Non-pharmaceutical interventions during Covid: glaring evidence gaps

At the start of the pandemic, governments worldwide imposed various combinations of restrictions including stay-at-home orders and closures of schools or businesses.


More than two years later, despite billions of people worldwide having being affected, there is still considerable uncertainty about the benefits and harms of these measures.


Why is there so little robust evidence?

Note: This blog is part of a series presenting the findings of a recent report by Health Action International and TranspariMED. Previous blog discussed Covid research waste and the global trial registry system. A future blog will discuss the transparency of vaccine trials. The full report can be downloaded below.


Early warnings


Over the past two years, many heated political debates have revolved around which non-pharmaceutical interventions (NPIs) to impose at what points in time. However, there was often little to no ‘robust’ evidence from randomized controlled trials on which decision-makers (or their critics) could draw.


Concerns over the weak evidence base for the public health benefits of some NPIs were raised very early in the pandemic, coupled with urgent pleas for more and better research.


Where are the trials?


Nonetheless, two years into the pandemic, only 57 randomised trials assessing NPIs had been registered. Around half of these NPI trials were focused on just two interventions: protective equipment and information or education programmes.


Only 11 NPI trials had published their results by February 2022.


A Cochrane review of interventions to reduce the risk of Covid infection outside of healthcare settings published in May 2022 found only one relevant completed trial.

In contrast, over 300 trials for the drug hydroxychloroquine alone, and more than 4,000 COVID-19-related clinical trials overall, had been registered by that time. (Note that interventional studies of “behavioural treatments” are explicitly included the WHO definition of clinical trials.)


According to one calculation, only 4% of global COVID-19 research funding was allocated to researching public health measures.


Where were the research funders?


Responsibility for this research gap lies primarily with governments, which typically implemented NPIs across the board instead of running cluster randomised trials to generate robust evidence before further rollout.


In addition, research funders – many of which are public bodies – appear to have neglected to encourage and fund relevant research.


Negative impact on global health


The failure to generate robust evidence on NPIs probably had a major negative impact on global health, and will undermine responses to future pandemics.


The WHO has argued that “evidence-informed decision-making is essential to ensure that the intervention burden of [NPIs] does not outweigh their benefits,” but has concluded that there is still a lack of “studies disentangling the relative effects of various measures, their intervention burden and risk–benefit ratios.”


Similarly, a recent OECD review of 67 government evaluations concluded that “issues relating to policies’ proportionality and coherence are still largely under-explored”.


Policy makers reviewing lessons learned from Covid during the outbreak of the next pandemic will fail to find strong scientific consensus on which NPIs had a positive benefit-harm balance for what population in what settings unless whatever evidence is available now is carefully synthesized.


Where are the policy makers?


Now that NPIs are being discontinued in most countries, there is an acute danger of this highly consequential research failure of the pandemic being forgotten – until the next pandemic strikes.


While a low profile WHO working group is currently attempting to strengthen the evidence base on NPIs, there currently appear to be no high-level policy initiatives promoting the generation of robust evidence on NPIs.


(The COVID-evidence team is continuously keeping track of NPI trials and their results.)


The European Commission should form a working group to develop actionable recommendations for European bodies and national governments on how to generate and synthesize robust evidence on NPIs.


Download the full report


The full report by Health Action International and TranspariMED from which this blog was extracted can be accessed online or downloaded below.

Covid clinical trial integrity_TranspariMED_HAI_20220516
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