S4-2_Andreas Reis

Strengthening research ethics oversight: the work of WHO
Dr Andreas Reis, PD, MD, MSc
Co-Unit Head, Health Ethics & Governance,
Department of Research for Health, WHO Geneva
Outline
⚫ Background
⚫ Research ethics during emergencies: Key WHO documents & actions
⚫ WHO’s work on capacity building in research ethics:
Tool for Benchmarking Ethics Oversight of Health-Related Research
⚫ Conclusion
Background
13th Global Programme of Work, WHO
⚫ 2019-2024
⚫ ambitious programme,
structured around three
interconnected strategic
priorities to ensure
healthy lives and well-
being for all at all ages
⚫ Ethics a key component
Ethics at the heart of GPW
“…WHO must continue to ensure that policy-makers and health implementers – both at
the international and at the national level − keep ethics at the heart of their decision-
making. By focusing on individual values such as human dignity, and respect; by bringing
in the language of obligations and responsibilities; and by advocating at a national and
global level for solidarity, reciprocity, and mutual understanding amongst other values,
WHO can foster trust, improve transparency, and enhance accountability. WHO will work
to ensure that all policies, public health interventions and research are grounded in
ethics……..”
Thirteenth Global Programme of Work (2019-2024)
WHO & Global Health Ethics
“WHO’s normative guidance will
be informed by developments at
the frontier of new scientific
disciplines such as genomics,
epigenetics, gene editing,
artificial intelligence, and big
data, all of which pose
transformational opportunities
but also risks to global health.”
WHO Clinical Trials Resolution (2022)
… Underscoring that clinical trials should be
health-needs driven, evidence based, well designed
and well implemented and be guided by
established ethical guidance, including principles
of fairness, equity, justice, beneficence and
autonomy; and that clinical trials should be
considered a shared responsibility;
…to support ethics committees and
regulatory authorities to enable
efficient governance processes to
focus on the fundamental scientific
and ethical principles that underpin
randomized controlled trials…
Research ethics during emergencie
Key WHO documents & actions
Outbreaks: WHO guidance on ethical issues
– Ethical Standards for Research
During Public Health Emergencies:
Distilling Existing Guidance to
Support COVID-19 R&D
– Emergency Use Designation of
COVID-19 candidate vaccines:
Ethical considerations for current
and future COVID-19 placebo-
controlled vaccine trials and trial
unblinding
– Key Criteria for the Ethical
Acceptability of COVID-19 of
Human Challenge Studies
– Guidance for Research Ethics
Committees for Rapid Review of
Research During Public Health
Emergencies
09/09/2020
| Beyond the Rhetoric: Key ethical issues and outputs in COVID-
10
Ethics of COVID-19 Research – WHO Ethics Guidance
Rapid review of research
during public health
emergencies (SOPs)
25/10/2020 | Rapid Ethics Review in Pandemics 11
WHO guidance for research ethics committees
▪ Guidance to be implemented on declaration of emergency
▪ Aim: accelerate study commencement
▪ Virtual meetings and processes
▪ Language considerations – core documents in the official language of the
reviewing country
▪ 20 recommendations to facilitate rapid review
Guidance for research ethics committees for rapid review of research during public health emergencies
12
⚫ Source: WHO (2020) https://www.who.int/publications/i/item/9789240006218
WHO emergency SOPs
• – Checklist of items & additional documents to facilitate fast-tracking of
outbreak related research – study structure, oversight, data-sharing plan and
MTAs, dissemination plan, insurance
• – Agreed process for rapid review – clearly communicated to stakeholders
• Emergency use of unproven clinical interventions outside
clinical trials – including “off-label” interventions – surged
during the COVID-19 pandemic
• unjustified, unconstrained use of unproven interventions
• serious ethical concerns
COVID-19 – Emergency use of unproven clinical interventions
• In the face of the outbreak of Ebola virus disease
(EBV) in West Africa in 2014, WHO issued a framework
for the ethical permissibility of use of unproven
interventions outside clinical trials during public health
emergencies.
• “monitored emergency use of unregistered and
experimental interventions” (MEURI), known as “the
MEURI ethical framework”, avoids the common yet
misleading designation of “compassionate use”, which
is associated with too narrow a scope of unproven
interventions and is not based on harmonized ethical
and regulatory criteria
Ebola 2014 – MEURI
WHO Guidance on ethics and emergency use
of unproven clinical interventions
• Developed by WHO Expert Group
• published in April 2022
• Update of the 2014 & 2016 ethical
frameworks
• Spells out key ethical aspects
WHO MEURI Working Group – 2021/2022
Lead writer: Ignacio Mastroleo, National Scientific and Technical Research Council
and Facultad Latinoamericana de Ciencias Sociales, Argentina
Chair of the WHO Working Group: Ross Upshur, University of Toronto, Canada
Members: Neill Adhikari (Sunnybrook Health Sciences Centre and University of
Toronto, Canada); Aasim Ahmad (Aga Khan University, Karachi, Pakistan); Dereck
Angus (University of Pittsburgh (PA), USA); Yaseen Arabi (King Saud Bin Abdulaziz
University for Health Sciences, Riyadh, Saudi Arabia); Arthur Caplan (New York
University School of Medicine, New York City (NY), USA); Stéphanie Dagron
(University of Geneva, Switzerland); John Marshall (Maimonides Medical Center,
New York City (NY), USA); Roli Mathur (Indian Council of Medical Research
Bioethics Unit, Bangalore, India); Keymanthri Moodley (Stellenbosch University,
South Africa); Srinivas Murthy (University of British Columbia, Canada); Tina Garani-
Papadatos (National School of Public Health, Athens, Greece); Virginie Pirard
(Université Libre de Bruxelles, Belgium); Lembit Rago (Council for International
Organizations of Medical Sciences, Geneva, Switzerland); Maxwell Smith (Western
University, London, Canada); Le Van Tan (Oxford University, United Kingdom of
Great Britain and Northern Ireland); Voo Teck Chuan (National University of
Singapore); Béatriz Thomé (University of São Paolo, Brazil)
WHO’s updated ethical framework for emergency use of
unproven clinical interventions outside clinical trials
Way forward
Lessons Learned
build an evidence base
and strengthen
relationship between
global/local and
technical
Defining Solidarity,
Equity and Access:
Ethics to Policy
Programme of Work
work building on
Pandemic Summit to
more effectively
operationalize ethics
Trust and
Trustworthiness:
Ethics, social listening
and infodemic
management
sub-group established
to develop WHO
guidance (publication
early 2024)
Ethical Governance
follow-up work
Public-private
partnerships
New models of global
governance architecture
– regional hubs?
Research Ethics
Oversight/Governance
Input into Clinical trial
resolution
Addressing gaps in guidance –
adaptive trial designs,
evidence & ethics
Focusing on underrepresented
& marginalized populations
Strengthening capacity –
WHO benchmarking tool
Reforming ethics oversight –
i.e. follow-up to Lisbon
meeting and survey
Strengthening Research Ethics Oversight:
the WHO Benchmarking Tool
Background
⚫ Most countries have established some sort
of system for ethical oversight of research.
⚫ WHO Standards for the functioning of
research ethics have existed since 2011.
⚫ Yet, little is known about how well these
systems are working.
https://iris.who.int/bitstream/handle/10665/44783/9789241
502948_eng.pdf?sequence=1
WHO TOOL: BENCHMARKING ETHICS OVERSIGHT OF HEALTH-
RELATED RESEARCH WITH HUMAN PARTICIPANTS
Objectives:
➢ To assist in evaluating the existing
capacity to provide appropriate ethical
oversight
➢ To guide the development of
recommendations to address the
identified gaps
➢ To assist in capacity-building efforts
➢ To promote policy convergence and
best practices in research ethics
oversight and to enhance public trust
in health research.
Scope:
Designed for all entities involved in the
ethical oversight of health-related research
involving humans, including research ethics
committees (RECs) at the national, sub
national, or institutional levels, and
institutions whose employees or agents
conduct health-related research involving
humans.
WHO Global Benchmarking Tool (GBT) for evaluation of
national regulatory systems of medical products: Revision VI
Link: https://apps.who.int/iris/handle/10665/341243
Link: https://www.who.int/tools/global-benchmarking-tools
2020 2021 2022 2023 2024
Development of the Benchmarking Tool
First draft
working
document
(March – May)
Public
Consultation
(Dec to Jan)
Consolidation
of comments
(March – Aug)
Draft tool
published
(Oct)
Second draft
working
document
(Jun to Oct)
Piloting in Nigeria,
Kenya, Nepal, India,
Egypt and Pakistan
Reflecting
on the
comments
and
finalization
(Q2)
Various pre-cursor
initiatives by
Ethics &
Regulatory Teams
WHO
Working
Group
established
Publication
(September
2023)
Implementation
Link:
https://iris.who.int/bitstream/handle/10665/372984/9789240076426-eng.pdf
• Developed with support of WHO Expert Group
• 100+ Research Ethics Committees involved
• WHO Secretariat:
• Alireza Khadem, Regulatory System Strengthening
• Andreas Reis, Health Ethics & Governance Unit
Ethics Oversight Benchmarking Tool:
Overview
1: Legal
provisions
5:
Mechanisms
to promote
REC
transparency
2: REC
structure and
composition
6:
Mechanisms
for RECs to
monitor their
performance
3: REC
resources
7:
Responsible
Research
Institutions
4: REC
procedures
Structure of the Tool
7
Categories
48
Indicators
Guidance for Assessors
Category 1 = Legal provisions (National context)
Category 2 = Structure and composition (RECs)
Category 3 = Resources (RECs)
Category 4 = Procedures (RECs)
Category 5 = Transparency (RECs)
Category 6 = Performance (RECs)
Category 7 = Responsible research institutions
• Objective
• Description
• Evidence to review
• Rating scale
Example: Category 1 = Legal provisions
Indicator 1.1: Legal provisions requiring health-related research
with humans to be reviewed and approved by RECs.
Indicator 1.2: Legal provision ensuring that RECs have the
authority to function independently.
Indicator 1.3: Legal provision requiring RECs to review
proposed research to determine that it satisfies the
ethical standards…
….
Category 1:
Indicators for Assessment of the
Legal and Regulatory Context
Category 2 = Structure and composition (RECs)
Category 3 = Resources (RECs)
Category 4 = Procedures (RECs)
Category 5 = Transparency (RECs)
Category 6 = Performance monitoring (RECs)
Categories 2-6:
Indicators for assessment of
individual Research Ethics Committees
Category 7:
Indicators for assessment of
Research institutions
Implementation &
impact in countries
Piloting the tool
The draft tool was piloted in workshops in the following countries:
• Nairobi, Kenya, 10-14 October 2022
• Lagos, Nigeria, 17-21 October 2022
• Kathmandu, Nepal, 14-16 November 2022
• Bengaluru, India, 6-7 December 2022
• Cairo, Egypt, 22 January 2023
• Karachi, Pakistan, March 3-4, 2023
Country Workshops
Benchmarking Tool Workshop 14-16 November, Kathmandu, Nepal
Benchmarking Tool Workshop 6-7 December, 2022, Bengaluru, India
Implementation in countries
Various options:
– Self-assessments
– Collaborative assessments / peer review
– Nationally coordinated assessment
– External assessments
After assessment:
– Report with areas for further improvement
– Follow-up plan
Link: https://iris.who.int/bitstream/handle/10665/373001/9789240080713-eng.pdf
Implementation in countries
• Launch 25th September 2023
• Dissemination and translation
• Self-assessments/ peer review
• Implementation workshops (in country or online)
• Collaboration with regional and national networks, e.g. AVAREF, FERCAP,
FERCI, EURECNET etc.
• Future revisions
Conclusion
• (Research) Ethics – a key component of WHO’s Programme of Work 2019-2024
• Adequate capacity for research ethics oversight is crucial for implementing
international research ethics standards
• Robust capacity needs to be built in «normal» times, so it can also function during
emergencies
• WHO and partners are supporting Member States by providing specific guidance
and tools for research ethics oversight
Thank you very much!