FDA drug‑evaluation chief warns against over‑reliance on placebo effect in trials

“He's the chief watchdog, who watches over all the other watchdogs—but this must be his night off-” no magic bullets for most of the problems that ail us today,” Jonas said. “Diabetes, immune-system disorders, chronic pain, cancer. Our illnesses are complex, and we need to approach them in more compre- hensive ways. We try to identify drugs that will eliminate disease. Yet the way we go about delivering those agents—the interaction between doctor and patient, for example—often has a bigger impact than the agent we focus on. More than the drug and more than the surgery. And that has been collectively called the pla- cebo effect.” he headquarters of the Food and Drug Administration, situated on a campus called White Oak, on the far edge of Silver Spring, Maryland, seems as close to the rest of the federal medi- cal establishment as it is to Pluto. There is no Metro to White Oak, and it takes half an hour to drive from the sprawling campus to the National Institutes of Health, in Bethesda. The F.D.A.’s physical isolation belies its position as the nation’s principal regulator of con- sumer products. No drug is sold with- out the agency’s approval. There will be no prescriptions for any placebo, either, unless clinical trials have demonstrated its effectiveness to the satisfaction of the F.D.A. “One of the absolutely fundamental problems that we have is the use of the 34 THE NEW YORKER, DECEMBER 12, 2011 term ‘placebo, which does nobody any good,” Robert Temple told me, echoing a complaint made by virtually every- one who deals with the subject. Temple, who has for many years run the F.D.A’s drug-evaluation department, is an owlish man with a short, thick mustache and cir- cular glasses. His office is so filled with towering stacks of files that, after you enter, it takes a moment to find him. “Just because something is called a ‘placebo eroup, ” he said, “everyone assumes that what happens in that group is a result of the placebo effect. And that is absolutely not true.” Temple, who has worked at the F.D.A. for four decades, rarely makes a decision without angering somebody. He has been regarded as a meddlesome reac- tionary by H.1.V. activists and others who insist that drugs be released more rapidly. The more conservative medical establishment frequently accuses the agency of endorsing the wishful thinking of drug manufacturers. And to the large and growing community that supports alternative approaches to medicine Tem- ple is Dr. No. Temple said that he understands why placebos attract people who become frus- trated when science fails to provide definitive answers. “The persistence of what people believe will save their lives as opposed to the evidence is staggering,” he said. “So people are talking about using placebos as drugs. But I have no idea what that means in practical terms. How would it work?” Tantalizing hints and possible effects are not data, and Temple says there are no data that would suggest that place- bos are drugs. There are several studies, though, that illustrate the basis for his skepticism. A placebo effect is commonly ob- served during trials of blood-pressure medications. To qualify for such studies, subjects are supposed to have blood pres- sure that exceeds a hundred and forty over ninety in at least one of the two measurements. “As soon as somebody enters those studies, his or her blood pressure falls an average of five or six mil- limetres of mercury,” Temple said. “That is significant, but it is not a placebo re- sponse, and it is not a response to being in the study. It is often the result of doc- tors’ inflating readings—of rounding up.” Ifa person's blood pressure is a hundred and thirty-eight over eighty-eight, for ex- ample, investigators will often include him. “When you use an automatic blood- pressure cuff to establish a baseline for these kinds of studies, the entire placebo effect vanishes,” Temple said. When a drug (or a placebo) is under study, subjects are usually divided into two groups. Neither group knows exactly what it is getting (nor do the doctors), but one group generally receives the drug and the other a placebo. “There is a better way,” Temple said. “If you want to see if there is a placebo effect, use three arms in a drug trial, not two. Tell them, ‘Some of you will be getting a drug, some will get a tablet that looks like a drug but is nothing but a sugar pill, and some of you will get noth- ing at all’ “It seems to me,” he went on, “that if there is any substantial placebo effect, there ought to be a difference between the group that knows it’s getting nothing and the group that doesn’t know it’s getting nothing. If there is no difference, then what are we talking about? Because it’s not a placebo effect.” It turns out that there have been many trials of the type Temple mentioned. In 2001, the Danish epidemiologist As- bjorn Hrébjartsson, of Copenhagen’s Nordic Cochrane Center, along with his colleague Peter Getzsche, published a systematic review of a hundred and four- teen clinical trials that compared patients who received a placebo with subjects who HOUSE_OVERSIGHT_029929