ArticlePDF Available

Abstract and Figures

The last decade has witnessed the emergence of international ethics guidelines discussing the importance of disclosing global and also, in certain circumstances, individual genetic research results to participants. This discussion is all the more important considering the advent of pharmacogenomics and the increasing incidence of 'translational' genetic research in the post-genomic era. We surveyed both the literature and the ethical guidelines using selective keywords. We then analyzed our data using a qualitative method approach and singled out countries or policies that were representative of certain positions. From our findings, we conclude that at the international level, there now exists an ethical duty to return individual genetic research results subject to the existence of proof of validity, significance and benefit. Even where these criteria are met, the right of the research participant not to know also has to be taken into consideration. The existence of an ethical duty to return individual genetic research results begs several other questions: Who should have the responsibility of disclosing such results and when? To whom should the results be disclosed? How? Finally, will this ethical 'imperative' become a legally recognized duty as well?
Content may be subject to copyright.
ARTICLE
The emergence of an ethical duty to disclose genetic
research results: international perspectives
Bartha Maria Knoppers
1
, Yann Joly*
,1
, Jacques Simard
2
and Francine Durocher
2
1
Centre de recherche en droit public, Universite
´
de Montre
´
al, Montre
´
al, Quebec, Canada;
2
Department of Anatomy-
Physiology, CHUQ Research Centre CHUL, Laval University, Quebec, Canada
The last decade has witnessed the emergence of international ethics guidelines discussing the importance
of disclosing global and also, in certain circumstances, individual genetic research results to participants.
This discussion is all the more important considering the advent of pharmacogenomics and the increasing
incidence of ‘translational’ genetic research in the post-genomic era. We surveyed both the literature and
the ethical guidelines using selective keywords. We then analyzed our data using a qualitative method
approach and singled out countries or policies that were representative of certain positions. From our
findings, we conclude that at the international level, there now exists an ethical duty to return individual
genetic research results subject to the existence of proof of validity, significance and benefit. Even where
these criteria are met, the right of the research participant not to know also has to be taken into
consideration. The existence of an ethical duty to return individual genetic research results begs several
other questions: Who should have the responsibility of disclosing such results and when? To whom should
the results be disclosed? How? Finally, will this ethical ‘imperative’ become a legally recognized duty as
well?
European Journal of Human Genetics (2006) 14, 11701178. doi:10.1038/sj.ejhg.5201690; published online 26 July 2006
Keywords: duty to re-contact; right to know; right not to know; communication of results; genetic research;
bioethics
Introduction
The last decade has witnessed the emergence of inter-
national ethics guidelines individual to genetic research
involving humans (Table 1). Focusing mainly on these
international texts, is there an ethical obligation on
researchers to disclose genetic research results to
participants or even to provide access to them? Authors
of a recent article on the return of research results
contend that: ‘There are no conditions under which an
offer of disclosure of research results should not be
made.’
1
This approach is problematic in that whereas on
the one hand, the return of clinical trial results (Table 2)
relevant to health has long been the norm,
2,3
on the
other hand, fundamental research (Table 2) results are
by their very nature not individually identifiable,
understandable or significant. Early genetic association
studies imperfectly predict the development and severity of
a condition. Associations with disease are often not
validated in more extensive studies and could mislead
participants to overestimate the significance of the
results.
4,5
Indeed, ‘the difficulty in deciding whether to
return research results lies in the fact that exploratory
genetic factors have not yet reached the point of
general clinical acceptance.’
6
Yet, it is self-evident that
ongoing communication with participants is important in
order to respect their voluntary decision to continue
or to withdraw once they have agreed to participate in
research as well as to recognize the importance of their
altruistic contribution to the progress of research in the
field of genetics.
Received 28 November 2005; revised 6 June 2006; accepted 13 June 2006;
published online 26 July 2006
*Correspondence: Y Joly, Centre de recherche en droit public, Universite
´
de Montre
´
al, CP 6128, succ. Centre-Ville, Montreal, Quebec, Canada. H3C
3J7. Tel: þ 1 514 343 6111 ext 5020; Fax: þ 1 514 343 6233;
E-mail: yann.joly@umontreal.ca
European Journal of Human Genetics (2006) 14, 11701178
&
2006 Nature Publishing Group All rights reserved 1018-4813/06
$30.00
www.nature.com/ejhg
Table 1 Selected policies and guidelines concerning the duty to return research results
Scope Organization Title Date
Genetic
specific?
a
International Pharmacogenetics Working
Group
Returning Genetic Research Results to Individuals:
Points-to-Consider
2006 Yes
UNESCO, International Bioethics
Committee
International Declaration on Human Genetic Data 2003 Yes
World Health Organization Genetic Databases: Assessing the Benefits and the
Impact on Human and Patient Rights
2003 Yes
Council for International
Organization of Medical Sciences
International Ethical Guidelines for Biomedical
Research Involving Human Subjects
2002 No
Pharmacogenetics Working
Group
Elements of Informed Consent for
Pharmacogenetic Research
2002 Yes
Human Genome Organization Statement on DNA Sampling: Control and Access 1998 Yes
World Health Organization Proposed International Guidelines on Ethical Issues
in Medical Genetics and Genetic Services
1997 Yes
International Conference on
Harmonisation of Technical
Requirements for Registration of
Pharmaceuticals for Human Use
Good Clinical Practices Consolidated Guidelines 1996 No
Human Genome Organization Statement on the Principled Conduct of Genetic
Research
1996 Yes
World Medical Association Declaration on the Human Genome Project 1992 Yes
Council for International
Organization of Medical Sciences
International Guidelines for Ethical Review of
Epidemiological Studies
1991 No
World Medical Association Declaration on the Rights of the Patient 1981 No
World Medical Association World Medical Association Declaration of Helsinki
F Ethical Principles for Medical Research Involving
Human Subjects
1964
(2000)
No
Regional
(Europe)
European Commission Expert
Group on Genetic Testing
25 Recommendations on the Ethical, Legal and
Social Implications of Genetic Testing
2004 Yes
Council of Europe Additional Protocol to the Convention on Human
Rights and Biomedicine Concerning Biomedical
Research
2004 No
European Federation of the
International Epidemiology
Association
Good Epidemiological Practice (GEP) Proper
Conduct in Epidemiologic Research
2002
(2004)
No
European Parliament F Council
of the European Union
Directive 2001/20/EC of the European Parliament
and of the Council of 4 April 2001 on the
approximation of laws, regulations and
administrative provisions of the Members States
relating to the implementation of good clinical
practice in the conduct of clinical trials on
medicinal products for human use
2001 No
Council of Europe Convention for the Protection of Human Rights and
Dignity of the Human Being with Regard to the
Application of Biology and Medicine: Convention
on Human Rights and Biomedicine
1997 No
European Parliament Council of
the European Union
Directive 95/46/EC of the European Parliament and
of the Council of 24 October 1995 on the
protection of individuals with regard to the
processing of personal data and on the free
movement of such data
1995 No
National (United
Kingdom)
Nuffield Council on Bioethics Pharmacogenetics: Ethical Issues 2003 Yes
Medical Research Council Human Tissue and Biological Samples for Use in
Research- Operational and Ethical Guidelines,
2001 No
National (United
States)
NHLBI Working Group on
Reporting Genetic Results in
Research Studies
Reporting Genetic Results in Research Studies 2006 Yes
Consortium on Pharmacogenetics Ethical and Regulatory Issues in Research and
Clinical Practice
2002 Yes
National Bioethics Advisory
Commission (NBAC)
Research Involving Human Biological Materials:
Ethical Issues and Policy Guidance
1999 Yes
United States Government Clinical Laboratory Improvement Amendments
Regulations (CLIA)
1988 No
International perspectives ofdisclosing genetic research
BM Knoppers et al
1171
European Journal of Human Genetics
Recently, as concerns research involving human partici-
pants, authors have begun promoting the return of all peer
reviewed results whether negative or positive.
1
More
specifically, some maintain the need to return individual
genetic research results to participants.
7
Several factors are
contributing to the transfer of this approach to the specific
field of genetic research. The first is a confusion in the
ethics guidelines between fundamental results and clinical
trial results (see in particular such ‘conflation’ in the
European Federation of the International Epidemiology
Association (IEA)’s Good Epidemiological Practice (GEP),
Proper Conduct in Epidemiologic Research
8
and in the
Canada’s three granting councils’ Policy Statement: Ethical
Conduct for Research Involving Humans.
9
The second is the
influence of general research ethics guidelines and of
personal data access legislation mandating access to
results.
10,11
The third is the desire to counter a possible
negative public image of genetic research including
allegations of ‘biopiracy’.
12,13
Finally, the most important
factor is the recent marriage of classical clinical trials with
genomic research in the field of pharmacogenomics.
14
In
the post-genomic era, this new type of ‘translational’
(Table 2) research is increasingly surfacing in the field of
genetics.
Seemingly, returning individual fundamental research
results is impossible and nonsensical as the very purpose of
this type of research is not the production of individual but
generalizable knowledge. Thus, in this context, the con-
cept of individual research results is a scientific misnomer.
To avoid confusion, both translational research and the
clinical trial context where the individual receives a drug or
undergoes some intervention (or even a placebo) need to
be distinguished from fundamental research.
Beginning then with a brief contextual snapshot of the
international guidelines demonstrating the emergence of
an ethical duty to share genetic research results (along with
Table 1 (Continued)
Scope Organization Title Date
Genetic
specific?
a
National
(Canada)
Medical Research Council of
Canada, Natural Sciences and
Engineering Research Council of
Canada, Social Sciences and
Humanities Research Council of
Canada
Tri-Council Policy Statement F Ethical Conduct for
Research Involving Humans
1998
(2000,
2002,
2005)
No
Canadian College of Medical
Geneticists
Policy Statement Concerning DNA Banking and
Molecular Genetic Diagnosis
1991 Yes
National
(France)
National Consultative Bioethics
Committee
Opinion and Recommendations on ‘Genetics and
Medicine: from Prediction to Prevention’
1995 Yes
National
(Singapore)
Bioethics Advisory Committee Genetic Testing and Genetic Research 2005 Yes
Local (Quebec,
Canada)
Quebec Network of Applied
Genetic Medicine
Statement of principles: Human Genomic Research 2000 Yes
a
Does the selected policy/guideline broadly apply to all type of research (including genetic) or does it specifically address genetic research?
Table 2 The research continuum
Fundamental
research
Although there is no unanimously accepted definition of what constitutes fundamental research, in practice one can
identify and distinguish from other types of research those that are carried out with no direct link to a given
application and, if not exclusively, in any case and above all with the intent of progressing scientific knowledge
(see Commission of the European Communities, Communication from the Commission. Europe and Basic Research,
Brussels, 2004)
Translational
research
This emerging type of research aims to validate new genetic tools, assays and other analytical processes and to
assess their clinical validity and utility before their introduction in the clinic.
Clinical trials Any investigation in human research participants intended to discover or verify the clinical, pharmacological and/or
other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an
investigational product(s), and/or to study absorption, distribution, metabolism and excretion of an investigational
product(s) with the object of ascertaining its safety and/or efficacy
(see International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for
Human Use (ICH), Guidance for Industry E6 Good Clinical Practice Consolidated Guideline, Geneva, 1996)
International perspectives ofdisclosing genetic research
BM Knoppers et al
1172
European Journal of Human Genetics
the existence of the right not to know) (A), the issues of
which genetic results and when? (B), by whom? (C) and, to
whom? (D), need to be addressed before concluding (E).
Guidelines are neither standards nor laws. But, if over time
they become professional norms, they may become the
legal standard of care for both clinical practice and for
research.
Materials and methods
In order to identify and assess international perspectives on
the return of research results, we undertook an empirical
analysis of both the literature and the ethical guidelines
found on major electronic databases using selective key-
words. The search profile contained the following key-
words: research, study, disclosure, communication, duty to
warn, inform, return, reporting, results, right to know,
genetics and genomics. The databases searched were Med-
line, PubMed, Google Scholar, WHO’s International Digest
of Health Legislation and HumGen (an international
database on the ethical, legal and social issues of human
genetics; www.humgen.umontreal.ca). Following this pre-
liminary search, the selected items were scrutinized for
relevant sources warranting closer reading. Only docu-
ments directly relevant to the ethical issues surrounding
the communication of research results were kept. The
documents were grouped chronologically and by jurisdic-
tion (see Table 1). Then, they were analyzed using a
qualitative method approach. The INHERIT BRCAs re-
search program (Interdisciplinary Health Research Inter-
national Team on Breast Cancer Susceptibility) gave us an
appropriate platform to assess the pitfalls, limitations and
benefits of our approach.
(A) Emergence of an ethical duty to share genetic
research results
Global research results
The usual avenue for commu-
nication of research results is through scientific publica-
tion. According to the revised Declaration of Helsinki
(2000), at a minimum, ‘negative as well as positive (global)
research results should be published or otherwise publicly
available.’
15
This is certainly becoming the norm in clinical
research where failure to publish results is now viewed as a
form of scientific misconduct. Unpublished data can lead
to additional, redundant trials being performed, useless or
even harmful interventions remaining in use and, ulti-
mately, do not contribute to the growth of society’s
collective knowledge.
16
However, publishing clinical research results in a scien-
tific journal or in a regulatory database is no longer
ethically sufficient. The ethical principles of respect for
the person, beneficence and justice obligate the researcher
to offer results in a manner that is clear and understandable
to the research participants.
1,17
The recent draft guidelines of the European Federation of
the IEA) state that,
Research results should be published without undue
delay, and disseminated critically and in good faith,
supported by proper documentation. Findings that
contradict the main results should always be pre-
sented in the text.
It is advisable to publish the main
results in a form that reaches the participants of the
study and other interested members of the commu-
nity where the study took place (eg a newsletter, local
newspapers etc.) (emphasis added).
8
Communication can take the form of a personal letter, a
news bulletin, a newspaper article, website or a similar
forum. In the actual context, the chosen media should be
specified at the beginning of the consent process. Such
transparency in the communication of global results (often
the only benefit from research) is not the same, however, as
giving back individual results.
Individual research results To illustrate the evolution of
the concept of returning individual research results, the
1991 Council for International Organizations of Medical
Sciences (CIOMS) International Guidelines for Ethical Review
of Epidemiological Studies maintained that being informed
of findings ‘that pertain to their health’ is one of the
‘reasonable’ benefits of participation for ‘communities,
groups and individuals’ in research.
18
A decade later, this
position was underscored by CIOMS by not only suggest-
ing informing participants of the findings of the research
in general but also by clarifying that ‘individual subjects
will be informed of any finding that relates to their
particular health status’ (emphasis added).
10
A similar
position was also expressed by the Council of Europe
19
and, in the specific context of genetic research, by
UNESCO
20
and the WHO (World Health Organization).
21
All these international guidelines also recognize the logical
a contrario position, that of the ‘right not to know’.
The emergence of this nebulous ‘right not to know’
further confounds the determination of whether an ethical
duty to return genetic research results exists. Indeed, this
right depends on the informed consent process and
therefore needs to be discussed before the research even
begins. At that time, the participant can exercise a choice
concerning possible future communication of research
results.
The right not to know was legally consecrated in the
1997 Council of Europe’s Convention on Human Rights and
Biomedicine.
22
The Convention is a legally binding instru-
ment in the European countries that have ratified it
23
(ie
before ratification, each State has to bring its laws in
comformity with the Convention. Such legislation must
include legal sanctions and require compensation for
individuals who have suffered undue harm following
International perspectives ofdisclosing genetic research
BM Knoppers et al
1173
European Journal of Human Genetics
medical treatment or research). Article 10 on the right to
privacy and to information states: ‘everyone is entitled to
know any information collected about his or her health.
However, the wishes of individuals not to be so informed
shall be observed.’
22
Whereas the Convention was on
biomedicine generally, UNESCO’s 2003 International De-
claration on Human Genetic Data
20
conferred this right not
to be informed ‘where appropriate (to)
identified relatives
who may be affected by the results’ (art. 10) (emphasis
added).
It should be noted that earlier statements on the right
not to be informed contained provisions that the interests
of others could override this right of the individual not to
receive information. In 1981, the World Medical Associa-
tion (WMA), as concerns patients’ rights generally, would
not respect the refusal by an individual to receive results if
‘required for the protection of another person’s life’ (7.d).
24
Likewise, in 1997, WHO’s Proposed International Guidelines
on Ethical Issues in Medical Genetics and Genetic Services
would override the wish of an individual not to know
clinical test results in the situation of the ‘testing of
newborns or children for treatable conditions.’
25
(B) Which genetic research results and when?
International guidelines generally address neither the
specific issue of which results nor the timing of their
communication, except the obvious obligation to ‘inform
a subject when medical care is needed’(4.3.2).
3
We have
already noted the position of CIOMS on the return of any
finding that relates to particular health status.
8
Thus, can
we presume a duty to return global results to all
participants as well as the need to return individual results
if reliable and clinically significant? Nowhere is this more
problematic than in the specific context of genetic
research. This is because, ‘human genetic research is not
conducted with the aim of providing research participants
with specific information about their genetic status or
health. Generally, genetic information derived from re-
search is of unknown or uncertain predictive value.
Therefore, special care must be taken to prevent inad-
vertent release of immature data’ (emphasis added).
26
The 2002 Consortium on Pharmacogenetics maintains
that ‘researchers are obligated to
offer the research
participant the
option of disclosure of research informa-
tion when its
reliability has been established and when the
disclosure is of potential
benefit to the subject’ (emphasis
added).
27
The Consortium, however, did not attempt to
define what would constitute ‘potentially beneficial’ or
‘reliable’ results, presumably preferring to leave a margin of
professional interpretation to the research team. According
to the Pharmacogenetics Working Group, the issue of
whether to disclose also depends on other criteria such as
the standard operating procedure of the research sponsor,
the scientific validity, the clinical relevance, quality
assurance, the measures to maintain confidentiality, the
ability of researchers or sponsors to provide the appropriate
counselling, the legal and ethical framework, etc.
6,28
A distinction must be made between pharmacogenetic
drug trials where it could be considered a requirement to
disclose individual results of direct interest and benefit to
the participant and hypothesis testing studies of no direct
medical relevance which would not need to be shared with
the participant.
27
This latter position reflects the current
trend as concerns fundamental genetic and pharmaco-
genetic research. In Europe, see for example the Medical
Research Council’s Human Tissue and Biological Samples for
Use in Research- Operational and Ethical Guidelines.
29
Indeed, in 2003, this position was affirmed at the
international level by WHO in its report on Genetic
Databases: Assessing the Benefits and the Impact on Human
and Patient Rights. Although WHO states that in most
situations, genetic research data will remain of abstract
significance, it maintains that there may be situations
where data might be of value in a clinical setting. Even
so, the following conditions should be met before
disclosure:
(a) ‘the data have been instrumental in identifying a clear
clinical benefit to identifiable individuals;
(b) the disclosure of the data to the relevant individuals
will avert or minimize significant harm to those
individuals;
(c) there is no indication that the individuals in question
would prefer not to know.’
21
In short, if individual genetic research results are to be
returned at all, at a minimum, they should meet the
requirements of scientific validity, clinical significance,
benefit (ie existence of prevention or treatment) and the
absence of an explicit refusal to know. However, it could
well be that a result that has no clear clinical benefit at the
time of the research will turn out to be very important to
the participant at a later time. This raises the question of
how long can the ethical duty to return results last?
Members from the Pharmacogenetics Working Group have
recently suggested that ‘some pragmatic limitations on the
research endeavor should be put in place so that respon-
sibilities of investigators, sponsors, participants, and ethics
committees are not left open ended.’
6
More specifically, the
American National, Heart, Lung, and Blood Institute
(NHLBI) Working Group on Reporting Genetic Results
in Research Studies stipulates that ‘responsibilities of
the investigators cannot extend beyond the period of
funding.’
4
The requirements of validity, significance, and benefit
could be assessed by answering the following questions:
(1) ‘Does the genetic test that generated the results
accurately identify the genetic variant of interest?
International perspectives ofdisclosing genetic research
BM Knoppers et al
1174
European Journal of Human Genetics
(2) Does the identification of the variant permit an
accurate prediction of the presence (or risk) of a clinical
condition?
(3) Can the identification of the clinical condition (either
disease or risk for developing a disease) improve the
patient’s health outcome?’
30
To be truly effective, evaluation methods to assess the
clinical significance of genetic tests will need to be as
complete and unbiased as possible.
30
In the past, when the above three criteria were met, the
researcher retained discretion over the decision to com-
municate research results or not. Recent international
norms now suggest an ethical obligation to disclose all
research results meeting these criteria. This is illustrated
by the 2004 Additional Protocol to the Convention on
Human Rights and Biomedicine Concerning Biomedical Re-
search recently issued by the Council of Europe; ‘If research
gives rise to information of
relevance to the current
or future health or quality of life of research participants,
this information
must be offered to them’ (emphasis
added).
19
But how can one determine what is relevant
for each research participant? For example, an argument
could be made that an information about a genetic
predisposition can be relevant to the participant even
though it is unlikely to affect immediate health outcomes
(eg lifestyle). One solution, advanced by the Pharma-
cogenetics Working Party, would be to subject research
findings to both peer review and ethics review before
disclosure.
31
The NHLBI Working Group on Reporting
Genetic Results in Research Studies also maintains that
decisions regarding reporting of research results should
only be made with IRB approval.
4
It remains to be seen
what will be the effect of this extensive duty on genetic
research results.
An important precaution that genetic researchers would
be wise to take is to validate their research results via a
licensed or accredited clinical laboratory. This is in fact a
legal obligation in the United States.
32,33
However, this
solution might be difficult to implement in some countries
as the qualities, accessibility and availability of tests vary
greatly and validating research results in a clinical labora-
tory is not always economically feasible for researchers.
(C) By whom?
While this obligation to disclose both individual and
global genetic results is developing, few guidelines at the
international level specify with whom this duty lies.
Generally, no person is named specifically to carry out
this task. The 1998 WHO Proposed International Guidelines
on Ethical Issues in Medical Genetics and Genetic Services
mentions ‘professionals.’
25
Concerning results in clinical
trials generally, the International Conference on Harmo-
nization speaks of the investigator or institution (4.3.2).
3
The Pharmacogenetics Working Group also makes a
specific suggestion: according to them, ‘the subject’s
physician may be in the best position thoughtfully to
communicate these results as part of follow-up healthcare
contacts’.
28
Neither UNESCO nor WHO address this topic
in their recent norms governing genetic data.
20,21
At the national level, several groups have come up with
suggestions. According to the Consortium on Pharmaco-
genetics, the consent form should state who will make the
determination of reliability and who will have the
responsibility of informing the participants.
27
A consensus
seems to be that a researcher would not be the
appropriate person to disclose the results. For instance,
both the American Society of Human Genetics and the
Canadian College of Medical Geneticists hold that ‘the
results of DNA analyses should be reported to the
appropriate health care professional, who in turn has the
responsibility of informing individuals or family of the
results and their meaning.’
34,35
The Quebec Network of
Applied Genetic Medicine (RMGA) suggests communica-
tion by the ‘treating physician’ in the case of specific,
individual genetic research results.
36
In France, the Na-
tional Consultative Ethics Committee for Health and Life
Sciences recommends that ‘the results of the tests must be
communicated in person by a physician whose compe-
tence permits a full explanation of the significance of the
results.’
37
Canada’s three granting councils, in their Policy State-
ment, seem to recommend that the genetic researcher
be the one to report results back to the individuals:
‘The genetic researcher shall seek free and informed
consent from the individual and report results to that
individual if the individual so desires.’
9
However, even
they recognize that ‘considerations should be given to
combining clinical expertise with that of the research
geneticist.’
9
Thus, it could be posited that the participant’s treating
physician or at the very least a clinician involved with the
research team would be an appropriate person to report the
research results rather than the researcher. However, this
implies that from that point on, the research findings will
be entered in the medical record of the research partici-
pants. They then will be afforded the same level of
confidentiality protection as any other kind of medical
information.
Another important person to involve in the process is
the genetic counselor. In recent applications, concerning
research projects on predictive testing, pre- and post-test
genetic counseling is seen as integral to the research. Both
researchers and the institutional review board now have to
ensure the availability of such counseling when appro-
priate,
9
that is when genetic tests become available. On
that topic, UNESCO takes the position that
It is ethically imperative that when genetic testing
that may have significant implications for a person’s
International perspectives ofdisclosing genetic research
BM Knoppers et al
1175
European Journal of Human Genetics
health is being considered, genetic counselling
should be made available in an appropriate man-
ner.
20
(D) To whom?
First in 1996
38
and later in 1998,
39
the Ethics Committee of
the Human Genome Organisation (HUGO) affirmed the
longstanding ethical tenet of no communication to the
person tested or to others without consent. Nevertheless,
[S]pecial considerations should be made for access by
immediate relatives. Where there is a high risk of
having or transmitting a serious disorder and pre-
vention or treatment is available, immediate relatives
should have access to stored DNA for the purpose of
learning their own status. These exceptional circum-
stances should be made generally known at both the
institutional level and in the research relationship.
39
Thus, while not supporting the notion of an obligation
to communicate genetic results to relatives, it supports the
position of access to such information by immediate
relatives. HUGO avoided defining what is meant by
‘immediate relatives’. Generally, these exceptional circum-
stances should be made known during the process of
obtaining consent. The WMA in its 1992 Declaration on the
Human Genome Project mentioned the
at risk family
members’ of the patient (emphasis added).
40
UNESCO distinguishes between identified relatives and
those who cannot be found owing to anonymization of
data. It goes further, however, by adding the right of such
identified relatives not to be informed. Indeed, we have
seen that according to article 10 of UNESCO’s 2003
International Declaration on Human Genetic Data, ‘Where
appropriate, the right not to be informed should be
extended to identified relatives who may be affected by
the results.’
20
Recommendation 8 of WHO’s 2003 report on Genetic
Databases speaks of ‘relevant individuals’ without further
qualification, thus seemingly including others not just the
research participant or the family. It is interesting to note
that WHO maintains its long-held position on the
possibility of overriding the objection of participants to
the release of clinically relevant data to third parties:
Disclosure in these circumstances is permissible even
in the face of objection from the person who
originally contributed data to the database. The onus
is on those who would seek to disclose to justify this
action. Ethical approval for such disclosures should
be sought.
21
Acknowledging that ‘an individual’s privacy interest in
his genetic information might not be absolute’ yet fully
realizing the complexity of the issues involved, the
Pharmacogenetics Working Group recommended that
any decision regarding familial disclosure be made on a
case-by-case basis.
6
Conclusion
Resolution of the question of whether there is a duty to
return global or individual genetic research results depends
on the type of study, the clinical significance and reliability
of the information, and whether the study involves
patients, genetically ‘at-risk’ families for a tested predis-
position or healthy volunteers. Further confounding the
emerging duty to return genetic research results is the
situation in which the researcher is also a clinician and the
participant is also a patient.
However handled, the issue of notifying (or not)
participants of results should be disclosed and agreed to
in advance (ie on the consent form). As stated by the
European Commission in 2004: lie on the consent form
Public trust in research surrounding genetic testing is
largely dependent on how the use of samples and
data in and from biobanks is undertaken and
communicated. This applies in particular to [t]he
communication of study results and, where appro-
priate, of individual test results.
17
Finally, although at the international level there may be
an emerging ethical ‘imperative’ to return results in genetic
research, this begs the further question of whether this
duty should be legally recognized. It is hoped that fear of
potential legal liability will not give rise to protectionist
approaches mandating such a duty under law. Like research
‘results’, an ethical ‘imperative’ is also a misnomer, for the
ethics of decision-making in the research context depends
on dialogue and agreement between participants and
researchers.
Acknowledgements
We acknowledge the financial support of the Canadian Institutes of
Health Research (CIHR) for the INHERIT BRCAs project: Genome
Canada/Genome Quebec and The Quebec Network of Applied Genetic
Medicine (RMGA) of the Fonds de la recherche en sante
´
du Que
´
bec
(FRSQ). We thank Guillaume Sillon from the Centre de recherche en
droit public, Universite
´
de Montre
´
al, for his invaluable assistance with
the manuscript.
References
1 Fernandez CV, Kodish E, Weijer C: Informing study participants
of research results: an ethical imperative. IRB: Ethics Hum Res
2003; 25: 12 19.
2 Mann H: Research ethics committees and public dissemination of
clinical trial consults. Lancet 2002; 359: 406 408.
3 The International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use
(ICH): Good Clinical Practices Consolidated Guidelines. Ottawa:
International perspectives ofdisclosing genetic research
BM Knoppers et al
1176
European Journal of Human Genetics
Therapeutic Products Directorate, 1997. Available from: http://
www.ncehr-cnerh.org/english/gcp/.
4 Bookman EB, Langehorne AA, Eckfeldt JH et al: Reporting genetic
results in research studies: summary and recommendations
of an NHLBI working group. Am J Med Genet 2006; 140 (Part A):
1033 1040.
5 Trikalinos TA, Ntzani EE, Contopoulos-Ioannidis DG, Ioannidis
JP: Establishment of genetic associations for complex diseases is
independent of early study findings. Eur J Hum Genet 2004; 12:
762 769.
6 Renegar G, Webster CJ, Stuerzebecher S et al: Returning genetic
research results to individuals: points-to-consider. Bioethics 2006;
20: 24 36.
7 Banks TM: Misusing informed consent: a critique of limitations
on research subjects’ access to genetic research results. Sask Law
Rev 2000; 63: 539 580.
8 European Federation of the International Epidemiologist Associa-
tion (IEA): Good epidemiological practice (GEP) proper conduct in
epidemiologic research. Berne: European Federation of the Interna-
tional Epidemiologist Association, 2002, (updated June 2004).
Available from: http://www.dundee.ac.uk/iea/GoodPract.htm;.
9 Medical Research Council of Canada, Natural Sciences and
Engineering Research Council of Canada, Social Sciences and
Humanities Research Council of Canada (IRSC, CRSNG and
CRSH): Tri-council policy statement: ethical conduct for research
involving humans. Ottawa: IRSC, CRSNG and CRSH; October
2005. Available from: http://www.pre.ethics.gc.ca/english/pdf/
TCPS%20October%202005_E.pdf.
10 Council for International Organization of Medical Sciences
(CIOMS): International ethical guidelines for biomedical research
involving human subjects. Geneva: Council for International
Organization of Medical Sciences; November 2002. Available
from: http://www.cioms.ch/frame_guidelines_nov_2002.htm.
11 European Parliament. Directive 95/46/EC of the European
Parliament and of the Council of 24 October 1995 on the
protection of individuals with regard to the processing of
personal data and on the free movement of such data (1995)
O.J.L. 281/31 art. 12. Available from: http://www.cdt.org/privacy/
eudirective/EU_Directive_html.
12 Knoppers BM, Chadwick R, Takebe H et al: HUGO urges genetic
benefit-sharing. Commun Genet 2000; 3: 88 92.
13 Knoppers BM: Population genetics and benefit sharing. Commun
Genet 2000; 3: 212 214.
14 Nuffield Council on Bioethics: Pharmacogenetics ethical issues.
London: Nuffield Council on Bioethics, 2003, pp 22 23.
Available from: http://www.nuffieldbioethics.org/go/ourwork/
pharmacogenetics/introduction.
15 World Medical Association (WMA): World medical association
declaration of Helsinki, ethical principles for medical research involving
human subjects. Edinburgh: World Medical Association, 2000.
Available from: http://www.wma.net/e/policy/b3.htm.
16 Tumber MB, Dickersin K: Publication of clinical trials: account-
ability and accessibility. J Intern Med 2004; 256: 273.
17 European Commission: 25 Recommendations on the ethical, legal
and social implications of genetic testing. Brussels: European
Commission, 2004. Available from: http://europa.eu.int/comm/
research/conferences/2004/genetic/pdf/recommendation-
s_en.pdf.
18 Council for International Organization of Medical Sciences
(CIOMS): International guidelines for ethical review of epidemiological
studies. Geneva: Council for International Organization of
Medical Sciences, 1991. Available from: http://www.cioms.ch/
frame_1991_texts_of_guidelines.htm.
19 Council of Europe: Additional protocol to the convention on human
rights and biomedicine concerning biomedical research. Strasbourg:
Council of Europe, 2004 Available from: http://www.coe.int/T/E/
Legal_affairs/Legal_co-operation/Bioethics/Activities/Biomedical_
research/Protocol_Biomedical_research.pdf.
20 UNESCO, International Bioethics Committee (IBC): International
declaration on human genetic data. Paris: UNESCO, International
Bioethics Committee (IBC), 2003. Available from: http://portal.
unesco.org/en/ev.php-URL_ID ¼ 17720&URL_DO ¼ DO_TOPIC
&URL_SECTION ¼ 201.html.
21 World Health Organisation (WHO): Genetic databases: assessing
the benefits and the impact on human and patient rights. Geneva:
World Health Organisation, 2003. Available from: http://www.
law.ed.ac.uk/ahrb/publications/online/whofinalreport.doc.
22 Council of Europe: Convention for the protection of human rights and
dignity of the human being with regard to the application of biology
and medicine: convention on human rights and biomedicine. Oviedo:
Council of Europe, 1997. Available from: http://convention-
s.coe.int/treaty/en/Treaties/Html/164.htm.
23 Lemmens T, Joly Y, Knoppers BM: Genetic and life insurance: a
comparative analysis. GenEdit 2004; 2: 1 15. Available
from: http://www.humgen.umontreal.ca/int/GE_Arch_v.cfm?
an ¼ 2004&no ¼ 2.
24 World Medical Association (WMA): World medical association
declaration on the rights of the patient. Lisbon: World Medical
Association, 1981. Available from: http://www.wma.net/e/policy/
l4.htm.
25 World Health Organisation (WHO): Proposed international guide-
lines on ethical issues in medical genetics and genetic services. Geneva:
World Health Organisation, 1997, Available from: http://whqlibdoc.
who.int/hq/1998/WHO_HGN_GL_ETH_98.1.pdf.
26 The Bioethics Advisory Committee: Genetic testing and genetic
research. Singapore: The Bioethics Advisory Committee, 2005.
Available from: http://www.bioethics-singapore.org/resources/
pdf/GTGR%20Report.pdf.
27 Consortium on Pharmacogenetics: Ethical and regulatory issues in
research and clinical practice. Minneapolis: Consortium on Phar-
macogenetics, 2002. Available from: http://www.bioethics.umn.
edu/News/pharm_report.pdf.
28 Anderson DC, Gomez-Mancilla B, Spear BB et al: Elements of
informed consent for pharmacogenetic research; perspective of
the pharmacogenetics working group. Pharmacogenomics J 2002;
2: 284 292.
29 Medical Research Council (MRC): Human tissue and biological
samples for use in research operational and ethical guidelines.
London: Medical Research Council, 2001. Available from: http://
www.mrc.ac.uk/pdf-tissue_guide_fin.pdf.
30 Pinsky L, Atkins D, Ramsey S, Burke W: Developing guidelines for
the clinical use of genetic tests: a US perspective; in Khoury MJ,
Burke W, Little J (eds): Human genome epidemiology: a scientific
foundation for using genetic information to improve health and prevent
disease. Oxford: Oxford university Press, 2003.
31 Clarke A, English V, Harris H, Wells F: Ethical considerations. Int J
Pharmaceutical Med 2001; 15: 89 94.
32 US Department of health and human services: Medicare,
Medicaid and CLIA programs: Laboratory requirements relating
to quality systems and certain personnel qualifications. Final
rule. Fed Regist 2003; 68: 3640 3714, Available from:
www.phppo.cdc.gov/clia/pdf/CMS-2226-F.pdf.
33 Quaid KA, Jessup NM, Meslin EM: Disclosure of genetic infor-
mation obtained through research. Genet Testing 2004; 8:
347 355.
34 American Society of Human Genetics (ASHG): DNA banking and
DNA analysis: points to consider. Bethesda: American Society of
Human Genetics, 1988. Available from: http://genetics.faseb.org/
genetics/ashg/policy/pol-02.htm.
35 Canadian College of Medical Geneticists: Policy statement
concerning DNA banking and molecular genetic diagnosis. Clin
Invest Med 1991; 14: 363 365.
36 Quebec Network of Applied Genetic Medicine (RMGA): Statement
of principles: human genomic research. Montreal: Quebec Network
of Applied Genetic Medicine, 2000. Available from: http://
www.rmga.qc.ca/doc/principes_en_2000.html.
37 National Consultative Ethics Committee for Health and Life
Sciences: Opinion and recommendations on ‘genetics and medicine:
from prediction to prevention’. Paris: National Consultative Ethics
International perspectives ofdisclosing genetic research
BM Knoppers et al
1177
European Journal of Human Genetics
Committee for Health and Life Sciences, 1995. Available from:
http://www.ccne-ethique.fr/english/start.htm.
38 Human Genome Organisation (HUGO): Statement on the prin-
cipled conduct of genetic research. London: Human Genome
Organisation, 1996. Available from: http://www.gene.ucl.ac.uk/
hugo/conduct.htm.
39 Human Genome Organisation (HUGO): Statement on DNA sampling:
control and access. London: Human Genome Organisation, 1998.
Available from: http://www.gene.ucl.ac.uk/hugo/sampling.html.
40 World Medical Association (WMA): Declaration on the human
genome project. Marbella: World Medical Association, 1992.
Available from: http://www.wma.net/e/policy/g6.htm.
International perspectives ofdisclosing genetic research
BM Knoppers et al
1178
European Journal of Human Genetics
... The return of individual, incidental genetic ndings to research participants has been controversial 1,2 and uncommonly undertaken until recent movement in that direction. 3,4 Reluctance on the part of investigators to commit to this practice derives from a number of valid concerns, such as lack of Clinical Laboratory Improvement Amendments (CLIA) certi ed results, frequent uncertainty as to the clinical implications of a particular genetic variant, lack of long-term grant funding to maintain contact with participants, and often insu cient support to provide adequate communication and counseling. 5 In counter balance to these concerns is the inherent wish to provide potential bene t to individual participants who generously engage in research, a desire to prevent harm to a participant that is unaware of a potentially remediable genetic risk, and a respect for the autonomy of participants who wish to have information they feel may be useful. ...
Preprint
Full-text available
Purpose: The proper communication of clinically actionable findings to participants of genetic research entails important ethical considerations, but has been challenging for a variety of reasons. We document an instance of return of individual genetic results in the context of a very rural American Indian community, in hopes of providing insight to other investigators about potentially superior or inferior courses of action. Methods: The original study was a case/control study of asthma among 324 pediatric participants. The study utilized a genotyping microarray assessing over 2 million variants, including one conferring risk for hypertrophic cardiomyopathy for which the American College of Medical Genetics recommends return of results to participants. The study investigators engaged in extensive consultation with the IRB, the Tribal government and local clinicians to better inform our approach. Results: With some difficulty we were able to notify the 2 participants heterozygous for this variant. One participant welcomed this information and proceeded to obtain further clinical work-up; the other participant declined further follow-up. Conclusion: While demanding of considerable time and effort, the return of clinically actionable genetic results is important from both an ethical perspective and to provide an improved trust relationship with the community of research participants.
... Making aggregate research results available to participants has been widely supported by health researchers and bioethicists, 16 , 17 , 18 , 19 , 20 and recommended by international ethical guidelines. 21 Making these results available is argued to follow from three principles of research ethics: respect for persons, beneficence/non-maleficence, and justice. However, dementia research presents challenges to the generalized obligation to make aggregate results available, specifically due to fear of dementia. ...
Article
Full-text available
A general obligation to make aggregate research results available to participants has been widely supported in the bioethics literature. However, dementia research presents several challenges to this perspective, particularly because of the fear associated with developing dementia. The authors argue that considerations of respect for persons, beneficence, and justice fail to justify an obligation to make aggregate research results available to participants in dementia research. Nevertheless, there are positive reasons in favor of making aggregate research results available; when the decision is made to do so, it is critical that a clear strategy for communicating results is developed, including what support will be provided to participants receiving aggregate research results.
... This is in line with an assertion that research participants must be allowed satisfactory information about the procedure of research, the purpose of the study, risks and, anticipated benefits and alternative procedures (Smith, 2003). Furthermore, the principle of beneficence was observed too, the principle argues the researcher to avoid sensitive and private questions that might cause harm to the respondents (Knoppers & Joly, 2006) Confidentiality, Privacy and anonymity; care was taken by identifying the selected schools and study participants using codes rather than names. This follows the guideline that of anonymization of research participants identity (Barbour, 2000). ...
... Some authors argue that sharing aggregate findings from genomic studies should be viewed as 'sharing knowledge' rather than 'returning results' [28]. The impact of genomic research will be enhanced when communities embrace the results and fully understand its value to their families and future generations [29,30]. If appropriately communicated, the results are likely to foster a sense of uniqueness in the context of a larger population. ...
Article
Full-text available
Background A fundamental ethical challenge in conducting genomics research is the question of what and how individual level genetic findings and aggregate genomic results should be conveyed to research participants and communities. This is within the context of minimal guidance, policies, and experiences, particularly in Africa. The aim of this study was to explore the perspectives of key stakeholders' on returning genomics research results to participants in Kenya. Methods This qualitative study involved focus group discussions (FGDs) and in-depth interviews (IDIs) with 69 stakeholders. The purposively selected participants, included research ethics committee (REC) members (8), community members (44), community resource persons (8), and researchers (9). A semi-structured interview guide was used to facilitate discussions. Six FGDs and twenty-five (IDIs) were conducted among the different stakeholders. The issues explored in the interviews included: (1) views on returning results, (2) kind of results to be returned, (3) value of returning results to participants, and (4) challenges anticipated in returning results to participants and communities. The interviews were audio-recorded, transcribed verbatim, and coded in Nvivo 12 pro. Thematic and content analysis was conducted. Results Participants agreed on the importance of returning genomic results either as individual or aggregate results. The most cited reasons for returning of genomic results included recognizing participants' contribution to research, encouraging participation in future research, and increasing the awareness of scientific progress. Other aspects on how genomic research results should be shared included sharing easy to understand results in the shortest time possible and maintaining confidentiality when sharing sensitive results. Conclusions This study identified key stakeholders’ perspectives on returning genomic results at the individual and community levels in two urban informal settlements of Nairobi. The majority of the participants expect to receive feedback about their genomic results, and it is an obligation for researchers to see how to best fulfil it.
Article
Geographical ancestry has been associated with an increased risk of various genetic conditions. Race and ethnicity often have been used as proxies for geographical ancestry. Despite numerous problems associated with the crude reliance on race and ethnicity as proxies for geographical ancestry, some genetic testing in the clinical, research, and employment settings has been and continues to be race‐ or ethnicity‐based. Race‐based or race‐targeted genetic testing refers to genetic testing offered only or primarily to people of particular racial or ethnic groups because of presumed differences among groups. One current example is APOL1 testing of Black kidney donors. Race‐based genetic testing raises numerous ethical and policy questions. Given the ongoing reliance on the Black race in genetic testing, it is important to understand the views of people who identify as Black or are identified as Black (including African American, Afro‐Caribbean, and Hispanic Black) regarding race‐based genetic testing that targets Black people because of their race. We conducted a systematic review of studies and reports of stakeholder‐engaged projects that examined how people who identify as or are identified as Black perceive genetic testing that specifically presumes genetic differences exist among racial groups or uses race as a surrogate for ancestral genetic variation and targets Black people. Our review identified 14 studies that explicitly studied this question and another 13 that implicitly or tacitly studied this matter. We found four main factors that contribute to a positive attitude toward race‐targeted genetic testing (facilitators) and eight main factors that are associated with concerns regarding race‐targeted genetic testing (barriers). This review fills an important gap. These findings should inform future genetic research and the policies and practices developed in clinical, research, public health, or other settings regarding genetic testing.
Chapter
The privacy concerns discussed in the 1990s in relation to the New Genetics failed to anticipate the relevant issues for individuals, families, geneticists and society. Consumers, for example, can now buy their personal genetic information and share it online. The challenges facing genetic privacy have evolved as new biotechnologies have developed, and personal privacy is increasingly challenged by the irrepressible flow of electronic data between the personal and public spheres and by surveillance for terrorism and security risks. This book considers the right to know and the right not to know about your own and others' genomes. It discusses new privacy concerns and developments in ethical thinking, with the greater emphasis on solidarity and equity. The multidisciplinary approach covers current topics such as biobanks and forensic databases, DIY testing, group rights and accountability, the food we eat and the role of the press and the new digital media.
Chapter
The privacy concerns discussed in the 1990s in relation to the New Genetics failed to anticipate the relevant issues for individuals, families, geneticists and society. Consumers, for example, can now buy their personal genetic information and share it online. The challenges facing genetic privacy have evolved as new biotechnologies have developed, and personal privacy is increasingly challenged by the irrepressible flow of electronic data between the personal and public spheres and by surveillance for terrorism and security risks. This book considers the right to know and the right not to know about your own and others' genomes. It discusses new privacy concerns and developments in ethical thinking, with the greater emphasis on solidarity and equity. The multidisciplinary approach covers current topics such as biobanks and forensic databases, DIY testing, group rights and accountability, the food we eat and the role of the press and the new digital media.
Chapter
The privacy concerns discussed in the 1990s in relation to the New Genetics failed to anticipate the relevant issues for individuals, families, geneticists and society. Consumers, for example, can now buy their personal genetic information and share it online. The challenges facing genetic privacy have evolved as new biotechnologies have developed, and personal privacy is increasingly challenged by the irrepressible flow of electronic data between the personal and public spheres and by surveillance for terrorism and security risks. This book considers the right to know and the right not to know about your own and others' genomes. It discusses new privacy concerns and developments in ethical thinking, with the greater emphasis on solidarity and equity. The multidisciplinary approach covers current topics such as biobanks and forensic databases, DIY testing, group rights and accountability, the food we eat and the role of the press and the new digital media.
Chapter
The privacy concerns discussed in the 1990s in relation to the New Genetics failed to anticipate the relevant issues for individuals, families, geneticists and society. Consumers, for example, can now buy their personal genetic information and share it online. The challenges facing genetic privacy have evolved as new biotechnologies have developed, and personal privacy is increasingly challenged by the irrepressible flow of electronic data between the personal and public spheres and by surveillance for terrorism and security risks. This book considers the right to know and the right not to know about your own and others' genomes. It discusses new privacy concerns and developments in ethical thinking, with the greater emphasis on solidarity and equity. The multidisciplinary approach covers current topics such as biobanks and forensic databases, DIY testing, group rights and accountability, the food we eat and the role of the press and the new digital media.
Article
Aim: This study aimed to determine knowledge and attitudes toward induced pluripotent stem cell technology and biobanking. Methods: A survey instrument was developed to determine individuals’ knowledge of and attitudes toward these technologies. Results: Results from 276 ethnically diverse participants who took the online survey demonstrated significant associations (p ≤ 0. 05) in knowledge by ethnicity and race regarding properties of stem cells, different types of stem cells and previous sample donation behavior. Significantly more Whites 39% (n = 53) compared with Blacks or African–Americans 19.2% (n = 14) had previous knowledge of induced pluripotent stem cells (χ ² = 8.544; p = 0.003) Conclusion: Overall, White race was associated with greater knowledge about stem cells and biobanks and greater willingness to donate samples for future research.
Article
Full-text available
The debate surrounding the role of life insurance, the necessity of risk rating, and the notion of “acceptable discrimination” has raised questions about the larger social role of insurance. Recent developments in the field of genetics, allowing insurers to make use of genetic testing technology as a new underwriting tool, have reinvigorated this debate. This article presents a comparative study of positions taken in countries on issues in genetics and life insurance. We will analyze the 43 selected countries and comment on their potential for ensuring a more equitable access for life insurance applicants.
Article
In view of the fact that for-profit enterprise exceeds public expenditures on genetic research and that benefits from the Human Genome Project may accrue only to rich people in rich nations, the HUGO Ethics Committee discussed the necessity of benefit-sharing. Discussions involved case examples ranging from single-gene to multifactorial disorders and included the difficulties of defining community, especially when multifactorial diseases are involved. The Committee discussed arguments for benefit-sharing, including common heritage, the genome as a common resource, and three types of justice: compensatory, procedural, and distributive. The Committee also discussed the importance of community participation in defining benefit, agreed that companies involved in health have special obligations beyond paying taxes, and recommended they devote 1–3% of net profits to healthcare infrastructure or humanitarian efforts.