Introduction
In the past few years, a second phase of biomedical ethics in Japan
has begun to surface with a succession of governmental guidelines and
laws regulating biomedical technology.1
Akabayashi A, Slingsby BT. Biomedical ethics in Japan: the
second stage. Cambridge Quarterly of Healthcare Ethics
2003;12(3):261–4.
Although this rush of guidelines
exemplifies a heightened awareness concerning ethical standards for
healthcare research, it also invites several practical, political, and
procedural problems.
In this report, we first provide an explanation of each of the main
ministries involved with the drafting and implementation of these
guidelines. Next, we present a table of the major guidelines and laws
passed during the last two decades, describe the classification and
legal binding power of governmental guidelines, and briefly explain the
infrastructure of ethics committees in Japan. We then explore several
shortcomings common among recent governmental guidelines. In
particular, we highlight five possible limitations, including a lack of
set standards for ethical reviews and the need for specific procedural
instructions. Finally, we examine four specific guidelines in terms of
social and historical necessity, political affiliation, content, and
possible limitations specific to each guideline. In this analysis, we
demonstrate how each guideline entails both common and specific
limitations.
Description of Involved Ministries
Ministry of Education, Culture, Sports, Science, and
Technology (MEXT)
The MEXT has the following three roles: (1) to reform the systems of
education, culture enrichment, and science and technology; (2) to
regulate those systems; and (3) to promote education, science and
technology, culture, and sports. The bureau most involved with the
drafting of ethical guidelines is the Science and Technology Policy
Bureau, which is responsible for the planning and drafting of basic
science and technology policies, including development programs and
promotion of research evaluation.
Ministry of Health, Labor, and Welfare (MHLW)
The MHLW is dedicated to the protection and improvement of
people's health and welfare. The MHLW serves as the authority for
all matters of health and welfare, medical science, and technology.
Medical institutions, including general hospitals, are under the
jurisdiction of the MHLW (whereas academic institutions are under the
jurisdiction of the MEXT). The Health Sciences Council of the MHLW has
been active in the recent drafting of scientific and ethical
guidelines.
Ministry of Economy, Trade, and Industry (METI)
The METI is responsible for all policies covering the nation's
various industries, sources of energy, and foreign trade (except
agricultural products and foods). The Commerce and Information Policy
Bureau and the Industrial Science, Technology Policy, and Environmental
Bureau are the two bureaus that have been most involved with
discussions on scientific and ethical guidelines (e.g., industrial
patents).
Overview of Guidelines and Laws
Table 1 lists the guidelines and laws
(1989–2003) relevant to biomedical research and medical
treatment. The Ministry of Health and Welfare (MHW), presently the
MHLW, created the original Guideline for Good Clinical Practice (GCP)
as a circular in 1989 to regulate clinical drug trials. The GCP was
amended as a ministerial ordinance in 1997, along with the
Pharmaceutical Affairs Law (1996), to harmonize domestic regulations of
pharmaceutical testing with those in the United States and the European
Union.2
Ono S, Kodama Y. Clinical trials
and the new Good Clinical Practice guideline in Japan: an economic
perspective. Pharmacoeconomics
2000;18(2):125–41.
The new GCP lies in accordance with
the GCP issued by the International Conference on Harmonization
(ICH-GCP), which provides a unified standard for the United States, the
European Union, and Japan.
Recent guidelines on scientific and ethical standards
Since 2000, five guidelines have been created, one has been amended,
and one is currently being laid out. This highlights a succession of
statutory measures over the past three years. Among these seven
guidelines, the Ethical Guideline for Human Genome and Gene Analysis
Research (2001) is the result of a collaborative effort by three
ministries. The MEXT and the MHLW also collaboratively drafted the
Ethical Guideline for Epidemiological Research (2002) and Guideline for
Clinical Research on Gene Therapy (2002). The remaining four guidelines
were either drafted or are currently being drafted by the MEXT or the
MHLW.
Guidelines: Statutory Instruments
Japan's governmental scientific and ethical guidelines are
classified as administrative legislation (gyouseirippou) and
not as law (see Figure 1). In our
interpretation, administrative legislation consists of statutory orders
(houkimeirei) and administrative regulation
(gyouseikisoku). The former includes, but is not restricted
to, ministerial ordinances (shourei) and government ordinances
(seirei). Although these apply to civil rights and duty, the
latter includes notifications (kokuji), circulars
(tsuutatsu), and other documents not concerning civil rights
and duty. For example, the original GCP (1989) was a circular
(tsuutatsu), whereas the new GCP (1997) is based on the
amended Pharmaceutical Affairs Law (1996) and is classified as a
ministerial ordinance (shourei). In contrast, the remaining
guidelines listed in Table 1 are formally
classified as ministerial notifications (kokuji).
Statutory classification of guidelines (the authors'
interpretation). *“The New Guideline for Good Clinical
Practice” is a ministerial ordinance. **“The Original
Guideline for Good Clinical Practice” was a circular issued by
the Ministry of Health and Welfare, the Former Ministry of Health,
Labour, and Welfare. ***All other guidelines are classified as
ministerial notifications.
Ethics Committees in Japan
Although the Japanese term for ethics committees
(rinri-iinkai) has been translated as institutional review
board (IRB),3
Ministry of Education,
Culture, Sports, Science, and Technology. The Guidelines
for Derivation and Utilization of Human Embryonic Stem Cells.
2001. Available at:
http://www.mext.go.jp/a_menu/shinkou/seimei/2001/es/020101.pdf
[English];
http://www.mext.go.jp/a_menu/shinkou/seimei/2001/es/010901a.pdf
[Japanese].
the infrastructure of ethics committees
in Japan differs from that in the United States. There are two types of
committees in Japan: (1)
chiken-shinsa-iinkai, a review and
monitoring committee (RMC) for drug clinical trials; and (2)
rinri-iinkai, an ethics committee. RMCs review only drug
clinical-trial protocols and monitor those trials; they are regulated
by the MHLW and function in accordance with the ICH-GCP. Likewise,
researchers of drug clinical trials are required by the new GCP to
receive approval from an RMC. Conversely, an ethics committee is a
self-governing body established by each institution and falls under the
jurisdiction of neither the MHLW nor the MEXT. Ethics committees
commonly review protocols from researchers affiliated with medical
schools and general hospitals and also deal with hospital affairs,
including hospital policymaking and clinical ethics consultation. In
light of these disparities between RMCs and ethics committees, the
English translation “institutional review board” is
misleading in that the infrastructure and role of ethics committees in
Japan fundamentally differ from IRBs in the United States. Although we
noted that ethics committees are not under the jurisdiction of
ministries, the guidelines set around 2000 strongly recommend that
institution heads establish ethics committees.
Common Limitations among the Guidelines
The governmental guidelines, although capable of ensuring a high
level of ethical and scientific standards for carrying out research
projects, have several possible limitations. One consistent limitation
pertains to the issue of no set standards for the process of ethical
review. None of the guidelines provide procedural details concerning
the evaluation of a submitted study and standards of that evaluation.
Given that standards may fluctuate among studies depending on
methodology, samples, or subjects, further specification is needed to
ensure a consistently high level of review. An additional problem is
the entrusting of perfunctory procedures (e.g., the public release of
information) to the discretion of ethics committees and/or
individual researchers. The public release of information is intended
to act as a double check and to ensure social accountability. Yet,
without set standards and the proper release of information, half
measures may be deemed as qualified standards, causing risks of social
accountability, ethical obligation, and legal liabilities.
Another major issue is the lack of a central regulating body for
local ethics committees. The lineup of guidelines has shifted the
mainstay of responsibility to local institutional ethics committees.
Yet, current local ethics committees have problems with infrastructure,
management, and the recruiting of competent members. For each
institution, deciding precisely how to run the committee efficiently
and effectively is a persistent problem. For instance, the lack of set
standards of organization for ethics committees leads to an
inconsistent level of review between institutions. Without a central
regulating body, insufficient evaluation may lead to approval of
unethical practices and, eventually, procedural loopholes may be used
intentionally.
A further problem is that the presence of several guidelines,
although intended to safeguard against ethical risks, has caused
difficulty and confusion for researchers. For instance, certain studies
(e.g., epidemiological studies with human genome analysis) fall under
both the Guideline for Human Genome and Gene Analysis Research (2001)
and the Ethical Guideline for Epidemiological Research (2002). The
former requires researchers to obtain written informed consent from all
participants and to submit an annual written report; it also requires
ethics committees to have at least two external members (preferably,
more than half of an ethics committee). In contrast, the Ethical
Guideline for Epidemiological Research addresses studies that do not
require written informed consent, leaves the period for submitting a
written report up to the discretion of the researcher, and only
mentions that an ethics committee should have an external member(s).
These disparities not only confuse researchers but also leave room for
researchers to choose the easier route and circumvent a strict review
process.
Another question that deserves attention is why are there so many
guidelines and so few laws. Numerous guidelines have been published
during the last three years, but only two laws concerning healthcare
research have concurrently been passed (see Table
1). Whereas a law has definite binding power and can be strictly
enforced, administrative legislation, as in the case of guidelines, has
relatively less legal binding power. Nonetheless, governmental
guidelines have significantly more binding power than guidelines
published by academic societies or professional organizations such as
the Japan Medical Association or the Japan Society of Obstetrics and
Gynecology.
In sum, we believe the following five shortcomings require additional
attention: the lack of set standards for ethical reviews, the necessity
of a central regulating body for local ethics committees, the need for
specific procedural instructions, possible inconsistencies between
guidelines, and the regulatory limitations of partial binding power.
Four Representative Guidelines
The following discussion describes four guidelines in terms of (a)
social and practical necessity, (b) administrative bodies involved, (c)
content and purpose, and (d) possible limitations specific to each
guideline.
Ethical Guideline for Human Genome and Gene Analysis
Research4 Ministry of Education, Culture,
Sports, Science, and Technology, The Ministry of Health, Labour, and
Welfare, The Ministry of Economy, Trade, and Industry. Ethical
Guideline for Human Genome and Gene Analysis Research. 2001.
Available at:
http://www2.ncc.go.jp/elsi/html/shishin/rinrishishin_zentai.pdf
[Japanese].
Social and practical necessity
Human genome research and gene analysis involves many ethical
concerns. The need for strict standards has been expressed by both
UNESCO's Universal Declaration on the Human Genome and Human
Rights5
UNESCO. Universal Declaration
on the Human Genome and Human Rights. 1997. Available at:
www.unesco.org/shs/human_rights/hrbc.htm.
and the
Basic Principles of Human Genome Research
6 Ethics Committee of the Council for Science and Technology.
Basic Principles of the Human Genome Research. 2000. Available at:
http://www.mext.go.jp/a_menu/shinkou/shisaku/gensoku.htm
[Japanese].
developed by the Ethics Committee of the
MEXT Council for Science and Technology.
Ministrative bodies
The MEXT, MHLW, and METI collaboratively drafted the guideline.
Contents and purpose
Chapter 1 defines seven basic principles including human dignity,
confidentiality of personal information, and the priority of
individuals' human rights over that of scientific or social
benefits. Chapter 2 lays out the responsibilities of researchers,
including the head of the research institution, the chief researcher,
the personal information manager, and the ethics review committee.
Chapter 3 attends to informed consent, disclosure of genetic
information, and genetic counseling. Chapter 4 describes specific
methods for the handling of samples.
Possible limitations
This guideline and its details attend to the “procedural
minutes” in general but do not provide actual instructions for
carrying out ethical and effective study and review. Although all
facilities that offer specimens and samples are required to have an
institutional ethics committee, small-scale cooperative facilities
often face financial and administrative difficulties in running such
committees. Also, the guideline lists several subsidiary rules
concerning informed consent documents, but it remains unclear how to
conduct proper informed consent under actual circumstances.
Additionally, there is no outline for the process of genetic counseling
even though the necessity of genetic counseling is stated. Monitoring
is consigned to institution heads, which invites an almost unrealistic
administrative burden. Finally, instructions for handling of human
materials collected prior to the publication of this guideline are
noted but lack clarity.
Ethical Guideline for Epidemiological Research7 Ministry of Health, Labour, and Welfare,
Ministry of Education, Culture, Sports, Science, and Technology.
Ethical Guideline for Epidemiological Research. 2002.
Available at:
http://www.mhlw.go.jp/general/seido/kousei/i-kenkyu/sisin2.html
[Japanese].
Social and practical necessity
The collection of data in epidemiological studies often involves the
risks of infringement of individual human rights and emerging of
privacy protection. In response to the public's heightened
awareness concerning the issue of privacy protection, the amended
Privacy Protection Law (2003) aims to better protect individual rights.
This law, although comprehensive, is not specific enough to attend to
the risks involved with epidemiological research.
Ministrative bodies
The MHLW and MEXT are the authorities for this guideline.
Contents and purpose
The guideline provides ethical standards for designing, conducting,
recording, and reporting epidemiological research that involves human
subjects. It defines all terms concerned with epidemiological research,
including “informed consent” and “ethics
committee.” The guideline stresses the protection of privacy and
personal information and the priority of individuals' human rights
over that of scientific or social benefits.
Possible limitations
Studies that include medical treatment, which constitute a major part
of clinical epidemiological research, are excluded from the scope of
this guideline. And although the guideline addresses studies that do
not require individual informed consent and stresses the public release
of information and the assurance of subjects' rights to decline
participation in these cases, it is insufficient in detail as to how to
carry out these ideals. Finally, the guideline addresses neither
epidemiological gene analysis research nor refers to the Guideline for
Human Genome and Gene Analysis Research.
Guideline for Derivation and Utilization of Human
Embryonic Stem (hES) Cells8
Social and practical necessity
Following the discovery of hES cells in 1998, Japanese researchers
began to conduct similar projects. Soon thereafter, a committee for hES
cell research was established and the Bioethics Committee of the
Cabinet's Science and Technology Council set up the Advisory
Council for Human ES Cell Research.
Ministrative bodies
This guideline is under the auspices of the MEXT.
Contents and purpose
The guideline defines (1) standards for the derivation of hES cells,
including requirements for human embryo use, (2) requirements for
distribution of hES cells, (3) criteria for a deriving institution, (4)
instructions on how to apply for approval through an institution's
research ethics committee, and (5) donation of human fertilized
embryos, including requirements for utilization and informed consent
procedures. Each procedural step (derivation, distribution,
utilization) requires a separate review. Each review process also
consists of a double review aimed to ensure a high level of
surveillance and regulation. The first review is performed by a
researcher's institutional ethics committee and, on approval, the
senior researcher applies for official approval to the MEXT. The
guideline also spells out the penalties for breaking regulation (e.g.,
publication of researcher's name).
Possible limitations
The specific roles of each committee of the two-step review are
unclear. So we have to ask: Without specific roles, is there meaning in
a two-step review? And finally, the guideline lacks any mention of
patent rights (i.e., filing for patents).
Guideline for Clinical Research9 Ministry of Health, Labour, and Welfare. Guideline for
Clinical Research. 2003. Available at:
http://www.mhlw.go.jp/topics/2003/07/tp0730-2b.html
[Japanese].
Social and practical necessity
Between 2000 and 2003, a series of five guidelines were published,
all of which were specific to a certain field of research (i.e.,
epidemiology) or methodology (i.e., gene analysis). Nonetheless, the
specificity of these guidelines has also resulted in the lack of a
general and comprehensive guideline for clinical studies.
Ministrative bodies
Given that clinical research (e.g., the testing of new therapeutic
methods, diagnostics, and sociocultural aspects of patient care)
comprises several apparent ethical risks, the MHLW drafted a
comprehensive guideline for clinical research.
Contents and purpose
The guideline begins by defining all specific terms concerned with
clinical research (e.g., subjects, researchers, chief researcher,
informed consent, research institution, ethics committee). It then lays
out the responsibilities of researchers including the institution head,
the chief researcher, and the ethics committee. The guideline also
specifies the parameters and methodology of informed consent,
disclosure, and the protection of personal information.
Possible limitations
Because the guideline aims to fill in the gaps left by other
guidelines, it inherently lacks any specification. It is abstract and
does not offer practical guidance to researchers, and its scope is
unclear in terms of both field and methodology.
Conclusion
According to the National Science and Technology Basic Plan, the
Japanese government in 1995 and 2000 expanded their budget for
healthcare research grants.10
Cabinet
Office of Japan. The Science and Technology Basic Plan
(2001–2005). 30 Mar 2001. Available at:
http://www8.cao.go.jp/cstp/english/basicplan01-05.pdf
[English].
The drastic increase in healthcare
research that resulted makes apparent the political and ethical need
for scientific and ethical guidelines. Guidelines provide researchers
with the standards and parameters necessary to carry out effective and
ethical studies in an age of advancing technology. These guidelines, if
enforced properly, could ensure a high level of ethical standards for
designing, conducting, recording, and reporting scientific research
projects.
However, as highlighted by this report, the guidelines have several
shortcomings. To summarize, we found five possible limitations
including: (1) the lack of set standards for ethical reviews, (2) the
necessity of a central regulating body for local ethics committees, (3)
the need for specific procedural instructions, (4) possible
inconsistencies between guidelines, and (5) the regulatory limitations
of partial binding power. Furthermore, our examination of four sample
guidelines revealed several limitations specific to each guideline. The
current situation, without a doubt, highlights the need for further
discussion concerning these limitations and their implications on the
ethical standards for scientific research and medical treatment. The
rush of legislation on ethical standards for healthcare research
exemplifies the active movement in Japan's political, public, and
academic circles.
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