Draft Policy Recommendations Self-directed Interactive Review
Category 2: Researchers - Protocols
These policy recommendations primarily affect how clinical trials are designed, approved and
implemented to ensure the inclusion of traditionally underrepresented populations.
Section 1: Institutional Review Boards
Background:
Institutional Review Boards (IRBs) are often referred to as "gatekeepers" for the conduct
of biomedical research involving human subjects. They are federally mandated under the
National Research Act of 1974 and 45 C.F.R. § 46 et seq. Virtually all research involving
human subjects, whether publicly or privately sponsored, must earn IRB approval.
Unfortunately, IRBs often lack the training needed to recognize how disparities may
manifest themselves in a research protocol and what the scientific and ethical implications of
those disparities might be. For example, they may be ill prepared to review a research protocol
with a complete understanding of the extent to which disparities may affect the enrollment of a
diverse cohort of participants that includes underrepresented populations. Moreover, the
Belmont Report (link to relevant section of Belmont Report, indicates that justice, construed primarily
as fairness in subject selection, is a key principle in rendering human subjects research ethical.
IRBs are indispensable in invigorating this third principle of the Report.
Policy Recommendation 1: Disparities Training/AAHRPP
Because education of IRBs is crucial to ameliorating disparities in clinical trials, the EDICT Team recommends:
(a) The Association for the Accreditation of Human Protections Programs (AAHRPP)
includes the requirement that IRBs receive training in health care disparities and
clinical trials in order to qualify for accreditation.
Rationale behind this recommendation:
Despite the criticism directed at the IRB system in the past few years, it nevertheless
remains an integral player in clinical research for the simple reason that no protocol involving
human subjects may be conducted without IRB approval. While privately-sponsored clinical
research is often excluded from statutory and regulatory requirements that govern research
funded with public monies, all research involving human subjects must receive IRB approval
under 45 C.F.R. § 46 et seq.
Because IRBs act as gatekeepers for clinical research, their awareness of the widespread
disparities in clinical trials is crucial. If IRBs are unaware of the scope of the problem as to
disparities, they are unlikely to exercise their authority in ways that will ameliorate disparities in
clinical trials. IRBs themselves serve an educative function in some sense inasmuch as they
by necessity educate investigators and research teams on the ethical and legal requirements for
permissible human subjects research. Educating IRBs on the scope of the problem of disparities
and on ways of increasing participation by underrepresented populations is therefore a way of
simultaneously educating academic health center administrations, commercial funders of clinical
research, and central or commercial review boards.
As to AAHRPP, it is a fairly new organization that has, as its founding members, credible
and influential organizations who support the accreditation of IRBs (e.g., AAMC, FASEB, etc.).
The AAHRPP has accredited a significant number of IRBs all over the world, including
academic and commercial review boards (thereby reflecting the global character of clinical
research). The AAHRPP conducts site visits and evaluations to reinforce its accreditation
policies.
Accordingly, if the AAHRPP were to adopt accreditation standards relating to disparities
in clinical trials, it could have significant impact in educating both IRBs and other major players
(academic health centers, investigators, private sponsors, etc.) on the issue of disparities. Such
awareness is a necessary first step to ameliorating disparities in clinical trials.
Policy Maker Focus: The Association for the Accreditation of Human Research Protection
Program (AAHRPP) (link to AAHRPP, http://aahrpp.org/www.aspx), the accreditation body for
IRBs both in the U.S. and globally.
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Policy Recommendation 2: Disparities Training /OHRP
Because education of IRBs is crucial to ameliorating disparities in clinical trials, the EDICT Team recommends:
(b) The Office of Human Research Protections (OHRP) issue policy guidance
materials designed to enhance IRBs knowledge as to inclusion of
underrepresented populations in clinical trials.
Rationale behind this recommendation: same as for previous recommendation plus the following
Because AAHRPP accreditation is currently voluntary, federal involvement could prompt
key policyholders to move swiftly in making mandatory IRB training on disparities in clinical
trials. As such, there is a role for OHRP to play in setting policy on this issue. Issuance of
OHRP-sponsored materials designed to train IRBs on disparities in clinical trials is a key
component of policy change as to IRBs.
Policy Maker Focus: The Office of Human Research Protections (OHRP), the federal body most directly involved with IRB oversight.
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Section 2: Pharma/Industry Trials
Background:
For some time, there has been concern with disparities in the representation of
underrepresented populations in clinical trials. Given that conducting high-quality clinical trials is an
enormous task, implementing programs designed to ameliorate these disparities has proven
difficult for research sponsors throughout the clinical trials paradigm. As the driving force for
75% of human subjects research conducted around the world, pharmaceutical and biotechnology
companies are exceptionally positioned to institute measures designed to ensure appropriate
representation in clinical trials.1
We note that the efforts that have been made in pediatric studies have resulted in a sea
change in how the clinical programs are designed. We believe that the same kind of beneficial
effect can be obtained by a focus on underrepresented populations.
Policy Recommendation 1: Assessment
Because the elimination of disparities in clinical trials is good ethics, good science, as well as
good business, the EDICT Team recommends that industry sponsors adopt policies to ensure that
decisions to implement clinical trials will include:
(1) Assessment of whether a given intervention is targeted to the general population or to
specific subgroups within the general population.
Rationale behind this recommendation:
A commitment to evidence-based medicine requires being able to define what counts as
better evidence and why. The team believes that evidence from clinical trials that has
representation based on disease prevalence is superior to evidence from trials that lack such
representation.2 As a recent Endocrine Society White Paper put it, clinical trial data based on
studies that lack appropriate representation cannot be presumed to be applicable to "all the key
ethnic minorities who suffer a higher burden of these diseases . . . ."3 "Scientifically, it makes no
sense to develop new treatments among populations of patients who are different from those who
will be using them." 4
In general, the clinical trial should provide evidence of applicability of the intervention
across the entire patient population. In other cases, a clinical trial is designed to provide
evidence of the effect of an intervention in a specific target population (whether identified by
race, ethnicity, gender, disability status, or age). Therefore, clinical trials with diverse
representation assure better scientific evidence, which can then be translated into better clinical
practice, and greater benefit to the public.
The EDICT Team recognizes that industry-sponsored clinical trials reflect the realities of
globalization. However variations in environment, habits, practices, lifestyle, genetics, nutrition,
etc. have the potential to impact responses to medical interventions. Accordingly, inclusion of
under represented populations from any specific state, country, or region may not provide crucial
information regarding how a given intervention will affect underrepresented communities
within the U.S. The EDICT Team also recognizes that race is a social concept with no essential
biological definition. Despite the global character of clinical research, the best evidence of how
a given intervention will work within the American population comes from clinical trials in
which the diversity of America is well represented.
Ultimately, pharmaceutical and biotechnology companies are critical to the success of the
overall project to reduce disparities in clinical trials. These sponsors have the authority and the
means to mandate representation that can eliminate such disparities.
Policy Maker Focus: Industry sponsors of clinical trials
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Policy Recommendation 2: Appropriate Representation
Because the elimination of disparities in clinical trials is good ethics, good science, as well as
good business, the EDICT Team recommends that industry sponsors adopt policies to ensure that
decisions to implement clinical trials will include:
(2) Requirements of investigators that the subject population include members of
underrepresented communities that correspond to the proportions such communities comprise in the targeted population;
Rationale behind this recommendation: same as those for other pharma/industry recommendations
Policy Maker Focus: Industry sponsors of clinical trials
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Policy Recommendation 3: Investigator Diversity
Because the elimination of disparities in clinical trials is good ethics, good science, as well as
good business, the EDICT Team recommends that industrial sponsors adopt policies to ensure
that decisions to implement clinical trials will include:
(3) Development and selection of investigators with the capability of achieving diversity
of inclusion based on the population served.
Rationale behind this recommendation: same as those for other pharma/industry recommendations
Policy Maker Focus: Industry sponsors of clinical trials
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Policy Recommendation 4: Return on Community Investment
Because the elimination of disparities in clinical trials is good ethics, good science, as well as
good business, the EDICT Team recommends that industrial sponsors adopt policies to ensure
that decisions to implement clinical trials will include:
(4) Requirement that clinical trial plan takes account of how the communities affected
will receive information and other benefits as a result of the trial.
Rationale behind this recommendation: same as those for other pharma/industry recommendations
Policy Maker Focus: Industry sponsors of clinical trials
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1 See, e.g., General Accounting Office, NIH Clinical Trials: Various Factors Affect Patient Participation 1, 4 (1999),
available at http://www.gao.gov/archive/1999/he99182.pdf (last accessed August 18, 2007); see also Hamilton
Moses III, E. Ray Dorsey, David H. Matheson, and Samuel O. Thier, Financial Anatomy of Biomedical Research,
294 JAMA 1333, 1335 (2005).
2 See, e.g., J.G. Ford, et al., Knowledge and Access to Information on Recruitment of Underrepresented
Populations to Cancer Clinical Trials, Evidence Report: Technology Assessment (Summary), 2005(122):
p. 1-1l; Giselle Corbie-Smith, William C. Miller, and David Ransohoff, Interpretations of 'Appropriate' Minority
Inclusion in Clinical Research, 116(4) AM. J. MED. 249, 251 (2004); National Heart Lung and Blood Institute/NIH.
Questions and Answers on Inclusion of Minorities and Women in Study Populations. 2002. Available from:
http://www.nhlbi.nih.gov/funding/policies/nhlbigui.htm.
3 The Endocrine Society, White Paper: Increasing Minority Representation in Clinical Trials, at 3, 8 (2007).
4 Ibid.
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