S1-2 Immanuel DoH Vatican
PDF Upload
23/01/2024
1
Medical Research Today :
The Geography of Vulnerable Populations
Gifty Immanuel MD,PhD
Center for AIDS & Antiviral Research
Synergia Pandemic Foundation, India
1
Global Race for Excellence in Research
India and China (both LMIC) have produced highest
STEMgraduates.
Nature and other Journals Waiver of Open Access Fees
for LMIC
Pressure to Publish and Conduct Large Scale Research
LMIC Huge Population, Technical Workforce, Cheaper
Medications, Less Regulatory Control
2
23/01/2024
2
Scientific Workforce, Global Ambitions and
Research Advancement
3
Population Vulnerability
Ruth Macklin- “ vulnerable people can be exploited even if they are not harmed,
and harmed even if they are not exploited’.
Vulnerability is understood to be a Universal
Ontological Condition of Human Existence
Incapable of Protecting their Own Interests,
Greatest Risk, Poor Physical, Socioeconomic Status
Most Disadvantaged sub-segment of the
Population, Need Maximum Protection in Research
Due to their Circumstances, Vulnerable
Communities Inclined to Participate in Studies
Extreme Poverty, History of Colonialism, Lack of
Transparency and Accountability
Macklin R. (2003). Bioethics, vulnerability, and protection. Bioethics, 17(5-6), 472–486.
Schroeder, D., et al (2019). Exploitation Risks in Collaborative International Research. In:
Equitable Research Partnerships. Springer Briefs in Research and Innovation Governance.
Springer, Cham.
4
23/01/2024
3
Ethical Dumping – Exploitation/Misconduct
in Collaborative Global Research
• Extreme Power Differentials between Researchers in
HICs and Stakeholders in LMICs
• Exploitation -Coercive/ Moral Failing , Instrumentalizes
People , Disadvantages the Vulnerable
• Moral Decision – Exploiter(Intended/Unintended),
Ignorance Not a Justification for Exploitation
• Vulnerable Population Coerced to Accept ( No
alternatives- ART Pregnant Women/Placebo)
Schroeder, D., et al (2019). ExploitationRisks inCollaborativeInternational Research. In: EquitableResearch
Partnerships. SpringerBriefsinResearchandInnovationGovernance. Springer, Cham.
5
Bioethics, Vulnerability and Declaration of Helsinki
Rogers, W., Mackenzie, C., & Dodds, S. (2012). Why bioethics needs a concept of vulnerability. International Journal of Feminist Approaches to Bioethics,
5(2), 11–38.
Core of Bioethical Inquiry, Early Bioethical Literature Lacked the
Concept of Vulnerability.
DOH Landmark Mandated-Protection of the Individual -Vulnerable to
Harm through Research
Individuals, Groups or Entire Country can be Vulnerable, Giant
Pharma/Industrialized Researchers
Lack of Oversight of Research Ethics Compliance, Lack of Resources.
Infrastructure- Compliance
Unethical Practices Considered Acceptable ( in certain institutions
and situations)
6
23/01/2024
4
Chronicles of Ethical Violations in Vulnerable Populations ( since DOH 2103 update)
A Spill Over Virus Study in Bat Hunting Tribe ( Bomrr Tribe) in Nagaland India 2019
Bat Hunting/ Eating for Centuries without Overt Viral Diseases, Filovirus Antibodies
International Collaborators Involved – NUS Duke University Singapore, NCBS India,
Wuhan Institute of Virology – Plos Neglected Tropical Diseases
All Clearances were Obtained, Protected Tribe – Blood Withdrawal without
Informed Consent
Dovih, P., et al (2019). Filovirus-reactive antibodies in humans and bats in
Northeast India imply zoonotic spillover. PLoS neglected tropical diseases,
13(10), e0007733.
7
Chronicles of Ethical Violations in Vulnerable Populations (since DOH 2103 update)
Ethical violations during a clinical trial of a covid-19 vaccine by India’s Bharat Biotech and ICMR
8
23/01/2024
5
The Forum for Medical Ethics “The testimonies demonstrate inducement which represents a breach of the
tenet of voluntary participation without inducement or coercion. Many participants were misled to enroll in
the trial, their vulnerabilities preyed upon.”
BMJ I C. India: Doctors call for investigation into allegations of ethical abuse in covid-19 vaccine trial BMJ 2021; 372 :n131
7 Participants in Peoples
Hospital Bhopal were not
informed if they were
given the Vaccine or the
Placebo
The Trial Objectives were
not Disclosed,
Reimbursement and
Medical Management of
Adverse Reactions were
not Mentioned.
Death of 1 trial Participant,
Silence of All Agencies
Involved
9
Chronicles of
Ethical Violations
in Vulnerable
Populations (
since DOH 2103
update)
• ICMR and PATH / GATES
Foundation HPV Vaccine
“Demonstration Project” India –
2009-2011.
• Gardasil, MSD, the Indian
subsidiary of Merck and Co. Inc.
14000 children in Rural Andhra ,
16000 girls in Gujarath- 7 deaths
• 30 million girls in 40 nations by
2020 ( Africa, South America,
Vietnam -Poorest Vulnerable
Countries)
• HPV Vaccine administered before
Marketing Approval, Lack of
Consent and Clarity . Terminology (
Demonstration Project Instead of
Clinical Trials)
Sharma D. C. (2013). Rights violation found in HPV vaccine
studies in India. The Lancet. Oncology, 14(11), e443.
Shetty, P. Vaccine trial’s ethics criticized. Nature 474, 427–
428 (2011).
10
23/01/2024
6
Sharma D. C. (2013). Rights violation found in HPV vaccine studies in India. The Lancet. Oncology, 14(11), e443.
Shetty, P. Vaccine trial’s ethics criticized. Nature 474, 427–428 (2011).
11
Chronicles of Ethical Violations in Vulnerable Populations
( since DOH 2103 update)
Seeding Trial ( Marketing Project ) Compensation for Faulty Hip Replacements – ASR
(Articular Surface Replacement) Johnson and Johnson 2004-2010
12
23/01/2024
7
Kindsfater, Kirk & Lesko, Jim. (2017). Survivorship of a modular acetabular cup system: medium- to long-term follow-up. Arthroplasty.
Egilman, D. S., Steffen, J. E., Fassler, E. A., & Reardon, K. J. (2018). Letter to the editor on ” Survivorship of a modular acetabular cup system: medium- to long-
term follow-up”. Arthroplasty today, 4(3), 392–393.
Steffen, J. E., Fassler, E. A., Reardon, K. J., & Egilman, D. S. (2018). Grave fraudulence in medical device research: a narrative review of the PIN seeding study
for the Pinnacle hip system. Accountability in research, 25(1), 37–66.
4700 Patients Underwent
Hip Replacement, 1080
Traceable, Revision
Surgery (15000 units
India)
Problem with the
Quantum of
Compensation in 2017
(2.5 billion USD for 8000
US Patients)
No Faulty Findings in Trial
– Journal Article and its
Rebuttal
13
HIV Cure
Research and
Quality of
Informed
Consent
• Cure trials – Minimizing or
Eradication Virus in
Circulation and Reservoirs
• Balanced Ethical Oversight-
Cautious Use of the Word
“Cure”
• HIV Remission Vs
Eradication- Over
Amplification of Benefits of
Intervention
• Conflicting Messaging –
Lexicon- Functional Cure,
Permanent Cure
• Surrogate End Points-
Modify CCR5 Protein, Viral
Load Changes
Henderson G. E. (2015). The ethics of HIV
“cure” research: what can we learn from
consent forms?. AIDS research and human
retroviruses, 31(1), 56–63.
14
23/01/2024
8
HIV Cure
Research and
Global
Implementation
• HIV Cure Research- Uncertain Outcomes
Boston Patient HST, Mississippi Child ART
• Lack of Biomarkers to Accurately Predict
Rebound
• Countries with Larger Pool of PLWH (
Thailand, India, Africa)
• Indian Institute of Science Education and
Research Bhopal circRNA (ciTRAN)
• Analytical treatment interruption (ATI),
Infection Transmission to Partners
• Separate Section of Scientific Uncertainty
of Intervention ( Informed Consent)
Dubé, K., Kanazawa, Jet al (2021). Ethics of HIV cure
research: an unfinished agenda. BMC medical ethics,
22(1), 83
15
ECHO Consortium
Trial and Ethical
Violations in Africa
( since DOH 2103
update)
• Incentives, Coercive
Language, Concealing the
real nature Trial during
Recruitment
• ECHO Consortium Trial (
WHO, Gates Foundation)
DMPA, LNG, IUD (2015)
• HIV acquisition by Three
Methods ( Labelling RCT-
Clinical versus Controlled)
• Lack of Literacy to
Understand IC ( regional
language), Increase HIV
with DMPA(Equipoise)
• Violation of Central Tenet
of DOH, Disregard for
Women/Girls LICs.
Generating new knowledge “this goal can never
take precedence over the rights and interests of
individual research subjects’ (World Medical
Association, 1964)
Sathyamala C. (2022). In the name of science:
Ethical violations in the ECHOrandomised trial.
Global public health, 17(12), 4014–4029
Image IPPF
16
23/01/2024
9
HIV/AIDS Research : Sub-Saharan Africa
Koen, J., Wassenaar, D., & Mamotte, N. (2017). The ‘over-researched community’: An ethics analysis of stakeholder views at two South African HIV prevention research
sites. Social science & medicine (1982), 194, 1–9.
Over Researched Community and Vulnerable to Ethical Violations,
Research Fatigue
Many Academics Studying the Same Problem, Proxy Ethical
Standards and Safeguards
Sub-Saharan Africa in particular bears 50% of the global burden of
the HIV Pandemic
Potential Barrier to Community Participation in Research
17
Future Directives :
HIV Research in
Vulnerable
Populations in
Resource Limited
Settings
• Ethical Issues in Vulnerable Population
Centers around Informed Consent, Despite
the Heterogeneity of Studies and Settings.
• Fundamental Pre-requisite- Adequate and
Comprehensive Informed Consent Tailored
to the Population
• Involvement of Cultural Representatives
and Community Leaders
• Complex Issues Include- Diminished
Autonomy, Language Barriers, Monetary
Inducement and Lack of Transparency.
• Promotion of Higher Ethical Standards for
Future Research, an Informed Consent
that is Truly and Culturally Relevant.
Mystakidou, K., Panagiotou, I., Katsaragakis, S., Tsilika, E., & Parpa, E. (2009).
Ethical and practical challenges in implementing informed consent in HIV/AIDS
clinical trials in developing or resource-limited countries. SAHARA J : journal of
Social Aspects of HIV/AIDS Research Alliance, 6(2), 46–57.
18
23/01/2024
10
THANK YOU
19