Interim Analysis of WHO SOLIDARITY study bad news for Remdesivir and other treatments

The WHO has published a medRxiv report of an interim analysis of their SOLIDARITY study, a large international randomized study comparing Remdesivir, Hydroxychloroquine (HCQ), Lopinavir, and Interferon , and "no study drug" controls for treatment of hospitalized COVID-19 patients.


The study found no benefit of Remdesivir over control in terms of survival, need for ventilation, or hospitalization duration, and it did not do demonstratively better than HCQ, Lopinavir, Interferon, three treatments that are not thought not to work. This means the only drug that has been rigorously shown to provide a survival benefit is Dexamethasone, a cheap, readily available steroid that reduces inflammation.


The study seems rigorously designed: it has 11,266 adult patients from 405 hospitals and 30 countries, with 2750 allocated Remdesivir, 954 HCQ, 1411 Lopinavir, 651 Interferon plus Lopinavir, 1412 only Interferon, and 4088 no study drug. The compliance was exceptionally high. The randomization and inclusion of a "no study drug" control makes this the strongest study to date investigating clinical benefit of these drugs, and their results suggest patient characteristics were well balanced between the study drug and control groups, ensuring they were not confounding factors in any comparisons.


It is beyond disappointing that no clinical benefit was shown for any of these drugs, especially Remdesivir, that has been broadly discussed as a great treatment success by the media, scientific community, and major national scientific leaders since its emergency use approval (based on scant evidence), even mentioned by some as a potential key factor explaining why COVID-19 mortality has decreased so rapidly since the spring. At $2340 per 5 day course, it is questionable whether that cost is justified for a drug that has no demonstrative clinical benefit in this large randomized trial. It is possible that Remdesivir works under certain circumstances, but in this trial it showed no benefit in any of the subgroups considered, either. The paper also presents a meta-analysis combining information across all current randomized trials involving Remdesivir, including this SOLIDARITY trial, ACTT study, a Wuhan study, and SIMPLE trial, and found the meta-analysis also suggested no survival benefit for Remdesivir.


This is one of the hazards of Wartime Science, our necessarily accelerated efforts to study emerging drugs and providing quick access to any that show promise so that we have alternatives for the millions of patients currently infected. Based on this trial, all of the major treatments we have tried do not provide improved clinical response, outside of the anti-inflammatory steroid Dexamethasone, which is a clear success. Along with the HCQ fiasco, this demonstrates that we need to be careful not to get carried away with unwarranted optimism based on limited results from preliminary studies -- it is reasonable to give emergency use authorizations under these circumstances, but we need to keep in mind that these authorizations are given based on scant evidence and we need to wait for results from more rigorous studies before we can confidently conclude they are safe and providing a clear clinical benefit.


The study is successful in the sense that it demonstrates it is possible to set up, coordinate, and conduct a large, multinational randomized clinical trial of numerous emerging treatments in real time during a pandemic. The fact that they were able to conduct such a rigorous trial, and with such high compliance, during the pandemic and obtain results in just 6 months or so is a testament to the scientific cooperation and competence that bodes well for our ability to rigorously learn in real time. Even negative studies have value, since they keep us from putting hope in ideas that don't work, and hopefully focus our efforts and finances on the ones that do, and motivate us to keep looking for better options.



 

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