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Krimsky claims such dangerous drugs have been allowed to reach the market because “conflicts of interest have become endemic in the system of drug evaluation,” a trend that “has been exacerbated by the rise of for-profit clinical trials, fast-tracking drug approvals, government-industry partnerships, direct consumer advertising and industry-funded salaries for FDA regulators” since the mid-1990s.
There’s little evidence that the FDA is more likely to approve harmful drugs than it was in the past. A 2005 report by the Tufts University Center for the Study of Drug Development found that faster approval times do not correlate with more frequent drug withdrawals. The share of drugs withdrawn for safety reasons was 3.2 percent in the 1980s, 3.5 percent in the ’90s, and 1.6 percent from 2000 to 2004. The approval times for drugs that are withdrawn are not appreciably shorter than the average approval time for all drugs.
Meanwhile, the FDA removes dangerous drugs from the market much sooner than it used to. The average time between FDA approval and subsequent safety withdrawal dropped from 3.7 years in the 1980s to 1.4 years in the ’90s and is now seven-tenths of a year. The bad news is that an overcautious FDA can kill people too. A 2005 study by economists at the University of Chicago calculated that the speed-up in FDA drug approvals that occurred after 1992 may have been responsible for saving the equivalent of 180,000 to 310,000 life-years (the sum of the years of life that would have been lost had the new drugs not been available). Over the same period, about 56,000 life-years at worst were lost to drugs that were eventually withdrawn for safety reasons.
Unfortunately, it’s much easier to identify people who are harmed by drugs than those who are saved by drugs. In the face of this information asymmetry, regulators tend to focus on reducing lives lost to unsafe drugs rather than preventing deaths by speeding effective new therapies to patients.
Saving Money by Spending More
What about the charge that biased reporting of scientific results boosts overall medical costs by encouraging physicians and patients to select new, expensive treat-ments that are no better than older, cheaper medicines? “The cost of pharmaceutical drugs—and health care in general—in America continues to skyrocket,” Jennifer Washburn of the New America Foundation wrote in the June 2005 In These Times. “Expensive new drugs are aggressively marketed on TV and in doctors’ offices the moment they hit the market. Yet physicians warn that many of these hyped prescriptions are simply ‘me-too drugs’ that vary only slightly from medications already on the market, despite being far more expensive.”
Health care as a share of U.S. gross domestic product has tripled from 5 percent in 1960 to 16 percent today. Some analyses project the number will reach 25 percent by 2030. But this inflation is not due to spending on drugs. In a 2002 study for the National Bureau of Economic Research, the Columbia University economist Frank Lichtenberg estimated that, on average, “reducing the mean age of drugs used to treat a condition from 15 years to 5.5 years…increases prescription drug spending by $18 [averaged over the total population] but reduces other medical spending by $129, yielding a $111 net reduction in total health spending. Most of the savings are due to reductions in hospital expenditure ($80) and in physician office-visit expenditures ($24).” In other words, using newer drugs reduces other medical expenditures by more than seven times the extra amount spent on drugs.
Today 30 percent of the $2.2 trillion Americans spend on health care each year goes to hospitals. Physicians get 20 percent, and 10 percent pays for dental and other professional services. All of these are labor-intensive treatments. By comparison, prescription drugs account for about 10 percent of health care spending. “Within a generation or two,” Peter Huber of the Manhattan Institute noted in the July 2006 Commentary, “they will undoubtedly account for most of it—which will be another good thing. Pharma’s biochemical cures always end up far cheaper than the people-centered services they replace.”
Marcia Angell rails against the pharmaceutical industry’s “obscene profits.” But Princeton health economist Uwe Reinhardt told USA Today in October 2006 that he had “once calculated that if you rebated all the drug company profits to patients, health spending would only go down by 1.2%.” Seizing drug company profits would do nothing to address the current health care spending “crisis,” but it would shut off the flow of funds to many biomedical researchers and drastically slow the discovery and development of new and more effective drugs.
As for “me-too” drugs, the implication is that companies are trying to take market share from each other without providing any “real” benefits to patients. Of course, “trying to take market share away” is better known as “competition,” which ultimately results in lower prices.
Everybody’s a Critic
Although critics of the drug industry exaggerate the problems created by conflicts of interest, in rare instances drug companies have withheld or misreported data, and some researchers have put their financial gain above the safety of their patients. It therefore makes sense to keep an eye on potential conflicts.
One safeguard—disclosure in journals—is here to stay. Even Stossel, a strong proponent of industry-financed research, favors disclosure. “To be sure,” he wrote in a February 2005 Forbes column, “it is reasonable to require disclosure of corporate sponsorship by investigators and institutional monitoring of collaborations. But academic administrators and government officials respond to rare incidents of misconduct and to the barrage of criticism that follows by rushing to pile on restrictions.”
Peer review has been the traditional means of assuring a study’s validity. By requiring disclosure, journal editors are in effect admitting peer review’s failure. Since their reviewers are not competent to evaluate findings based solely on the data, warning labels need to be slapped onto industry-funded studies. And peer review overlooks honest errors as well as deliberate fraud. “Peer review doesn’t necessarily say that a paper is right,” said Martin Blume, editor-in-chief of the American Physical Society’s nine journals, in a January 2006 interview with Science. “It says it’s worth publishing.”
Fortunately, a new age of more-robust peer review is dawning. With the advent of online journals like those published by the Public Library of Science (PLoS), peer review is changing from a one-time appraisal of a self-contained research article to a continuous online process. Since 2003 PLoS has launched eight open-access, peer-reviewed biomedical journals. In 2006 it started a new comprehensive online journal, PLoS One, which will feature reports of primary research from all disciplines in the biological and physical sciences. The editorial board will make prompt decisions on whether papers merit publication and may refer them to outside reviewers.
With PLoS, unlike print journals, publication is not the end of the peer review process. Once an article has een published in PLoS One, community-based post-publication peer review begins, in full view of anyone who visits the site. Post-publication reviewers can post corrections, additions, or links to other relevant articles. They can engage in online debates concerning the content, conclusions, and consequences of a specific paper. Users can assign ratings to papers. (Anonymous annotations are not allowed.)
According to the PLoS good practice guidelines, post-publication reviewers should confine their criticisms to the content of papers and avoid speculation about the motivations or prejudices of authors. That may be considered good practice now, but in the future post-publication reviewers may begin to note any associations they believe relevant to the findings reported in the paper. In other words, if a researcher doesn’t disclose potential conflicts, someone will do it for him.