As a community we have willfully ignored the obvious about people’s reluctance to enroll in a study and risk being allocated to the placebo arm. All the innumerable market signals of efficacy and side effects from all the preclinical and clinical studies would, at each and every stage, be part of the entire mix as individuals, physicians, researchers, institutions, regulators, and funders make optimal decisions around the margin. Any deviation from the margin would be rapidly corrected. This method of market signaling is established in economics.
Indeed, the lack of participants who would be willing to chance being randomized to a placebo arm is a significant signal. This may prompt regulatory approval for limited use prior to exhaustive randomized controlled trials (RCTs). Future patients would then weigh the lack of an exhaustive RCT against the drugs’ efficacy and side effects in what are termed pre-Phase III trials. The system would be self-correcting. If there was clinical uptake of a newly approved treatment that subsequently proved to be disappointing, this would create market signals to patients and clinicians. This new information would make patients less confident and potentially amenable to an RCT.
While pretest probability is a clinical and statistical axiom, it is flagrantly ignored by regulators. In this regard there is a potential for an enormous generational disequilibrium to exist between patients. For example, there may be a new cancer drug or vaccine with incredible promise in different phases of testing. Current patients may have an inordinate desire for the drug. But they may be sacrificed in order for exhaustive RCTs to be performed so that future patients may receive only a relatively small degree of extra surety that the drug is effective.
Without a comprehensive RCT (and ironically even with such an RCT) it is possible that after widespread use the new drug might be found to be not so effective. Prospectively, the likelihood of this would be dependent on the pretest probability determined with all information at hand. And yes, in this instance, future patients may be inconvenienced. However, why insist that the lives of current patients be sacrificed for the (often false) comfort of future patients to have marginally more information regarding their treatment? Why not turn it around and say, sorry, but future patients will have to accept some degree less certainty in their treatments for the benefit of current patients. Some may argue that the sacrifice of a few now will benefit large numbers in the future. Only a free-market approach will see an overall minimization of those competing interests as the system forms an equilibrium. Remember that even if a new drug is “proven” to be effective, when background treatments change and alternatives arise, the new drug might not be more effective in the new context. At each and every stage clinicians and patients weigh up all the updated knowledge.
Furthermore, the risk-benefit calculation of any intervention is dependent on the circumstances of the individual not just the profile of a new drug per se. And this also involves willingness to be part of a controlled trial. If you are 80 and have had a good life and an intervention is likely to extend life by only a few years, or you are unconvinced by the efficacy, you may willingly enroll in a trial. If you are young and desperate for five extra years you may want to access the unproven drug. It is conceded that this would select out skeptical patients to RCTs and thus bias the results. But life is complicated and the knowledge of that bias would be weighed when reviewing the results of the trial.
As a society, why do we actively intervene against the voluntary donation of potentially lifesaving medicines to autonomous, informed patients who desperately want them? What we are saying is this; sorry, you have been selected to die for the greater good and future benefit of others. The form of this argument must be openly discussed; if accepted, it would be breathtaking in its expansive scope. And for what? A system of trial-driven regulation of medicine that is hopelessly unsophisticated, almost ritualistic, lacking any acknowledgment of the complexity of weighing evidence that occurs across all other disciplines, which treats the pretest probability of the effectiveness of all drugs the same, doesn’t even pass the laugh test (as exemplified by Smith and Pell) and allows disequilibriums of demand and supply that would not be tolerated in any other social context.
If nothing else, this issue gives a stark reminder of the superiority of the market as a means of protecting the individual. On this issue, the market wins hands down over the liberal regulatory state in the morality stakes.