Bharat Biotech’s COVAXIN trial at People’s Hospital, Bhopal; initiating an investigation into legal and ethical violations; and providing compensation for trial participants
Civil Society Statement in support of demands for stopping
Bharat Biotech’s COVAXIN trial at People’s Hospital, Bhopal; initiating an investigation into legal and ethical violations; and providing compensation for trial participants
14 January 2021
At the online press conference on Sunday, 10 January 2021 organised by Bhopal-based civil society organisations, several people from communities affected by the 1984 Bhopal gas tragedy shared their experiences related to the COVAXIN Phase 3 clinical trial. The clinical trial of Bharat Biotech’s COVAXIN, co-sponsored by ICMR, is taking place at the People’s College of Medical Sciences & Research Centre, Bhopal.
The testimonies given by several people who were inducted into the clinical trial indicate that there have been gross violations of laws and guidelines governing clinical trials in India, namely the New Drugs and Clinical Trials Rules, 2019 and the National Ethical Guidelines for Biomedical and Health Research involving Human Participant, 2017 and the National Guidelines for Ethics Committees Reviewing Biomedical and Health Research During COVID-19 Pandemic, April 2020 published by ICMR. In fact almost every tenet of ethical conduct in a clinical trial appears to have been violated.
The death of a male trial participant has come to light recently through the media, and not because the regulator or sponsors chose to share this information.
It is particularly alarming that a clinical trial that is co-sponsored by ICMR is violating both statutory provisions and ethical guidelines laid down by ICMR pertaining to conduct of clinical trials.
Exploitation of Participants’ Vulnerability
A large number of people who were enrolled into the clinical trial are vulnerable people living in bastis affected by the Bhopal gas disaster and by contamination of groundwater. Many of the residents of these communities have been born with congenital disorders and already suffer compromised health because of the 1984 gas disaster. These background conditions of these communities make the selection for the COVAXIN trial questionable given the multiple vulnerabilities that these communities suffer from.
It is important to investigate on what ground ethics review board/s (ERBs/IECs) permitted the inclusion of these and similar communities in the trials, and what protection mechanisms were made necessary by them to avert exploitation of vulnerable participants in the trial as per the ICMR Ethics Guidelines 2017.
The participant testimonies vividly brought forth that the process of seeking informed consent implemented by the local trial staff/team members was of poor quality and failed to comply with ICMR Ethics Guidelines 2017. Some of the trial participants said that they did not know what was written in the papers they were given as they were non-literate. Some trial participants expressed that they were told they were getting an injection to protect them from COVID-19 and were not made fully, properly aware of the meaning of a clinical trial.
As per the New Drugs and Clinical Trials Rules, 2019, Third Schedule (2.g) mandates: “An audio-video recording of the informed consent process in case of vulnerable subjects in clinical trials of New Chemical Entity or New Molecular Entity including procedure of providing information to the subject and his understanding on such consent, shall be maintained by the investigator for record”. This was not done as per the testimonies of many trial participants indicating a violation of the regulatory framework.
Given the extreme economic vulnerability which was further exacerbated due to the already nine-month long pandemic which has adversely impacted the livelihood means of vulnerable sections of population such as the ones in this case, the payment of Rs. 750 served as inducement. Many testified this by saying that they participated in the trial as they were promised Rs. 750. Also and as a result, a large number of people from these bastis, sometimes entire families, joined the trial.
Therefore, many participants from these bastis were misled to enroll in the trial, most of whom cannot even read and write, and their vulnerabilities preyed upon. Further, the legal and ethical requirements to follow additional safeguards in conducting a trial involving vulnerable persons were not followed.
Compromised Ethics in the Informed Consent Process
The four core elements of seeking informed consent from research participants are: 1) full disclosure of all the study related information to prospective research participants; 2) comprehension of the information given to participants by researchers; 3) voluntary participation without inducement and/or coercion; and 4) appropriate documentation of consent. In case of vulnerable populations there are additional mechanisms and due diligence mandated both in the regulatory framework and the ICMR Ethics Guidelines 2017. We elaborate on the four elements below:
1) The ethical obligation of disclosure of study information ought to include, amongst other things, disclosure about the trial design, potential risks, potential benefits, and any contraindications and health conditions that should be considered by the researchers.
It is alarming to learn from the participants that they were not informed that they may experience medical issues and adverse reactions, and that these will be attended to by the trial personnel. Some participants who approached the trial site after suffering medical issues were denied care by the trial personnel, and were asked to pay for treatment and medicines out of their own pocket. In other cases, participants did not go back to the trial site when they were facing medical issues because they were not aware that they were entitled to free medical management. Bharat Biotech’s consent form talks of an insurance policy for participants about which no information or details were shared. Therefore, based on the testimonies, it appears that the obligation of disclosure of full information about the study was compromised.
2) Participants’ testimonies revealed that many of them did not comprehend the trial design. Disclosure of study information requires to be done in a manner that it is accessible to prospective research participants to help them comprehend fully. As a result, the obligation of ‘ensuring comprehension’ on part of study participants was compromised.
The first inclusion criterion on basis of which participants can be enrolled in the Phase 3 trial is the “ability to provide written informed consent and availability to fulfill the study requirements”. It is unclear how many of the participants met this criterion. Majority of the participants from these communities are illiterate. They were not in a position to fulfill the study requirements such as filling the booklet/diary to record any adverse reactions post dosing, which would compromise their own safety and the data being collected in the trial.
3) As discussed previously, the testimonies demonstrate inducement which represents a breach of the tenet of voluntary participation without inducement or coercion.
4) Considering that these participants belong to a vulnerable group, the investigators were duty bound to enquire about their vulnerability and education status, and in compliance with the law to ensure audio-visual recording of the informed consent process, an impartial witness to co-sign the informed consent form and implement other safeguards to protect the rights of the participants. However, trial participants reported that this was not done.
In fact it seems that participants were not even provided with copies of the signed participant information sheet and consent form. This has also been confirmed by Dr. Rajesh Kapur, Vice Chancellor of People’s University Bhopal in an interview that he gave on 6 January 2021, where he admitted that signed consent forms and participant information sheets were not routinely given to participants and shared only if a participant asked for them. This demonstrates that the fourth element of ‘documentation’ in informed consent has also been compromised.
Failure to monitor trial participants
Participants’ testimonies indicate a distinct failure of the site investigator and the implementing team to ensure consistent and sustained follow up and monitoring of trial participants after they received the doses, towards safety and well-being of the participants.
Seeking accountability to ensure scientific and ethical validity of the trial towards maintaining public trust
The death of a trial participant is of grave concern, particularly because no information is available regarding the process through which the death is being investigated by the trial Data Safety Monitoring Board, DCGI etc. Any conclusions of the PI and the Institutional Ethics Committee cannot be trusted given the negligence in conduct of the trial, in contravention of the law and ethical guidelines. The family of the participant must be compensated as per prevalent laws.
Overall, testimonies demonstrate that the clinical trial of COVAXIN at People’s Hospital is compromised. Therefore, the data of this trial site must not be included in the data that will be analysed for the Phase III trial.
If the Phase III trial at Bhopal with the primary endpoint of efficacy is being conducted in such a slipshod manner, it raises valid concerns about other trial sites in terms of quality and level of compliance with the regulatory and ethics standards set by Indian regulatory and ethics bodies.
A detailed letter  has been sent to the Prime Minister, Health Minister and relevant Central and State level authorities from civil society organisations working with gas-affected communities. We are supportive of the demands put up by the Bhopal-based organisations on behalf of the trial participants (reproduced in Annexure A).
Against this backdrop, we demand an immediate, thorough investigation of the issue at hand from the concerned regulatory and ethics compliance offices to look into gross violations. Suitable action needs to be taken against all individuals and structures that are found to be responsible for ethical violations, negligence and endangering the safety of trial participants including investigators, Ethics Committee, administrators of People’s Hospital and the trial sponsors.
The immediate action warranted is that the trial at People’s Hospital, Bhopal must be immediately brought to a complete halt. The trial sponsors, Bharat Biotech and ICMR, must take full responsibility for the serious, unconscionable and unlawful lapses in the Bhopal trial.
1. Abha Bhaiya, India Coordinator, One Billion Rising Network
2. AJMG Foundation
3. All India Drug Action Network (AIDAN)
4. All India Forum for Right to Education (AIFRTE)
5. Ambar Koiri, Awaken India Movement, Mumbai
6. Arundhati Dhuru, National Convenor, National Alliance of People’s Movements (NAPM)
7. Benny Ouso, Director, Sneharam Social Welfare and Charitable Society
8. Bharat Gyan Vigyan Samiti (BGVS), Odisha
9. Campaign for Affordable and Dignified Healthcare (CDAH)
10. Campaign for Change
11. Doctors with Disabilities: Agents of Change
12. Dr. Gopal Dabade, Presiden, Drug Action Forum – Karnataka
13. Dr. Sanjay Nagral, Chair, Forum for Medical Ethics Society (FMES)
14. Dr. Sunil Kaul, Founder & Managing Trustee, the ant (the action northeast trust)
15. Dr. Shakeel, Centre for Health and Resource Management
16. Eldred Tellis, Sankalp Rehabilitation Trust
17. Forum Against Oppression of Women, Mumbai
18. Jan Swasthya Abhiyan (JSA)
19. Jan Swasthya Abhiyan – Mumbai
20. Justice Coalition of Religious, West India
21. Karnataka Janaarogya Chaluvali
22. Krantikari Yuva Sangathan (KYS)
23. LABIA – A Queer Feminist LBT Collective, Mumbai
24. Lawyers for Detainees (L4D)
25. Lok Manch
26. S. Srinivasan, Managing Trustee, Low Cost Standard Therapeutics (LOCOST)
27. Meghna Mehra, Founder, All India Queer Association
28. National Alliance of People’s Movement (NAPM), Delhi
29. National Federation of Indian Women (NFIW)
30. National Federation of Indian Women (NFIW), Delhi Unit
31. National Platform for the Rights of the Disabled (NPRD)
32. Neev Foundation for Legal Aid
33. Patient Rights Group
34. Progressive Medicos & Scientists Forum (PMSF)
35. Raju Behara, National President, All India Queer Association
36. Ramji Sharan Rai, Chief Executive and Programme Coordinator, Swadesh Gramotthan Samiti Datia, Madhya Pradesh
37. Saheli- Women’s Resource Centre, New Delhi
38. Sandeep Pandey Vice President, Socialist Party (India)
39. Shishir Chand, People for Better Treatment (PBT), India
40. Shramik Adivasi Sanghatana, Madhya Pradesh
41. Sruti Disability Rights Centre, Kolkata
42. Women Against Sexual Violence and State Repression (WSS)
1. A O Pinto
2. Aanchal Sawa, Centre for Human Rights and Duties
3. Abha Jeurkar, Teacher
4. Abhay Shukla, Jan Swasthya Abhiyan (JSA)
5. Aditi Thakur, Psychotherapist; Phd scholar at Tata Institute of Social Sciences
6. Adv. Mini Mathew
7. Ahmed Shabin, PhD scholar, BITS Hyderabad
8. Aisha Farooqui, Retired Academic
9. Amalendu Jajodia, Retired
10. Amar Jesani, Independent Researcher/teacher, Bioethics & Public Health
11. Amit Kumar, Student, Faculty of Law, University of Delhi
12. Amita Pitre, Gender And Health Policy Analyst and Researcher
13. Amitabha Basu, Retired scientist, CSIR-NPL, New Delhi
14. Ammu Abraham, Feminist and civil liberties activist; FAOW & PUCL Maharashtra
15. Anand Kundaji, Publisher
16. Anant Bhan, Researcher
17. Anomita Sen
18. Anu Bajpai
19. Anubhuti Sharma, Research Scholar
20. Anuradha Rajan, Gender specialist
21. Arjun Sheoran, Advocate. National Organising Secretary, People’s Union for Civil Liberties
22. Arokia Mary, Social Activist, JSA-Mumbai
24. Ashima Roy Chowdhury, Feminist Activist of Saheli Women’s Resource Centre
25. Ashok Sharma, Retired Diplomat
26. Astrid Lobo, Scientist
27. Azam Khan
28. Barathi, Independent Researcher
29. Beena Choksi, Education Consultant
30. Bharat A. Bhatt, Independent, retired professional, voluntary servant
31. Bindhulakshmi Pattadath, Faculty, TISS
32. Biswajit Dhar, JNU
33. Bobby Ramakant, Activist, Asha Parivar
34. Brinelle D’souza, Tata Institute of Social Sciences
35. Chandni B
36. Chandrima Nath, Housewife
37. Chayanika Shah, Researcher and Teacher
38. Debarati, NAPM Yuva
39. Deepika Joshi, PUCL Chhattisgarh
40. Devaki Khanna, Freelance editor
41. Dheeraj, Development Worker
42. Dimple Oberoi Vahali, Independent Activist
43. Dr. Dewal Sawarkar, Public Health Worker
44. Dr. Frazer Mascarenhas S.J., Academic Administrator
45. Dr. Geeta Sodhi, Pediatrician and public health consultant
46. Dr. John Puntis, Former Chair, Leeds West Research Ethics Committee, UK
47. Dr. Mohan Rao, Independent public health researcher, Bangalore.
48. Dr. Namitha A Kumar
49. Dr. Nitin Jadhav
50. Dr. P. B. M. Basaiawmoit, Shillong, Activist
51. Dr. Sejal Tambat, JSA – Mumbai
52. Dr. Shaihla Ansari, Medical consultant and public health activist
53. Dr. Shivanand Pawar, DAF-K
54. Dr. Usha Ubale, Medical doctor
55. Dr. Vandana Prasad, Public Health Professional
56. Dr. Veena Shatrugna, Medical Scientist (Rtd.)
57. Dyuti A, PhD Researcher, University of Sussex
58. Ekramul Haque, AMU
59. Francesca Fernandes
60. Gaurav Lalwani
61. Geeta Seshu, journalist
62. Gouranga Mohapatra, Odisha
63. Gurpreet Kaur, Researcher
64. Gurumoorthy M, Social sector
65. Habung Dunya
66. Hana Hsin-wei Cheng, Centre for Women’s Studies, JNU
67. Hena Faqurudheen, Psychotherapist
68. Imran Rizvi
69. Inayat Singh Kakar, Public Health Researcher
70. Indra Munshi, Social Scientist
71. Indranee Dutta, Retired Professor
72. Indranil, Academic
73. Indukumar Jani
74. Jagannath Chatterjee, Health Activist
75. Jagdish Patel, Social Worker
76. Janhavi Verma
77. Jasmine Kalha, Researcher
78. Jayashree Venkatesh, Teacher
79. Jinee Lokaneeta, Professor
80. Joanita Figueiredo
81. Joe Thomas, Professor
82. K Akash
83. K. Elu Ndang, Social Activist
84. Kabi S, People’s Union for Civil Liberties (PUCL)
85. Kamayani Bali Mahabal, Human Rights Activist
86. Kamlesh Khantwal, Social Worker, BGVS ; Jan Swasthy Abhiyan – Uttarakhand
87. Kamlesh Pal
88. Kapila Gureja, Social Worker
89. Kiki, Researcher
90. Kopal Khare
91. Kuldip Chand
92. Lakshmi Krishnamurty (retd), Alarippu
93. Lara Jesani, Advocate, Mumbai
94. Lateef Mohammed Khan, Civil Liberties Monitoring Committee
96. Malaika Dhar James, Student
97. Malini Aisola, AIDAN
98. Manisha Shastri, Social Worker
99. Manmeet Kaur
100. Manorama Sharma, Retired Professor, NEHU, Shillong.
101. Manoranjan Sarma, Self employed
102. Mathew George, Public Health Faculty
103. Maya Sharma
104. Meena Gopal, TISS Mumbai
105. Meenakshi D’Cruz
106. Meera Ahmad
107. Millind Khandate, Government Service
108. Mira Sadgopal, Health Researcher
109. Monica Nanjunda, Artist
110. Mrs. Fernandes
111. N Vallath
112. Nalini Nayak, Protsahan
113. Nandini Manjrekar, Teacher
114. Nandini Rao Akkaraju
115. Natta Habravysh, Student
116. Neena Shah More, Home maker and social health and wellbeing engineer
117. Nidhin Joseph
118. Nisha Biswas, Activist
119. Nisreen Ebrahim, Development Sector Professional
120. Nivrita Durgvanshi
121. Oishik Sircar, Legal Academic
122. Padma Prakash, Editor, sociologist
123. Pallavi Gupta, Public health researcher
124. Pamela Philipose, Journalist
125. Payal, Journalist
126. Prabir Chatterjee, Independent Public Health Practitioner
127. Pradeep Narayanan, Social Worker
128. Pramod Tiwari
129. Prasanna Saligram, Jan Swasthya Abhiyan (JSA) Karnataka
130. Pravesh Sharma, Retired
131. Priya K, Student, Jawaharlal Nehru University (JNU)
132. R D Mathur, Retired
133. R Srivatsan, Independent health activist
134. Rabindra Nath Dutta, Rtd. Govt Pensioner
135. Radha Holla, Independent Researcher
136. Radhika Radhakrishnan
137. Rafi Malek
138. Rahul Dwivedi, Operations Director CNS
139. Rajeev B R, Public Health Dentist
140. Rajesh Umadevi Srinivas, Activist
141. Rajiv Kumar, RTI Activist
142. Raju Behara, National President, All India Queer Association
143. Ravi Duggal, Public Health Activist
144. Ravi Prakash, I Concern, Bihar
145. Rehana Sikora, Medical Professional
146. Richa Chandra
147. Rohini Hensman, writer and independent scholar
148. Rohit Prajapati, Environment Activist, Paryavaran Suraksha Samiti
149. Sabita Lahkar, Journalism
150. Sajida Khan
151. Sandhya Gokhale, IT Professional, Forum Against Oppression of Women
152. Sandhya Srinivasan, Indian Journal of Medical Ethics
153. Sangeeta, Social Activist
154. Sanjay Dabhade, Doctor and Health Activist, Pune
155. Sarojini N, Public Health Researcher
156. Shakuntala, Working in NGO on health rights
157. Shams Imran
158. Sheeba Abidi, Social Worker
159. Shefalee Jain, artist
160. Sheshmani Shukla, Srijan Seva Samiti
161. Shilpaa Anand, HSS Department, BITS-Pilani Hyderabad Campus
162. Shiraz Bulsara Prabhu, Retired
163. Shivani Taneja
164. Shobha Shukla, Executive Director, CNS
165. Shrinidhi Rao
166. Shriyuta Abhishek, Infosys Fellow in Public Health, SEARCH.
167. Shweta Damle, Platform for Social Justice
168. Siddhartha Das, Postdoctoral Fellow
169. Simona Sawhney
170. Smriti, Social Worker, Maternal Health Rights Campaign
171. Srilatha Juvva
172. Subuhi Jiwani, Independent writer and filmmaker
173. Sudha N, Independent Researcher & Activist
174. Sujata Gothoskar, Researcher and Activist
175. Sujatha V, Social worker
176. Sulakshana Nandi, Public Health Researcher, Chhattisgarh
177. Suneeta Bandewar, Health, Ethics and Law Institute of FMES;Vidhayak Trust
178. Sunil Tamminaina
179. Suresh Melettukochy
180. Surya Prakash, Advocate
181. Sweta Dash, Independent Journalist and Researcher
182. Teena Xavier, Social activist and public health person
183. Upreet Dhaliwal, Former professor of Ophthalmology, UCMS, Delhi
184. Urmila Salunkhe, Activist
185. Usha Raman, Professor, University of Hyderabad
186. Vaishnavi Prasad, Law Student
187. Vasantha, Activist
188. Vertika Mani, Lawyer
189. Vikash Prakash, Banaras Hindu University
Demands of the COVAXIN Phase 3 Trial Affected Participants in Bhopal
extract from the letter sent to the PM, Union Health Minister and other authorities on 10 Jan 2021
“In view of the above egregious violations by the trial site, we urge you to:
(a) Immediately stop the clinical trial for Bharat Biotech’s COVAXIN at People’s College of Medical Sciences & Research, Bhopal given the severity of the violations of ethical standards set by the ICMR and statutory provisions, and the gross negligence in taking care of the trial participants.
b) Form an independent body to conduct an impartial, transparent, thorough, and time-bound investigation to ascertain violations of ethics, protocols and legal requirements pertaining to conduct of the clinical trial. The findings of this enquiry must be put in public domain. The independent body must consist of experts, especially civil society representatives who do not have any conflict of interest or connection with the sponsors (BBIL and ICMR), the site (People’s College of Medical Sciences & Research, Bhopal) or the researchers.
(c)The Principal Investigator and the Co-investigators of the clinical trial at the site, the People’s Hospital, have failed to adhere to the scientific and ethics standards, legal requirements, and have been insensitive and negligent in ensuring safety, well-being and the rights of the participants of the trial. All the responsible parties found to be negligent of their duties must be punished. They must be suspended from all research forthwith and their competence to do such research must be reviewed in addition to making them accountable for the violations and negligence.
(d)The People’s College Institution Ethics Committee is a body registered with the CDSCO. It has failed to demonstrate its independence and competence in monitoring the COVAXIN trial and ensuring that all protocols and statutory requirements are adhered to. Its registration may be suspended forthwith and the CDSCO must inspect and audit its functioning and make its Chair and Member-Secretary accountable for the lapses in the conduct of the clinical trial, and resultant harm to people’s lives.
(e) Conduct a separate audit of the People’s College of Medical Sciences & Research, Bhopal for its scientific and ethical standards of drugs, biomedical and health research. If such standards are found to be deficient, it should not be allowed to undertake any research unless the institution carries out necessary improvements.
(f) Due to shoddy follow up of the participants, prima facie it appears that the COVAXIN trial at People’s College has violated not only ethics, but also compromised scientific integrity. The deficient scientific data would lead to wrong and misleading conclusions of the research. Thus, the vaccine trial data of this site should be separated out and not used in the trial outcome analysis.
(g) Ensure that all the trial participants from the vulnerable sections who were enrolled in the trial get access to free medical care and compensation for any injuries or death related to the trial.
(h) Share details of the process and timelines through which the death of the trial participant is being investigated by the various parties – the PI, Ethics Committee, DSMB, and DCGI – and the findings when the final determination has been completed.”