NIH COVID-19 treatment analysis

Authority review was extremely slow and overlooked most research Official treatment recommendations were often made based on a small fraction of the evidence, with substantial bias in the selection of studies. Just as 78% of experts polled regarding the origin of COVID-19 were not familiar with the DEFUSE protocol4, experts on COVID-19 treatments were not familiar with much of the key evidence. In some cases, recommendations were made without reviewing any clinical evidence, for example the US FDA recommended against ivermectin in an article that stated "The FDA has not reviewed data to support use of ivermectin in COVID-19"5. In cases where the people involved in recommendations are known, they were often busy professionals that could not realistically have time to carefully review all evidence6.

NIH reviews NIH treatment reviews were done by a panel of 40+ external experts with extensive conflicts of interest towards high-profit treatments6,7. Out of 10,208 proposed treatments8, they found only three high-profit drugs from top lobbying companies to be beneficial for early treatment(a). Most others received either "insufficient evidence" or no review at all, despite extensive unreviewed evidence.

Across all low-cost treatments that reduce risk (within the 180 we cover), the NIH only referenced 2% of the studies. For vitamin D, the NIH claims "There is insufficient evidence for the Panel to recommend either for or against the use of vitamin D"9. No authors are listed, they provide only a brief narrative review with no quantitative analysis, and they reference only 5 of the 126 controlled studies (30 RCTs). The state is similar or worse for other treatments (Table 1). The NIH provides no quantitative analysis for any of the treatments listed.

Considering RCTs for vitamin D, the NIH references only 410-13, missing 26 other RCTs (Figure 114). The NIH selection does not correspond to the most relevant and highest quality studies, for example including Murai et al.11 and Mariani et al.12, which study very late treatment using bolus doses of cholecalciferol—a trifecta of poor design and low relevance compared to recommended use: early treatment is better, continuous dosing is more effective than bolus doses, and calcifediol, calcitriol, or analogs avoid long delays in conversion. They include none of the early treatment RCTs. We provide similar analysis for vitamin C15 and zinc16.

Waiting for RCTs costs lives While the NIH examined few of the RCTs, they dismissed almost all observational studies. RCTs can provide significant advantages, however they show no benefit for COVID-19 and they introduce significantly delay. For the 180 treatments analyzed, there is no difference in results between RCTs and observational studies, RR 0.98 [0.92‑1.05]17 (Figure 4). Observational studies do not systematically over- or underestimate efficacy, as found in previous research18,19, and they provided confirmation of efficacy 7+ months faster. RCTs aim to equalize study groups, but add their own biases. For acute diseases with strong benefits for earlier treatment, the typical increased treatment delay adds a major confounding factor. Both RCTs and observational studies span the bias spectrum, from minimal to extreme. Studies must be evaluated individually. While observational studies require greater expertise to analyze, the advantages in practicality, cost, time, and ethics are substantial.

Waiting for specific outcomes costs lives While patented treatments may be approved with a single non-clinical result20, authorities often dismiss results for low-cost treatments where studies report different outcomes. To avoid delay and unnecessary mortality, we must use all available information. Logically, minimizing viral replication will minimize serious outcomes. Singh et al.21 confirm, showing that improved viral clearance was significantly associated with lower hospitalization/death. We confirm this across all 180 treatments covered, finding improved viral clearance strongly associated with lower serious outcomes, p = 0.00000000069 (see22 for details). Authorities may not pool any outcomes, e.g., separating studies reporting mortality and studies reporting ICU admission, however data shows that—for COVID-19—it is valid to combine outcomes from viral clearance to mortality.

Novel treatments are high risk, existing treatments have a critical safety advantage Existing treatments have a strong advantage with known pharmacokinetics and safety profiles. New agents are more risky. By definition, long-term risks cannot be known, and known risks may not be acknowledged for some time. For example, molnupiravir's potential risks include the creation of dangerous variants23-27, mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity28-42. While the risk always exceeded the benefits within the context of all treatments, and confirmation of harm continues to accumulate, the treatment is still used in 2025 in some locations. Novel treatments saw limited use during the pandemic43,44, partly due to prescription requirements, limited availability, high cost, and, for certain treatments, administration requirements and extensive drug interactions.