A new study has identified 29 clinical trials of multiple sclerosis drugs whose results remain completely unknown to scientists and doctors. The authors believe that the results are unlikely to ever be made public, adding to the multi-billion dollar mountain of medical research waste.
Non-publication of trial results is unethical – and in some cases illegal – because it leaves gaps in the evidence base on drugs’ safety and effectiveness that can harm patients.
The authors of the study identified 150 clinical trials of multiple sclerosis drugs carried out between 2010 and 2019. They limited their search to Phase III and Phase IV trials, which involve drugs that appear to be highly promising or that are already on the market.
One in five trials never made public
They found that one in five trials, 29 trials total, had never made their results public in any form.
The study also confirms the importance of clinical trial registries:
Results for some trials were available on registries, but not in the scientific literature. Without registries, over a third of all multiple sclerosis trials, 54 in total, would have ended up as research waste.
Trials that showed that a drug did not help patients, or caused more harm than good, were far less likely to be reported in scientific journals. Thus, relying on journals alone to analyse trial outcomes would paint an excessively rosy picture of the investigated drugs. In the words of the authors, this publication bias “clearly compromises the available medical evidence by distorting the apparent safety and efficacy of interventions.”
Medical evidence lost forever
The authors believe that the 29 missing trial results are unlikely to ever be made public:
“[S]ome trials might be still on their way to publication. Nonetheless, taking into account the median time of 28.1 months from trial completion to publication and the median time of 77.5 months from the unpublished trials completion to the publication search date, this possibility seems improbable.”
In total, the 150 trials included in the study had enrolled 59,209 people. The study does not state how many of those patients participated in the completely unreported trials, or which drugs were involved.
Where is the FDA?
A 2007 law gives the FDA the power to fine companies over $13,000 for each day a clinical trial result remains unreported. However, the FDA has yet to impose a single fine.
Yesterday student activists from Universities Allied for Essential Medicines (UAEM) protested outside the agency to urge it to finally start enforcing the law.
Study strengths and weaknesses
A key strength of this study is that the authors emailed both principal investigators and sponsors up to three times to make sure that no results were overlooked. (This is not only a quality assurance mechanism, but may also help to prompt those responsible to make their results public.) The authors also searched for results on multiple trial registries.
A key weakness of the study is that the authors did not publish their dataset of multiple sclerosis trials.
TranspariMED contacted the authors requesting the dataset. We wanted to directly follow up with the sponsors of the 29 completely unreported trials and put on some pressure, to try and save those results from being lost forever. The authors provided a valid reason (which we cannot disclose) for not sharing the data at this point in time. They plan to publish additional research based on this trial cohort. TranspariMED trusts that they will make the full dataset public in future.
The study includes many additional metrics and findings not discussed in this blog. It can be accessed here (paywalled).