S5-3 Glasa DoH Vatican

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POST-TRIAL ACCESS
AND THE DECLARATION OF HELSINKI
Clinical Researcher’s & Patients’ View
Prof. Jozef Glasa, MD, PhD2
DCP FM & IHCE FNPHS SMU in Bratislava (Slovakia)
EF GCP, EUPATI, CDBIO, PAL, EACPT
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Conflict of Interest Declaration
Nothing to declare.
————————————-
N.B.
A strong, long-lasting professional and
personal interest in the topics covered
in this presentation.
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Overview
• definitions
• evolution of DoH language (1964 – 2013)
• scope of the post-trial access
• stakeholders in the post-trial access
• benefits/risks/burdens of a subject’s participation in biomedical
research/clinical trials
(in low resource settings)
• benefits/burdens/risks of a physician’s/other health
professional’s participation in biomedical research/clinical trials
(in low resource settings)
• responsible (bio)medicine
• conclusions
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Post-trial access, Low-resource settings research
Definitions
• post-trial access – access to IMP (investigational medicinal product) to the
subjects after completion of their participation in a clinical trial (research)
• post-trial access provision – two main options:
ü open-label extension trials: extensions of the original clinical trial, where
patients who participated in the trial are given continued access to the IMP
under an open-label condition
ü expanded access programs: separate programs that provide access to the IMP
outside of the clinical trial setting, typically to patients who do not meet the
inclusion criteria for the trial but have a serious or life-threatening condition
for which there is no other satisfactory treatment
• low-resource settings research: research conducted in regions, where inadequate
healthcare resources exist and the healthcare system does not meet the acceptable
global standards
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Evolution of DoH language (1964 – 2013)
• 2000 (Edinburgh)
• 8. Some research populations are vulnerable and need special protection. The particular
needs of the economically and medically disadvantaged must be recognized.
• 30. 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.
• 2004 (Tokyo)
• 2Note of clarification on paragraph 30 of the WMA Declaration of Helsinki.
The WMA hereby reaffirms its position that it is necessary during the study planning
process to identify post-trial access by study participants to prophylactic, diagnostic
and therapeutic procedures identified as beneficial in the study or access to other
appropriate care. Post-trial access arrangements or other care must be described in the
study protocol so the ethical review committee may consider such arrangements during
its review.
• 2008 (Seoul)
• 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.
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Evolution of DoH language (1964 – 2013)
• 2008 (Seoul)
• 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.
• 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.
• 2013 (Fortaleza)
• 13. Groups that are underrepresented in medical research should be provided appropriate
access to participation in research.
• 19. Some groups and individuals are particularly vulnerable and may have an increased
likelihood of being wronged or of incurring additional harm. All vulnerable groups and
individuals should receive specifically considered protection.
• 20. Medical research with a vulnerable group is only justified if the research is responsive to
the health needs or priorities of this group and the research cannot be carried out in a non-
vulnerable group. In addition, this group should stand to benefit from the knowledge,
practices or interventions that result from the research.
• 34. 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 trial. This information must also be disclosed to participants
during the informed consent process.
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Scope of the post-trial access
• scope of what goes to the trial: HEALTH TECHNOLOGIES
► medicaments, medical devices, in vitro diagnostics
► other, e.g., IT, AI applications, telemedicine, digital health, nursing procedures,
novel diets, new materials, instruments, appliances, etc.
→ scope of the post-trial access
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PHYSICIANs, HEALTH
PROFESSIONALs
CAREGIVERS
HEALTH CARE
PROVIDERS
RESEARCHERS,
RESEARCH
ORGANIZATIONS
PAYERS
(e.g., health insurance
companies)
INDUSTRY
ELSI issues,
solutions
(e. g., ethics codes, guidelines,
regulations, policies, etc.)
COMPETENT
BODIES
PATIENTs
TRIAL
SPONSORS
REGULATORS
(parliaments,
governments)
PATIENTs’
RELATIVES
PATIENTs’
ORGANIZATIONS
[(unmet) needs, benefits, burdens, risks, harms, damages, competing) interests, conflicts, etc.]
Stakeholders in the post-trial access
RESOURCES
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Advantages and Disadvantages of Post-Trial Access Solutions
Criterion Open-label extension trials Expanded access programs
Definition An extension of a clinical trial in which all
participants receive the investigational
medicine product (IMP), usually after the
placebo-controlled phase was completed.
A program that provides access to an IMP
to patients who do not qualify for a
clinical trial or have completed a trial.
Advantages for sponsors Enables collection of long-term safety and
efficacy data, can potentially lead to
FDA/EMA approval, helps to retain
participants in the study.
Provides an alternative mechanism for
patients who do not qualify for a clinical
trial, generates real-world safety and
efficacy data, and can build goodwill with
patient communities.
Advantages for patients Provides access to an IMP, which may have
benefits for their health, and ensures
continued monitoring and follow-up.
Provides access to an IMP, which may
have benefits for their health, and allows
patients to contribute to research efforts.
Disadvantages for sponsors May be costly and time-consuming to
conduct and may not always lead to
regulatory approval or iincreased market
share.
May be logistically challenging to set up
and manage, may not be financially
sustainable, and may generate data that
is difficult to interpret.
Disadvantages for patients Patient may be required to continue to
comply with the study protocol, which may
include frequent visits to the study site/and
or regular monitoring, and they may not
have access to the IMP after the study ends.
Patients may not qualify for this program,
and even if they do, there is no
guarantee that the IMP will have benefits
for their health.
According to Volkov D. (2023) https://www.linkedin.com/pulse/choosing-right-path-key-considerations-sponsors-access-den-volkov/
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Responsible (bio) medicine
• responsibility to:
• patient, his/her relatives, friends, ‘important ones’,…
• society (incl. future generations and the ‘Mankind’)
• environment (incl. biodiversity,…)
• own profession (professional standards, ethics…)
• efficacy, safety, effectiveness, sustainability, accessibility,
affordability, etc.
• ‘old’ and ‘new’ roles and goals in community and society
• ethical-moral, social values – protection, development
• misuse/abuse – prevention, detection, adequate addressing
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Giordano, Luca (1632-1705) The Good Samaritan, 1685, Musée des Beaux-Arts, Rouen
How to become, in a personal (and institutional) manner, the „Good Samaritans“,
bringing and adequate help, treatment, and care to the needy ones
in our very complex, dynamically developing (or degenerating (?)) World ?
Source: Wikimedia
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Conclusions
• in post-trial access solutions, the present scope of health technologies tested
should be considered (incl. the applicable results of HTA – Health Technology
Assessment)
• in post-trial access solutions, the needs, rights, legitimate interests of all relevant
stakeholders should be considered and appropriately balanced
• in addressing post-trial access issues, effective procedures should be put in place
to enable adequate dialogue and solutions finding process involving, without
unjust discrimination, all the respective stakeholders
• the roles of research ethics committees and of the national competent authorities
in dealing with the post-trial access issues should be strengthened and enabled
• the development and implementation of adequate national legislation and
guidance on post-trial access should be encouraged, promoted (and required)
worldwide, with a special attention to vulnerable and disadvantaged individuals,
groups and communities, and to the low resource settings
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Thank you for your attention!
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