COVID 19 human infection challenge studies: a practical guide for ethical review

Oxford A Research Ethics Committee
 
Under international guidance, research involving human subjects requires a favourable opinion from a Research Ethics Committee (REC) or Institutional Review Board (IRB). To develop a practical guide, we report a survey of members of the Oxford A REC (n=15), an NHS committee with experience of reviewing Human Infection Challenge studies (HCS), to seek their views on the ethical issues of proposed COVID 19 or SARS COV-2 HCS and their requirements for a favourable opinion, mapping them to the World Health Organisations proposed key ethical criteria. These were then re-shaped as “Questions and Considerations - a framework for review”  adding material to help reviewers make judgments.
 
Requirements for a favourable opinion
1.Scientific justification “SARS CoV-2 challenge studies must have strong scientific justification.” WHO
i. Independent, expert clinician and researcher review along with public involvement
ii. A systematic, up to date, review of current literature
iii. The study as designed will provide meaningful information
iv. The results from the sample recruited will be generalizable to the population.
v. The project will not detract from pandemic care.
vi. A trial steering committee will be documented and in place.
vii. A data monitoring and safety committee will be in place.
viii. Scientific confirmation that a placebo arm is needed and justified.
 
2.Risks and benefits “It must be reasonable to expect that the potential benefits of SARS-CoV-2 challenge studies outweigh risks.” WHO
• There is independent confirmation of risk/benefit balance by expert and public opinion.
• The quality of the infecting agent is adequately ensured by independent expert review.
• Containment will meet current agreed standards for COVID 19.
 
Medical care of volunteers
• There is an agreed, written protocol for support, accommodation and treatment of the participants after challenge
• There is assurance of monitoring of participants throughout with demonstrable facilities and capacity for this.
 
Payment and compensation
• The participant will bear no cost for care.
• Payment for participation should be fair and not undue influence.
• Unconditional compensation is in place for harm (provided the protocol was adhered to).
• Arrangements for non-negligent harm are in place
 
3. Consultation and engagement “SARS-CoV-2 challenge research programmes should be informed by consultation and engagement with the public as well as relevant experts and policy-makers.” WHO
• There is robust public input from design, conduct through to dissemination of results.
 
4. Coordination “SARS-CoV-2 challenge study research programmes should involve close coordination between researchers, funders, policy-makers and regulators” WHO
This wasn’t brought up, members being only asked to comment on problematic issues within a possible COVID 19 HCS but they recognised they could not and should not review alone.
 
5. Site selection “SARS-CoV-2 challenge studies should be situated where the research can be conducted to the highest scientific, clinical and ethical standards.” WHO
• The research team will have expertise in this field and conduct the study with a unit that has current experience of dealing with seriously ill people with COVID 19 and agreed capacity to deal with possible illness.
• The research team will work under appropriate legal, institutional and professional accountability.
• The sites administering and monitoring the response to the challenge will be independently assessed that they can conduct the study according to the protocol.
 
6. Participant selection “SARS-CoV-2 challenge study researchers should ensure that participant selection criteria limit and minimize risk.” WHO
• COVID 19 Challenge studies will enroll the group at least risk from the infection.
• There is screening of participants to assess mental as well as physical health.
• There will be contact with the volunteer’s Health Care Professional to confirm suitability.
 
7. Expert review “SARS-CoV-2 challenge studies should be reviewed by a specialized independent committee” WHO
This was neither categorised nor explicitly mentioned although members did record the importance of expert and lay input into these studies.
 
8. Informed consent: “SARS-CoV-2 challenge studies must involve rigorous informed consent” WHO
• Design of consent procedures will involve public representation.
• The consent discussion will have a clear, documented framework.
• There will be time for the volunteers to discuss, read material and then reflect with the opportunity to talk to others.
• The discussion will in the presence of a counsellor or advocate.
• Consent will be in two stages separated to accommodate this.
• The discussion will be video recorded.
• There will be a written list of issues to be covered in the protocol.
• Researchers taking consent will have appropriate training, experience, qualifications and accountability.
• Researchers taking consent will demonstrably be able to ensure the participants receive necessary information and that consent procedures follow the protocol.
• Researchers taking consent will ensure the volunteer is able to decide for him or herself (has capacity) and is not unduly influenced by the research team.
• Volunteer’s understating will be confirmed by an agreed multiple-choice quiz.
• Consent will be recorded as a signature, itemised detailing with agreed key issues.
 
But it’s important to recognise that considering the proposal itself can only be our “first moral first base”. On its own this is inadequate and review must ask “What are the possible alternative courses of action?” considering these along with their consequences (benefits and harms):-
• Option 1: Continue as is without these studies.
• Option 2: Conduct the proposed study.
• Option 3: Undertake a study with a different design.
The potential benefits of all three should be modelled, quantified if possible and compared, asking questions “Are there alternative, less intrusive methods that could provide equivalent and reliable data as rapidly?”
 
Review needs answers to all these questions for these alternatives. Any decision must be based on these.
 
Favourable opinion will then depend on the proposed study being the favoured choice.
 
References
1. World Health Organization 2020. Key criteria for the ethical acceptability of COVID-19 human challenge studies 6 May 2020 accessed June 2020.https://www.who.int/ethics/publications/key-criteria-ethical-acceptability-of-covid-19-human-challenge/en/ accessed June 20th 2020
2. The UK Academy of Medical Sciences report “Microbial Challenge Studies of Human Volunteers” https://acmedsci.ac.uk/file-download/34726-1127728424.pdf accessed July 202

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