The FDA has authorised remdesivir for use in COVID-19 patients: but there’s no good evidence it reduces mortality – a lay summary
At the end of April, the US National Institutes for Health (NIH) announced in a press release that their clinical trial on the experimental antiviral drug remdesivir had shown that it “accelerates recovery from advanced COVID-19”. Two days later, the drug was authorized by the US FDA to be “distributed and used by licensed health care providers to treat adults and children hospitalized with severe COVID-19”. This may look like an important breakthrough in treatment. However, there are concerns over the trial, and with how the results have been used.
According to the press release, Covid patients in the trial who received remdesivir recovered 31% faster than those who received placebo. This single isolated positive result was used to inform policy and treatment decisions on a massive scale. Yet, apart from the press release, the full details of the trial itself had not yet been published. This information is essential for doctors, patients, and policymakers to interpret the results of the trial accurately and make an informed judgement about the benefits and harms of remdesivir.
Concerns over the trial
- Preliminary results were announced early, “out of ethical concerns”, so that patients receiving a placebo or “dummy pill” could opt to receive the real drug instead. But, without knowing the drug’s effects on survival, this could be premature – if the placebo control is stopped early, we may never know if the real drug saves lives or not.
- The researchers running the remdesivir trial had changed course mid-trial. At the outset their key objectives had included measuring the drug’s effect on factors such as survival rates, and how many patients went on to require mechanical ventilation. But on 16 April the trial’s primary outcome was changed to “time to recovery”. Mid-trial changes, known as “outcome switching”, should be declared along with the results, and the reasons for the changes fully explained, to avoid distorting the eventual results. There is a grim history of patient deaths resulting from treatment decisions made on the basis of results from drug trials in which outcome switches had been undeclared. In the case of remdesivir, there are concerns that “time to recovery” might have been chosen because it was more likely to yield a positive result.
- “Time to recovery”, is far less critical to patients and health care professionals than death rates, adverse effects of the drug, or the need for mechanical ventilation. As one commentator said, “The reason we have shut our whole society down is not to prevent Covid-19 patients from spending a few more days in the hospital. It is to prevent patients from dying.”
- There is, at time of writing, no good evidence that remdesivir reduces the number of people who die from COVID-19. Another trial already published found that it did not reduce numbers of deaths, time to clinical improvement, duration of mechanical ventilation, or levels of the virus in the body. Could using remdesivir in COVID-19 now take funding away from other vital healthcare resources and research, without saving any lives?
COVID-19 is so new that the science is having to progress at lightning speed and doctors and policy-makers are making the best decisions they can amidst an ever-changing evidence landscape. Undeclared outcome-switching, using isolated results without publishing the trial, and generating media hype over modest findings is not helpful to healthcare professionals or to the patients suffering and dying.
Mandy Payne, 22nd May 2020
This is a lay summary of a report prepared for the Oxford COVID-19 Evidence Service by the Oxford Centre for Evidence Based Medicine by Henry M Drysdale, Nicholas J DeVito and Jeffrey K Aronson dated 12th May 2020.
Disclaimer: the article has not been peer-reviewed; it should not replace individual clinical judgement and the sources cited in the original report should be checked. The views expressed in this commentary represent an interpretation by HealthWatch and do not necessarily represent those of Oxford CEBM, the NHS, the NIHR, or the Department of Health and Social Care. The views are not a substitute for professional medical advice.