Here is an irresistible news headline: “Public Policy That Makes Test Subjects of Us All.”(New York Times, April 6, 2009). Then you open to the story only to discover, to your disappointment, that the piece is written by John Tierney, probably the most uninformed and underqualified members of the NYTimes staff.
His argument is ridiculous: that the New York City mayor’s initiative to “pressure” the food industry to cut salt amounts to a big experiment that would normally have to undergo IRB review and informed consent (never mind that the initiative is not an experiment designed to further knowledge. Never mind that the initiative is not aimed at generalizable knowledge, or that public health initiatives grounded in a state-based interest that are enacted by elected leaders have the “consent of the governed”).
But in the most recent issue of JAMA, a news story (Bridget M. Kuehn, “Rare Neurological Condition Linked to Newer Monoclonal Antibody Biologics,” April 8, 2009) reminds us that, in some small sense, licensure of novel biologics makes guinea pigs of us all. The report describes how FDA recently issued an advisory on the psoriasis drug efalizumab after reports emerged that it may be associated with a risk of developing a rare and fatal brainwasting disease (progressive multifocal leukoencephalopathy, or PML). FDA had previously issued warnings on two similar, immunomodulating drugs, and established a restricted distribution system for a third (natalizumab– for multiple sclerosis).
In the case of natalizumab, cases of PML occurred in pre-marketing clinical trials. For the other drugs, knowledge of the risk emerged only after drug licensing. Risk of PML was totally unexpected, and is a reminder of the high degree of uncertainty surrounding interventions directed at the immune system.
Premarketing clinical trials are statistically powered only to detect common, “signature” adverse events. As we move into an era of biologics-based pharmaceuticals (and accelerated approval), expect that many adverse events will only be discovered once a drug is in widespread use. Robust systems of pharmacovigilence will be especially critical (photo credit: Peter Guthrie, 2006).