Autopsy: consent, completion and communication in Alzheimer's disease research

Elizabeth M-F. O. King

Introduction

The importance of autopsy in the advancement of medical and scientific knowledge has been well documented over the centuries [1]. However, autopsy rates in both the United States of America and the United Kingdom have declined since the Second World War, recently reaching an all-time low. As both the medical profession and the lay public become less familiar with the uses and benefits of autopsy, the principle of |mortui vivos docent' (|the dead teach the living') has been largely forgotten [24]. Nowhere is this more important than in Alzheimer's disease where the definitive diagnosis remains histopathological and where many published studies are limited by being based upon clinical diagnosis alone which is known to have a false positive rate of between 12% and 35% [5]. Antemortem brain biopsy is rarely justifiable in dementia; autopsy is therefore essential for diagnosis [6].

The Oxford Project to Investigate Memory and Ageing (OPTIMA) began in 1988 as a prospective longitudinal study, aiming to improve understanding of the disease process and to develop an antemortem diagnostic test for Alzheimer's disease [7-9] . Subjects with and without significant cognitive deficit have detailed and repeated assessments during life concluding with histopathological examination of the brain.

To date, 260 subjects have been assessed in life and 250 (96%) have consented to autopsy. Ten consent forms (4%) remain unsigned. Sixty-one subjects have died and 59 have undergone autopsy (97%).

In this paper we describe five main factors that we have found to be critical in achieving this very high completion rate which we think may be of benefit to others studying conditions in which autopsy is an important investigation: 1. The fact that one asks at all and that all are asked 2. The way in which one asks 3. Existing attitudes to autopsy:

(a) co-operation

(b) pursuit of knowledge

(c) hope and purpose

(d) endorsing subjects, wishes

(e) unresolved questions

(f) obstacles to consent 4. A clear administrative infrastructure 5. Post-autopsy visits.

1. The fact that one asks at all and all are asked

This may seem self-evident. However, the declining autopsy rate although attributed in large part to better diagnostic techniques may also reflect a reluctance on the part of the medical profession to request autopsy consent [10, 11].

In discussing autopsy we breach the taboos of our culture by confronting people with the inevitability of death. Understanding why autopsy is needed enables professionals to broach the subject with confidence. In designing our protocol we recognized that we should be prepared for whatever reaction our request might provoke in our patients, their families and other professionals.

2. The way in which one asks

People vary in the extent to which they understand and accept the course of a dementing illness. The way in which they cope with the losses that it inevitably involves has meant that we have encountered reactions which range from indignant refusal, anger, fearfulness and evasiveness through a matter-of-fact acceptance to an eager, positive wish for autopsy. The sadness, incomprehension, disbelief and denial which may also be encountered are part of anticipatory grief which is the experience of the painful reality of relentless loss prior to death [12]. Discussion of autopsy may therefore provide a valuable opportunity for the expression of emotion and appropriate bereavement counselling [13].

Integral to our request is the commitment we make to both the family and other professionals to share the detailed results of autopsy when they are known.

The question of autopsy is introduced to those participating in the research when the protocol is explained at the initial visit, although signed consent may not be obtained until a later date. If the person is able to understand the request and the reason for it, his or her consent will be sought, in addition to that of the next of kin. Discussion is encouraged within the family, allowing as much time as is required to reach a consensus decision.

3. Existing attitudes to autopsy

It is important to recognize that each individual and family entering research is unique. Culture, class, belief systems, present circumstances and past experiences all shape attitudes to loss, illness, death and autopsy [14]. When the reasons for autopsy are understood many people are willing to give their consent at once. Indeed, as has been the case in other studies, we have found that many have considered it well in advance [15].

A number of families in our study have expressed their thoughts and feelings about autopsy both in conversation and in writing. Their various motives and goals are described below using illustrations from letters we have received from relatives of those who have had an autopsy as part of the study.

(a) Co-operation: For some it is sufficient that their co-operation is requested by those in perceived positions of authority, for example medical and/or nursing professionals. This has obvious ethical implications regarding informed consent and requires diligence on the part of the research team to ensure that information and explanations are given and understood and that people's trust is not abused [16].

Another common reason for wishing to cooperate is the belief that after death and in some cases before death, |the person one has known for so many years is no longer there just a shell'. If the body is seen as a |shell' which has served its purpose, then what happens to it after death cannot affect the individual who is no longer there. As one person said, |For me, my mother died many months before her physical death', also, |giving consent to autopsy was the easy part' and ultimately that |death would release her soul from her physical body'.

(b) Pursuit of knowledge: Some people have strong wishes to help further scientific and medical knowledge, |if an autopsy on suspected sufferers will advance the research in any way, then naturally I would give consent'. |I was very keen for my mother's body to be used for research'.

(c) Hope and purpose: Many people see autopsy as a means of salvaging some meaning and hope from an otherwise desperate situation, for example: |granting consent for autopsy was a positive step towards helping others,' |I just felt I wanted to do anything that was in my power to help forward research into this dreadful disease'. For some the meaning exists in the context of other people as yet unknown to them; |in some small way I might relieve the suffering of someone in the future', and perhaps the ultimate expression being |then all of her suffering and our witness of that suffering would have had a purpose'.

(d) Endorsing subjects, wishes: For some relatives the knowledge that the person who has died had already expressed the wish to leave their body to medical science or would have approved of autopsy, enables them to accept the idea as shown in the following; |he would have wanted to help too' and |I think mother would also have been quite happy to think she was of use in this way' or as one of the relatives said so eloquently: |I felt very strange and proud that even after her death M. was in her element, helping people'.

(e) Unresolved personal questions: For some there may be unanswered questions about the disease process. The autopsy affords the opportunity to resolve at least some of these questions and doubts. One of our respondents wrote as follows: |Would earlier and correct diagnosis . . . have given the chance of some possible cure?'. Or, as someone else wrote: "For my part, it answered some of the many |what if?' and |if only?' questions".

(f) Obstacles to consent: Not everyone comes with positive attitudes towards autopsy. There may be ambivalence, prejudice and fear associated with the taboos about death and what happens to the body after death. Sometimes there is an initial lack of understanding regarding the reason for the request and the procedure itself. Clear information and explanations can help to overcome this. For example, it is often helpful to state that the autopsy is to be performed for specific reasons, by a senior neuropathologist, and not for teaching purposes alone. The fear of disfigurement can be dispelled by reassurance that the body may be viewed after the autopsy and will appear no different once the brain has been removed.

Other practicalities should also be addressed, such as, for example, that normal funeral arrangements need not be delayed. Questions about the cost of autopsy are often raised and should be clarified at the beginning of any discussion. Within the OPTIMA project, for example, all expenses other than those of the funeral are covered by the research budget.

Objections may also be voiced on religious grounds. Whilst maintaining respect for any individual's beliefs, it may be possible to suggest that a discussion with other members or representatives of a particular faith could be useful in clarifying the issues. It is a fact, however, that none of the major religions absolutely prohibits autopsy [17, 18]. A minority of people may have superstitious reasons for not consenting. For example, the fear that giving written consent may actually hasten death, or in other cases the feeling of some relatives that a person has suffered enough and that autopsy at the end of it all would be too much. Individuals may be aware that these fears are illogical but it is important that they are expressed and respected. In our experience consent may still be granted at the time of death, providing autopsy has been discussed previously.

In some circumstances the next of kin is unwilling to assume responsibility for consent on behalf of other family members. In such cases we encourage discussion within the wider family which may result in a consensus decision, shared responsibility and multiple signatories.

Occasionally subjects themselves or their close relatives have expressed negative views regarding autopsy in the past. When this happens their views can only be accepted and respected, and autopsy consent remains unobtainable. Even in such cases, if a coroner's autopsy is indicated and the coroner agrees, and providing other professionals are aware of the need for autopsy for research reasons, the necessary tissue may still be obtained.

Perhaps one of the most significant obstacles to consent is an inadequate understanding and acceptance of the inexorability of the disease process. For example, one of our patients, relatives wrote: |The decision making itself presented no problem. But it confronted me with a far bigger, deeper problem. I had considerable difficulty in accepting the brutally hard fact which lay behind the doctor's request--that T. (my wife) must be suffering from a disease which he believed or knew would be fatal over an unspecified time.'

Expressions of denial or anger when the initial request for autopsy consent is made indicate that persistence at this point would not only be insensitive but also counter-productive. Each individual situation needs to be approached with empathy. A knowledge and understanding of the process of anticipatory grief and bereavement counselling skills facilitate this.

4. A clear administrative infrastructure

Once consent has been obtained it is essential that everyone involved is aware of the arrangements, thereby avoiding unnecessary stress for the family at the time of death. This depends upon effective communication and inter-disciplinary co-operation. In countries other than the United Kingdom, legal and administrative procedures regarding autopsy may vary. The OPTIMA study has developed the following administrative protocol:

Copies of the signed consent to autopsy form are sent to the family doctor, family or next-ofkin, and for inclusion in the general hospital notes, psychiatric notes, residential or nursing-home notes and our office administrative files. A further copy is kept in the OPTIMA study notes, together with the original form. An explanatory letter and an alerting label for affixing to any relevant notes accompanies these copies giving contact telephone numbers providing 24-hour, 7-days-per-week cover.

When the researchers are informed of death, the family is contacted and asked to re-endorse the consent form which should accompany the body. This is necessary in order to fulfil legal requirements and simply involves re-signing and dating the previously signed form. Where this is not possible, verbal re-endorsement will suffice providing a written form can be obtained by return of post. The relevant doctor issues the death certificate which enables the body to be released for autopsy. The pathologist is told of the death, and transport of the body is arranged.

In our case we have been careful to establish a reliable relationship with one particular undertaking firm prepared to travel far afield and who understand and support our specific requirements. Such an arrangement ensures both a committed and high-quality service. The family is informed when the autopsy is to take place so that funeral arrangements can be made.

5. Post-autopsy visits

In our experience, as in that of Valdes-Dapena, the post-autopsy visit is a vital part of the whole autopsy process [19]. Results are often keenly awaited by both families and clinicians. There is no doubt that the shorter the delay the better it is for the grieving process of the family, the collaboration of other professionals and the research [20, 21]. Regular clinico-pathological meetings which include all those who have played a part in the management and investigation of a case, enable those involved in medical, nursing, and diagnostic procedures to increase their skills and to become better informed.

It is very important that the research team fulfil their commitment to the family by contacting them as soon as the histopathology is available. An open invitation is made to meet either at the hospital or in the home of a relative and can include as many of the family as are interested .

The opportunity to ask questions, discuss specific findings and perhaps to resolve some of the lingering doubts and uncertainties helps the bereaved to accept the reality of the loss and to provide reassurance as they re-evaluate the past. In the words of a relative of one of our patients |I now have the answers to my questions and my mind is at rest on these points'.

Conclusion

Our experience of designing a protocol in which obtaining autopsy is essential has produced mutually beneficial results meeting the needs of families and scientific enquiry alike. We have identified five main factors which have enabled us to achieve a very high (97%) autopsy completion rate. The first request for autopsy consent made at the initial screening interview revealed that many families already held positive attitudes to autopsy. Our approach in making the request has been influenced by our own work in acquiring counselling skills and our understanding of the process of anticipatory grief, which, with clear explanations and information, enables negative attitudes to be explored and reassessed.

An administrative infrastructure, built upon effective communication and interdisciplinary co-operation, ensures that everyone involved is aware of the necessary arrangements and minimizes the stress and inconvenience for all concerned at the time of death.

The post-autopsy visit is an integral part of the whole process in the OPTIMA protocol, enabling results to be shared with the family so that their doubts and uncertainties can be resolved .

In this way we have both achieved the autopsy rate essential to furthering our research, and have been able to support families through what is often a very difficult time for them, reciprocating with them hope and confidence for the future.

Acknowledgements

We would like to thank all the patients, their families, carers and clinicians involved in this study; Dr Andrew Jaskowski, Lin Barnetson, Clare Bateman, Sue Stannard for help with the manuscript; Reeves and Paine funeral directors; all those in the Department of Neuropathology; Drs Margaret Esiri, James Morris, Brendan McDonald and in particular Professor A. David Smith. This work is supported by a grant from Bristol-Myers Squibb.

References

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Authors, address Oxford Project to Investigate Memory and Ageing (OPTIMA) University Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE

Address correspondence to: Dr K. A. Jobst and E. King

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