Volume 11, Issue 2, September 2014

Return of the Genetic Search Results: the Japanese Experience and its Implications for the International Debate

Jusaku Minari,* Donald
Chalmers
** and Kazuto Kato***

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

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DOI: 10.2966/scrip.110214.180



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  1. 1. Introduction

In recent years,
there has been vigorous debate on the ethics and law
of disclosure of individual genetic and genomic results in the setting
of
clinical care and
research
. This
intensification of the debate is mainly due to rapid technological
advancement in human genome research, as represented by
“next-generation” sequencers and improved information-analysis
techniques.
2 Genome analysis
using these techniques enables the identification of several clinically
significant loci in the course of clinical care and research. In
response to this situation, some recommendations have already been made
by professional organisations such as the
American College of Medical Genetics and Genomics
(ACMG) and the European Society of Human Genetics
(ESHG) in clinical settings.
3 Notably, the ACMG
recommended that patients undergoing clinical genome sequencing be
tested for a specified set of 56 genes with established pathogenic or
high risk variants as the most likely source of
incidental” findings. This
recommendation has resulted in a great deal of controversy since its
release
,4 not least since it
proposed that patient consent should not be a requirement and feedback
of these results should be mandatory. Indeed, the ACMG recently shifted
their position to allow patient opt-out of incidental
findings.
5 On the other
hand,
in research settings, this type of
guidance seems to be less clear.

For this reason, one of the most controversial
debates of disclosure is on the creation of specific guidance in genome
research. In addition to many attempts to develop specific guidelines
from ethical perspectives,
6 several legal
experts have presented thorough and informative arguments, concerning
the legal basis of research participant’s access rights and
researcher’s obligations of disclosure to research
participants.
7 Moreover, Kaye et al and
Jarvik et al have recently reported several areas of
consensus, regarding the extent of researchers’ duty to disclose
clinically significant findings and the identification of appropriate
management pathways for such findings, within particular large scale
research projects in the UK and US respectively.
8 However, these
series of discussions
have been
centred mainly in Europe and
North America, and there has been less discussion regarding disclosure
in other countries/regions of the world.

It is becoming imperative to consider international
harmonization in disclosure policy, as a growing number of
international research projects, involving broad sharing of data and
samples, have
been carried out across the
world. One major approach to addressing this is to compare the
disclosure policies of different countries. In this regard, Knoppers et
al and others have proactively contributed a wide-ranging comparison of
existing disclosure policies regarding primary results, secondary
results via biobanks, and incidental findings.
9 In addition, in-depth examination and
analysis of specific national disclosure policies can be extremely
valuable in reaching a deeper understanding of the historical and
cultural context within which policies are developed in a particular
region or country.
In line with this approach,
this study will focus on the current policies relating to disclosure of
findings from genetic and genomic research in Japan.

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
.

  1. 2. Ethical regulations in Japan and the revised Ethical Guidelines

  1. 2.1 The
    background to government guidelines, the APPI and the
    Ethical Guidelines:

Biomedical research in Japan
is primarily subject to soft regulation, through numerous subdivided
government guidelines, without a binding legal
framework.
10 Many of these
government guidelines were created between 2000 and 2003, during which
time seven government guidelines were issued. The government guidelines
have since undergone a number of revisions, and in particular, several
of them have been markedly revised in response to the enactment of
the
APPI
in 2003,11 which
is legally binding legislation. As a result of the APPI, those guidelines now incorporate
detailed stipulations concerning the protection and disclosure of
personal information, but most of the guidelines do not address the
disclosure of research results including incidental findings. The
government guidelines for human genetic research, described as
the
Ethical Guidelines above, are a notable exception, covering
a specific disclosure policy for research results.

The need for specific regulations in human genetic research was identified
around the year 2000, in response to the rapid growth in that research
field. This resulted in the establishment in 2000 of the Fundamental
Principles of Research on the Human Genome (
Fundamental Principles) by the Bioethics
Committee of the Council for Science and Technology,
Japan.
12 The
Fundamental Principles describe the conceptual framework for human genome research and
play a fundamental role in establishing relevant guidelines. With
regard to disclosure in general, they stipulate that research
participants have the right to be informed and the right not to be
informed based on individual preference. Based on the concepts
described in the
Fundamental
Principles
, 2001 saw the publication of
the
Ethical Guidelines.13 In particular,
these Guidelines adopted “the policy of disclosure in principle”, which
emphasises the right of research participants to receive their research
results when they so request. Although
neither
the
Fundamental Principles nor the Ethical Guidelines
are legally binding, they have been widely adopted,
and are in general adhered to by the research community

in Japan.
As such, since their
enactment in 2001
the Ethical Guidelines have set
the disclosure
policy
, and
have
been subject to continued
debate among
stakeholders.
14

2.2 The latest revision of the Ethical Guidelines:

Recently, during the full revision process of
the
Ethical Guidelines, there was significant debate of the disclosure policy. In
response to government requests, the revision of the

Ethical Guidelines started
in 2011, with revised guidelines coming into effect in April 2013. The
revision was conducted according to procedures set out by a
Govern
ment Committee, with one of the most important discussions relating to whether “the policy of
disclosure in principle” should be retained.
A number of the Committee members
strongly advocated against “the policy of disclosure in principle”, and
desired the alternative approach involving non-disclosure in principle
(with appropriate measures for returning medically useful results).
This was mainly due to the practical premise that, at present, most
research results from genome analysis are still uncertain and not
suitable to serve as clinical information for research
participants.
Nevertheless,
this Committee ultimately decided to retain “the
policy of disclosure in principle”, meaning that research results are
disclosed only in circumstances where researchers are requested to do
so by research participants. The key reason for retention of the policy
was to strictly follow Art 25 (Disclosure) of the
APPI, which enshrines the disclosure
principle.
15

2.3 The influence of the APPI on the Ethical
Guidelines:

It is not immediately clear why the Committee should
have adopted the disclosure principle based on consistency with
the
APPI on the
outcome of the
Ethical Guidelines
revision. The APPI
was originally designed to deal with the regulation
of personal informatio
n with significance in
commerce or business, rather than in academic research.

With consideration of
“academic freedom”, which is
guaranteed in Art 23 of the Constitution of Japan,
academic research was
exempted from the provisions
of
the
APPI, as indicated in Art 50 (Exclusion from
Application)
. The exemption of the APPI itself, naturally, covers genome
research, including the matter of disclosure
. There are, however, other laws
regarding personal information, which are closely related to the

APPI but partly apply to
academic research.
16 The mandate of
the Committee on the
Ethical Guidelines
incorporated an imperative to ensure a consistent
legal framework for the updated guidelines which necessitated
redressing this discrepancy over academic research between the

APPI and the other laws. As
a result, in order to have clear legal guidance on personal information
in the academic context, the
APPI,
as well as other laws, were found to be applicable to
the
Ethical Guidelines despite the fact that the APPI
was not originally designed for this purpose.

Another noteworthy influence of the APPI is seen
in
the exemption clause of the disclosure
policy of the
newly-revised Ethical Guidelines.
Originally, the exemption
clause
of the disclosure policy
was set alongside the policy of disclosure in
principle in the enactment of the
Ethical
Guidelines
in 2001, as follows: the policy of
disclosure in prin
ciple “shall not, however,
apply if there is no adequate significance in providing genetic
information and informed consent to non-disclosure has been obtained
from the donor”.
17 This clause was immediately changed to
precisely follow the description of the APPI
in its enactment of 2003. Specifically,
the condition of the exemption clause turned from “no adequate
significance
to
“likely to harm the life, body, property or other rights or interests
of the donor or a third party”.
18 In the current
revision of 2013 another exemption from the
APPI was added into the
Ethical Guidelines where the
disclosure is “likely to seriously impede the proper execution of the
research study” (referred to here as “the research study
exemption”).
19 Both of these
exemptions clauses, except for the requirements of informed consent for
non-disclosure, are the result of the influence of the

APPI. In this regard the
addition of the second condition in this revision means that the

Ethical Guidelines more
strictly respect the
APPI than before. This has the effect of making the
Ethical Guidelines somewhat
more complex, but also potentially offering researchers greater
flexibility in interpreting the remit of terms such as

likely to seriously impede
the proper execution of the research study”.

2.4 The specific researcher disclosure
policy in the revised
Ethical
Guidelines:

The revised Ethical
Guidelines
incorporate one further important
clause on disclosure which provides researcher’s with the discretion to
create their own specific disclosure policy. This clause states that
researchers should take the initiative in creating in advance a policy
for the disclosure of research results.
20 Three points for
researchers to consider in preparing this front-end disclosure policy
for the project are emphasized in the clause: the accuracy and validity
of genetic research results, the potential health benefits of their
results for research participants, and the risk of impeding the
research study. The clause further includes detailed rules concerning
the management of incidental findings which are defined in the

Ethical Guidelines as
“originally unexpected research results that have significant impact on
the lives of research participant’s and their relative’s”. It specifies
that researchers should make every effort to consider a disclosure
policy relating to potential incidental findings in advance and
facilitate research participants understanding of the disclosure policy
as part of informed consent.

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.

  1. 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.

  1. 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.

  1. 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.

The blurring of this boundary in genomics could
potentially lead to the therapeutic misconception which is said to
occur “when a research participant mistakenly believes that the primary
aim of the research project is therapeutic”.
21 With regard to
“the disclosure policy in principle”, the term “in principle” is
ambiguous, and therefore can be broadly interpreted by stakeholders.
Consequently, research participants may assume that they can request
researchers to disclose their research results for their own
therapeutic benefits, and thus confuse the concept of research with one
of clinical care. From this standpoint, it can be argued that “the
disclosure policy in principle” may be legally valid but not
necessarily ethical.

A second challenge arises from the newly-added
exemption clause, “the research study exemption”, allowing researchers
considerable leeway to decide which circumstances might amount to
a
serious
impediment” to the research study. Potentially this exemption clause
fails to carefully consider respect for persons or respect for
autonomy. Respect for persons is referred to as “a basic ethical
principle that gives rise to obligations regarding how competent adults
should be treated”.
22 This
incorporates respect for participants’ self-determination, and leads to
the following ethical justification:

“It would be disrespectful to treat research
volunteers as conduits for generating scientific data without giving
due consideration to their interest in receiving information about
themselves derived from their participation in
research”.
23

This is reinforced by the Declaration of Helsinki,
which has enshrined that “[w]hile the primary purpose of medical
research is to generate new knowledge, this goal can never take
precedence over the rights and interests of individual research
subjects”.
24 With regard to
“the research study exemption”, the clause fully takes into account the
interests of researchers but little of the interests of research
participants. Any decision to restrict disclosure where the research
study may be “impeded” is open to varying interpretation. This
guideline would be undermined if stakeholders could interpret the
“research study” exemption as allowing them not to disclose research
results only for their own practical convenience. In short, this
“research study” exemption has the potential to be used as an excuse
not to disclose. Therefore,
“the research study exemption” clause
may not adequately respect the autonomy and interests of research
participants rendering these principle-based approaches of the
disclosure policy ethically undesirable.

  1. 3.3 Ethical
    challenges of the
    Ethical Guidelines in general:

There is more general ethical challenge in the
disclosure policy in the
Ethical
Guidelines.
Arguably, they do not adequately consider certain
aspects of research participants’ choices in research. In the

Ethical Guidelines, the
disclosure policy sets out “the disclosure policy in principle”
regarding the right to know, and also referred to the right not to
know.
25 In this regard,
the disclosure policy considers a research participant’s rights.
However, the disclosure policy does not clearly encourage researchers
to offer opportunities for participants to express and incorporate
their wishes and opinions into a disclosure decision. It may be more
ethically considered for researchers to create a disclosure policy
relying not only on their own perspective, but also taking in to
account the views of participants in line with the principle of respect
for persons, as men
tioned above. Furthermore,
the 2003 UNESCO declarations formally stipulate research participants’
right to choose in advance whether or not they are informed of the
results
in Article 10
(the right to decide whether or not to be informed about research
results).
26 In fact, there
has been an absence of discussion among researchers in Japan on the
ethical need to incorporate the opinions of research participants into
research design.
27 In addition,
researchers have formulated previous policies for return of genetic
research results without external input, though in some cases the
researchers consult experts in ethics and/or law. In such circumstances
there is a possibility that researchers fail to give sufficient ethical
consideration to research participants. Therefore, at least, as stated
in the 2003 UNESCO declarations, the disclosure policy of the

Ethical Guidelines would
have to positively value those research participants’ informed
choice.

  1. 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
.

First, as a research collective approach,
academic societies and research projects could create
their own policies for disclosure of research results to research
participants. In this approach, the compliance with such a policy is a
requirement of project participation, whilst in others the policy is
provided as a recommendation only. Such policies might take the form of
a flowchart describing the passage of results from researchers to
research participants, and describe the decision processes involved.
They
can provide further guidance of how to
treat findings in different circumstances, including the types of
research methods, research findings and researchers and they could
provide an
a priori list of clinically significant findings, based upon the genomes
of the population in the relevant country/countries. In

research collective approaches, it may be valuable to consider the disclosure models
of previous activities, such as the UK 10K project, ACMG and Clinical
Sequencing Exploratory Research (CSER) consortium,
28 and use these
approaches to inform new policies specific to the research endeavour.
While, in Japan, there is still a difficulty regarding the lack of a
common certification for clinical sequencing in laboratories, like the
Clinical Laboratory Improvement Amendments (CLIA) in the US and
Clinical Pathology Accreditation (CPA) in the UK, the development of
those policies in Japan through a
bottom-up” approach would provide more
guidance to researchers, who could create a practical disclosure
policy, and be valuable in particular, when research is integrated with
clinical care.

In our second approach, individual researchers could
create their own disclosure policies, particularly by flexible
interpretation of the
Ethical
Guidelines
. This
approach requires that the “principles” and “exceptions” of the
disclosure policy in the
Ethical
Guidelines
are broadly and flexibly
interpreted, which includes that stakeholders do not necessarily regard
“principles” and “exceptions” to apply to “most cases” and “some
cases”, respectively. The approach is also particularly desirable when
considering “the research study exemption” which will require careful
consideration of the research participants’ interests. In these cases,
researchers have an opportunity to offer useful results to research
participants within their capability, while avoiding therapeutic
misconceptions, and decision making based solely on their own practical
convenience. This approach by researchers can be ethically justified by
the beneficence principle, simply stated as “doing good for the sake of
others”.
29 In this
approach, it would be important for members of ethics review committees
to support these interpretations of the disclosure policy. For this, it
could be effective to hold meetings/workshops for members of ethics
review committees across the country on an ongoing basis, which would
facilitate knowledge sharing and policy discussion of basic rules for
the ethical review and state-of-the-art research between research
ethics committees.
30

For the third individual research participants
approach, researchers could
assign the decision process of disclosure to individual participants.
For example, in the process of obtaining consent, researchers can
proactively offer identifiable research participants a choice regarding
disclosure. In some research projects, there may be several options
depending on research results with different
characteristics.
31 There may be
primary research results and incidental findings in the course of
original research, or secondary research results obtained through
biobanks and databases. In this approach, it would be important for
researchers to anticipate, in advance, the potential of clinically
significant findings in their own research. Equally, it may be
necessary for research participants to understand the potential
implications of those findings before giving consent. This approach
requires a thorough consideration by the research team of the findings
before creating any consent form, and detailed project information, for
the participants. This approach, however, may be limited and
constrained in a static, one-time consent in
advance,
32 where there may
often be difficulty in adapting to changes in research progress and
research participants’ preference. This difficulty has received
considerable attention, more recently, in the light of the introduction
of information and communication technologies for decision making on
disclosure. Technologies can be used for the selection of options such
as My46
33 but also for
on-going consent such as dynamic consent.
34 Dynamic consent is a flexible and continuously personalized consent,
and allows participants to choose from a range of
consent preferences and
to change their
mind
over time. These approaches enable both
researcher and research participants to manage the decision making on
disclosure by working in partnership. This opportunity involving
research participants could ensure further research advancements and
research participants’ trust and better understanding of research
fields.

  1. 4. Conclusion

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
.

Acknowledgements

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 Sci
entific 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.

Abbreviations

ACMG: American College of Medical Genetics
and Genomics; APPI: Act on the Protection of Personal Information.

Competing interests

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:
minari@eth.med.osaka-u.ac.jp

**** 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:
kato@eth.med.osaka-u.ac.jp

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.

5 https://www.acmg.net/docs/Release_ACMGUpdatesRecommendations_final.pdf

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
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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).

19 Ibid.

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.


Return of Genetic Research Results: The Japanese Experience and its Implications for the International Debate