Publication bias concerns grow

CONCERN that published research does not provide doctors with the full evidence base about medications is increasing, with an analysis of antipsychotic trials finding several examples of publication bias.

The research, published in PLoS Medicine, analysed 24 trials registered with the US Food and Drug Administration of eight second-generation antipsychotics. (1)

The study found that four of the trials were never published. Of these, three failed to show that the study drug was significantly better than placebo, and one showed the drug was statistically inferior to the active comparator.

It is the latest example of researchers using data from published and unpublished research in their analysis — and finding discrepancies between the two sources.

An analysis of antidepressant trials by the same researchers in 2008 found that publication bias nearly doubled the apparent proportion of positive trials and increased the apparent effect size of antidepressants by one third. (2)

A recent reanalysis of neuraminidase inhibitors for influenza using primary trial data was conducted after researchers found that 60% of patient data from oseltamivir trials had never been published. The reanalysis found that oseltamivir did not seem to reduce hospitalisations, contrary to the findings of published reports. (3)

One of the authors of the oseltamivir review was Professor Chris Del Mar, professor of public health at Queensland’s Bond University. Professor Del Mar told MJA InSight that the latest research on antipsychotics showed that if doctors only read published research, they would get a biased view of these medications.

“This is another indication that, at the moment, our system for providing information to clinicians about the efficacy of commercially sensitive products is broken. More and more, it seems to look as if medical journals are simply becoming the marketing arm of commercial interests such as the pharmaceutical industry”, he said.

While the association between trial outcome and publication status in the latest research did not reach statistical significance — probably due to the low number of relevant trials — Professor Del Mar said the numbers speak for themselves.

He said although the publication bias in the latest analysis was not as strong as found for antidepressants or neuraminidase inhibitors, it was another example of the problem.

“We’re beginning to see a pattern that what goes through the regulators is not what we see in journals”, he said.

Professor Gordon Parker, Scientia professor of psychiatry at the University of NSW, said the latest analysis of antipsychotics showed that “if we are to rely on the evidence base, then we do need to examine the data from unpublished studies as well as published”.

However, he said the bigger issue was the real-world effectiveness of psychopharmacological drugs.

He cited the 2005 Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, which unexpectedly found that a first-generation antipsychotic, perphenazine, performed generally as well as newer atypical antipsychotics, with fewer side effects. (4)

“I think the more important question is the one raised by the CATIE study — if short-term efficacy doesn’t really differentiate the old typical and new atypical drugs, then what are the meaningful drug profile differences (eg, rates of tardive dyskinesia, metabolic syndrome) over the years that they are used”, Professor Parker said.

He said pharma-sponsored trials give little useful information because trial patients and real-world clinical patients contrast like apples and oranges, so that the real-world effectiveness and true side-effect profile often took years of naturalistic observation by clinicians to identify.

“If you walk around psych wards, just look at the size of patients — their BMIs are around 30 to 40. There’s an accruing database that shows some of these drugs are linked to metabolic syndrome, diabetes, hypertension.”

Professor Parker called for more clinical effectiveness studies in psychiatry.

“Real-world research would tell a more coherent, informative and discriminating story”, he said.

- Sophie McNamara

1. PLoS Medicine 2012; Online 20 March
2. N Engl J Med 2008; 358: 252-260
3. Cochrane Database Syst Rev 2012; (1): CD008965
4. N Engl J Med 2005; 353: 1209-1223

Posted 26 March 2012

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