On July 10, 2006, Dr. Scott Gottlieb, Deputy Commissioner for Medical and Scientific Affairs at FDA delivered a speech before the 2006 Conference on Adaptive Trial Design that was very interesting for those contemplating the future of clinical trials design.
He describes many potential benefits of adaptive clinical trials. One point of interest, in the wake of the COX-2 safety meetings, it became clear that there was overwhelming sentiment to make future clinical trials longer and larger, which would of course, also make them more expensive. However, Dr. Gottlieb outlined a way for clinical trials to be more precise in both safety and efficacy, while being shorter in duration and smaller in size through the effective use of adaptive clinical trial tools. This kind of design would allow for results to be considered as clinical trials progress and the use of that information in the ongoing conduct and design of the trial – a learn and adapt as you go approach, rather than the more rigid, empiric system we have today.
One of the other important aspects, Dr. Gottlieb pointed out, was that physicians would be able to use medications more precisely. In other words, in a clinical trial today, a drug gets approved even if only a portion of the study subjects respond to it, as long as that portion is greater than those who responded to placebo. Then a physician prescribes the drug once its is approved with no real way of knowing whether the patient will fall in with those responders, or be a non-responder. A benefit of adaptive trial design would help better identify the responders so that the drug is more appropriately prescribed.
There are obstacles, however. If a drug that goes through the approval process is gong to sell less because it is now more targeted, will that make the drugs more expensive? Right now, we are in an era of blockbusters. If blockbusters are now only prescribed to responders and not to non-responders, does the market for those drugs shrink to the point that some drugs might not be sustainable?
Another problem is that, as he said "adaptive procedures are more complicated to design and analyze, and in some settings more difficult to implement." If that is true, then the agency and industry will have a tough time selling the concept to policy makers and to a public that is already skeptical of clinical trial design and safety. To bring adaptive clinical trials into being, the agency and industry are going to have to work hard from a public affairs perspective to sell the concept broadly.
An obstacle is that the agency has not laid out any guidelines on how to do this, though two are planned in the near future with three to follow further down the line at an undesignated time. FDA will also be holding a two day workshop in November to further explore the issues associated with adaptive clinical trial design.
One additional point needs to be considered – that of cost. Dr. Gottlieb hopes that PDUFA re-authorization may be an opportunity to bring resources for this effort. There is a LOT getting laid at the feet of PDUFA re-authorization and the FDA is in less and less of a position each day to dictate priorities for those fees.
Lastly, the agency and policy makers are going to have to consider some incentives for industry to take the challenge here. One answer might be providing patent extensions for drugs that go through an adaptive clinical trial design process.
In any case, there certainly is great promise in adaptive clinical trial design as described by Dr. Gottlieb. But the agency and industry are going to have to clear several rather formidable hurdles that go beyond the science of the issue, to make them a reality.