Macklin

Science at the heart of medicine
Ruth Macklin, PhD
The Future of the Declaration of
Helsinki
Maintaining a leadership role in global health research
ethics
| 17/3/2012
What will the future be?
Sciencat the heart of medicine
• No crystal ball to guide predictions
• Ethics deals with what should be, not what will be the
case
| 27/3/2012
What should the DoH be?
• DoH has stood the test of time since its first skeletal
version in 1964 through many revisions and
amendments in almost 50 years
• DoH should remain relevant to changing
social circumstances and scientific advances
• DoH should be leading the way toward global justice in
health research
Sciencat the heart of medicine
| 37/3/2012
DoH 2008 and “standards”
• “Medical research is subject to ethical
standards that promote respect for all human
subjects and protect their health and rights”
(Paragraph 9)
> Noble statement but does not give specific guidance
> If the statement were amended to read equal respect
for all human subjects, it could be interpreted to
endorse a single global ethical standard
Scienceat the heart of medicine
| 47/3/2012
DoH 2008 and “standards”
• Physicians should consider the ethical, legal and
regulatory norms and standards for research
involving human subjects in their own countries as
well as applicable international norms and
standards (Paragraph 10)
> What follows from exhorting physicians to “consider” the
norms and standards?
• Anyone may “consider,” then reject norms
> Insufficient clarity to determine whether the Declaration calls for
a single international standard or can permit
“double” standards
Sciencat the heart of medicine
| 57/3/2012
| 67/3/2012
International standard: CIOMS guideline
• In externally sponsored research “…the ethical
standards applied should be no less stringent than they
would be for research carried out in [the sponsoring]
country”
– Guideline 3, Ethical Review of Externally Sponsored
Research
> Still not enough clarity on what constitutes “standards”
> But requires standards in developing countries to be
equal or equivalent to those in industrialized countries
Sciencat the heart of medicine
| 77/3/2012
Recent revisions of the DoH
• Weakened in some respects
• Strengthened in other respects
Sciencat the heart of medicine
| 87/3/2012
2000-2002 statement on post-trial obligations
• At the conclusion of the study, every patient
entered into the study should be assured of
access to the best proven prophylactic,
diagnostic and therapeutic methods
identified by the study.
Sciencat the heart of medicine
| 97/3/2012
Weakening the DoH: 2008
• At the conclusion of the study, patients entered into
the study are entitled to be informed about the
outcome of the study and to share any benefits that
result from it, for example, access to interventions
identified as beneficial in the study or to other
appropriate care or benefits (Para. 33)
> No clear obligation to provide beneficial interventions
> What other care is appropriate?
> What other benefits are appropriate?
> Who is under an obligation to share the benefits?
> Who should decide?
Sciencat the heart of medicine
| 107/3/2012
2002 paragraph on control groups
• A placebo-controlled trial may be ethically acceptable,
even if proven therapy is available, under the following
circumstances:
> Where for compelling and scientifically sound
methodological reasons its use is necessary to determine
the efficacy or safety of a prophylactic, diagnostic or
therapeutic method; OR
> Where a prophylactic, diagnostic or therapeutic method is
being investigated for a minor condition and the patients
who receive placebo will not be subject to any additional
risk of serious or irreversible harm.
Sciencat the heart of medicine
| 117/3/2012
Strengthening the DoH: 2008
• The benefits, risks, burdens and effectiveness of a new
intervention must be tested against those of the best
current proven intervention, except in the following
circumstances:
> The use of placebo, or no treatment, is acceptable in studies
where no current proven intervention exists; or
> Where for compelling and scientifically sound methodological
reasons the use of placebo is necessary to determine the
efficacy or safety of an intervention and the patients who
receive placebo or no treatment will not be subject to any risk of
serious or irreversible harm. Extreme care must
be taken to avoid abuse of this option
Sciencat the heart of medicine
| 127/3/2012
The way forward
• What’s missing from the current DoH?
> A paragraph addressing women in biomedical research
• Other leading international ethical guidance address
women
– CIOMS International Ethical Guidelines
– UNAIDS/WHO Guidance Document
> Community participation
• Community engagement before, during, and after
research concludes
– UNAIDS/WHO Guidance Document
Sciencat the heart of medicine
| 137/3/2012
Women in research
• Long history of excluding women from biomedical
research
• Current restrictions still exclude pregnant women from
most research not directed at pregnancy
• Potentially relevant paragraph in DoH
> Paragraph 5: Medical progress is based on research that
ultimately must include studies involving human subjects.
Populations that are under-represented in medical
research should be provided appropriate access to
participation in research
Sciencat the heart of medicine
| 147/3/2012
Example: CIOMS Guidelines 16 & 17
• Guideline 16 Women as research subjects
> Investigators, sponsors or ethical review committees
should not exclude women of reproductive age from
biomedical research. The potential for becoming pregnant
during a study should not, in itself, be used as a reason
for precluding or limiting participation….
• Guideline 17 Pregnant women
> Pregnant women should be presumed to be eligible for
participation in biomedical research….
Sciencat the heart of medicine
| 157/3/2012
Community engagement
• Current paragraph addressing communities
> 18. Every medical research study involving human
subjects must be preceded by careful assessment of
predictable risks and burdens to the individuals and
communities involved in the research in comparison with
foreseeable benefits to them and to other individuals or
communities affected by the condition under investigation.
• What more is needed?
Sciencat the heart of medicine
| 167/3/2012
Example: UNAIDS/WHO Guidance document
• Community Participation: Guidance Point 2
> To ensure the ethical and scientific quality and outcome of
proposed research, its relevance to the affected
community, and its acceptance by the affected
community, researchers and trial sponsors should consult
communities through a transparent and meaningful
participatory process which involves them in an early and
sustained manner in the design, development,
implementation, monitoring, and distribution of results of
biomedical HIV prevention trials
• This provision need not apply only to HIV
prevention trials
Sciencat the heart of medicine
| 177/3/2012
Conclusion
• The US FDA abandoned adherence to the DoH for
foreign studies
> The rest of the world still looks to the DoH as
the leading ethical guidance for research
• The World Health Organization’s Ethics Review
Committee is guided in its work by the Declaration of
Helsinki
• To remain timely and relevant, the Declaration of
Helsinki should remain at the forefront of international
ethical guidance for research involving
human beings
Sciencat the heart of medicine
| 187/3/2012
Global Justice in Health Research
Sciencat the heart of medicine