the frenzied match of ping pong: the last stand…

Posted on Sunday 30 October 2016

by Peter Doshi, associate editor
British Medical Journal. 2016 355:i5543
We all agree that the participants in trials should be randomly assigned to the various arms of the study, and about the conditions of the double-blind design. The old pharma trick of not publishing negative studies has been mostly eliminated by required registration. So what’s left to complain about? I’ve been borrowing Ben Goldacre et al’s COMPare study, some of the Journal Editors’ responses, and Peter Doshi’s reporting aiming at a particular point – the a-priori-ness of the outcome variables in the analysis of the clinical trial results. I see it as the last big hurrah – a place where there seems to be no enduring consensus supporting its importance. That’s apparent in some of the editor’s responses to COMPare.
Outraged editors

The long awaited goal of universal registration of trials now seemed achievable.5 and medical journal editors issued an ultimatum: preregister your trial or forgo publication in our pages. “Honest reporting begins with revealing the existence of all clinical studies, even those that reflect unfavourably on a research sponsor’s product,” a group of influential editors declared. “Unfortunately, selective reporting of trials does occur, and it distorts the body of evidence available for clinical decision-making.” The declaration had enormous impact, and public trial registers remain a key mechanism to prevent investigators from hiding or spinning unfavourable results.

But more than a decade on, a small project from Oxford University’s Centre for Evidence Based Medicine seems to have journal editors eating their own words, with some of the world’s most powerful editors arguing that strict adherence to the registry entry’ or trial protocol may not always make sense…
Journal dissent

“Upon receipt of COMPARED initial communication, our editorial team (comprised of physicians and statisticians)thoroughly re-reviewed materials associated with the articles.” Annals’ editor in chief. Christine Laine, told The BMJ. “We concluded that the information reported in the articles audited by COMPare accurately represents the scientific and clinical intent detailed in the protocols.” In notices posted to the journal’s website, Annals editors acknowledged the good intentions of COMPare but warned people to be wary.

“Until the COMPare Project’s methodology’ is modified to provide a more accurate, complete and nuanced evaluation of published trial reports, we caution readers and the research community’ against considering COMPare’s assessments as an accurate reflection of the quality’ of the conduct or reporting of clinical trials”…

NEJM also flunked COMPare’s test. The journal’s editors refused to publicly engage with the group, rejecting all of  COMPare’s 20 letters, most with a tightly worded statement saying “we have not identified any clinically meaningful discrepancies between the protocol and the published paper that are of sufficient concern to require correction of the record… NEJM’s response has a certain irony. The journal’s editor, Jeffrey Drazen, has been a longtime supporter of trial registration, and NEJM was the first of its peers to publish trial protocols alongside trial publications, a practice now followed by JAMA, The BMJ, and most recendy-in part thanks to COMPare — Annals.

The BMJ did not escape criticism but ultimately got a greenlight. COMPare sent rapid responses for two of the three trials evaluated, one of which led to a correction. It was “an example of best practice,” the group said in a blog. What about JAMA and the Lancet? JAMA rejected all 11 letters the group sent, and the Lancet rejected some but published others…

Frankly, while "a more accurate, complete and nuanced evaluation of published trial reports" sounds really good, it’s well off the mark. The whole point of a clinical trial is objectification, hard core evidence-based medicine. Of course there are instances where common sense says that the preregistered outcome need to be reconsidered, but that’s not what’s on the table here. COMPare found that the majority of the articles had some outcome changed. And the changes weren’t flagged or explained.

So some editors don’t really accept that the a priori declaration of outcome variables is a fundamental element of a scientifically conducted Randomized Clinical Trial [RCT]. That’s what COMPare shows, and that’s what the editors’ responses say as well. Their proper response to COMPare would’ve been "Whoops." In spite of their comments to the contrary, they’re keeping the multi-billion loophole from being closed – making a "last stand."

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