CROs and sponsors need to get better at defining the questions they are asking in clinical trials according to researchers who say developers often fail to plan for “intercurrent events.”
The conclusion is set out in a paper published in the British Medical Journal (BMJ) in June that looked at “estimands,” the precise primary question being addressed about an intervention in a clinical trial.
The research also examined strategies used to handle post-randomization events - such as intervention discontinuations or uses of additional drug treatments, which are known as intercurrent events.
Results
In all, 255 randomized clinical trials were included in the review. And the key finding is that none of the studies clearly stated all the attributes of the estimand under examination according to the authors.
In 117 of 255 trials, the primary estimand could be determined from the reported methods. Intercurrent events were reported in 242 of 255 trials; but the handling of these could only be determined in 125 of 255 trials.
And in those trials that did report intercurrent events, most did not consider it in the calculation of the treatment effect.
Solutions
The findings suggest drug firms and their CRO partners need to be clearer about their intentions from the outset according to the authors.
“Researchers should describe estimands in trial reports so that the precise research questions being addressed for medical interventions can be understood by all. While 46% of primary estimands could be inferred from the reported methods by our statistical reviewers, inferability is likely to be lower for typical clinical readers and other non-methodologists, including patients reading trial results.
“Specifying estimands has a clear benefit here: it breaks down the details behind technical language, enabling transparent interpretation for all without the need for statistical knowledge or input,” they write.
They add that “use of estimands can help clarify the precise study question. Trialists should explicitly describe estimands in trial reports, thereby allowing all stakeholders - including clinicians, patients, and policy makers - to make fully informed decisions about medical interventions.”
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