1 Boring Old Man

^{So do I think that editors and researchers sit around thinking, "We’ve got to keep them from nailing down the process to insure that there’s some official copy of the a priori Primary and Secondary Outcome variables publicly available"? I kind of doubt it. I expect there are some people inside the walls of Pharma whose understanding of this is more intentional, who consciously know that if they don’t keep this question always open and unresolved, they will lose an extremely valuable tool to market their drugs. But editors? I expect they think the reformers are just being too picky or are anti-pharmacology types or something like that. Maybe they feel like the lady outside the gala whose mink coat has just been sprayed with red paint by some unwashed hippie activist. Or maybe they don’t buy the scientific explanation for preregistration [see de Groot]. I doubt that it occurs to them that there was some savvy ghost·organizer in the background carefully orchestrating what Outcomes got presented in the article they published. But the net result is the same – the issue of the a priori Primary and Secondary Outcome variables just never gets resolved…}

So here we are with the powerful publication editors, an astute investigative editor [Peter Doshi], and a preeminent clinical trial researcher [Ben Goldacre] engaged in a tête-à-tête about Clinical Trial preregistration, a priori variables, and "Outcome Switching" [that’s occurring after the fact, disconnected from the specific trial reports]. The clinicians who read all of those trials in their journals likely have no idea that this debate is taking place, and even more to the point, they didn’t and don’t know that the paper they read had the "Outcome Switched" [a selective reporting that may well have painted a picture of the results through rose colored glasses]. The discussion in Is this trial misreported? Truth seeking in the burgeoning age of trial transparency by the editors is focused on COMPare’s methodology, whether the prespecifieded Outcome Variables are the best choice, or whether Goldacre’s team made an "accurate, complete and nuanced evaluation of the published trial reports."

We have to wonder "Why are they talking about that?" Only the BMJ editor seems to have responded to the cogent question, "Did you know you were publishing an article where the Outcome Parameters had been switched?" The editors of the Annals of Internal Medicine and the New England Journal of Medicine either denied the facts or said that it didn’t make any difference – essentially ignoring the question. And Doshi’s article doesn’t address the Sponsors who submitted the articles or ask them the pertinent questions: "Why did you switch the Outcomes?" and "Why didn’t you tell us that you switched the Outcomes?"

the first step

“COMPare objects to the format in which the data are communicated, but COMPare is silent about whether they dispute the key clinical message of the article,” NEJM editor Jeffrey Drazen said through a spokesperson.

Annals echoed this sentiment: “COMPare’s methodology suggests a lack of recognition of the importance of clinical judgment when assessing pre-stated outcomes.”

"Our gold standard for finding pre-specified outcomes is a trial protocol that pre-dates trial commencement, as this is where CONSORT states outcomes should be pre-specified. However this is often not available, in which case, as a second best, we get the pre-specified outcomes from the trial registry entry that pre-dates the trial commencement. Where the registry entry has been modified since the trial began, we access the archived versions, and take the pre-specified outcomes from the last registry entry before the trial began."