Monday, February 6, 2012

Day 46 GMC Fitness to Practice hearing for Andrew Wakefield



Thursday 18 October 2007

Regents Place, 350 Euston Road, London NW1 3JN

Chairman: Dr Surendra Kumar, MB BS FRCGP

Panel Members: Mrs Sylvia Dean
Ms Wendy Golding
Dr Parimala Moodley
Dr Stephen Webster

Legal Assessor: Mr Nigel Seed QC


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


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


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.


Page No


Cross-examined by MR HOPKINS, continued 1

THE CHAIRMAN: Good morning, everyone. Before we begin this morning. For the benefit of the transcript as well as for everybody else who is present here, I am not feeling very well this morning. I do not think that I will be able to sit for the whole day. We will see how things progress during the day. My apologies for causing any inconvenience to anyone who is here. Mr Hopkins?

MR HOPKINS: Sir, thank you for that indication and no doubt, if you feel the need to break, you will let us all know.

THE CHAIRMAN: I have all my medication here with me.

Cross-examined by MR HOPKINS, continued

Q Professor Booth, I want to turn to the individuals colonoscoped by Dr Murch as he then was. You have already debated whether Professor Walker-Smith was justified in requesting these procedures to be carried out when he saw the patients in outpatients and I will not revisit that debate. You know that I am adopting the questioning you have had by Mr Miller. In order that we make the position clear, it is Professor Murch’s position that he primarily relied on the judgment of Professor Walker-Smith on the need for colonoscopy in all the patients where he saw them – there is only one patient where he did not and that is Child 4 – but what I want to do is to look at the additional factors that would have been available to Professor Murch. So, the clinical information that Professor Walker-Smith had obtained in outpatients, the fact that Professor Walker-Smith was expressing his judgment that a colonoscopy was needed and any additional clinical information after that outpatient assessment. So, I think you understand the process I am about to go through.
A Yes.

Q May we have a look, please, at Child 2 and for that you will need the Royal Free Hospital notes for Child 2. Would you turn to page 25. You will recall that this was the child who was seen back in 1995 at Bart’s. If we look halfway down the page to see what history was being obtained then by Professor Walker-Smith in August 1995, we see that the child was recorded as beginning to have diarrhoea at 18 months of age and that the child had had diarrhoea ever since.
A Yes.

Q If we look a few lines below that about two thirds of the way down, in deciphering the handwriting I think we can make out that it records that there has been lots of pain, five to six stools a day, lots of mucous and occasional blood.
A Yes.

Q The position as of August 1995 is that there is a history of diarrhoea, mucous and occasional blood. I think you would agree from what you said before that the presence of mucous and blood can be caused by IBD.
A Yes, it can be. I think that, as you have said, if Professor Murch was relying on Professor Walker-Smith’s opinion at this stage, Professor Walker-Smith clearly expressed a view that he thought this was not likely to be inflammatory bowel disease; he used the term “no evidence of Crohn’s disease” and suggested that the diagnosis was multiple food allergy or irritable bowel syndrome.

Q Of course, his opinion was not crystallised at this point; this is simply part of the factual background; his opinion moves on, as we know, into the next year.
A He expressed that view in August 1995 in an outpatient letter.

Q I understand that. The point I am putting to you however is that things move on by the middle of 1996, but we are looking at the clinical information that is available and here we have a history of diarrhoea from the age of 18 months, lots of mucous and occasional blood.
A Yes.

Q I think you would accept that those features would raise the prospect of inflammatory bowel disease, IBD.
A Yes, you would certainly consider it.

Q May we move on to 1996 and just remind ourselves. There was an outpatient assessment on 21 June at page 28 where he records one third of the way down,

“After seen last had diarrhoea, weight loss, very ill”.

In other words, a worsening of this child’s condition.
A Well, as we have discussed before – I am not clear to what extent you want to reheat the discussions we have already had – it is not clear from that whether that severe illness was some sort of inter-current infection or whether it continued. It does say in the next line that Child 2 saw Dr Hunter and went on to an exclusion diet.

Q Indeed and I think your point is, as I understood what you said yesterday, that there may indeed be a food allergy in this child.
A That, I think, was the view of Dr Hunter, yes, and also Professor Walker-Smith’s view when he first saw the patient.

Q I think you would accept that a food allergy can co-exist with IBD, would you not?
A Well … It is possible.

Q Indeed, it is quite common for patients with IBD to have food intolerance, is it not?
A You mean that they respond to specific foods?

Q Yes.
A Food exclusion diets are not currently recommended as mainstream management for inflammatory bowel disease. We know that liquid diets work but we do not know whether they work on the basis of excluding antigens or not.

Q That is not the point I was making. Patients with IBD can have food intolerance and that is quite common, is it not?
A It is no more common than in the general population.

Q It is clear when we look at the correspondence, if we go, for example, to page 160 when Professor Walker-Smith is writing to the GP on 24 June 1996, that although he still thinks Crohn’s disease itself is unlikely, his thought process is that there may be some other inflammation.
A Yes, that is what he states.

Q That therefore was the snapshot of his view by June 1996. We know that the child is subsequently admitted following that letter to the GP, but more information then becomes available and would have been available to Professor Murch. Would you look at page 155 which is a letter from Dr Hunter to whom you have just made reference, a consultant physician, writing on 3 July 1996 to Professor Walker-Smith and, if we look on page 156 at the penultimate paragraph, he refers to blood tests that have been carried out at Addenbrooke’s and then gives the various indices that have come back and he points out that the ESR was raised at 40.
A Yes.

Q This represents a raised inflammatory marker, does it not?
A Yes, it does.

Q Therefore, in effect, screening blood tests have been carried out and an index has come back which is raised which raises the suspicion of IBD, does it not?
A Yes. In his letter, Dr Hunter also says that he would have been reluctant to do a colonoscopy.

Q That may have been his personal view, but the point I am putting to you is that that raised inflammatory marker raises the suspicion of IBD and I think you accept that proposition.
A It would certainly be worth repeating it before proceeding, yes.

Q Well, not simply repeating it. If you get an abnormal result, you are not suggesting that, for screening tests, you need to keep repeating them, are you?
A No, but an ESR can go up for a minor inter-current infection. We do not know what this patient’s clinical status was when he had that blood test taken when either Professor Walker-Smith or Professor Murch were there.

Q Dr Hunter is not saying, “Be cautious about this because he had an inter-current illness”, is he? He is pointing out that these are the results of the blood test.
A He is giving the results of the blood test, sure.

Q We then move on to this child’s admission and the notes start at page 15 and run through to page 18. We know that the child comes in on 2 September, he is clerked in by Dr Casson – and I think I can take this shortly as we have looked at the notes – and Dr Casson in effect confirms the history of diarrhoea dating back to an early age with intermittent weight loss, abdominal pain and, since the age of 20 months, diarrhoea starting at that point with “mucous++” but says “only one episode of blood”.

“At 3 yr → sudden onset of weight loss, [very] pale, ill, miserable, lethargic, [increasing] frequency of diarrhoea”.

All those would be features of IBD, would they not?
A Yes, if the weight loss was persistent but I am not clear whether this was a persistent weight loss. It is not unusual to have a transient episode of weight loss during some inter-current illness.

Q I think that you have established in your answers to questions from Mr Miller yesterday that IBD signs and symptoms wax and wane, do they not?
A Yes, they can do.

Q If we move on to what he is saying about 4 years of age on page 16, he picks up the story and goes over to the top of page 17, and he is saying that there was a similar episode at four years of age with “diarrhoea/lethargy/weight loss/loss of skills”, and that is right, is it not?
A Yes.

Q If we go to the bottom of the page, we can see that there is a reference to the food intolerance concern of the mother and, if we go to the top of the page, we see that the child is recorded as having been referred to Professor Warner at Southampton. Are you aware of Professor Warner?
A Yes.

Q Can you tell us who he is, please.
A He was at that time Professor of Paediatrics in Southampton.

Q We see in brackets that it says “allergies” and then “didn’t find any allergies” and would you take that note to mean that this child had been investigated for food allergy and that none had been found?
A At that time, yes, at that age.

Q He was four.
A Yes.

Q Then the note goes on two thirds of the way down page 17,

“Presently → has ‘episodes’ every [18 months]. Last in April. Lasted up to [three weeks]”.

There is reference to

“jaundice + pale stool.
Poor sleep. [increasing] diarrhoea. Screaming.”

There is also a reference towards the bottom of the page to the exclusion diet – and I think that you yourself place weight on this – where we can see in the last few lines on page 17 that it suggests that the exclusion diet which started in April of that year “seems to have eased the [abdominal] pain”.
A Yes. That was Dr Hunter’s view as well. He stated that the bowel symptoms had improved as well.

Q We need to be careful about our choice of words here. It is not saying that the pain had gone away altogether, it is simply saying that it had eased. Would you agree with that?
A It depends what you mean by “improved”.

Q I am looking at the phrase that is being used at the bottom of the page in the last couple of lines,

“Started April ’96 → seems to have eased abdo pain”.

The history that Dr Casson was getting was that although the pain had been alleviated, it had not gone. That was a fair interpretation of that note.
A It is saying “Presently → has ‘episodes’ …” It does not say that that includes abdominal pain.

Q If you look at the very last two lines, there is a clear reference to abdominal pain and, although the abdominal pain is described as having been eased, the plain meaning of that is that there is still abdominal pain going on but not as severe as before; do you accept that?
A You could put that interpretation on it, yes.

Q This clerking note would confirm the history that Professor Walker-Smith had elicited earlier in the year and a continuation of diarrhoea and abdominal pain, albeit that that abdominal pain had eased.
A The patient’s symptoms seemed to have improved since the patient saw Professor Walker-Smith. The nature of the symptoms does not seem to have changed at all. Professor Walker-Smith came to a view that this patient probably did not have inflammatory bowel disease and probably had multiple food intolerances or irritable bowel syndrome based on the symptoms that he elicited which you are saying continued. So, I do not see any substantial difference in this patient’s symptoms between 1996 and 1995 other than that there is quite good evidence that they had improved.

Q What I am going to do is run through with you the list of symptoms that this review of the documents has elicited and I am prefacing this by suggesting to you that it was reasonable for Dr Murch to act on Professor Walker-Smith’s request for colonoscopy. The symptoms that had been elicited that I suggest raised a suspicion of IBD were a combination of these: recurrent diarrhoea, abdominal pain, a history of occasional blood in the past, mucous, weight loss, lethargy and a raised inflammatory marker. Those were all features, were they not, of this child’s history and presenting condition?
A Yes.

Q In terms of what is a classic triad for symptoms of Crohn's disease, that classic triad is abdominal pain, diarrhoea and weight loss, is it not?
A Yes.

Q In addition therefore to that classic triad which clearly this child had, there were other symptoms that would support a suspicion of IBD, such as the lethargy, such as the mucus, such as the raised inflammatory marker. Would you agree?
A Yes.

Q Therefore in these circumstances the child would fall within the Porto Criteria because there would have been a suspicion of IBD.
A I think it is important that I make my position clear on the Porto Criteria, which I think as a basis for making detailed decisions on specific patients I could not endorse. I agree that this patient exhibited symptoms where you might raise a suspicion of inflammatory bowel disease; that was clearly in Professor Walker-Smith’s mind, otherwise he would not have said he did not think that this patient had inflammatory bowel disease.

Yesterday you took me in the document to a number of specific recommendations that were included in the Porto Criteria, for example would I agree that upper gastrointestinal endoscopy was appropriate, and I said yes; would I agree that colonoscopy was an important component of the investigation of inflammatory bowel disease, and I agreed with you. You took me to a publication that was cited there that had evidence from a UK inflammatory bowel disease registry, and asked me if I agreed with what it stated about the findings, and I said yes. But I did express major reservations about accepting a mere symptom list as the sole basis for suspecting inflammatory bowel disease. The symptoms that were listed in that publication that you took me to were certainly not new, and had first been published over 40 years ago. So I think that the symptoms, if you are going to say because they are listed in the Porto Criteria are the gold standard for recommending that a patient has a colonoscopy or does not have a colonoscopy, are not valid. I do not think that a list, unweighted for the relative importance of each symptom, either singly or in combination, is an inherently sound way of identifying how to investigate a specific patient.

Q Professor Booth, do you accept that this child would fall within the Porto Criteria for carrying out a colonoscopy?
A I do not quite understand what the Porto Criteria are, and I do not accept that the Porto Criteria represent a valid basis for making decisions on individual children.

Q What was the point ---
A I would accept that if you have a patient with abdominal pain, diarrhoea and persistent weight loss, of course you would suspect inflammatory bowel disease; but if you are going to suggest to me that you just go down a tick list, and every time you see a symptom that is listed in that list you therefore put the patient forward for a colonoscopy, I could not accept that.

Q I think you accepted when you answered questions by Mr Miller that the whole point of the Porto Criteria was for practitioners who were expert in this field to share what was common working practice and knowledge, to put forward guidelines for the benefit of practitioners in this field. That was the whole aim of the process, was it not?
A The aim of the process, as I understand it, was to provide some guidance for people who may not be familiar with inflammatory bowel disease about how these patients might be identified and investigated. If you are suggesting to me that when any of the four experienced paediatric gastroenterologists in this room read the Porto Criteria they would suddenly say “My goodness, I didn’t realise that weight loss was possibly associated with inflammatory bowel disease”, I could not possibly accept that. The recommendations there I assume are aimed at practitioners who do not have a detailed knowledge of inflammatory bowel disease; they are not aimed for tertiary level specialists, as I understand it, who I assume would understand what the symptoms of inflammatory bowel disease are.

Q The whole point of this was, was it not, to give guidelines to the profession as to when colonoscopy for example should be carried out? It is plain from the documents.
A What I am saying is that I cannot endorse a mere list as published in the guideline. If it was just very simple, and you had for example a list of symptoms that were just the basis for deciding on that basis alone whether a patient should have a colonoscopy or not, then we could avoid training doctors and sub-specialists.

Q Professor, you are taking the argument, I am afraid, to an extreme ---
A No, I am not ---

Q --- in suggesting a check list without any clinical judgement.
A No, I am not. If you just have a list of symptoms and you use that in an unweighted way for making clinically important decisions, you will make clinically wrong decisions. There was no sensitivity analysis in the list of symptoms that were presented there. If, for example, you were to look at Professor Walker-Smith’s bundle in a publication that is at tab 5, you would see that in his analysis of a large number of children undergoing colonoscopy in his hospital some years ago, he looked at the sensitivity of different types of symptoms in whether or not that patient was going to have a positive result from the colonoscopy. So there were over 190 children who formed part of the analysis, and when abdominal pain only, just as an example, was the indication for carrying out the endoscopy, the number of children who had an abnormality was zero per cent. If you just look at children who had a colonoscopy because they only had diarrhoea, the clinical yield was only 11 per cent. If you put abdominal pain and diarrhoea together it is still only 21 per cent in his analysis.

I agree entirely that if you are looking at abdominal pain and weight loss you get a much higher clinical yield. So the lack of sensitivity in the analysis calls very much into question the validity of the Porto Criteria as a guideline because, as I say, a symptom list is largely meaningless. If you actually examine the scientific methods and the scientific rigour that went into the publication known as the Porto guideline you would find that it falls substantially short of current best practice when it comes to publication of clinical guidelines, because it is not evidence based.

Q Professor, I have allowed you a little time to develop your argument, and now I will bring you back to Child 2, but I sense from what you are saying that you are now trying to distance yourself from their Porto Criteria and their relevance. I am afraid I must put it to you that the reason you are doing that is you realise it is undermining a significant amount of the evidence that you have given to this Panel.
A No, I am trying to present a balanced view of the Porto Criteria. The Porto Criteria as published in the journal could not be published in many publications at the moment; they would not be acceptable as a guideline, for example, by the British Society of Gastroenterology.

Q These Porto Criteria were aimed at practitioners including those in the tertiary level, were they not?
A I could not say. I would be very surprised if any tertiary level practitioner was not aware that abdominal pain or weight loss or diarrhoea or any of the other symptoms were features of inflammatory bowel disease, given that they were first published over 40 years ago.

Q Let us not descend into that type of trivial argument. What I am suggesting to you
is ---
A I do not think it is a trivial argument, Mr Hopkins. You are taking me to a publication, the scientific basis and rigour of which I am not accepting. It is not an evidence-based guideline. The reason ---

Q You have been taken at length, Professor Booth, through the background to this paper. Let us turn to it, just to remind you what the position is, so we will go to D5. If we look at the title at page 51, “Medical Position Paper”, we will see it says a few lines down:

“IBD Working Group of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition”.

That is a respected European society, is it not?
A It is a respected European society. The criteria for membership – if you call it membership – of the IBD working group, as far as I am aware, is that people just turn up to the meetings. There are no criteria that are expressed in this publication about what the qualifications are of the people present at the meetings and listed at the end of the publication, for actually expressing this view.

Q Can we turn to page 57. You have been taken to the list of names there, and I would like you to look at it again. Are you suggesting that any of these contributors to these criteria as listed there were in any way non-expert in this field?
A That is not the issue. I would not dispute ---

Q Will you please answer my question.
A I would not dispute that they were expert, but this publication has been produced by a methodology that is no longer found to be scientifically credible.

Q Let us just be clear what you are saying, and I want to put this proposition to you: a group of experts in this field, internationally recognised as experts, have come together to pool their experience and put forward guidelines for investigation of children suspected of IBD. That is the situation with this paper, is it not?
A That is the situation of this paper, but the production of guidelines has gone through an evolutionary process over the last 30 or 40 years. If you go back 30 years you find the sort of single- or double-author publications that we were looking at yesterday, where one or two people sit down, look at the literature and use a combination of their clinical experience and their views on the literature to produce some statements about clinical management. The process then went through what is known as the ‘GOBSAT’ process, which stands for ‘good old boys sat at a table’, and that is what this process represents. It represents people coming together and deciding what they think is best.

The reasons why that process has fallen into disrepute – and it fell into disrepute many years ago – the reason why it has fallen into disrepute is that you get a number of people on a group like that who may be particularly forceful in imposing their views on the rest of the group. You also get people taking part in that group who push forward their own publications, so that if, for example, you look at the section in this publication on patient history you find that there is a substantial piece of writing there on patient history for which there is only one publication. If you look at the authors of the publication at reference 20 you find that they are Sawczenko and Sandhu. If you then look at the list of people taking part you find at the bottom of the list it is Sandhu and Sawczenko. So I would put to you that under patient history there is far more information available in the scientific literature than just one publication from Sandhu and Sawczenko. So what happens ---

Q I would disagree with that, Professor. Yesterday you ---
A What happens now is that there is a scientifically valid way of producing guidelines which the Porto Criteria people have not followed. It involves making it very clear in your publication what the aims are, and how you have researched the literature, and what research criteria you have used, so that it can be clear to everybody which publications you are looking at. Then there is a sifting process that is carried out by experts in looking at the quality of certain publications that come out of the search. Then the publications are graded for their quality, so that everyone can be clear about what the evidence that goes into the guidelines actually is. That process has not been followed here. All I am saying is that the Porto Criteria are scientifically invalid and clinically naïve.

Q There were no internationally recognised guidelines prior to the Porto Criteria, were there?
A That does not make the Porto Criteria any better than they are.

Q Will you answer my question, Professor Booth. There were none before, were there?
A I could not say. It depends on what you regard as a guideline. There were plenty of publications from experts like Professor Walker-Smith, for example ---

Q Let us just deal with the question I am asking you. There were no, that you can point to, international guidelines before the Porto Criteria?
A That is correct, as far as I am aware.

Q In your preparation of the case you have made reference and cross-reference to texts and articles by individuals or a group of a few practitioners; that is right, is it not?
A I have made reference to, for example, original pieces of work relating to screening blood tests, for example, but that is not the same as a multi-author review.

Q When we went through the Porto Criteria yesterday I took you to “Patient History” on page 52, and I put the various propositions there. You agreed with each of them, did you not?
A I agreed with specific points related to your questions about colonoscopy and upper GI endoscopy. I agreed with you ---

Q I am asking you about the patient history; let us focus on that.
A I agreed with you on the content of reference 20, which is the sole publication cited in this document relating to patient history, whereas in fact I would suspect there are probably 40 or 50 studies that could have been cited – but they chose this particular one. I am not arguing within the context of how this study was done; all I am saying is that people who take part in this get their own publications cited. That is why it is invalid.

Q Professor, can I bring you back to the point. The point I am putting to you is that the propositions set out under “Patient History” you have previously agreed with.
A I have not agreed ---

Q If need be we will look at the transcript.
A Let me make it clear: I have not agreed that a simple list of symptoms on its own without any weighting or sensitivity analysis is a valid method of deciding who should have a colonoscopy. For the reasons I have just pointed out to you from Professor Walker-Smith’s study, different symptoms yield different clinical yields.

Q Let us go back to Child 2. We have had a wide-ranging debate about the Porto Criteria; let us go back to Child 2. I have put to you a whole list of symptoms in this child’s history. You have agreed that abdominal pain, diarrhoea and weight loss are the classic triad for Crohn's disease; you have agreed that he had additional symptoms that would be supportive of IBD – such as mucus, lethargy and a raised inflammatory marker. Do you accept that IBD should have been within the differential diagnosis for this child?
A The problem I am struggling with at the moment, Mr Hopkins, is that you told me Professor Murch accepts absolutely Professor Walker-Smith’s analysis of this patient. Professor Walker-Smith has said he does not think this patient has Crohn's disease, he thinks he has multiple food allergy ---

Q I am not asking you ---
A --- or irritable bowel syndrome.

Q I am stopping you, Professor Booth. I am not asking you about Professor
Walker-Smith’s opinion, I am asking for your opinion. Do you agree that this child, with those symptoms, could properly be said to have a differential diagnosis of IBD?
A It would be included in the differential diagnosis, yes.

Q Thank you. Therefore, because it was in the differential diagnosis, I suggest it was reasonable to carry out a colonoscopy.
A Not without previous investigations, no. Not every patient who has gastrointestinal symptoms has inflammatory bowel disease.

Q Can we look, please, at page 263A in the Royal Free notes. This may have been a document that was not available to you when you wrote your report. This represents a two-page document, does it not, where it is a request for histology to be carried out on specimens taken during the colonoscopy procedure?
A It is normally completed after the colonoscopy procedure.

Q Indeed – once the samples have been taken. If we look at the box entitled “Clinical Details”, it there sets out, does it not, some background information by those carrying out the procedure for the benefit of the histology department?
A Yes, it does.

Q We see they have listed there:

Diarrhoea – intermittent – x many years
3 x obstructive jaundice episodes”

Then they have said this:


That would stand for impression would it not?
A That is correct, yes.

Q “? Crohn's disease”
A Yes.

Q That would be therefore suggesting that the people filling out this form suspected IBD – just as a simple matter of fact. Were they right or wrong, that is what it is indicating. Would you agree?
A I think I would need to go and see what the colonoscopy report said.

Q Let us just leave that aside for a moment.
A Well, this was ---

Q On the face of this document do you agree that it is communicating a suspicion of IBD?
A It is communicating a suspicion of IBD after the colonoscopy has been carried out.

Q Is that right, Professor? Because this is setting out, is it not, the background clinical details.
A Normally what happens in my unit is that you fill out the histopathology form after you have carried out the investigation because normally what you would do is indicate in the histopathology form what the macroscopic findings were in order to help histopathologists in arriving at a diagnosis. This must have been carried out after the colonoscopy had been performed because the colonoscopists could not possibly have known before the colonoscopy took place that they were going to take specimens from (one) terminal ileum, (two) caecum, (three) ascending colon and so on.

Q I am not suggesting that the time of when it was filled out is different. What I am suggesting is that the clinical information that is being put down is the basis for “? IBD”?
A The impression “? Crohn's disease” will be informed by both the history and the colonoscopic findings, and there is clear evidence that this was filled out after the colonoscopy.

Q I am not suggesting otherwise. You have been taken through the histopathology report. You have been asked for your observations on that. I think you accept that inflammatory changes were identified?
A Yes.

Q That being so – and I am not using this as a justification for this procedure – but that being so, with findings of inflammation it would be reinforcing, would it not, or it would be reasonable for it to be reinforcing in Dr Murch’s mind that there was confidence in Professor Walker-Smith’s clinical acumen in thinking there might be inflammatory changes in this child?
A I think you could draw the converse conclusion; Professor Walker-Smith has made a clear statement he did not think this patient had got Crohn's disease.

Q We have seen the correspondence in June 1996 which led Professor Walker-Smith to arrange for this child to be admitted for colonoscopy. It is quite clear from that, as we have looked, that he was suggesting there may well be inflammatory changes in the bowel. What I am suggesting to you is, the actual finding of inflammatory changes in the child’s bowel would reinforce Dr Murch’s confidence in Professor Walker-Smith’s clinical acumen. Do you accept that?
A I do not know. Professor Walker-Smith in August 1995 put in a letter to Dr Wozencroft, “No evidence of Crohn's disease”.

Q Let me move to a different topic that related to this child. By Ms Smith, you were asked about mitochondrial disorders and lumbar punctures?
A Yes.

Q In dealing with that – and for the Panel’s reference it is the transcript on Day 40/28G-29C – you said this:

“[A] I think the tests that were going to be done on the CSF were not relevant, in the research ethical committee application, to the diagnosis of the mitochondrial disorder anyway.”

You went on to say:

“I think the paper was looking for CSF antibody and cytokine profiles, which would not be relevant to a mitochondrial disorder.”

A Yes.

Q If I understand the evidence that you gave there, what you are saying is, the 172/96 paper, where it lists CSF antibody and cytokine profiles, would not help in working out whether a child had a mitochondrial disorder?
A Yes.

Q Just so the Panel is not misled or given the wrong impression about lumbar punctures in these cases, the fact is the CSF was not being examined solely for CSF antibodies and cytokine profiles, were they?
A That is correct.

Q We can see that by looking at Child 2. Can we go, please, to page 18. This is still under the previous page we have looked at, which was 2 September. On page 18 we see, quarter of the way down “WR”, which presumably will stand for “ward round”. Then, half-way down, we see a reference to “LP”. Then there is a line going to CSF. Then, from the CSF, there are various lines going out which, of course, includes measles and cytokines, but it also includes lactate, pyruvate and glucose, does it not?
A Yes.

Q The testing of lactate and pyruvate would be relevant to testing for a mitochondrial disorder, would it not?
A If you thought this patient had a mitochondrial disorder.

Q Yes, or might potentially have one.
A Yes, although it is relevant here that this patient had recently seen, according to the note at the top of that page, Dr Robert Surtees at Great Ormond Street who, as it indicates here, is an expert in neurometabolic disease.

Q Indeed. And the Panel knows, and has seen, attempts to contact him, and the fax that has come back. These tests, the lactate, pyruvate, glucose, were not listed, were they, in the 172/96 application?
A That is correct.

Q I need not take you to it, but just for the Panel’s reference – and I will put the question in a moment, but just for the Panel’s reference, CSF lactate is referred to in most of the other children. May I give you a list, rather than wasting time going to each one? For Child 1, Royal Free bundles, pages 12 and 15. Child 2 we have just looked at. Child 3, Royal Free notes, pages 15 and 16. In Child 4 there was no LP. In Child 5, Royal Free, page 7. In Child 6, Royal Free, pages 39 and 42. In Child 7, the only reference we can find is to glucose, which is Royal Free, page 10 – CSF testing. Child 8 there was no LP. Child 9, Royal Free, pages 62 and 13. Child 10, Royal Free, page 64 and in Child 12, Royal Free at page 104, where it mentions glucose and protein.

Professor, just going back to Child 2, can we also please look at page 22, where we see, do we not, a whole list of investigations that were to be carried out on this child?
A Yes, that is right.

Q I just want to highlight some of them that did not feature in the 172/96 protocol. The very first one: white cell enzymes was not a feature of the protocol, was it?
A I cannot remember, but I am prepared to accept your assertion.

Q Then if we go five lines down – I will probably mispronounce this – paroxysmal function tests. They did not feature, did they, in the 172/96?
A I honestly cannot remember without going back, but I accept that you are correct.

Q Then, two lines down, carotene profile – that did not feature?
A Yes.

Q The next one, blood lead, did not feature. The next one, copper, did not feature and then the next two relating to the CSF, those two did not feature; organic acids did not feature, nor did the AFP. So it would seem there is a whole battery of investigations being carried out on Child 2 that just were not part and parcel of 172/96. Will you accept that?
A Yes.

Q That is the end of Child 2. We move on, please, to Child 1 and you will need the Royal Free notes. Could we turn, please, to page 13? Again, I will take it shortly, if I may, on this. This was Professor Walker-Smith’s outpatient assessment in June 1996. The Panel has looked as this now quite a few times. I will just pick out a few things. Professor Walker-Smith established, did he not, that the child had undigested food in the stools, and had no control over bowel motions; has had blood occasionally in the stools?
A Yes.

Q He carried out an abdominal examination, which is referred to, I think, on the next page, page 14. He recorded that he found no abnormality. Would you expect that abdominal examination in part to be performed to see if there was any evidence of faecal loading or constipation?
A Yes.

Q We then know the child writes to the GP at page 54, saying the child has features of toddler’s diarrhoea. We know that a screening blood test was done. Can we turn to page 97, we find a list of various tests, but it is the first dated column of 25 June. The haemoglobin was sat 10.8, which would have been abnormal, because it was below the range of 11.5-14.5 – would you agree?
A It depends why you are doing it. The cut-off in the publication was 10.

Q But that is below the normal laboratory range, is it not, in this laboratory?
A This patient was three. I cannot just remember what the lower limit was. I think it may have been 11 in this laboratory.

Q It was 11.5.
A So it is below their normal range, but above the cut-off in the screening test publication.

Q Can we just consider what the potential cause of a lower haemoglobin can be? I do not think there is any controversy about this: it could be due to inadequate iron intake, so lack of iron in the diet?
A Yes, that is possible. Yes.

Q It could be due to poor absorption of iron in the gut?
A Yes – much less common.

Q Or it could be blood loss in the stools?
A If there was a lot of blood loss, yes.

Q Then, if we turn on to see what information was then available on admission, the admission note is at pages 9-10. Again, I think I can run through this fairly quickly as we have looked at this in detail quite a few times. In this child, the history of diarrhoea was confirmed. It was said to start around the age of 18 months, five times daily; watery with no blood or mucous. It was now occurring seven times a day, so that would represent, would it not, a slight worsening of the position as far as the diarrhoea is concerned?
A Yes. Toddler diarrhoea often waxes and wanes.

Q Referred to as having no bowel control, no blood but query occasional mucous; a small, picky appetite; occasional vomiting. That can be a sign of IBD, can it not?
A Yes. If the patient has, for example, an intestinal stricture, then they can vomit, yes. You see it in patients with severe inflammatory bowel disease certainly.

Q And there is then a reference to one episode of bleeding fresh red blood. That could, of course, be a reference to a lower GI bleed. That is possible, is it not?
A It says “one episode of bleeding fresh red blood, resolved”.

Q It may have resolved, but there was one episode?
A There is one resolved episode.

Q Can you answer my question? Could an episode of fresh red blood loss be a sign of a lower GI bleed?
A One episode in itself to produce an anaemia would have to be so large it would be very unusual that the patient was not taken to hospital and investigated.

Q Can we then look at the compilation of information available at the time of colonoscopy from these records. Two years of diarrhoea since the age of 18 months that had got worse. No control over the bowels. A confused history of bleeding. Professor Walker-Smith’s history was “Occasional blood loss in the stools” versus, on admission, this one episode of fresh red blood. A low haemoglobin level. A history of occasional mucous. Poor appetite. Occasional vomiting. In those circumstances Professor Walker-Smith’s recommendation for colonoscopy would appear to have a justified basis, would it not?
A No. I do not follow what you are saying. The patient has symptoms consistent with toddler diarrhoea. There is one episode of fresh blood although that is rather confused in the history. It says, towards the top of page 10, “No blood” on two occasions. The bleeding was not sufficiently significant for Professor Walker-Smith to mention it in his outpatient letter, and it is not made reference to in the discharge summary.

Q We know in his outpatient assessment, he has recorded, “Occasionally blood in the stools”. Now, whether or not he chooses to put it in a letter is a different matter. The fact is, on the face of these documents, there is that history, is there not?
A There is no dispute that that is written in the notes. That is correct.

Q And the point of the exercise I am carrying out with you is to see what information would have been available to Dr Murch. What I am suggesting to you is the combination and of the history that I have put would make IBD part of the differential diagnosis. Do you agree?
A Inflammatory bowel disease is difficult to exclude in the differential diagnosis completely, as we have discussed, with any patient with any constellation of gastrointestinal symptoms. The point I would make here is that Professor Walker-Smith has made a judgment that the symptoms are consistent with toddler diarrhoea. I do not think any of the information that is available in the clerking note would dissuade me from thinking otherwise. Patients with diarrhoea might, for example, have blood in the stool because they have excoriation around the anus, which is bleeding. I do not think the two references to the absence of blood in the stool would make me think this patient is consistently passing blood in the stool. There is a reference to one episode of fresh blood, which had resolved.

Q There is no evidence on examination, is there, of excoriation round the anus as a cause of bleeding?
A Which would be consistent with the episode having resolved.

Q And if there bleeding round the anus, you would not expect the blood to actually be within the stool, would you?
A It does not say it is within the stool in the note.

Q Let us go back to Professor Walker-Smith’s assessment.
A Sorry. Which episode are we referring to?

Q In the outpatient assessment, Professor Walker-Smith recorded that the child occasionally had blood in the stools.
A Okay. Which the inpatient clerking indicates has resolved on three separate occasions in that note at the top of page 10. At the top it says “No blood”. A few lines lower down it says, “No blood” and then it says, “One episode of bleeding fresh red blood, resolved”.

Q If it had been picked up with some inconsistency in the history, then that may well be a matter that would have been further discussed with the accompanying parent prior to colonoscopy. Would you agree?
A It may have been, yes.

Q Professor, what I am suggesting to you ---
A I am sorry. I got the impression from you yesterday that, because of time constraints, those discussions did not take place. Perhaps I misunderstood you, in which case I apologise. I thought you were telling me that because of the time constraints, those discussions had not taken place.

Q Professor, you know very well I was not telling you that. What I was suggesting is that there were a number of things to be done, but they would all have been done under pressure of time, and therefore there is a limit to the extent of the exercise that could be carried out.
A If the presence or absence of blood is an issue, that can be dealt with quite quickly with parents, surely?

Q I agree. I am not suggesting otherwise. As we know, the first attempted colonoscopy was abandoned due to faecal loading and the inevitable consequence to that would mean that the lining of the bowel could not properly be visualised by the procedure, I think you would agree?
A Yes.

Q And it also therefore means there is no opportunity to take tissue sampling.
A Yes.

Q We know, of course, that Professor Walker-Smith had examined the abdomen of this child in outpatients back in June 1996, when no abnormality had been detected?
A Yes.

Q I think you accepted when you were cross-examined by Mr Miller about this that faecal loading, as was found at colonoscopy, would not fit with a diagnosis of toddler diarrhoea?
A No, but one of the treatments that Professor Walker-Smith recommended in his outpatient letter was loperamide, which is an anti-diarrhoeal agent if the patient had been taking that, and it is often quite successful in the treatment of toddler diarrhoea when it is particularly troublesome, that may have accounted for this patient’s marked constipation on admission.

Q I am not going to dispute whether that is the case or not with you. For my purpose, that does not matter.
A But that means that the finding of constipation of a severe degree in this patient is not inconsistent with the working diagnosis of toddler diarrhoea, if this patient had been getting a lot of loperamide.

Q Faecal loading would not explain, would it, this child’s history of blood in the stools?
A It could well explain the history of blood in the stool. When children pass large, hard stools as a manifestation of their constipation, it can cause bleeding.

Q I accept it can cause bleeding, but the point I am making is, blood the stools?
A When a patient had blood in the stools, when the patient saw Professor Walker-Smith, the patient did not have constipation. The patient had diarrhoea.

Q Can you just answer my question, please. Do you accept that faecal loading would not be an explanation for blood in the stools?
A It would not be an explanation for blood in the stools.

Q Thank you. Faecal loading would not be an explanation for there being a low haemoglobin?
A Well, it depends on how the faecal loading is affecting the child’s appetite. Children who are severely constipated often exhibit a low appetite, and it is very clear that when the constipation resolves, their appetite improves. So this child’s intake of iron and iron-containing foods may have been rather low. I have not actually gone back to the specific results on the blood test to see whether there was any evidence that this was an iron deficiency.

Q The faecal loading will not explain occasional mucous being passed, would it?
A Often, when children are constipated – for example, when they are constipated as part of inflammatory bowel disease, it is a common feature for mucous to be present in the stool.

Q What I suggest to you is that the same justification that existed for the first attempted colonoscopy remained when the second colonoscopy was carried out. In other words, the whole purpose was to look at the lining of the bowel, to take tissue sampling because an inflammatory process was being suspected, and there was no reason for that view to change?
A I think it is an odd concept to consider that a patient may have significant colonic inflammation in the presence of massive faecal loading except in the presence of children who have cow’s milk intolerance.

Q Would you go to the histology request form which is at page 100C and we see in the box “Clinical Details: ? IBD”, so I am going to put to you the same question that was put in before. Simply as a matter of fact, do you accept that that is a statement by those involved in this colonoscopy procedure querying whether or not this child is suffering from IBD?
A Yes.

Q We know, if we turn to page … (Pause) Sir, I will move on from that. I do not need the point and, if need be, I will come back to it later. (To the witness) Professor, may I take you next to the histology report at page 103. If we look at the microscopic description under II describing the large bowel mucosa, it says this,

“II. 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”.

Dr Murch therefore, in obtaining samples then reviewed, would have seen from this information that an inflammatory process had been identified on histology, would he not?
A Yes.

Q Again, in terms, not in justifying the procedure but in terms, of reinforcing his view on the clinical wisdom of carrying out this procedure, that view would have been reinforced, would it not?
A If you are talking about clinical wisdom, I think it would be appropriate to think about why this patient’s colon did exhibit this particular degree and type of inflammation at this time given that the colonoscopy had been carried out under circumstances which, in my clinical experience, were exceptional. I have not been able to recollect an example in which a patient is admitted to hospital for colonoscopy where the degree of faecal loading is so severe that you have to then go back again when you are looking for suspected inflammatory bowel disease because constipation is the exact opposite of what you would normally be looking for clinically in terms of symptomotology in a patient with inflammatory bowel disease.

Q You have just given us what may well be an explanation for this child being constipated which was the tablets he had been put on.
A Inflammatory bowel disease patients who have diarrhoea resulting from their colitis do not exhibit this degree of constipation which, from the description, looked to be very severe indeed.

Q Professor, forgive me but there seems to be some inconsistency with your view that this child had toddler’s diarrhoea and the stance that you seem now to be taking suggesting that this child’s problem had been constipation all along.
A I am putting forward the notion that this patient had toddler diarrhoea, received loperamide which is a powerful anti-diarrhoeal agent and became severely constipated as a result of it.

Q This of course I put to you a couple of minutes ago.
A The finding of inflammation in the colon under circumstances of profound constipation raises the question of whether the constipation was responsible for these inflammatory changes. One would not normally carry out a colonoscopy in a patient who was so severely constipated. We do not know from clinical observations back in 1996 whether that was likely or not but it was certainly something that was very worthy of consideration.

Q In order that we understand the force of the observation you are making, I think you accept that, back in the mid-1990s, there was no scientific evidence to support the view you have just propounded and the view that you have just propounded is one simply of speculation.
A There was good scientific evidence that colonic stagnation resulted in lymphoid nodular hyperplasia and cryptitis.

Q Is that the paper to which you referred us yesterday?
A That would be one of the papers. There were further publications. One came out at around the time that these patients were being investigated.

Q I want to move on to Child 4. I want to put a few propositions to you, so we had better get the Child 4 Royal Free notes to hand. I am passing over Child 3 because the colonoscopy in that case was done by Dr Thomson and you have been questioned about that in any event. May I put forward first of all, please, some principles of good medicine to see if you agree with these propositions. Do you agree that a good clinician learns from his or her experience?
A Yes.

Q Do you agree that one should not assess or treat each patient in isolation?
A I that is more difficult. There was, for example, a publication which is in one of the bundles suggesting that there are abnormalities in the upper gastrointestinal tract of patients with autism that was published, I think, in 1998-99, and it was accompanied by an editorial which, amongst other things, posed the questions, should autistic children therefore be exposed to these particular investigations and the editorial went on to say, no, that each patient with autism should have their symptoms assessed in the same way as other children. So, I would agree, outside a research study, that holds true. If you are carrying out a research study on these children, then you are carrying out the investigations according to an agreed, defined protocol.

Q May I bring you back to the point, please.
A You were asking me whether patients should be investigated and managed in their own right or not and I was just making the point that it is quite difficult but, in general, they demand investigation on the basis of their own particular symptoms.

Q What I was suggesting to you is that it is good clinical practice to bring one’s knowledge and things learned from previous cases to bear when assessing and investigating new cases; do you accept that proposition?
A Yes.

Q Therefore, I suggest that, by the time Dr Murch came to Child 4, the first two cases to be colonoscoped, Children 2 and 1, had had findings of inflammation on colonoscopy and I suggest that those findings would lower the threshold for colonoscopy, in other words raise the index of suspicion higher for IBD in new cases with a similar presentation; do you accept that?
A They may do but it would depend on your interpretation of the previous histological findings. As I have said, there was evidence in the literature at the time that inflammatory changes in the colon could result from colonic stagnation and constipation. So, if you are going to start using normal observations in routine patient management, you have to be absolutely clear that the novel observations that you are making are valid and I have made the point before that many of these children, including the last patient we looked at, were, or it became subsequently clear, suffering from major constipation which is a variable that you would need to control for when interpreting the observations that had been made histologically.

Q I challenge the view you have suggested that the other two children were suffering from major constipation. We know in the outpatient assessments of both of them on abdominal examination that there was no finding of major constipation clinically, was there?
A I am sorry, are you suggesting to me that the last patient we considered was not severely constipated at the time of the colonoscopy?

Q I am suggesting that, in the outpatient assessment when these children were presenting with their bowel problems to Professor Walker-Smith, there was no clinical evidence of constipation.
A Not at that time, no, but the biopsies were not taken at that time.

Q May we consider Child 4. There was a referral letter from the GP which is at page 27 dated 1 July 1996, so three months before the colonoscopy, and, with that referral letter at which the Panel has looked before, there was an enclosure which we see at page 29 of a letter to Dr Wraith. If we look at page 30 in the paragraph numbered (3) which starts halfway down the page, it makes reference to investigations Child 4 has undergone and I want to pick it up five lines from the bottom of that paragraph where he says this,

“[Child 4] as I say has also had recurrent problems with diarrhoea and has on occasions had infections which have been difficult to treat”.

I want to ask you about that history. Do you agree that repeated infections can be a cause of diarrhoea?
A Yes.

Q But, if one is suffering from IBD, do you accept that the gut is sensitive to repeated infection?
A Do you mean by that that patients with inflammatory bowel disease have more frequent gastrointestinal infections?

Q No, I mean simply the question I am putting to you. A damaged gut, if one is suffering from IBD, can be more sensitive to repeated infection.
A I am not quite sure what you are asking me, Mr Hopkins. When you say “sensitive”, can you clarify what you mean. You could interpret it as, it is sensitive because it gets more infections.

Q Yes, that is one possibility. Let us go back to basics. If you have damaged tissue through IBD, you can get infection more readily in damaged tissue, can you not?
A I am not aware of any good studies that would suggest that gastrointestinal infections are more common in patients with inflammatory bowel disease. They may or may not be, I just do not know.

Q I am not dealing with the incidence, just the commonsense position. If you have damaged tissue, that is going to be more readily prone to infection, is it not?
A When you say “prone to infection”, that means an increased frequency, surely.

Q It may result in that.
A If you are asking, is there an increased frequency of infection in patients with inflammatory bowel disease, I do not know the answer to that question. I am not aware of any study.

Q Just so that we understand your position, Professor, are you saying that you are not able to express an opinion on whether a gut that is being damaged by IBD is more prone or sensitive to repeat infection, just so that we are quite clear about what you are saying?
A I am not aware. We certainly use a lot of powerful immunosuppressant agents in the management of inflammatory bowel disease and it is well recognised that those patients are more prone to infection, but the infection that one is particularly worried about is chickenpox. I am not sure if that answers your question.

Q Let me put it another way round. Do you accept that IBD can be the underlying cause of infections that are difficult to treat?
A I am not aware that when patients with inflammatory bowel disease get infections, they are more difficult to treat. I would accept that, if a patient with a severe colitis on treatment developed an infection which was of a kind that caused damage to the colon, like shigella for example, then that would worsen the patient’s inflammatory bowel disease symptoms. I would accept that. Does that answer your question?

Q No. What I am suggesting to you is that, if one is suffering from IBD, it damages the lining of the bowel, it makes the bowel more prone to infection and therefore, if a child has a history of infections which are difficult to treat, it raises a suspicion of an underlying IBD. That is what I am suggesting to you.
A I am saying that I am not aware of evidence to confirm that notion.

Q Or refute it, presumably.
A Or refute it.

Q If we go back to the GP’s referral letter on page 27 and look at the last paragraph on that page, we see that, as of 1 July, the GP is writing that this child has continued to have intermittent problems with his bowels [and] with diarrhoea that the mother is relating to food intake,

“He has had a negative test for coeliac disease and has on at least 2 occasions had giardia but he has had no further investigations regarding the causes of these symptoms.”

The present tense “has continued to have intermittent problems” suggests that his GI are ongoing at the time of this referral; do you accept that?
A Yes.

Q We know that this patient was living in XXX and it has been suggested that one reason why an outpatient assessment was not carried out in this case was the difficulty of the location. Whether that is right or wrong I need not trouble you with. May we look at the information that is then available on admission which starts at page 5 where we see that this child was clerked in – and we know from other evidence that that was by Dr Casson who was the senior registrar – on 29 September. I will run through it fairly quickly because you have been taken through this recently. Near the top of the page,

“[complaining of] -diarrhoea ? food related
-behavioural ? food related/hyperactivity”

and a reference to developmental regression and, a couple of lines down, we see that there is a reference to

“-skin rashes/eczema ? food related.”

I would like to pause there. Would it be fair to say that skin rash may be a sign of IBD?
A Skin rash known as erythema nodosum which is a very specific raised red lesion on the shins is related to inflammatory bowel disease. I do not think that you would confuse it with eczema.

Q No, but it has “skin rashes/eczema”.
A Yes. I do not think that Dr Casson would have … Well …

Q Are you suggesting that all he means by that is eczema?
A No, I am saying that erythema nodosum is a very florid complication of inflammatory bowel disease and, if you elicited it, you would not describe it as “skin rash/eczema”, not in my experience anyway because it is florid and painful.

Q May I take you to the literature again and may we turn back to D5 and divider 6. This is a paper at which the Panel has not looked before but I think you have had an opportunity to look at. This is effectively the precursor to the Porto Criteria, is it not?
A I will read out the title,

“Inflammatory Bowel Disease in Children and Adolescents Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology and Nutrition”

and then we see who the authors are. It starts off with the lead author of Buller, it includes Professor Murch and we see in small italics below the list of authors from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and then the list of other international bodies. Is this something you have seen before, Professor?
A Yes. I am not clear where, in relation to your comment about the first meeting of the … Yes, I have seen this before.

Q I do not need to take you through the paper, it is just a point I want to put to you by looking in the left-hand column, which we see is entitled “Summary of the Problem”, which is obviously dealing with inflammatory bowel disease. But if we go down to the last paragraph in the left-hand column it gives a little history about the first description of ulcerative colitis and then the landmark paper of Crohn. Then four lines below the start of the paragraph it says:

“The symptoms of IBD are protean,” –

and I think you agreed with that suggestion yesterday.
A Yes.

Q - “but commonly include intestinal symptoms such as” –

and then it gives the list. It goes on to say –

“… and at times a wide range of extraintestinal manifestations including fever, arthritis, skin rashes, renal calculi and hepatobiliary disease, …”.

So there is a reference there just to the broad term “skin rashes”. Would you accept that that could be a non-intestinal sign, manifestation, of IBD?
A Yes, there are very specific skin rashes that one sees in inflammatory bowel disease, as I have said. Erythema nodosum would be one example.

Q Yes, just one; but there are others, are there not?
A There are others, like pyoderma gangrenosum. There are others where you have so-called metastatic Crohn's disease, where you get changes in the skin as a result of Crohn's disease, yes.

Q We can put that literature to one side, and go back to the clerking-in note of Dr Casson, please, in the Royal Free notes. I will run through this at a canter, as we looked at this yesterday. We were looking at page 5. We know, if we turn the page, there is a reference on page 6 to a list of dietary restrictions and a history of reaction to food; and we know, looking at page 7 towards the bottom of the page we see that Dr Casson carried out an abdominal examination, and specifically recorded no evidence of faecal loading.

If we go to page 8 we then see his detailed history of the gastrointestinal symptoms that were read out to you by Mr Miller yesterday, and they included, did they not, a history of diarrhoea, weight loss, lethargy and abdominal pain?
A Yes. That was not the whole story on this clerking, though.

Q No, but those symptoms were included in that history, were they not?
A Yes.

Q All of those symptoms are symptoms of IBD?
A What the clerking note says is that the patient’s symptoms seem to be food precipitated and related, which would not be a characteristic of IBD.

Q I will come on to that in a moment, but let us just deal with the symptoms I have put to you. Diarrhoea, weight loss, lethargy and abdominal pain are all symptoms of IBD, are they not?
A They are, yes.

Q As you rightly point out, a third of the way down the page there is reference to diet, and an exclusion diet, and the way the patient appeared to react to that, half-way down suggesting that the patient was well most of the time, but there were exacerbations in the condition that seemed to be related to food.
A Yes.

Q I think you accept that food allergy – from a discussion we had earlier this morning – can co-exist with IBD?
A It can co-exist with IBD, but what this note says is that when this patient is on the exclusion diet they are well, and that gastrointestinal symptoms are food precipitated. If they co-existed – in other words if a patient had food allergies and IBD – you would expect some improvement in their GI symptoms when they were on the exclusion diet, but there would be a baseline level of symptoms that did not get better – which is not my interpretation of this note.

Q I think you have accepted that the symptoms of IBD can wax and wane, so the fact that one has episodes when the patient appears well or improved is not ruling out an underlying process that can be debilitating.
A It would not be the case that symptoms of inflammatory bowel disease were precipitated by so-called new foods as stated here.

Q When you were asked about your views on this patient by Mr Miller, I think you said that IBD would be within the differential diagnosis.
A With a disorder, as we have said, with such a protean number of symptoms and ways of presenting, it is often the case that you include inflammatory bowel disease in your initial differential diagnosis.

Q Then it comes down to a clinical judgement, does it not, whether or not when it is included in the differential diagnosis one proceeds to colonoscopy?
A No. As we have looked at in, for example, Professor Walker-Smith’s publications, you get as much useful information as you can. Equally, as I have discussed this morning, the symptoms are evaluated very specifically, so that not all patients with abdominal pain per se need a colonoscopy, as we have already looked. The diagnostic yield for doing colonoscopy, for example in patients just with abdominal pain, is very poor. So you do not go straight from just a checklist of symptoms to saying “The patient has got to have a colonoscopy”.

Q What I suggest is there was a reasonable suspicion of IBD in this case, and taking account of what was known from the cases of Child 1 and Child 2, the threshold for carrying out a colonoscopy in this case was low and it was reasonable to proceed with it.
A I disagree with you.

Q Can we look at the thinking that may be shown as a matter of fact on the histology request form. Could we go to page 33A, please. Again, under “Clinical Details” it has been recorded – I think that is “history of”, or it may be “PC” –

“1) Diarrhoea
2) Abdominal pain
Has disintegrative disorder”

Then it says “Query IBD”. Would you accept that as a matter of fact the thinking at the time was that this child may be suffering from IBD?
A Yes, it is stated there “Query IBD”.

Q Then in this case, during the course of the colonoscopy, photographs were taken which we can see at pages 9 and 10 of this bundle, and I am hoping that you have colour photos as well as just the plain black and white. Looking at the colour photo on page 9, can you tell us what that is showing? Are you able to interpret what is on the photo?
A It is a photograph of inside some sort of abdominal viscus, presumably. Presumably it is the colon.

Q If we move on to the colour photo on page 10, that is showing, is it not, what the colonoscopist believes is an abnormality; would you agree?
A I cannot see what the ---

Q Is it not showing marked lymphoid nodular hyperplasia?
A Yes, there is a lymphoid nodule there. The problem is if you look at the previous photograph on page 9 there is an endoscopic biopsy forceps in the lumen, which is a useful guide to size when you are sizing things in the colon. The problem with the pictures on page 10 is that it is not clear what the scale is.

Q Let us just think about the practical reality of this. The whole point of taking the photograph and keeping it in the records is to show what the colonoscopist believes is abnormal; would you agree?
A It may or may not be. People take photographs inside the colon for a number of reasons. We take a lot of colonoscopic photographs with a very low threshold because of a particular interest in colonoscopy. It is true to say that you are more likely to take pictures of what you perceive as being abnormal. The fact that you take a photograph of something does not automatically classify it as abnormal, though. But in the perception of the endoscopist, fine, yes.

Q A final matter – it is separate but I want to pick it up with this patient. Would you go to page 68, please. There we see a report for Child 4 in relation to the VEP to binocular flash. You looked at this report with Ms Smith. It says:

“Normal waveform. We do not have latency values from control subjects for this test. One would guess this is a normal response.”

You were criticising the carrying out of this procedure if the results were going to be uninterpretable.
A Yes.

Q Can I first of all put this proposition to you: the person carrying out the test, if they knew they would not be able to interpret their findings, surely that person is the one to draw that to the clinician’s attention who has requested the test? Would you agree?
A They have drawn it to the attention, in that ---

Q Before carrying it out.
A You are saying they should draw it to the attention before it is carried out?

Q Yes.
A That would be good practice, yes.

Q If we think of what has gone before – in other words, the other children who had undergone the same investigation – and I am sorry, we are going to have to look at three more volumes. It is a very short point, but we need to do it. Go back to Child 2 first of all, please, Royal Free at page 258. We see, do we not, for Child 2, the report for the same investigation, where it says:

“Reproducible responses, of appropriate latency were readily obtained.

CONCLUSION: A normal study.”

There is no suggestion there that they were not able to interpret the findings of the examination, do you agree?
A There is no suggestion there that they cannot interpret it, that is correct.

Q Professor, I can take it to you if need be, but I will just give the Panel the references, to save digging out the other bundles. Child 1, Royal Free page 134C, and Child 3, Royal Free page 79. Again, if you want me to I will take you to them, but in respect of those reports again there is no suggestion that the person carrying them out cannot interpret the results.
A I think the issue here is the age of the patients at the time that they had the investigation. Reference values in children vary according to age. So I am sorry to labour the point – if you tell me that these patients were all exactly the same age as Patient 2 when they had the test, then fine, but there is already a difference of one year in age as far as I can understand it between Patient 4 and Patient 2.

MR HOPKINS: What I am putting to you ---

THE CHAIRMAN: I think Ms Smith is trying to say something.

MS SMITH: I am sorry to interrupt Mr Hopkins, but I am anxious that the Panel should not be completely confused about all this, and I would just remind everybody that this is a charge against Dr Wakefield alone; it does not affect either of these two clinicians.

MR HOPKINS: I will persist with the question. What I am suggesting to you is that unless and until the person carrying out the test informs the clinician requesting it that they cannot interpret the results, it is reasonable for the test to be carried out, is it not?
A I think if you were carrying this out as part of a research study it would be crucially important to discuss with the department involved, before you submitted patients for the examination, that they could interpret the studies for you.

Q We have already known by looking at project 192/96, which is what you attach weight to, that these investigations were all within the expertise and remit of the neurology department, headed by Dr Harvey. I think you accepted my question to you about it yesterday, that the gastroenterologists were entitled to rely on the expertise of others who were more specialist in the subject that they were advising on.
A Yes.

MR HOPKINS: Sir, that completes Child 4, and maybe that is an appropriate time.

THE CHAIRMAN: Yes, indeed. It is now a quarter past eleven. We will adjourn and resume at 11.35.

(The Panel adjourned for a short time)


MR HOPKINS: Sir, the next patient is Child 5, and could you have the Royal Free notes for Child 5, please. (To the witness) Professor, if we look simply to see the information available at the out-patient assessment in the notes, page 40 in the Royal Free notes, this was an out-patient assessment by Professor Walker-Smith in November 1996. If we go just half-way down the page, I think I can summarise it because we have looked at the contents before. There was a history of abdominal pain since the age of two, nearly every day, is that right?
A Yes.

Q This child was almost eight when seen at the Royal Free, so that abdominal pain had been going on for some five or six years.
A Yes.

Q With bouts of diarrhoea every month.
A Yes.

Q We know by turning the page that Professor Walker-Smith examined the abdomen and recorded that there was no abnormality detected, so in other words no clinical evidence on examination of constipation as a cause for the pain, or diarrhoea. Is that right?
A Yes.

Q He writes to the GP – the letter is at page 361 – and again I think I can summarise it, saying that there have been episodes of abdominal pain and intermittent diarrhoea in several other similar children where a GI pathology had been found, and he was therefore arranging for a colonoscopy. If we pick up the thread of information on admission, go back to page 38, at the top of the page it confirms the history of diarrhoea and says “Abdominal pain off and on” – I think it is “off and on for six years”. Just looking therefore at the information available immediately prior to colonoscopy, diarrhoea from the age of two that had been intermittent, so come and gone; abdominal pain recurrent over six years; abdominal examination finding no abnormality, and Professor Walker-Smith’s opinion that a colonoscopy is appropriate. In those circumstances I suggest it was reasonable for Dr Murch as he then was to put IBD in the differential diagnosis. Would you agree with that?
A If you look at patients who undergo colonoscopy just with symptoms of diarrhoea and abdominal pain, without any other previous investigation, the diagnostic yield at colonoscopy is only of the order of 20 per cent. I am quoting Professor Walker-Smith’s data there.

Q The question I asked you is whether IBD would be within the differential diagnosis?
A It would be within the differential diagnosis, certainly.

Q And it would be appropriate, would it not, to factor in one’s experience of other cases, indeed the other cases we have been looking at that Dr Murch had experience of?
A When you make clinical decisions you are factoring in a wide range of experience, yes; but we commented in the interpretation of the histological findings in these patients previously.

Q If we go to page 456 in the bundle we see the endoscopic clerking sheet, do we not?
A Yes.

Q In the second box down, under “Reason for Procedure”, it says:

“Complaining of Autism and behavioural problems.
Recurrent abdominal pains & diarrhoea.
To rule out [GI] pathology.”

Would you agree?
A Yes, it says that, yes.

Q So the thinking here, again I suggest shown by this document, is that there may well be a gastrointestinal pathology which would explain this child’s presenting problems from the bowel.
A I think that is always the reason why you do a colonoscopy. I do not think you would do it for any reason other than explaining symptoms, I agree.

Q If we go to page 424A we see the histology request form, and in the box dealing with clinical details it says:

“Child with autism + diarrhoea + abdominal pain”,

and it says:

“Possible inflammatory bowel disease” –

and it goes on to describe what was found on endoscopy. So again this is revealing the thought at the time that this child might be suffering from IBD; do you agree?
A As we have discussed, entertaining a possible diagnosis of inflammatory bowel disease would not be unreasonable with this patient’s symptoms. It just depends on where you would place an invasive investigation in the order of clinical priorities for investigating a patient. Generally speaking, going straight in without any further ado and doing a colonoscopy would not in my opinion be appropriate.

Q I can finish there with this child, and I want to move on to Child 6 next, please. We need the Royal Free notes there. I will be dealing with Child 6 very briefly, because of the opinion you have already expressed. This is a child who had a history of abdominal pain. I want to summarise the outpatient assessment information for this child: had abdominal pain, diarrhoea and blood in the stools, and mucous. Is that right?
A Sorry. Which page are you looking at, Mr Hopkins?

Q I am just summarising. I do not have a page open for this. If you look at your own report, I think you accept that this child had a presenting history of abdominal pain, diarrhoea, blood in stools and mucous?
A That is right, yes.

Q And because of that presentation, you accepted that it was reasonable to proceed to colonoscopy effectively straight away in this case?
A Yes. With those symptoms, the likely diagnostic yield of a colonoscopy is very much higher, and so I think that a colonoscopy would be an early investigation, yes.

Q And you were asked about blood tests in relation to this case. I think you were looking at page 117 of the additional GP and RF records for Child 6. We were looking at a table with Mr Miller asking you questions about the data in the column dated 28 October. You were being asked about the blood results in the column under the date 28 October?
A Yes.

Q And that, we know, is the date of the colonoscopy, and you pointed to the platelets being abnormal on that day?
A Yes.

Q You will see there is a column immediately before that that is dated 2 October, but no information written there. I would like you in fact, please, to have a look at the very next page.
A Sorry. When you say “No information”, I have something against CRP on 2 October.

Q Yes. You have zero right at the bottom. I am sorry.
A Yes.

Q There is one piece of information. Otherwise it is blank. Would you go to page 118, please. We see, do we not, a full blood count taken for this child, with the sample being received on 2 October?
A Yes.

Q So that would tie in with the outpatient assessment screening blood that was being asked for?
A Yes.

Q If we look at the values that we see there, they are all normal, are they not?
A Yes.

Q This is, in fact, a case, is it not, where on the clinical presentation you feel colonoscopy was justified, but in terms of the blood test results, as screening results they are all negative?
A Yes. There is no ESR or ---

Q Professor, you drew our attention to the fact that CRP was zero on the day before?
A Yes.

Q On the page before. So on the information we have, the inflammatory markers are not raised and on the clinical information, colonoscopy justified. It is just a case that illustrates the point, does it not?
A Yes.

Q That is all I need ask you about Child 6. Child 7, Child 8 and Child 9, Dr Thomson carried out the colonoscopy and I will not be asking you about those three. Can we move on to Child 10, please. For that you will need the Royal Free, Volume 1 and Volume 2. Starting with Royal Free Volume 1 at pages 17-18, we see Professor Walker-Smith’s note of his outpatient assessment. Two-thirds of the way down we can see, can we not, a reference to this child having low iron and having iron therapy. Do you have that?
A Is that page 17?

Q Yes. Do you have the right pages? It is 8 November 1996.
A Yes, I do.

Q Would you go about two-thirds of the way down, just below the bottom hole punch where the crossing-out is, the words immediately before the crossing out say “low iron” and immediately afterwards “Rx for therapy” and then “iron therapy”, I think it says.
A I could not comment on my copy, but I am prepared to accept that is what it says.

Q If that is, in fact, the history that is obtained, I think it is a point we considered with another patient, the significance of having low iron could be due to diet, malabsorption or blood loss. Do you agree?
A Yes.

Q We also know, and it is at the bottom of the page – I think a bit easier to read the last four lines – the history was obtained of screaming and clutching the abdomen for several months?
A Yes.

Q Which Professor Walker-Smith thought could be due to abdominal pain. We can see that in the letter to the GP at page 33. On the next page, page 18, he also established a history of episodes of watery diarrhoea with up to five stools a day. He carried out again an abdominal examination and found no abnormality. In other words, no faecal loading was detected clinically. Would that be right?
A Yes.

Q We know from the letter – and if just move on to page 33 in this same bundle – that in writing to the GP, Professor Walker-Smith confirms the history in the notes. He makes reference to a high measles antibody, which we know from the GP’s referral letter, the GP had mentioned and he take into account a possible relationship between measles immunisation and IBD?
A Yes.

Q And then he goes on to arrange a colonoscopy. That is the background from the outpatient assessment and the information available from that. We then know this child was admitted on 16 February 1997, and the clerking note begins at page 10. Again, he was clerked in by Dr Casson. You have been taken through this because Mr Miller read through various sections of it, but I would like to pick out some highlights. A record towards the top of page 10:

“? Abdominal pain
Occasional diarrhoea”

Over the page, on page 11, starting about quarter of the way down, a reference to a deterioration in the summer of 1996, pulling knees up, clutching the abdomen, stopping taking dairy products, improved. Subsequently screaming with bread or sponge cake and Hoola Hoops, and then there was some improvement after that. No bowel control. So in other words, a history confirming the account given to Professor Walker-Smith clutching the abdomen and diet associated with behaviour. Is that right?
A Yes. Thought to be abdominal pain.

Q Then just below half-way down the page, “GIT”, the gastrointestinal tract symptoms: there is reference to occasional watery, occasionally dry, occasionally has to strain at stool but no pain, two to six times a day, no blood or mucous. The mother’s association of abdominal pain with diet, Hoola Hoops. Again, just a point I have asked you about before: even if food allergy is at work in this case, that does not rule out IBD. I think you accept that?
A No. I think you would within your differential diagnosis include IBD.

Q And therefore, what I suggest to you again, again given Professor Walker-Smith’s request for colonoscopy and given that IBD was within the differential diagnosis, it would be entirely reasonable for Dr Murch to proceed with the colonoscopy when he did?
A No. I think that having a different diagnosis, which it would be reasonable to make IBD one of the components, does not necessarily mean that because IBD is included on your differential diagnosis, that colonoscopy should be your first investigation. It is a question of how you rank the likelihood of IBD against other possibilities. We know from Professor Walker-Smith’s observations that when you colonoscope patients who have abdominal pain and diarrhoea without any other features of inflammatory bowel disease, the diagnostic yield is really quite low.

Q Let us just see what the yield was in this case. Can we go to the other bundle, please? This is RF2 and that page is page 45. I will just read out again. We have looked at it, but I think the wording is important.

“This colonoscopy was definitely abnormal, in probably a more striking example of the pattern seen in the cohort of the autistic children. The rectum showed definite mild abnormality, with a slightly granular mucosa and abnormal vascular pattern. Prominent lymphoid follicles could be seen throughout 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.”

Then, going on:

“I suspect that the biopsies will show unequivocal abnormality!”

It would appear from that description, would it not, that the colonoscopists – in other words, Dr Murch – thought there was striking abnormality macroscopically. Would you agree?
A That was his view, yes.

Q And we know that he took a series of photos which we see in this volume start at page 5A. Again, you may have a mix of colour, and black and white photos.
A Yes.

Q If we look at 5A, the middle photo, that would purport to show what?
A Lymphoid nodular hyperplasia, I would imagine.

Q Then the bottom one – would that be trying to show the vascular pattern that is seen?
A Yes, possibly. It is a little difficult to know. All I can say is, I can see some blood vessels.

Q Then if we move on to the colour photo at 8A, and then run through 8A, 8B and 8C, again what do you think that shows?
A That shows lymphoid nodular hyperplasia.

Q That is all on Child 10. Can I move – and you will be pleased to know it is the last – to Child 12, the Royal Free notes, please. I am sorry, Professor; I need to take you to the GP bundle as well, please. It is there we find the GP referral letter. This is a letter dated 23 September 1996. I just want to consider the bowel problems that were being mentioned. Could we look at the end of the first paragraph, the last few lines, where the GP is writing:

“He has for sometime had bowel problems, but did not present … until March [1996] … [with] soiling…”.

A I am sorry; I think I must have the wrong page. Could you tell me the page again, Mr Hopkins.

Q It is page 124 in the GP bundle. It is the paragraph beginning “Thank you…”. Do you have that?
A Oh, right.

Q Would you go to the last few lines of that paragraph.

“He has for sometime had bowel problems, but did not present to my surgery until March this year when Mrs 12 came along to discuss his soiling habit.”

A Yes.

Q Then it goes on to say:

“On examination at that time his abdomen was normal with an empty rectum,”

A Yes.

Q Again, the GP would have been examining presumably with constipation in mind, and not finding faecal loading. Would you agree with that?
A At that time, no. That is correct.

Q We then move on to Professor Walker-Smith’s outpatient assessment. We can now go back to the Royal Free bundle, starting at page 12. We see the note runs pages 12-13. Again, I will try and summarise the salient points that I need to put to you. Professor Walker-Smith established that the child appeared to be toilet trained at the age of three but was soiling but not had diarrhoea. Had variable abdominal pain occurring every week which was stopping him eating and he also, as we can see on page 13, carried out his own abdominal examination and found nothing abnormal, in other words, no clinical finding by him either of constipation. Do you agree?
A Yes. I just make the point that generally, surprisingly, abdominal examination in children with faecal loading does not always detect faecal loading. That is a point confirmed in a publication by Professor Murch on these children subsequent to their investigation where he showed that an abdominal film is a more effective way of making the diagnosis.

Q That may well be right. There will be cases that will be missed on abdominal examination. Nevertheless, it is an important part of the clinical assessment and a factor to be taken into account.
A Yes, but when Patient 12 was examined, only Patients 4, 8 and 9 had not had constipation at this point.

Q You have had the issue of constipation debated on all the other children. I am not going to rehearse it. Can we see what other information was available by the time of colonoscopy. Would you go to page 68 where you will see Mrs 12’s letter of 20 October to Professor Walker-Smith where she goes on to give further information about the soiling describing it as foul smelling, pale and very loose, but she also said that the child was not growing or putting on weight like the other two siblings. Would you think that is potentially important information, in other words information that the child appeared to be failing to thrive?
A Yes, it is always important.

Q And, as we have already established, a failure to thrive again might be a sign of IBD; do you accept that?
A It is in the list in the much discussed Porto Criteria.

Q We know that, for this child – I do not need to take you to the page – screening blood tests were done and it came back with the raised CRP at 6.
A Yes, we have had that discussions.

Q We know Professor Walker-Smith’s view on that because he wrote to the mother on 29 November saying, “One of the inflammatory markers was slightly above the normal which means we should go ahead” and he therefore arranged the colonoscopy. The child then comes in on 5 January and we can pick up the clerking note at page 19. One quarter of the way down the page we see in the left-hand column “PC” which would be presenting complaint.
A Yes.

Q A reference to autism, a reference to soiling and a reference to abdominal pain and, if you would go to the bottom of the page and the last five or six lines, we see that there is a reference then to the GI symptoms and history confirming that the child had been clean and dry by the age of three and then started soiling some time later but the query after that as to when,

“- now soils up to [eight times] a day”

and, turning the page, goes on to describe the stools as being loose, pale and very smelly, and then goes on, on page 20, to describe the abdominal pain being,

“- about once a week
- sometimes waking him at night.”

That would be a significant level of pain and frequency for a child, would it not?
A Yes. It is a classic description of constipation with overflow.

Q I will come back to that point in a minute.

“- sometimes vomiting with pain”

we see recorded here. That can be a sign of IBD, can it not?
A Vomiting can be, yes. As I said before, it is unusual but it can be associated.

Q And then says,

“- often has anorexia with pain”,

so we have a level of pain that is affecting the child’s ability to eat.
A Yes. When children have abdominal pain, they do not eat. It is not implying that he has persistent anorexia which is what you would expect in a patient who has inflammatory bowel disease. It says that he has abdominal pain about once a week and, when he has the pain, he does not eat, which would not be exceptional.

Q If we cover that with the information in the mother’s letter effectively saying that there was a failure to thrive, there could well be a link, could there not?
A Yes. One of the features of children who have marked constipation is that they do not eat very well. That is because, when the rectum is full, it delays the speed at which the stomach empties, so children with constipation often have a low appetite.

Q If you would turn to page 71, you will see the endoscopy clerking sheet and, under the middle box which is “Fitness for General Anaesthetic”, it records the fact that the child has autistic features and,

“Soling - /pale stools/occasional abdominal pain”

and it then says, “? Joint pain (knee). A pain in a joint could be arthropathy, could it not?
A Frequently, the arthropathy that can complicate inflammatory bowel disease is associated with joint swelling and reduction in movement. This just says “? Joint pain …”, it is very non-specific.

Q But it could be, could it not?
A It could be. All things are possible. It could be.

Q The point you have made to me before is that it is a question of putting together signs and symptoms in whatever constellation they may appear and forming a clinical judgment.
A Yes.

Q If we go to the next box, “Examination”, there is obviously an examination of the chest and the heart and also the abdomen and it says that it was soft with no mass, although there was some tenderness.
A Yes.

Q Again, clinically, no evidence of faecal loading.
A We have discussed – and it has been pointed out by Professor Murch in his publication – the unreliability of abdominal examination in making a diagnosis of constipation.

Q I suggest that the information that is available to Dr Much when he carries out this procedure is one of persistent soiling; abdominal pain that is weekly disturbing sleep; a pain that is affecting the ability to eat; sometimes the child is vomiting; the child has joint pain in the knee; he has a raised CRP inflammatory marker; and he has Professor Walker-Smith’s opinion that this child needs a colonoscopy. In those circumstances, is it not entirely reasonable for him to proceed with that investigation?
A We have a child with a history of soiling and abdominal pain which, as I said, would be characteristic symptoms of constipation with overflow. We have a CRP that could not be raised by a smaller amount. We have a history of “? Joint pain (knee)” which, as far as I recall, has not appeared anywhere else in the previous clerkings, including the clerking that took place when this patient was admitted to hospital and Professor Walker-Smith’s opinion in his letter to Dr Wakefield at RFH66 that this child really has rather minimal gastrointestinal symptoms, “I did not feel it right to proceed”. So, I cannot, on that basis, agree that colonoscopy was indicated at this time.

Q Do you accept that IBD was part of the differential diagnosis?
A I cannot refute that it was part of the differential diagnosis. I cannot agree that it would have been anywhere near the top of a differential diagnosis, in my opinion.

Q Professor, I move away from Child 12 and there are a couple of strands that I want to pull together now generally. What I am going to do first of all is suggest that there is a difference between your approach to children with bowel problems and that of the Walker-Smith team in this sense, that, in your practice, colonoscopy would not be frontline as an investigation unless there were clear-cut clinical case of IBD and, in your practice, you place more weight on blood test results for inflammatory markers; would that be fair?
A No, I do not think that is fair. I think that my practice would take into account the detailed history examination and, if necessary, the results of other investigations before proceeding to colonoscopy. Sometimes, patients present to you who have a history of bloody diarrhoea and it is absolutely clear that they need a colonoscopy. Sometimes, patients present to you with growth failure, abdominal pain, diarrhoea, anorexia and peri-anal disease and it is absolutely crystal clear on examination in the outpatient clinic that they have Crohn’s disease and that they need to come in. Between that extreme and the patient who has recurrent abdominal pain which affects ten per cent of the childhood population are a large group of patients where individualised decisions need to be taken. I do not accept that I am reluctant to colonoscope patients when it is necessary.

Q May I suggest to you that, certainly at the Royal Free, the paediatric enterologists have a lower threshold for colonoscopy than you. Would you accept that?
A I think from the evidence of these 12 patients at which we have looked I would have to agree with you, yes.

Q In terms of inflammatory markers – I think you will agree with this proposition – they can be negative even in the presence of IBD.
A Yes. No one is disputing that. That is, by definition, what a screening test involves.

Q Yes. Indeed, they are likely to be negative in subtle cases of IBD; do you agree with that?
A They can sometimes, but one needs to place that view against the prominence that the Royal Free team have given to the need to carry out screening investigations in many of their publications.

Q I think you accept from previous answers that IBD signs and symptoms can wax and wane.
A Yes and the argument put forward in the publication from the Royal Free in 1996 is that, because the diagnosis can be difficult, you need all the information that is available and a good screening test to help you is to look at inflammatory markers.

Q I think I have already put to you that inflammatory markers can screen you in for colonoscopy but they cannot screen you out of it and I think you accepted that.
A So, you are saying that ---

Q It is a simple proposition.
A Yes. I am just trying to make sure that I understand your question. If you have a patient where you are considering inflammatory bowel disease as a diagnosis and you do a screening test and they are all absolutely normal, you would not take any notice of that because you would not use it to screen the patient out? Do I understand your question correctly?

Q Professor, the question is really a very simple one. If the tests come back positive, that can screen you in for the investigation.
A Yes.

Q If they come back negative, it does not automatically screen you out. Do you accept that?
A It does not automatically screen you out?

Q Yes. It is plain English.
A Well, if it did not influence your decision … It would lower your threshold for carrying out an endoscopy if you knew that all those investigations were normal and you were undecided. You may say, “Let us wait and see what happens over the next few months”.

Q I think you accept that one needs to apply clinical acumen and judgment as to whether the presenting condition warrants colonoscopy regardless of the blood test results.
A Yes.

Q And I think you accept that, if there is a reasonable suspicion of IBD, then it is reasonable to carry out colonoscopy.
A Well, it depends what you mean by “reasonable suspicion”. If you say, “Well, I think it is reasonable to suspect IBD because this patient has recurrent abdominal pain”, it would depend very much on what the nature of the recurrent abdominal pain was but, in general, if you colonoscope patients who just have recurrent abdominal pain and no other symptoms or signs, you do not find inflammatory bowel disease at colonoscopy.

Q In issue, I think, in this case in the views you have expressed is the index of suspicion of IBD which is of course a clinical judgment issue; do you accept that?
A Yes.

Q And I think you would accept the proposition that it is important to diagnosis IBD early in children to avoid IBD causing them any long-term harm or affecting their physical development?
A Yes, but are you suggesting to me that the 12 patients here have inflammatory bowel disease?

MR HOPKINS: Professor, I have already put to you the justification for the investigations and I am not going over that again. That completes my cross-examination.

THE CHAIRMAN: Professor Booth, after this cross-examination, Ms Smith is entitled to
re-examine you on certain issues. That may not have been clear to you.

MS SMITH: Sir, may I respectfully ask what your position is. I was told by the Legal Assessor at the coffee break that you were going to stop at this point.

THE CHAIRMAN: Actually, I was hoping to go up to about lunchtime but, if you are not going to finish your re-examination by that stage, then it would probably be better to leave it now and start tomorrow morning.

MS SMITH: I am afraid that I am not going to finish my re-examination at that stage, I can confidently say, and, in normal circumstances, I was going to ask for half an hour before
I re-examined, not least because the other thing the Legal Assessor has indicated to me, which equally I was going to deal with, was that the Panel were interested in some of the literature to which Professor Booth has referred and I need to follow that up.

THE CHAIRMAN: That is helpful. Legal Assessor?

THE LEGAL ASSESSOR: It was not clear to me but yesterday – I think it was during Mr Hopkins’s cross-examination – on the transcript of Day 45 beginning at page 63, I think, Professor Booth was making reference certainly to another paper to which Mr Hopkins was not referring which is on Day 45/64C-D, a Beattie, Murch and Walker-Smith publication in 1995, which I have worked out is in D6 at tab 16, but I think he also made reference to another paper which he has read and on which he based some of his evidence, which is not before the Panel. Dr Webster has certainly expressed interest in seeing that and I hope that any re-examination will cover this missing paper, if there is one.

MS SMITH: I was certainly intending that in any event, sir, and I think in fact Professor Booth has referred to another paper as well which is not in the bundle.

MR MILLER: There was only one.

MS SMITH: Anyway, we will sort it out, if we may, before tomorrow morning.

THE CHAIRMAN: Thank you. The other thing that the Panel is probably going to do – and I am certainly going to do it – is to take our own notes with us to try and focus our minds on the issues that are not quite clear to us that we might need to ask Professor Booth about.

(To the witness) Professor Booth, I think this has already been explained to you and I do hope you will forgive me for asking you to come tomorrow morning.
A I had already made provision for attendance tomorrow.

THE CHAIRMAN: Thank you. That is again extremely helpful. We will now rise and, as I have said, we will obviously take our own papers with us and reflect on the evidence that Professor Booth has given over the last week and a half.

MS SMITH: Sir, I wonder if I could ask for some assistance with one matter and, if not at this moment, then perhaps the Legal Assessor could convey it to us, and that is what time you wish to sit to tomorrow.

THE CHAIRMAN: I have not spoken to the panellists at this stage but may I ask whether we can start at 9.00 tomorrow morning. First of all, is a 9.00 start going to create any difficulty for any of you in view of this early rising today, and I am also looking at the Panel Secretary as well? (Pause while the Chairman conferred with the members of the Panel) One of the panellists has a difficulty starting in the morning; she says that she does not mind if we sit a little later but she cannot start early in the morning. We will start at 9.30. The answer to your question, until what time are we able to sit, is maybe a little more difficult. If necessary, we hope to be flexible about it. I think that is probably as far as I can go at this stage and hopefully we can still stick to the timetable for tomorrow. Again, it is extremely difficult. I can see your position as well thinking about your next witness.

MS SMITH: It is in my mind, sir.

THE CHAIRMAN: I do apologise for this difficulty but we will hopefully try to do our best tomorrow. We will adjourn until 9.30 tomorrow morning. We will now rise. (To the witness) Professor Booth, you are still in the middle of giving your evidence and still under oath. Please, do not discuss the case. I am sure you are quite used to it by now. We will see you tomorrow morning.

(The Panel adjourned until Friday 19 October 2007 at 9.30 a.m.)

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