Drugs

Steps When a Clinical Trial Primary Outcome Fails

Scientists in New York and London say there are steps researchers can take when a trial’s primary outcome fails to achieve statistical significance. Writing in the New England Journal of Medicine, they suggest that researchers ask a set of 12 questions to help them clarify whether the new treatment may still have some value.

The questions are:

Is there some indication of potential benefit?
Was the trial underpowered?
Was the primary outcome appropriate (or accurately defined)?
Was the population appropriate?
Was the treatment regimen appropriate?
Were there deficiencies in trial conduct?
Is a claim of non-inferiority of value?
Do subgroup findings elicit positive signals?
Do secondary outcomes reveal positive findings?
Can alternative analyses help?
Does more positive external evidence exist?
Is there a strong biologic rationale that favors the treatment?

The options, the authors say, are to claim success on the basis of the total evidence (an option that is rarely used), plan a future trial with design improvements (very costly), or accept that the new treatment is likely to be ineffective (frustrating).

“However,” they write, “the best option is to avoid this scenario altogether through rigorous upfront planning. By making sure there is evidence of strong pathophysiological and mechanistic underpinnings that are common to both the new therapy and the disease, by selecting appropriate patients and endpoints, by calculating an adequate sample size, by paying meticulous attention to dosing, definitions of disease and outcomes, and all procedural processes, and by anticipating the ways in which the trial might fail and give rise to criticisms, one can enhance the likelihood of reaching a decisive conclusion.”

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FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

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FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome

FDA has approved Roche’s Gazyva (obinutuzumab) for reducing the risk of relapse in adults and children aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome who are in remission. The expanded approval covers the use of the CD20-directed antibody beyond its existing

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Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome