— An excerpt from Avorn’s book, Rethinking Medications
by Jerry Avorn, MD
May 22, 2025 • 5 min read
Ideally, the approval of a new drug should be exclusively the province of science, but for a more than half-trillion-dollar-a-year industry, it couldn’t possibly remain so. The same libertarian posture of the earlier twentieth century — the spirit that opposed the government’s right to require accurate drug labeling and prevent toxicity — lives on in the insistence by some advocates on the far right that the government shouldn’t even be in the business of determining whether a drug works or not. Physicians and patients could determine which drugs work best and which don’t, their argument goes, through decisions reflecting their individual clinical experiences.
This is such a bad idea that it’s hard to know where to start in debunking it. Here are some basics: Some of the detailed data the FDA receives from a drug’s manufacturer is considered the company’s private property and is kept secret, so any outside reviewer isn’t playing with a full deck.
Furthermore, evaluating the results of a clinical trial can be tricky:
Were the study groups truly comparable at the start of the trial?
Were the randomization and blinding done appropriately?
What statistical methods were used to compare outcomes?
If the differences were statistically significant, were they also large enough to be clinically meaningful?
Were the patients studied comparable to people a doctor is treating or (as often occurs) healthier and younger?
If the comparison drug was a placebo, how does the new drug stack up against all the evidence on other relevant treatment choices out there (perhaps including nondrug options) that weren’t in the trial?
Beyond all that, the issue of selective publication of favorable results has bedeviled all of us who look to the peer-reviewed medical literature to guide our decisions about how well drugs work, a problem several researchers have documented. A worrisome analysis of this issue was published in the New England Journal of Medicine by Erick Turner, MD, a psychiatrist who had spent several years at the FDA reviewing new drug applications. While there, he noticed that the more favorable studies that crossed his desk were more likely to end up being published in medical journals than the less favorable ones. Once he left the agency, he and his colleagues followed up on the concern that drugmakers who sponsor studies have in the past published the results they liked and spent far less effort to get non-favorable trial findings into the medical literature. Turner et al. reviewed the raw data on 74 clinical trials submitted to the FDA evaluating 12 different antidepressants and found that almost a third of them had never been published. Virtually all those that depicted favorable outcomes made it into medical journals; but of the studies with negative or questionable results, nearly all were never published, or appeared with a positive spin on the results.
How are we clinicians or our patients supposed to independently rethink these approval decisions, if the totality of the evidence never sees the light of day? Put differently, Turner’s study found that if you looked at the then-extant medical literature you’d find that 94% of published trials of antidepressants found the drugs were effective; by contrast, only about half of all the original studies submitted to the FDA showed the medications worked.
In response to problems like these, reforms were passed in 2007 to require public disclosure of plans for all clinical trials before they are launched. The less good news is that disclosure of their results is still far from complete.
Still, many libertarians argue that Americans should be able to “do their own research” to decide which drugs work and which don’t. But going over the terabytes of data the FDA receives for a new drug submission takes large teams of smart, dedicated, specialized scientists months to get right. Over many years, we’ve found how hard it is to do this work well in our educational outreach programs when we try to synthesize such data to guide doctors toward better prescribing decisions. So how could it make sense to let individual freedom decide what drugs are available for use? Surely no responsible government scientist would advocate for that, right?
One odd presentation of this anti-big government perspective was offered in an op-ed in the Wall Street Journal that argued for an approach in which the FDA wouldn’t assess the effectiveness of new drugs. Instead, the author proposed, the agency should just make sure new products aren’t terribly unsafe and then release them to the magic of the marketplace, so doctors and patients could figure out which ones work and which don’t. Efficacy could be tested later in post-market studies.
That strange op-ed was written by Andrew von Eschenbach, MD, appointed by George W. Bush as FDA commissioner in 2005. While at the FDA, von Eschenbach, whose clinical expertise was as a prostate surgeon, prolonged the agency’s yearslong refusal to approve greater access to the morning-after contraceptive pill despite its proven safety and effectiveness. Apparently, he felt there are some issues the marketplace shouldn’t be allowed to decide on its own.
The same motif of laissez-faire, caveat emptor has inspired a nationwide “right to try” movement for unapproved medications, pursued aggressively in several states by conservative legislators seeking to enable patients to take unproven drugs. But this is a solution to a problem that doesn’t really exist. For many years, to avoid being in the middle of this unwinnable debate, the FDA has allowed any physician to ask a company for access to an investigational drug that hasn’t been approved by the FDA. The agency itself approves about 99% of such request; when there is an access problem, it’s usually the company that resists making the product available. But if a drug hasn’t been determined to work, should such liberated patients expect their health insurer, or a government program, to pay for it? And if there is a dangerous side effect, would they expect society to cover the costs of caring for those consequences as well?
When my colleagues and I wrote a paper for the New England Journal of Medicine about this issue, we used a common term to describe the policy: “compassionate use.” The editors wisely made us change that to “expanded access,” pointing out that there’s not necessarily anything compassionate about helping people take an untested drug that may not work and could hurt them.
Jerry Avorn, MD, is a professor of medicine at Harvard Medical School in Boston. He is the author of Rethinking Medications: Truth, Power, and the Drugs You Take, from which this piece was excerpted. Copyright © 2025 by Jerry Avorn. Reprinted by permission of Simon & Schuster, New York.
