Keeping Evidence-Based in the Midst of a Pandemic

The Covid-19 pandemic requires urgent scientific knowledge about how to best diagnose, treat, and prevent the spread of the SARS-CoV-2 virus. This is at odds with the deliberate nature of evidence-based medicine (EBM), where it is important to use more deliberate methods to discern the best evidence.

Another challenge is to disseminate the results of research as quickly as possible. The availability of preprint servers and other modern Internet tools allow us to publish first and peer review later. But of course that raises worry that inadvertent error or even deliberate falsehoods might taint the quickly expanding evidence base.

How do we achieve a balance? We have already seen the downside of actions moving ahead of the science. Probably the best example of this is the drug hydroxychloroquine. While this drug may prove of value in preventing and treating SARS-CoV-2, it does have significant adverse effects, especially when taken in doses that exceed the normal therapeutic level. In addition, it is a drug whose availability for other diseases it treats, such as lupus, must be maintained for those patients.

Clearly hydroxychloroquine should be studied, but it should ideally be done in as controlled a way as possible, lest we not cause harm or generate false hope. We may not be able to perform classic double-blind, placebo-controlled randomized controlled trials, but we should still enroll and track patients in highly controlled manners. We cannot forget that this is a disease from which the majority of patients fully recover, so we need to make certain that improvements due to any treatment are not just due to normal recovery from the disease. There must be some sort of control group and a diligent follow-up to insure no missing data in control or experimental groups.

In my view, there are a number of critical questions to answer about SARS-CoV-2:

• How well do tests diagnose active infection with the disease?
• How well do tests diagnose serum antibodies indicating immunity?
• What treatments are available for the disease?
• Are there any preventive treatments for the disease, from drugs to immunizations?
• What is the best way to prevent spread in the general population?
• What is the best way to protect healthcare workers treatment patients with the disease?

All of these can be answered with the usual EBM methods of controlled studies that have served us well. They can also be augmented with large-scale data sources from which we are learning to do better observational studies. We can also carry out systematic reviews, with meta-analysis when appropriate, to collate the results of many studies.

Unfortunately, the deliberate pace of EBM must be balanced with the urgency to develop treatments, vaccinations, and methods to curtail spread of the virus. Likewise, the rapid publication of results on preprint servers and other sources must be followed with peer review and collation into systematic reviews and meta-analyses. Hopefully this will give us the best evidence based for treating and preventing this disease.