Evaluation of publication bias for 12 clinical trials of molnupiravir to treat SARS-CoV-2 infection in 13,694 patients

Abstract

Introduction: During the COVID-19 pandemic, Merck Sharp and Dohme (MSD) acquired the global licensing rights for molnupiravir. MSD allowed Indian manufacturers to produce the drug under voluntary license. Indian companies conducted local clinical trials to evaluate the efficacy and safety of molnupiravir. Methods Searches of the Clinical Trials Registry-India (CTRI) were conducted to find registered trials of molnupiravir in India. Subsequent investigations were performed to assess which clinical trials had been presented or published. Results According to the CTRI, 12 randomised trials of molnupiravir were conducted in India, in 13,694 patients, starting in late May 2021. By July 2022, none of the 12 trials has been published, one was presented at a medical conference, and two were announced in press releases suggesting failure of treatment. Results from three trials were shared with the World Health Organisation. One of these three trials had many unexplained results, with effects of treatment significantly different from the MSD MOVE-OUT trial in a similar population. Discussion The lack of results runs counter to established practices and leaves a situation where approximately 90% of the global data on molnupiravir has not been published in any form. Access to patient-level databases is required to investigate risks of bias or medical fraud.

Molnupiravir Plus Usual Care Versus Usual Care Alone as Early Treatment for Adults with COVID-19 at Increased Risk of Adverse Outcomes (PANORAMIC): Preliminary Analysis from the United Kingdom Randomised, Controlled Open-Label, Platform Adaptive Trial

“…Concern has been raised regarding the lack of public sharing or formal publication of the findings of these three trials, along with nine others, all of which were conducted in India. 23 The reviews found that molnupiravir probably reduces: hospitalisation (odds ratio 0•54; 95% CI: 0•30 to 0•90; n=5 trials); and, time to symptom resolution (-3•3 days; 95% CI: -4•8 days to -1•6 days; n=3 trials). The WHO therefore advises that molnupiravir may be of benefit in outpatients with mild-moderate COVID-19 at the highest risk of an adverse outcome.…”

“…The observed median (IQR) time-to-first-recovery from randomisation was 9 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) 2). Subgroup analysis demonstrated that this benefit was consistent across all studied groups.…”

“…Estimates were similar for all subgroups. The observed median (IQR) time-to-first-recovery from randomisation was 9 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) days in molnupiravir and 15 ( Interpretation In this preliminary analysis, we found that molnupiravir did not reduce already low hospitalisations/deaths among higher risk, vaccinated adults with COVID-19 in the community, but resulted in faster time to recovery, and reduced viral detection and load.…”

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

“…Concern has been raised about the lack of public sharing or formal publication of the findings of these three trials, along with those of nine others, all of which were done in India. 21 The reviews 19,20 reported that molnupiravir probably reduces hospitalisation (odds ratio 0•54 [95% CI 0•30 to 0•90]; based on five trials) and time to symptom resolution (-3•3 days [-4•8 days to -1•6 days]; based on three trials). WHO therefore advises that molnupiravir might benefit outpatients with mild-to-moderate COVID-19 at the highest risk of adverse outcomes.…”