The ethics of CoVID-19 vaccine trials and impending state penalties for unethical publishing were key topics in the session on Ethical Research and Integrity at the 6th Biennial Research and Innovation Dialogue, that was hosted virtually by Universities South Africa’s Research and Innovation Strategy Group (RISG), on June 11.
Professor Jerome Singh (left), who spoke on “Research ethics in a pandemic context”, is Adjunct Professor in the Dalla Lana School of Public Health at the University of Toronto, Canada. He is also an Honorary Research Fellow at the Howard College School of Law at the University of KwaZulu-Natal.
He is one of six members of the World Health Organisation (WHO) Technical Advisory Group (TAG) for Emergency Use Listing of CoVID-19 vaccines, which evaluated and approved six vaccines being used around the world. These include Pfizer and Johnson & Johnson, and most recently, CoronaVac (Sinovac), approved on 1 June 2021.
As a member of WHO ACT – Accelerator Ethics & Governance Working Group – Access to CoVID-19 Tools, he led the drafting of the WHO’s Policy Brief of 18 December 2020 about ethical considerations for current and future COVID-19 placebo-controlled vaccine trials and trial unblinding.
Singh said it has been quite heartening to see how fast the scientific community has rallied around CoVID-19 to produce world class science.At least 260 CoVID-19 vaccines are under various stages of research and development globally, and about 82 candidate vaccines are being tested in clinical trials.
Even though worldwide public deployment of CoVID-19 vaccines has already commenced, clinical trials are still being conducted, with hundreds of thousands of people enrolled. Most of these trials will run for two years.
Now the big ethical dilemma is whether future vaccine trials should continue to be randomized and placebo-controlled. This is regarded as the scientific gold standard for evaluating the safety and efficacy of a new intervention. Yet, said Singh, they raise many ethical concerns: “When you have a major trial, and half the people are getting an intervention that’s useless and not going to provide any effect, you essentially are depriving those people of an intervention that could possibly work.”
The other concern is: should participants in existing clinical trials be unblinded (told whether they are being given the vaccine or the placebo)? In countries where their candidate vaccine is already being deployed, this could give those at higher risk – such as health workers and those aged over 65 – the option to leave the trial and be vaccinated. Or should all research participants be kept on the trial for two years to determine longer-term safety and evidence?
The answer seems quite simple, said Singh. “Of course, they should be unblinding people, but this is not what’s necessarily happening globally.”
Essentially, the emergency use listing of a vaccine does not equate to the “best proven intervention” or an “established effective intervention”. It is the absence of these criteria which makes it acceptable to use a placebo, according to the Helsinki Declaration (published by the World Medical Association), and the Council for International Organisations of Medical Sciences (CIOMS) Guidelines (published by WHO), respectively.
However, neither of those guidance documents were designed for the context of an international health emergency. “And that puts research institutions and regulators in quite a difficult position,” said Singh, “because if you are now looking at a trial, what do you actually do about this?” WHO’s stance, as published in December, is that placebo-controlled trials are still necessary. It has not developed further guidance on that or on unblinding.
What are the ethical implications of all this for South Africa hosting new CoVID vaccine trials? Singh posed three questions: Does the public deployment of CoVID-19 vaccines establish a standard of prevention? If so, which vaccine should be considered the “established effective intervention” and “best proven intervention”: J&J’s or Pfizer’s? And should new investigational CoVID-19 vaccines be tested against a placebo, or J&J, or Pfizer (or other candidate vaccines, should they also obtain approval)?
Claims need evidence
Comments from Professor Calvin Gwandure, Head of the School of Social Sciences at the University of Mpumalanga, on Professor Singh’s presentation, included that risk evidence seems to show young people are not as vulnerable to CoVID-19 as old people. Now schools are in a predicament. They want to open. Looking at evidence, do we have evidence that school children are dying, and do we have evidence that students are dying of CoVID-19 globally, without specifying South Africa?
He said they were encountering disturbing features of research trying to prove that CoVID is linked to race and ethnicity. “Do we have evidence that a race is more vulnerable, or this disease is affecting a particular race? As researchers, we need to base our decisions on evidence,” said Gwendure.
DHET is poised to clamp down on institutions that tolerate unethical publishing
Mr Mahlubi Chief Mabizela (right), Chief Director: University Education Policy and Research Support in the Department of Higher Education and Training (DHET), said he had been asked to answer the question on what government was doing regarding the issue of research ethics and integrity. He did exactly that.
Mabizela, who anchored the Policy Framework on Internationalisation of Higher Education in South Africa and the revised Language Policy Framework, spoke on “Addressing ethical research and publications: lessons from international & national initiatives”. He first shared, in detail, how they had learnt lessons from, for instance, the Singapore Statement on Research Integrity adopted in 2010; the 2017 European Code of Ethical Research and Integrity, and how previous initiatives included the 2018 workshop with USAf, the National Research Foundation (NRF) and the Academy of Science of South Africa (ASSAf) — resulting in a Declaration on Research Ethics in South Africa.
Mabizela said predatory publishing is declining internationally because there is a squeeze on it “and we are part of that”. Questionable editorial practices were not only in journals.
He said South Africa had experienced “a huge problem of excessive conference publishing” (by this he referred to claims, by some scholars, of presenting papers at what is considered an excessive number of conferences in one year) to the point that “in certain instances I find it embarrassing to even talk about it”, he said.
DHET had since taken steps to ensure its research output policy, meant to incentivise publishing, was not abused. These actions, based largely on the recommendation of the Quality of South Africa’s Research Publications Report of 2019, included:
- becoming co-signatories to the “Statement on Ethical Research and Scholarly Publishing Practices” with ASSAf, the NRF and USAf and the Council on Higher Education CHE (CHE), which sends a message of curbing unethical practice;
- developing a Research Quality Framework (RQF) that will be used nationally to guide interventions to ensure university research publications that qualify for funding under the research output policy meet the stringent criteria of quality and integrity that funding is meant to reward. They had convened an advisory committee in September, and there would be more meetings this year “because we want some of these to be introduced immediately. Watch this space because we want to consult the sector once we have a solid draft on the measures that we will be implementing”, Mabizela said;
- Rejecting publications found to have not met the criteria of ethical publishing, DHET is using the same conventions academics are used to, such as peer review, and, to avoid conflict of interest, prohibiting publishing in the journal that one edits, except under certain circumstances such as a special issue.
- Penalties are “one of the areas we want to introduce immediately”, Mabizela said. He added that the responsibility would fall on institutions. “The cost of rewarding research outputs is around R5 billion and it is growing. Unfortunately, it is growing with these unethical practices.”
In his closing comments, Mabizela emphasised that monitoring and policing the ethics and quality of research publications was not the sole responsibility of government. “This should be dealt with at institutional level; institutions ought to be more passionate about this than government trying to protect the integrity of the system, and the subsidy that goes into this,” he said.
He said universities should start working on tightening their ethical practices, and not expose themselves to the embarrassment that will be accompanied by the introduction of penalties when their outputs have been found out to be ethically wanting.
He commended the RISG Dialogue’s afternoon session on Ethical Research and Integrity and suggested that it be made the topic of a stand-alone and dedicated colloquium, allowing more detailed
Engagement, in future. “I would have loved to give some examples that we come across when dealing with research outputs, because we do analyse them,” he said.
Professor Ahmed Bawa, USAf’s CEO, commented during the discussion session that they had ask to themselves whether they were doing enough work in terms of the scholarship around publishing.
Mr Samson Khene, Senior Lecturer in Physical Chemistry at Nottingham Trent University, and formerly an associate professor at Rhodes University, posted a question in the chat forum: “Is there a record or a systematic study that indicates or quantifies how much of the research done in South Africa contributes to the growth of South African society?
Professor Ahmed Bawa responded by saying the NRF was putting in place a new project relating to the impact of research on social development and growth. This was recognition of the need for this type of research. There were also some psychometric studies which, in societies around the world, showed the extent to which research outputs related to innovation. Professor Bawa said Khene had asked an important question which USAf, through the RISG, needed to address.
Gillian Anstey is a contract writer for Universities South Africa.