GENERAL MEDICAL COUNCIL
FITNESS TO PRACTISE PANEL (MISCONDUCT)
Monday 20 August 2007
Regents Place, 350 Euston Road, London NW1 3JN
Chairman: Dr Surendra Kumar, MB BS FRCGP
Panel Members: Mrs Sylvia Dean
Ms Wendy Golding
Dr Parimala Moodley
Dr Stephen Webster
Legal Assessor: Mr Nigel Seed QC
WAKEFIELD, Dr Andrew Jeremy
WALKER-SMITH, Professor John Angus
MURCH, Professor Simon Harry
(Transcript of the shorthand notes of T. A. Reed & Co.
Tel No: 01992 465900)
A P P E A R A N C E S
MS SALLY SMITH QC and MR CHRIS MELLOR and MR OWAIN THOMAS of counsel, instructed by Messrs Field Fisher Waterhouse, solicitors, appeared on behalf of the General Medical Council.
MR KIERAN COONAN QC and MR NEIL SHELDON of counsel, instructed by Messrs RadcliffesLeBrasseur, Solicitors, appeared on behalf of Dr Wakefield, who was present.
MR STEPHEN MILLER QC and MS ANDREA LINDSAY-STRUGO of counsel, instructed by Messrs Eastwoods, Solicitors, appeared on behalf of Professor Walker-Smith, who was present.
MR ADRIAN HOPKINS QC and MR RICHARD PARTRIDGE of counsel, instructed by Messrs Berrymans, Solicitors, appeared on behalf of Professor Murch, who was present.
I N D E X
DAVID HOWARD CASSON, Affirmed
Examination by MS SMITH 1
Cross-examined by MR MILLER 59
THE CHAIRMAN: Good morning. Ms Smith, you were going to introduce a new witness this morning.
MS SMITH: Yes, that is Dr Casson.
DAVID HOWARD CASSON, Affirmed
Examined by MS SMITH
(Following introductions by the Chairman):
Q Could I ask you first of all to tell us your full name and address and your professional qualifications?
A David Howard Casson, XXX, MB BS, BA (Oxen), MRCPI.
Q I think it is correct, Dr Casson, that your present post is as consultant gastroenterologist at the Royal Liverpool Children’s Hospital, is that correct?
A That is correct.
THE CHAIRMAN: I come from Widnes. The Royal Liverpool Hospital is virtually within the catchment area of our area but I certainly do not remember seeing Dr Casson anywhere in my professional capacity or in any other capacity. I just wanted to declare that.
MS SMITH: Thank you very much. As you know, we are concerned with a time when you were employed at the Royal Free Hospital and I think it is right that you took up a post there in 1995 as an honorary senior registrar and lecturer in the department of paediatric gastroenterology, is that correct?
A That is correct.
Q Can you tell us when in 1995 you took up that post, Doctor?
A I think it must have been round about the middle of the year some time.
Q You left in 1998, is that correct?
A That is correct.
Q I think you left at that time to move to Australia on an exchange programme organised by Professor Walker-Smith.
A That is correct.
Q How long were you in Australia before you came back to the Royal Liverpool Hospital?
A A year.
Q You have been a consultant since when?
A December 1999.
Q Returning to 1995, when you began your post at the Royal Free Hospital was that your first post specifically involved with paediatric gastroenterology?
A Yes, it was.
Q Can you tell us in brief terms your work history prior to that? What specialisms had you been working in?
A I had done the usual grounding in general medicine and general surgery and then moved on to the rotation in general paediatrics which covered just general paediatrics and nothing much in the way of specialities. I worked for a six month period in Pakistan and then following that I came back to the UK. It was then I did my general paediatrics and decided I wanted to pursue a career in paediatric gastroenterology and sought the post in the Royal Free.
Q We know that Professor Walker-Smith came to the Royal Free Hospital from St Bartholomew's Hospital. Can you tell us what your understanding was as to how the post that you took at the Royal Free Hospital had become available?
A I understood that Professor Walker-Smith had moved from St Bartholomew's with the majority of his team and that the post of senior registrar was vacant. That was a post I applied for and that is what I entered into at the Royal Free.
Q Can you assist us when you arrived as to who the senior members of Professor Walker-Smith’s team were – the consultants, in other words?
A Yes, it was Professor Walker-Smith and Dr (as he was then) Simon Murch. Dr Thomson was there at the time or he started a little after I started.
Q They were the three consultants.
A They were the three consultants, yes.
Q As the senior registrar, and you have told us the first time you have been involved specifically with paediatric gastroenterology, did the post involve you receiving training from the senior members of the team?
A Yes, it did.
Q In very broad terms, remembering there are lay members on the Panel, what did that training involve? What were you being trained in?
A It was training in the knowledge and understanding of paediatric gastroenterology so it would have involved exposure to the majority of conditions that we see and also for thinking through various differential diagnoses for the problems that were presented to us and how they would be investigated and what investigations I would be doing and trained in the role of endoscopy as well.
Q Did it involve any general paediatrics or was it all specifically geared to gastroenterological problems?
A I did some general paediatric on-call which meant that I would have been on call over a given 24-hour period for general paediatric intake.
Q Was a majority of the work gastroenterological?
Q You have mentioned Dr Murch and Professor Walker-Smith and Dr Thomson arriving you think a little later. Were you specifically being trained by one of them or did all of them take a hand in that?
A All of them.
Q Did there come a time when you came across Dr Andrew Wakefield?
Q Can you tell us, if you recall it, first of all what post did he occupy as far as you were aware?
A As far as I was aware he was a researcher within the hospital.
Q When you arrived at the Royal Free Hospital were you at that time aware of research work that Dr Wakefield had undertaken?
A I do not think I was specifically aware, no.
Q After you started in the department, did you become aware of any collaboration or joint enterprises between the department that you were working for and Dr Wakefield as a research doctor?
Q Can you tell us in broad terms what that was?
A There were discussions around inflammatory bowel disease and possible cause of inflammatory bowel disease as postulated by Dr Wakefield.
Q What was the cause that he was postulating?
A There was thought to be possibly an infective element associated with inflammatory bowel disease, possibly a measles association.
Q Do you recall whether that was something you were aware of as soon as you arrived at the Royal Free or you learned about it later on in the post?
A I cannot recall exactly when I got to know about it.
Q You say that Dr Wakefield had hypothesized that measles might have some part to play in inflammatory bowel disease. Were you aware that Professor Walker-Smith had any interest in that direction or was pursuing that with Dr Wakefield?
A I think he was interested in all possible causes of inflammatory bowel disease and this was one of several that he would have been interested in.
Q Did there come a time when that research evolved to encompass behavioural disorders?
Q Can you explain, if you recall, how that shift occurred? How did you become aware of it?
A I cannot recall clearly how I became aware of that. It was just a change that became apparent.
Q You say that it was a shift that became apparent. What did you understand that the department were investigating with regard to inflammatory bowel disease and behavioural disorders?
A I think there was an association recognised that some children with some similar neurological disorders also had bowel complaints and that was the primary focus of the investigation.
Q Were there causes postulated in relation to that, in particular environmental exposures?
A One of the environmental exposures would have been measles immunisation or MMR immunisation.
Q Can you assist at all as to how that came about that shift from measles and IBD into behavioural disorders and measles vaccination? Do you recall how it came about?
A Not specifically. I think one of the pertinent factors was there appeared to be a temporal association between administration of the vaccine and parental perception of onset of these disorders.
Q I would like you to turn to file FTP1, page 200. It is an application to the Ethical Practices Subcommittee and we see it is signed by the head of department, Professor Pounder, with a date of 6 August 1996. If you go to page 233, which is the last page, you will see that it is signed by Dr Wakefield and dated 16 September 1996. Are you with me?
Q Going back to page 200 we see the responsible consultants are Professor Walker-Smith, Dr Murch and Dr Wakefield.
Q Going down, we see the research workers involved: Dr Subhani, who is a clinical research fellow, and then your own name, Dr David Casson, lecturer in paediatric gastroenterology, is that correct?
Q If we turn to page 201, we see the title, “A New Paediatric Syndrome Enteritis and Disintegrative Disorder Following Measles/Rubella Vaccination”. On 201 still, “Design of the Study” setting our a series of investigations that the children were to undergo, including colonoscopy and a barium meal and follow-through and MRI, EEG, lumbar puncture, blood tests and urine collections and tests. There is reference to a full protocol attached. Perhaps you will take it from me rather than referring you to it that that includes detailed virology tests. If we go on, there is a working hypothesis at page 204 and 205 (at the bottom of the page on 204) and then you see the two models which are the hypothesis for how a genetically susceptible well child develops enteritis, and then it goes on to disintegrative disorder through two different methods. At 208, “Selection criteria, presence of disintegrative disorder, symptoms and signs of intestinal dysfunction, parental request for investigation to be undertaken.” The number of subjects is 25. Then the information to be given to parents is at page 211. At 234, there is the consent form that was to signed for the research project. At 232 is a timetable for the investigations setting out those to be arranged by Dr Wakefield and those by the Department of Paediatric Gastroenterology. If we go back to 212 and your name on 213, at the top of the page under “Investigators”, we see: Dr Simon Murch, Dr Alan Phillips (Senior Lecturer) and Dr David Casson (Lecturer). I want to ask you, first of all, did you know at the time about the details of that ethics committee application?
A Not the precise details, no.
Q Given the nature of your status in the department, would you in fact have expected to be consulted about the detail of the application?
Q Whose responsibility, if a research project is going on involving children in the department, generally would you have regarded it as being to ensure that ethical approval was properly obtained and that the ethical side of the research study was being properly carried out?
A The senior consultants.
Q Do you remember whether you were told that your name appeared on it?
A I cannot recall.
Q If I can put it like this, you are not suggesting you were not told?
A No. I just do not remember.
Q Did you have any involvement in any drafting of that application? You said you did not see this final form, but were you involved in any earlier drafts or conversations about what was to go in it?
A I do not recall clearly being asked specifically. I think some of the other investigations, apart from the gastroenterological ones, may have been the subject of general discussion, but, other than that, no.
Q I will come on to ask you that in a moment. As far as the date of it is concerned, you have seen it has been signed off by Professor Pounder in August ’96 and submitted in September ’96, but does that fit in with your recollection, in broad terms, of the timescale relating to this research project?
A In broad terms it does, yes.
Q Just going to page 208, we see set out there the selection criteria. Did you have anything to do with the way in which the children were selected for the study?
Q Going to page 232l, which is the handout to parents and guardians, can you assist us at all as to the nature of the information, as you understood it, that was being given to parents as to the therapeutic value of the tests that were being undertaken?
A Can you phrase that again?
Q You told us you did not actually see these documents but I was asking whether you could assist at all as to your understanding of the information that was to be given to the parents as to the therapeutic or otherwise nature of the procedures that were being undertaken?
A As far as I recall, it was mainly about the gastroenterological side of the condition and the possible underlying causes for that would be investigated, and that would be the thrust of the therapeutic benefit.
Q What about other investigations?
A Other investigations, but I do not recall whether it was suggested that they would have a therapeutic benefit.
Q Did you know anything about the way any project was being funded?
Q I would like you to leave aside this particular study, the research study, for them moment, and to tell us what your role in the unit generally was. In other words, leaving aside these particular children with behavioural disorders, generally speaking, what did your role involve?
A In broad terms, it was involved with the day-to-day running of the unit, involving taking histories from patients who were admitted on to the ward and ensuring that investigations were arranged and performed as they should have been done, assembling results and presenting information to the senior consultants, and also taking part in clinics with other consultants present.
Q Did you take your instructions from any one individual?
Q So, generally speaking, who would – I will not say tell you what to do – give you any guidance you needed and ask you to do things?
A The consultants would have been the people who I took instruction from or sought advice from.
Q Normally speaking, if a child was being admitted for investigation of inflammatory bowel disease, what was the standard procedure that they would undergo?
A The standard procedure would be: upper and lower endoscopy and a barium meal and follow-through.
Q What did that involve? Did that involve bowel preparation beforehand?
A The endoscopic procedures would involve bowel preparation in order to clear stool from the bowel and allow a good view to be made.
Q Just remembering again that there are lay members, Dr Casson, can you just tell us what that involved? How long before the actual endoscopy procedure does it have to be done?
A As I recall, the patients came in on the Sunday and received their bowel prep over the Sunday and possibly on the following morning, and then went to theatre to have their endoscopy done on Monday, as far as I recall.
Q And the clear-out of the bowel, that involved an enema, is that correct?
A It may have involved an enema; it generally involved oral medication and possibly an enema as well.
Q With the ordinary child, if I can put it in those terms with inflammatory bowel disease, how long after that procedure would they then go home, generally?
A Generally there would be a week’s programme, as it were, of investigation and hopefully at the end of that the diagnosis would be available and treatment could be started.
Q Can you help us as far as you can recall. Children who were admitted for the particular investigation of the hypothesis you have told us about – namely autism or behavioural disorders and bowel disease – how did their investigations differ, if at all, from the standard that you have told us about?
A As I recall, they would also have an MRI scan of the brain, have a lumbar puncture to obtain fluid from around the spine, and I think they also had certain other blood tests done. Evoke potentials were I think brain responses to external stimuli and psychological assessment.
Q How long was the admission for?
A I think again it would have been encompassed within a week.
Q If we can just look again in the volume you were looking in before, volume 1, at page 231, which was the timetable I referred you to, were you involved in the actual arranging of these tests?
Q Did they follow a timetable in broad terms, as it set out there, or were they more flexible than that, do you remember?
A In broad terms, I think they did. I do not remember exactly.
Q Did you have some sort of protocol that you were following? Did you have something you ticked off the investigations against?
A I think there was, yes.
Q What was it?
A It would have been an instruction for what investigations were required by the terms of the investigation.
Q Was it in a book or some written form?
A I do not recall exactly where it was. I think we had a protocol booking in which details of all the procedures were kept so that if any patient came into the ward, a procedure would be recorded. That would be where we would take information from, and it may be that it was within that document.
Q Children who were part of the research protocol, were they differentiated from those who were coming through? They obviously were in terms of the tests that were undertaken because you have just told us that, but were they kept separate in any other way from the general throughput of the unit?
Q So how did you know, as someone who was involved in arranging the investigations, that a particular child was to be admitted as part of the research project rather than as part of the general throughput?
A I think I must have received information from the consultant staff.
Q That would be whom?
A From Dr Murch or Professor Walker-Smith.
Q When the child came in, was it your understanding that they would have been seen in outpatients before that?
Q Did you have anything to do with seeing the children in outpatients?
A I cannot recall that I saw any in outpatient before admission.
Q Who would you have expected that to have been?
A One of the consultants.
Q You say you must have been told if a child was being admitted as part of the research project. What would you then do? Once you knew that; you were not involved in outpatients; the child then comes into hospital; and then what do you do?
A I would have ensured that all the bowel prep was written up to be administered and that the investigations intended were planned.
Q Either with respect to these children or generally, Dr Casson, did you have any involvement with the actual undertaking of endoscopies and colonoscopies?
A I was in a training post and therefore would have been trained in doing endoscopies. I cannot recall specifically whether I ever took part in any of the endoscopies to which this refers, although I probably was present at several of them at least, and may well have taken part.
Q Would you always be in an assisting role?
A Certainly, yes.
Q Who in the department carried out endoscopies?
A Dr Murch and Dr Thompson.
Q Just so the panel can get an idea of the relative numbers of children, how did the number of children undergoing colonoscopy who were part of the research project compare with the number being admitted for colonoscopy generally?
A The general throughput for investigation by colonoscopy or endoscopy was four patients a week. I do not know quite how that relates to the numbers but four patients a week would have been the standard throughput of the department.
Q Looking at page 234, which is the consent documentation for the ethics committee, and again tell us if you do not remember, Doctor: do you remember whether you were actually involved in consenting the children to take part in the research study as opposed to consenting them for separate investigations?
A I cannot recall whether I consented for the study.
Q Can you help at all as to what your understanding was as to the requirements for obtaining consent to participate in the research study as opposed to consent for the individual procedures?
A I think the requirements, generally speaking, would be that the parents or guardian understood that this was a research project and also understood what investigations were to be undertaken under the terms of the research remit.
Q We have also seen, and we have heard evidence about, a generalised consent to take extra biopsies for research projects generally when colonoscopy was undertaken. Can you help us: do you have a recollection of that, first of all?
Q Can you just help us as to how that is different from the particular research study, if it is?
A In the more general sense, biopsies were taken as part of a bank of tissue that was available for research and those would have been the biopsies which people were asked if we could take for research, although without a specified research with a specific aim in mind.
Q I did not hear you, I am afraid. Did you say “without a specific purpose”?
A It would have been as part of a tissue bank which was held for requirements later on potentially. In this research project biopsies were taken for specific purposes.
Q Just reminding you of page 201, doctor, this is a matter that you touched on earlier in your evidence, that is the list of investigations under “Design of the Study” that the children were to undergo. Do you know who decided on the investigations that are set out in the protocol?
A It would have been through discussion with the senior consultants and with Mr Wakefield.
Q When you say “senior consultants”, could you say who?
A Professor Walker-Smith and Dr Murch.
Q Have you any knowledge as to who decided on what?
A The gastroenterological investigations would have been decided specifically by the gastroenterologists, that would be Professor Walker-Smith and Dr Murch.
Q What did you, as a junior member of the team, understand the aim behind this list of investigations to be?
A I think it was to identify whether there was any inflammatory bowel disease associated with this condition and to look for possible associations with that and with the neurological disorder that was being looked at.
Q You have told us already the role of measles; what about the measles aspects of it?
A They would be looking for the presence of measles as well, yes.
Q What was your understanding as to what was being said to be the indication for the procedures that were being carried out on the children who were part of this research study? Did you understand them to be clinically indicated or research investigations or both or some of each?
A For both, I think. The endoscopic examination and some of the investigations would have been there to identify any specific ongoing disease process. Other aspects of the investigations would be to identify measles or whatever.
Q You have told us about the general input of children through the department and those who were being investigated for suspected inflammatory bowel disease would have colonoscopies and you have now said that, as you understood it, these children were being investigated also for the presence of inflammatory bowel disease. How did you see the two groups differing, if at all, that is the generally admitted and these children?
A The obvious difference was whether they had an autism type of disorder or not. That would be the main distinction between the two groups.
Q Whose decision would it be whether the nature of the child’s symptoms was such that a colonoscopy was indicated?
A That would be the consultant decision, once again Professor Walker-Smith or Dr Simon Murch.
Q At that stage in your career, Dr Casson, would that have been a decision that you would have questioned at all or would you have respected it as being the appropriate one?
A I would have respected that decision.
Q Do you have particular memory or knowledge of the Schilling Test, what that was for and what it involved?
A It is to check for problems in vitamin B12 absorption. I know practically what it involves and what was undertaken. I seem to remember … I do not remember clearly, to be honest. I think it involved eventually making a urine collection and that being analysed.
Q Was that something that would have been envisaged in the normal child coming through the department?
Q What about the lumbar puncture? First of all, was that a standard investigation for children coming to the department investigated for IBD?
Q What was your understanding, if any, as to why lumbar punctures were included in the research protocol?
A My understanding was that it was to look for other potential causes or neurological problems.
Q Do you recall any discussion in the department about whether lumbar puncture was an appropriate investigation on these children?
A I do recall discussion, yes.
Q Can you tell us, if you can recall it, what the nature of that discussion was.
A I think the discussion was about whether it was an investigation which was indicated in children in these clinical circumstances.
Q Again, was that a discussion in which you would have played any determinative part?
A Not a determinative part, no.
Q Obviously, the reason for the lumbar puncture was to obtain the cerebrospinal fluid and that was then tested. What did you understand it was being tested for?
A I understood that it would undergo the usual tests which cerebrospinal fluid undergoes; it would also be looking for lactate and I think also be looking for evidence of presence of measles.
Q You say “the usual tests”; you told us that it was not usual to do them in this department.
A When a lumbar puncture is undertaken, part of the usual analysis that cerebrospinal fluid undergoes is to look for the glucose levels, to look for the protein levels and to look for the presence of cells within it.
Q As far as the testing for measles were concerned, who was, as far as you were aware, doing that?
A I do not know who was doing that.
Q Lastly, the blood tests. What was your understanding as to the blood tests that were being done on those who were admitted to the research protocol?
A My understanding was that they were being looked at with the usual blood tests that we would look at in any inflammatory bowel disease to indicate ongoing inflammation but also to be looking for the presence or evidence of measles.
Q So, normally speaking, when a child came into the department with suspected inflammatory bowel disease, you would do blood tests and test them for inflammatory markers; is that correct?
A That is correct.
Q You are saying that that would have been done on these children but that, in addition, there were other blood tests done.
A That is correct.
Q You may not know the answer but you talked about testing for measles. Do you know whether any other specialised blood tests were being done and what they were being done for?
A I do not remember whether any other specialised tests were done.
Q I am going to take you in a moment to some of the individual cases with which you were involved, Dr Casson. Before I do so, I think you are aware that your name appears in the records of a number of children who were subsequently written up in The Lancet. Generally speaking, what was your involvement with those children who came in for a research project?
A My involvement would be to ensure that they were admitted appropriately, that they were clerked in appropriately, that means the history was taken, that investigations were undertaken as planned and then, in many cases, to draw together the results that were available and to write a discharge summary.
Q Who was the discharge summary for?
A It would have been for a referring doctor or for the general practitioner or any other doctor who had been involved in the care of the patient.
Q Can you tell us how you wrote those. Did you do it by reference to looking back at the medical records whether you had actually been involved or not?
A Yes, it was with reference to the medical records.
Q I am going to deal with these children in fact in the order in which they were referred to the department rather than the order that they appear in the statement you gave for us and, just so that you understand, that actually means starting with Child 2 because, just to make life difficult, Child 2 was the first child. First of all, you should have in front of you a plastic anonymisation sheet and you can see on that the number of the child and that is the number that was ultimately used in The Lancet article. (Pause) Do not worry, Dr Casson, I will tell you how to refer to them in a moment. I would say to you first of all that we are referring to the child by the number that is on that sheet, if you can possibly remember to, but do not worry if you do not and you call them by their name because the press have been warned not to report their names to respect their confidentiality.
Would you take up the volume of Royal Free Hospital records for Child 2. The first chronologically, your name first appears in Child 2’s records at page 151 which is a letter from you to Mr and Mrs 2 dated 28 August 1996,
“Dear [Mr & Mrs 2],
This letter is to confirm that [Child 2] is to be admitted to Malcolm Ward at the Royal Free Hospital on Sunday 1st September 1996 for colonoscopy and Schilling test.
Any further investigations required will be decided on another occasion following consultation with Dr Wakefield”
and it is then signed on your behalf. That was a letter obviously informing the parents as to when the child was to be admitted. All the children were admitted to Malcolm Ward, as we will see. Can you tell us as far as that is concerned, was that purely paediatric gastroenterology or did it have some gastroenterology beds in it in other specialties?
A It was purely gastroenterology.
Q We see that it says, “Any further investigations required will be decided on another occasion …” Do you know what investigations you may have been referring to there?
A I could not be specific about that.
Q It appears that you were envisaging the admission being simply for colonoscopy and Schilling test. Who, in broad terms, would have given you the information to enable you to send that letter to the parents?
A It would have been one of the consultants.
Q Can you help us as to why you say that those investigations would be decided on following consultation with Dr Wakefield?
A I cannot recall specifically why I would have made that statement.
Q First of all, would you have said that off your own bat, so to speak, or would somebody have given you instructions along those lines?
A I would have been instructed along those lines.
Q You were aware, I think you said from the outset of this particular study, that there was an involvement by Dr Wakefield in relation to the hypothesis that was being tested; is that correct?
A That is correct.
Q And you have told us that your understanding was that he was a researcher.
Q Did you have any understanding as to the role that he was actually playing in relation to the determination of any investigations?
A I think that any investigations would have been decided by discussion between Dr Wakefield and the consultant staff.
Q Would this letter, as far as your understanding is concerned, have been preceded by an outpatients appointment?
A I would have assumed so, yes.
Q Why would you have made that assumption?
A Because that was the standard way in which patients would come into the ward; they would be seen and assessed first in an outpatient department and then the decision would be taken to admit them for investigation.
Q Did you yourself have any direct communication with Dr Wakefield in relation to the fact of or the nature of the investigations that were being carried out on these children?
A The department was a very open place for discussion and so general discussion would have taken place and I think everybody was encouraged to take part in discussion, so all members would have been involved. The specifics of who determined what I could not recall for you but certainly I would have been party to discussion.
Q May we go backwards to page 4. That is the printout of the Royal Free Hospital patient details and, if we look down under “Patient episode summary”, we see that this little boy was an inpatient from 1 September 1996 to 6 September 1996 in the Malcolm Ward which you have told us about and the consultant was Professor J. Walker-Smith; is that correct?
Q What determined the name of the consultant under whom a child was admitted?
A I cannot be entirely clear about that. I think that there was a rota operated by consultant staff which would mean that, for a given period, patients entered would be under them and then subsequently, at other time periods, another consultant would have been allocated that period, so a patient would have come under them. I think that is what happened.
Q Generally speaking – and I am now asking general questions rather than particularly about Child 2 – was a child always admitted at least nominally under someone’s responsibility?
Q Was there a name at the head of the bed, so to speak, for every child?
A I think there was, yes.
Q Would you go on to page 8 where we see a note which in fact was prepared not by you but by Dr Thomson and it does indeed show that this little boy was admitted on 1 September 1996 as we have seen on the printout and we see under that, “Admitted for colonoscopy and Schilling test”; is that correct?
Q Would you turn on to page 15 where we see the first note by you, I think. That is seemingly dated 20 September, doctor, but we think that it must in fact be the 2nd because, if you look at page 17, you will see at the top, “2/9/06 cont’d” and we know that he came in on the 1st, so it seems a fairly safe assumption, does it not?
Q Going back to page 15, is this in fact your handwriting?
Q On page 15, would you tell us what it says at the top in the first sentence, “8 years …” and then?
A Eight years is the age.
“Referred for investigation of ? association between gastrointestinal [disease]/autism/measles.”
Q Does that note indicate to you whether this child was admitted as part of the study or not or whether it was a standard investigation?
A It was not a standard investigation in terms of investigation for inflammatory bowel disease as such.
Q Who would the history that you then set out be taken from?
A Presumably from the child’s parent.
Q Would you go on to page 17 where we see his present symptoms at the bottom of the page under “Presently”; do you see where I am?
Q Would you help us, please, as to what you said under that heading.
“Presently has ‘episodes’ approximately every 18 months, last [being] in April.
[They] last up to 3 weeks
[Possibly] associated with jaundice and with pale stool
Poor sleep [and increased] diarrhoea” and I think “screaming”.
Would you like me to carry on?
Q Yes, please, to the end of the page.
A Treatment is a composite mixture, presumably which contains several bacteria, four bacteria,
“from Dr Hunter at Addenbrooke’s Hospital for Crohn’s disease [and] exclusion diet”
and this is in reference to the exclusion diet which
“(had previously only contained chicken/rice/soya/cod/olive oil/salt/banana/tuna)
[any other ingredients] cause pain.
[That was commenced in] April 1996 [and] seems to have eased abdominal pain.”
Q Going on to the next page, can you help us with that?
A “Presently being investigated by Dr Hilary Cass at the Woolfson Centre at Great Ormond Street.” It deals with children with … I think it must be communication problems. “Last week saw Dr Surtees at Great Ormond Street (neuro-metabolic)”. That would presumably have been Dr Surtees’ area of expertise “possibly for metabolic tests”.
Q We see the words “WR” underlined. Is that ward round?
A Yes, that is ward round.
Q That would have been a ward round by whom?
A I think by a consultant.
Q Run us through the notes under that ward round.
A Blood tests as indicated by list of metabolic disorders. Note – that would be drawing attention to the fact that multiple abnormalities on colonoscopy. Request to recheck the anti-endomysial antibody, which is a test for celiac disease to do blood tests for T cell subsets, CD4 – I am not sure what the fourth letter on that line recalls – for peripheral blood lymphocytes. That would have been the subclasses of certain of the white cells in his blood. MRI specifically of temporal lobes, sleep eletrocephalogram, lumbar puncture, to collect CSF for measles, cytokines, RT-PCR (reverse transcriptase-polymerase chain reaction) a way of looking at DNA, lactate, pyruvate and glucose, barium meal and follow through, arrange Schilling test. Tests during week and home over the weekend. Also to look for trace elements: zinc, copper, magnesium, iron and calcium, I think. Then under the date 3/9/1996, Schilling test. I think that says “Kit and analysis performed by medical physics. Contact names: Andy Irvine or David Kingston extension 3058, for Thursday as per protocol.”
Q What protocol would that be a reference to?
A I presume it was the schedule of planned investigations that we have looked at previously.
Q The note that you make of a ward round – you said it would be a consultant ward round, Doctor – would he or you have made that decision that those investigations were to be undertaken?
A The consultant would have made those decisions.
Q We see, looking back under ward round, that they involve a number of blood tests, MRI, EEG, lumbar puncture and then there are various testings of the CSF and then barium meal and follow through and the Schilling test. Can you give us any assistance as to how that came about when the initial letter I took you to indicated to the parents that the child was going to have a colonoscopy and Schilling test as to why these decisions were made?
A I cannot tell you specifically why those decisions were made, nor who made them.
Q You have told us that you assumed the protocol was referring to the protocol we have already spoken about. Do the tests that are listed there accord with your recollection and understanding of the tests that were to be carried out under the protocol?
A Without referring to it directly again, but generally I think they are pretty much representative of the tests that were indicated in that protocol.
Q Going back to page 9, is this your handwriting?
A Yes, it is.
Q This is on 4 September, two days later, and it says MRI with a tick, LP with a tick. It gives testing that was going to be done on the LP is that correct?
Q Protein electrophoreses, lactate – can you help me from there?
A “Lactate/pyruvate/glucose” with a blood glucose done at the same time for reference. “Measles antibody”. These should be sent to Nick Chadwick.
Q Do you recall who Nick Chadwick was?
A I think he was a researcher working with Mr Wakefield.
Q On page 14 we see your handwriting again.
Q 13 September – histology meeting. Can you tell us, before we look at the actual note, what that is a reference to?
A There was a departmental meeting on a Friday at which the tissue samples that should have been taken during the endoscopy in the mean time they would have been prepared and on slides and looked at by the pathologist and the pathologist would then show the slides to the team. That was the histology meeting that we had in the histopathology department.
Q Was it a normal part of your job to take notes at that meeting?
Q Would you be involved in the actual discussion between the histopathologists and the clinicians in relation to what the slides showed?
A My job was to give a brief history and then to record briefly the discussion.
Q As far as that note is concerned, would that be the normal place for you to record in the specific medical records for you to record your notes as to a histology meeting you attended?
Q Did you always attend them?
A Not always.
Q Could you help us by reading through that note, please?
A 13/9/1996, histology meeting. “Terminal ileum – no obvious inflammation. Entire colonic series” – that would have implied all the biopsies taken from the colon “an increase in chronic inflammatory cells in mucosa with some oedema”, swelling of the tissue. One section was odd, possibly epithelial cell, marked lymphoid hyperplasia with some evidence of neutrophil infiltration of the crypt. Unusual to see such lymphoid changes in the transverse colon. Rectum slightly degenerate epithelium with a collection of polymorphs.
Q Going to back 145, which is the discharge summary in relation to this little boy, you have told us in general terms that you would write a discharge summary from a review of the medical records, is that correct?
Q Presumably if you had had any involvement yourself with a recollection of your personal involvement.
Q We see on page 145 the diagnosis: apparent neurogenic degenerative disorder and a provisional diagnosis of Crohn’s disease.
“[Child 2] was admitted to our ward on 2 September 1996 for further investigation of several problems. The main problems are of developmental regression from 20 months of age, diarrhoea from 20 months of age and abdominal pain from the same period.”
In the next paragraph you say:
“Mum notes a normal developmental progress. Mum does recount that at 13 months of age he had his MMR immunisation and two weeks following this had started with head banging behaviour and screaming throughout the night. Subsequently seemed generally sickly but nevertheless the main changes appeared to have stemmed from the age of 20 months when he started losing words and became hyperactive and stopped recognising people and responding normally.
Diarrhoea started at that time occurring ten times a day and contained mucous. Only one episode where it contained blood. This time there was undigested food in the stool.”
You set out the various investigations that had been carried out on this child in the past. Going to page 147:
“He was extensively investigated. A full panel of blood tests was performed with regard to his developmental regression. He had a colonoscopy. He had an MRI. He had a sleep EEG and evoked responses. A Schilling test was performed.
You set out the findings.
“The terminal ileum appeared abnormal showing marked lymphonodular hyperplasia though no ulceration. Histology possibly demonstrates mild chronic inflammation within the lamina propria of the terminal ileum. Difficult to estimate whether or not this is within normal limits. Throughout the large bowel there was a patchy increase in chronic inflammatory cells with an occasional prominent lymphoid follicle with a germinal centre. The patchy distribution of this inflammation and the involvement of the terminal ileum are in keeping with a diagnosis of Crohn’s disease.”
Then you set out the Schilling test, the MRI, the Electrophysiology, blood tests and on the next page CSF results, Urine, Barium meal and follow through, and Plan:
“In view of the colonic inflammation it was decided to treat him with an enteral feeding regime.”
Is that a liquid regime, Doctor?
A That is a liquid diet which is used for the treatment of Crohn’s disease.
Q He was to have that for eight weeks.
“We will consider reintroduction of food and review him regularly.
With regard to his neurological problems an opinion of a neurologist and a child psychiatrist have been sought. I am sure that they will forward further information to you.
We will review him in clinic in two weeks time. As with all children who start on enteral feeding, he will need a repeat colonoscopy after having been on the diet for eight weeks. We will also need to arrange an upper endoscopy in the near future.”
Is that in fact the case that a child who was on enteral feeding would have a repeat colonoscopy?
A At eight weeks, yes.
Q Whose decisions were the decisions as to treatment that you set out in that letter, Doctor?
A They would have been the consultant decision.
Q As far as your actual discharge letters are concerned, did you run them past anybody more senior to yourself or were you in charge of them and responsible for writing and sending them?
A Whether I run them past, I am not sure, but certainly they would have been based on discussion with the consultants.
Q The discharge letter at page 148 is signed by you and page 149 we see that it is copied to Dr Wakefield and Professor Walker-Smith amongst others, is that correct?
Q It included Dr Hunter, who is a gastroenterologist who had been treating the child at Addenbrooke’s. Would that be the norm to include both the consultants at the Royal Free and people who were treating him outside the hospital other than the GP?
Q At page 150 we see that you sent a discharge summary for Child 2 to Dr Youl in the EEG Department.
Q It seems to have been as requested, but would that have been the norm? Was there anything unusual about that?
A I think we would have responded to any doctor who wanted a copy of the letter who had been involved and it seemed appropriate to send a copy of the letter.
Q On 16 September 1996 and the last involvement you had was in August 1997 when you wrote to mum [page 98]:
“Further to our telephone conversation, please take this form to the x-ray department on the morning prior to your appointment for abdominal x-ray. Please bring the x-ray film to clinic for us to see.
I hope things are improving with the increased Salazopyrine.”
It would appear that later on this little boy had an abdominal x-ray.
Q Can you assist at all as to what that would have been for?
A I cannot be specific but I suspect it was to look for any evidence of constipation.
MS SMITH: Sir, that is all the questions I have to ask about Child 2. I am going on now to Child 1. I see it is quarter to eleven. I do not know whether you think it appropriate to have our short break now?
THE CHAIRMAN: Yes, indeed. We will adjourn now and resume at ten past eleven. (Usual warning given to the witness)
(The Panel adjourned for a short time)
MS SMITH: You will next need the Royal Free Hospital records for Child 1, page 9. Is this your handwriting, Doctor?
Q This is the admission clerking note for this child, is that correct?
A I would assume so, yes.
Q I meant to ask you this question in relation to Child 2, but I can ask you just as well in relation to Child 1 if it is your handwriting. Was it usual for you to do the clerking notes in the department?
A Yes, it would have been myself and any of the junior doctors.
Q It says 3½ years – that is the age again, is that correct?
Q Can you read out what it says referred for?
A “Referred for work up of ? relation between autism, measles and IBD” and then “c/o” is complaining of classical autism diagnosed one year ago, diarrhoea, concern over deterioration of eyesight.
Q In the middle of the page, “First awareness of problem at 18 months,” is that correct?
A That is correct.
Q Can you read what it says in brackets?
A “Whilst other child who is part of autistic continuum noted to be having problems with speech”.
Q Turning over, we see the gastrointestinal tract under GIT.
Q What does it say there, please?
A Diarrhoea started at approximately 18 months of age five times a day, watery with no blood and no mucous with undigested feeds. Since then has had undigested food in it. Now seven times a day with no bowel control, no blood, possibly occasional mucous, not offence [not offensive smelling] and occasionally pale. Appetite small and picky. He is a picky eater. Occasional vomiting approximately once every four to five months.
Q The information that you would put in this note, in normal circumstances where would that come from?
A It would normally come from a parent.
Q As far as your observations at the very top of the note on page 9, “Referred for work up of ? relationship between autism/measles/IBD”, where would your understanding as to why the child was being referred have come from?
A the referral would have come from one of the consultants.
Q Going to page 49, this is the discharge summary dated 9 August, 1996.
Q On page 51 we see that it was signed on your behalf with a copy to Dr Wakefield.
“Child 1 was admitted for further investigation of his autism and specifically to look into a possible association between his neurological condition and any gastrointestinal disorders. The main problems are a “classical” autism diagnosed a year ago and of diarrhoea.”
On page 50:
“His diarrhoea started approximately 18 months ago. He passes five watery stools a day which contain no blood or mucous. They do contain some undigested food. He appears to have no control over his bowel movements and frequency is increasing. His appetite has always been poor and there has been no obvious change in this. He has only very occasional episodes of vomiting.
He is up-to-date with his immunisations, including his MMR at 12 months of age. There is obvious parental concern that this has some bearing on his subsequent condition.”
It then refers to a five-year-old brother with a speech problem also described as part of the autistic continuum. He also has Toddler’s diarrhoea. Does that mean the brother?
Q You deal with his weight and height.
“An initial colonoscopy on 22 July had to be abandoned due to gross faecal loading. Subsequently cleared out and the procedure was repeated three days later. On this occasion the caecum was reached although it was impossible to pass further due once again to accumulated faecal matter. Macroscopically no abnormality noted. An upper endoscopy was also performed. No obvious lesion to the second part of the duodenum. A small amount of altered blood.”
You set out the histological examination had demonstrated a small degree of focal active and chronic inflammation within the caecum. Small bowel series demonstrated occasional foci of chronic inflammatory cells within the lamina propria of the gastric body. No active inflammation seen. No helicobacter seen. Further biopsies from the oesophagus. Samples were also sent in view of chronic diarrhoea, awaiting results.
A brain MRI was performed. At the bottom you say:
“We would like to review Child 1 in clinic to discuss the implication of the mild degree of inflammation seen in his biopsies. It is also not entirely clear whether his neurological condition in fact represents a neurological deterioration in view of lost milestones, or whether it is a classical autistic picture.
We will consider these features when we see him again.”
I have referred to the fact that it is signed on your behalf, Dr Casson, and copied to Dr Wakefield, is that correct?
Q With regard to the plan that appears to be being made or the wish that you would see the child again, going on to page 52 a letter of 8 August 1996 from you to Dr Wakefield:
When would you like us to review this patient again and are there any other procedures we should be performing?”
There is no response in the medical records to that letter, Dr Casson. I do not know whether you have any recollection of it. Do you recall whether there was any response?
A No, I do not recall.
Q As far as that letter is concerned, can you recollect at all the circumstances in which you were asking Dr Wakefield when he would like the patient to be reviewed again and what other procedures should be performed? Can you recall anything of the circumstances of the letter?
A No, I cannot.
Q Would you have written a letter of that kind to Dr Wakefield off your own bat, so to speak, or would someone have requested you to do so?
A I do not think I would have written it off my own bat, no.
Q Who would have requested you to do so?
A Presumably one of the consultants.
Q Again say if you cannot recall, but can you assist us at all as to the nature of the other procedures that you might have had in mind, given what you have said in the discharge summary about the tests the child has had?
A In the discharge summary I make no mention of other investigations which made up part of the general investigation for children as part of our protocols. It may have been a reference to those sorts of investigations.
Q I am sorry, you say the general investigations for children as part of the protocol?
A I am not saying this child – I do not know whether he was or he was not – but I presume that those would have been the sorts of investigations that I would have been indicating in that letter.
Q You say you do not know whether he was or was not, Doctor, but if we go back to page 9, does that help you at all with what you say he was referred for?
A That lists the peripheral work of the possible relationship between those conditions. It does not say specifically whether it was as part of a protocol or not.
Q If we go on to page 47, please, this is a letter that you wrote to the mother:
“Dear Mrs [One]
Further to our telephone conversation, this letter is to confirm that [One] should be admitted to Malcolm Ward on Wednesday 23 October 1996. He should arrive on the ward at 8.30 a.m. starved. If this is a problem do please contact the ward so that they can arrange admission the night before.
He is due to have a barium meal and follow-through on Wednesday. He will have an EEG and evoked potentials at 11 a.m. on Thursday. This will be performed under sedation. In association with this, whilst still sedated, he will need a lumbar puncture. During the admission various blood tests will also be taken. I hope this is satisfactory.”
Does that assist you at all as to whether this child was part of what we describe as the protocol?
A The investigations are those which are included in the protocol.
Q Can you help as to who would have decided that this boy was to undergo those tests for you – to write that letter, I mean?
A I cannot recall specifically who would have instructed me to write that letter, but I would have taken instruction from one of the consultants.
Q When you say “one of the consultants”, Doctor, who exactly do you mean by that?
A From Professor Walker-Smith or from Dr Murch.
Q Would Dr Wakefield have played any part in the decision making as to the investigations?
A I cannot recall whether for specific patients he would have made a decision about what investigations would be undertaken.
Q If we go on to page 91, this is a consent form for a lumbar puncture under sedation on this child on 26 October. It is signed by you, is that correct?
Q Can you help us as to the nature of that consent form, Doctor? Is that a standard consent form, a consent form for research purposes? What is it?
A This is a standard consent form.
Q Would you have been guided at all as to what consent forms you were to use on these, or indeed any patients, or did you choose the nature of the form?
A I cannot remember any guidance as such, no.
Q I think you have answered this generally but if any other consent form was to be used, in other words any relating in particular to this protocol, did you have anything to do with that?
A I do not recall taking specific consent for entering into a research protocol. My recollection is of consenting for individual procedures.
Q If you go back to page 43, this is the discharge summary, again as signed by you, which you sent to the GP:
“Further to [One’s] last admission, he was re-admitted in order to perform the various tests which were not performed.
Faecal loading throughout.
BARIUM MEAL AND FOLLOW THROUGH
Difficult study to perform…… appear normal.
You then set out the various blood tests that were carried out. “EEG & Visually Evoked Responses” – no signs of major cerebral dysfunction, and a simple wave form “probably normal”.
“We will need to arrange a further admission for [One] in order to repeat the colonoscopy. Previously we have not visualised terminal ileum due to marked constipation.
I have advised that treatment for the constipation should initially be 10-15 mls of liquid paraffin bd.”
Then there is concern about the inability to pay for nappies and you said you would find out whether you could help her with that. Is that correct?
Q You say,
“I have advised that treatment for the constipation should initially be …. liquid paraffin…”
Would that in fact have been your advice? Would that have been advice you could have given?
A I cannot recall specifically whether that was advice that I would have given or whether it was an instruction, but treatment for constipation for children with neurological disorders often did involve liquid paraffin, and therefore if treatment was required, it would have been liquid paraffin.
Q Is that consistent with the abdominal X-ray, that constipation is a problem?
Q I am now going to ask you to turn to Patient 3, and again it is the Royal Free Hospital records as far as the panel is concerned. Would you go to page 49? This is a letter dated 18 July 1996. In fact it is from Professor Walker-Smith to Dr Wakefield. It says:
“This child with autism has had no evidence of bowel inflammation on routine blood tests; however we are arranging his admission for colonoscopy on Sunday the 8th September, followed by your intensive investigations. I would be very grateful if you could arrange the other aspects of his admission.”
That has a note on it, and I think the note is from you. Is that correct?
Q It says:
“For colonoscopy only as discussed with” and is that Professor Walker Smith’s initials?
Q “and Dr Murch”. Is that correct?
Q Can you assist us at all as to the circumstances in which you would write that sort of note on a letter, and we see it is dated 23 August 1996, so a bit later than the actual letter to Dr Wakefield? Can you recall the circumstances of writing that?
A I cannot recall the circumstances of writing that, no.
Q Whose decision would it have been to admit this child for colonoscopy?
A Professor Walker-Smith or Dr Murch.
Q Again, I ask you this question generally: would you have felt able to question the reasons for that admission?
A I am sure we could have discussed it but I respected their opinion.
Q If we go on to page 45, this is a letter dated 28 August 1996, so four or five days after you wrote the note of your discussions for colonoscopy only. This is to the mother of the child. It says:
“Dear Ms [Three],
This letter is to confirm that [Three] is to be admitted to Malcolm Ward on Sunday 8th September 1996 for colonoscopy.
Any further investigations required will be decided on another occasion following consultation with Dr Wakefield.”
Is that correct?
Q Again, Doctor, the same questions and you must tell me if the answers are the same. What investigations would you have had in mind when you wrote that?
A I cannot be specific but again I assume they refer to some of the investigations which made up part of the wider scheme of investigations for children with this disorder.
Q The consultation with Dr Wakefield, would that have been between you and Dr Wakefield?
A I do not recall specifically but, as I say, the department was an open department and it may well have been that I had discussion with him.
Q Then, if you go onto page 3, please, we will see that is the printout again of admissions and we see under the patient episode summary, admission as an inpatient between 8 September 1996 and 13 September 1996. Is that correct?
Q To Malcolm Ward and Professor Walker-Smith’s name under the consultant’s column?
Q If you go on to page 16, is this your handwriting that we see at 1800 hours on 13 September?
Q Can you see what it says; “Discussed with Mum…”
A Would you like me to read it?
Q Yes, please, just read the note out?
A “Her main concern is over constipation, therefore for liquid paraffin 15mls once a day. NB Note, no bowel opening until 5 days of age.”
That would have been a reference to when he first had his bowels open following birth.
“? need to exclude Hirschsprung’s disease
NB It has not been possible to do evoke potentials or Schilling test. Need MRI, EG and Barium follow-through results.
Recall antigens awaited.”
Do you want me to carry on with this?
Q Can you tell us, are the rest blood results and cerebro spinal fluid results? You help me. It says “lumbar puncture”, does it not, half-way down. What are these results? Are they all blood tests or are some of them cerebro spinal fluid? If you turn over, Doctor, you will see that they go on down to the bottom of the page. We have CSF results in the middle of the page there.
A I am really not sure whether those first two, pyruate and lactate, relate to lumbar puncture. It is most likely they refer to lumbar puncture. That would be a lactate/pyruate ratio presumably.
Q What about the rest?
A The rest are blood tests.
Q We see the results, including measles results, is that correct?
A That is correct.
Q That is for testing the blood, is it?
Q Then over on to the next page, are the first lot down to the CSF protein result all blood tests?
A Down as far as IGM 0.8, those would be blood tests. Protein plasma freezes, that would be a blood test, and then here is CSF protein, CSF glucose and CSF lactate, which would mean that the previous results were blood tests. The previous lactate and pyruate presumably then were blood tests and these are the results from the CSF.
Q Then going down to the next heading of barium meal and follow through; is that correct?
Q Can you read to us what the note under that says?
A “Small bowel normal with no evidence of” and there is hardly anything here, I am afraid, “terminal ileum well visualized as normal”.
Q Then the results of the MRI, is that correct?
A Yes. Do you want me to read that?
Q Yes, you can read out what you regard as being the salient information in it.
A “Saggetal axial coronal imaging, The ventricular system and subarach. spaces normal. Small patches of hi. Ts and low T1 signal in the left frontal” central of ileac presumably. No evidence of further abnormalities. Appearances are non-specific but suggest a small area of small damage ? ischemia. EEG within normal limits. (EPs [evoke potentials] unsuccessful).”
Q Thank you. Before I go on, perhaps I can ask you the question I asked you for the previous patient and again I do not mean this critically in any way. Can you assist us at all as to how it is that the original letter for admission has the handwritten note on it saying “for colonoscopy only after discussions with Professor Walker-Smith and Dr Murch”, but then we have this list of all the tests that were carried out under that admission?
A I wonder whether “for colonoscopy” meant “not for upper endoscopy”, so refers mainly only to the endoscopic procedures rather than to everything else.
Q I see. Can you help at all on the reference to other investigations being decided on another occasion. Would they have been over and above all these investigations which we have just run through or are they are a reference to that?
A I think that they are probably a reference to that.
Q If we go on, we see that you have written a discharge summary and that is on pages 26 to 28. Would you turn to page 28 which is signed on your behalf and with a copy to Dr Wakefield, Dr Rosenbloom at the Alder Hey, who is a paediatric neurologist; is that correct?
Q And Dr Alton who is in electrophysiology. Going back to page 26,
“[Child 3] was admitted for possible inflammatory bowel disease and a possible association of this with his autism”
and then under “DEVELOPMENT” it sets out his birth history and,
“He had his MMR injection at 13 months of age and on the 2nd day after injection he had a fever and a rash. Overall mum considers that his developmental regression has progressed since this time.
As regards bowel symptoms, he intermittently suffers from quite marked constipation. He has had occasional rectal bleeding although this does seem to accompany passage of a hard stool.
Colonoscopy was performed under sedation. This was reported as normal to the terminal ileum but with increase in the number of lymphoid follicles within the terminal ileum. An upper endoscopy was also performed on this occasion and was reported as normal.”
That suggests, does it, that your interpretation of the “colonoscopy only” note is not correct.
A It may do. It may be that the decision was taken later to do an upper endoscopy as well.
Q The histology is set out,
“Small bowel mucosa showed an increase in intra-epithelial lymphocytes but there were no architectural abnormalities. Histology of the terminal ileum showed prominent lymphoid follicles. Colonic histology was also reported as within normal histological limits. Overall there appeared to be therefore mild inflammatory reactive changes in the small bowel samples. No granulomas were identified”
and you set out the investigations which we have been through both in relation to blood tests and CSF results and to the barium meal and follow-through, the MRI scan and the EEGs and in conclusion you say,
“Therefore he does not appear to have significant bowel disease. There are several mildly aberrant blood results specifically an elevated blood lead and an elevated lactation. No other metabolic abnormalities were detected. The significance of the MRI findings are uncertain.
We will have to re-consider these findings when we review him again in clinic. As regards the protocol that patients who are being investigated as [Child 3] is concerned, we have been unable to perform the Schilling test and the evoked potentials.”
As regards the view that the child did not appear to have significant bowel disease, we saw the letter that Professor Walker-Smith had originally written saying that there was no evidence of bowel inflammation on routine blood tests. Would this conclusion in the discharge have been a reference to the consultant’s views or would it have been your own interpretation of the results that there was no evidence of significant bowel disease?
A I think that it would have been a consultant decision. These were results that were discussed generally, for example at the histology meeting, and those were the forums at which we decided whether changes were significant or not.
Q Would you go on to page 35 where we see that there was a revised discharge summary and I would like to run through that. It was revised on 31 December 1996 and a diagnosis has been inserted of “indeterminate ileo-colitis & lymphoid nodular hyperplasia” and, if we go on to the next page under “histology”, we see that “small bowel” is crossed out and “ileal” has been inserted and then, where it said, “Colonic histology was all reported as within normal histological limits” that has been crossed out and “Colonic histology revealed an increase of inflammatory cells” has been inserted. Down the page, where it said “Full blood count normal”, that has been deleted. On page 37, “Therefore he does not appear to have significant bowel disease” has been crossed out and instead has been inserted, “He thus had evidence of indeterminate ileal colitis & lymphoid nodular hyperplasia” and “are” has been crossed out and “were” included, in that “There were several mildly aberrant blood results …”
First of all, are you able to help us as to whether those are your alternations to the discharge summary?
A It is not my handwriting.
Q How usual or unusual is it to have a revised discharge summary in this way?
A It is unusual.
Q Can you assist first of all as to who made the amendments to it?
A I do not know who made those amendments.
Q Can you assist at all as to how they may have come about?
A It may be that biopsies were reviewed and the interpretation was reconsidered at a later date.
Q You said that it may be; do you have any recollection or is that you trying to construct why it might have come about?
A I am trying to suggest why it might have come about.
Q I think you said that your original conclusions in the discharge summary you wrote would have been in some sort of consultation with the consultants; is that correct?
Q You have told us that it would be unusual to see a discharge summary amended. In your experience, was it ever the case that there were amended histology reports in the records?
A The process of reviewing the biopsies often meant that the conclusions reached by the histopathologist might have been changed following discussion with members of the team. I do not recall specifically whether a copy had been made of the original opinion of the pathologist and then subsequently changed on the basis of the discussion but it is certainly possible that opinion was refined following the histopathology meeting.
Q Can you help us – again, say if you cannot recall – and I am not really now asking particularly about this or indeed any of these cases but, generally speaking, if there is a change of view when a histopathologist has a consultation with a clinician, do you see a revised histology report in medical records? Do you expect to see one?
Q I think it is right, although you may or may not recall, that in this particular child’s case, you became involved in his care a significant time later by which time you had become a consultant at the Alder Hey and you need now to refer to a different volume which is the local hospital records for this little boy, Child 3, please. They are in another file and I am on page 123. This is much later on, on 12 November 2001, a letter to you, now consultant paediatric gastroenterologist at the Alder Hey Hospital and it is from Dr Rosenbloom, the paediatric neurologist, and he says that he closes the medical records for the child, an autistic boy at a residential school, and he says,
“My involvement with him has been limited.
He was first referred to my service in 1992 and was recognised as being autistic at that time. He has remained overtly autistic since.
His mother was convinced that this was secondary to MMR immunisation and subsequently found her way to the Royal Free Hospital where it is my understanding that Andrew Wakefield on endoscopy found evidence of what he considers to be inflammatory bowel disease and has treated [Child 3] since then with Salazopyrin and Sytron.
I am on record as being sceptical about the various hypothesis advanced by Andrew Wakefield firstly on the relationship between MMR and autism and secondly on the concept of autistic enterocolitis.
Having not seen [Child 3] for some time I then heard from the school doctor … recently asking if I would review him …”
and he says on the next page,
“The ostensible reason for my being asked to see [Child 3] was to comment on his best management but clearly what [mum] wanted was a re-prescription for Salazopyrin.
This I am afraid I am not prepared to do but I did arrange to check [Child 3]’s haemoglobin given that he is also taking Sytron and has been for a long time.
My difficulty is not only the conceptual one of not accepting the concept of autistic enterocolitis but also the fact that nowhere within the Alder Hey records is there any correspondence from the Royal Free Hospital.
[Mrs 3] and I reached an impasse therefore.
In the circumstances I wonder if you would be prepared to see [Child 3] … and comment on whether there is gastroenterological diagnosis and whether treatment for this is indicated.
I suspect that you might be in a good position to get useful information from the Royal Free Hospital.”
If we turn to page 125, we see that you did indeed see this little boy on 27 February 2002; is that correct?
Q You say,
“[Complaining of] bowel problems → constipation.”
Perhaps you would read out what it says thereafter as mine is very faint.
“[History of presenting complaint] was present at 3 years”
and that was constipation.
“Dr Wakefield” and it indicates that a colonoscopy had been performed
“raised concerns over measles.
Since then on Salazopyrin → no difference.
bowels are open once a week with significant straining. No blood. He gets distressed and becomes aggressive. Appetite and weight are all stable. He is not on any exclusion diet.”
Q Turning over, we see “Not possible to examine”. Would that have been because of his behavioural problems?
Q A long discussion and then can you tell us what you advised?
A (1) stop Salazopyrin and (2) treat constipation with liquid paraffin.
Q Going to page 129 we see the letter that you wrote thereafter to the GP:
“Dear Dr Shantha,
I reviewed [Child 3] in clinic. The main concern is constipation. He had been seen at the Royal Free Hospital several years ago and a diagnosis of MMR associated colitis was made. Subsequently he has been treated with sulphasalazine but has been no follow up and there did not appear to be any useful outcome from this medication.
Presently he opens his bowels once a week. He strains and passes a large hard stool. In himself he is otherwise well with no other signs of note. I could not examine him today.
I had a long discussion and have advised stopping the sulphasalazine as it has obviously not been providing any relief. I started him on an aggressive anti-constipation regime involving the use of liquid paraffin with very, very gradual reduction. They should not stop the treatment as I suspect he will need it lifelong and need to achieve a dose that provides best results.
I will review him again in clinic in three months’ time.”
Was that the view that you reached having seen this child in the early 2000s?
Q Lastly, page 133, by August 2003 the child had failed to attend your outpatients on two consecutive occasions and in those circumstances you say he had been treated with problems for constipation.
“I trust that his bowel symptoms are generally under control now and I have therefore not sent him a further appointment.”
Q That is the end of your involvement. Thank you, Doctor. That is all I have to ask you about Child 3.
Turning to Child 4, you will need the Royal Free Hospital records on Child 4. Going to page 25, first of all, this is a letter from you to the parents dated 28 August 1996:
“Dear Mr and Mrs Four
This letter is to confirm that [Child 4] is to be admitted to Malcolm Ward at the Royal Free Hospital on Sunday 15 September 1996 for colonoscopy. Any further investigations required will be decided on another occasion following consultation with Dr Wakefield.”
Do the same responses apply as you have made in relation to the other children that I have asked you about in regard to this letter, Dr Casson?
Q Do you have any recollection other than what is contained in that letter?
Q Taking the documents chronologically, there is an admission clerking note from you, I think, which starts on page 5, dated 29 September 1996. Is that your handwriting?
Q I asked you this on the previous child, Doctor, whether it was usual for you to do the admission clerking notes and you said yes, one of the junior doctors. I think I ought to be clear about exactly what you mean by that. Would you normally call yourself a junior doctor at that stage?
Q Who else would there have been junior? I do not mean their names but their status?
A I think there was a senior house officer as well. The date of 29th I suspect is a Sunday and I had a habit of coming in on a Sunday to clerk these patients in anyway so I presume that is why most of them would have been clerked by me initially.
Q When you say you had a habit of coming in on a Sunday to clerk these patients …
A Sorry, any patients who were admitted on a Sunday for any work involving endoscopy.
Q You say this is your note.
Q Can you read out what it says at the top for us?
A “Admitted for study of disintegrative disorder/colitis/MMR.”
Q Beside that?
A The note in the column?
Q On the right-hand side.
A I presume it says “Admitted for study”.
Q We see underneath, “Complaining of diarrhoea ? food related”, is that right?
Q “Behavioural ? – food related/hyperactivity.”
Q Developmental regression, sleep problems, ---
MR HOPKIN: Sir, if I might interrupt a moment, Ms Smith has referred to the handwriting in the right-hand column. We think it is possibly a Post-it and it may well be something that lawyers looking at these notes have put on when photocopying. If any issue is to arise on this, I wonder if the originals could be called for?
MS SMITH: That is helpful. I was simply making sure that we read out everything on the page. I should have asked is that not your handwriting, Dr Casson?
A That is not my handwriting.
Q We will get the originals but I am perfectly happy to accept that that may be the case. There is a reference to some sort of skin condition, eczema ? food related and then abdominal pain. Is that correct?
A That is correct.
Q Going to page 6 we see reference four lines down, “Had had MMR” ---
A I think that is “Had had ? MMR”.
Q Could you read the rest of that?
A “Approximately four weeks before the loss of skills. (NB had previously had measles at 15 months of age).”
Q The gastrointestinal symptoms are set out on page 8.
A I wonder if they are slightly out of order.
Q I think you are correct in that page 9 appears to be out of order and I was going to ask you to go on to that, but you think 8 is as well, do you?
A Possibly 8 should come before 7.
Q It is probably right that 9 is out of order. It should go on to 10 because we see at the top of the page the plan. Do you see where I am?
Q Taking you back to page 8, can you tell us what it says about the gastrointestinal symptoms.
A Diarrhoea - roughly became a problem between one to one and a half years. Initially the stool was loose and watery with increased frequency up to three or four times a day, no blood, no mucous and no soreness around his bottom. The stool contained undigested food and continued to about 4½ years of age about the same time as his behavioural deterioration. There was increased frequency of stool and it was more watery than previously up to between two and six times a day, once again without blood and uncertain whether it contained undigested food on this occasion. There is no known associated infection to accompany this deterioration. His weight appeared to fall, his appetite was stable and he was possibly lethargic. It was associated with some abdominal pain and he appeared to cry with the pain. Three years ago he started with exclusion diets and he seemed to respond to withdrawal of yoghurt. Reintroduction of milk for eight weeks which resulted in diarrhoea. Fruit juices reintroduced caused diarrhoea once again after four days and fruits – I cannot decipher the precise meaning of what that is. Presently he is well most of the time. If he does get an exacerbation it seems to be related to new foods. He is opening his bowels once or twice a day and this is normal without any straining at stool. Pear juice – there is a reference there to constipation – whether that is causing or treating, I am not sure. Abdominal pain appears to have resolved. He possibly had two episodes of giardia proved on one occasion a year ago for which he received no treatment. There are no pets at home.
Q What is giardia, please?
A Giardia is a gastrointestinal infection.
Q You need not worry with the rest of it which I think deals with a skin condition and sleep. If we are right about the page order, going to page 10, is that still your writing at the top of the page where it says “plan”?
Q Can you tell us what it says?
A Plan – needs (1) OGD, which is upper endoscopy, and colonoscopy, (2) MRI, (3) EEG and I think that must be EP (evoke potentials), (4) lumbar puncture, (5) bloods as indicated, (6) ECG and chest x-ray.
Q What is the wording beside it with the bracketing?
A “Needs to be booked” I think it probably says.
Q Beside it we see “planned tests” – is that your handwriting?
Q In the column to the right it says “Planned tests”.
A I do not have that.
Q That proves Mr Hopkins’ point that it was a Post-it and I will not ask you any more about it. Mine says “Planned tests” in another handwriting. As far as those tests are concerned, Doctor, would you have made the decision as to the tests that were to be undergone?
A Generally not. I think I detected a heart murmur and therefore possibly the ECG and the chest x-ray were a general decision.
Q How do you differentiate that from the rest?
A They would have been following discussion.
Q With Child 4, as we have seen from page 25, the admission originally was envisaged for colonoscopy with any other investigations required to be decided following consultation with Dr Wakefield, but these tests seem to have been decided at the time of the same admission. Can you help as to that?
A I am not sure what stage they would have been decided, but obviously it was listed as indicated at this time.
Q The tests that you had set out previously, other than the chest x-ray which you have said was because you thought there might be a heart problem, did the rest of them conform with the protocol tests? (Page 10)
Q Turning to page 80, which is the consent form for colonoscopy and upper endoscopy with biopsy, is that correct?
Q That is taken by you.
Q Is that a standard clinical consent form for colonoscopy?
A Yes, it is.
Q What is the reference there to biopsies?
A It is that every procedure that is going to be undertaken should be explained and consent obtained for everything.
Q The reason for biopsies in a standard colonoscopy, what is that?
A The biopsies provide the most important diagnostic evidence in many circumstances.
Q Going back to page 13, this is 4 October, so during the inpatient admission which began on 29 September. Are there two notes by you on that page, both dated 4 October 1996?
Q Can you read them for us, please?
A “Now well. No further vomiting. Explained to mum that we need to wait for the histology report and uncertainty around when he will come back for further investigation.”
Q Looking at the second note, is that a note again of the histology meeting?
Q Can you read that out to us, please?
A “Ileum – dense lymphoid pattern – no acute inflammation – normal architecture. Colon – prominent lymphoid follicle – no active inflammation. Rectum – I have not made a note but overall no granulomas.”
Q Would that have been a note of the histology meeting as you have described to us previously?
Q Going to page 21 we see your discharged summary. This goes on to page 24 and we see your signature. This is dated 16 October 1996:
“Diagnoses: Autism/Development regression; Food related symptoms including diarrhoea, rashes and abdominal pain; and lymphonodular hyperplasia of the terminal ileum.
[Child 4] was admitted to the Royal Free Hospital for further investigation of a possible link between a disintegrative disorder and colitis. His main problems are:
Behavioural disorder manifest by hyperactivity
Going to page 22:
“He had his measles immunisation initially at 15 months of age and a second subsequent measles immunisation at approximately 2½ years of age. Mum relates a change in his behaviour from a period extending four weeks after the second measles immunisation.
Socially mum noticed that behaviour responded to dietary variation.”
You set out those terms. In the next paragraph:
“The diarrhoea also appears to be food related. This became a problem at between 1-1½ years of age. His stool was initially loose and watery and then became increased in frequency. It contained no blood or mucous and he has no peri-anal soreness. It generally contains undigested food. His diarrhoea became significantly worse from 4½ years of age. There was a marked increase in frequency and it became increasingly watery. In association with this his weight fell and he became increasingly lethargic. There were associated abdominal pains. Mum started excluding various foods and noted that he seemed to respond specifically to withdrawal milk, fruit juices and fruits. On his present exclusion diet he remains well most of the time. If he does get an exacerbation of diarrhoea it does seem to be relate to introduction of new foods. He now has his bowels open once or twice a day and this is of normal consistency. Abdominal pain has largely resolved. It is worthy note that he had Giardia grown from his stool a year ago.
His present medication involves Evening Primrose Oil. Mum feels that this has made a marked improvement in his behaviour.”
Turning to page 23:
“Colonoscopy was performed under sedation. Mild granularity of the rectum with slight distension of the vascular pattern. The colon was normal, however the ileum showed marked lymphonodular hyperplasia. Histology of the ileum showed a dense lymphoid aggregate with no obvious acute inflammation and normal architecture. Within the colon there was noted to be several prominent lymphoid follicles but again no active inflammation. Rectum was normal. There were no granulomas.
Barium meal and follow through – unable to perform
MRI Scan – no abnormality.
Lumbar puncture and Schilling test not performed.
EEG and evoked responses/blood results.”
At the end we see why these investigations were not performed:
“Unfortunately because he had a period of vomiting and became generally unwell it as impossible to complete all the investigations. We will therefore need to consider repeating these on a further occasion, i.e. barium meal and lumbar puncture.”
You say that an ECG was performed. The reference to needing to come back for a barium meal and lumbar puncture – what would be the reason for that? Why would he have to come back for those tests?
A Presumably because we had been unable to perform those tests because he was unwell.
Q Those tests were being performed on him for what reason?
A The barium meal is a test to outline the lining of the bowel and give an image of whether there is any inflammation or other changes within that and the lumbar puncture would have been to further pursue his neurological problem.
Q The overall series of tests which we have gone through, which you have set out in that letter, of colonoscopy, the MRI scan, the EEG and evoked responses, the blood results and the envisaged barium meal and lumbar puncture, what were they in accordance with?
A They were in accordance with various investigations that were outlined for investigation of children with this problem.
Q Could you put away that file, please and turn to file 6? This is slightly confusing. Can I just tell the panel that Child 6 is the brother of Child 7. Dr Casson, what you need are the additional records bundle for Child 6 and the Royal Free Hospital records for Child 7 because there is some reference to Child 6 in there. Please go in the additional GP records for Child 6 to page 41. This again is the printout for admissions. If you look under “Patient episode summary” we see an inpatient admission for this child from 27 October ’96 to 1 November ’96. Is that correct?
Q We see again Malcolm Ward and the consultant, Professor Walker-Smith?
Q If we go to page 45, this is a consent form signed by you, for MRI, EEG and lumbar puncture. Is that under sedation?
Q Again, is this, as far as you are concerned, the standard consent form for a clinical investigation?
Q Do you have any recollection or knowledge of what the position was as far as a research consent form was concerned?
A I cannot recollect that.
Q If you go over on to page 46, again we see the notes of a histology meeting signed by you. I would be grateful if you could just read through those for us, please.
A “TI” is terminal ileum,
“3 lymph follicles in the biopsy. Slight increase in chronic inflammatory cells within the lamina propria. Few cells infiltrate surface epithelium in a patchy manner. Occasional polymorph in crypt.
I think that must be:
“Similar throughout”; i.e. all the biopsies from the colon were largely similar with “normal crypt architecture. Minor goblet cell depletion with patchy polymorph infiltration of epithelium.”
The conclusion is: “A microscopic colitis” which is not lymphocytic and it is in a patchy active distribution throughout the colon, and the suggestion is to treat with Azacol or Olsalazine and there is a dose for the Olsalazine of 250 mg three times a day.
Q If we turn back to page 12 in the same bundle, we see a letter or statement dated 26 March 1997, signed by you,
“To whom it may concern
[Six] who had previously been diagnosed as Aspergers syndrome and was investigated by us for intermittent abdominal pain and diarrhoea. Diarrhoea occasionally contains blood and mucous.
Investigations that we performed showed some abnormalities of the lining of the bowel. Specifically the rectum show minor abnormality of the vascular pattern, the caecum and ileum showed lympho-nodular hyperplasia. Under the microscope the appearances of tissue taken during this procedure showed a mild patchy increase in inflammatory cells throughout the colon. There was also mild architectural distortion within this tissue.
We have started him in anti-inflammatory medication Olsalazine 250 mg three times a day.
He appears to have made a good response to this medication and therefore should continue on it for the foreseeable future.
I hope this is sufficient information. If you require more treatment, please do not hesitate to contact us.”
Can you help us at all, Doctor. First of all, Olsalazine is an anti-inflammatory. Is that correct?
A That is correct.
Q Again, who would have made the decision as to whether to start this child on an anti-inflammatory?
A It would have been again one of the consultants who made the decision but it looked like that decision was taken, as I said previously, within the histology meeting as it comes at the end of that report.
Q Can you assist at all as to whom this letter was addressed “To whom it may concern” and what its purpose was?
A I cannot specifically say what purpose this formed or what this was for.
Q Is it a usual thing to write in those terms just “To whom it may concern”?
A Again, I do not know specifically. Occasionally such letters are written as an information letter for the parents to hold and to present to other doctors, if need be. I think the last line should probably be “more information” rather than “more treatment”. “I hope this is sufficient information. If you require more information, please do not hesitate to contact us” That is a typographical error.
Q If you look in the Royal Free Hospital records for Child 7 at page 57, this was a letter which was written in relation to both Child 6 and his brother, who was Child 7. I am going to come back to it obviously with Child 7 but at this point I am only concerned with that part that relates to Child 6.
“Dear Dr Bennett,
Thank you for your letter of 23trd April 1997 regarding [Child 6]… I have also had a discussion with… the Headmaster…. Who has been involve in assessing the educational requirements…
[Child 6] was admitted to our Unit in October of last year. He is one of a group of children we have been investigating for a possible association between part of the autistic spectrum and gastro-intestinal symptoms. There is also a possible association of these problems with measles immunisation.
Mum gave a history in [Child 6] of changes in social interaction following on immediately from his MMR vaccination. She also noted that 2 months following his MMR he started to develop abdominal pain before having his bowels open. She occasionally noted blood and mucous in the stool.
We performed a colonoscopy on [Child 6]. As with previous children investigated as part of this spectrum, his rectum showed minor abnormality of vascular pattern and the caecum showed prominent lymph nodes. Furthermore in the terminal ileum there was marked lymphonodular hyperplasia. Histology of biopsies taken were consistent with a mild indeterminate colitis.
In view of these findings he was started on a dose of Olsalazine….
Theoretically we have postulated that resolving colonic inflammation may in some way ameliorate behavioural problems. Obviously it is difficult to find an objective measure of this and it was with regard to this that Professor Walker-Smith contacted Mr Jedruf.”
We can see from the top of the page that Mr XXX is the head teacher at the autistic unit. This is a letter signed by you with a copy sent to the GP and to Dr Wakefield and Dr Berelowitz. Is that correct?
Q That is not in quite the same terms as the other discharge summaries we have been looking at, Dr Casson, but in broad terms was it performing the same function, would you imagine?
A It was addressed to a community paediatrician and presumably was in relation specifically to Dr Bennett’s involvement with the children.
Q If you go back to the additional records for Child 6, this is a letter written in June 1998. It is page 23. It is a letter from you of 23 June 1998 to this child’s GP who has also been anonymised and we are referring to as Dr N. This is headed “Discharge Summary” but it is in briefer terms.
“Dear Dr N,
[Child 6] was admitted to our ward on 5th May 1008 for further management of his constipation. His medication at the time of admission was Olsalazine
250 mg tds. I note that his lactulose and senna had been stopped 2 weeks previously.
It was initially decided to start him on Klean-Prep. However, Mum during the first day of admission declared that she had problems in arranging child care for her other son and decided to go home. If appropriate, we will arrange a further admission date when it is possible for Mum to arrange further child care.
We also took this opportunity to take bloods from [Child 6’s] brother for measles serology.”
Can you help as to who would have made that decision, first of all, to take bloods from the child’s brother when this child came in?
A I cannot tell you whose decision. I do not remember whose decision that was.
Q Would it have been yours?
Q On page 213, Klean-Prep, is that a treatment relating to constipation?
A It is a solution which helps to clear the bowel out, often used prior to colonoscopy.
Q If we go on to page 24, we see just the end of that story, a letter to Dr N of 6 August 1998.
“[Child 6] was admitted to the ward at the Royal Free Hospital on 11th July 1998 for Klean-Prep treatment to clear his constipation. This was administered successfully over the course of 2 days by which stage his bowel was effectively cleared.
He was discharged to continue on his lactulose medication.
He will be reviewed in clinic to assess his progress.”
That is the last letter. Just reverting to the issue of the child’s brother and the bloods for measles serology, Dr Casson, can you help at all as to why blood would have been taken for measles serology? This is another of the children who was investigated and we are going on to look at his records in a moment.
A I do not know specifically why the decision was taken to take blood at that stage from the brother.
Q But at whatever stage, what was the significance of the measles serology?
A It would have to be conjecture if I was to say. Possibly there was concern that both brothers had a similar problem and therefore a similar cause was being sought.
Q I am now going on to Child 9. Could you find the Royal Free Hospital records for Child 9.
A I do not have that file here.
Q I will provide you with an unmarked copy. (Same handed to witness) Will you turn to page 31? This is a discharge summary and I am taking you to it just so that you know a little of the context for the questions I am going to ask of your involvement but in fact this is one of the ones that is not written by you. It is written by Dr Malik, who was the registrar in paediatric gastroenterology. Was he your co registrar, so to speak?
Q It is a letter dated 14 January 1997 to Dr Spratt, who was the child’s consultant paediatrician in XXX, and copied to Professor Walker-Smith and Dr Wakefield. We see at the beginning,
“[Child 9] was admitted to Malcolm Ward on the 17/11/96 for investigation of his autistic behaviour and gastro-intestinal symptoms.”
It sets out his history and, if we go on to the next page, it reads,
“… started to regressing mentally. His mother links for that with MMR which was given at 16 months of age. He started having loose stools around the age of 2-3 years, but with no blood or mucous. There is also a history of screaming episodes … investigation for vitamin B12 … There is no family history of gastro-intestinal disorder. … His general physical examination was unremarkable. … he also underwent neurodevelopment assessment, the results of which will be forwarded to you. He had a colonoscopy done on 18th which showed a marked increase in size and number of lymphoid follicle in terminal ileum. Histology of the large bowel mucosa also showed prominent lymphoid follicle and increase in chronic inflammatory cell infiltrate. An attempt was made at barium meal and follow through but he was not co-operative so it could not be done.
Other investigations he had …”
were blood tests.
“All his investigations were normal except very high lead level …”
and asking the doctor to repeat that.
“As part of the investigation protocol he also had an MRI of his brain which was normal.
In summary the gastroenterological investigation suggested a diagnosis of indeterminate colitis and lymphoid nodular hyperplasia …”
and suggesting Asacol to be prescribed. That was on 14 January 1997. If we look at the clinical note for December 1996 which is on page 12, is that a note by you?
Q Would you read out to us what that says, please.
“Readmitted for MRI, lumbar puncture”
and blood tests under general anaesthetic.
[On examination] well → continue.”
Q What would have been the reason for those investigations?
A Presumably, because they had not been able to be done on a previous occasion.
Q Yes, but for what reason were you doing them then? As part of what?
A Again, as part of the series of investigations that were being conducted on children who came in for this series of investigations.
Q We now move on to Child 5, the Royal Free Hospital records and page 351. This is a discharge summary and this time it is written by you as we can see on page 353, with a copy to Dr Wakefield. It is dated 27 December 1996 and it says,
“Dear Dr Shillam,
Diagnosis: 1. Part of autistic spectrum
2. Persistent diarrhoea
[Child 5] was admitted to our ward at the Royal Free Hospital on 10th December for assessment of his persistent diarrhoea.”
It sets out his development and then says,
“With regard to his diarrhoea, he has apparently been having bouts of diarrhoea on and off since he was 4 years of age. There is no blood or mucous in the stool. He has occasional abdominal pain during which he suddenly clutches his abdomen and flexes his knees. This has a duration of about 10 minutes and then resolves.
His parents feel that the onset of his neuro-developmental symptoms stems from the period 2 months after having had the MMR vaccination which he received on the 10th April 1990. A few months subsequent to this he started losing his skills.
He had a colonoscopy performed under sedation. This demonstrated a mild proctitis with a granular mucosa and loss of the vascular pattern, but there was no friability or ulceration. The colon was otherwise normal throughout. There did appear to be a slight loss of vascular pattern in the caecum without any ulceration. There was prominent lymphoid follicles within the ileum. The ileal mucosa appeared normal. Biopsies showed normal crypt architecture. There was a very minimal increase in the chronic inflammatory cells within the superficial laminar propria although no active inflammation was seen. Very occasional polymorphus were seen within the surface crypt epithelium. No granulomas were seen. Overall it appears that these are minor changes, the significance of which is uncertain”
and then it says that blood tests were performed and they are set out with the detailed results.
“Barium meal and follow through demonstrated a 5cm stricture just proximal to the terminal ileum. This appearance is highly suggestive of Crohn’s disease.
We are still awaiting results of his CNS …”
Is that central nervous system?
“… MRI scan and lumbar puncture. It is therefore apparent that although there is no histological evidence of overt inflammatory bowel disease, there was some hyperplasia of the terminal ileal lymph nodes. The barium would suggest the presence of a structure which would be in keeping with Crohn’s disease. We will need to consider these findings at greater length when we review him in clinic.”
It appears that this child underwent a colonoscopy, MRI scan, lumbar puncture, barium meal, follow through and blood tests; is that correct?
Q Would you turn to page 7 of the clinical notes, we see that there is a later edition; this is 15 January 1997 and we have just read the discharge summary of December 1997. The note at the top of the page is not yours; is that correct?
A That is correct.
Q But it says that he has been admitted for barium meal and follow through under sedation and then we go down to a note which I think is in your handwriting under the heading, “lumbar puncture”; is that correct?
Q Would you read us that note, please, doctor.
Sedation iv midazolam 4mg
iv pethidine 50mg.”
The lumbar puncture was between the lumbar vertebra at number 3 and 4.
“Unsuccessful 1st attempt
OK 2nd attempt.”
Bloods were taken for Fragile X which had previously been negative, chromosomes and PBM, though I am not sure what that is. CSF, which is cerebrospinal fluid, was taken for protein electrophoreses, lactate, glucose and measles analysis.
Q Do we understand from that note that you actually performed this procedure?
A That would be probable.
A I assume that I did that lumbar puncture, yes.
Q Whose decision would it have been for this child to undergo a lumbar puncture?
A Again, I presume it would have been one of the consultants involved.
Q Your notes of the intention for what the CSF was to be tested for, who would have determined that?
A Again, the same consultants.
Q There is some uncertainty about the actual dates on which the lumbar puncture was performed on this child, despite the fact that there is that clear note there. I want to ask you about that. The discharge summary to which we have already referred – if you want to look back to that, it is at page 352 – which is earlier, 27 December 1996, says that the results of the lumbar puncture are being awaited at the bottom of the page; do you see that?
Q That discharge letter suggests that the child was admitted on 10 December if we look at the first sentence of it on page 351, “Admitted to our ward … on 10th December …” but, if we look at page 361, we see that at least the plan was for him to be admitted on Sunday 1 December; do you see that at the bottom of that letter from Professor Walker-Smith to the GP?
Q Then we have the admission on 15 January and your note of a lumbar puncture being undertaken.
Q If you would go to page 423, we have the actual results of the lumbar puncture. Do you see at the top of the page under the date, we have one on 15 January 1997 and one on 5December 1996 with results apparently for 15 January but not for the 5th? Do you see where I am?
Q Can you help at all as to that? You have made a note, so one assumes that that is pretty reliable as far as when the lumbar puncture was performed. Can you assist as to whether there may have been another one previously?
A I cannot. Without looking in detail through the notes and looking for evidence of a previously recorded lumbar puncture, I could not confirm that one way or the other.
Q As far as anyway the one that you did perform which we have looked at on page 7 of the notes, you have said that one of the consultants would have made the decision as to that being carried out. In pursuit of what would you have been carrying out that lumbar puncture going by your note?
A As part of this series of investigations that these children were undergoing.
Q Now, further notes by you. If we look at page 8, this is the day after the lumbar puncture which was on 15 January, this is the 16 January. Would you read us the note on 16 January, please.
“Long discussion [with mum and dad]”
and this is listing the outcome of that discussion,
“1. Treat constipation with liquid paraffin & senna
2. Inflammation in large bowel is significant as estimated when Professor
and Alan” who was one of the academic staff in the unit “reviewed biopsies [and therefore] to start mesalazine
3. Follow up [in outpatients department in three weeks’ time]”.
When we see “… is significant as estimated when Professor and Alan reviewed the biopsies …” would that have been something that you were told about prior to the discussion with the parents or would they have been there then?
A I assume it was something that took place at a histology meeting which was when the biopsies would have been shown on a larger screen and would have been seen by other members of the team apart from the pathologist and then they would have made comment and there would have been discussion which reached a consensus on whether the changes on the biopsy were significant or not.
Q Then there is another note which again is by you on 27 January, “X-ray meeting”; is that right?
Q Can you tell us what that is about.
A X-ray meeting, barium meal and follow through. This would have been in the same format as the other meetings, that the films would have been shown and we would have discussed the
“unusual anatomy of insertion of the terminal ileum, i.e. inserts laterally.
The possibility was raised that this might be compatible with ? volvulus”
that is a twist in the bowel. Then there is a note that says,
“To be reviewed by Great Ormond Street”.
Presumably the idea was that they would be reviewed by somebody else.
Q In relation to the note on 16 January where you say that the inflammation was significant as estimated when Professor Walker-Smith and Alan viewed the biopsies and we know that there had been a conclusion in the discharge summary that there was no histological evidence of overt inflammatory bowel disease, would that reassessment also have occurred at a histology meeting or would it have occurred in some other context?
A I am sorry, the reassessment that I have handwritten or the assessment from the discharge summary?
Q The handwritten observation that it was more significant than would appear to have been the conclusion on the discharge summary. I am asking whether that handwritten observation would have arisen as a result of a histology meeting in the previous way that you have told us about.
A Yes, it would have done.
Q Or in some other context.
A No, it would have occurred in the context of a histology meeting.
Q Can you explain why we do not have a note of the histology meeting. We have a note in a different way on that occasion.
A I am not sure why that is not there and whether I was not at the meeting on that occasion, I do not know.
Q At any rate, would that be a judgment that you would have made without the views being expressed of the consultants?
A No, I would have been party to their opinion.
Q We see Professor Walker-Smith and Alan; is Alan a consultant?
A He was a researcher with an integral part of the unit as well.
Q A researcher? Can you elaborate a little on that.
A I think that Alan Phillips was a scientist who had a long history of association with the paediatric gastroenterology unit at St Bartholomew’s Hospital and then subsequently at the Royal Free Hospital and his particular expertise, amongst many areas of expertise, was familiarity with biopsies of the sort that we took.
MS SMITH: Sir, that is all I have on Child 9 and I am going on to Child 12 next. I do not know whether you feel that is an appropriate moment to have a rest.
THE CHAIRMAN: Yes, I am sure that it would be appropriate for us now to adjourn for lunch. (To the witness) Dr Casson, I have to remind you once again that you are still under oath and still in the middle of giving your evidence, so, please, do not discuss with anyone and I am sure that someone will look after you and make arrangements for you to have a sandwich.
We will now adjourn and resume at 2.00.
MS SMITH: Dr Casson, I was going on to Child 12, the next chronologically, and you will need the Royal Free Hospital records for Child 12, page 32. This is your discharge summary to Dr Stuart, the GP, dated 22 January 1997.
“Diagnosis: (1) Part of the autistic spectrum ? Aspergers; (2) Faecal soiling; and (3) Abdominal Pain.
Further to having been seen in clinic, [Child 12] was admitted to the Royal Free Hospital for further investigations of his gastrointestinal problems.”
It sets out his birth history and at the bottom of the page:
“In regard to gastrointestinal symptoms he was noted to be clean and dry by the age of three years. Subsequent to this his soiling started and he is presently soiling up to eight times a day. He does not realise he has opened his bowels and that he has soiled. The faeces are very pale, loose and smelly. The abdominal pain occurs approximately once a week, occasionally associated with vomiting and anorexia.
He had his measles vaccination at 15 months of age and is fully immunised.”
It gives the results of the blood tests that were performed and says:
“A colonoscopy was performed under sedation. This recorded almost normal appearances to the caecum, minor changes in the rectum and the caecum, these consisting of slight changes in vascularity and prominent lymphoid follicles. The ilial-caecal valve could not be identified. Histological report on the biopsies taken on this series do not show any significant abnormality. A barium meal and follow through demonstrated lymphonodular hyperplasia of the terminal ileum.
It was notable that following the bowel clear out, prior to the colonoscopy, [Child 12’s] behaviour appeared to improve, as did his soiling. It is therefore conceivable that many of his problems are associated with a degree of constipation. In view of this he has been started on liquid paraffin medication 10ml nightly. This should continue for at least six months in order to sufficiently counteract constipation. He will be reviewed in clinic.”
That is the terms of your discharge letter. Is that correct, Dr Casson?
Q If you go back to page 14, we see your notes of an outpatients’ appointment some months after that in May 1997. We see the stamp of the Paediatric Food Allergy Clinic. Was that a special clinic that was held?
A Yes, I think it was, although children are often seen in any clinic that was available so it might have been a designated food allergy clinic but there would have been other patients seen within that clinic as well.
Q Could you read to us your notes of 30 May, please?
A “Presently recent chest infection - treatment with antibiotics. Did try to take liquid paraffin and took it for only two to three weeks. Still soiling ++, occasional abdominal pain which coincides with temperature. Appetite is variable. Abdominal examination was unremarkable. Discussed with Professor Walker-Smith for abdominal x-ray to exclude constipation. Start olsalazine and follow up in one month to assess any difference.” Point (3) I cannot read the first word.
Q It is something if constipation, is it not?
A Yes, “if constipation – no treatment at present”.
Q Is that your handwriting on 4 July 1997?
Q Going to page 126, is that the results of the abdominal x-ray that was conducted on 30 May? We see “faeces throughout the coon and possibly some loading in the rectum”. Is that correct?
Q Following that, if you look at the letter that you wrote to the GP on page 29, a letter dated 2 June 1997 from you to Dr Stuart:
“I reviewed [Child 12] in Professor Walker-Smith’s clinic today. Basically he remains as he has previously. Unfortunately he has not persisted in taking the liquid paraffin as mum was concerned that it made his soiling worse. He still experiences occasionally abdominal pain. He is otherwise well. Abdominal examination was unremarkable.
An abdominal x-ray was performed today which demonstrated marked faecal loading. I have discussed the situation with Professor Walker-Smith and we feel that we should initially start treating with olsalazine 250mg to assess whether this makes an effect. We should hold fire on treating his constipation.
We will review [Child 12] in a month’s time at which stage it will be important to reassess treatment and consider whether any further treatment is required.”
Whose decisions would it have been to treat with olsalazine and hold fire on treating the constipation?
A That would have resulted from a discussion with Professor Walker-Smith.
Q Do you have any recollection of it?
Q Olsalazine is an anti-inflammatory, is that correct?
Q That is all I have to ask you about that child. I would like to turn to Child 8. On this occasion you will need his GP records at page 76. This is a letter, turning to page 77, signed on your behalf, Dr Casson, witness a copy to Dr Wakefield, is that correct?
Q And to Jill Thomas. Can you tell us who she was?
A She was a research nurse.
Q When you say a research nurse, what was her role in relation to this child, do you recall?
A In relation to this child?
Q There is a copy sent to her. You say she was a research nurse. What role did she play?
A I cannot clearly recall. I think she was involved in just helping to orchestrate the study.
Q I am sorry?
A To coordinate patients being admitted and investigations being done.
Q Did you say “to orchestrate the study”?
A To coordinate, yes.
Q It is dated 27 November 1997 to Dr Jelley.
“Child 8 was admitted to our ward at the Royal Free Hospital on 20 January 1997 for further investigation of a possible association between developmental delay, gastrointestinal symptoms and vaccination.”
It then sets out her birth history. Looking at page 77:
“Colonoscopy was performed which was macroscopically normal except for mild increase in lymph node tissue within the terminal ileum. Histology of biopsies taken during this procedure noted lymphoid follicles within the terminal ileum. All pieces of colonic tissue demonstrated minimal inflammatory changes. A barium meal and follow through was normal, as was an MRI scan. Blood results performed on this occasion demonstrated …”
They are then set out.
“These results therefore are not indicative of marked ongoing inflammation. The results from Dr Wakefield’s specific investigations concerning the measles antibody would be available from him.”
There is a long lapse between the admission of this child on 20 January 1997 and the discharge summary of November 1997. Might there be any particular reason for that?
A Is that admission date correct?
Q Looking at the Royal Free records, Dr Casson, it is pages 7 and 8.
A I do not know why there was that delay in writing that discharge summary.
Q We see from that that the child had colonoscopy, barium meal and follow through blood results and you say the results from Dr Wakefield’s specific investigations concerning the measles antibody would be available from him. How would you envisage the GP obtaining those if they were required?
A If the GP wanted those results he could have contacted the department of Dr Wakefield.
Q When you say the department, which department?
A Paediatric Gastroenterology Department.
Q Turning to Child 7, and for this child you will need the Royal Free Hospital records. We are going back to a letter that you saw before in relation to Child 6, who you will recall is Child 7’s brother. It is page 57. This is a letter from you to Dr Bennett, the consultant community paediatrician. You will remember we read out the first half of it relating to Child 6. On page 58, it says:
“With regard to [Child 7] he was referred to Professor Walker-Smith by Dr N. He is not thought to have features of autism. There was concern over a previous fit-like episode which occurred 24 hours following his measles vaccination. There was also concern that from the age of 2 years he had intermittent passage of blood per rectum with alternating constipation and diarrhoea.
It was decided in view of the findings in his brother to investigate [Child 7] further. He was therefore admitted for a colonoscopy on 27 January 1997. This demonstrated very mild evidence of vascular abnormality in the rectum and sigmoid but was otherwise essentially normal. However, the terminal ileum demonstrated a marked degree of lymphonodular hyperplasia. Histology from this procedure was reported as normal.
When [Child 7] was seen subsequently by Professor Walker-Smith in clinic he felt that a therapeutic trial of olsalazine was indicated. This was empirical treatment chosen as mum had reported a marked improvement in [Child 6].
I hope this is sufficient information and would be extremely pleased to keep in close contact with yourself and let you know of any further developments. If you require further information please do not hesitate to contact us.”
That is from you a copied to Dr Wakefield and Dr Berelowitz, is that correct?
Q What do you mean by “empirical treatment”?
A Empirical in that it might have evidence that ongoing inflammation was not overwhelming, nevertheless he obviously had symptoms which were causing distress and on the basis of a similarity with his brother that it might be a useful therapeutic intervention.
Q Can you help on the interpretation of the letter. Where it says “empirical treatment chosen as mum had reported a marked improvement in [Child 6]”, can you help us as to what you would have meant? What sort of improvement? Behavioural or gastrointestinal or both or neither?
A It is difficult to be accurate about that because this was improvement as reported from the parents and often related to gastrointestinal symptoms and may also have related to behaviour as well.
Q You cannot recall?
A I cannot recall.
Q With regard to your further involvement with this child, going to pages 14 and 15, this is a clinical note dated 9 September 1997 and appears to be related through phone calls with mum. Could you read that note out to us, please?
“I have taken several phone calls from the mother of these patients who is concerned that olsalazine may be improving his behaviour but worsening his bowel condition. She had been advised to observe the effect of stopping the olsalazine for a period of three weeks and subsequently restarting it. This appears to have confirmed her opinion. I requested an abdominal x-ray to exclude the possibility of constipation. She has sent me the x-ray. It does not show faecal loading but is suggestive of a Riddell’s lobe giving the impression of hepatomegaly. [A large liver]
I have discussed this today and on several previous occasions with the GP. On this occasion he will arrange an ultrasound scan of the abdomen to confirm this.
Now [Child 7] is off the olsalazine. If the diarrhoea persists we will arrange to review him again in our clinic.
There are concerns because mum is contacting Jill Thomas almost every day with concerns over [Child 7]. The GP is aware that she seeks very frequent medical advice and has had difficult relationships in the past with medical personnel. We have agreed therefore that the GP should be central to all dealings with Mrs Seven in order to coordinate help and advise in the most consistent way.”
Q You have told us that Jill Thomas was the research nurse, Doctor. Whereabouts was she based?
A At the Royal Free.
Q Yes, but what department?
A The Paediatric Gastroenterology Department.
Q How did she become involved? You say she was a research nurse. Can you differentiate that for the panel?
A I cannot be clear because I seem to recall she was quite clinically involved with these children as well, hence the repeated phone calls.
Q That is why I was asking.
A I think these children had many problems and were seeking advice and help from people who were involved, whatever, within the medical profession and hence by the very nature of the illness they had, she would have become involved.
Q Can we now go on to Child 10, please, and the Royal Free Hospital records volume 2 and the GP records. In volume 2 of the Royal Free Hospital records could you turn to page 11? Is the record on that page the admission clerking note dated 16 February 1997 in your handwriting?
A Yes, it is.
Q Could you help us by reading out first what was the admission for?
A “Admitted for investigation of disintegrative disorder, measles and inflammatory bowel disease, complaining of learning difficulties, possible abdominal pain, occasional diarrhoea. Hearing problems, required grommets, now resolved. Parents, contacted Andy Wakefield.”
Do you want me to go on?
Q No, that is fine. Can we go down to the history, we see that he had his MMR, is that correct?
Q Can you tell us what it says after that – June ’94?
A “June ’94 at 16 months had measles infection, diagnosed by the general practitioner, not the family GP, who thought it was German measles, advised Calpol. Mum does not remember a rash.”
He was pyrexial and had a temperature and he was floppy, no oral lesions, no bowel problems, seemed to recover, and the episode lasted four days. Over the next few months, and then this is in inverted commas so presumably a quotation from the parents, “person gradually disappeared” and then eye contact was lost over the period from September to December. Word like sounds appeared lost. There was no loss of motor skills,. Had always been outgoing and became less happy and outgoing.
Q Can you turn over and identify any reference to bowel problems? I think it is in the summer of ’96, is it not?
A “Summer of ’96 seemed to deteriorate, pulling knees up, clutching abdomen. Seemed to stop taking dairy products and the situation improved. Subsequently began screaming with bread or sponge cake. Hoola hoops only, not crisps in general.”
I do not know what that word is. Query. Improved, calmed down, especially in unknown environment. Socially better, sense of humour, more variety of facial expression, comprehension of language, still no speech. Bowels, no bowel control. Urogenital system, no urinary control. Gastrointestinal symptoms, bowels open, occasionally watery, occasionally very dry, occasionally has to strain at stool, no pain. Opens his bowels two to six time a day with no blood or mucous. Abdominal pain Mum contends to hoola hoops.
Q Then it deals with the respiratory system. If we go on to page 13, past medical history, we can seen in June ’95 you have a record of an MRI which was normal. Is that correct?
Q An EEG which was normal?
Q Blood tests normal?
Q And checked measles antibodies, is that?
Q What does it say after that?
A I think it is “was high”.
Q This, it appears, was all done in XXX by Dr Paul Davies, the community paediatrician.
Q Can we turn to page 74 in the GP notes, which is the discharge summary. This is from you, Dr Casson, dated 17 March 1197 to the GP. Is that correct?
Q We see: “Diagnosis: 1. Learning difficulties
2. Abdominal pain with occasional diarrhoea
3. Noted elevated measles titres
4. Microscopic colonic inflammation with lymphoid hyperplasia of ileum
Admitted: 16/2/97 Discharged: 19/2/97
[Child 10] was admitted for other investigations of his bowel symptoms in association with possible disintegrative neurological disorder and possible association with measles vaccination.”
It sets out his history. It says at the bottom of the page:
“He never had any bowel control nor urinary control.”
At the top of page 75:
“On review of systems he has a variable bowel habit. His stools are occasionally watery and he has occasionally to strain at stool. He evacuates his bowel between 2-6 times a day. Further review of systems was unremarkable. He never has any oral ulceration or joint problems.
He was previously investigated in XXX by Dr Paul Davies, Community Paediatrician. Under Dr Davies an MRI, EEG and various blood tests have all been reported as normal. Nevertheless, a measles antibody titre was noted to be quite elevated…..
Colonoscopy was performed and demonstrated a granular rectal mucosa and an abnormal rectal vascular pattern. There were prominent lymphoid follicles throughout the colon but no other mucosal abnormalities of note within the colon. His caecum had a slightly erythematous granular rectal mucosa and a swollen ileo-caecal valve. The terminal ileum showed very striking lymphonodular hyperplasia with only minor inflammatory changes.
Biopsies were taken during this procedure and demonstrated normal crypt architecture but with mild, increased distribution of chronic inflammatory cells throughout the colon.”
Then you set out all the blood test results and the CSF (cerebro spinal fluid) from the lumbar puncture.
“Also during his admission he was reviewed by the child psychiatrists who will be forwarding a report.
In view of the definite inflammatory changes noted in his colonic biopsy we feel it would be appropriate with anti-inflammatory medication and therefore will recommend treatment with Sulphasalazine….which we would be grateful if you would prescribe.”
Again, would that prescription have been your decision or that of the consultants?
A It would have been in discussion with the consultants.
Q Can we go on in the GP records to page 72, a letter dated 15 April 1997, again signed on your behalf to Dr Jenkins, who is a consultant paediatric gastroenterologist at University Hospital of Wales.
“Professor Walker-Smith would be extremely grateful for your assistance in managing this child. As you know, we have now seen several children with a syndrome comprising a neurological disintegrative disorder (part of the autistic spectrum) and bowel problems. In [Child 10] we noted similar colonoscopic and histological findings to several of the other children. In view of this, he was started on Salazopyrine 250 mg …. Nevertheless, mum has not noticed a significant improvement and remains convinced that there may be an element of reaction to certain foods. On discussion with her, it is also possible that constipation has a role to play in his symptoms.
Please find enclosed a discharge summary letter. Would it be possible for you to see them in your outpatients department as it is obviously difficult for them to be seen in London
Hope this is appropriate.”
Was that letter written on Professor Walker-Smith’s instructions, Doctor, going by the first sentence?
A I think so , on the basis of that, yes.
Q If we go on to page 67, we see the reply from Dr Jenkins dated 30 April ’97.
“Many thanks for your letter regarding [Child 10]. I would be very happy to see [Child 10] regarding his non-specific colitis that was found as part of your recent investigations. He is at present looked after by Dr Paul Davies, Consultant Community Child Physician, and I would need to have his approval, as well as the approval of [Child 10’s] general practitioner, before arranging to see him. I have copied this letter to both of them and will in the meantime send a provisional appointment for a couple of months, provided that [Child 10’s] general practitioner and Dr Davis are happy with this.”
Then, if we turn on to 68, this is your letter, apparently in reply to a telephone call from the GP in relation to the use of Salazopyrine.
“I should reassure you that it is a medication that we have had very few problems with regarding adverse side effects. Nevertheless side effects are more notable with this 1st generation 5-ASA derivative as opposed to the newer one, e.g. Mesalazine. Unfortunately, however the newer ones are not generally available in liquid form and therefore children such as [Child 10] find them difficult to take.
Side effects comprise very occasional idiosyncratic renal dysfunction. They also include ongoing liver dysfunction, skin rashes and haematological dyscrasias. There is no recommended protocol for following up these children, nevertheless I would recommend that he should have his renal and liver functions and FBC with while cell differential and amylase checked monthly for 3 months and then at 3 monthly intervals.”
That is his full blood count, is that correct?
Q That was obviously a letter that you wrote in response to a query from the GP as to the use of these drugs. If you can put yourself back to then rather than whatever your understanding may be now, was it your understanding then that they were widely used or unusually used or what was the position as far as children were concerned?
A They were widely used drugs for the treatment of inflammatory bowel diseases.
Q But what about children?
A And in children.
Q In children as well as adults?
Q Then if we turn over to page 69, and I am not going to take you through all the details of this letter, Doctor, this is just the GP writing to you in relation to the monitoring and expressing some concerns about whether there was a need for monitoring or not and saying he was leaving it up to you and Dr Jenkins to sort out between you, as you see in the last paragraph. Is that correct?
Q That concludes the records in relation to that child and the last child in fact of those I am going to ask you about. I want to ask you just a few general questions, Doctor. I know this is difficult because you have an expertises over the last 10 years in this particular subject. If you could try and put your mind back to how it was in 1996-97, which is the period that we are considering, you have sometimes referred to the phrase ‘lymphoid nodular hyperplasia’ in your discharge summaries. Can you give us broadly, in lay terms, what your understanding then was of what was being observed in the children whose discharge summaries you wrote?
A This was the appearance of prominent nodularity within the terminal ileum, and that is the area of the small bowel where it joins on to the larger bowel and this nodularity was composed of lymph tissue similar to the glands that you might find swollen when you get any infection and the appearance was of mild nodularity within the terminal ileum due to apparently enlarged lymph nodes.
Q You have told us that you were in training as far as endoscopy was concerned. Do you recall whether it was a condition that was pointed out to you during that training?
A It was a condition that was pointed out because it seemed so significantly present in these children.
Q As I understand it, you do not know whether you assisted in the endoscopies actually on these specific children.
Q How would you have known what you should say about the findings in the discharge summaries that you wrote?
A I may not have assisted but I certainly observed on occasions. There were also images taken, so I would have seen those and it was also apparent from discussion and it may have been also have been apparent in some cases from the barium study on which this pattern can also be picked up on. So, from all of those sources as well as general discussion within the department I would have been aware of the presence of lymphoid nodular hyperplasia.
Q Do you have a recollection as to the view within the department as to the significance of the finding of lymphoid nodular hyperplasia?
A It is difficult to say what it was felt the significance was. The observation was that it appeared to be there and quite markedly so to a particular degree in these children and whether it was an indicator of something was uncertain.
Q I am sorry. You said that it would be difficult to know what the significance was and whether it was an indicator of something was uncertain. In order that we are all clear, are you expressing your own view or your understanding of the consensus view in the department?
A I think that the consensus view in the department was that this was an observation that was made and that this was seen on a regular basis in these children. I do not remember any specific comment on what would have been the cause of that as such.
Q Do you remember whether there was any comment as to whether or not the finding had clinical significance as far as the child was concerned?
A I think that the inference would have been that it may have had a significance in delineating a possible abnormality and a marker for a specific condition.
Q The discharge summaries to which I have taken you refer to MMR vaccination and many of them refer to the parents associating the onset of symptoms with that vaccination. Can you tell us what your understanding was as to the relevance of vaccination and that association that was being made by the parents to the investigations that were being carried out.
A The temporal association was made by parents and therefore the hypothesis would have been that there may have been some relation between the immunisation and the symptoms as reported by the parents. Investigations would have been planned in order to try and address that issue.
Q What about the lymphoid nodular hyperplasia? What was your understanding of the view as to whether or not that was or could be related to vaccination?
A It is difficult to answer because I think that these were observations which were made without try to understand the significance and the observations were important because it was felt that it might define a disease entity. The actual specific association between all these features was not clear.
Q Were you clear at the time that some sort of link was being hypothesised?
Q I would like you to turn – you can put away any children’s records that you have – to FPT2 which is The Lancet paper. Would you turn to page 783. We see in that paper that you are named as one of the co-authors.
Q Were you involved at all in the writing, the actual drafting of that paper?
Q What about the intellectual thrust, what the paper was concluding? Did you play any part in that?
A These sort of topics would have been discussed within the department, but I did not have a major part to play in the intellectual thrust of the paper.
Q First of all, were you happy to be named as a co-author?
A I was happy because I felt that it reflected the work that I put in, in terms of organising the patients to be admitted and investigated.
Q Was that your understanding as to the basis of your inclusion?
Q If we go to page 787, under the heading, “Contributors”; do you see where I am at the bottom of the page in the left-hand column?
Q We see, “Drs Casson and Malik” who you have told us was your co-registrar “did the clinical assessment.” What did that mean precisely?
A I think it meant the initial clerking of the patient and examination.
Q I am sorry, the initial …?
A The taking of the history and examination of the patient.
Q Do you recall at the time discussion within the department about the nature of the hypothesis relating to MMR vaccine, whether it was felt to be proven or discussion as to how it was to be worded or anything of that nature?
A I cannot remember specifics. I think the general feeling was that this was generally reporting observation as opposed to any causality.
Q If we move to FTP3, the next bundle, and to page 1210, I am sure that this is a document with which you are familiar. This is the retraction of an interpretation that was ultimately published in The Lancet in relation to this paper; are you with me?
Q It is right, is it not, that you were one of the cosignatories to that retraction.
Q Can you tell us from your point of view how that came about. Who, if anybody, asked you to be involved?
A That came from Professor Murch who contacted me.
Q Did he convey to you that others were intending to sign that retraction?
A He conveyed to me that others would be approached who had been involved within the original paper.
Q Can you tell us entirely from your own point of view at that time – and we are now in 2004 – why you felt that it was appropriate that you should be a co-author in the retraction.
A I felt that the impact that the paper had had or that the whole incident had had was detrimental to children’s health and that therefore retraction was an appropriate way to address that issue.
Q When you say “the whole incident had had”, can you explain what you mean by that. You say that it was detrimental to children’s health but what in particular were you concerned about?
A I was concerned with the poor uptake of MMR.
Q Was it that matter that made you make the decision you did to sign the retraction?
A That was a major driving force, yes.
Q You say that that was a major driving force, Dr Casson. If there was anything else which played a part in your decision, could you assist the Panel with that.
A Professor Murch also explained that there were concerns over recruitment of patients within the study and therefore maybe the paper did not stand so well on its own and therefore retraction seemed once again an appropriate response to that.
Q Did you have yourself – I think you have already answered this – any personal knowledge of the way in which the patients were recruited?
MS SMITH: Thank you very much. If you wait there, doctor, you will be asked some questions.
THE CHAIRMAN: I am in your hands – it is now 2.50 – as to whether you would wish to have a break now and undertake the cross-examination in one go.
MR MILLER: I cannot do it in one go anyway. I shall be some time because we have to go back over the cases again with a significant amount of detail which has not been gone through yet, but I am happy to break off now for your mid-afternoon break.
THE CHAIRMAN: I am also thinking of the witness; he has been in the witness box since this morning and I think it is wise that we give him a little break as well.
MR MILLER: Sir, may I tell you what I understand the position to be, recognising that the Panel may have some questions for this witness. I do not anticipate that either Mr Coonan or Mr Hopkins will have very much to ask because I am going to go through general matters first with the witness and then deal with the individual cases, which means going through the notes and we can get a sequence from that. It is likely that I will be doing 9/10ths of the cross-examination of this witness. I do not know whether that helps you, sir. I have general matters that I would like to deal with certainly after the adjournment. If you wish then to break off and have all the cases done tomorrow in one go, I would be equally happy with that.
THE CHAIRMAN: That sounds quite a reasonable suggestion.
MR MILLER: I am conscious of the fact that it may be good exercise to leap up and down and get the bundles for each of these cases, but there is a lot of work involved in following the sequence in all these cases when you leap from one case to another. We are going to have to do that to some extent with my questions and it is difficult to take it all in if we are doing it at the speed we have done up to now.
THE CHAIRMAN: We have become quite used to getting up and getting the bundles!
MR MILLER: And you always seem to know where the bundles are, but I am afraid that it is going to happen again.
THE CHAIRMAN: What we will do is adjourn now. I am also very conscious of Dr Casson who has been in the witness box since this morning. It is now 2.55. We will now adjourn and resume at 3.15.
(To the witness) Dr Casson, once again you are still under oath and still in the middle of giving your evidence, so, please, do not discuss this matter with anyone. We will resume at 3.15
(The Panel adjourned for a short while)
THE CHAIRMAN: Dr Casson, as I said earlier this morning, it will now be the opportunity for the three counsel to cross-examine you if they feel it appropriate. Mr Miller represents Professor Walker-Smith.
Cross-examined by MR MILLER
Q Dr Casson, I want to go back to the beginning and your arrival at the Royal Free Hospital. You went there as a lecturer in the Department of Paediatric Gastroenterology and an honorary senior registrar in the same paediatric gastroenterology.
Q There are a number of features to that. If you went there to take up that job it would follow that by the time you got there, Professor Walker-Smith’s unit had transferred from St Bartholomew's and had set up at the Royal Free.
A Yes, although there was still a lot of liaison work to be done.
Q That was in September 1995, I think, that the department started and it looks as though you arrived at around the same time, but certainly in the latter part of 1995.
Q You had either a substantive post as a paediatric senior registrar or a substantive post as a lecturer with an honorary contract as a senior registrar within the trust, but you had the latter.
Q You were to be Professor Walker-Smith’s lecturer.
Q You knew presumably at the time that quite a large part of the department had moved from St Bartholomew's with him?
Q He brought a team to a hospital where we have been told by other witnesses who have already given evidence that there was not a paediatric gastroenterology department there before he arrived, so it had come over. This was the first time they had had a dedicated paediatric gastroenterology department.
Q We can see from the letterhead that appears to have been in use from the beginning who the various people were. As an example, if you look at FTP1, page 291, a letter of 11 November to Dr Michael S Pegg, it is just the people involved who are shown no the letterhead. We can see the team at consultant level anyway. It was called, was it not, the University Department of Paediatric Gastroenterology?
Q Head of Department Professor J Walker-Smith. Senior lecturers: Dr Simon Murch and Dr Alan Phillips. Consultant: Dr Mike Thomson.
Q I think that was as it remained throughout the time that you were there during your lectureship.
Q Did you understand that as far as Dr Thomson was concerned I think he may have arrived at about the same time as you but that he had not come from Bart’s; he had come from Birmingham, I think.
Q He was a relatively newly-appointed consultant.
Q His position is slightly different because he is an NHS consultant within the department as opposed to one of the senior lecturers.
Q Its heading shows University Department of Paediatric Gastroenterology and the features of that would be the fact that you had senior lecturers, a lecturer and a professor, so an academic department, but of course it provided the National Health Service paediatric gastroenterology care first for sick children in the area in its own catchment area and, secondly, as a tertiary referral centre in that specialty for patients referred from elsewhere.
Q Although it has the academic heading, it is in fact providing NHS care for those two classes of patients on a regular basis. You are, as it were, parachuted into a hearing which has been going for some weeks and quite a lot of evidence has been heard already, but the Panel has had to concentrate on a small number of patients who were initially seen in 1996 and 1997, 11 of whose cases were written up in The Lancet paper of which you were a co-author in circumstances which you have explained and a twelfth who was seen by the team in late 1997 with which I do not think you were concerned. That is what the focus has been on – one aspect of the case from the Panel’s point of view. Of those 12 children in all, all had colonoscopies performed either by Dr Murch or by Dr Thomson and that would be the case, would it not, because they were the endoscopists attached to the unit?
Q They did almost all of the colonoscopies on the children that came through the unit.
Q And, as you have rightly said, that involved two aspects: first that they be doing diagnostic colonoscopies to see if they could identify pathology, but also it was part of their job to teach the training staff colonoscopy.
Q That would allow for you to have been present and to have played a role with some of these colonoscopies in these individual cases although you cannot remember being involved in any particular case.
A That is correct.
Q The position is that the colonoscopy would be done by the consultant, Dr Murch or Dr Thomson. What would be seen would be shown on a screen at the time so that anybody present would see as the instrument moved up the gastrointestinal tract what, if any, pathology was there.
A They would see the images of the colonoscopy, yes.
Q Biopsies would be taken as well as part of the procedure and then the tissue would be analysed to see whether or not what was provisionally seen on the screen was actually mirrored by something in the tissue; in other words, you might be able to see something that looked like lymphonodular hyperplasia but it would be confirmed on histology in due course.
A I think in endoscopy what you see with the naked eye or with the instrument macroscopically and microscopically are important. You may not see pathology and then it may be indicated on the histology and occasionally vice versa. The lymphonodular hyperplasia was an observation of the macroscopic – that is the naked eye appearance of the ileum.
Q Going forward, one of the important features of the way in which the unit worked was that the two would come together in relation to each patient at the end of the week – that is the pathologists and the clinicians – to put together their views as to what, if anything, had been found.
Q It is pretty important because the combination was likely in the end to be more useful than either one or the other.
Q When the colonoscopy was being done if you were present would the consultant who was doing it point out features as it was going ahead? In other words, if they saw something which they considered important, would they tell anybody who was watching what was there on the screen as part of teaching?
Q Can we go back to page 291 for a moment. There were, in effect, three consultants sharing the workload, including Professor Walker-Smith because he was a consultant as well, although he did not do colonoscopy, did he?
Q In terms of looking after the children, they would be dealt with by way of rota and they would see either one or other of the three consultants at any given time.
Q Dr Phillips was not involved in seeing patients but he was, as we can see, a senior lecturer and he was a non-medical academic who provided his expertise in the provision of NHS care but was also involved in research and in teaching.
A He was not actually involved with care of patients.
Q He lent his expertise in his particular area in things like looking at histology.
Q As far as the consultants were concerned, they were dedicated paediatric gastroenterologists, although all I think had a general paediatric background, but they were pretty informed about what they saw on the histology slides when they were presented at the weekly meetings.
Q You were the lecturer, senior registrar. Was there also a senior registrar as well through the whole time that you were there?
A I do not think there was through the whole time I was there but certainly latterly there was.
Q We have seen Dr Malik’s name as one of the authors.
Q He was a senior registrar.
Q He was there for part of the time.
Q He would have shared the senior registrar responsibilities with you.
Q Were there any registrars?
A I do not think there were. I cannot be clear.
Q But there were SHOs or there may have been certainly one SHO.
Q You told the Panel that you used to like going in on a Sunday and therefore you would, more often than not, be the person responsible for clerking any child when they came in if they came in on a Sunday.
Q The general routine, to which we will come back to in a moment, was that if they were going to come in for a colonoscopy there would be admission on a Sunday with bowel preparation commenced anyway on the Sunday with a view to colonoscopy on Monday. That was the general pattern for all IBD children.
Q We have concentrated on these various named or numbered children but there were many, many cases being referred through the department at this time way beyond the 12 with which we are concerned in this case.
Q It was a busy department, was it not?
Q I think you said that there were four colonoscopies or four endoscopies a week throughout this period. That would be four colonoscopies, would it not?
Q Sometimes there would be upper endoscopies as well if it was felt appropriate to carry them out.
Q They would be done by Dr Thomson and Dr Murch as well.
Q Did it feel a busy department?
Q Did you know what sort of reputation it had when you joined it?
Q It was known to have a culture of energetic investigation, did it not?
A It was a well-recognised and widely acknowledged to be a very good department.
Q The purpose of the department was to discover children’s problems and then, if possible, to treat them. That was the underlying purpose.
A The underlying purpose was to diagnose gastroenterological illness and to treat it, yes.
Q Presumably that was an approach with which you agreed?
Q Do you think that you learnt during your time there a lot about, for example, colonoscopy?
A Yes, I did.
Q You had done a general paediatric training up to that point so this was your first specialist post.
Q A sub-specialist, I am sorry, in paediatrics and in fact it is what you had chosen as where you wanted to make your career.
Q You were eager to learn the whole aspect of paediatric gastroenterology including endoscopy.
Q I want to ask you about Dr Wakefield. We see from page 291 that he was not somebody who was part of the University Department of Paediatric Gastroenterology, although he had a well-known interest in gastrointestinal pathology. If you look back, you must have written to and received letters over the time that you were there from Dr Wakefield.
Q Just again as an example, could you look in the same bundle for ease of reference and turn back to page 237b, and again ignore the content of the letter. I am just looking at the department and the way in which it was signed. It is from the Academic Department of Medicine and he signs that letter “A J Wakefield, FRCS, Senior Lecturer in Histopathology and Medicine, Honorary Consultant in Experimental Gastroenterology to the Royal Free NHS Trust Director, Inflammatory Bowel Disease Study Group”. I just want to ask you about that last point – Inflammatory Bowel Disease Study Group. We have been told by other witnesses that that was a group that had been in place at the Royal Free for a number of years, and the Director of it, the main person concerned with it, was Dr Wakefield. Was that your understanding when you arrived at the Royal Free?
A Yes. I did not know a lot about the Inflammatory Bowel Disease Study Group when I arrived but, yes, generally speaking, that would be right.
Q Did you meet Professor Pounder?
A Yes, I know Professor Pounder.
Q Professor Pounder was, I think, one of the Heads anyway of the Academic Department of Medicine to which Dr Wakefield was attached. As far as Dr Wakefield was concerned, and you understood this to be the case, he was a research doctor attached to this department, the Academic Department of Medicine.
Q He was never involved in carrying out any investigations on any of the children who were patients in your department?
Q I have in mind obviously a number of the investigations which have been written up in the notes: colonoscopy, upper endoscopy, MRI, EEG, lumbar puncture and blood tests. He was not involved in any of that. If they were being carried out, they were being carried out either in your department or in the radiology department as far as MRI, and EEG would be again in its own department?
Q Again, you never had to consult him in relation to any aspect of the clinical care or treatment of children, because that would be something that would be discussed between you and the three consultants, depending upon what their involvement was with any particular patient?
Q Because you have said, and it obviously makes sense, that when you are writing your letters, which contain quite a lot of detail, there are aspects of the history, for instance, which would come to you direct from the parents. There would be aspects or the results of tests which would be recorded in the notes, but there would also be decisions that would have to be made about how a child was going to be treated, which would obviously come from discussion with those with more experience?
Q And so it is a combination of all of those and it would depend upon which of the consultants had been most involved with that patient as to whether or not a particular line of treatment was going to be used or not?
A The discussion was pretty evenly based because everybody had wide experience.
Q It looks as though quite a lot arose out of the last day, the Friday meeting, when everything came together and that in most cases you would write your discharge letter some time after that meeting but that the whole case would be discussed in that meeting and a general consensus view would be reached from all concerned?
A Yes, that happened in many cases.
Q And in your position you had to be sometimes anyway the scribe for what was decided at that meeting and subsequently of a person who wrote the detailed discharge letter from all sources of information which you had?
Q I call him Dr Wakefield because that is how he signs himself in many of the letters, and I know he is a Fellow of the Royal College of Surgeons, but not in the one I am showing you at the moment. If you do not mind I will call him Dr Wakefield because he has been called Dr Wakefield throughout this hearing. There is no doubt, however, that Dr Wakefield did collaborate with the paediatric and gastroenterology department on some aspects of the research in which he was concerned?
Q Particularly but not exclusively in relation to a proposed study of a possible link between what was termed disintegrative disorder, inflammatory bowel disease and measles or measles rubella vaccination?
Q You have been shown what is said to be a protocol for a proposed study, and you are mentioned in it as one of the doctors concerned, as you have noted, and you were aware of the clinical aspects of what was involved, the investigations that were going to be involved?
Q Looking forward, there were clinical aspects to that proposed study which involved the investigation of the child’s conditions and there were two aspects to that: the bowel disorder and the reported development problems as well, so two aspects. There were clinical aspects and in most cases the last piece of clinical input before they left the Royal Free was a decision as to how, if at all, the child was going to be treated?
A Yes, that was about the gastroenterological side.
Q Yes, that is all I am talking about. I am trying to confine it to your own department and your own involvement for the moment, but recognising that in the background there is also the suggestion of a possible link between the developmental condition and the bowel condition but, as far as your department was concerned, there were investigations that were carried out to identify the nature of any pathology, decisions made as to what, if anything, had been found, and then decisions made as to whether or not the child was going to be treated and, if so, how?
Q There were research aspects proposed in this study which involved further examination of specimens taken – blood, CSF and histology – which obviously would not have had anything to do with the diagnosis or treatment of the children. That would be simply looking for other aspects which were produced by that evidence.
A Histology was important in the diagnosis.
Q I was going to come to that. To some extent we can look at histology in two different ways. The first is as it was generated in time for the Friday meeting so that for the purpose of discussing what was going to happen to the child, there would be a report obtained from the histology department and then discussion about that report. That clearly would inform the treatment for that patient, but we have seen from the list of co-authors in the paper that there were other people involved in the analysis of the biopsies who were not regularly taking part in those meetings. They were doing laboratory work and applying their own judgment to what they found. I take your point that histology was important but there seems to be two stage histology: the first is generated at the time that the child was in hospital and leading to the decision as to how to treat the child; and then subsequently other pathologists may have looked at the same or similar material in order to decide what, if anything, it said.
A I am not clear about that distinction.
Q I was just thinking about Dr Andrew Anthony: was he in your department?
A I think he worked with Dr Wakefield.
Q But he would not be one of the people who was reporting on the slides and discussing them in the meeting. That would be Dr Davis and some of the other histopathologists. So there was a short-term result obtained from them and then, in circumstances with which you would not have been concerned, others may have looked at the slides elsewhere for different purposes?
Q I think it is an important point because the timetable seems to have relied upon the fact that a child would be admitted on the Sunday and by the Friday all the material that was necessary to make a decision would be available, which would include, in most cases anyway, a written report from the pathologist and discussions between the pathologist and the clinicians on the Friday at the meeting?
Q We have seen, as we will look at in a bit more detail tomorrow in the evidence that you have already given, that the children were being seen in the department as early as I think the spring of 1996. We will have a look at the particular dates tomorrow. They may not have had colonoscopies but they were being referred to the department some time at the beginning of 1996. I am not going to ask you to comment. Tomorrow when we look at the individual patients, you will see the dates at which they first come into the sight, as it were, of the hospital. You will have seen, Dr Casson, from the ethics committee application that was subsequently made in September of 1996 --- I think it is only fair that you turn it up and have a look at it in that same bundle at 209. This is the application that went before the ethics committee. This is in a pro forma that is put out by the ethics committee with questions and answers and the answer at the bottom of the page on 209 reads:
“In view of the symptoms and signs manifested by these patients, all of the procedures and the majority of samples are clinically indicated.”
Then it deals with additional intestinal biopsies. That is in response to a question:
“Would the procedure(s) and sample(s) be taken especially for this investigation or as part of normal patient care?”
What the ethics committee was being told was that the procedures and the majority of the samples are clinically indicated, and we have understood that to mean that was for the benefit of the children as part of their care. Do you see that?
MR MILLER: I do not know whether you would have seen it at the time?
MS SMITH: This witness has already indicated that he did not see the ethics committee application and he had nothing to do with its drafting. It is my submission that these questions about what is meant by the ethics committee application are inappropriately aimed at this witness.
THE CHAIRMAN: I call on the Legal Assessor.
THE LEGAL ASSESSOR: That is correct if he has said he did not see it. I do not have a note.
MR MILLER: I do not have a note either. I do not know if it is as strong as is being put. Tell me, Dr Casson, it is easier at the same time if you answer: were you aware of the contents of this proposed protocol at the time that it was produced?
A No. I do not recall being aware of it.
Q This data, as you say, is September of 1996, although there is another date in August at the beginning of the document, but, from the evidence that you have given, children were already being seen in the department before those dates?
Q Can we explore that because I think it is quite an important point. Twelve children formed the basis of the Lancet article, which is the end point of the investigation of these children. There is a report in the Lancet of investigations and findings in 12 children.
Q All of whom were seen and investigated in 1996 and the early part of 1997. However, your department continued regularly to see and investigate and treat similar patients, similar children, right up to the time when you left I think, according to the evidence that the panel has, and beyond that time. So on the one hand you have 12 children but children were being seen and investigated and treated throughout this time up to the time when you left – similar children?
A Yes. I have no direct recollection of them but I am sure that is right. Yes.
MR MILLER: Please do not think there is any criticism there. It is just a statement of fact. Time does not stop in the spring of 1997. Children would have been coming in and being seen and investigated.
MS SMITH: This witness has just said he has no recollection of that. It is inappropriate for Mr Miller to tell him what the fact is. That is for a latter stage. The witness says he has no recollection of it.
MR MILLER: I am sorry. He said he was sure that that was right and he has no recollection of individual patients. We are going to be here most of the night if there are going to be objections of this nature. This man is in the department, as he told us, in the period from the autumn of 1995 to some time in 1998. It is a simple question: were children with similar conditions being seen – and I am entitled to put it in the leading form, which I did – during that time? Of course he cannot be expected to provide the details of the children. It is a simple proposition.
MS SMITH: That is not what he said . He said, “I have no recollection of the fact”. He was not asked about specific details, so perhaps we could be clear as to whether he has a recollection before we go on to Mr Miller telling him what the fact is.
MR MILLER: I am sorry, sir. I do not understand the objection. Here is a doctor--- I have explained that already. I am going to explore the question with him.
THE CHAIRMAN: I am sure if you put the question again, if there is a problem with the question, the Legal Assessor will intervene.
MR MILER; Please do not think there is either any criticism of you or any catch in the question. We have looked at 12 cases and I am asking you whether or not other children were being seen throughout the whole of the period that you were there with broadly similar conditions – namely a bowel disorder and developmental problems –seen and investigated in your department and in most cases treated as well.
A I think there were children who had investigations for bowel disease along those lines.
Q And in some cases – if it helps you, it is said in a postscript to the Lancet paper – it is seen that a number of other children, 30 to 40, had been seen since that time – I will turn it up so you can see it at page 787 as an addendum – up to January 28, which is I think 1998. Have you got the point there?
A Yes, I can see.
Q In order to make sure that there is no misunderstanding, at the top of the page in the top of the left-hand column, the paragraph that starts, “We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described”, the syndrome described in that paper was, as the heading suggests on page 783, a combination of those two features.
Q So, that is “ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children” and, in the addendum, it says, “Up to January 28” for which we read 1998, “a further 40 patients had been assessed, 39 with the syndrome”.
Q So, it appears that is correct to follow that a further 40 patients had been assessed apart from the 12 who were reported and 39 of them had the syndrome.
Q Does that help you at all to remember in general terms whether you were seeing other similar children during that period up to January 1998?
A I think other children and their bowel disorders were investigated.
Q When did you leave and take up your appointment in Australia?
A I took up the appointment in Australia in January 1999.
Q And you came back to take up your consultant appointment in XXX in December?
A Yes, December 1999.
Q In general terms, the children, if they were in there for a week, were quite difficult to manage or could be quite difficult to manage.
Q Because, even if their parents were there, they had major problems and they had to be accommodated on the ward and looked after by nurses and the medical staff there.
Q And they could be quite disruptive.
Q I would like to ask you about something else. This department you said was an open department and there was a lot of discussion about all aspects of the cases, investigation and treatment. Do you recall a meeting in about April 1996 in the paediatric gastroenterology department when the possible link between inflammatory bowel disease and developmental problems, autistic spectrum problems, was discussed and the types of investigations that might be used were generally gone through?
A I do not remember a specific meeting. There was obviously discussion in the department about a possible association. I do not remember in detail or specifically what investigations it was felt would be appropriate for that.
Q But there were discussions among the members of the department?
A I am sure there were, yes.
Q I want to ask you about how it ultimately came to end up with a range of investigations which we have looked at as we have been going through the notes and that the range of investigations were upper and lower endoscopy, if felt appropriate, in other words if it was felt appropriate to do both.
Q Barium meal and follow through.
Q EEG, MRI, visual evoked responses and lumbar puncture. It was decided at the beginning anyway that these were going to be the investigations that were carried out.
Q As far as lumbar puncture was concerned, I think this was something that was suggested by Dr Thomson, who had been in Birmingham immediately before he came to the Royal Free, as something which they had used in cases of regressive or degenerative disorder.
A Yes, in different sort of disorders but possibly compatible disorders, yes.
Q The primary purpose as far as your team was concerned, the gastroenterologists, would be to exclude an organic or a metabolic cause for the child’s apparent development disorder.
Q The CSF was to be examined for lactate/pyruvate ratio because we see it in some of the notes which you have written to make sure that this was not something which had an organic cause.
A A recognised organic cause, yes.
Q In the same way, the MRI and EEG would again be investigations to identify whether or not there was any organic brain damage demonstrable on MRI.
Q Or any irregularities in terms of the EEG which again might be indicative of some sort of organic brain damage.
Q Did you have anything to do with Dr Harvey? Do you remember him at all in the unit? Dr Peter Harvey? He is a consultant neurologist.
A I have a vague recollection, yes.
Q He takes up a page of the notes in the notes that he writes, his writing is very distinctive and, in some of the cases, we can see his handwriting there as having visited and assessed the children.
Q Do you remember him ever coming to the ward?
A I am sorry, I do not have a detailed recollection of that name.
Q All of the investigations which I went through with you a moment ago were all used for some of the early patients including the 12 who were written up in The Lancet although upper endoscopy I think was only decided upon in a small minority of the cases.
A Yes. On the whole, the colonoscopies were done under sedation and it was not common practice certainly when I arrived that those patients have an upper endoscopy but colonoscopy was the routine procedure although an upper endoscopy could have been done if required.
Q If there is an upper endoscopy, it would be noted in the notes that it took place and the results.
A Yes and the biopsy samples would have been available.
Q By early 1997/spring 1997, it was decided that no useful information was being obtained from the lumbar puncture, the MRI or the EEG and they were discontinued and a cut-down number of investigations was used.
A I am sorry …
Q Do you want me to ask you again?
A Yes, please.
Q Again, I do not expect you to put a date on it but some time in the early part of the spring of 1997, it was decided that no useful information was being obtained from MRI, EEG and lumbar puncture and your department stopped arranging for these to be carried out. So, although the earlier ones had it, subsequently from the spring of 1997 they did not.
A I would have to see the notes to be confident about that.
Q Do you remember a time when certain investigations were no longer used? Not a time, but do you remember a time coming when they were discontinued?
A I am afraid that I cannot say I do specifically remember that.
Q Can we then discuss the normal patient versus the patients which had been going through in the notes. You said that with a normal, although it is obviously not a normal – an ordinary inflammatory bowel disease patient, they would have presumably an outpatient clinic appointment in which they would be assessed to see whether or not it was appropriate to come in.
A Yes, or they may come from another consultant who felt the history was indicative.
Q So, they could be referred straight in by another consultant?
Q The routine for practical reasons was that they would come in on a Sunday night.
A Sunday morning.
Q A Sunday. You would in many cases be there to do the clerking.
Q They would have bowel preparation on Sunday and possibly Monday but certainly started on Sunday, colonoscopy on Monday and then other investigations principally blood tests while they were in there.
Q What was different with the ones that again you have been going through in the notes was that other investigations were employed because they were not children with straightforward inflammatory bowel disease, they were children with an added feature, namely developmental disorder, however you have described it.
Q So, these additional investigations related to that aspect of the child’s condition.
Q And, as we have said, MRI looking for organic brain damage, EEG the same and lumbar puncture to see whether there was an organic or metabolic cause for their apparent condition.
Q That was the distinction between these children, however many of them there were, and children with straightforward inflammatory bowel disease.
Q May we turn to histopathology. Had you been in a department before which relied so heavily on histopathology?
Q Presumably, it would have been obvious to you at a very early stage how important the link between the two would be.
Q Because the patient could not properly be cared for without them working together.
Q We have seen from the notes that in most cases but not all histopathology reports were generated and in fact it may well have been histopathology reports in all cases but they are no longer in the notes.
A Every patient would have had a formal histopathology report done.
Q So, when we go through tomorrow, I know that in one of the cases there is not apparently a report in the notes, it would mean that that has in some way gone missing.
Q There were also what you described as histology meetings which you noted in the patients’ notes which you have already said were extremely important because they allowed the communication between clinicians and pathologists in open forum to discuss the nuances of the findings and it worked both ways but certainly, to your knowledge, provisional views about histopathology changed sometimes during those meetings with general discussion about what was being shown on the slides.
Q And this might lead to a change in interpretation of the slides from that which had been originally in the pathologist report.
Q Having seen them at close quarters, the senior clinicians in your department, the three consultants, were very experienced in interpreting such slides.
Q As I understand it, what would happen then would be that a decision would be taken by general discussion to which you would be a party on how the child was going to be treated.
Q And that is why, in many cases in the discharge summary which you write which may follow the time that the child has been discharged from the hospital, you end by telling the general practitioner or the referring doctor that you have already started the child on some form of treatment.
Q And that was the norm, was it not? If you could reach a view as to what the appropriate treatment was, that would be started as soon as possible although prescriptions would have to be done by the general practitioner in the long run.
Q Then, as I have asked you before, others may well have looked at the slides later and reached their own views about them but that would not be part of the process of informing the clinicians as to how to treat the child.
A That may be so, yes.
Q I would like to ask you about The Lancet paper. Do you still have it open?
Q It starts at page 783. We have already noted the title of it. It is an early report and in effect it is a report of 12 cases and observations made from what has been seen.
Q Either with a colonoscope or with histology or what has been observed by or discussed with Dr Berelowitz or with you in terms of the history that was given to you.
Q A combination of all of these things. It does not in the title anyway make any sort of linkage with MMR or MR or measles vaccination.
A I know.
Q If we look at the paper, the syndrome is identified and if you look at page 785 under “Discussion”,
“We describe a pattern of colitis and ileal-lymphoid-nodular hyperplasia in children with developmental disorders. Intestinal and behavioural pathologies may have occurred together by chance, reflecting a selection bias in a self-referred group …”
and then, right at the end of the paper on page 787, the last paragraph,
“We have identified a chronic enterocolitis in children that may be related to neuropsychiatric dysfunction.”
Pausing there, it is the gastro-intestinal symptoms, or signs rather, and possibly related to a developmental neuropsychiatric condition. That is the syndrome that is being postulated, is it not?
“In most cases, onset of symptoms was after measles, mumps, and rubella immunisation. Further investigations are needed to examine this syndrome and its possible relation to this vaccine.”
I think that you had seen this paper before, it had been sent to you in draft and you saw it before it was sent off to The Lancet.
Q Did you have any qualms about the publication of this paper in the form in which you saw it before it went out?
A I was happy that it did not make a definite association.
Q It positively said that you had not found an association, did it not?
A Yes, that is what I mean.
Q If you look at the top of page 787, “We did not prove an association between the measles mumps and rubella vaccine and the syndrome described”.
Q I want you to distinguish between the paper and what may have happened at around the time of its publication, but in terms of the paper itself you had no qualms about publication of the paper in this form describing what it did.
A No, it was a descriptive paper.
Q Did it strike you in that form that it asserted that a link had been established between MMR and the syndrome?
A It did not assert that.
Q The central thrust – an expression which you have used or may have been asked to consider – of the paper was the new paediatric syndrome.
Q Albeit only on the evidence of 12 cases, but the suggestion anyway that it needed to be looked at further to see whether it was, in truth, a new paediatric syndrome.
Q That is really what the paper was saying.
Q We have been told that there was a press briefing at around the time of publication. Were you aware of that at the time?
Q Did you attend it?
Q Obviously not if you were not aware. Did you hear about it after the event?
Q In what circumstances?
A In the press. I heard about it after the event.
Q Was that concentrating on the new paediatric syndrome or other aspects?
A It was concentrating on concerns over MMR.
Q As you have said, that is a regret that as a paediatrician you had that it may have had an effect on the uptake. Did you believe that the paper in the form in which you put your signature to it would have had that effect?
Q Many years afterwards you were approached by Dr Murch. Professor Walker-Smith had retired I think four or so years before in 2000, but you were approached by Dr Murch and those whose names we can see on page 1210, which is in FTP3, its heading is: “Retraction of an interpretation” – I will come back to the text in a minute but it was quite a substantial volume of The Lancet because it also contained in the same volume a statement from the editors of The Lancet and also some correspondence from Dr Murch and Professor Walker-Smith. If you turn forward to the next page, 1211, which is the statement, and page 1212 a statement by Dr Simon Murch and then 1213 a statement by Professor John Walker-Smith. Did you read those at the time that they came out in The Lancet as well as the retraction?
Q Going to page 1211, The Lancet editors canvassed a number of allegations relating to the obtaining of ethical approval and the selection of patients which were answered to the satisfaction of The Lancet at the time. That is what they are saying about the allegations not being found proved 1, 2 and 3 in the right-hand column on page 1211. You were aware of that at the time?
Q There are a number of allegations but I am only concerned with the first three where the explanation is given - the doctors appear to have satisfied The Lancet anyway when they investigated them. That is allegations 1, 2 and 3 in the right-hand column. In the letters that follow at page 1212, Dr Murch gave an explanation for the ethics approval position at the time of the application for ethics approval in 1996 and its number is 172-96. Did you see his explanation at the time?
Q That was one aspect which The Lancet had dealt with. The second was the allegation of systematic bias which was addressed by Professor Walker-Smith at page 1213 and again you saw that at the time.
Q At the end of that series we get your actual involvement in the retraction in the same volume 60-70 pages earlier, but it is headed “Retraction of interpretation”. Can we look at that? It is page 1210. This is what you were happy to sign up to. The second paragraph:
“The main thrust of this paper [the original paper] was the first description of an unexpected intestinal lesion in the children reported.”
Do you agree with that?
“Further evidence has been forthcoming in studies from the Royal Free Centre for Paediatric Gastroenterology and other groups to support and extend these findings.”
There are references there, one from Dr Murch and one from Horvath and others. Were you aware that other studies had supported and extended the original findings?
A I was aware that there were further studies which claimed to do that, yes.
Q This is your document partly because you have signed up to it.
“While much uncertainty remains about the nature of these changes, we believe it important that such work continues, as autistic children can potentially be helped by recognition and treatment of gastrointestinal problems.”
Was that your view at the time that you signed this document?
Q Then we come to the retraction in the last paragraph:
“We wish to make it clear that in this paper no causal link was established between MMR vaccine and autism as the data were insufficient. However, the possibility of such a link was raised …”
You accept that it was raised as a possibility in the original paper.
“… and consequent events have had major implications for public health.”
What were the consequent events?
A Poor uptake of the MMR.
“In view of this, we consider now is the appropriate time that we should together formally retract the interpretation placed upon these findings in the paper according to precedent.”
Whatever that may mean. You were happy to sign up to this.
Q Included in the signatories were the three consultants who had been in the gastroenterology unit at the time that you had been there.
Q Dr Murch, Dr Thomson and Professor Walker-Smith.
MR MILLER: Sir, I wonder if that would be a convenient point to break off? I am going to go on to deal with the individual cases.
THE CHAIRMAN: Yes, indeed. I am sure Dr Casson would be relieved to hear that as well. We will now adjourn. Dr Casson, I know that it is never appropriate to leave the witness under oath overnight but we really have no choice in this situation. You remain under oath and you are still giving your evidence so please make sure that you do not discuss it with anybody over the adjournment. We will resume at 9.30 tomorrow morning.
(The Panel adjourned until Tuesday, 21 August 2007 at 9.30 am)