London_Post-trial_Access-London

Post-Study Arrangements
Alex John London, Ph.D.
Professor of Philosophy &
Director, Center for Ethics and Policy
Carnegie Mellon University
“Benefits” of Research
I. DoH 5: (Populations.) Access to research
connected to the benefit of improved care.
II. DoH 17: (Populations.) “results of
research” which could be new knowledge,
information, practices, interventions, or
profits.
III. DoH 33: (Participants.) Study findings
IV. DoH 14 & 33: (Participants.) Access to care
or other benefits.
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Research and Fairness
I. Research can overlap with, augment or supplant delivery of
health services to participants.
• Participants sometimes access improved standard of care
• Assume research related risks
• Care must be transferred back to providers after research.
II. Can reconfigure the way resources are used in a community
during and after research:
• Utilizes personnel, equipment, supplies, time, clinical space,
treatment, funding and other resources.
• Who benefits from this raises issues of equity and fairness
• Participants / non-participants
• Host countries / other countries
III. Has diverse connections to health system:
• Shapes provider practice and patient expectation.
• Affects entitlements.
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Integrity of a Social Good
I. From person-to-person relations to research as a
system of social interaction.
II. System in which diverse stakeholders, who may
have differing and even conflicting mandates,
pursue diverse interests and goals.
a. access to care
b. profit / personal advancement
c. scientific advance
d. improving standard of care
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An Adequate Research Ethics
III. Set terms under which diverse stakeholders can
participate in the research enterprise and be
assured that the pursuit of private or personal
interests does not compromise its ability to
produce the unique social good of new knowledge
and interventions that enable health systems to
better meet health needs of the people they serve.*
*London AJ. 2012. A Non-Paternalistic Model of Research Ethics and Oversight: Assessing
the Benefits of Prospective Review. Journal of Law, Medicine, and Ethics forthcoming.
*London AJ, Carlisle B and Kimmelman J. 2012. Rethinking Research Ethics: The Case of
Postmarketing Trials. Science 336 (May 4):544-545.
*London AJ. 2005. “Justice and the Human Development Approach to International
Research.” The Hastings Center Report 35(1):24-37.
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An Adequate Research Ethics
I. Secure the rights and welfare of participants.
• Traditional research ethics focus.
II. Safeguard the integrity and reliability of research from
various parochial interests.
• Registration, publication, and oversight.
III. Preserve the connection between research and the
health systems that rely on it for new knowledge
and interventions.
• Equity and fairness in resource use, access to research
(DoH 5), and improved health systems.
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Information as a Benefit
I. Treatment of information in the DoH has some exemplary
features. A model for interventions.
a. Recognized as a central benefit of research.
b. Emphasis on responsiveness and access.
c. Issues dealt with across the lifecycle of research.
d. Requirements identified related to preserving the integrity of
research.
1. Registration.
2. Publication, including negative findings.
e. Fuller range of stakeholders identified.
II. Access to other benefits—which may also be important—
should not eclipse the centrality of the connection between
research and health systems.
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Information Across the Research
Lifecycle
I. Access to research affects the ability of health systems to
improve care for populations (DoH 5).
II. Study should be relevant to the health needs and priorities of the
host community (DoH 17).
• Responsibility of: researchers, sponsors, and local / national
health authorities.
III. Trial publically registered (DoH 19)
• Responsibility of: Researchers and sponsors.
IV. Participants should be informed of study outcomes (DoH 33)
• Responsibility of: Researchers and sponsors.
V. Findings (including negative) should be published (DoH 30)
• Responsibility of: researchers and sponsors, editors.
VI. Information should be integrated into health practices and
policies.
• Responsibility of: Local and national health authorities with
assistance from sponsors or other development entities.
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Suggested Language Para 5.
New text is in italics:
Medical progress is based on research that ultimately
must include studies involving human subjects. Research
should be designed and conducted in ways that do not
degrade, and are likely to enhance, the capacity of local
and national health institutions to provide equitable
access to effective health services. Populations that are
underrepresented in medical research should be provided
appropriate access to participation in research.
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Rationale
• Explicitly connects access to research with
improvements in health systems.
• Assurance that research will not be
conducted in ways that leave communities
worse off.
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Suggested Language Para 17
Medical research involving a disadvantaged or
vulnerable population or community is only
justified if the research is responsive to the
health needs and priorities of this population or
community and if there is a reasonable
likelihood that this population or community
stands to benefit from the results of the
research. from the knowledge, practices, or
interventions that result from the research.
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Rationale
• 5 & 17: communities should reasonably
expect to benefit from research via the
questions it addresses and the interventions
it assesses.
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Suggested Language Para 14
…The protocol should describe arrangements
for post-study access by study subjects to
interventions identified as beneficial in the
study or access to other appropriate care or
benefits. This information should also be
disclosed to participants during the informed
consent process.
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Suggested Language Para 33
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.
I agree with the Macklin’s proposed revisions to paragraph 33:
“In advance of a clinical trial, sponsors, researchers, and
host-country governments should make provisions for post-
trial access for all participants who still need an intervention
identified as beneficial in the study. All study participants
should be informed about the outcome of the study.”
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Participant Welfare
I. When researchers and sponsors assume
responsibility for participant care, they assume
some fiduciary responsibilities to participants.
II. The force of responsibility may vary according
to:
a. Severity of the health consequences for
participants and others (e.g., drug resistance).
b. The ease of transitioning the care of participants to
another provider (e.g., the local or national health
system).
c. The availability of the intervention or adequate
alternatives.
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Appropriate Continuity of Care
III. When participant health requires
continuing treatment, researchers,
sponsors, and local health authorities have
a duty to ensure appropriate continuity of
care.
IV. This should normally be understood as a
duty of researchers and sponsors to
facilitate continued provision of care until
that responsibility can be discharged within
the relevant local or national health system.
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Justice and Equity
IV. Equitable provision of health services is the
function of the health system.
a. Prior to regulatory approval or sale, sponsors
may need to facilitate access to study
interventions.
V. In low-resource settings, inequitable
resource allocation in the health system
may result if disproportionate share of host
community resources are diverted to fulfill
post-trial obligations to participants.
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Justice and Equity
VI.Sponsors, researchers, and host
governments should negotiate
mechanisms to avoid inequitable
resource allocation in under-
resourced settings.
a. Pricing / licensing
b. Funding commitments
c. Partnerships
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Conclusion
• Communities should reasonably expect
research:
• to address questions and study
interventions that are likely to expand the
capacity of their health institutions to meet
community health needs.
• To be carried out in a way that improves
capacity of health institutions.
• Participants should reasonably expect:
• Respect for their rights and welfare.
• Appropriate continuity of care.
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