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

Abstract

Objectives: 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.Study Design and Setting: PubMed was searched for recently published noncommercial, placebo-controlled randomized drug trials. Corresponding authors were invited to participate in an online survey.Results: 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$ 2,428e US$ 160,770; n 5 24), accounting for a median of 10.3% of the overall trial budget.Conclusion: 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.

Identifying obstacles hindering the conduct of academic-sponsored trials for drug repurposing on rare-diseases: an analysis of six use cases

“…A recent meta-research study [26] describes a series of challenges in obtaining placebo for investigator-initiated drug trials, including the high cost for production and packaging and the unwillingness of manufactures to provide placebos for RCTs without previous assessment and approval of protocols [27]. Five of the six trials analyzed in this work were placebo-controlled.…”

Investigational medicinal products, related costs and hospital pharmacy services for investigator-initiated trials: A mixed-methods study

“…The absolute IMP costs in the Belgian paper are by a factor of 10 higher than the median actual IMP costs in our sample, but the IMP cost proportions of the total costs in both cases are well within the IQR of IMP cost proportions in our sample (3%-12%). A recent meta-research study examined costs of placebos used in IITs [21]; median costs for placebos and packaging were 58'286 US$ (IQR, US$ 2'428 to 160'770), accounting for a median of 10.3% of the total trial budget, which is somewhat higher than the median IMP costs found in our study including both, verum and placebo costs (US$ 15'000; median of 5% of total trial budget). Other studies have discussed various fee structures for pharmacy services related to IMPs all dating back to the 1990s [22][23][24][25][26][27], or evaluated cost savings with pharmacy managed IMPs in breast cancer trials compared to standard treatment for the healthcare system between 2014 and 2016 in Spain [28].…”

“…Only few pharmaceutical companies are willing or in a position to manufacture matching placebos on demand. In addition, pharmaceutical companies appear more willing to provide the placebo if a clinical trial is within their interest [21].…”

Nutzenbewertung digitaler Gesundheitsanwendungen – Herausforderungen und Möglichkeiten

“…Strikte Einschlusskriterien erschweren die Rekrutierung und können die Anwendbarkeit der Ergebnisse einschränken. Placebos erhöhen den Aufwand zudem mitunter beträchtlich (geschätzt 10 % des Gesamtstudienbudgets [ 27 ]) und führen zu einem Behandlungsvergleich, der unter Real-World-Bedingungen nicht existiert und reale Therapieentscheidungen nicht abbildet [ 24 ].…”