Non-randomized observational studies used during the COVID-19 pandemic to evaluate drug treatments showed benefits that were not confirmed in high-quality randomized controlled trials. Studies on drugs like hydroxychloroquine, remdesivir, ivermectin, aspirin, molnupiravir, and tenofovir found positive results in observational studies but not in randomized trials. This suggests that observational studies may not be as reliable for determining the effectiveness of treatments and should not be the sole basis for regulatory decisions.