The U.S. Food and Drug Administration is always between a rock and a hard place. Consumers want the latest and best drugs NOW and they want them thoroughly tested for safety and effectiveness, a process that takes years.
Seeking to introduce efficiencies into the process of conducting the trials to speed them up and lower costs that are passed along to consumers, FDA's deputy commissioner Scott Gottlieb has announced plans to develop guidelines for "adaptive trials." An "adaptive trial" would allow a very different model from the classic scientific testing where the hypothesis is clearly stated at the outset and "post-hoc" adjustments are greeted with great skepticism or rejected automatically. Only an ethical or safety issue would adjust, or more likely, terminate, a clinical trial under the current rules.
Nobody can be for long and costly trials, but "trials" are what they are: not the real thing. If we shortcut the careful and objective science, already compromised by hidden agendas of funding agencies or researchers out to bolster their credentials and their careers, we risk undermining the credibility of our regulatory watchdog. This will bear careful watching.
For example, if the new rules were to apply to non-pharmacolgic investigations as well as trials of new drugs, the reported conclusions of the massive, to-be-definitive Intersalt Study back in 1998 would have been far different. The primary hypothesis was stated that evidence would show that sodium excretion (salt intake) was directly related to population systolic blood pressure. The secondary hypothesis was that sodium excretion (salt intake) was directly related to population diastolic blood pressure. The evidence did NOT confirm these hypotheses, but the reseachers wanted to conclude that salt was problematic so they performed a cohort analysis and constructed a new hypothesis of "blood pressure rise with age" (also subsequently debunked).
Another example, the federal government conducted its Trials of Hypetension Prevention Part II and found that in the first six months, systolic blood pressure fell sharply by about 6-7 mmHg from 127.7 mmHg. It issued news releases and has continued to tout this result for years. But the trial was a 36-month trial and, although sodium intakes remained 920 milligrams below baseline after 36 months after initally declining by 1,150 mg, blood pressure regressed back to its high "normal" of 127.1 mmHg, a statistically insignificant change -- so insigificant that the government sponsors decided to ignore it and use only the 6 months figures which did find the "correct" change.
If the government cooks the books under the current, more rigorous rules, we need to put into place additional guidelines to restore the credibility of its analyses, not further erode the process and our confidence in its conclusions.
