The COVID-19 pandemic has triggered the biggest mobilization of scientific effort in a generation. Scientists from fields as diverse as immunology and computer science quickly pivoted to studying drivers of the epidemic and potential countermeasures. More than 54,000 articles relating to the SARS-CoV-2 virus have been published in academic journals in the biomedical and life sciences to date.
This scientific surge is astounding and inspiring, but it has produced some ethical dilemmas. The urgency of the crisis has led to a proliferation of studies, some of which short-circuit the most rigorous scientific standards. Results often get disseminated to the public before they’ve been reviewed by experts, which can lead to a situation in which doctors, politicians and others advocate unproven cures.
The gold standard for scientific learning is the randomized, controlled trial (RCT), in which a group of participants is randomly assigned to receive either the treatment being investigated or a comparison treatment, which might be a placebo. Randomly assigning participants to these two groups ensures that the groups are similar, reducing the possibility of bias.
Although SARS-CoV-2 vaccines are being tested using RCTs, nonrandomized studies have been common for COVID-19 therapies. Many have occurred within “expanded access programs,” through which the Food and Drug Administration allows patients to access therapies that have not yet received marketing approval. For instance, for convalescent plasma (blood plasma from disease survivors), evidence from case reports and animal studies was provocative enough to justify launching an RCT to test it for COVID-19. However, the federal government instead approved an expanded access program through which physicians administered plasma to nearly 70,000 patients without any control groups. Without randomization, researchers have not conclusively shown that improved outcomes are the result of taking plasma. Nevertheless, the FDA granted an emergency-use authorization for convalescent plasma in August. Another cautionary tale is hydroxychloroquine, the drug President Trump began touting in March. The FDA authorized it on the basis of observational studies and later had to reverse itself when RCTs showed it to be ineffective and unsafe.