The use of human samples obtained during medicolegal autopsies in research: An introduction to current conditions and initiatives in Japan

Abstract

Background

Leftover samples obtained during autopsies are extremely important basic materials for forensic research. However, there are no established practices for research-related use of obtained samples.

Objective

This study discusses good practice for the secondary use of samples collected during medicolegal autopsies.

Methods

A questionnaire was posted to all 76 departments of forensic medicine performing medicolegal autopsies in Japan, and 48 responses were received (response rate: 63.2%). As a secondary analysis, we surveyed information provided on department websites.

Results

Ethical reviews conducted when samples were to be used for research varied greatly among departments, with 21 (43.8%) departments reporting ‘fundamentally, all cases are subject to review’, eight (16.7%) reporting ‘only some are subject to review’ and 17 (39.6%) reporting ‘none are subject to review’. Information made available on websites indicated that 11 departments had a statement of some type to bereaved families about the potential research use of human samples obtained during autopsies. Nine of these included a notice stating that bereaved families may revoke their consent for use. Several departments used an opt-out system.

Conclusion

There is no common practice in the field of legal medicine on the ethical use for medical research of leftover samples from medicolegal autopsies. The trust of not only bereaved families but also society in general is required for the scientific validity and social benefits of medical studies using leftover samples from medicolegal autopsies through the use of opt-out consenting and offline and online dissemination and public-relations activities.

Keywords

Medicolegal autopsy bereaved families leftover samples secondary use communication

Introduction

In this study, we explored the current conditions, experiences and problems in Japan regarding procedures for the secondary use of samples obtained during medicolegal autopsies for medical research.

Forensics has advanced a great deal through the use of cadavers and tissue samples from the deceased. For example, in the field of forensic toxicology, important data have been obtained through chemical analysis of blood and urine, including identification of drugs and toxins that a person used before death and how much of a substance is fatal. In the field of forensic pathology, organ tissues and prepared specimens are important resources to help understand the pathology of the deceased before death and to elucidate the mechanisms leading to death. Therefore, human samples obtained during autopsies are extremely important basic materials for a variety of forensic research procedures.

In Japan, medicolegal autopsies are typically conducted at university forensic medicine departments as part of a criminal investigation, according to the Code of Criminal Procedure.¹ As in many other countries, medicolegal autopsies do not require the consent of the family of the deceased. In an autopsy, sections of organs and other samples are collected in accordance with requests from the investigating authorities. Samples are regularly stored at departments of forensic medicine in case of re-evaluation and re-examination, which may be requested after the autopsy is completed. However, such stored samples have also been used in medical research. The use of these samples for research rather than for the original purpose of the autopsy often becomes a point of contention. Many bereaved families in Japan are unaware of how human samples collected from their relatives are handled at departments of forensic medicine. This is because in order to ensure that investigations remain neutral and impartial, forensic departments have traditionally been instructed not to contact bereaved families (who can be suspects in some cases) before or after the autopsy. In addition, in some situations, police may not have had sufficient contact with bereaved families. In a previous study, we found that many departments do receive enquiries from bereaved families regarding the storage and use of such samples, including requests that the samples be returned to the family.²

The fact that the use of these samples generally ignores the wishes of bereaved families may have a negative effect on the future supply of research material.

Beginning in the 1990s, debate has increased on regulations for the handling of human samples earmarked for research, brought about, in part, by cases in which samples from deceased individuals were improperly stored and used. For example, in the United Kingdom, a brain collected by a coroner during an autopsy was used in research without the permission of the bereaved family.³

Some countries have created rules for the use of samples from cadavers. In the United States, the use of existing samples in research has been legally accepted, as long as the samples are anonymous (45 CFR 46.101(b)(4)). The College of American Pathologists quotes from this policy,⁴ but the National Association of Medical Examiners states that the use of such samples in research ‘specifically requires the consent of the next of kin’.⁵ In the United States, the Department of Health and Human Services solicited opinions for the revised version of its Common Rule, which was released in 2011. One major point of debate was how consent should be obtained for the use of stored samples. The revised version may have an effect on how samples collected from cadavers are used.⁶ In the United Kingdom, the Human Tissue Act 2004⁷ and the Coroners (Amendment) Rules 2005⁸ stipulate that the secondary use of samples derived from cadavers requires that bereaved family members be informed. In Japan, 2002 guidelines by the Japanese Society of Legal Medicine stipulated that the consent of the bereaved family ‘should be obtained’ before such use of specimens collected from autopsied cadavers.⁹ In the 2006 guidelines, however, this was changed to ‘it is desirable’ to obtain the consent of the bereaved family,¹⁰ and in 2015, returned to the expression that the consent of bereaved family members ‘should be obtained’.¹¹

For researchers to determine on their own whether to use samples from legally required medicolegal autopsies for research is made even more difficult by their responsibility to explain autopsies to society in general.

As there seems to be no consensus, we investigated how the use of human samples derived from medicolegal autopsies has been handled in Japan previously. The present paper introduces the results of a pilot study on the current situation regarding the research use of stored samples from medicolegal autopsies in Japan, and proposes a course of action for the future.

Material and methods

Intra-organisational secondary use procedures (2010)

Survey subjects and methods

We posted a questionnaire to all 76 university departments that perform medicolegal autopsies in Japan in 2010, allowing two weeks for responses. Universities that did not respond were sent a reminder by email.

Survey questionnaire

The questionnaire addressed the following points: general policies for storing samples or standards for the period of storage (Q1); ethical review requirements for research use of these samples (Q2); and control mechanisms for third-party access to samples (Q3). In addition, a section of the questionnaire allowed the respondent departments to comment freely on the topic (Figure 1).

Figure 1.

Questionnaire form.

External disclosure and provision of information regarding secondary use (2016)

Methods

We investigated whether all 76 departments in Japan that were asked to complete the questionnaire disclosed information and provided explanations to bereaved family members in pamphlets. For those using pamphlets, we reviewed the contents of those pamphlets. The source of this information was either from a department’s own website or from referral by the department to another website as at February 2016.

Survey points

For each department that had a website, we investigated whether they disclosed information regarding the use of autopsy samples in research, what specific information was disclosed, whether they provided explanations to bereaved families using pamphlets, and what the specific contents of those pamphlets were.

Results: Intra-organisational procedures for secondary use of samples (2010 survey)

Overview of survey respondents

Of the 76 forensic medicine departments in Japan, 48 responded to the survey (response rate 63.2%). Twenty-two departments conducted more than 100 autopsies, and 26 conducted fewer than 100 (data not shown in Table). These figures were generally in line with the average number of autopsies conducted in all forensic medicine departments in Japan, and there was no significant difference in the number or type of autopsies conducted among the respondents (Table 1).

Table 1.

Comparison between all departments of forensic medicine in Japan and survey respondents.

	Respondent department (n = 48)		All departments (n = 76)^a
	2013	2011	2013	2011
Average number of autopsies (range)	150.2 (2–462)	133 (0–385)	153.4 (2–734)	138.4 (0–734)
Type of autopsies performed (average number of autopsies)
Medicolegal 77.2% (116.1)		84.5% (112.3)	75.9% (116.4)	80.9% (112.1)
Other^b 22.7% (34.1)		15.5% (21.0)	24.1% (36.9)	19.9% (26.5)

Information from the Japanese Society of Legal Medicine. List of Legal Medicine Activities in Japan 2011, 2013.

Including administrative autopsies under the Postmortem Examination and Corpse Preservation Act and new law autopsies under the Death Investigation Act.

Departments were asked if they had specific standards for storage time (Q1). Twenty-nine (60.4%) departments responded that ‘standards are in place’, and 19 (39.6%) stated that they had ‘no set standards in particular’. Of the departments with standards for regular storage, six stored samples for fewer than five years, 11 stored for samples for five years, and 10 stored samples for more than five years.

Responses to survey questions

Ethical review of research using autopsy tissue samples (Q2)

All or some research projects that used samples stored after autopsy were subject to ethical review at 29 (60.4%) departments (Table 2). At 15 (31.3%) departments, all research projects were subject to review in advance. Among departments where research projects were only partially subject to review, four (8.3%) gave the reason as ‘thought unnecessary given the mandatory nature of the autopsy’, and one (2.1%) as ‘ethics committee judged additional discussion unnecessary’. Among departments that did not implement ethical review, seven (14.6%) gave the reason as ‘thought unnecessary given the mandatory nature of the autopsy’.

Table 2.

Detailed survey responses about forensic medicine department policies on ethical review for research use of autopsy tissue samples.

	All (n = 48)
Ethical review required for use
Yes	29 (60.4)
All	21 (43.8)
Each case	15 (31.3)
Comprehensive	2 (4.2)
Other	4 (8.3)
Partly	8 (16.7)
Ethics committee judged additional discussion unnecessary	1 (2.1)
Concerns about workload and delay in plans because of review	0 (0.0)
Thought unnecessary given the nature of the autopsy	4 (8.3)
Other	3 (6.3)
No	19 (39.4)
Ethics committee judged additional discussion unnecessary	1 (2.1)
Concerns about workload and delay in plans because of review	0 (14.6)
Thought unnecessary given the character of the autopsy	7 (14.6)
Other	9 (18.8)
No answer	2 (4.2)
Requirements for use by third-party researchers^a
Yes	30 (62.5)
Ethical review approval	2 (4.2)
Permission from department chair	6 (12.5)
Not permitted	22 (45.8)
No	14 (29.2)

Data are presented as number of respondents (percentage).

Invalid responses not included.

Nineteen (39.6%) departments did not require review. The following reasons were written in the comment field: ‘The Ethics Committee of the University has determined that medicolegal autopsies are not within the scope of their review (because the consent of bereaved families is not required); as a result, ethical reviews were not conducted’; and ‘Because of the nature of medicolegal autopsies, it is practically difficult to implement procedures for obtaining the consent of bereaved families. Thus, we have arrived at the consensus that as long as physicians and researchers remain fully aware of the need to protect private information, such consent will not be requested’. Interestingly, the following comment was also received: ‘If the arbitrary use of autopsy samples in research becomes a social issue, it would be difficult to determine how specifically to handle such cases’.

Use of autopsy tissue samples outside the department or by third-party researchers (Q3)

Thirty departments (62.5%) had policies governing the use of samples outside the department or by researchers from other institutions (Table 2). The policies included ‘ethical review’ (two departments, 4.2%) and ‘only by permission of the department chair’ (six departments, 12.5%). Twenty-two (45.8%) departments did not permit releasing any samples, whereas 14 (29.2%) had no particular policy in place.

Results: Disclosure and provision of information regarding secondary use (2016 survey)

Provision of information on websites

Forty (52.6%) departments had their own websites. Eleven (14.4%) departments mentioned the handling of autopsy samples on their websites, of which five provided general information about the possible future use of samples. These explanations varied. In some cases, a comprehensive explanation was given for how the samples are handled and of the privacy policy. For example, ‘Some blood and tissue samples from deceased persons that are stored at this department may be used in research and education. In such cases, information that can be used to identify the deceased and his or her families is completely removed. Paramount consideration is paid to the protection of privacy and human rights’.¹² In other cases, the issue was mentioned only as part of the general explanation of medicolegal autopsies. For example, ‘There are many examples of medicolegal autopsies being performed because of a variety of incidents. Therefore, we store samples for the purpose of maintaining the reliability of diagnoses”.¹³ Six (7.9%) departments specifically mentioned the types of samples and methods of analysis they would use after the department or researchers at the department determined individual research plans. For example, ‘As a research objective, we sought to develop a new diagnostic method for drowning. This department uses blood collected from medicolegal autopsies to investigate the effectiveness of a method of detecting plankton and an enzyme immunoassay in which lung-specific proteins thought to be released into the blood during alveolar wall breakdown are used as markers’.¹⁴ Of the 11 departments that mentioned the handling of autopsy samples, nine (81.8%) mentioned the possibility that consent to use human samples collected from a deceased person in research is revoked if the bereaved family so wishes.

Examples of documents available from police and websites

An example of an explanation provided to bereaved families is shown in Figure 2. The purpose of this document is to disclose information to bereaved families and society in general through the department’s website. It is also distributed to bereaved families through the police before and after the medicolegal autopsy is performed to share information about how human samples collected during autopsies are subsequently handled. This document explains that such samples may be used in research, that bereaved families may refuse to allow collected samples to be used in research, and that they also can withdraw consent via an opt-out procedure. In addition, it explains that the document is intended to provide information to bereaved families and that the ethical procedures for the use of samples in research has been investigated by the organisation’s ethics committee and certified as valid.

Figure 2.

Example of the contents of a pamphlet used to provide information to bereaved families.

Currently, of the five departments that provide comprehensive information on their websites regarding the possibility that samples may be used in research, three refer to the document created by the authors of this study (Figure 2). Since we began using this form, there have been a few cases in which consent was revoked at the authors’ university. However, there have been no reports of complaints from bereaved families or conflict between them and departments of forensic medicine.

Discussion

In this study, we surveyed the current situation and the new initiatives being adopted in Japan in relation to the use of human samples derived from medicolegal autopsies for medical research purposes. Although there were examples in which this use was subject to review by individual ethics committees, some responses indicated that an ethics committee determined that such a review was unnecessary. In addition to the lack of clear guidelines for the use of leftover samples in research and the transfer of such samples to third-party organisations, our findings suggest that there are no established practices on this topic at a number of forensic departments.

As in other countries, there is increasing concern in Japan from bereaved families regarding the handling of leftover samples after medicolegal autopsies.² We expect that this concern is not only from families but is shared in society about the gap between the original legally established purpose of autopsies performed to determine the cause of death and to help criminal investigations and the use of samples derived from these autopsies for research purposes.

The results of the current study suggest the need for increased basic awareness of issues on the handling of samples from medicolegal autopsies and that standardised procedures need to be established.

It is not easy for forensic researchers to obtain individual consent to research use from a bereaved family. This is because to maintain objectivity in their evaluations, forensic researchers are neither permitted to contact bereaved families directly nor given the names and contact information. The problem is compounded, as families have no right to approve/decline a medicolegal autopsy, including the collection of samples from the procedure. Furthermore, in some cases, for example those of unidentified bodies, the family does not know their family member has been subjected to an autopsy. Therefore, we propose the following three approaches in Japan as practical ways of addressing the problems as they arise under current circumstances.

Approach 1: Obtaining consent through the opt-out method – from departments of forensic medicine to bereaved families

Medicolegal autopsies themselves are a compulsory type of legal procedure that is according to the Code of Criminal Procedure. Therefore, it is impossible to obtain the consent of bereaved families according to the opt-in method that is used in pathological autopsies before using leftover samples after the autopsy is complete. Although a medicolegal autopsy does not require the consent of the family, the maximum possible effort must be made to inform the next of kin and bereaved families and obtain their consent when researchers use samples collected during the autopsy.

Currently in Japan, it is mainly the police who deal with bereaved families before and after medicolegal autopsies. One option is to allow the police to obtain consent from bereaved families for the possible future use of samples in research. However, when explaining that the original purpose of a medicolegal autopsy is to determine the cause of death and assist in a possible criminal investigation, it may seem inappropriate for the police also to explain the possibility that autopsy samples may be used in the future for research unrelated to the original purpose of the autopsy. Therefore, although it is essential to have in place initiatives to ensure the bereaved families understand, ideally in a face-to-face situation, we believe that one practical method of supplementing oral explanation is by providing information through web-based documents such as those described above, and ensuring that bereaved families have the opportunity to express their opinion and to opt out.

Many medicolegal autopsies are performed because of death caused by crime or accidents. The families in such cases are already likely to be confused and agitated, as well as dealing with extremely strong feelings of attachment, loss and grief. Bereaved families may experience shock and anger upon learning that samples collected during the autopsy were, unbeknownst to them, subsequently used in medical research.² By ensuring that the next of kin know that they can opt out and are given an opportunity to revoke consent at the time the autopsy is explained to them, they are provided the opportunity to make their own choice.

Approach 2: Communication from the police to the bereaved family

When medicolegal autopsies are performed, in addition to departments of forensic medicine, the police also play an important role. This is because autopsies are conducted upon the request of the police and prosecutor, and the police are the primary entity dealing with the bereaved family. There has been insufficient communication between the police and bereaved families regarding the handling of samples. However, the police have recently been paying close attention to how they deal with bereaved families, and they are attempting to develop better communication ‘from the police to the bereaved family’ and vice versa. For example, in 2014, the National Police Agency compiled guidelines for providing explanations to bereaved families regarding the handling and storage of organs collected during autopsies and instructed police officers throughout the country to provide explanations to bereaved families according to these guidelines.¹⁵ The guidelines ensure seamless communication between the police and bereaved families before and after the autopsy. They also instruct the police to inform departments of forensic medicine if bereaved families have expressed to the police the desire to have samples returned to them. In the past, there was no guarantee that bereaved families would receive an explanation when organs collected during autopsies were stored by departments of forensic medicine.² The fact that they now receive such an explanation from the police, and that they are encouraged to communicate their desires to the police, are major developments.

Approach 3: Efforts to educate and inform the public

We expect that the public will be concerned about the use of autopsy samples in research – a purpose that differs from the original purpose of the autopsy. Therefore, in addition to our focus on bereaved families, we believe it is necessary to work towards educating the public. There will always be cases in which it is impossible to contact bereaved families to provide them with information on the use of samples for research. Therefore, it is desirable that the general public knows about forensic research and understands that forensic research activities are conducted upon request from the society.

As seen in the results about the disclosure and provision of information regarding secondary use (2016 survey), when university departments of forensic medicine disclose information on websites that they maintain, private individuals who are interested in medicolegal autopsies and the handling of samples have access to the information. These websites may be used to improve the level of general knowledge and address the concerns of the public.

Increasing our understanding of disease and mechanisms of death that remain poorly understood not only increases our ability to determine the cause of death in any particular case accurately but also eventually contributes to increased benefits for a larger number of people. Because medical research is conducted to achieve these goals, it is important that the field of forensics and forensic researchers are trusted by both bereaved family members and the general public. If such trust does not exist, it will be impossible to sustain forensic research for the future as scientifically valid and socially valuable research.

Compared with research areas in clinical medicine, the field of forensics includes aspects that are difficult to disclose actively to the public through forums such as public lectures. Therefore, this topic – including considering specific ways to maintain contact with the public – is an important issue that needs to be addressed.

We believe that it is vital for the forensic science community to inform the public of the importance and benefits that arise not only to the deceased and their family but also to society in general through the use of samples collected during autopsies in forensic research. Such efforts will provide people who themselves someday may be the bereaved family with an opportunity to understand autopsies and the use of autopsy samples, which we believe will minimise the shock if such an unfortunate circumstance does arise.

Conclusion

The results of this study indicate that the ethical issues related to the use of autopsy samples collected without consent during medicolegal autopsies are handled in different ways at different departments of forensic medicine. Understanding the validity of these activities similarly differs. These circumstances are problematic in terms of transparency towards bereaved families and in terms of public trust regarding forensics research, which is dependent upon such samples. However, we are beginning to see researchers independently fulfilling their responsibility to provide explanations to both bereaved families and the public in an effort to address these concerns. A limitation of this study is that the pilot study is only on Japan, and it is difficult to standardise for forensic research worldwide. Although this approach is not yet in general use, and there are systemic limits to what can be done, we believe such efforts will be recognised as one way researchers can fulfil their responsibilities to contribute to the development of forensic research. To advance medical research and improve scientific knowledge appropriately in the field of forensics and the quality of legal evidence, it is necessary to standardise procedures for the appropriate use of leftover samples in a way that is acceptable to both bereaved families and the public.

Footnotes

Acknowledgements

We sincerely thank all the respondents for providing valuable information and comments.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study described in this report was funded in part by a Research Fellowship granted to Dr. Tsujimura by the Japan Society for the Promotion of Science for Young Scientists (grant number 22-5031), and the Japan Society for the Promotion of Science KAKENHI (numbers 22-5031 and 24830021 to Dr. Tsujimura; numbers 15H02518 and 24720073 to Dr. Inoue).

References

Yoshida K. Report of unusual death and the postmortem inspection system. In: Encyclopedia of forensic and legal medicine. Vol 2. Oxford: Elsevier Academic Press, 2005, pp.123–128.

Tsujimura-Ito

Inoue

Yoshida

. Organ retention and communication of research use following medico-legal autopsy: a pilot survey of university forensic medicine departments in Japan. J Med Ethics 2014; 40: 603–608.

UK Department of Health. The investigation of events that followed the death of Cyril Mark Isaacs. London, TS, 2003.

Grizzle

Grody

Noll

. Recommended policies for uses of human tissue in research, education, and quality control. Ad Hoc Committee on Stored Tissue, College of American Pathologists. Arch Pathol Lab Med 1999; 123: 296–300.

National Association of Medical Examiners. NAME Position Statement on Collection, Retention, and Disposition of Biologic Specimens by Medicolegal Investigative Agencies, 2008.

Federal Register 76(143), 44512–44531.

Human Tissue Act. London, HMSO, 2004.

Coroners (Amendment) Rules: Statutory Instruments 2005. No. 420. London, HMSO, 2005.

The Ethics Committee, Japanese Society of Legal Medicine. Using retained and stored organs/fluids from forensic autopsies for legal medical research. Japan J Leg Med 2002; 56: 319–322. (in Japanese).

10.

Japanese Society of Legal Medicine. JSLM Privacy policy, 2006 (in Japanese).

11.

Japanese Society of Legal Medicine. JSLM Privacy policy (in Japanese), www.jslm.jp/ethic/privacy_policy.html (2015, accessed 31 October 2016).

12.

Department of Forensic Medicine, Asahikawa Medical University. Information for bereaved families (in Japanese), www.asahikawa-med.ac.jp/dept/mc/legal/index.php/shihou/ (2016, accessed 31 October 2016).

13.

Department of Forensic Medicine, Tohoku University School of Medicine. Information for bereaved families (in Japanese), www.forensic.med.tohoku.ac.jp/anat/izokunominasama_2015.pdf (2016, accssed 31 October 2016).

14.

Department of Forensic Medicine, Oita University Faculty of Medicine. Information for bereaved families who experiences medico-legal autopsy in our forensic medicine department. Cooperation for our research activities (in Japanese). www.med.oita-u.ac.jp/joho/rinri/iinkai/rinri/file/h23/23-23.pdf#search='%E5%A4%A7%E5%88%86%E5%A4%A7%E5%AD%A6+%E6%B3%95%E5%8C%BB%E5%AD%A6+%E6%BA%BA%E6%AD%BB' (2016, accessed 31 October 2016).

15.

Information for bereaved. The store of samples collected during medico-legal autopsy. National Police Agency First Investigation Division No. 82. Instructions for police officers (in Japanese), www.npa.go.jp/pdc/notification/keiji/souichi/souichi20140801.pdf (accessed 31 October 2016).