A meta-research study revealed several challenges in obtaining placebos for investigator-initiated drug trials

To systematically assess the kind of placebos used in investigator-initiated randomized controlled trials (RCTs), from where they are obtained, and the hurdles that exist in obtaining them. PubMed was searched for recently published noncommercial, placebo-controlled randomized drug trials. Corresponding authors were invited to participate in an online survey. From 423 eligible articles, 109 (26%) corresponding authors (partially) participated. Twenty-one of 102 (21%) authors reported that the placebos used were not matching (correctly labeled in only one publication). The main sources in obtaining placebos were hospital pharmacies (32 of 107; 30%) and the manufacturer of the study drug (28 of 107; 26%). RCTs with a hypothesis in the interest of the manufacturer of the study drug were more likely to have obtained placebos from the drug manufacturer (18 of 49; 37% vs. 5 of 29; 17%). Median costs for placebos and packaging were US$ 58,286 (IQR US$ 2,428– US$ 160,770; n = 24), accounting for a median of 10.3% of the overall trial budget. Although using matching placebos is widely accepted as a basic practice in RCTs, there seems to be no standard source to acquire them. Obtaining placebos requires substantial resources, and using nonmatching placebos is common. Graphical abstract: Summary of key results from the survey. a “Using simple saline” (n = 3); “Pharmaceutical” department (n = 3); “Self-made” placebos (n = 2); “Guys and ST Thomas” manufacturing (n = 1); Demonstration” samples used (n = 1). b “Container for liquid/cream were identical (n = 4); “used a commercially available” similar product (n = 2); “We were able to produce them identical” (n = 2); “same color and other characteristics” (n = 2); sterile water (n = 1); “Pharmaceutical manufacturer provided” placebo (n = 1); “hospital pharmacy produced” identical gel (n = 1); “used only excipients” (n = 1). [Display omitted]