DoH for GA Keynote Oct 2024 Helsinki v1

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The Declaration of Helsinki
Proposed Revisions 2024
WMA General Assembly
Helsinki, Finland
October 2024
Jack Resneck, Jr., MD
Former President, American Medical Association
Chair of Finance and Planning, World Medical Association
Chair, WMA Declaration of Helsinki Workgroup
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The Declaration of Helsinki
The First Set of International Principles Guiding Medical Research involving
Human Participants
…and A Prominent Pillar in the WMA’s Seminal Ethical Documents
• Declaration of Geneva (1948)
• Pledge outlining basic ethical principles for physicians
• The International Code of Medical Ethics (ICoME) (1948)
• Ethical principles defining professional duties of physicians
• Declaration of Helsinki (DOH) (1964, 60 years ago)
• Ethical principles for medical research involving human subjects/participants
• Declaration of Tokyo (1975)
• Guidelines for Physicians Concerning Torture and other Cruel, Inhuman or Degrading
Treatment or Punishment in Relation to Detention and Imprisonment
• Declaration of Lisbon (1982)
• Rights of the Patient
• Declaration of Taipei (2016)
• Ethical considerations regarding health databases and biobanks
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• World Health Organization (WHO) Guidance for Best Practices
• Council for International Organizations of Medical Research (CIOMS)
• International Conference for Harmonization (ICH) Good Clinical Practice
(GCP) Guideline
• Regulation 536/2014 of the European Parliament on Clinical Trials
• UNESCO Universal Declaration on Bioethics and Human Rights
• US Belmont Report of 1979
• US Subpart A of 45 CFR Part 46 (Common Rule): no specific reference
• Codified in many national laws / regulations
The DoH in Context
An Important Set of High-Level Principles Referenced by many
International Bodies and by More Granular Guidelines
© 2024 American Medical Association. All rights reserved.
The DoH as a Living Document
1954 • Resolution on Human Experimentation endorsed by WMA
1961 • Draft Code on Human Experimentation by WMA Cmte on Med Ethics published in BMJ
1964 • Declaration of Helsinki Adopted
1975 •Tokyo: Ethics committees, Research protocols, Environment, Animal use
1983 •Venice
1989 •Hong Kong
1996 •Somerset West: Limited placebos to when no proven therapy exists
2000 •Edinburgh: Test against best current, Post-trial Access, Vulnerable Populations, Monitoring
2002 •Washington: Clarification on Placebos (compelling methodological reasons, minor conditions)
2004 •Tokyo: Clarification on Post-Trial Access (considered, not required)
2008 •Seoul: Trial registration, dissemination of results
2013 •Fortaleza: New structure, stronger protection for vulnerable groups, compensation for harm
2024 •Helsinki: (in progress)
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Why Revise?
• Some argue ethical principles should be timeless
• Sustaining relevance requires the Declaration evolve as
• Evidence of new risks/harms comes to light
• Research enterprise presents new challenges
• Society Advances
• Stresses and tensions are inherent as ethical principles
sometimes collide and resonate differently across
cultures/geographies
• Openly wrestling with them is essential
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The 2024 Revisions
A 30-month, Thorough, Inclusive Process
• WMA Council established Working Group in April 2022
• 19 Countries and Associate WMA members represented, plus many invited
bioethics expert advisors
• Smaller Drafting Group also engaged
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• Associate Members: Syed
Hussain, Natalia Solenkova,
Anthea Mowat
• Bangladesh: Jamal Chowdhury
• Belgium: Vincent Lamy
• Brazil: Carlos Serrano
• China: Yuguang Huang, Yali
Cong, Haihong Zhang
• Denmark: Camilla Rathcke,
Jeppe Berggreen Hoj, Katrine
Krause-Jensen
• Finland: Janne Aaltonen, Mervi
Kattelus
• Germany: Ramin Parsa-Parsi
• Israel: Leah Wapner, Malke
Borrow
• Japan: Hidehito Imamura
• Malaysia: Ashok Philip, Azizan
binti Abdul Aziz
• Netherlands: Rene Heman,
Krista Tromp, Antina De Jong
• Nigeria: Joan Emien Enabulele
• South Africa: Mvuyisi Mzukwa
• Taiwan: Brian Chang, Daniel Tsai
• UK: Dominic Norcliffe-Brown,
Julian Sheather
• Vatican: Pablo Requena
• Uruguay: Alarico Rodriguez
• USA: Jack Resneck
• Bioethics Advisors: Dominique
Sprumont, Hans Van Delden,
Urban Weising, Amber Comer,
Elliott Crigger, Jake Young
• WMA Staff: Otmar Kloiber,
Sunny Park, Julia Tainijoki
• AMA Staff: Beth LaRocca,
Hannah Longstaff
© 2024 American Medical Association. All rights reserved.
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The 2024 Revisions
A 30-month, Thorough, Inclusive Process
• WMA Council established Working Group in April 2022
• 19 Countries and Associate WMA members represented, plus many invited
bioethics expert advisors
• Smaller Drafting Group also engaged
• Regional and Topical Meetings Across the Globe to Gather Feedback
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Regional and Topical Meetings
• Tel Aviv: Implications of Big Data, Machine Learning, AI
• São Paulo: Ethical Considerations on Use of Placebo
• Copenhagen: Emerging Trial Designs
• Tokyo: Research During Public Health Emergencies /
Pandemics
• Vatican: Research in Resource-Poor Settings, Global Justice
• Johannesburg: Community Inclusiveness, Post-Trial Access,
Vulnerability
• Munich: Specific and Particularly Vulnerable Groups
• Washington, DC: Final Consolidation
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The 2024 Revisions
A 30-month, Thorough, Inclusive Process
• WMA Council established Working Group in April 2022
• 19 Countries represented (including Associate WMA members), plus many
invited bioethics expert advisors
• Smaller Drafting Group also engaged
• Regional and Topical Meetings Across the Globe
to Gather Feedback
• Public Comment Periods
• Phase 1 Occurred last winter
• Phase 2 Occurred earlier this summer
© 2024 American Medical Association. All rights reserved.
Key Revisions Proposed for 2024
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Participant and Community Engagement
• Replaced subjects with participants throughout the DoH out of respect
for the rights, agency, and importance of those individuals
• Recognizes that participants may include patients and healthy
volunteers
• New language in ¶6 demands “meaningful engagement with potential
and enrolled participants and their communities … before, during, and
following medical research” in recognition of study participants as
partners in co-creation.
• Specifically sharing priorities/values, participating in study
design/implementation, engaging in understanding/disseminating results
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WMA Urging DoH to be Broadly Upheld
• New language in ¶2 states that “these principles should be upheld by all
individuals, teams, and organizations involved in medical research, as
[they] are fundamental to respect for and protection of all research
participants….”
• Language in many paragraphs now addresses “physicians and other
researchers”
• While some question the WMA’s authority to address nonphysicians, the
Declaration is more than solely an exercise in self-regulation
• The medical profession’s morals and broader ethics include a duty to ensure
respect for the health, dignity, integrity, autonomy, and privacy of research
participants, no matter who is performing the research
• New ¶8: Essential to uphold DoH principles during public health
emergencies
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Distributive and Global Justice
• New language in ¶6 calls on researchers to “carefully consider how the
benefits, risks, and burdens of research are distributed.”
• Also recognizes that medical research enterprise does not have the capacity
or bear sole responsibility to resolve all structural inequities
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Purposes of Medical Research
• Contemplated adding “social value” to revised ¶7
• but there was public concern with vagueness and different interpretations
across cultures
• Instead added that new knowledge generation, in addition to
furthering understanding of diseases and improving interventions,
should ultimately “advance individual and public health.”
• Retained existing language about those purposes never taking
“precedence over the rights and interests of individual research
participants”
• Does not negate the fact that participants, with freely given informed
consent, often make benevolent choices to take risks for the good of
others with minimal expectation of personal benefit
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Vulnerability
• Rewritten ¶19 Recognizes that:
• individuals, groups, and communities may be in situations of vulnerability due to
factors that may be fixed or contextual and dynamic.
• their default exclusion from medical research has resulted in enormous gaps in
medical knowledge and can potentially perpetuate or exacerbate disparities.
• Requires that “the harms of exclusion must be considered and weighed
against the harms of inclusion”
• Calls for fair and responsible inclusion with specially considered support
and protections
• Rewritten ¶20 retains additional protections for some particularly vulnerable
groups.
• Responsive to their health needs/priorities
• Stand to benefit
• Cannot be carried out in non-vulnerable (unless exclusion perpetuates or
exacerbates disparities)
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Scientific Requirements
• ¶21 newly calls out importance of scientific rigor to avoid research
waste
• New language in ¶12: “Scientific integrity is essential in the conduct of
medical research involving human participants. Involved individuals,
teams, and organizations must never engage in research misconduct.”
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Research Ethics Committees
• ¶23 specifies need for ethics committees to have
• Adequate “independence and authority to resist undue influence”
• “Sufficient resources to fulfill its duties”
• “Adequate education, training, qualifications, and diversity” among its
members and staff
• At least one public member and “familiarity with local circumstances and
context”
• Authority to “withdraw approval and suspend ongoing research”
• Inclusion of ethics review in both sponsoring and host countries when
collaborative international research is performed
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Growing Use and Risks of Personal
Data Stored After Trials
• Complete rewrite of ¶32
• Calls for free and informed consent for the “collection, processing, storage,
and foreseeable secondary use of biological material and identifiable or re-
identifiable data,” and for ethics committee approval and monitoring of such
databases and biobanks.
• Cross-references the WMA DoT’s more detailed guidelines on rights of
individuals and principles of governance for health databases and biobanks
• Pertains to data collected “from research participants for multiple and indefinite
uses” beyond the clinical care of individual patients”
• Acknowledges that consent for unanticipated secondary research on
stored data is sometimes impossible or impracticable to obtain – but requires
ethics committee consideration and approval of such unforeseen uses.
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Use of Placebo
• Maintenance of balanced language in ¶33 limiting use of placebo or
no intervention, or control groups using anything other than best
proven intervention(s).
• Amendment was considered broadening use of placebo to when no
“proven safe and effective intervention exists”
• Ultimately rejected after extensive consultations
• São Paolo regional DoH meeting with participants from >10 countries in
WMA’s Latin American region, and leaders from CONFEMEL and the Pan-
American Health Organization
• Feedback from CONFEMEL
• Focused session on DoH revisions at the World Conference in Bioethics in
Brasília
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Other Revised Principles
• Strengthening post-trial provisions in ¶34
• Must be arranged for participants who still need intervention identified as
beneficial and reasonably safe in a trial
• Recognition that access can be provided by researchers, sponsors,
healthcare systems, or governments
• Exceptions allowed but require ethics committee approval
• ¶28/29: When seeking informed consent from legally authorized
representative, must consider the preferences and values expressed by
the potential participant
• ¶37: Use of unproven interventions (compassionate use) must never be
undertaken to circumvent the protections for research participants
• Strengthened ¶11: “Medical research should be designed and conducted
in a manner that avoids or minimizes possible harm to the
environment and strives for environmental sustainability.”
© 2024 American Medical Association. All rights reserved.
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The 2024 Proposed Revisions
• Emerged from inclusive and lengthy worldwide stakeholder
engagement
• Entail substantial changes to address a rapidly innovating
research ecosystem and enhance future relevance
• Maintain brevity while some thirst for specificity
• Meaningfully renew this seminal ethical document that demands
respect for and protection of all medical research participants
© 2024 American Medical Association. All rights reserved.
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• Associate Members: Syed
Hussain, Natalia Solenkova,
Anthea Mowat
• Bangladesh: Jamal Chowdhury
• Belgium: Vincent Lamy
• Brazil: Carlos Serrano
• China: Yuguang Huang, Yali
Cong, Haihong Zhang
• Denmark: Camilla Rathcke,
Jeppe Berggreen Hoj, Katrine
Krause-Jensen
• Finland: Janne Aaltonen, Mervi
Kattelus
• Germany: Ramin Parsa-Parsi
• Israel: Leah Wapner, Malke
Borrow
• Japan: Hidehito Imamura
• Malaysia: Ashok Philip, Azizan
binti Abdul Aziz
• Netherlands: Rene Heman,
Krista Tromp, Antina De Jong
• Nigeria: Joan Emien Enabulele
• South Africa: Mvuyisi Mzukwa
• Taiwan: Brian Chang, Daniel Tsai
• UK: Dominic Norcliffe-Brown,
Julian Sheather
• Vatican: Pablo Requena
• Uruguay: Alarico Rodriguez
• USA: Jack Resneck
• Bioethics Advisors: Dominique
Sprumont, Hans Van Delden,
Urban Weising, Amber Comer,
Elliott Crigger, Jake Young
• WMA Staff: Otmar Kloiber,
Sunny Park, Julia Tainijoki
• AMA Staff: Beth LaRocca,
Hannah Longstaff