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 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[1] and the National Guidelines for Ethics Committees Reviewing Biomedical and Health Research During COVID-19 Pandemic[2], 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”[3]. 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[4], 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 of quality and level of compliance with the regulatory and ethics standards set by Indian regulatory and ethics bodies.

A detailed letter [5] 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. 

Signed by,

Organisations

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)

Individuals

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 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

23.  Asha

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

95.  Latifa

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 , 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

Annexure A

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.”


[1] https://ethics.ncdirindia.org/asset/pdf/ICMR_National_Ethical_Guidelines.pdf

[2] https://www.icmr.gov.in/pdf/covid/techdoc/EC_Guidance_COVID19_06052020.pdf

[3] http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=48057&EncHid=&userName=Inactivated%20SARS-CoV

[4] https://youtu.be/E4Z-UF7WGtE?t=139 ; https://epapers.peoplessamachar.in/epaper/edition/3959/bhopal-city

[5] https://fmesinstitute.org/blog-20-heal-institute-ijme-covid-19-insights-jan-11-2021/–
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