On September 18, 2007, a few dozen neuroscientists, psychiatrists, and drug company executives gathered in a hotel conference room in Brussels to hear some startling news. It had to do with a class of drugs known as atypical or second-generation antipsy- chotics, which came on the market in the early nineties. The drugs, sold under brand names such as Abilify, Seroquel, and Zyprexa, had been tested on schizo- phrenics in several large clinical trials, all of which had demonstrated a dramatic decrease in the subjects’ psychiatric symptoms. As a result, second-generation antipsychotics had become one of the fastest-growing and most profitable pharmaceutical classes. By 2001, Eli Lilly’s Zyprexa was generating more revenue than Prozac. It remains the company’s top-selling drug.Amen, ahem.
But the data presented at the Brussels meeting made it clear that something strange was happening: the ther- apeutic power of the drugs appeared to be steadily waning. A recent study showed an effect that was less than half of that documented in the first trials, in the early nineteen-nineties. Many re- searchers began to argue that the expen- sive pharmaceuticals weren’t any better than first-generation antipsychotics, which have been in use since the fifties. “In fact, sometimes they now look even worse,” John Davis, a professor of psychiatry at the University of Illinois at Chicago, told me.
Before the effectiveness of a drug can be confirmed, it must be tested and tested again. Different scientists in different labs need to repeat the protocols and publish their results. The test of replicability, as it’s known, is the foundation of modern research. Replicability is how the community enforces itself. It’s a safeguard for the creep of subjectivity. Most of the time, scientists know what results they want, and that can influence the results they get. The premise of replicability is that the scientific community can correct for these flaws.
But now all sorts of well-established, multiply confirmed findings have started to look increasingly uncertain. It’s as if our facts were losing their truth: claims that have been enshrined in textbooks are suddenly unprovable. This phenomenon doesn’t yet have an official name, but it’s occurring across a wide range of fields, from psychology to ecology. In the field of medicine, the phenomenon seems extremely widespread, affecting not only antipsychotics but also therapies ranging from cardiac stents to Vitamin E and antidepressants: Davis has a forthcoming analysis demonstrating that the efficacy of antidepressants has gone down as much as threefold in recent decades.
For many scientists, the effect is especially troubling because of what it exposes about the scientific process. If replication is what separates the rigor of science from the squishiness of pseudoscience, where do we put all these rigorously validated findings that can no longer be proved? Which results should we believe? Francis Bacon, the early-modern philosopher and pioneer of the scientific method, once declared that experiments were essential, because they allowed us to “put nature to the question.” But it appears that nature often gives us different answers.
Sunday, December 12, 2010
Science Sunday: When Stuff Wears Off
The Decline Effect is the tendency of scientific results to shrink over time. Initial data might appear to be very robust but then decays. Writing in the New Yorker (subscription required), Johan Lehrer tells a scary, fascinating story: