Volume 11, Issue 2, September 2014
Return of the Genetic Search Results: the Japanese Experience and its Implications for the International Debate
Cite as: J Minari, D Chalmers and K Kato, “Return of the Genetic Search Results: the Japanese Experience and its Implications for the International Debate”, (2014) 11:2 SCRIPTed 180 http://script-ed.org/?p=1543
© Jusaku Minari, Donald Chalmers and Kazuto Kato 2014. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Please click on the link to read the terms and conditions.
In this article, we explore the character of the disclosure policy in ethical regulations of human genome research in Japan. In particular, we focus on the disclosure policy outlined in the newly revised government ethical guidelines for human genetic research, Ethical Guidelines for Human Genome/Gene Analysis Research (Ethical Guidelines). “Disclosure” here is taken to cover the issue of so called incidental findings in research settings, including biobank research. We analyse the revision process and resultant policies of the Ethical Guidelines on disclosure, based on the ethical principles related to researchers and research participants, and the provisions of the Act on the Protection of Personal Information (APPI), 2003. We show some of the key challenges of the revised Ethical Guidelines associated with policy design of disclosure in Japan. Furthermore, we propose as a means to achieve the potential benefits of personal genome research, the favouring of the disclosure of clinically significant findings, including incidental findings, to research participants as an ethical (if not necessarily legal) imperative. This study could be useful to similar debates in other countries and could contribute to efforts to establish an internationally harmonised disclosure policy where understanding different policies and national contexts internationally is a first step and a necessary precursor to harmonization.
2. Ethical regulations in Japan and the revised Ethical Guidelines
2.1 The background to government guidelines, the APPI and the Ethical Guidelines:
2.2 The latest revision of the Ethical Guidelines:
2.3 The influence of the APPI on the Ethical Guidelines:
2.4 The specific researcher disclosure policy in the revised Ethical Guidelines:
In this latest revision of the Ethical Guidelines, the revised disclosure policy for research has been essentially amended in a manner consistent with the commerce or business provisions of the APPI, which was not originally intended to apply to academic research.
3. Challenges and opportunities regarding the revised Ethical Guidelines
The fundamental question is whether the disclosure policy in the 2013 revised version of the Ethical Guidelines can provide appropriate guidance to researchers and adequately protect the interests of research participants. Based on the analysis of the revised Ethical Guidelines above, we here argue that there are both practical and ethical challenges in the revised disclosure policy, and propose some of suggestions to address those challenges.
3.1 Practical challenges of the revised disclosure policy:
One of the challenges in the current revision of the Ethical Guidelines is that the disclosure guidelines have not sufficiently described the practical requirements/issues. The new Ethical Guidelines present a broad description of the disclosure policy detailed in the APPI and refer to “the disclosure policy in principle” and its broad exceptions. However, this broad reference to the disclosure policy is not supported by specific and practical guidance on applying this disclosure policy in research practice. The revised disclosure policy could play a minor and limited role in influencing and changing researchers’ practices in response to the development for their own specific disclosure policies. One factor causing this conservative approach is that, as shown in the current process, priority has been given to ensuring compliance with the existing legal framework on control of personal information rather than facilitating practical application in the creation of disclosure policies in the Ethical Guidelines. In order to reorient and achieve the purpose of the revised Guidelines towards more practical implementation a first step would be to separate, at least in part, the Ethical Guidelines from the APPI. Such an approach could focus both on the purpose and the revision process of the Ethical Guidelines themselves.
3.2 Ethical challenges of the revised disclosure policy:
The revised disclosure policy potentially raises two ethical challenges. First, “the disclosure policy in principle” may, in some cases, lead to a therapeutic misconception by research participants. Fundamentally, the concept of research is different from one of clinical care in at least two respects:
Research primarily emphasizes the creation of new knowledge for the public, rather than for the of benefit individual patients
Research findings can be held to appropriate scientific standards of data collection, analysis and application, but this is not a guarantee of clinical utility.
3.3 Ethical challenges of the Ethical Guidelines in general:
3.4 Opportunities in the Ethical Guidelines:
Despite the practical and ethical challenges outlined above, the revised Ethical Guidelines do have the potential to provide opportunities for the research community. These opportunities could be achieved through the provision of additional mechanisms for governing disclosure decisions in relation to the identified challenges, in three proactive approaches of the research collective, individual researchers and individual research participants, respectively.
The disclosure policy in the revised Japanese Ethical Guidelines gives priority to adherence to related legal regulations, with easing the limitation of non-disclosure, and to granting researchers greater discretion to create their own disclosure policy. In particular, the revised disclosure policy has been significantly influenced by the personal information privacy protection law, despite its original design exempting academic research. We argue that there are several challenges regarding the revised disclosure policy, and propose interpretive ways to address these challenges, specifically the necessity for additional governance systems shaped by three distinct approaches of the research collective, individual researchers and individual research participants. We do not advocate disclosing all potentially beneficial research results to the research participants. Rather, we emphasize that the new version of the Ethical Guidelines should be interpreted to consider and favour the interests of research participants. In the three proposed approaches, the revised Ethical Guidelines should enable researchers to make their own research design decisions on a case-by-case basis by considering both the purpose of the research and the interests of research participants. We consider that the revised Ethical Guidelines will be successful provided they are clearly understood and translated into participant-focused disclosure policies and practices in Japan.
In our research, the Japanese experience provides two messages, which have implications for the international debate. First the duty of genomics researchers to carefully interpret the Guidelines for the benefit of research participants, and secondly the need for thoughtful consideration of the Guidelines in the context of established ethical principles. The Japanese experience may be useful in considerations of disclosure policies in other countries with personal information privacy protection laws and without specific laws on human genome research. In the absence of clear international standards on disclosure of genetic research results to participants, it is noted that research is moving towards disclosure of beneficial results to research participants. The revised Ethical Guidelines move Japan in this direction, if the Guidelines are interpreted as we argue. There is a pressing need to move towards an international harmonization on disclosure policy, particularly in light of global collaborative projects, and the Japanese experience may go some modest way to contributing towards establishing global standardised ethical policies on disclosure.
The authors thank Ellen Wright Clayton, Jane Kaye, Michael Morrison and Sarah Coy for valuable advice and comments. This work was supported by Grants-in-Aid for Scientific Research on Innovative Areas, “Genome Science” (Grant No. 221S0002) and Young Scientists (B) (Grant No. 25860381) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.
ACMG: American College of Medical Genetics and Genomics; APPI: Act on the Protection of Personal Information.
The authors declare that they have no competing interests.
1 Assistant Professor, Department of Biomedical Ethics and Public Policy, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan: firstname.lastname@example.org
**** Professor, Faculty of Law, University of Tasmania, Hobart, Tasmania 7001, Australia: Don.Chalmers@utas.edu.au
****** Professor, Department of Biomedical Ethics and Public Policy, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan., Project Professor, Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501, Japan: email@example.com
2 ER Mardis, “A decade’s perspective on DNA sequencing technology” (2011) 470 Nature 198-203; J Shendure and EL Aiden, “The expanding scope of DNA sequencing” (2012) 30 Nature Biotechnology 1084-1094.
3 RC Green et al, “ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing” (2013) 15 Genetics in Medicine 565-574; CG van El et al, “Whole-genome sequencing in health care” (2013) 21 European Journal of Human Genetics 580-584.
4 W Burke et al, “Recommendations for returning genomic incidental findings? We need to talk!” (2013) 15 Genetics in Medicine 854-859; E Vayena and J Tasioulas, “Genetic incidental findings: autonomy regained?” (2013) 15 Genetics in Medicine 868-870.
6 AL Bredenoord et al, “Disclosure of individual genetic data to research participants: the debate reconsidered” (2011) 27 Trends in Genetics 41-47.
7 EW Clayton and AL McGuire, “The legal risks of returning results of genomics research” (2012) 14 Genetics in Medicine 473-477; J Kaye et al, “Can I access my personal genome? The current legal position in the UK” (2014) 22 Medical Law Review 64-86; AL McGuire et al, “Can I be sued for that? Liability risk and the disclosure of clinically significant genetic research findings” (2014) 24 Genome Research 719-723.
8 J Kaye et al, “Managing clinically significant findings in research: the UK10K example” (2014) European Journal of Human Genetics (doi: 10.1038/ejhg.2013.290); GP Jarvik et al, “Return of genomic results to research participants: the floor, the ceiling, and the choices in between” (2014) 94 American Journal of Human Genetics 818-826.
9 BM Knoppers et al, “The emergence of an ethical duty to disclose genetic research results: international perspectives” (2006) European Journal of Human Genetics 14, 1170-1178; Renegar G et al, “Returning genetic research results to individuals: points-to-consider” (2006) 20 Bioethics 24-36; E Levesque, Y Joly and J Simard, “Return of research results: general principles and international perspectives” (2011) 39 The Journal of Law, Medicine and Ethics 583-592; MH Zawati, B Van Ness and BM Knoppers, “Incidental findings in genomic research: a review of international norms” (2011) 9 GenEdit 1-8; Knoppers BM and Zawati MH, “International normative perspectives on the return of individual research results and incidental findings in genomic biobanks” (2012) 14 Genetics in Medicine 484-489.
10 BT Slingsby, N Nagao and A Akabayashi, “Administrative legislation in Japan: guidelines on scientific and ethical standards” (2004) 13 Cambridge Quarterly of Healthcare Ethics 245-253; S Tashiro, “Unintended consequences of “soft” regulations: the social control of human biomedical research in Japan” (2010) 19 International Journal of Japanese Sociology 4-17.
11 Act on the Protection of Personal Information 2003 (Act No. 57 of 2003, Japan) (hereafter APPI).
12 Bioethics Committee, Council for Science and Technology, “Fundamental Principles of Research on the Human Genome“ (2000).
13 Ministry of Education, Culture, Sports, Science and Technology (MEXT), Ministry of Health, Labour and Welfare (MHLW), and Ministry of Economy Trade and Industry (METI), “Ethical Guidelines for Human Genome/Gene Analysis Research” (2001). Fully revised in 2004 and 2013, partially revised in 2005 and 2008.
14 A Nomura and G Yoshizawa, “Critical discourse analysis of the revision of the Ethical Guidelines for Human Genome/Gene Analysis Research” (2013) 22 Japanese Journal for Science, Technology and Society 47-88.
15 APPI, Art 25(1). “When a business operator handling personal information is requested by a person to disclose such retained personal data as may lead to the identification of the person (such disclosure includes notifying the person that the business operator has no such retained personal data as may lead to the identification of the person concerned. The same shall apply hereinafter.), the business operator shall disclose the retained personal data without delay by a method prescribed by a Cabinet Order. However, in falling under any of the following items, the business operator may keep all or part of the retained personal data undisclosed: (i) Cases in which disclosure is likely to harm the life, body, property, or other rights or interests of the person or a third party, (ii) Cases in which disclosure is likely to seriously impede the proper execution of the business of the business operator handling personal information, (iii) Cases in which disclosure violates other laws and regulations.”
16 Act on the Protection of Personal Information Held by Administrative Organs 2003 (Act No. 58 of 2003, Japan); Act on the Protection of Personal Information Held by Independent Administrative Agencies, etc. 2003 (Act No. 59 of 2003, Japan).
17 See note 12 above. Part III, s 9(1) (2001 edition).
18 See note 12 above. Part III, s 8(1).
20 See note 12 above. Part III, s 8(2).
21 PS Appelbaum, LH Roth and C Lidz, “The therapeutic misconception: Informed consent in psychiatric research” (1982) 5 International Journal of Law and Psychiatry 319-329; AL Bredenoord et al, see note 5 above.
22 DI Shalowitz and FG Miller, “Disclosing Individual Results of Clinical Research” (2005) 294 JAMA 737-740.
23 DI Shalowitz and FG Miller, see note 21 above; SM Wolf, J Paradise and C Caga-anan, “The law of incidental findings in human subjects research: establishing researchers’ duties” (2008) 36 The Journal of Law, Medicine and Ethics 361-383.
24 World Medical Association of Helsinki, Declaration of Helsinki, “Ethical Principles for Medical Research Involving Human Subjects” (1964).
25 See note 12 above. Part III, s 8(4) With regard to human genome/gene analysis research through which the genetic information of individual donors is revealed, when a donor has not requested disclosure of his/her own genetic information, the research director shall not disclose the requested information.
26 UNESCO International Declaration on Human Genetic Data (2003).
27 Research Unit for the ELSI of Genomics, “Report of a meeting to consider research ethical review in human genome research” (2014).
28 RC Green et al and J Kaye et al, see note 2 and 7 above, respectively; JS Berg et al, “Processes and preliminary outputs for identification of actionable genes as incidental findings in genomic sequence data in the Clinical Sequencing Exploratory Research Consortium” (2013) 15 Genetics in Medicine 860-867.
29 AL Bredenoord et al, see note 5 above.
30 J Minari, T Shirai and K Kato, “Ethical considerations of research policy for personal genome analysis: the approach of the Genome Science Project in Japan” (2014) 10:4 Life Sciences, Society and Policy; G Yoshizawa et al, “ELSI practices in genomic research in East Asia: implications for research collaboration and public participation” (2014) 6:39 Genome Medicine.
31 LM Beskow and W Burke, “Offering individual genetic research results: context matters” 2010 2 Science Translational Medicine 38cm20.
32 M Watanabe et al, “For what am I participating? The need for communication after receiving consent from biobanking project participants: experience in Japan” (2011) 56 Journal of Human Genetics 358-363.
33 Available at http://www.my46.org
34 J Kaye et al, “Dynamic consent: a patient interface for twenty-first century research networks” (2014) European Journal of Human Genetics (doi: 10.1038/ejhg.2014.71); JH Yu et al, “Self-guided management of exome and whole-genome sequencing results: changing the results return model” (2013) 15 Genetics in Medicine 684-690.