1 Boring Old Man

^{A commenter recently asked "who is your audience?" He was apparently bumfuzzled by my choice of topics [Emil Kraepelin’s politics: all ears…, an open question…]. It’s a good question, but I don’t know the answer [and I’m still cogitating about Kraepelin]. I’m old now, so I guess I write about what I’m thinking about. But I take his point, and will try not to ‘start in the middle" so much.}

This one is easy to introduce. There’s something of a conflict brewing between two people I like – Ben Goldacre and David Healy. Goldacre is an epidemiologist associated with the Cochrane Group who is well versed in the way PHARMA has regularly manipulated clinical trial data the their advantage, and he has developed a presentation style that gets his point across effectively. He started the AllTrials campaign to get the subject level data from all clinical trials published. His strategy is to right the wrongs that have plagued us all – distorted, manipulated clinical trials used for marketing.

While many of us are excited about this project, There are some worrisome aspects along the way. For example. GSK signed on with much fanfare, but want to set up an independent panel to decide who gets the data. The same with Roche. And we’re not hearing the "Hell No!" we want to hear coming from the AllTrial people. And they keep talking about "Study Reports." We don’t want metabolized data. We want the real thing – raw patient level data. But these are political times and watching Dr. Goldacre in the hearing [Ben vs. Roche…], I was encouraged that he’s not going to be pushed around for long.

• Beware of the Wolf in Sheep’s clothing: Given  the past consistent behavior of the pharmaceutical industry, it make sense to look at everything they say as suspect, or worse. Dr. Goldacre called GSK signing on to AllTrials a cartwheel moment. But the motives of PHARMA remain the same – to sell the most drugs. So "yes" to data transparency, "but we’ll decide who gets it" and probably add in confidentiality agreements etc. Semi-transparency at best, more like Pseudo-transparency. And two companies [AbbVie and InterMune] have stopped data release by the EMA for the moment, on claims of confidentiality [what don’t they understand about the word “All”?…]. So there’s a cynicism in Dr. Healy’s take on things, born from  experience – the wisdom of a veteran.
• Beware of the primacy of Clinical Trials: Clinical Drug Trials hardly reflect actual practice conditions. They’re done on recruited, paid subjects. Some may have been on a waiting list, yet the have to be certified ill when they enter the study. Many studies have been done overseas in unspecified cultural or economic circumstances. In some cases, one can question whether the data has been doctored. And Clinical Drug Trials are often of short duration and have high drop-out rates. At best, they might answer the questions, "Does this drug have anti-something properties? Are there prohibitive short-tern adverse effects?" But because they have demonstrated documented efficacy, that information becomes digitized – yes/no. "Is Paxil effective in depressed adolescents?" There’s nothing in the trial data that suggests that a doctor can answer the t.v. question, "Ask your doctor if some drug is right for you?" Who knows? The only way to know is to try it [which is, of course, the reason for the ads]. Well designed studies that allow calculation of effect size might give have a Number Needed to Treat or an odds ratio, but that’s only valid under the study conditions. So Clinical Trials are weak instruments, only really definitive if they’re negative.

  

  But beyond the intrinsic problems with the Clinical Trials themselves, it creates the scenario in my overused diagram above. Diagnosis by Manual; Treatment by Algorithm; based on Evidence from [jury-rigged] Clinical Trials. It’s a chain constructed of only "weakest links."

  "Your doctor" [the one you are supposed to "ask"] isn’t in this equation. This is like Managed Care and the Pharmaceutical Industry would like for medicine to be – predictable, routinized, known at a level that could be handled by algorithm. If one argues against this formula, it is countered with all sorts of things that imply that this is a self-serving argument incompatible with the tenets of Evidence-Based Medicine – doctors just justifying their existence. The question comes down to would you prefer to have as your interface with the world of medicine your physician or your insurance carrier [whose primary goal is cost containment] and your pharmaceutical company [whose bottom line  is corporate profits].

  I didn’t say that in any way like Dr. Healy does [Brand Fascism], but the conclusion remains the same. Evidence-Based Medicine and Randomized Clinical Trials are, at their best, only information to consider. Extrapolating them to their current primacy has created an open conduit for bad science, corruption, and contributed to a general decline in medical care – proxy doctors operating in a domain controlled by various industrial interests, particularly in psychiatry. It’s a simple truth.