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The Investigation of Events that followed the death of Cyril Mark Isaacs
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| This chapter summarises the involvement of Research Ethics Committees in considering research protocols submitted by the joint programme. The chapter describes key features of the protocols considered by RECs. | |
| Professor Deakin states that 'All Ethical Committee applications had the sole and explicit purpose of obtaining approval to approach relatives for hospital post mortems on their deceased relatives'. | |
| The protocols omitted any reference to the collection of brains from Coroners' cases. Professor Deakin has commented that 'reference to control brains was for information and to demonstrate the scientific design'. However, the references to controls did not address the source or the inclusion of Coroners' cases. | |
The titles of the projects submitted |
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| With the exception of the first protocol that was submitted to Salford Ethics Committee, Professor Deakin is sure that all other Ethics Committees received the same proposal. Professor Deakin states this was the protocol dated 17 July 1986 which is on a South Manchester Ethics Committee (SMEC) form. | |
| While several Ethics Committees may have received the same protocol, the titles by which they referred to the protocol were different. | |
| Titles of applications used in correspondence with Ethics Committees | |
| Salford Ethics Committee, Chapter 12 | |
| The Salford EC considered and approved the protocol entitled: 'Brain research in schizophrenia and tardive dyskinesia'. | |
| South Manchester Ethics Committee | |
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The South Manchester EC received the protocol signed by Dr Deakin on behalf of Dr Slater and himself on 17 July 1986. The title was: 'Post-Mortem Brain Neurochemistry and the Major Psychoses'. No record is available about when the protocol was considered by the Ethics Committee for the University Hospital of South Manchester. The only document available is a copy of an unsigned letter dated 26 November 1986 to Dr Brookes. Professor Deakin reports that Dr Brookes was Secretary of the Ethics Committee responsible for the South Manchester hospitals. |
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| This letter asks for comments on a draft letter which Dr Deakin planned to send to general practitioners. The draft letter itself is not attached and the terms in which the South Manchester Ethics Committee responded are not available. | |
| However, the letter to Dr Brookes refers to 'Control samples (of brains) are obtained from patients who have died in the Community and who come to post mortem at Prestwich or North Manchester'. | |
| There is no reference to Coroner's cases and the terms 'deaths in the community' is not synonymous with deaths reported to the Coroner. | |
| It is also notable that the letter is addressed to South Manchester in respect of cases occurring in Salford (Prestwich) and North Manchester districts with which there was no similar correspondence. | |
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North Manchester Ethics Committee, Chapter 13 |
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| The North Manchester EC received the same protocol as South Manchester EC. The title is to be found in the approval letter dated 11 September 1986. It appears from the date of the letter to Dr Brookes that consideration by the North Manchester EC preceded consideration by the South Manchester EC, but in the absence of other documents, this cannot be confirmed. Later correspondence with the North Manchester EC refers simply to: 'post mortem brain studies in mental illness'. | |
| Warrington Ethics Committee, Chapter 15 | |
| The correspondence with Warrington EC refers to: 'Post-Mortem Neurochemical Studies in Schizophrenia'. | |
| Oldham, Rochdale and Wigan Ethics Committees, Chapter 14 | |
| Correspondence with these three Ethics Committees refers to: 'Brain Research in Schizophrenia'. | |
| Macclesfield Ethics Committee |
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| The correspondence with Macclesfield EC refers to: 'Post-mortem brain studies in Schizophrenia'. | |
| Professor Deakin assures me that the Committees, with the exception of Salford, received the protocol dated 17 July 1986. As the Committees no longer have the protocols that were considered more than 10 years ago, I am unable to check the titles or explain the variations used by the Ethics Committees in correspondence. | |
| Professor Deakin states that the difference in the titles probably followed the heading he used in his letters to the Committees. However, the letters available to me all have the same title 'Post-mortem brain studies in Schizophrenia'. It is improbable that the Ethics Committees decided to change the titles of protocols submitted to them. | |
| In view of my discussions with those who were Chairmen of Ethics Committees in the late 1980s, I am surprised that each Committee did not insist on receiving an application on its own form. One Committee Chairman has told me that the Committees in the Manchester area were very particular on this point. | |
References to approval by other Ethics Committees |
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| After protocols had been approved by Salford and North and South Manchester ECs, other Committees were told of the approvals already received. | |
The consent of the relatives |
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| In the protocols that survive, the team emphasise the importance of obtaining consent from relatives. This was included in the 1988 notes prepared for consultants to give to relatives of patients with schizophrenia in hospitals participating in the research. | |
| The protocols submitted to the Ethics Committees state clearly that the relatives would be asked to consent to the retention of brains of patients. The psychiatrist who had been looking after the patient will: 'seek permission from the nearest relative to remove brain tissue at post mortem'. | |
| (The need for consent was emphasised by Oldham Ethics Committee. In their approval letter dated 2 November 1990 the Committee Chairman wrote: 'It was the considered opinion of the members that a direct approach to the relative was preferable to a telephone call and that contact should be made either by you or a senior clinician'.) | |
| The applications to the Ethics Committees are less specific about consent to the retention of 'control' brains but state: 'We would also like to collect some brains of patients who have died from medical conditions who have not suffered from mental illness'. | |
| The letter to Dr Brookes refers only to 'patients who have died in the Community', but does not refer to consent from the relatives of these patients from whom 'control samples' were obtained. | |
Access to patients' medical records |
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| On access to the patients' medical records, the protocols to Ethics Committees include: 'We will need to look at the deceased patient's notes at some stage after collecting each patient's brain'. | |
| The protocols do not state how the records of 'control' cases would be accessed. | |
Collection of brains from Coroners' cases |
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| While the protocols to Ethics Committees (and applications for research funds) referred to collection of 'control' brains, they failed to disclose that most of the control brains were obtained from Coroners' cases. There was, therefore, nothing in the protocol that would prompt an Ethics Committee to ask about the consent or collection arrangements for brains removed from Coroners' cases. | |
| The assumption appears to be that Ethics Committees did not need to know about the collection of brains from Coroners' cases. This, in my view, did not absolve the research team from making full and complete disclosure to the Ethics Committees of their proposed activities. | |
Letters to general practitioners |
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| In practice, when the team obtained a brain from a Coroner's case a letter was sent to the deceased's general practitioner. The reason for this was to establish that the patient had had no dementia and no mental illness which would exclude the use of their brain as a 'control' and to identify relevant drug treatment at the time of death which might interfere with neurochemical measures. | |
| The letter to the general practitioners in the first paragraph states: 'We are carrying out research into brain chemistry and mental illness. We collect post-mortem brain samples and these are analysed in the department of physiology in the Medical School. These studies have ethical committee approval'. | |
| The letter sent to Dr Rosenberg, Mr Isaacs' general practitioner, is one such example. | |
| The second and subsequent paragraphs request particular information about the deceased's health and medication at the time of death. | |
| At a later but unrecorded date the format of the letter to general practitioners was changed. The wording of the second letter indicates that it would have been preceded by a telephone conversation. The letter maintains the reference to 'samples of brain tissue' but Ethics Committees are referred to at the foot of the letter: 'This research is carried out under the auspices of all local ethics committees'. These letters, like the earlier version, were sent on behalf of Dr Deakin, but were usually signed by other members of the team. | |
| Professor Deakin states that the first letter had been referred in draft to Dr Brookes, Secretary of the Ethics Committee responsible for South Manchester hospitals. However, the application to the South Manchester Ethics Committee and the letter dated 21 November 1986 do not mention the collection of brains from Coroner's cases, although both refer to collection of 'control' samples from patients who died in the community. | |
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The initial letter was also sent to general practitioners in respect of Coroner's cases whose bodies had been taken to Prestwich Hospital, although the Salford EC had not been approached. The Salford EC were unaware of the collection of 'control' brains from Coroner's cases or of the use of this letter. |
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Misleading statements |
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| The Ethics Committees had not been told the relevant facts. They had been told about the collection of controls but not that these would be mainly brains from Coroners' cases. In particular, the Salford and North Manchester ECs were unaware of the collection of brains from Coroners' cases. | |
The assertion in the letters to general practitioners that 'these studies have ethical committee approval' was regarded as misleading by at least one general practitioner. |
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The letter to general practitioners was also misleading in referring to 'brain samples' when in fact the whole brain had been retained. |
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| General practitioners would expect that, in some cases, samples of brain tissue would be retained, but would have taken issue with the University had they realised that the whole brain had been removed and retained without the knowledge of the relatives. | |
General Medical Council guidance |
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| The claim of Ethics Committee approval must also be considered in the light of the General Medical Council's guidance that information for research should only be disclosed for projects that have been approved by a recognised Ethics Committee, Chapter 6. | |
| General practitioner recipients of these letters, whose patients had been the subject of a Coroner's post mortem, would have concluded that the Ethics Committees had been informed that the research would include Coroners' cases. They could not have known that they were being asked to provide details outside the GMC guidelines. It was also not made clear that a brain from a Coroner's case had been obtained without the knowledge or consent of the relatives. | |
| Professor Deakin's observations on consent - June 2001 | |
| In a letter dated 11 June 2001 to the General Medical Council, Professor Deakin notes: 'Dr Slater initially set the system up for Alzheimer's disease but I began collaborating with him with schizophrenia sometime afterwards. The local mortuaries and coroner's offices would telephone Dr Slater's laboratory if possible cases of Alzheimer's disease or schizophrenia were undergoing post-mortem and also if non-psychiatric control subjects were. | |
| This system continued an earlier one in which brains from all over the country were supplied to the Medical Research Council Brain Bank at Addenbrooke's Hospital. My understanding is that in Coroners' cases of non-patient deaths in the community, consent was not routinely sought in the 1970s and early 80s. In contrast, where deaths occurred in hospitals, removal of tissue could not happen without written consent of the relatives. We continued existing practise (sic) in the NW. As far as I could see, this did not differ from practises (sic) in the previous research institute where I trained or from practise (sic) in other hospitals at that time. | |
| I became increasingly uncomfortable about not consulting relatives and after a discussion with Mr Gorodkin the Manchester Coroner, instigated by me in 1995; my involvement ceased. | |
| I did obtain Ethical Committee permission as part of an attempt to set up a prospective collection. In other words, to approach patients and their relatives for brain donation in the event of subsequent death of the patient and also to approach relatives after the death. However, we had no funding to set up the ante-mortem consent scheme and nothing further came of it. | |
We did not have Ethics Committee permission to collect brains from Coroners' post-mortems because we did not believe it was necessary. It never entered our minds that this was required, especially as the pathologists were willing to remove tissue. We understood from our contact with other researchers and from previous experience that it was universal practice for tissue and organs to be removed for research purposes during Coroner's post-mortems'. |
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| Professor Deakin's observations in his letter of June 2001 explain why he did not seek the approval of Ethics Committees before obtaining brains from Coroners' post mortems and why he did not ask permission of the relatives. | |
| Professor Deakin makes the same point in a letter to me dated 8 November 2001: 'It is certainly the case that Coroners' post-mortems were frequently used as a source of supply for brain and other organ material to form the control sample and indeed consent was not routinely obtained. Brains were collected from Coroners' post-mortems at Northwick Park where I trained and Professor Tim Crow would be able to tell you about that. Other collections active at the time (were) at Nottingham, Oxford, Institute of Psychiatry, Newcastle and Edinburgh'. | |
| Summary | |
| Although the same protocol was said to have been sent to a number of Ethics Committees, the subsequent correspondence refers to different project titles. The reasons for this variation have not been satisfactorily explained. | |
| Protocols submitted to Ethics Committees must include all the relevant facts. The joint research team did not include significant features in their protocols. | |
| Ethics Committees who were later asked for approval may have been mistakenly reassured by references to approval given by other Ethics Committees who had not been given the full facts. The Committees could not have known that almost all control brains were obtained from Coroners' cases. | |
| The protocols sent to Ethics Committees state clearly that the consent of relatives would be obtained when the deceased had been under the care of a psychiatrist, but are silent about whether relatives of control cases would be similarly asked for consent. | |
| The letters to general practitioners are misleading: | |
| - Ethics Committees had not been aware of, or approved, the inclusion of brains from Coroners' cases. The provenance of control brains was not explained; | |
| - the statement that 'these studies have ethical committee approval' obscured the real provenance of most of the brains collected as 'controls' and the reference to 'brain samples' hid the fact that the whole brain was retained; | |
| - the request for medical information about the deceased's health does not appear to satisfy the GMC requirements for Ethics Committee approval. | |