The Integrative Stream

Do you want a new drug?

NPR’s Morning Edition on Thursday devoted a lot of time to the final report of the space shuttle Columbia accident review board. It’s quite clear that we’ve changed our standards for space exploration. Without the Soviets to compete against, we’ve changed our safety expectations; the clear goal being to take the risk entirely out of space travel. Even with the Columbia tragedy, the shuttle program has a 98% safe return ratio, which is probably better than any series of exploratory ventures in history. Apollo, by contrast, opened with the Apollo 1 disaster and was punctuated by Apollo 13. That’s an 83% success rate, but Apollo 13 was followed by Apollo 14 in less than seven months. NASA in the 1960s may have been a more dynamic and aggressive organization than today, but public attitudes have clearly changed; risk, even risk that the crew might happily accept, is out of the equation.

Which brings me back to Thursday morning. I heard the Columbia report on the way to an MIT Center for Biomedical Innovation forum titled “New Medicines: Can Innovation and Safety Coexist?” The issue was more or less the same, just with drugs rather than spaceships. How do we balance the need to provide safe and effective medicines with the risk associated with developing innovative treatments? If even a small percentage of negative outcomes triggers a backlash as large as yesterday’s Vioxx Verdict, will it be possible to develop novel treatments without setting aside billions for lawsuits?

It’s almost impossible to conduct a clinical trial large enough to identify all the potential side effects of a drug. In the case of Rotarix, a rotavirus vaccine marketed by GSK, a 75,000 person trial was conducted, and even that might not have been sufficient to determine whether the incidence of certain complications was statistically above the background level. The vaccine still isn’t available in the US; GSK launched it internationally, and will likely try to bring it to the US market based on post-marketing surveillance of foreign patients (MIT’s Technology Review has an excellent article on the development of the Rotavirus vaccine, and one of the principals from GSK’s biotech partner, Avant, participated in the CBI conference).

I don’t see much difference between giving a drug to a hundred thousand people in a clinical trial setting and giving a drug to a hundred thousand people with a reasonable level of post marketing surveillance. Many people, myself included, try to avoid taking anything that hasn’t been on the market for a few years anyway. We treat new drugs as intrinsically risky. So why not create a probationary category? Start with smaller clinical trials and an expedited approval process. Then, for several years, require the same disclosures as for a clinical trial, and create patient registries to track everyone who is taking the drug – and include the rest of their medical histories, too. Give drug companies the opportunity to release new products through the current system or the new one, and give patients the opportunity to decide what risk/benefit profile they’re willing to accept.

Careful readers will notice that the proposal above requires complete patient registries for probationary drugs, and will likely comment that the infrastructure to deploy those registries in an efficient manner across all participating doctors would be hideously expensive and difficult. And the careful reader would be right. Requiring entry of a patient’s entire medical history, which would be required to properly screen for negative drug interactions, into a separate system for each probationary drug would be extremely time consuming. So the proposal doesn’t work without standardized electronic medical histories, which come with a host of practical and privacy concerns.