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Improvement needed in Multiple Sclerosis drug trials

Randomised controlled trials of multiple sclerosis drugs have consistently improved since the first positive result in 1993, but more transparent methodology is required as trials enter a “new era”, experts argue.

After analysing the methodology of 53 eligible RCTs that took place in the eighteen years up to 2010, the Italian trio note a steady rise in quality – mainly down to “many journals having statistical refereeing and clearer guidelines to authors.”

But with the clinical scenario in MS changing “rapidly” as trials become increasingly benign, certain questionable practices need closer scrutiny, the authors say.

“The advent of new therapies has made the use of placebo unethical, at least in trials lasting more than six months,” they write in Multiple Sclerosis Journal.

Despite general improvements there also remain problems with the use of significance tests for detecting baseline differences.

Occurring in about half of the trials analysed, the authors argue its use is null since randomisation guarantees that any baseline differences are due to chance.

A more significant practice would be to provide information on whether baseline factors are associated with outcome. This, however, is rare.

As well, there are enduring problems with subgroup analysis.

Interaction tests, used to assess the heterogeneity of treatment effect across different subgroups, are the “correct approach” but remain underused.

Smaller trials are often underpowered to use such tests effectively, say the authors, who argue for companies to work together and pool collective analyses – something they habitually avoid out of a reluctance to share information.

It is up to journals, so instrumental in boosting methodological quality to date, to encourage pooled analysis, they conclude.

Multiple Sclerosis Journal, 2012; doi:10.1177/1352458512444327

Source: Neurology Update (01/05/12)