In response to my post about the trouble with randomized controlled trials (RCTs), Bruce Charlton, the editor of Medical Hypotheses, wrote me:
The golden age of medical discovery came before the widespread usage of RCTs. This golden age was all but over by the end of the 1960s; since then the rate of progress has declined (see refs such as Horrobin, Le Fanu and Wurtman in https://www.hedweb.com/bgcharlton/funding.html).
The earliest big and influential RCT in psychiatry was in the mid 1960s, and it was – in retrospect – misleading wrt MAOIs due to too low a dosage. Now that RCTs are regarded as indispensible, medical research is captive to Big Pharma
https://www.guardian.co.uk/commentisfree/2009/aug/08/seroxat-pharmaceutical-birth-defect
Another area of medicine [in addition to obstetrics] that has made big progress without being RCT-led is anesthetics. Dentistry is a third. These specialties are instead technology-led.
He also pointed me to an article by David Horrobin, the founder of Medical Hypotheses, titled “Are large clinical trials in rapidly lethal diseases usually unethical?” His answer was that some of their aspects are unethical: Prospective subjects (sick persons) are not told the low chance of benefit, the high chance of bad side effects, and the great financial benefit of such trials to the institutions that run them.
Horrobin’s article also made the point I made: The emphasis on RCTs suppresses innovation because only big well-established companies can afford them:
50 years ago, good scientific evidence of a potential therapeutic effect would quickly have generated a small clinical trial in one or two centers with perhaps 30 or 40 patients. Such a trial would have cost almost nothing. It would certainly have missed small or marginal effects, but it would not have missed the sort of large effect that most patients want. Unfortunately, now, such an approach has become impossible. . . . The escalation of costs has therefore drastically reduced the range of compounds from which new treatments can be drawn.
My reading of history is that suppression of innovation can last a long time but eventually change comes from the outside and the system collapses. Detroit, for example, has collapsed. General Motors was once as dominant as big drug companies are now.
so the japanese and german car companies aren’t part of “the inside”?
The insistance on RCTs (as opposed to trials with dosages that vary between groups, or other more ethical methods) looks a lot like fetishism.
Nathan, why wouldn’t an RCT be able to have multiple groups at different dosages?
Mike: The “C” in RCT means “controls”, implying they get placebos.
One of the ways trials fail is when they shovel together a load of people with what seem to have the same symptoms, and assume their problems all have the same cause. The fraction who actually respond to treatment, because the treatment helps with their actual problem, might be too small a fraction to be “significant”.
Le Fanu’s book is very fine. But if I remember correctly, he makes a case that it’s not just drug innovation that has slowed, so RCTs can’t carry all of the blame.
Nathan, “controls” do not always get placebo (meaning inert substance or treatment).
For example most omega -3 studies are done with control group on omega -6 oils to guarantee “positive” effects of intervention. Were they given placebo (some inert gum, for example), results would be most likely quite different (as small effects seen in such interventions, and also studies of PUFA deficient diets, suggest). So correctly choosing the “control group” is another way to add bias to the study to prove what you want to prove, and then trumpet the results as being “scientific”.
controls generally don’t get placebo. often it’s not ethical to do so. for instance if i were designing a trial for a pain reliever for people with painful bone cancer, i’d have to use the “standard” pain therapy as the control, as it would be cruel to intentionally give someone an ineffective treatment.
q, lack of innovation by Detroit car companies was one reason outside forces — foreign car companies — took over much of their market. Of course, labor costs were another reason, so Detroit isn’t the best example. Clayton Christensen has written a whole book about the way big successful companies stop innovating and often collapse (The Innovator’s Dilemma). Heard of Digital Equipment Corporation?