Covid-19 vaccine trials in low and middle-income countries: what’s the benefit?

Low and middle-income countries that hosted trials for approved vaccines are not receiving vaccine doses as expected

There is a great inequity in the distribution of vaccines worldwide. Eighty-five per cent of doses have been administered in high-income and upper-middle-income countries, while only 0.3% have reached low-income countries. [1] The US is vaccinating a very low-risk population (adolescents) while the virus runs free in other low and middle-income countries (LMIC), such as India, affecting the most vulnerable groups. There has been criticism of how high-income countries have stockpiled an immoral surplus of vaccines while other countries struggle to strike deals for vaccinating highly prioritised groups in what has been called vaccine nationalism. [2,3]. Moreover, I have detailed how LMICs use vaccines for which we have little data beyond press releases. [4]

LMIC countries hosted large phase III randomised controlled trials for vaccines that are now being widely distributed in high-income countries (HIC). Some of the LMIC countries with the highest number of phase III trials include India, South Africa, Argentina, and Brazil. [5] The three latter hosted the Pfizer/BioNTech vaccine trials and subsequently authorised its use, but received too little of the vaccines, and too late. By May 2021: Argentina (population 45 million) has not been able to agree on any purchases, South Africa (population 58 million) received 325k doses (with a promise of 4.5 m), and Brazil (population 211 million) received 1.6 m doses (with a promise of 100m). [6,7]. Negotiations with vaccine companies have reportedly been problematic with some of these countries. [8,9] 

As the gap in the proportion of vaccinated people in HICs and LMICs increases, leading to worse control of the pandemic in the latter, LMIC countries become an attractive location for phase III trials for vaccine candidates. In an analysis by Dal-Ré et al, they outline a series of opportunities for the conduct of placebo-controlled crossover trials in these settings, highlighting that the use of placebo might be reasonable if the “standard of care” (in this case, the use of efficacious vaccines) is not possible to implement at a widescale. [10]

In their analysis, Dal-Ré and colleagues say that research participants and their host communities should benefit from the research. Iyer et al. go further and say that these countries should receive higher priority for any resulting vaccine. [11] These recommendations align with the International Ethical Guidelines for Health-Related Research Involving Humans by the Council for International Organizations of Medical Sciences (CIOMS). [12] However, the definition of what constitutes “benefit” for the community remains elusive. Based on the principle of justice as equality, reciprocity, and beneficence, we need to define who should benefit in vaccine trials. This could be restrictive to the trial participants (or even a subset of participants at high risk for covid) or expansive to the whole community. [13] Considering that the covid-19 pandemic will not be under some control until a large proportion of the community is immunised, if we restrict the benefit to the trial participant, not even the participant will be receiving optimal care in the context of rising cases and vaccine shortages in the community. Even if the participant remains unaffected by covid due to immunisation, the rising occupation of ICU beds and the following restrictions to care could result in serious harm if affected by another critical illness. Therefore, we need to adopt the broadest definition for those who would benefit from trials in LMIC countries. Pharmaceutical companies and regulatory agencies need to establish ethical safeguards to guarantee the benefit to the community, including prioritisation in the purchase and distribution agreements, prior to the conduct of the vaccine trials. Otherwise, we will effectively be saying that people living in LMIC countries are good for experiments, but bad for business.

Juan Víctor Ariel Franco is the Editor-in-Chief BMJ Evidence-Based Medicine and a Full Professor at the Research Department at the Instituto Universitario Hospital Italiano de Buenos Aires (Argentina).

Karin Kopitowski is the Director of the Research Department at the Instituto Universitario Hospital Italiano de Buenos Aires and ex-chair of the Institutional Review Board at Hospital Italiano de Buenos Aires (Argentina)

Twitter handle @juan_francomd @karinkopitow

Competing interests: JVAF none declared (full statement available here). KK none declared.


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