I am not going to ask you about your case which you produced this morning – the literature that you produced this morning – because obviously neither I, nor my expert, has had an opportunity to see it. In due course we will look at it. Perhaps you would just give us the reference, would you? Would you give us the title of the reference?
A It is called “Hyperplasia of Lymphoid…”.

Q Yes.
A Is that the information you require?

Q No, no. Where is it reported?
A It is from Paediatric Pathology 1992. I think it is Volume 12, 575 to 581.

Q The theme of your evidence is that you say, “This is what I would have done. I think that if I had been faced with a suggested diagnosis of toddler diarrhoea, I would not have done a colonoscopy in this case.” But that is your opinion, is it not? This is the way in which you would approach the case. You have told us how you would have done it?
A I would not have done a colonoscopy if I had made a diagnosis of toddler diarrhoea. Yes, that is correct. The diagnosis of constipation was made again four months later on a plain abdominal film on 23 October.

Q The first time it is made is when the child is faecally loaded. Just to get it out of the way, there is a phenomenon that you have described – and others have described before you – of constipation which gives the outward appearance of diarrhoea but in fact it is overflow diarrhoea because it is the bowel contents leaking past an obstruction caused by the constipation?
A Yes, that is true. Yes.

Q That is a different thing from toddler diarrhoea – just to get it out of the way?
A That is a different thing, yes.

Q And in fact your point, as I understand it, about toddler diarrhoea is that is often a self-limiting condition which will go when the child reaches five or six years old?
A That is correct, yes.

Q I suggest, Professor Booth, that other equally experienced paediatric gastroenterologists might not necessarily take the same view as you?
A Professor Walker-Smith did not originally plan to do a colonoscopy, because in his letter to Dr Burrow of 9 June he said, “My plan would be to see him again in three months’ time. Then, if Mrs 1 feels it is appropriate, we could consider endoscopy and further assessments, etc.”

Q That does not shut the door on colonoscopy for ever, does it?
A No.

Q You have made this point before in relation to the previous patient; that because a decision is made in 1995, it has to remain immutable and that is a decision that stays for ever. That is clearly not the way in which medicine is practised?
A No. I am saying that the notion that colonoscopy was undertaken to provide immediate diagnosis of constipation would not be the case.

Q Is that being suggested? They presumably did not think the child was faecally loaded, otherwise they would not have done the colonoscopy?
A I could not say. I do not know.

Q Can I just ask you about the barium meal because on this occasion they were unable to get to the ileum and they had discovered the presence of not insignificant pathology in the colon. Therefore it would be reasonable in those circumstances to do a barium meal, to see if they could get into the ileum to see whether there was pathology there rather than do another colonoscopy?
A Yes. If you think that the patient had significant inflammatory change in the colon, notwithstanding the fact that there was gross faecal loading at the time, then it would be reasonable to do a barium follow through.

Q Thank you. Could we turn to Child 3, please. I am simply going to go through them numerically rather than jump around. Royal Free Hospital notes. Child 3 had a history of severe constipation requiring frequent enemas and oral medication – lactulose, I think. There is a note from Professor Walker-Smith’s outpatient clinic, that the child had had a sore bottom with bleeding from about the age of six months. That is at page 9 of the Royal Free notes. I am sorry – just to orientate you, it is at the bottom of page 9, I think. I think it is about six lines up:

“He [suffered] constipation from age six months. Had sore bottom with bleeding from about 6 months.”

That is the note that is there in his outpatient clinic note. He was the first of the children that we have seen to be referred to the Royal Free, but from the letter to the general practitioner of 4 April 1996, which is at page 55 it looks, certainly chronologically, as though they had by then seen a number of children who had features of both Crohn's disease and autistic behaviour following MMR. That appears from that letter to the general practitioner back from the referral letter. Screening tests in this child came back negative. I am sorry, Professor. I am going through these things – I just simply want to get the highlight points because you have been through the documents.
A Yes, of course.

Q Could I just put to you propositions rather than in each case taking you to the records? The screening tests in this case came back negative but a decision was taken by Professor Walker-Smith to do a colonoscopy, to see if there was any evidence of bowel inflammation. You take the point rightly, the penultimate line of the main paragraph on page 55: he refers to any “ongoing infection”. I should tell you that that, unfortunately, is a typo. It should be “inflammation” because the whole case is involved with inflammation and it is clear that one would not do a colonoscopy to see if there was infection in the bowel, would one?
A I would be very surprised if that was what Professor Walker-Smith had dictated to his secretary, yes.

Q Because the point of doing it is to see if there is any ongoing inflammation in the gastrointestinal tract?
A Yes.

Q And you are content to accept the sense of that?
A Yes, absolutely.

Q Then if we look at page 51, this is a letter to the school doctor, I think, at the child’s school:

“Many thanks for your query concern [Child3], our initial screen for Crohn's disease was quite negative. His C-reactive protein was within the normal range, his blood tests were all normal. However, we are pursuing further the relationship between bowel inflammation and autism and have arranged for [Child3] to be admitted on Sunday the 8th September for colonoscopy and biopsy followed by further investigations.”

There on the face of it, he is saying they are looking to see whether there is a relationship between bowel inflammation and autism. You say that you would not have considered bowel inflammation with a history of constipation, even if there was a note of bleeding?
A If it was coming from a sore bottom as was indicated in the notes, I do not think I would have been pushed towards doing a colonoscopy just on that basis, no. Not with a history of ongoing constipation.

Q That, as I understand it, is mechanical bleeding caused by the stool forcing its way out, so it would be a fissure, or something like that, that would be causing the bleeding. Is that right?
A My interpretation of the notes when it talked about a sore bottom is that there was some excoriation round the anus, perhaps as a result of soiling. That is how I interpret that, but it is not clear; it could be a fissure.

Q Whatever it is, it has been there from the age of six months, but we do not know precisely what has been described. Dr Casson, in his discharge letter, sets out a family history of colitis. Is that relevant?
A Is ---?

Q I am sorry. Is a family history of colitis relevant?
A Yes. It often is, yes.

Q Just for reference, that is not page 26. I will take you to it. Page 27, the second paragraph.

“He has 2 brothers and 2 sisters all of whom are well. He has a XXX who has colitis.”

It may be relevant, but you do not know the circumstances?
A That is correct.

Q Can I just ask you about constipation. As a matter of common sense, constipation does not necessarily preclude other intestinal pathology. It is only a symptom of something, is it not? It is not a condition, a disease in itself. It is a symptom of some problem within the bowel?
A I think it is a diagnosis, in the sense that it has a defined set of clinical symptoms. It has a recognised set of physical signs on examination . It has a defined natural history. There are well characterised therapeutic interventions but in common with many disorders, we do not understand entirely what the cause is, probably in most cases in children. So I do not know that it differs in such a fundamental sense from other diagnoses that we make.

Q Take Crohn's disease as an example, although I appreciate yesterday you said that the cause of Crohn's disease is not understood. At least in Crohn's disease you have signs and symptoms which are well recognised and presumably you can draw a link between the pathology that is found in the bowel, to say that they are in some way related to the signs and symptoms from which the patient suffers?
A Yes.

Q My point was, what you described are signs, which means things that you can see or identify – it might be bleeding, it might be other things – symptoms which are what the patient complains of, but you do not have any identifiable cause on the face of it. You simply say, “The child is constipated and we do not know what the reason for it is.” What I am saying is, on its own you cannot say what it is that is causing the child to be constipated?
A In that sense, it is no different from Crohn's disease, I agree.

Q At least in Crohn's disease you can make the tentative link between the symptoms and what you have discovered within the bowel and lesions within the bowel, which it is reasonable to associate with those signs and symptoms
A Equally well you can show that in constipation there are abnormalities in colonic transit in many patients. I am not quite sure there is such a ---

Q Is that not a symptom?
A It is an abnormality in an investigation.

Q But it is a symptom. It is the fact that the bowel contents are not being moved properly down through the bowel. Is that not a symptom rather than a cause? It is not a disease. It is a symptom.
A I think if you talk to patients with constipation, I think they would recognise that constipation was a symptom and also a disease, or a disorder.

Q If you ask a patient whether they have a headache they would say, “I have a headache,” but it is a symptom rather than a disease. The thing is, it is easy top say, “This child is constipated” but it does not preclude there being a physical problem within the bowel that may be causing constipation?
A There may be a cause of constipation, yes, but if you are saying is colonic inflammation frequently associated with constipation, the answer would be in general no, it is not a recognised frequent symptom of colonic inflammation, which was, as you were saying, one of the rationales for carrying out this investigation.

Q It does not look as though in this child’s case treatment with enemas and lactulose had been effective in treating the constipation. It may have ameliorated it, but it does not look as though they were effective in treating it – or treating the cause of it – because the child had remained for a number of years with severe constipation.
A Yes. This child, as is frequently the case, continued to have symptoms of constipation, yes.

Q There was no explanation for why the child was constipated.
A I do not know if there was any investigation of why the child was constipated.

Q There does not appear to have been. I have not seen in the notes ---
A But if there was no investigation you could not explain why the child was constipated.

Q But Professor Walker-Smith’s team – who were, after all, investigating the child, and that would include the consultant gastroenterologist who was going to carry out the colonoscopy – they presumably must have had some suspicion that there was bowel inflammation?
A I was not able to detect any evidence of that in the notes up until the child was admitted. As we have been labouring, the clinical diagnosis was toddler diarrhoea.

Q With this child? Are we talking about Child 3?
A Yes. Sorry, I beg your pardon, I am getting confused here.

Q Child 2. Child 1.
A There was no suggestion that I am aware of that there was any preceding inflammation, from the history.

Q If they did not suspect – and I include the consultant who did the colonoscopy – then the decision to do a colonoscopy would in your position be perverse, would it not, because, (a) they would not, you say, do it simply because of constipation; and (b) because if, as you say, this was part of a research study, one of the three core features of that study was the presence of enterocolitis, which appears to be, you are saying, they could have had no suspicion that that existed.
A I am saying that if you have a patient with severe constipation you would not under normal circumstances carry out a colonoscopy. You might treat the constipation effectively, and then review. I mean, if there was a lingering issue about whether the blood was coming from this patient as a result of constipation or not, you might treat the constipation until the colon was demonstrably empty, and see if the patient was still bleeding; and if the patient was still bleeding under those circumstances it would be entirely reasonable to do a colonoscopy.

Q I am just trying to think through your thought process about the fact that this is all a research trial, because, as we went through at some length yesterday, one of the three parts of that trial would have been to establish the presence of enterocolitis, whatever that may mean, but it must involve some bowel pathology, must it not?
A Yes.

Q So if the whole purpose was to look for that, and if they did not have a suspicion that it might be there, there would be no point in doing a colonoscopy, because you could have had no suspicion that it was there, and therefore this child was never going to fit into the category who had enterocolitis.
A So you are saying that the reason for the colonoscopy was nothing to do with the constipation; it was because of the hypothesis that this patient may have an enterocolitis?

Q Yes.
A Right.

Q If they suspected that this child’s condition was caused by or might be caused by some inflammatory bowel disease, then they did a colonoscopy – otherwise, on our reasoning, there could have been no reason for doing a colonoscopy simply because the child was constipated. That is your case?
A Yes, doing a colonoscopy in a patient with severe constipation would fall outside normal clinical practice, yes.

Q Leave aside the question of the child being referred to the hospital, if there had been no suspicion at the time of inflammatory bowel disease, presumably the colonoscopist, if it was unreasonable to proceed to colonoscopy, the colonoscopist would have said “I’m not interested, I’m not prepared to do it, because I think it’s only constipation”.
A They may have done, yes.

Q If one follows through your thesis that you would not suspect inflammatory bowel disease with a child with a history of constipation – which is your thesis?
A Yes.

Q --- then there would be no way in which an experienced gastroenterologist would contemplate doing a colonoscopy for that reason, unless he suspected that inflammatory bowel disease might be present?
A You mean as part of a research protocol?

Q It is almost stronger if you say it is part of a research protocol, because you say they were positively looking for that condition; it is not a question of just having the child there with symptoms. If they were doing it in order to establish an hypothesis then they needed to have children who were likely to have some form of enterocolitis, otherwise it is pointless. If you chose a child who has no prospect of having it, then that child is never going to be part of the study, because they would not fulfil that one-third of the part of the study.
A So if this patient was investigated as part of the research study, they would have to fulfil the inclusion criteria for the research study.

Q That is what you say after all is the whole purpose of this admission, and I am trying to test it to see if that is right, and you say that nobody would, or you would not, have considered bowel pathology or enterocolitis in this case. But if that is right, that nobody else would have, it is difficult to see why they would have bothered, if this was part of a research study, to do a colonoscopy, knowing that they were unlikely to find any bowel pathology.
A I could accept that a more plausible reason for doing the colonoscopy in a patient with long-standing constipation would be that it was carried out as part of a research study

Q To what aim? To what end?
A Within the aims of the study as set out in the protocol.

Q The aims were to provide a link between enterocolitis and disintegrative disorder, if you say it is the study 172/96. But that presupposes that they think it is likely that they are going to find enterocolitis. As I say, I do not want to go back over it, because we spent rather a lot of time on it yesterday, but there were three features which had to be married up if this was going to have any scientific meaning. One of those three features was enterocolitis, because the proposition was that there might be a link between disintegrative disorder, enterocolitis and measles or measles/rubella.
A Mmmm.

Q So if they were recruiting for that trial it would seem to be folly ---

MS SMITH: Sir, I have let this go on for some while, but I think if this line of questioning is going to be pursued then Mr Miller should take Professor Booth back to what the gastrointestinal inclusions for the study are, and they are not simply enterocolitis. It is at page 203 of FTP1.

MR MILLER: I am happy to do that. It is a matter clearly that can be taken up in re-examination. It is not being unfair to the witness; I simply want to understand what he is saying about the reason for doing a colonoscopy.
A What I am saying is that I cannot find a clinical indication for carrying out a colonoscopy in a patient with severe constipation. There is correspondence in the clinical notes between Professor Walker-Smith and Dr Wakefield about this patient, with reference to investigative protocols, and so on. I assume therefore that this patient was being investigated as part of a research study. I cannot think of a valid clinical reason for carrying out these invasive investigations for purely clinical reasons. I do not know if that answers your question, Mr Miller?

Q It does answer it to the extent that you say if you look at the documentation, you say that leads you to conclude that this was a research study, and at the same time you say “I don’t see any clinical reason myself for doing a colonoscopy with these presenting symptoms”.
A I do not, no, that is right.

Q So the preferred route would be to try to eliminate the constipation and see whether the child was still bleeding.
A I think that would be the usual route.

Q Presumably if the child was still bleeding, then obviously the criteria are there for proceeding to colonoscopy?
A That would be a much more valid clinical indication for a colonoscopy , yes.

Q Can we look at what happened in the colonoscopy . It is the Royal Free at page 105. This is Dr Thomson:

“Normal to terminal ileum, but with increase in the number of lymphoid follicles in the terminal ileum.”

Then the histology at page 75. At the bottom of the page, I and II are the small bowel, I think, and the rest are the large bowel:

“I. shows small bowel mucosa with an increase in intra-epithelial small lymphocytes, but not architectural abnormality.”

What is “an increase in intra-epithelial small lymphocytes”?
A It is an increase in lymphocytes that are insinuated between the lining cells of the small intestine.

Q So is that an inflammatory change?
A It is an increase in inflammatory cells, yes.

Q Then:

“II. shows small bowel mucosa” –

this is the ileum or small bowel –

“with prominent lymphoid follicles”.

We have heard from Dr Davies about that. That is a finding about the small bowel, and I think it is not uncommon to find prominent lymphoid follicles in the small bowel?
A Yes, that is correct.

Q It is less common to find them, if they are sufficient to amount to lymphoid nodular hyperplasia, in the large bowel, in the colon?
A Yes, generally, yes.

Q Then we look over the page at the large bowel histology, “within normal limits”.

“Comment: Mild inflammatory and reactive changes …”.

What do you understand by “reactive?
A Sorry?

Q Do you see, it is at the top of page 76.
A Yes. I do not know.

Q You do not know?
A It is not made clear what the changes are a reaction to.

Q What does “reactive” usually mean in this context?
A It could be a reaction to some dietary antigen, for example. It is just not clear – as indeed the histopathologist says. It says “of uncertain significance”. I do not know what it means.

Q When we see the word “reactive” – I am asking you as a gastroenterologist – “reactive changes” implies that something is going on?
A Yes, it would, yes. The curious thing is when this patient appeared in The Lancet publication there was no mention of these changes. I do not know why.

Q Again this is a matter – I am going to try, if I can, to confine you to providing expert evidence of a gastroenterological matters rather than doing the research yourself, or the detective work yourself. We are going to have to look in due course – we can see what is there in The Lancet paper, and we have heard from Dr Davies in detail about her descriptions of what she found and how they correlated with The Lancet paper, and she is presumably somebody, as the histopathologist concerned in the weekly meetings, whose view about them would carry more weight?
A Yes. I am just not clear, with these two conflicting reports, what was actually felt at the time about what was going on here. What was the clinically relevant report?

Q The two conflicting reports? I am sorry ---
A You have drawn my attention to “reactive changes in the small bowel mucosa”, which as far as I am aware was not subsequently reported, so I am not sure whether the clinicians involved with this patient did or did not think that was clinically relevant.

Q Dr Davies told us that the histopathologist on the rota who reported this reported it for the histology meeting on the Friday as part of the general histology meeting for all of the children who had been seen that week, and that was the purpose for which she or they were making that report. She then attended the meeting and spoke to that report and discussed it. She also told us that when it came to the paper, others had looked at these slides again and given their interpretation of them, not for the purpose of treating the child or managing the child, but looked at them subsequently; and that is clear from the body of the paper.

Can we look at Child 4, please, Royal Free hospital notes. Professor Booth, I do not have your report in front of me, but do take your time to find the part of your report that deals with this patient.
A Thank you.

Q Do you have it?
A Yes, I do.

Q This child and Child 8 came from the same area, in fact the same general practitioner in XXX, and I think they are the only two children who were seen, from the ones we have considered, who did not have an out-patient clinic appointment. You have made the point that they did not have a clinic appointment, and therefore that may be an indication of the fact that they were part of a research study; but in fact they were the only two who came from XXX, or around XXX. That may or may not be relevant to that issue; we know that the others all did. It does not carry much weight. You may say it is poor practice for them not to have been seen in the out-patient clinic first.
A (The witness nodded)

Q You are nodding, and we will put that down on the transcript as a nod.
A Are you asking me to agree or disagree with that statement?

Q I am asking you really to agree. It does not carry much weight as far as research, but you say it would have been good practice ---
A It is good, normal practice to see patients before they are admitted unless there is some overriding reason ---

Q And clearly that is demonstrated by the fact that the others, and presumably many others, had out-patient clinic appointments first. There is a note at the beginning of the bundle at page 5, I think, which is Dr Casson’s note. It is dated 29 September 1996. Diarrhoea became a problem between one and one and a half years of age. Initially loose, watery, with increased frequency, three to four times a day. No blood, no mucus. Soreness peri-anally. Contained undigested food. Continued until four and a half years, approximately the same time as behavioural deterioration. Increased frequency of stool, increased watery – diarrhoea. Times six a day. No blood. Query undigested food on occasions. No known associated infection. Weight down. That looks like “constant”, does it not, if it goes in a straight line across?
A I am sorry, Mr Miller, I am finding it difficult to locate the precise section on page 5.

Q I am sorry, it is page 8. I should have taken you to that. I will start again, if you want. We will start again, because people were scanning page 5:

“Diarrhoea – became a problem between 1 – 1 ½ years
Initially loose [and] watery [with increased frequency], 3-4 times a day.
No blood, no mucus, no soreness peri-anally.
Contained undigested food
Till 4 ½ years of age [approximately] same time as behavioural deterioration”.

Then one assumes he means “then” –

“Then increased frequency, increased watery[ness] x 2 – x 6 a day.
No blood
? undigested food on occasions.
No known associated infection.
Weight down, Appetite” –

As I say, that straight across arrow presumably means “constant”?
A “Unchanged”, I think.

Q
“Lethargic [increase]
[associated with abdominal pain crying with pain]”

and then he deals with the food, starting on the exclusion diet.

“Presently – well most of time
if does get exacerbation seems to be related to new foods”

and then

“[one two times a day] normal [I imagine consistency]. [No] straining.
Pear juice [leads to] constipation.
Abdominal pain resolved”

and then he refers to the giardia,

“giardia [twice] proved on one occasion one year ago.
No treatment.
(No pets at home).”

These are signs and symptoms which would make you suspicious of inflammatory bowel disease.
A Well, you would consider it in your differential diagnosis. There is evidence here of response to dietary manipulation and, in particular, when the patient came into hospital [they were] having normal stools and, if they were abnormal, it was related to foods; any abdominal pain had resolved.

Q I would like to ask about giardia. There is some discussion or controversy about the role of this organism, is there not? Some consider that it is a pathogen that causes bowel damage leading to malabsorption and others regard it as opportunistic and invading already damaged bowel.
A I think that it can probably fulfil both roles. Some patients do seem to get an acute episode of diarrhoea when they are exposed to it. It is quite a common cause of travellers’ diarrhoea, for example. Patients can become chronically infected. Some of them seem to live with it and others get persistent gastrointestinal symptoms.

Q It can in fact be present and unrecognised.
A Yes, it can be.

Q Looking at the history, the giardia established in the past had not been treated according to Dr Casson’s note – there had been no treatment for the two occasions in the past.
A That is not my note at GPR14 on this patient. The patient was treated.

Q I am going by what Dr Casson was told when he says that there was no treatment on page 8. Have I read that correctly two thirds of the way down the page?
A
“? giardia x 2 proved on one occasion 1 year ago.
No treatment.”

Yes.

Q Subject to that point you make about the general practice note which of course would not be present in the Royal Free notes, it does not look as though the bowel symptoms had been investigated; is that right?
A In some ways, the response to an exclusion diet is an investigation. It is the gold standard for investigating food allergy. There are a number of investigations that one can do that the diagnosis rests on resolution of the symptoms when the offending food is withdrawn. This patient had been on an exclusion diet which I would suggest was therapeutic but also important diagnostically as well.

Q As you have pointed out, there is no outpatient clinic appointment with Professor Walker-Smith and no evidence of incision by Professor Walker-Smith for colonoscopy, unlike the evidence in relation to most of the other children. We do not have a letter from him back to the general practitioner.
A At page 26 in the Royal Free Hospital records is some correspondence that may be relevant.

Q That is a slightly different point. That is in advance of the admission; in fact two months before it or a little than that.
A The point I am making is that some discussion/interchange appears to have taken place in relation to this patient before ---

Q We see a note on the right-hand side “[To come in] What for. ? Possible endoscopy”.
A Yes.

Q My point which I was asking about. We do not have a letter which we have in all but the other XXX case back from Professor Walker-Smith saying that the child was going to be admitted for the colonoscopy and setting out his findings at the outpatient clinic.
A That is correct.

Q And there is no evidence. I do not think there is anything particularly sinister about this but the evidence will have to be given about where Professor Walker-Smith was, but there is nothing in the notes to say with this child that he was there at the time the child was admitted: on the day that he was admitted or the day following. What you would have, you say as a matter of course, would be a decision made by the person who carried out the colonoscopy as to whether or not it was appropriate in that child’s case to do it. That would follow from what you have said in relation to all of the cases, that it would inevitably have to be a two-stage process because consultants were involved at those stages, that first of all the decision to admit would be taken if there had been an outpatient clinic and then, before proceeding with the colonoscopy, the consultant concerned, whichever one it was, would have to make a decision as to whether or not it was appropriate.
A Yes. If the endoscopy was being done by somebody else who had not made the original decision to carry out the endoscopy, yes.

Q I am not going to take you to all the records but I think that we have been through them. I think that most of the endoscopies are done by Dr Murch, some are done by Dr Thomson, but we have been told that they, with Professor Walker-Smith, were the three consultants involved in this unit and Professor Walker-Smith did not carry out any of the colonoscopies. So, it applies in all the cases but applies in this case because we do not see the outpatient clinic (note?) so it is different from all but one of the others. You still say that the consultant who decided to do the colonoscopy would have to satisfy himself that it was appropriate clinically to do so.
A Either that it was appropriate clinically or that the indications for carrying it out conformed to any research protocol that was relevant to the patient’s admission.

Q So, that would mean that that would contemplate something which you say you could not contemplate, which is doing a colonoscopy without there being any clinical indication for it.
A I would not do a colonoscopy unless I felt there was a valid clinical indication for doing it.

Q That is what I have just said.
A Yes.

Q May we look at page 32, please. This is the short report of the colonoscopy carried out by Dr Murch,

“Mild granularity of rectum, with slight disturbance of vascular pattern (‘neovascularisation’). Normal colon, but ileum showed marked lymphoid nodular hyperplasia.”

What is granularity? I am talking about it in terms of the endoscopy. What is granularity of the bowel?
A Normally, the lining of the bowel is smooth and fairly shiny and I think this must refer to a more roughened appearance.

Q What is the significance of that?
A I do not know.

Q But it is worthy of comment as being a non-normal if not abnormal finding?
A It is referring to a perceived abnormality. I do not know to what it refers specifically, I am afraid.

Q May we look at – and I am trying to take this reasonably quickly – the histology report which is at page 33C. Perhaps we should turn first to page 13 in the clinical notes. The 4 October, the histology meeting. Do you have that?
A Yes, I do.

Q
“Ileum - dense lymphoid pattern
- no acute inflammation
- normal architecture
Colon - prominent lymphoid follicles
- no active inflammation”
-
and nothing about the rectum and no granulomas.
A Yes.

Q Page 33C is a document that I do not think was in the notes and was produced during the course of the hearing. This is Dr Rees’s and Dr Davies’s description of the histology under “Microscopic Description”. “I” is the small bowel and then “II-VII” is the large bowel.

“I. Small bowel type mucosa with lymphoid follicle.

II-VII Large bowel mucosa” this is the colon “some with attached muscularis mucosae with no evidence of architectural distortion or increase in inflammatory cells in the lamina propria. Lymphoid follicles with germinal centres are present in many of the biopsies. No cryptitis or crypt abscesses are seen. The surface epithelium appears intact. No granulomas, ova or parasites are seen.

Comment: Large bowel series with terminal ileum, with no histopathological abnormality.”

Dr Davies told us, when she was explaining what these findings mean, that lymphoid follicles with germinal centres are histologically significant. You were asked to deal with this yesterday in relation to the first child we reviewed, Child 2. Follicles with germinal centres are important. They are abnormal, are they not?
A It is not my understanding that they are uniformly abnormal and I cannot quite see why Dr Davies has said “no abnormality” if she feels that the germinal centres are abnormal.

Q What is the difference between prominent lymphoid follicles and lymphoid nodular hyperplasia?
A I think that the term “lymphoid nodular hyperplasia” is a difficult term to define. “Hyperplasia” almost by definition means that something is larger than it would otherwise be, but it is used to describe both circumstances where lymphoid nodules appear to be normal in size and frequency but also the circumstance where they are larger and more numerous. So, I think that lymphoid nodular hyperplasia is a rather fuzzy term.

Q It means that they are larger than normal and ---
A But if they are prominent in the view of the histopathologist, it just means that they are bigger than they would normally be.

Q You said that although they are a common finding in the ileum, they are not as common a finding in the colon. You said that in relation to the previous question.
A Yes.

Q And they are an abnormality in the colon.
A They are found in the normal colon.

Q What they mean is that there is some activity going on in that part of the bowel.
A Well, it may, yes. There is activity going on in the bowel most of the time. It is not a dormant organ. Dr Davies does not seem to be in any difficulty in describing lymphoid follicles with germinal centres and then going on to say “no histopathological abnormality”.

Q She did say in her evidence that the reference to germinal centres was unusual enough to be worthy of comment in the report and a matter for discussion at the meeting.
A I cannot comment on that. I am only presented with her observations here where she says, ““no histopathological abnormality”.

Q You will appreciate that the Panel has already heard her discussing these in detail.
A Yes.

Q If you look at the letter of 20 March 1997, the same bundle at page 20, the reference in that letter to a colitis is not inconsistent with either the histology meeting note or the report generated by the histopathology department. The strict meaning of colitis is inflammation in the colon.
A I am having some difficulty in agreeing that the term “no histopathological abnormality” represents a colitis.

Q That is the description of the histopathologist. She says that she does not use the word “colitis”; it is not a term that histopathologists used or that she used then ---
A But she specifically says in her report, “No evidence of architectural distortion or increase in inflammatory cells”.

Q But there are prominent lymphoid follicles with germinal centres in the colon.
A That does not represent colitis.

Q It does, does it not?
A No.

Q The distinction, if there is any distinction which I do not accept, is a subtle one and clearly what she was describing is an abnormality in the colon.
A How can she be describing an abnormality in the colon when she says, “no histopathological abnormality”?

Q Because she is actually saying what is there.
A And then commenting? The note at the histology meeting also says, “No active inflammation”; that is in the clinical note at page 13. I cannot quite correlate those observations with a diagnosis of colitis.

Q It will be a matter for the Panel in due course. They will be reminded of the evidence that she gave about it, that she had no difficulty with the description of that as colitis.
A I am struggling to understand that. I am sorry; I was not there.

MR MILLER: Fortunately it is a matter for the Panel. Sir, I am going on to Child 5. I can either start him now or at ten past.

MS SMITH: I am suggesting that we stop every two patients whilst Professor Booth is having to concentrate like this. It seems to me two is enough before we have as very short break.

THE CHAIRMAN: I am just thinking. To make that a hard and fast rule, I think two may either be too many or too short. Let us just say this: I think this is probably the time to have the mid-morning break.

MR MILLER: Please do not make a hard and fast rule, because there are significant differences between some of these children.

THE CHAIRMAN: I accept that.

MR MILLER: Who might take five minutes to do or rather more.

THE CHAIRMAN: That is the point I was trying to make.

MR MILLER: I thought you were.

THE CHAIRMAN: Thank you. I think we will have the mid-morning break. It is ten to eleven, and we will resume at ten past eleven.

Professor Booth, my usual warning again: you are in the middle of giving evidence. Please do not discuss it.

THE WITNESS: Yes.

(The Panel adjourned for a short time)

THE CHAIRMAN: Mr Miller, which is the next child?

MR MILLER: Child 5, sir.

THE CHAIRMAN: And the Royal Free notes?

MR MILLER: Yes. (To the witness) This child was seen in the outpatient department on 8 November 1996, by which time, in terms of timing, Professor Walker-Smith and his team had seen the results of the colonoscopies and histology in a number of the other children whose cases we are going through. So they had seen these and observed what they had. On page 40, in his handwritten outpatient note, almost exactly half way down, it says, “Aet”. Do you see that?
A Yes.

Q
“[Aged] 2 years [he] began holding his abdomen – maybe … pain in his abdomen. Rigid. Has these episodes nearly every day. Can occur before or after eating. Mars [bars] and coke make him hyperactive. Has bouts of diarrhoea. Treated with Nystatin by Dr Richer – makes him constipated. Helped for 3-4 weeks a year ago.

Has one soft stool/day usually has episodes of diarrhoea once a month.”

I know you make light of this, but there is a letter at page 361. This is the letter form Professor Walker-Smith to Dr Shillam, the general practitioner, dated 12 November 1996.

“Many thanks … He demonstrated how difficult his behaviour can be when I saw him in the clinic and we did not proceed with any blood tests. He has a number of episodes which have been interpreted as abdominal pain when he draws up his legs and appears to suffer from abdominal pain. He has intermittent episodes of diarrhoea which apparently responded in part to Nystatin which has been prescribed over the past year. Several of these children with autism have had gastrointestinal symptoms and on investigations have proved to have gastrointestinal pathology. I am arranging for him to come in for a colonoscopy …”.

As I say, you make light of the difficulties of obtaining blood from this child because you say, if they really wanted to have blood from the child he should have persevered. Is that right?
A It is easier to take blood than to do a colonoscopy, certainly.

Q If he has found it not possible to do so and he considers that he has sufficient grounds to do a colonoscopy, then the fact that he was unable to get blood should not deter him from that?
A No. If the view is that there is a clear case for a colonoscopy as the first investigation in the absence of any other supportive investigations, then it would be appropriate, if that is the view, not to have the blood test, if that is the case.

Q He appears from the letter anyway to have had suspicions of inflammatory bowel disease raised by the experience with other children whom he had already seen and investigated?
A I would add that this is Child 5, and three out of the previous four children that have been seen by this time had all ended up with a diagnosis of constipation. I just make the point, if he had seen three out of four children previously in this study, you might have thought of this as a diagnosis at the time you saw the patient, because the symptoms would fit with constipation.

Q You say “ended up,” but they ended up in some cases quite far down the line with a diagnosis of constipation?
A In some cases, yes.

Q What Dr Casson records at page 38 – I am sorry, it is back near the front of the bundle again… I am sorry; it is one of the junior doctors, I think. It is over the page, and it is to correct something which I think you said earlier in your evidence. Do you have the last third of that note? “Abd pain”. Do you see that?
A Yes.

Q
“Abdomen Pain: Having episodes since the last 6 years when he suddenly clutches his abdomen and groans. Lasts for about 10 mins to one hour.”

I think earlier in your evidence you said “Up to ten minutes” but in fact the note here is “10 minutes to one hour”.
A Right, yes. I accept that.

Q I should say, in relation to your point constipation, these children also had evidence of inflammation in the bowel. Whatever was causing it, they had evidence per histology of inflammation in the bowel?
A I am not sure whose opinion we are using to come to that conclusion. I just cite the example of the last patient we looked at, where the clinical histopathologist concluded, “No histological abnormality”.

Q She is saying in relation to that, I point out to you, “The abnormalities that I see on the slides as a histopathologist, I do not see them as abnormalities”, but it is up to the clinicians to decide whether or not they are treatable abnormalities?
A Yes. It is just that it is obscure what the source is, in some of the cases, of the change in the histological diagnosis.

Q I allowed myself to get sidetracked from going through this because you introduced the idea of constipation, which meant going back. In relation to this child, you may not have chosen to go for a colonoscopy, and might instead have insisted that the child give blood, but it was not unreasonable for an extremely senior and experienced consultant gastroenterologist to take another view?
A Yes, entirely. I am just saying with this history my view would have been that I would not have gone straight in and done a colonoscopy, which is a view – as we have discussed – propagated repeatedly by Professor Walker-Smith in numerous publications, that preliminary investigations are often appropriate.

Q Could we just look at the colonoscopy report at page 424. This is by Dr Murch.

“Colonoscopy for investigation of autism with diarrhoeal features. There was mild proctitis…”.

Is that in the rectum?
A That is right, yes.

Q
“… with a granular mucosa and loss of vascular pattern, but no friability or ulceration.”

A Yes.

Q
“The colon was normal throughout otherwise, while the caecum showed patchy loss of vascular pattern without ulceration. There were prominent follicles in the ileum, but not sufficient to call lymphoid hyperplasia. The ileal mucosa appeared fully normal.”

Just to take up the point and put it to bed, as it were, Dr Murch appears to make a distinction between “prominent follicles” – leave aside where they are – and “lymphoid hyperplasia” as a colonoscopist?
A That is his interpretation, yes. He is saying, “Not sufficient…”.

Q It is just that with the previous patient, I asked you what the difference was between the two. You had something to say about that, but it looks as though the colonoscopist is concerned, he can see a distinction between prominent follicles and lymphoid hyperplasia?
A It would appear so, but the whole security of these observations is very difficult to be sure about, where the note here says “not sufficient to call lymphoid hyperplasia”, but when the patient is subsequently reported in the literature, that is changed. I am just uncertain about the security of these observations; that is all.

Q Can we have a look at the histology report at page 430. Specimen I, which is the small intestine –

“… consist of fragments of small intestinal mucosa which includes lymphoid follicles but which is without pathological abnormality.

Specimens II, II and IV are large bowel”

i.e. colon –

“mucosa fragments with normal crypt architecture. There is at best a minimal increase in chronic inflammatory cells within the superficial lamina propria. No active inflammation is seen.

Specimens II and IV show minor crypt architectural distortion including occasional bifid forms. Paneth cell metaplasia is not seen. No excess chronic inflammatory cells are seen. A very occasional polymorph is seen within surface crypt epithelium. No ova granulomas or parasites are seen in any of these biopsies.

Comment: Large bowel series; minor changes the significance of which are uncertain but do not amount to the diagnosis of inflammatory bowel disease.”

Then the note at the bottom says:

“Report when seen by Prof WS [Professor Walker-Smith] seemed to be more significant inflammation than indicated in this report.”

A Yes.

Q And in your evidence in chief in response to Ms Smith, you said that it is clearly recorded in the clinical record, and it is clear who made that decision, and it is appropriate for Professor Walker-Smith if he felt that that was the case to come to that conclusion.
A Entirely, yes.

Q And one has to allow for the fact that Professor Walker-Smith had been involved in looking at biopsies in cases involving pathology in the bowel for many, many years and would have got significant expertise in that?
A Yes.

Q In your report, Professor Booth, in the written report in relation to this child – I am sorry, I do not have the page in front of me but do you have the report there?
A Yes, I have.

Q You say that it is recorded in the clinical notes, RFH8, and in the histopathological report 430, that Professor Walker-Smith had considered the colonic inflammation to be significant and more severe than in the clinical histopathology report, description of an anti-inflammatory agent on this basis is rational.
A Yes.

MR MILLER: And that is your view. Child 6, please. Sir, this is the Royal Free. Could you have Child 6 and Child 7, the Royal Free notes in each case. I apologise – I am actually going to look at one note. I am note sure how you have the bundle. I have an additional set of Royal Free notes for this patient.

THE CHAIRMAN: I think we have additional notes as well.

MR MILLER: I think that is the only one I want to refer to. I think we can take this case and the next case quite shortly, Professor Booth. In the case of Child 6, you say that the history of abdominal pain and diarrhoea with blood in the stools merited investigation by colonoscopy without more, at the outset?
A Yes.

Q We know, in fact, that Professor Walker-Smith did arrange for blood tests for inflammatory markers in this child’s case, and I think they were normal. Is that right?
A I think in the notes that I had that was not entirely clear.

Q No.
A When I ---

Q These arrived quite late on, I think.
A I am prepared to accept if you tell me that they were done.

Q My recollection from when you were taken to the results by Ms Smith is that they were normal. Certainly the only one, when you went through the blood results, I think that was abnormal was in the case of Child 12, which was a C-reactive protein value, which I will come to in a moment. I believe in this case, because there was some question of whether or not it was necessary to do the blood testing, or whether it was reasonable to go straight to colonoscopy, and you said, “In fact he did not need to do them.” You are not critical of that, but in any event it could have been simply a first resort to colonoscopy.
A Yes.

Q We will find out. I am sure my memory is correct, that the inflammatory markers were normal. The histology report identifies significant bowel abnormalities, does it not?
Look at page 151. It starts at page 150:

“Microscopic description

1. Sections show pieces of small intestinal type mucosa with normal villous architecture and a piece of probable ileocaecal mucosa with prominent reactive lymphoid follicles and a mild focal cryptitis. …

II-V. Sections show large bowel mucosa, some with attached muscularis mucosae, with prominent lymphoid follicles. … a mild patchy increase in inflammatory cells in the lamina propria with focal cryptitis but no crypt abscess formation. There is a mild architectural distortion with focal irregularity of the surface epithelium. No granulomas or pathogens are identified.”

The comment is “… mild histologically non-specific proctocolitis”. So there was abnormal pathology in both the small bowel and the large bowel?
A Well ---

Q Mild focal cryptitis in the small bowel.
A No, I think that refers to – it says there is “small intestinal type mucosa with normal villous architecture and a piece of probable ileocaecal mucosa with prominent reactive lymphoid follicles and a mild focal cryptitis”, so I think that is referring to the ileocaecal mucosa rather than the small intestinal.

Q Right. Is that the join between ---
A That is where the small intestine goes into the large bowel, yes.

Q We have been through the large, but there is abnormal pathology there, is there not?
A Yes, there is mild abnormality , yes.

Q If the blood results were normal, that would be one of those cases where those screening tests did not pick up mild abnormality in the bowel?
A Yes. I have lost the place; I was just looking at a result earlier with a high platelet count. At 117, 28 October, platelets 480.

Q Yes. That is the one that is taken – that looks as though, if it is the 28th, that is the day of the colonoscopy, is it not?
A I think when I first had the notes it was not clear about the date of the colonoscopy.

Q It just says the receipt – if this is the 28th, I have not flagged up the colonoscopy, but the date of receipt of the biopsies was the 28th, was it not, if you look at page 150?
A Yes, but as far as I am aware this was the first time that the platelets had been examined.

Q Right.
A So it is not true to say that this would have given a negative screening test result.

Q So on the platelets parameter it is high?
A Yes.

Q In other words, everything else is – I am trying to find the other ones – haemoglobin, white cell count – are they all normal?
A Yes; and the CRP which was done on the 2nd, I think, looks as if it was zero – just down at the bottom of 117.

Q Yes. So the CRP is done on the 2nd, but that says zero.
A It looks as if the CRP was done on 2 October, which is strange, because my note says the first consultation at the Royal Free was on 4 October.

Q The date stamp on the out-patient note on page 38 is 2 October.
A Right.

Q 4 October is the letter ---
A That is the letter – sorry – so that must have been done when the patient was seen in the clinic, presumably.

Q Child 7, please. Again I think we can deal with this relatively shortly in terms of the decision, although there may have been other approaches, there was a history of blood and mucus and diarrhoea in his case.
A In Professor Walker-Smith’s letter to the GP he referred to intermittent episodes of blood associated with constipation and diarrhoea from the age of two.

Q We do not need to go to it. You dealt with your approach; I think you said there could have been other things you could have done, but with that sort of history he is in rather the same category as his brother – perhaps not quite so strong.
A I am not quite sure what you mean by “in the same category”.

Q That with those symptoms it was reasonable to proceed to colonoscopy. Your threshold for doing a colonoscopy would be quite low here, is what you said.
A Well, 6 had abdominal pain, diarrhoea, mucus and blood. 7 had constipation with blood in the stool.

Q Diarrhoea and blood.
A Yes, but a history going back before the referral of treatment for constipation, with laxatives.

Q Again I do not want to spend a lot of time on things where there is not very much between us. Your evidence in chief was that your threshold for doing a colonoscopy would be quite low.
A Yes.

Q If you look at page 109, this is Dr Thomson’s colonoscopy:

“Slight evidence of vascular abnormality in rectum and sigmoid but otherwise essentially normal. The terminal ileum however demonstrated a marked degree of lymphonodular hyperplasia.”

This I think was confirmed in the barium meal and follow-through, which is at page 111. It is difficult to read, but it is two pages further on. I am going to suggest, Professor Booth, that in view of the child’s persistent symptoms it was entirely reasonable in his case to treat him with anti-inflammatory medication, not least because of the success with the brother.
A The first comment to make is that there are substantial differences between the report at 111 by Dr Edwards, the consultant radiologist, who talks about “Small filling defects consistent with lymphoid nodular hyperplasia”. There is no mention of them being marked or particularly large, so that is just an observation. As a consultant radiologist presumably Dr Edwards would have seen a lot of terminal ileums. The histology on this patient ---

Q Page 151, I think. Do you have it?
A Yes, I have, and 152.

Q At the bottom of 149:

“I. Two pieces of small intestinal type mucosa with essentially normal villous architecture. … no increase in inflammatory cells in the lamina propria or in intraepithelial lymphocytes. Part of a lymphoid follicle is included. No parasites or granulomas are identified.”

Then II-VI, the large bowel:

“… no abnormality of crypt architecture or significant increase in inflammatory cells in the lamina propria. Some of the biopsies contain lymphoid follicles. No granulomas or parasites are seen.”

Professor Walker-Smith’s letter to the general practitioner says at page 59:

“Basically though, he had lymphoid nodular hyperplasia but on this occasion no evidence of inflammation in the distal bowel. Nevertheless he continues to have symptoms, although these are chiefly behavioural.”

This child was reported in The Lancet as having histological abnormality.
A Yes, that is correct.

MR MILLER: Child 8, please. Sir, I do not know how you and the witness are bearing up. We have done more than …

THE CHAIRMAN: These are quite short.

MR MILLER: Yes, this one is slightly longer but not significantly so.

MS SMITH: I wonder if we could ask Professor Booth. It is not the shortness but the similarity that concerns me.

THE CHAIRMAN: Absolutely, I have no problem with that. (To the witness) Professor Booth?
A I am very happy to talk about Patient 8.

MR MILLER: The Royal Free Hospital notes, please. This is the pair to Child 4, is she not?
A I beg your pardon?

Q She is the pair to Child 4, the other XXX patient.
A I do not have a note of her address in front of me; I cannot answer that.

Q She came from XXX and was attached to the same general practice with Dr Jelley and Dr Tapsfield.
A Yes.

Q And came down to the Royal Free without an outpatient clinic appointment. She is the only other one who did not have an outpatient clinic appointment. Dealing with this child in response to questions from Ms Smith, you said that there was a history of diarrhoea and that her referral to a specialist unit was indicated but it was not necessary for her to go the Royal Free because she would have to pass a number of specialist units on the way.
A Yes. If it was just an ordinary clinical referral, that would be the case.

Q The symptoms were intermittent and longstanding. From the records which we went through, she had diarrhoea over a number of years. She had developed diarrhoea and it had continued and we will deal in a moment with Dr Casson’s evidence about what the position was when the child presented to him. I would like to ask you about inflammatory bowel disease in general and conditions like indeterminate inflammatory bowel disease. They are in many cases relapsing and remitting conditions, are they not?
A Yes.

Q So, you can have quiescent periods, sometimes quite long periods, and then they will come back.
A Yes.

Q Would you look at page 15 which is the letter to Dr Jelley which is after the admission to the ward and the investigation. Perhaps we could start at page 7 as that is probably easier. This is Dr Casson’s note which reads at the top of the page,

“Problem:- Developmental delay
Diarrhoea since last 1½ years.”

We have been through this a number of times already. Over the page, it is talking about the deterioration in her general condition or her developmental condition. Page 8,

“About the same time she developed diarrhoea which continued for more than one year. 5-6 loose stools a day. According to her mother she tired primrose oil in November and her diarrhoea got better.”

You have interpreted that as being that it disappeared but it is clear from the discharge letter which he wrote that he was saying that it had improved rather than had gone away altogether. You have interpreted “got better” as “disappeared”, have you not?

MS SMITH: I want to put the factual basis of these questions right. This is not Dr Casson’s note in fact.

MR MILLER: Right, but it is his discharge letter on page 15 in which he says that subsequently her diarrhoea improved.

THE WITNESS: But he is not a first-hand witness to the history. It is not his history that he is transcribing.

MR MILLER: You would choose to put the interpretation which means that it actually disappeared whereas “got better” and “improved” and “resolved” are rather closer together than “disappeared”.
A Yes.

Q We know on the evidence in the correspondence that it recurred with particularly severe symptoms in January 1998 because it is referred to in the letter which you went to when you gave your evidence-in-chief, a letter from Dr Wakefield to Professor Walker-Smith.
A Perhaps that might have been a more appropriate time to consider investigating the patient with invasive tests, particularly as the patient had not been seen at the hospital before these were undertaken.

Q You say that that would be a reason for investigating here there. The point I make is a slightly different one, that you may get waxing and waning in symptoms and, within a couple of months of the visit, the mother is complaining that the gastrointestinal symptoms are particularly severe.
A The problem here is that no senior person had seen this patient before a decision was made to admit her for colonoscopy, so there were no other supportive pieces of evidence available other than that this patient had had troublesome diarrhoea and that, in response to the administration of evening primrose, it had got better. There was no evidence of which I am aware of other important aspects of the diagnosis of inflammatory bowel disease in children, like growth or nutritional status or indeed a detailed description of the symptoms that would allow one to make a rational judgment about whether colonoscopy was indicated or not. If you are saying that her symptoms were not present but then relapsed, I am saying that it would be more appropriate to wait until she had symptoms before carrying out these investigation, if her diarrhoea had got better, whatever way you choose to interpret the words “got better”.

Q What I am saying is that colonoscopy and barium studies were reasonable investigations given her history and given the experience that they had had up to that point with other children of the finding of bowel pathology when they did the colonoscopy.
A They were also making other diagnoses, in particular constipation.

Q Yes, but they were finding bowel pathology.
A It would seem reasonable in this case to follow Professor Walker-Smith’s well-publicised advice that preliminary investigations should proceed a decision to undertake an endoscopy, unless there are overwhelming reasons clinically for doing so, and I am saying that I do not find any overwhelming reasons for rushing into a colonoscopy in this child.

Q And that is your judgment?
A That is my view based on the clinical history.

Q Again, we have the situation where a consultant is choosing to do a colonoscopy and you do not understand it to be the practice of anybody in your field to do a colonoscopy without good clinical reasons.
A I find it particularly difficult to understand how a decision could be made to carry out a colonoscopy on this patient as the patient had not been seen.

Q There is a discussion, as we will hear, in relation to every patient before a colonoscopy takes place. There is a Monday meeting in which the particular patients are discussed before anybody is subjected to any sort of investigation.
A So, you get the patient down from XXX, having been bowel prepped for a colonoscopy presumably, and then tell them, when they arrive, whether or not they are going to have it?

Q You could not possibly on your account – and I think on anybody’s account – carry out a colonoscopy if you did not think it was appropriate to do so, if there were no clinical reasons for doing so. It is just the threshold of making the decision as to whether or not to do it. Nobody is saying that this child had no symptoms. It is just a question of whether the symptoms merited colonoscopy at that time.
A I am saying that I find the factual basis on which the decision was being made to bring the patient down for a colonoscopy rather scanty. I do not dispute the fact that, having arrived at the Royal Free Hospital, presumably someone spoke to the patient, but it seems rather flimsy evidence to bring them down bowel prepped for a colonoscopy and then tell them when they arrive whether or not they are going to have it done.

Q I am not suggesting that. I am taking your point that somebody had to decide whether or not in this child’s case with her signs and symptoms it was appropriate to do a colonoscopy. As I understand your evidence, that is at the heart of any decision as to whether or not to do a colonoscopy.
A The patient’s symptoms are, yes, but I do not really understand how they knew what the patient’s symptoms were in detail and other issues like growth and nutritional status before they got the patient down.

Q The child has been admitted and a detailed history has been taken, as we have seen, on admission. It is not as though they are taking her in for colonoscopy off the street. The fact is that she has been clerked into the system and her history and her signs and symptoms have been elicited.
A Well, it would appear from the notes that this patient was not seen by Professor Walker-Smith until four days after the patient had been admitted to hospital.

Q I want to ask you about the histology at page 53. Small bowel,

“… fragments of poorly orientated, but normal small bowel mucosa. A lymphoid reaction centre is seen in each sample.”

What does that mean?
A That there is a collection of lymphoid tissue, I think.

Q That identifies it but what, if anything, do you understand by a lymphoid reaction centre?
A Presumably, that the lymphocytes are so called reactive and presumably reacting to something in the lumen.

Q The colonic biopsies,

“These are all pieces of normal colonic type mucosa containing occasional lymphoid aggregates. Minimal inflammatory changes may be the result of operative artefact.”

You may or may not be able to answer this, but one can sometimes see in a report a reference to scope trauma where it is clear that the bowel has been damaged as a result of the endoscope.
A Yes, that is usually recorded when it is recorded as part of the macroscopic appearances rather than microscopic.

Q That will not produce inflammatory change in a biopsy taken as part of the colonoscopy procedure.
A It would be unusual unless the trauma was particularly severe and repeated over a period of time.

Q How would it produce an inflammatory reaction or inflammatory change?
A Inflammatory change can occur in response to trauma.

Q I recognise that but I am looking at the timing of it because this is a biopsy taken at the time of the colonoscopy, so they are taking the biopsy at the time. It is not as though there has been any time for the inflammatory change to take place. It was caused ---
A I think I have already commented that I am not sure what Dr McLaughlin means by “operative artefact”. I cannot help you with the interpretation of that terminology.

Q Would you look at page 14, please. This is 15 January 1998 from Dr Wakefield to Professor Walker-Smith and the sense of it appears to be relatively clear. The mother has been in contact with Dr Wakefield reporting the fact that the child’s gastrointestinal symptoms are particularly severe. In terms of The Lancet paper, it is on the point of being published at that time, is it not? It came out in February 1998.
A Yes, that is correct.

Q And the bowel findings of all of the children have been included including this child.
A Yes.

Q And Dr Wakefield had observed that she has not received any 5-ASA anti-inflammatory treatment and the Panel has already been told on a different point that he was at the time trying to set up a clinical trial of mesalazine with a German pharmaceutical company for the treatment of bowel disease.
A I see.

Q Dr Berelowitz went through some of the documentation in relation to that as did Professor Zuckerman. He makes it clear in that letter that the decision as to whether or not she was treated was down to Professor Walker-Smith, does he not? “If you decide to put her on this …”
A Yes.

Q The fact that he gets a steer in that direction because Dr Wakefield has been in contact with the mother does not take away from Professor Walker-Smith the clinical responsibility for deciding whether or not it would be appropriate to treat.
A Not the ultimate responsibility for treating, no, absolutely not.

Q Without the intervention of Dr Wakefield, as far as we can see, there is no other way in which Professor Walker-Smith would have learned about her symptoms.
A Well, there are other routes. Presumably if ---

Q In this case. There are potentially other routes but, in this case, I do not see any other route apart from being told by Dr Wakefield.
A There are other routes. The mother could have communicated to the Royal Free Hospital through her general practitioner which would be the usual route or, if she was concerned, she could have contacted Professor Walker-Smith direct, if she had chosen to. I do not think that going through Dr Wakefield is the sole route.

Q I am not suggesting that.
A I am sorry, I thought you were.

Q No. I am saying that, on the evidence in this case, she did not go through any other route. So, the fact that it came through Dr Wakefield is not in itself a reason for censure. He is informing Professor Walker-Smith that this child’s condition had deteriorated because somebody had told him that.
A Yes. He is passing the information on. I am saying that it is rather unusual route.

MR MILLER: Thank you. Sir, I was going to move on to Child 9.

THE CHAIRMAN: Professor Booth, you have been in the witness box for approaching an hour. First of all, how do you feel? Would you like to have a short break?
A Five minutes would be enough.

THE CHAIRMAN: We will have a ten-minute break. It is 12.10, so we will resume at 12.20.

(The Panel adjourned for a short time)

THE CHAIRMAN: Mr Miller. Now which child are we going to start with?

MR MILLER: Child 9, the Royal Free Hospital notes.

MR MILLER: Professor Booth, I am not going to ask you about the referral. That is a matter of fact for the Panel, and argument as to the inferences to be drawn. I want to start by asking about the referral letter, probably in response, from Professor Walker-Smith to Dr Spratt at page 36.

“I duly saw [Child 9] in the outpatients. From a gastrointestinal point of view it is interesting that he does pass 1 loose stool a day which in fact seems to be his pattern from the age of 2. He also has screaming attacks which are clearly related to food which his parents attribute to abdominal pain, it is difficult to interpret this.”

Have you come across that as a phenomenon – screaming attacks?
A Yes.

Q In what context?
A Well, a variety of contexts: in infants and toddlers with acute otitis media or urinary tract infections; or you see it in children with renal stones, gallstones, patients with constipation. You see screaming attacks in children with autism.

Q You have had experience of that, have you?
A I see patients with autism.

Q No, no; I am not asking you that. Do you have experience of children with autism having screaming attacks?
A Yes, often in my clinic.

Q And the parents in this case, according to the letter, appeared to attribute it to abdominal pain, “although it was difficult to interpret”.

“As you know his diet has become severely limited but despite this he is gaining weight and growing to above average with height and weight both above the 90th centile. We have now seen several children with autism and gastrointestinal symptoms, all of whom on gastrointestinal investigation have proved to have some kind of bowel inflammation. It is quite difficult to relate this directly to autism. Dr Wakefield as you know, believes that immunisation may play some part, although I remain neutral on this issue for the moment. However the parents are keen that we should endeavour to investigate [Child 9], and I have therefore arranged for him to come in to have a colonoscopy.”

Then it goes on with the other investigations that were also at the time. In your evidence in chief you said:

“I think if you were entertaining a possible diagnosis of inflammatory bowel disease in the presence of symptoms that were by no means typical, and you were considering a colonoscopy, it would be appropriate to check the inflammatory markers first before coming to definite decision.”

That is my note.
A That would be one way of addressing the problem, particularly in a patient who has very mild symptoms and the referring paediatrician, Dr Spratt, had made the comment that the subsequent diagnoses appeared to have been made in the virtual absence of gastrointestinal symptoms.

Q Again, you are arguing the case there. You are going forward to something else. I am asking you about your view as an expert gastroenterologist. Again, you go and take up the argument. Could you resist that, if you can?
A I am merely responding to issues about whether a colonoscopy was as appropriate as the initial investigation in this patient when there is a broad differential diagnosis.

Q It ignores the experience which Professor Walker-Smith sets out in the letter which he and his team had by then of symptoms which were not barn door IBD symptoms but had been underpinned by histological findings in the bowel, obtained from biopsies that had been taken by colonoscopy. In other words, they had found bowel pathology in the children whom they had already investigated. One cannot therefore treat this child in isolation. You cannot divorce from their thinking process the experience that they have had with other children. That is perfectly reasonable, is it not?
A Yes. I think my first comment would be that by this time a number of histological diagnoses had been made, many of which were at variance with the original clinical histopathological diagnoses and in several cases the source of those alternative histological diagnoses was unclear. If these diagnoses were coming from researchers, then it is important that the results of research observations, as opposed to observations made by the clinical histopathologist, are validated and – and – therefore one would need to know against what control material these patients’ biopsies were being compared. By this time, it was clear that many of these patients had constipation, for example, which raises the possibility that these minor changes, including the lymphoid nodular hyperplasia, was some aspect of constipation. Therefore, if you are going to use research-based observations in clinical management, it is absolutely crucial that they are validated. That is one of the issues, for example, that Dr Spratt was concerned about in his letter to Professor Walker-Smith when he was specifically asking about what control material had been used in these studies.

Q You are missing a point. That happens at a much later stage. What is being considered is whether or not the threshold has been lowered as a result of what appeared to be, and would have been known by Professor Walker-Smith from having managed the patients, to be bowel pathology that had been encountered in most of the previous children. It is not a question of just simply looking at one child, and then saying, “On those symptoms alone is it reasonable to proceed?” It is a question of saying, “This is a child who has problems, certainly developmental problems, and we found children with developmental problems with bowel symptoms had turned out to have abnormal guts.” Therefore it is reasonable to carry out an investigation in the child, not least because if they are abnormal, they may give a steer as to how to treat the child for those problems.
A No, I disagree. By this stage it was clear that many of these patients had quite marked constipation. It is also clear that observations being made by some single or group of histopathologists appeared to be ploughing their observations back into clinical management, because clinical pathology diagnoses were being changed. My point is, what is the validity of these observations of inflammation? All I am saying is that the routine prescription of anti-inflammatory agents is not necessarily an appropriate intervention unless you are prepared to compare the results that you obtain histologically and these patients with appropriate controls – which is exactly the point that Dr Spratt was making in his letter.

Q But it is not meeting the point as to whether or not, regardless of the science involved, and whether it was scientifically appropriate to rely upon an interpretation of the histology by somebody who had not been reporting from the clinico-pathological meeting. It is a question of whether or not, armed with what they appeared to be seeing, it was reasonable to have a lower threshold for investigating; to see whether or not there was this pathology present. We are not talking about something which is a majorly invasive investigation. We looked at the literature yesterday. This is a question of saying, for the benefit of the child we would like to see whether or not this unusual, abnormal pathology is present in this child as well. That is all it amounts to.
A I would take issue with you that this is not an overly invasive investigation. I think this is an invasive investigation in children.

Q I have not said that. I said we looked at the literature yesterday, including your literature, and I said it is not an overly invasive procedure, as you yourself say in your own writing about it. It is a safe procedure and history showed that it was a safe procedure in the hands of those who were conducting it in this case. I never sought to say that it was not an invasive procedure.
A So you are putting to me the notion that in a patient who has very mild symptoms, it is appropriate to investigate them with a colonoscopy as the first investigation, ignoring any other possible investigations that might explain why they have loose stools, out of curiosity, just to find out what ---

Q Not out of curiosity. To see whether they are consistent with the children that they have already seen. You know whether you like the conclusion or not; that was in fact the conclusion that was reached in the paper, that these children had a similar sort of bowel pathology in most of the cases.
A But there is no evidence that these patients derived any long-term benefit from anti-inflammatory medication.

Q That is a totally different point. That takes it much further forward. That means, you say, “Let us look two years down the line and say, ‘Did you prosper on liquid paraffin or ‘Did you prosper on olsalzine” and import that back to the decision time, when the colonoscopy was decided upon?
A Surely you have a responsibility to make sure that the investigations that you are carrying out are going to have some long term benefit in the management of the patients, and at this point there is no evidence of that nature.

Q This is early on, is it not? This is only a relatively few months after the first of these children was seen and they are investigating. If they found a bowel pathology which they believed could be treated, then a decision was made to treat. You may say they did not derive much benefit from it because three years later it was decided that it was not appropriate. That cannot be the thing that makes them decide whether or not to do the colonoscopy, because you want to know whether the pathology is present in the first place?
A Yes, but their finding purported evidence of abnormality, they are unable to interpret because they do not have any control material from children with constipation who do not have autistic spectrum disorder. I am putting to you the hypothesis that these changes could have been due to these children’s severe constipation, as something to consider. It has never been put to the test. All I am saying is, there are other explanations for these minor histological changes that were being found.

Q It depends surely upon what it is they are choosing to do. If they are choosing to investigate – that is what we are talking about. There is not an allegation that they should not have contemplated using anti-inflammatories in all these cases. It is a question of whether or not it was reasonable for them to choose to carry out a colonoscopy. If what you are looking for is something which may turn out to be important, and may turn out to be something which is capable of being treated, if necessary subsequently by doing a proper clinical trial, then you want to know whether or not these children, as a group, have bowel pathology which is unusual and which may be associated with their other problems. It is an early stage, as the paper made clear, and the purpose is to see whether or not there is anything there which might be capable of being treated, however it is going to be treated.
A I agree with the editorial that was accompanying one of the publications that was put to me in one of the bundles, which was published in the late 1990s; that children with autism who had gastrointestinal symptoms should be investigated according to the same clinical criteria as other children. You are putting to me that the clinical guidelines for investigating this child should be shifted because of previously research-based observations apparently. I am saying that if you are going to do that, it needs to be done as part of a clinical research protocol that has been approved by a research ethical committee if you are carrying out investigations on children with mild gastrointestinal symptoms to see if they have colonic inflammation.

Q You have decided that in all cases it is the research input that has turned a benign pathology report into a report which suggests that there is some pathology there?
A No. The point I am making is that children with autism and gastrointestinal symptoms merit investigation on the same basis, and according to the same guidelines, as other children that do not have autism, unless they are taking part in a research study. Then, if you are going to go off piste with your clinical indications, you need the approval of an ethics committee.

Q Can we look at the histology, please. It is page 48:

“Specimen I: Small bowel mucosa showing no histological abnormality.

Specimen II-VII: Large bowel mucosa showing prominent lymphoid follicles but not histological abnormality.”

In his letter to Dr Spratt, Professor Walker-Smith writes at page 33. We did not look at the endoscopy report, but the note of the endoscopy report:

“… revealed a marked increase in size and number of prominent lymph nodes in the terminal ileum i.e. lymphoid nodular hyperplasia. The colon was endoscopically normal except for an area at the hepatic flexure which was slightly erythematous.

Histologically there was an increase in chronic inflammatory cells throughout the colon with a moderate increase in intra-epithelial lymphocytes.

Other investigations were … normal and are being collected and you will have a discharge summary soon.

Our diagnosis is indeterminate colitis with lymphoid nodular hyperplasia.”

You made the point in your evidence-in-chief, and you have made it again since, that if that is informed by discussion with another histopathologist within the department, then the provenance of that view is not contained in the notes.
A Yes.

Q It is not a question of disputing the interpretation of the histology, merely the fact is that you do not have any indication from whichever histologist it may have been as to why there is more detail in that than was contained in the original histological report. That is the point, is it not?
A I do not think it is a matter of detail, I think it is a matter of conclusion. The histology at page 48 says “No histological abnormality”, and it has been changed in Professor Walker-Smith’s letter to Dr Spratt saying “There is an abnormality, and it is indeterminate colitis with lymphoid nodular hyperplasia”.

Q One must assume for the moment that that came from some source, but it is not declared on the face of the letter, is it?
A We do not know, that is correct.

Q But his description of indeterminate colitis with lymphoid nodular hyperplasia is not significantly different from prominent lymphoid follicles in the colon. You are describing effectively exactly the same thing.
A There are two features here. One is indeterminate colitis; the second is lymphoid nodular hyperplasia, and they can occur together or independently.

Q But indeterminate colitis means an inflammation in the colon without any obvious categorisation.
A Yes, it is not clear ---

Q What is causing it, in other words?
A Normally one is seeking to determine whether a patient who has colitis has Crohn's as the cause, or ulcerative colitis, but in a variable percentage it is not possible to determine.

Q It appears that the general description ‘inflammatory bowel disease’ is usually taken to refer to one of three things. The two most important and commonest are Crohn's disease and ulcerative colitis, but there is a third category in which you cannot say it is one or the other, but it is a colitis – an inflammation in the colon?
A Yes, it is a kind of holding bay until more evidence emerges with the passage of time.

Q I am going to turn to Child 10, and the Royal Free records. There are two volumes of this, I think. I am sorry; the copies are worse in some of these bundles. Can you look at page 11 in Royal Free bundle 1, please. Is there a poor quality copy there?
A No, it is fine, thank you.

Q It says:

“Summer of ’96 – seemed to deteriorate – pulling knees up, clutching abdomen … seemed to stop taking dairy products – improved.”

In other words it improved.

“Subsequently screaming with bread or sponge cake. Took Hula Hoops only (not crisps) …”.

Then:

“No improvement – calmed down, especially in unknown environment.
- socially better
- sense of humour/more variety …
- comprehension of language
Still no speech.”

Then:

“Bowels – no bowel control
- no urinary control

Gastrointestinal tract – bowels open – occasionally watery
Occasionally dry
Occasionally has to strain at stool
No pain”

As to regularity:

“x 2 to x 6 a day. No blood, no mucus.
Abdominal pain – mum connects this to Hula Hoops.”

Again to take it relatively shortly, Professor Booth, you have given your evidence about your view as to whether or not there was an overriding indication – I think that was your term – to carry out a colonoscopy as the first and only investigation.
A Yes.

Q You have dealt with that in response to Ms Smith, and the Panel will be reminded of that evidence obviously in due course, but I want to ask you about the colonoscopy and the histology. If we look at the colonoscopy report first, it is at page 57, a report by Dr Murch.
A Sorry, at 57 I have a result grid, I am afraid.

Q It is in volume 1.
A I beg your pardon. Yes.

Q The report starts: “This colonoscopy …”. Do you have that?
A Yes.

Q
“This colonoscopy was definitely abnormal, in probably a more striking example of the pattern seen in the cohort of the autistic children.”

This is 17 February 1997.

“The rectum showed definite mild abnormality, with a slightly granular mucosa and abnormal vascular pattern. Prominent lymphoid follicles could be seen through the colon, with no other mucosal abnormality. The caecum showed an erythematous, granular mucosa around a swollen ileo-caecal valve, while the terminal ileum showed minor inflammatory change and striking lymphoid hyperplasia distally.

I suspect that the biopsies will show unequivocal abnormality.”

So on the fact of it his macroscopic view was that there was significant abnormality in the colon.
A Yes.

Q There is an original histology report which is at page 59. It does not look as if it has a date on it. It says 17/2/93, but I do not think that is --- The original one I do not think is dated, but just have a quick look at that:

“Microscopic description
I. The specimen consists of small bowel and have sampled a Peyer’s patch.”

What is a Peyer’s patch?
A That is a specialised area of lymphoid tissue in the distal small bowel.

Q What is it?
A It is thought to be responsible for sampling antigens within the gut lumen and taking them into the gut immune system.

Q
“Where present, the overlying villi appear unremarkable. The lymphoid tissue shows reactive changes. Parasites and granulomas are not seen.”

II to VI – these are the colonic samples:

“All these biopsies show large bowel mucosa with occasional isolated bifid glands. The inflammatory population is within normal limits. Parasites and granulomas are not seen.”

Then the comment is:

“No significant histological abnormality.”

But the same histopathologist is involved in a supplementary report on the following page. Do you have 59A in your bundle?
A Yes, I do.

Q
“Supplementary Report

These biopsies have been reviewed following a clinicopathological meeting. The ileo biopsy shows confluent” –

I think that should be –

“lymphoid aggregates within otherwise unremarkable small intestine. The large bowel biopsies show a very subtle scattering of chronic inflammatory cells within the lamina propria. The superficial lamina propria contains focal nuclear debris and the surface epithelium appears slightly degenerate. No active inflammation is seen. More levels have been cut and no granulomas have been identified.”

So as a result of a meeting they add to the report, identifying a scattering of chronic inflammatory cells within the lamina propria of the large bowel.
A Right.

MS SMITH: (Inaudible).

THE CHAIRMAN: I do not think the shorthand writer would have heard that.

MR MILLER: She wanted me to ask the witness to look at the next page, the end of the report, for the conclusion or the comment. The comment is:

“Minor abnormalities. ? significance”.

A Right. That is 59B?

Q Yes; it is the end of the report; it is just copied on a different page. So whatever its significance to the histopathologist, there was an indication of inflammation being present in the bowel, a scattering of chronic inflammatory cells?
A Yes. I cannot deny that is what it says.

Q I think when we went through – and if necessary I can dig it up – with this child, the other records, we saw that the laboratory tests from the community paediatrician and those taken at the Royal Free were normal. I am not going to ask you to remember that, but if that is the case ---
A Are you referring specifically to the inflammatory indices?

Q Yes. Were they not sent up from Dr Davis? We can find them over the adjournment.
A My note just says that they were not measured before colonoscopy, but if there is some additional material ---

Q I think they were sent by Dr Davis. Page 31. I am not sure – the C-reactive protein is not there, is it?
A There is no C-reactive protein or ESR.

Q No, there is albumin and platelets --
A And haemoglobin.

Q And they are all normal?
A Yes, they are.

Q Can we leave it like this, Professor Booth, that in the next hour if we find other reports we can deal with them later?
A Yes, of course.

Q Do not waste your lunch hour looking for them, but we will see if we can find them. (Short pause) Page 27. These are the blood tests that were taken during the in-patient admission.
A Right.

Q These are the ones you went through before, at the bottom of the page. They are all normal, are they not?

THE CHAIRMAN: Page?

MR MILLER: Page 27, sir.
A Yes, the platelets, haemoglobin, C-reactive protein are normal.

MR MILLER: Sir, I have two more to go, quite short.

THE CHAIRMAN: Thank you. It is about five to one, so we will now adjourn and resume at five minutes to two.
(To the witness) Once again, Professor Booth, my usual reminder: please do not discuss this case during this lunch break.

(Luncheon adjournment)

THE CHAIRMAN: Good afternoon. Mr Miller, we have dealt with Child 10 and I suspect that the next one will be Child 12.

MR MILLER: Yes.

THE CHAIRMAN: Do we need the Royal Free Hospital notes?

MR MILLER: Yes. (To the witness) Professor Booth, I think I can take this case and the next one quite shortly. In this case, the reported bowel problem was soiling and variable abdominal pain occurring each week which stopped the child eating. That is what comes from the record of the outpatient visit to Professor Walker-Smith’s clinic. Is that your understanding?
A Yes.

Q We can see from page 13 that his decision was for there to be full blood counts, ESR and C-reactive protein which you say was the right decision.
A That would be relevant if you were considering that this patient may have inflammatory bowel disease. As we have already discussed, there are other diagnoses.

Q If that is what you had in your mind, the C-reactive protein would or might give you some indication of whether or not there was inflammation in the bowel.
A Yes, together with the other indices.

Q Obviously, what happens is that blood is taken at the outpatient clinic and then a request is made for that to be analysed.
A That is correct.

Q That is the practical way of dealing with it.
A Yes.

Q The results do not come back straightaway, they will take a little time to analyse and then to get back to the person who has asked for them.
A It is the next day for these sorts of tests.

Q On 20 October, which was two days after the outpatient clinic, Mrs 12 wrote to Professor Walker-Smith describing the child’s soiling habit. She wrote a letter to him. On 25 November, in the Royal Free bundle at page 38, Professor Walker-Smith wrote back to her. That is the sequence, is it not?
A Yes, I think that is right.

Q We have been through this sequence a number of times, but this is his response,

“Many thanks for your letter of 20 October. I have now got back the blood tests. One was slightly abnormal. As I see that you are keen for us to proceed with investigation I think it would be appropriate for us to arrange for [Child 12] to come in for a colonoscopy. I explained in the outpatients what this involved. Basically he is sedated and the colonoscope is passed through the lower bowel and pieces of tissue are taken. The children are usually admitted for the course of a week and various other aspects of the protocol are undertaken. If you would like us to proceed with this, please let my secretary know …”

etc and then somebody has written, “Go ahead and arrange colonoscopy” on that letter. That is what he is saying, that he has received the blood tests back and one was slightly abnormal. Mrs 12 responded on 28 November 1996 at page 37,

“Thank you for your letter …

I would like to confirm my agreement to the investigations going ahead.

Would it be possible for you to let know what the slight abnormality was with the blood test and when the implications are? I would be most grateful for this information.

I look forward to hearing from you soon with an admission date …”

The response to that is at page 35. There was a delay and it was written after Christmas.

“I apologise for the delay in replying to your letter of 28th November. The slight abnormality that you referred to in your letter was that one of the markers of inflammation was just slightly above the normal range, it just means that we should go ahead. I understand that [Child 12] is coming in in the New Year to have a colonoscopy.”

That is a perfectly reasonable approach, is it not? If you have a cut-off point and the result is above the cut-off point, you cannot argue that you should ignore it because it is only a little above the cut-off point or 20 per cent above the cut-off point.
A The so-called normal range for investigations is derived from measuring whatever particular variable you are concerned with. Everybody in this case would have a slightly different CRP. When establishing the reference range, most laboratories establish the reference range at around the so-called 95 per cent confidence interval, which means that 95 per cent of the normal population would lie within that distribution. That means that five per cent of the normal population would have a value outside that. So, if you have a very slight increase in a variable ---

Q Is it 20 per cent?
A With a bottom end of the reference range as zero, I do not know that you can make that inference. If you have an upper limit as five and the result comes in as six, it is difficult to record a smaller variation from the reference range. If you slavishly follow that and you do not take into account that this patient had relatively minor gastrointestinal symptoms, to use Professor Walker-Smith’s terminology, and had symptoms that would not immediately make you think that this patient had inflammatory bowel disease – he had soiling – then you might say, “Well, it is probably just a variation of normal.” If you are absolutely intent on doing a colonoscopy, then you would say, “It’s abnormal, let’s do it.”

Q In this regard, you would say, “It is abnormal but you should really treat it as almost normal”.
A The screening tests, as we discussed before, are not a gold-standard investigation and need to be evaluated in the light of all the other information that you have available.

Q In relation to one of the other children, I asked you about a result which you pointed out as being abnormal; I think it was platelets.
A I think that it was a platelet count of 480,000 with a cut-off of 400.

Q There you are. If it had been tested, there is no saying that it would not have shown inflammation being present.
A Under those circumstances, a platelet count of 480,000 with a cut-off of 400 would probably be outside the normal reference range. All I am saying here is that this is the smallest possible variation from the reference range.

Q I think that we have seen some 0.5s along the way.
A I am not aware that CRP in this laboratory is measured at less than single units.

Q You are saying that, in this case, you could just as well have ignored it and said, “It’s only just over and therefore let us look at the symptoms and judge by that”.
A If you are prepared to look at a single minor abnormality in a patient with minor gastrointestinal symptoms and with symptoms that do not immediately suggest inflammatory bowel disease, then, yes, you do a colonoscopy. All I am saying is that if you look at the information available at this point in its entirety, it is not clinically appropriate to do a colonoscopy as the first investigation.

Q That would be your approach?
A That would be my approach, yes.

Q Do you accept that others may not take the same approach with that abnormal value?
A We have evidence here that that is the case, that someone else had a different view.

Q You argue that this child’s problems were caused by constipation. You know that ---
A I am not arguing that they are improved (sic) by constipation; I am just reporting what is present in the clinical record in that it is said that it was notable that, following the bowel clearout prior to colonoscopy, Child 12’s behaviour appeared to improve as did his soiling. It is therefore conceivable that many of his problems are associated with a degree of constipation. I am just noting that, I am not arguing it.

Q You extrapolate from his reaction to the bowel clearout that that may have been a way of dealing with the soiling habit.
A No, I think that Dr Casson is making that implication. It is he who has written that.

Q I want to see how far you go because the GP referral letter had found a normal abdomen and empty rectum when she had referred the child – you have seen that in Dr Stewart’s referral letter.
A Yes.

Q And Professor Walker-Smith’s own examination showed that there was no evidence of faecal loading.
A That is correct, yes.

Q The strength of your argument – I am sorry, not your argument, your observation – is that, given the response of this child to the bowel clearout, in terms of the soiling problem but also as observed in his behaviour, that might have been the root of his problems all along.
A I think that is consistent with the discharge note to the general practitioner from the Royal Free Hospital on 10 January 1997 recommending treatment with paraffin as a laxative.

Q As that played out, it appears from Dr Casson’s letter that the treatment with liquid paraffin was not persevered with.
A I could not comment on that. I just note that a few months later, an abdominal film showed gross faecal loading.

Q You criticise the fact that a decision was taken to try anti-inflammatories rather than persist with liquid paraffin; is that right?
A The evidence at this point was that the patient’s symptoms had improved following the clearout before colonoscopy. The clinical histopathology on this patient I think was essentially normal and the patient subsequently reappeared with gross faecal loading on a plain abdominal film. So, I am not quite sure what was pushing the decision to use anti-inflammatory agents rather than to go for a laxative regime.

Q He was asked by Dr Moodley from the Panel about the letter that he wrote on 2 June 1997 which was at the clinic when he had reviewed the child which is at page 29 and he was asked,

“In the notes of your outpatient assessment you say that the mother had tried liquid paraffin but had not persisted. Could you say what you thought was the rationale for using olsalazine instead of being more aggressive with treating the constipation?

[A] I think the rationale would have been that initial attempts to treat the constipation had been unsuccessful; that bowel symptoms were possibly related to the syndrome that was being described and that the syndrome being described had anecdotally been improved by use of these agents and therefore it would seem a reasonable therapeutic alternative to try that direction rather than treating the constipation per se, which possibly may have been a result of the ongoing bowel problem and, furthermore, to try two treatments at the same time would lead to confusion as to what treatment was actually being helpful.”

That was his explanation to the Panel when asked that specific point. Is that a reasonable approach?
A It is one that I do not really understand. He had already commented in the discharge letter himself about the symptomatic improvement with respect to soiling and behaviour following clearout. He is already aware, by the time that outpatient consultation took place, that an abdominal film showed faecal loading and to say “Just because liquid paraffin has failed for whatever reason, we are therefore going to give up”, I do not understand particularly when the clinical histopathology was showing no evidence of colonic inflammation ---

Q It was not to give up, it was to try something else because, as you know, liquid paraffin was introduced again.
A Does one make the supposition that olsalazine was being used as a means of improving behaviour by a mechanism independent of any colonic inflammation?

Q No.
A That would seem to be the inference from what you are saying Dr Casson was telling the hearing.

MR MILLER: May I deal with Child JS who comes in a separate JS bundle.

THE CHAIRMAN: Is that just the Royal Free records?

MR MILLER: And the local hospital records as well. Professor Booth, page 216. It is local hospital records 1, page 216. I am not going to take you through the history up to this point, but there is an outpatient clinic appointment with Professor Walker-Smith on 30 July 1997. Then no inpatient admission was arranged but on 2 September 1997 Dr Mills, the Community Paediatrician, wrote to the parents, which is that letter at page 216, saying:

“… I am still not sure whether you wish me to make a formal referral to Professor Walker-Smith … for detail gastrointestinal investigations …

I note from Professor Walker-Smith’s letter … that he feels that … [the] gastrointestinal symptoms are ‘minor’, but he would be suitable to have investigations by colonoscopy etc.

How would you like me to proceed?”

There is a handwritten note at the bottom of that from 5 November 1997.

“Phone call to Mum. They did not receive the letter.”

So in fact there was no referral from either a general practitioner or Dr Mills in that case. That is just taking it from the beginning of the story, and getting towards the end of the story. You are aware of that evidence, are you not?
A Yes.

Q Can I ask you about the findings of “Piles” in this case. Do children of four years old get piles?
A It is pretty uncommon. A rectal prolapse would be the more common explanation for something appearing at the anal margin.

Q There are two possibilities. A rectal prolapse or skin tags?
A Piles and rectal prolapse tend to appear and disappear. Skin tags are on the outside, by definition, because they are covered in skin so they do not come and go.

Q What is the cause of rectal prolapse as opposed to piles, which are haemorrhoids?
A It is often associated with constipation and straining, and it is also seen in children who are malnourished. It used to be seen quite frequently in children, for example, with cystic fibrosis who were undernourished and who coughed a lot.

Q If you have a report of piles, you would not consider them to be haemorrhoids. You would think the likelihood is rectal prolapse with a child of this age?
A I think I would keep an open mind until I examined the patient.

Q And if it is rectal prolapse as opposed to haemorrhoids. Is it something that comes and goes?
A Rectal prolapse characteristically comes out for a time and then goes back in. Parents often push it back in.

Q In this child’s case, eventually he comes in to be seen and to be investigated. He is not involved in The Lancet paper. Look at page 50 in the Royal Free notes. This is the colonoscopy. The report is by Dr Thomson and Dr Heuschkel:

“↑[Increase] vascularity in recto sigmoid area to spl”

- “Spl” – is that splenic?
A Splenic flexure.

Q
“… spl. [splenic] flexure. ? ↑ granularity around caecum ± [plus or minus] ↑[increase] vascularity. Lymphoid nodular hyperplasia of the TI [terminal ileum].”

So that is the short report on the colonoscopy. Have I read that right? That the “± [plus or minus] ↑[increase] vascularity” ---
A Yes.

Q As opposed to granularity - sorry?
A Yes. I think he is saying he is not sure if there is a bit of increased vascularity or not.

Q Then, page 32 is the histology. Sorry, perhaps we should look back. Would you go back to page 51 at the moment. It is written on the proforma under:

“Histology, 21/11/97

Ileum: No acute inflammation.”

A I think that is “active inflammation”.

Q I am sorry – active inflammation.

“Colon: Patchy changes
Caecum: Lymphoid aggregates”

Is that “transverse colon”?
A Transverse colon, yes.

Q
“Active cryptitis.
Eosinophils + neutrophils”

What are eosinophils and neutrophils?
A They are particular types of inflammatory cells.

Q And they are the sorts of findings, are they, that would suggesting there was some inflammation in the transverse colon?
A Yes.

Q Go back to page 32, if you would. Under “Microscopic description”:

I. TERMINAL ILEUM

Unremarkable small bowel mucosa including prominent lymphoid tissue. There is no diagnostic pathology present.

II CAECUM

Unremarkable large bowel mucosa.

III and IV TRANSVERSE AND SIGMOID COLON

Large bowel mucosa in which there are small foci of cryptitis and crypt abscess formation (the latter in III). There are no granulomas present.”

So they have identified in the transverse and sigmoid colon small areas of cryptitis?
A Yes.

Q And crypt abscess formation. So there is an indication of inflammation being present?
A Yes.

Q By that stage – it remains to be seen when the evidence is given – but by November 1997 if one takes simply as a reference point The Lancet paper, which was published in February 1998, quite a large number of children had been seen and investigated, and more than the eleven whom we have, English-based ones from The Lancet paper.
A I see.

Q You have seen the footnote, have you, to the ---
A To The Lancet publication?

Q Yes.
A Yes.

Q I think by the time of publication, which is February 1998, something like fifty have been seen.
A Yes.

Q Given that pathology, Professor Booth, it was reasonable to treat with Pentasa, was it not?
A Yes.

MR MILLER: Thank you.

THE CHAIRMAN: Professor Booth, after Mr Miller’s cross-examination, who is representing Professor Walker-Smith, Mr Hopkins, who is representing Professor Murch, will cross-examine you. Do you wish to have a five minute break before he starts or are you happy to ---?
A I am very happy to continue.

THE CHAIRMAN: Right. Mr Hopkins.

Cross-examined by MR HOPKINS

MR HOPKINS: Thank you, sir. Good afternoon Professor Booth.
A Good afternoon.

(Short discussion on audibility)

Q Can I give you just an overview of the topics I wish to cover. Inevitably I am going to trespass on matters you have covered twice already. I apologise in advance, but I think you understand the need for the process.
A Yes.

Q I want to start by looking at the 172/96 project and the division of responsibility and expertise envisaged within it. I then want to move on to look at the role of teamwork within a department like the paediatric gastroenterology department at the Royal Free, and include within that reliance on the judgment of others, which is obviously relevant. Thirdly, to look at the role of someone carrying out a colonoscopy when they have not seen the patient before. Fourthly, to look at other bits of literature, some of which we have not yet looked at and some of which we have. Finally, sad to say, another look at the patients that we have been considering, but you will be pleased to know I will be confining myself to seven out of the twelve. Those are the seven that Professor Murch is concerned with.
A I understand.

Q Let us then start off with project 172/96. You will need to dig out again FTP1, please. Would you turn to page 200. Just in terms of looking at the beginning of this proforma, we can see – and the Panel has seen many times now – that this project envisaged a role for four departments, the paediatric gastroenterology department where Professor Walker-Smith and Dr Murch (as he then was) worked; the academic department, where Dr Wakefield worked; the department of neurology where Dr Harvey worked and the department of child health and child psychiatry were Dr Berelowitz worked. Would you agree?
A Yes.

Q We see a quarter of the way down the responsible consultants listed. I just wanted to ask you about that, as I have asked witnesses giving evidence on this matter. I think firstly you would agree, would you not, that the term “responsible consultant” is not defined within this project’s application?
A You mean in the sense that the responsibilities of all the applicants are not mapped out?

Q Yes.
A And specified. That is correct.

Q I just want to look at what the term “responsible consultant” could reasonably be taken to mean or not mean. First of all, I think you will accept that it will be taken to mean that the consultant would be participating in some way in this project?
A Yes.

Q That degree of participation may or may not be further described within the documentation itself?
A Yes. It may or may not be. I think probably these days there is a requirement to describe the roles more specifically, particularly as money to the department often follows someone’s role, and there is a need to be clear about what they are doing.

Q Yes.
A But I think in 1996 that requirement was much less strongly felt.

Q Indeed. This proforma and the contents of it did not identify the nature and extent of the duties of each responsible consultant?
A No. That is right. Or yes, that is right.

Q Can we then look at what it did not mean. What you agree that it did not mean a responsible consultant was responsible for matters outside of his control or expertise?
A Yes. Within certain limits, I think that. If, for example, the inclusion criteria for a study were very clearly defined as they are here, and you are aware that they are not being met, it is important, whoever you are or whatever your place on the application form is, you have responsibility to indicate that that is not being met.

Q Of course, if you were aware of a problem, then it would be the duty, even if you were not named in it but you were aware of a problem, it would be your professional duty to do something about it, would it not?
A Yes.

Q In terms of responsibility for the acts of others who you had no control over, if they were independent of you, you would not be held as the guarantor for them, would you?
A I think it would depend on what acts you were aware of, and if they were concerning you. If you were aware that your collaborators in the project, either singly or in concert, were carrying out activities that were concerning to you, then it would be your responsibility to make that known to the relevant body within your institution, whether or not you were their direct line manager, so to speak. I think that is a responsibility that certainly all doctors carry.

Q Certainly, Professor Booth, I am not going to disagree with that proposition. I am just looking at whether, simply by being named as a responsible consultant, one is deemed to be a guarantor of the conduct of others, and I think you would agree with me that that does not necessarily follow.
A No, it does not necessarily follow.

Q I think it is your view – and if you wish to refer to your general report at page 26 at the top of the page please do so – it is your view, is it not, that you would not expect colleagues from outside your own specialty to comment on the detail of your work or on the results as they related to that speciality?
A That is correct. You would rely on their expertise within their own discipline.

Q Indeed. Let us just follow through again with the practicalities of what a responsible consultant does not mean. The fact that Dr Murch was named responsible consultant did not mean that he would be present at each assessment of the patient for entry into the project itself?
A No, not present at the assessment.

Q No. Indeed he would not be expected to be present at each and every investigation carried out on that patient?
A That is correct.

Q I think it is your view, having looked at the documents and indeed the witness statements in advance of this hearing, as well as the transcripts that would have been shown to you, that Dr Murch appeared to play little other role in the activity that you believe was associated with 172/96, other than carrying out the colonoscopies.
A I have not been aware that Dr Murch took part, for example, in the type of correspondence that subsequently occurred between Dr Wakefield and Professor Walker-Smith. I am not aware that he saw any of the patients in the out-patient clinic, as far as I can remember, before they came in, and I do not think any of the patients were referred to him. So, yes, that is right.

Q Can I then also look at the notion or the concept of responsible consultant in the context of team working. It is a concept that has to take account of team working, would you agree, because that is the way a modern department functions?
A Yes, very much so.

Q In other words, it would recognise the fact that other members of the paediatric gastroenterology team or other specialist teams would be involved in a patient’s assessment and investigations and care during the admission?
A Yes. It is often the case that colleagues from other disciplines, other teams, are involved and also true that a number of colleagues from one’s own team are involved as well, yes.

Q Can we then see what this document says about the other specialties. We will start with psychiatry. Turn to page 214, if you will. If we go about a quarter of the way down, to paragraph 1.3, the Department of Child Psychiatry, it identifies Dr Berelowitz, and then half-way down under “Responsibilities” it gives him the responsibility of:

“Confirmation and characterisation of features of disintegrative disorder.”

A Yes.

Q So that is putting the psychiatric side in his ballpark, would you agree?
A Yes, in the sense that he has first line responsibility, yes.

Q Then if we look at the Department of Neurology, which is immediately below that, we see this identifies Dr Harvey, the consultant neurologist and coordinating investigator, with responsibilities for “Full neurological assessment and investigation”.
A Yes.

Q That is indeed further elaborated, if we move on to page 222, at the top of the page, at paragraph 3 we see:

“3. Neurological and neuroradiological studies” –

and Dr Harvey’s name against that. Then a list of things:

“Full clinical examination, MRI, Lumbar puncture and CSF antibody profile … cytokine measurement, … EEG with visual somatosensory and brain stem auditory evoked potentials.”

So it is putting that assessment and list of investigations within his discipline, would you agree?
A Yes, that is right, yes.

Q Then if we look at the paediatric gastroenterology department, go back please to page 213, paragraph 1.1 relating to this department, a third of the way down we see their responsibilities within this project.

“- Referral and coordination of patient admission for investigation:
- Clinical evaluation, procurement of blood, urine and serum samples.
- Colonoscopy and tissue procurement/processing.”

So that is an overview of what the project set out to do in terms of dividing between the specialties within the Royal Free, would you agree with that?
A Yes, it sets it out. I think under the responsibilities of the paediatric gastroenterology department where it talks about referral and coordination of patient admission, as part of the referral process and sifting of patients for possible inclusion in the study, you would anticipate that at that point they would be getting a fairly clear steer from whoever was referring the patients about whether or not the child being referred had good evidence of disintegrative disorder. So although Dr Berelowitz is charged with confirmation and characterisation, I think it does not remove the preliminary responsibility from the person handling the referral to get some fairly convincing evidence that the patients did or did not have disintegrative disorder.

Q Can I move away from that document now and just consider the set-up within the paediatric gastroenterology department, and I want to start by looking at the hierarchy. We know, starting at the top, that this department was headed by Professor Walker-Smith, and in 1996 he would have properly been regarded as an eminent professor in this field, would he not?
A Yes.

Q Indeed he would have been, in terms of experience, 25 years or so a consultant, and professor for about ten years by that time?
A Yes.

Q In terms of his standing within the UK, he would have been regarded as a senior paediatric gastroenterologist?
A Yes.

Q And indeed someone with an international reputation?
A Yes.

Q In his time up until that point he would have trained many junior paediatric gastroenterologists?
A Yes, undoubtedly.

Q And by 1996 therefore had quite a formidable reputation.
A I am not quite sure what you mean by “formidable”. Do you mean formidable in the sense that people were scared of him, or ---?

Q No – that may or may not have gone with the territory as well. Formidable in the sense of being very experienced and having a high status in this field.
A Yes, in that sense, yes.

Q Then next down in the department there were two relatively newly-appointed consultants: Dr Murch, as he then was, who had been appointed as a consultant in 1995, and Dr Thomson, who had followed some months after that.
A Right.

Q Both technically by reputation were regarded as being skilled in carrying out colonoscopies and upper endoscopies, would you agree with that?
A I find it difficult to comment on that with regard to their skills in 1996. I think Dr Thomson had only joined the department as a consultant some months before the studies took place that we have been examining, and I do not know how skilful he was or was not in colonoscopy at that time. He joined the Royal Free Hospital having been a trainee in Birmingham, in my department and Professor Kelly’s department, and I recall that when he came back from Australia there was a certain amount of displeasure on his part that he was going to be working with a hepatologist rather than a gastroenterologist, because I think he wanted to get some more endoscopy experience with us. So I do not know when he joined the Royal Free how much colonoscopy he had done. I think in Australia, and certainly when he was with us doing hepatology, he did a lot of upper GI endoscopy. It would be true to say that now Dr Thomson is probably the leading paediatric endoscopist in the UK. In the case of Dr Murch I could not comment on how much experience he had or had not had.

Q In terms of their own experience, and I think in a way you have made the point for me, in 1996, their experience compared with that of the head of their department, Professor Walker-Smith, it would have been quite reasonable for them, would it not, to put a lot of faith and store in the professional judgement of Professor Walker-Smith?
A Yes. Probably outside the interpretation of observations at endoscopy, because I do not think that was something that Professor Walker-Smith undertook.

Q I am sorry, I did not mean it in terms of carrying out the procedure and the interpretation of the procedure; I mean in terms of his clinical skills.
A In terms of his experience he would have been a lot more experienced than Dr Murch or Dr Thomson, yes; that would be undeniable, I think.

Q And reasonable for them to have faith in that experience and in his clinical acumen?
A Yes, although I think when you are appointed as a consultant you cross quite a big divide, and the big difference is that you have to start taking responsibility for decisions that you make yourself. I think certainly in 1996 that was the view of what a consultant was.

Q I think you would agree with this proposition, though, that a good doctor never stops learning, even if they have the label ‘consultant’ attached to them.
A Yes, that is true.

Q And often one learns from experience.
A Yes.

Q I am going to put a series of questions to you in a moment about teamwork and the weight it would be reasonable to attach to a referral from Professor Walker-Smith, but I want to preface these questions with this, so you understand Professor Murch’s position. Mr Miller on behalf of Professor Walker-Smith has set out Professor Walker-Smith’s justification for requesting these colonoscopies; and Professor Murch accepts that justification as has been put forward. His position is that these colonoscopies were clinically justified – so I want that to be clear at the outset.
A Yes.

Q In addition to that, however, I think you would agree it is necessary to look at events from Dr Murch’s perspective as he then was, as the endoscopist with the children on his list, so it is with that in mind that I am now going to ask a series of questions of you. Do you understand?
A Yes.

THE LEGAL ASSESSOR: Mr Hopkins, just before you move on to that, from my point of view, from a legal point of view, do I understand therefore when I have to come to advise the Panel that you are adopting the cross-examination of Mr Miller?

MR HOPKINS: I am indeed.

THE LEGAL ASSESSOR: With respect to the clinical colonoscopies.

MR HOPKINS: I am – which the Panel will be relieved to hear shortens the number of questions, and Professor Booth will be relieved to hear that, but it does not of course get rid of them.

THE LEGAL ASSESSOR: Thank you.

MR HOPKINS: (To the witness) If we then consider the functioning of a team within the paediatric gastroenterology department, an obvious point, there will be cross-over of patients between the Professor, between Dr Thomson and Dr Murch.
A By cross-over what do you mean?

Q For example, some patients will be seen or assessed by one of those three, and another one of those three may see them on the next occasion.
A That is one way of working. Some of my colleagues at the Children’s Hospital in Birmingham adopt that method of working, whereby there is no clearly-identified responsible consultant within the team. My colleagues and I and many other teams adopt a different approach, where there is a clearly-identified consultant. So there are differences. But if you are saying that within the Royal Free Hospital at that time there was free interchange of patients between consultants, that would not be abnormal.

Q What I am suggesting is, and we have seen in reality in the cases that this Panel has been looking at, out-patient assessments may well be done, for example, by Professor Walker-Smith, and yet when the patient is then admitted to hospital the first or the next consultant they see many not may be him.
A Yes, I understand.

Q It may be Dr Thomson or it may be Dr Murch.
A Yes.

Q I think it follows from the discussion that we have had that you accept that it is reasonable to rely on the judgement of your colleagues if you think they are competent.
A Yes, if that is your manner of working as well. It would not work if you did not rely on the judgement of your colleagues – which is not to say if you work in the alternative way I describe, you do not rely on their judgement, but it is not quite so much of an issue then.

Q It therefore has this very practical effect, does it not: if in fact Dr Murch sees a patient who has already been assessed by, say, Professor Walker-Smith and recommended for an investigation, you would not expect Dr Murch to re-invent the wheel and carry out the assessment all over again? He would be entitled to place weight and reliance, would he not, on that previous assessment by his colleague?
A I think it would not remove the responsibility for the second consultant involved, in this case Dr Murch, to satisfy himself that the tests that were being embarked upon were clinically indicated. You have indicated that Dr Murch did feel that, so presumably to be in that position he had carefully examined the history, the notes, and spoken to the parents, examined the child. That would be the practice in my unit, for example, when patients are endoscoped by another consultant, we have a slightly different manner of working, as I have described. But from time to time it is necessary for other consultants to endoscope one’s own patients.

Q Let me just bring you back to this point. I fully accept the point you are making, that if you as another consultant see a patient and you think something is being missed or something is wrong, then obviously your duty is to the patient to do something about it, and we are not going to disagree over that. What I am getting at is if you think an assessment has been carried out competently, and there is nothing that occurs to you that is flawed about that, then you are not going to carry out a further full assessment before you then act on the request of your colleague for an investigation. Would you agree with that?
A To have satisfied yourself that the investigation was clinically indicated you would have had to have looked at the notes, spoken to the parents and examined the child, otherwise I do not see how you would know that it was clinically indicated. If you in each case come to the same conclusion as your colleague, then an issue does not arise.

Q I can take you to the transcript of your answers to Ms Smith about this earlier this week. You were being asked about responsibility of the colonoscopist in carrying out colonoscopy that had been ordered by someone else, and you gave answers on this on two days. Just for the Panel’s reference, Day 40/31D-F, and the second time you came to this topic was Day 41/6-7. You certainly set out your store that there was a responsibility of the person carrying out the procedure to satisfy themselves that it was appropriate, but you recognised, did you not, that the practical reality is, with the time constraints involved, one would not be carrying out a further full assessment on the child?
A Not in the sense that you would take the same amount of time, in other words go into the same degree of detail that you would if you were seeing a patient for the first time in the out-patient clinic. Equally well, you would reassure yourself that the patient, for example, still had the symptoms that had led to them going on to the waiting list to come in for the investigation.

Q Let us consider the practice of how this would work and see where we agree and where we disagree. The system before a colonoscopy procedure is carried out in these cases: we have seen that usually the child is assessed in outpatients and that was done in all of these cases by Professor Walker-Smith.
A Yes.

Q If he considered it appropriate, he arranged for those children to be admitted for further investigation including colonoscopy.
A Yes.

Q The child then came into the hospital on a Sunday being placed on a list for colonoscopy the very next day to be carried out on the Monday.
A Right.

Q The child was usually clerked in by the senior registrar, Dr Casson, on the Sunday. The endoscopists carrying out the requested procedure were either Dr Thomson or Dr Murch. They had lists on the Monday, usually, for carrying out these procedures, on Monday morning. The Thursday before the child was admitted, there was a ward meeting in which the next week’s admissions were discussed and notes for those admissions may have been made available prior to the weekend.
A Would you clarify who is at the Thursday meeting.

Q Usually the consultants. There may on some occasions be reasons why they would not all be there but the aim was that that is what would happen. The endoscopists therefore, certainly in the cases this Panel is considering, would not have seen the child in outpatients before the child was admitted to hospital and I think bar one occasion, which was Child 2, Dr Thomson, and neither Dr Thomson nor Dr Murch saw them before the morning of the procedure.
A Right.

Q In terms of the evidence the Panel has then heard about the Monday procedure list, there were usually four colonoscopies for that as well as other procedures like upper endoscopy and, by the time of the colonoscopists being available to see the patients that morning, the children had already been prepared for colonoscopy with their bowel clearout, so they had been given medication before. Given that background, may we look at what the practical realities were for the endoscopist. If time permitted, he would be able to visit the child or the children on the ward before starting the list. May we run through the sequence of events.
A Yes.

Q One of the purposes in doing that – and I think that you have alluded to this already – would be to check that the child was fit enough to undergo the planned procedure.
A Yes and I think that, if you had not seen the child and the parents before, to quickly run over symptoms and examine the patient if that was relevant as well.

Q I will come on to that. May we go through a checklist and, if there are any other things, you can comment on them. One of the main things is to check the fitness of the child. In other words, is there an inter-current illness or some reason why the procedure should not go ahead associated with the child’s condition that day.
A Yes.

Q Secondly, to be given some information about that child and that may come either from looking at the notes or from a résumé by a junior doctor accompanying the consultant.
A Yes.

Q And that would accord again with normal practice, would it not?
A Yes.

Q One of the things that a colonoscopist would be looking for in particular would be potential risks for the procedure such as risks for an adverse reaction to sedation; would you agree?
A Yes.

Q Or joint hypermobility. In other words, in positioning the child. You want to know if you are likely to encounter any problems.
A Yes. If they had an abnormal posture particularly if it was going to impede the airway.

Q You would also be looking to see if there was any previous history of endoscopy because that may be relevant.
A Absolutely, yes.

Q And, if the parent were there, you would probably want to have a discussion with the parent about the child.
A Yes.

Q And make sure that the parent understood what the procedure was.
A Yes. It would depend on who was obtaining consent about the content of that because, if you were responsible for obtaining consent, you would need to have a very detailed discussion about the risks of the procedure but if someone else was obtaining the consent, as happened in those days, then that would not be necessary.

Q Of necessity, all these tasks that we have just been considering, bearing in mind that you have an endoscopy list that morning, occur under some degree of time constraint, do they not?
A I think it would depend on what time the endoscopy list started.

Q Of course, but the practical reality is that we are under pressure of time in a situation like that; would you agree?
A No, I do not entirely. I know that, on our endoscopy list at the moment, those are done under GA and the anaesthetist goes round and sees all the patients that he or she is going to anaesthetise before the list happens. So, the issue of there not being time to see the patient before the list does not have a resonance.

Q Professor, I need to be quite clear what I am putting to you. I am not saying no time to see the patient, what I am saying is that these tasks are done but they happen under time constraints and what I am suggesting to you is that there is not the luxury of time to reinvent the wheel and carry out the type of assessment that happens in outpatients.
A You probably only need to see the first patient because, between the first patient and the second patient, you could go and see the subsequent patients. It is rather different if you are the anaesthetist because you have to see all of them but, if you are the endoscopist, you would only have to see one patient who would be the first patient on the list. The remainder of patients on the list you could see later on in the morning between cases.

Q What I am putting to you is the reality on the ground which I suggest is, in a team situation like this, one does place a lot of weight in the opinion of a more senior colleague whose judgment is respected and only if there is some obvious flaw in the assessment does one then put on hold the investigation that has been planned; would you agree with that?
A I would agree that if, notwithstanding you are consultant, you are junior to your senior colleague by a long way. It makes it understandable that it would be less likely that you might challenge some of their clinical decisions.

Q I think that I am putting it a stage further than that. What I am suggesting is that one would have a low threshold for carrying out a colonoscopy that had been requested by a more senior colleague who had many more years of experience in assessing children.
A Yes although, if you had been trained by that person, you would image that the criteria for investigating the patient would be very similar indeed, if not identical, so that the likelihood under those circumstances of some dispute might be minimal.

Q Indeed and, as I think I have made clear, I am not suggesting that there was any dispute between Dr Murch and Professor Walker-Smith.
A Right.

MR HOPKIN: I want to move next to looking at some literature. Sir, I note the time and it may be a convenient moment.

THE CHAIRMAN: Yes, we will now adjourn. It is 3.05 and we will resume at 3.25. (To the witness) Professor Booth, you are still in the middle of giving your evidence. We will now rise.

(The Panel adjourned for a short while)

MR HOPKIN: Professor, may we look at some literature. You will need FTP5 first of all. Would you turn to tab 3 at page 27. We see here a paper entitled, “Colonoscopy and therapeutic intervention in infants and children” by Wylie and Kay in 1994 in Paediatric Endoscopy; is that right?
A Yes.

Q I think that this is a paper that you in fact provided.
A Yes.

Q Starting on page 27 and the introductory paragraph, it says this,

“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, diagnosis and management of inflammatory bowel disease, and therapeutic intervention.”

First of all, I think you would agree with those general statements, would you not?
A Yes.

Q Would you turn on to page 39 and I want to start, before we delve into the text, with this general proposition. Do you agree that inflammatory bowel disease in its early phase in children can be more subtle in its presentation than in adults?
A Yes. That is well recognised and was present in one of the reviews of my own that I was taken to in cross-examination yesterday from 1984.

Q If we look one quarter of the way down the page, we see that it deals in the paragraph beginning,

“With increasing patient age, inflammatory bowel disease including both ulcerative colitis and Crohn’s disease, becomes a more frequent causes of lower GI bleeding”

and then goes on to deal with ulcerative colitis, so let us just look at that.

“Presenting symptoms develop in 30% to 40% of patients with ulcerative colitis before 21 years of age. Diarrhea is the most frequent initial manifestation of this disorder. Almost 50% of pediatric and adolescent patients have an insidious onset characterized by low-grade fever associated with mild diarrhea.”

Do you agree with that?
A Yes.

Q It goes on to say,

“Other manifestations include rectal bleeding and abdominal pain, fatigue, weight loss, nausea and vomiting, and isolated fever.”

Do you agree with that?
A Yes.

Q It adds,

“Endoscopic examination with biopsy of the colonic mucosa is essential for diagnosis, as well as to determine the extent of disease and the response to therapy.”

Do you agree with that?
A Yes.

Q Would you drop lower down the page to the last paragraph and this then is dealing with Crohn’s disease,

“The most common presenting symptoms of Crohn’s disease are diarrhea, abdominal pain, and fever occurring in more than 70% of patients.”

Do you agree with that?
A I think that opinions or rather observations vary from study to study about precise percentages but diarrhoea, abdominal pain and fever would be certainly frequent.

Q I think the corollary of that is that, in 30 per cent of cases, that collection of symptoms is not present.
A Yes.

Q It goes on to say,

“In pediatric patients, the onset of symptoms may be subtle with long delays, often for several months or longer between symptom onset and diagnosis.”

Would you agree with that?
A Yes.

Q That is an important consideration, is it not? The subtlety of presentation of Crohn’s disease is something that a clinician has to take into account when deciding whether or not inflammatory bowel disease is being suspected.
A Yes, absolutely.

Q It goes on to say,

“In some cases, growth failure or the crossing of percentiles on a growth chart may be the only clue to the diagnosis. Weight loss is noted in approximately 40% of pediatric patients.”

Pausing there, the corollary of that is that, in 60 per cent of patients, there will not be weight loss at presentation.
A Yes.

Q
“Less frequent symptoms include rectal bleeding in 30%, arthritis in 20%, and a palpable inflammatory mass in 10% of children.”

Do you agree with those?
A Yes. They are broadly similar to most studies.

Q Would you agree with the proposition that presenting symptoms of inflammatory bowel disease are protean, in other words variable?
A Yes, they are many and varied.

Q We can put aside that article. I need next to take you back to the Porto Criteria, so for that you will need Professor Murch’s bundle of literature which is D5 and would you turn to divider 9 and to page 51. If we look at the abstract one third of the way down the page – the Panel has been through this before – I just want to pick it up at the bottom of the first paragraph on the left-hand side in the abstract.

“Diagnosis of Crohn disease, ulcerative colitis and indeterminate colitis is based on clinical signs and symptoms, endoscopy and histology and radiology.”

Let me just pause there. I think you would agree with that. It is similar to what we just read?
A Yes.

Q
“Every child suspected of inflammatory bowel disease should undergo a complete diagnostic program consisting of colonoscopy with ileal intubation, upper gastrointestinal endoscopy and (in all cases except in definite ulcerative colitis) radiologic contrast imaging of the small bowel.”

Would you agree with that?
A Yes. This is by virtue and abstract, and therefore does not include everything that is in the full publication which follows.

Q I appreciate that.
A For example, from the abstract, any mention of laboratory examination; so that if you look at the full paper you see that that is included in the text, but is missing from the abstract. So it is not a complete list.

Q I will come on to what is in the text, but do you agree with that as a broad proposition?
A Yes.

Q And it goes on:

“Multiple biopsies from all segments of the gastrointestinal tract are needed for a complete histologic evaluation. A diagnosis of indeterminate colitis cannot be made unless a full diagnostic program has been performed.”

A Yes.

Q Again, you agree with that?
A Yes.

Q Just looking at what arises from the abstract, and its use of the word “suspected” – so we are going near the top of the right hand column of the abstract, where it says, “Every child suspected of inflammatory bowel disease should undergo” this full diagnostic programme. The word “suspicion” obviously is language of a relatively low threshold – would you agree?
A It is a very broad, poorly defined term.

Q It is not using words like “probability” or “likelihood”. It is “suspicion”, and what I am suggesting to you is, this paper is indicating that if one is simply dealing with a suspicion, not a probability, that is enough to justify the intervention by colonoscopy. Would you agree with that?
A Yes.

Q And it is clear that this paper – and we will go into the body of it again – places colonoscopy as a very important part of the diagnostic work-up?
A Yes. No one would, I think, deny that.

Q And there are some obvious reasons – I do not think you will disagree with it – first of all colonoscopy enables the lining of the bowel to be visualised, so it gives more information from the bowel that you cannot tell otherwise. Would you agree?
A Yes.

Q It also, of course, enables tissue sampling, so histology can be obtained on that tissue?
A Yes.

Q And it therefore means that you can get tissue that you cannot otherwise get by less invasive means?
A Yes.

Q And the combination of the macroscopic findings at colonoscopy, together with the tissue findings on histopathology, provide two important ingredients going to enabling the diagnosis of whether or not there is inflammatory bowel disease present?
A Yes.

Q This paper also go on to deal with investigations after colonoscopy and it recommends, does it not, radiologic contrast imaging of the small bowel if, on colonoscopy, you do not find definite ulcerative colitis?
A Yes, you may image the small bowel in any case.

Q Can we then look at what it says about clinical suspicion of inflammatory bowel disease. Let us turn on to page 52 in the right column, a third of the way down, where it is dealing with patient history. It says this:

“A clinical suspicion of IBD is raised in children with persistent (≥4 weeks) or recurrent (≥2 episodes in 6 months) symptoms such as abdominal pain, diarrhea, rectal bleeding and weight loss.”

Let me just pause there. Would you agree with that general statement?
A It is not clear from that – and this is the problem with lists of this nature – whether, when it has “abdominal pain [comma]” it means abdominal pain and diarrhoea and rectal bleeding and weight loss, or whether it means “abdominal pain or diarrhoea or rectal bleeding and weight loss”. So if it says symptoms such as “abdominal pain or diarrhoea”, you would not immediately necessarily consider doing the colonoscopy unless the abdominal pain was associated with a number of other features, perhaps specific to the nature of the pain and also other symptoms that the pain may have, as well as physical signs on examination. So a list like that, I think, is singularly unhelpful when formulating a differential diagnosis.

Q Can I first of all put this suggestion to you. I think it is clear from the context of this whole passage – and we will look at the rest in a moment – this list is not conjunctive. In other words, you do not have to have pain, diarrhoea, rectal bleeding, weight loss all together before suspicion is raised, but it is a disjunctive list and that is quite clear from the context of what follows. Would you agree with that?
A I would not agree that abdominal pain in isolation was a first rank indication for colonoscopy in the absence of any other supporting symptoms or signs.

Q So if this list should be read disjunctively, you would be disagreeing with the authors, would you?
A No, I would not necessarily. I would be saying that the complexity of making a differential diagnosis, based on a constellation of signs and symptoms, is far more complex and sophisticated than just looking at a list like this.

Q It involves clinical judgment, does it not?
A Formulating a differential diagnosis based on a constellation of signs and symptoms usually starts with a fairly broad differential diagnosis, that is based on a knowledge of what is common and what is possibly explicable on the basis of the patient’s signs and symptoms. Then, I think, there is a fairly sophisticated sorting process that takes place, whereas the further history is elucidated, certain components of your differential diagnosis are excluded or move up as a likelihood. So the process is usually fairly convergent. So you start from a broad number of possibilities and hone down, and you end up with a differential diagnosis which is a list of possibilities in order of likelihood. I think that that is a sophisticated process which, for example, is slow to be acquired by medical students, for example. I think that is the whole reason why we take a very long time to train some specialists; because evaluating these sorts of symptoms is a sophisticated process and just a mere list of unqualified symptoms without any sensitivity analysis does not, I think, begin to help you towards formulating a differential diagnosis. It is true to say that all the symptoms occur in patients with inflammatory bowel disease, but just listing them does not necessarily tell you what relative merit they have.

Q Mr Miller, when he asked you questions, explored with you the status of the individuals who had comprised the working group that drew this up, and also the status of the paper. Let us go back to page 51. This is described as a “Medical Position Paper” is it not?
A Yes.

Q And the aim of this was to try and get consensus amongst practitioners in this field?
A Yes.

Q I think, when you looked at the list of authors who had contributed to this, if we go to the last page, page 57, I think you accepted it included individuals of high standing in this field?
A Yes, absolutely.

Q Including Dr Murphy from your own hospital?
A Yes.

Q Going back to page 52 ---
A Sorry. Equally well, I think it is important to recognise that there are differences of opinion and, in the particular cases we are considering, we are looking at patients who were selected for investigation by Professor Walker-Smith. Professor Walker-Smith, if you look at his publication, which is behind tab 7 in his bundle, expresses a view that is at variance with the more recently published Porto Criteria, where he is saying the triad of abdominal pain, chronic diarrhoea and weight loss so characteristic of Crohn's disease in adult life was commonly found in his paediatric series. All I am saying is, just looking at lists like this does not really do justice to the sophistication of the diagnostic process that takes place in an outpatient clinic.

Q Professor, let us just break this down. First of all this paper is trying to give guidance to the field, is it not?
A It is trying to give guidance, yes.

Q And secondly, the point you are making is, one does not approach patients just by list. It is more sophisticated. One has to take account of the individual before you and how they present?
A Yes. You need as much information as you possibly can obtain.

Q And one therefore factors into that clinical experience and judgment, and that has to be right?
A Yes.

Q If we look at what this paper is saying – let us go to the middle of page 52, right hand column – it says this:

“In this study, the ‘classic triad’ of CD [Crohn disease] symptoms (abdominal pain, diarrhea and weight loss) was present in a minority (25%) of CD [Crohn disease] patients.”

I think that is a reference to footnote 20, and what the footnote is on page –
A I am sorry. I am not quite sure what the relevance of a publication in 2005 is to clinical decisions that were being made in 1996 by someone who is not a co-author of this publication and who has published separate information about what his views are on the likely symptoms and signs of patients with inflammatory bowel disease.

Q First of all, are you suggesting that the signs and symptoms that would warrant intervention by colonoscopy have changed drastically since 1996?
A No. I am just pointing out that there are differences between Professor Walker-Smith’s view on this matter – and he was, after all, the consultant who was admitting these patients – and what is defined here. There are differences. That is all I am pointing out, and you may prefer towards the view in this publication that was published nearly ten years later.

Q You have just ---
A I am just pointing out that there was a publication by Professor Walker-Smith that may be more relevant.

Q First of all, you know I represent Professor Murch. Secondly, I have just asked you whether or not the indications for colonoscopy have changed significantly since 1996, and you told me no. Forgive me, but I am going to press you with what is contained in this article. If we look at footnote 20, I think it is referring to the paper of Sawczenko and Sandhu. Would that be right?
A Yes.

Q If we go back to what it says about that paper on page 52, in the middle of the page, on the right hand side:

“In this study,”

that is the Sawczenko and Sandhu study –

“the ‘classic triad’ of CD [Crohn disease] symptoms (abdominal pain, diarrhea and weight loss) was present in a minority (25%) of CD [Crohn disease] patients.”

In other words, 75 per cent of those children did not have all three symptoms. That is what it means?
A Yes.

Q And that would fit, would it not, with recognised clinical experience by the mid-nineties?
A That was the experience from a register that was carried out in the UK, yes. If you are saying, “Is this an observation that is not recognised”, I would have to say as I have already said, that an insidious, non-specific presentation of inflammatory bowel disease is well recognised, as we have already discussed.

Q Indeed. And it goes on to say:

“Many young CD [Crohn disease] patients present in a ‘non-classic manner’ with vague complaints of malaise or mild abdominal discomfort.”

Do you agree with that?
A Yes.

Q And that would have been the position by the mid-nineties, would it not?
A Yes. In general, yes.

Q It goes on to say:

“Other symptoms may be fever, growth retardation, malnutrition, nausea and/or vomiting, psychiatric symptoms, arthropathy, erythema nodosum, secondary amenorrhea, retardation of pubertal development or perianal disease.”

Do you agree?
A Yes.

Q And this goes back to the point that the presentation of inflammatory bowel disease symptoms can be quite variable?
A Yes, that is well recognised.

Q If we then move on to whether or not to perform a colonoscopy, we turn the page. You rely on laboratory examination by blood tests because it is your proposition that other than in a barn door case you need the screening tests, if I understand your opinion correctly.
A No. I do not think that is quite right. All I am saying is that in a situation where presentation can be subtle, insidious and non-specific, before exposing a patient to an invasive investigation it is appropriate to get as much useful information as possible before coming to that decision; in other words, I am just agreeing with the sentiment in the Beattie Murch and Walker-Smith publication of 1995.

Q I think you accept that, particularly even in subtle cases, the inflammatory markers may well not be raised in the blood test?
A Not always. As we have said, that is in the nature of a screening test.

Q Yes. So therefore it follows that when one is considering whether or not there is inflammatory bowel disease, a negative blood test is not going to alter one’s clinical suspicion, is it?
A I think that is a matter for clinical judgment. It comes back to the issue that we were talking about before, that certain symptoms have different impacts on your views about the likely diagnosis. So that, for example, perianal disease is mentioned in this list which, if you saw it in a patient with abdominal pain, would make you feel that the diagnosis of Crohn's disease was very likely, compared with a patient who had abdominal pain, but no other findings; you would be somewhat sceptical about inflammatory bowel disease as the most likely explanation. I am just saying that there are almost an infinite number of combinations of the symptoms that are on this list and to just say that anybody with abdominal pain should have a colonoscopy, for example, would not be right.

Q But that is not the situation in the cases we have been looking at. What has been put to you – and I will come back to the individual cases in due course – is that a clinical judgment was being exercised. It may well be a judgment you yourself would not share but it was a clinical judgment that inflammatory bowel disease was suspected.
A I find it difficult to understand why a group of investigators publish a paper pointing out the value of measuring inflammatory markers in 1995, pointing out that they are often useful in deciding whether or not a patient should or should not be considered for colonoscopy and twelve months later they seem to have changed their practice in relation to doing them, before considering whether or not a patient should have a colonoscopy.

Q But the gist of the advice given in that Beattie paper to which you have referred is that positive blood tests, as in raised inflammatory markers, screen inpatients for colonoscopy. It is not saying negative results screen them out, and that, I think, must follow from your opinion that blood tests themselves are not diagnostic because if they were, there would be no need for colonoscopy in any case?
A It is in the nature of a screening test. It points out that when all the results are normal, then chronic inflammatory bowel disease is an unlikely diagnosis. No one is saying that it is ruled out completely, but it would seem wise, when we all acknowledge that the diagnosis of inflammatory bowel disease can be difficult because it presents insidiously and subtly, in a variety of ways, not to get as much helpful if as possible before you make a judgment about whether the patient should or should not have a colonoscopy.

Q Let us just look at what they say in the main text about colonoscopy. We are on page 53 still, on the right hand side. It says:

“Colonoscopy including intubation of the terminal ileum and multiple biopsies for histology obtained from all segments of the lower intestinal tract…”

and it lists the places –

“is essential; it is the most important investigation to differentiate between CD [Crohn disease] and ulcerative colitis and identifies localization and extent of inflammatory disease.”

It is pretty strong language, is it not, when it uses the phrase “essential”?
A It is strong language, yes.

Q Would you agree with it?
A I am not disputing that colonoscopy is an essential investigation in the diagnosis of inflammatory bowel disease.

Q Do you agree that it is important to differentiate between Crohn's disease and ulcerative colitis?
A Wherever possible, yes, recognising that in some cases you cannot, and probably about 10 per cent that you diagnose as ulcerative colitis turn out to have Crohn's. But it is important to make that differentiation.

Q And important for the future management and treatment of patients?
A Yes.

Q The text goes on to say:

“Intubation of the terminal ileum with terminal ileum biopsies should always be attempted, as isolated ileal inflammation may occur in the presence of a normal colon in up to 9% of children with Crohn's disease.”

Do you agree with that observation?
A Yes.

Q In other words, the rationale is that you might not find the inflammatory bowel disease unless you reach the terminal ileum.
A Yes, you may not.

Q It then in the next paragraph goes on to deal with upper endoscopy, and I think I can deal with that briefly. It says it is:

“… advocated in all children irrespective of presence or absence of upper [GI] symptoms.”

It then goes on to deal with the histology of the upper GI tract:

“… may confirm a diagnosis of Crohn's disease that would otherwise have been missed in 11% to 29% of cases …”.

Do you agree with those observations?
A Yes. It is our practice to routinely carry out upper GI endoscopy and has been for quite some time, which is at variance with the practice with some of the patients we have been looking at in this hearing.

Q If you go to page 54, the left-hand column, half-way down, the section “Radiology”, it says:

“The finding of a normal terminal ileum on ileoscopy does not render radiologic examination of the small bowel obsolete. The small bowel may be abnormal even though the terminal ileum is normal … In addition, small bowel follow through … will give information on extent and possible complications of small bowel involvement in Crohn's disease including stenosis, stricture or internal fistulae.”

Do you agree with that?
A Yes, absolutely.

MR HOPKINS: Professor, that completes the review of the literature.

Sir, I note the time. My next task is to embark on the individual patients, and I know you have had a morning and a bit of that already, and quite frankly I am loath to go down that route unless I am pressed to.

THE CHAIRMAN: Thank you. No, I am sure that is the right course to adopt at this stage. It is now four o'clock. To start on something totally new and start going through the children again would probably not be the ideal situation at this stage, either for the Panel or for Professor Booth.

MR HOPKINS: Of course.

THE CHAIRMAN: So we will now adjourn, but can I ask you, Mr Hopkins, and also Ms Smith, the plans for the next two days. You are obviously in the middle of cross-examination at this stage.

MR HOPKINS: Sir, I can indicate that I will certainly – nothing is ever certain in this world, but I would hope to finish tomorrow morning, and significantly before lunch.

THE CHAIRMAN: Then of course there would be re-examination and then the Panel’s questions.

MS SMITH: Sir, I do not anticipate re-examination being very long, but I may have a few questions. It seemed to me that it was not appropriate to try and change Professor Lachmann’s slot of first thing on Friday morning, given the uncertainties about what time we will finish tomorrow. I believe he will be a short witness. It is a fatal thing to say, but I do believe he will, so it seemed to me best to leave him until Friday morning.

THE CHAIRMAN: I am sure that is a very wise approach. I think that is as far as we can go today. We will now adjourn, and resume at 9.30 tomorrow morning.
(To the witness) Professor Booth, again you are still under oath and still in the middle of cross-examination, so please do not speak to anyone, including any of the lawyers.

(The Panel adjourned to 9.30 a.m. on Thursday 18 October 2007)

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