Well, I didn’t know it when I wrote in the details… and achilles’ heel…, but I wanted to end with a conclusion before talking about the current controversies. It might be presumptuous of me to sound off about such things being just a retired doctor, but the Clinical Trials world has gotten itself in such a tangle, maybe as many outside views as can be mustered are a good thing. One part of this story that jumps off the page is how many attempts at reform have failed to rectify the many problems – things like ignoring reporting on clinicaltrials.gov. In fact, there are so many problems that a virtual cottage industry of technologies has developed to ferret them out. The state of play right now is a chess game between commercial and medicinal interests, both in terms of efficacy and of adverse effects – the Scylla and Charybdis of any medication.
My own thinking has hardened the more I’ve read actual Clinical Trials. The blinded part of the procedure is rigidly defined, but after the blind is broken, things become frazzled. The Results section of a published paper should be predetermined by the a priori protocol-defined primary and secondary variables, as determined by the IPDs and CRFs prepared before the blind is broken, and analyzed as specified by the protocol. Creativity is not an invited guest. Anything less than this has no place in a scientific journal. We wouldn’t allow the kind of manipulation of data happening every day in our medical journals to go on with the O-Rings on our spacecraft or the brake systems in our cars, why should we do it with medications? There would be a lot fewer medications on the market and patients would be prescribed or take many fewer pills. The impact on the pharmaceutical industry as it now exists would be massive. Not a problem for science to deal with. Many patients and doctors are willing to operate with difficult Risk/Benefit ratios in the face of dire medical illness, and that’s their prerogative. Even under those circumstances, they need accurate information to make those decisions.
I’m afraid that I can’t get away from the idea that the manufacturers have no real seat at the table when the topic is the truth about the outcome of Clinical Trials. They just haven’t earned that right. By allowing this kind of sheenanigans to go on, we have elevated the Patent Medicines of old to the realm of scientifically approved therapeutics. While I agree that too much emphasis is placed on short-term Clinical Trials in the first place, that’s where we are right now and that’s what we need to clean up first. Since we know that the majority of the misinformation comes from either manipulating or suppressing the analysis that follows the unblinding of the data, the solution of full raw Data Transparency is a good one – allowing independent analysis of the results. But another solution would be to insist on independent analysis from the start. Since Adverse Effects are the weakest link in this process, they deserve special attention to insure accurate coding. If rigidly controlled outcome reporting makes drug development and manufacturing unprofitable, we’ll just have to find another approach to scientific therapeutics. We are under no obligation to support the pharmaceutical industry as it exists today.
From Richard Feynman’s Appendix F to the Rogers Commission Report (here):
“It appears that there are enormous differences of opinion as to the probability of a failure with loss of vehicle and of human life. The estimates range from roughly 1 in 100 to 1 in 100,000. The higher figures come from the working engineers, and the very low figures from management. What are the causes and consequences of this lack of agreement? …
…
“For a successful technology, reality must take precedence over public relations, for nature cannot be fooled.”
I disagree with the analogy to 0-rings and brakes. When they are bad, there is usually only one or two outcomes that are fairly obvious. In addition, there is ample evidence of how poor engineering or manufacturing of automobiles has put us at risk, and evidence of when those who downplay risks in spaceships call the shots.
With that said, I agree that some entities other than drug companies need to test their meds because it makes sense logically. However, when even the FDA has hollow fangs, who do you think should step in? The accusations are already flying about those in the reform movement, and I certainly don’t trust one or two independent labs to remain independent over time (or the government for that matter as they’ve already proven they can be bought). Which is why I don’t understand why reform doesn’t start with patients and doctors just refusing to use these meds and reporting the side effects. If medications act differently in different people, and we are all guinea pigs to some extent, why not just walk away from them when they are not working or causing horrible side effects. I understand being so desperate that you will try anything, which is why I almost ended up on Seroquel so I could feel like I slept, but I also don’t believe that much effort is being put into every patient, in either the treatment or the diagnosis, before they are all at the end of the line and have to suffer under some of these meds. A few, yes, but the majority of patients? Also, in leaving it between patient and provider those that find the medications work for them are able to continue to use them.
Please let me know why I am wrong here as I would rather suffer admonishment than under ignorance or naïveté.