key: cord-0854616-dz1mzxbj
authors: Watson, Samuel I; Lilford, Richard J
title: Global COVID-19 vaccine roll-out: time to randomise vaccine allocation?
date: 2021-05-13
journal: Lancet
DOI: 10.1016/s0140-6736(21)00895-3
sha: 50c0ec2484d3318eef901b973579d57215d0d651
doc_id: 854616
cord_uid: dz1mzxbj

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To address COVID-19 vaccine scarcity, Ivan Sisa and colleagues 1 justify placebo-controlled trials in lowincome and middle-income countries (LMICs), arguing that these countries have "less capacity to negotiate and purchase vaccines than do highincome countries" and that the global shortage can be overcome with more vaccine producers coming from such trials. We are concerned that this reasoning sets the wrong precedent because approving such a trial should show that evidence can only be reached with this design. 2 Furthermore, LMICs should not ignore the urgent need to increase production and distribution 3 of already efficacious vaccines.

In the interest of saving people's lives, vaccine development demands working towards improved capacities on the road from discovery (free of patent restrictions) to manufacturing and equitable distribution. Therefore, clinical trials should be done simultaneously, engaging volunteers and researchers across a broad range of LMICs and high-income countries. Furthermore, study protocols should provide robust assurances that participants will have access to the vaccine when their priority group is eligible in the general population. Finally, emphasis should be made on other pressing issues, such as adopting low dead space syringes to prevent discarding residues, thus improving vaccine volume. 4 Ensuring efficacious vaccines are made widely available and at fair cost, when high-income countries are hoarding up to five times what they need 5 and prices are speculative, would require making alliances with countries (eg, Brazil or India) with the capacity to produce generic vaccines, alongside efficient syringes, and means of storage and transportation. Notwithstanding, LMICs will need support from additional partners in other regions of the world.

We declare no competing interests. In 2000, Lilford and colleagues 1 proposed the so-called tracker studies. Although the COVID-19 vaccine roll-out is on a different scale to most medical technologies, it is illustrative of the rapid change often associated with the development of new treatments in many areas of medicine. Health technologies, particularly devices, are subject to frequent modifications in their design once introduced, and the entry of new competitors with slight or large modifications is frequent. Adoption of these new technologies can happen uncritically 1,2 and independently of their actual effectiveness. 3,4 A tracker study would start early in periods of rapid technological change; patients would be randomised between reasonable alternatives, and new alternatives can be introduced into the randomisation scheme as they become available. Such a design can borrow features from adaptive randomised trials, 5 and it can incorporate features of network meta-analysis that permit the estimation of the difference in effectiveness of two alternatives, even if they were not directly compared. 6 These studies differ from conventional randomised trials that are typically one-off events following preset and rigid protocols.

With more vaccines in the pipeline, the global COVID-19 vaccine roll-out is the exact type of situation Lilford and colleagues 1 predicted. At present, there exists sufficient equipoise that it would not be unreasonable to randomise the type of vaccine an individual received. In high-income countries particularly, the public health infrastructure can track disease outcomes at the individual level. Given the unprecedented investment in COVID-19 preventive measures, there is an imperative to maximise our learning, which will become one of the best defences we have against future pandemics. For 60 years, Universidad Peruana Cayetano Heredia (UPCH) in Lima, Peru, has contributed to world-class knowledge in tropical medicine, highaltitude medicine and physiology, public health, and basic sciences with the highest research standards and ethics. We therefore read with interest the World Report by Lucien Chauvin, 1 in which we found some inaccuracies that we would like to clarify.

First, the Peruvian National Institute of Health has not suspended UPCH from conducting clinical trials. Only the site corresponding to Sinopharm's phase 3 BBIBP-CorV vaccine trial has been stopped from initiating future studies during the current investigations of research misconduct. This measure preserves the ongoing trial, protects its volunteers, and assures the study's completion, led by a newly designated principal investigator.

We also wish to stress that once we acknowledged the regrettable events associated with a batch of additional vaccine doses held outside of the study, the university's community demanded the removal of the researchers involved from the clinical trial. We also urged for the resignation of UPCH's president and vicepresidents for having received some of these doses. All university members involved in the scandal are under investigation and will face sanctions according to the statutory disciplinary and ethical regulations of UPCH.

As UPCH's leading researchers, and in line with the values that gave rise to our institution, we feel vicariously ashamed and apologise to the community for the involvement of UPCH's name in such an unfortunate case. We assure the national and international scientific community that we will continue our research activities at the highest standards according to our tradition.

We declare no competing interests. Signatories of this Correspondence are listed in the appendix.

Trials and fast changing technologies: the case for tracker studies

Technology follies: the uncritical acceptance of medical innovation

The role of hospital payments in the adoption of new medical technologies: an international survey of current practice

Socioeconomic differences in the adoption of new medical technologies

Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov

Network meta-analysis-highly attractive but more methodological research is needed