Altogether, data from 13,694 Indian trial participants has not been formally published, with data from 11,258 of these not being publicly available, not even in summary form e.g., in press releases. There is also a lack of transparency about what level of access the Indian drug regulator and the WHO have to the data. The companies themselves appear to be the only ones with complete access. The CDSCO is likely to be the best informed, having seen presentations of the data for all the trials (39). Meanwhile, the WHO appears to have access to only limited summary data from 3 of the 12 trials. The full extent of the information organisations such as the CDSCO and WHO have used to make national and international guidelines is unclear.
The Hetero trial’s interim analysis presents somewhat of a puzzling case. It is hard to understand how the Indian trial could have recruited, followed up and analysed a similar number of patients to the MSD trial in a far shorter period. Enrolling, treating, and assessing 741 patients across 15 sites in a few weeks and then immediately analysing and publishing this data is an unusual achievement – even for COVID-19 trials with accelerated timelines. Hetero’s timeline looks even more out of place in comparison to the interim analysis of the MSD run MOVe-OUT trial, which took almost five months to produce their interim analysis compared to just over six weeks for Hetero, as Table 2 demonstrates. This disparity is difficult to comprehend, especially when accounting for the reality that MSD’s annual revenue is 40–50 times greater than that of Hetero (40, 41). It is also troubling that both trials exhibit the same trend of very positive interim results followed by negative outcomes in post-interim analysis data. Concerningly, Hetero, has also been involved in numerous scandals over the past decade ranging from poor manufacturing practices (42–44), pollution breaches (45, 46), being accused of corruption and intimidation (45), and suspect accounting practices (47).
The Optimus Pharma data also raises questions for several reasons. Firstly, the trial was reported to have been completed in October 2021 in a press release containing very limited results (36) though this was not reported to the CTRI (see Table 1). Then, in December 2021, a new statement containing different results was released (37). While this may be because the October figures were based on interim results, this was not made clear in the press release. More generally, while PCR negativity in the molnupiravir arm varies somewhat, it fluctuates widely in the Standard of Care (SoC) arm. Of more concern is the fact that the PCR negativity reported by Optimus Pharma in the second set of figures they released in October 2021 is nearly identical to that reported by Hetero (29, 36). Neither of these results is consistent with the MOVe-OUT data (see Table 2).
Globally, the largest molnupiravir trial is the UK Panoramic trial coordinated by Oxford University, which has recruited over 20,000 patients to either molnupiravir or standard of care since December 2021 (48). This is over double the initial planned sample size of 10,600 (49), but no explanation is available for such a large increase in sample size.
While the results from Panonoramic are due imminently, they have not been published at the time of writing. Adding the number of patients from Panoramic to the unpublished Indian data leaves data for at least 31,258 molnupiravir patients unpublished (or 33,694 when including the Hetero and Optimus Pharma patients whose data was only partially released). Therefore, almost 90% of the global data on patient outcomes following treatment with molnupiravir are currently unavailable. Even when the Panoramic trial reports results, that will still leave at least a third of the global molnupiravir data unpublished. Previously, when it emerged that 60% of the patient data related to Tamiflu had not been published (50), this was viewed as a scandal; so far, there has been no similar level of concern regarding the molnupiravir data. Whether the Indian molnupiravir data is unreleased due to neglect or because of commercial considerations as occurred when GlaxoSmithKline concealed data regarding the lack of efficacy of the antidepressant paroxetine in patients under 18 (51) cannot be determined. Patient-level data would help answer many of the unanswered questions swirling around the molnupiravir trials; however, even summary data is largely absent, as discussed. The inherent danger of making decisions without access to all the relevant information is heightened, given the concerns about molnupiravir’s genotoxicity and potential risk to pregnant patients (52). Given the scale of the missing data, the MHRA’s decision to grant EUA for the drug seems premature, as others have previously argued (53).
Unfortunately, the problem of a lack of data transparency is not isolated to one country. While the USA has required trial sponsors to publish trial data within one year of study completion, these rules do not apply globally. Even in the US, compliance is poor, with only 41% of sponsors meeting this requirement (54). It is approaching 12 months since most of the 12 Indian trials concluded. While it is concerning that data from so many patients is missing, the circumstances are worsened because there is currently nothing to prevent the same situation from reoccurring with another drug.