1 Boring Old Man

"He who controls the narrative, controls the debate."

I’ve always had something of a love affair with the medical literature. I think I was awed that so many physicians contributed, and felt proud to be in a profession where there was such a rich community dialog among us. And for whatever reason, I was drawn to case reports rather than disease reports. I read the latter, and the review articles, but it usually started with a case and ended there too. And I’m sure that my wandering from internal medicine to psychiatry/psychoanalysis had something to do with the case by case focus in the mental health world. That’s still true for me today, 50+ years later. I don’t do it here because of confidentiality, but I often have to actively stop myself. When I left [or was extruded from] my full time academic position, I continued to teach a lot, but my reading seemed to change. It became more focused on the areas I taught and patients I treated, whereas before I read most everything that came in front of me. I realized later that the literature had changed on me. Case reports essentially disappeared, and I let my subscriptions run out. Everything seemed like speculations about future things and was frankly boring, too unpopulated for the likes of me. So I don’t know when the drug trial articles appeared. I think I must’ve been long gone by then.

I think if I had read our Petition [that one I keep talking about] even two years ago, I wouldn’t have understood it, even though by then I had filled this blog with complaints about the distortions in clinical trial reporting and matters ClinicalTrials.gov to overflowing. What wouldn’t I have understood? First, why the insistance on declaring the primary and secondary outcome variables and analytic methods in ClinicalTrials.gov before starting the study? And for that matter, why insist that the FDA review and certify those entries? Similarly, why insist on filling out the ClinicalTrials.gov RESULTS database before any FDA submission? And why demand that the FDA check it for concordance with the FDA information [and certify that concordance]? For further, why ask Congress to make these things part of the Law of the Land rather than ask for just a change in FDA/NIH procedures? That comes across as pretty controlling.Looking  Is it really necessary?

Looking back over this era, the majority of the FDA Approvals seem Legit to me. Efficacy standards are low, two statistically significant trials. The promary charge of the FDA is safety. Efficacy and usage is for the medical profession to work out. But there’s a huge loophole in the system in that the same trials that make it through the FDA as "weak sisters" look like "liquid gold" in the academic Journals that publish the self-same trials. And this discordance is never addressed, actually it’s often undetectable or at least undetected.  That’s what those two ostriches in the graphic are not seeing. How can the same data reach such divergent conclusions? Often, the answer is simple – what Ben Goldacre calls "outcome switching."

By the time a drug is in the NDA [New Drug Approval] Phase III trials, it has already shown that there’s a signal that it has the desired medicinal effect and that it’s probably safe [from Phase I and Phase II trials] approved as such by an Institutional Review Board. So the likelyhood that it’ll have some kind of significant result on some metric is high [if you look at enough metrics!]. But that’s not how statistical analysis works, poring over the data in search of something that suits [p-hacking]. You have to select your parameters in advance, 1° and 2°].  So that’s one reason for both insisting that the outcome parameters are set in stone before you start anything. To guarantee that you haven’t gone over and over the data to make something fit [which has happened over and over], but it can’t be proved because it all happens in secret. What if the Sponsor picked wromg? Do another study with the new choice. This loophole has been exploited quite enough, thank you!

And why so rigid about the RESULTS database? For one thing, there’s no reason for a lag. If you have done the analysis for the submission, you have the RESULTS. But beyond that, Journal Editors, Peers reviewers, Doctors, Patients – all need to see those RESULTS to evaluate the submissions, articles, and advertisement that we are being bombarded with. The journal can’t deny responsibility for what they publish if they have the FDA certified ClinicalTrials.gov data filled out in front of them. Without it, the editors, peer reviewers, clinicians, and patients only have the submitted article to go on – and we all know that has not been a reliable source. In my specialty, I’m having troub;e with coming up with any major articles that didn’t have some evidence of some of this kind of fudging along the way, in spite of the ouvert support for data integrity coming from industry [the narrative under control].