William B. Schultz is a partner at the law firm Zuckerman Spaeder, former general counsel of the Department of Health and Human Services during the Obama administration and former deputy commissioner for policy of the Food and Drug Administration during the Clinton administration.
Last week, the Senate confirmed Scott Gottlieb to lead the Food and Drug Administration. That puts the new commissioner in the hot seat to tackle several high-profile issues that are critically important to patients and consumers.
Among the most important decisions he’ll have to make early on is whether to accept industry proposals to reduce standards under which drugs can be advertised — regulations that have protected patients for more than 50 years.
In 1962, Congress passed a law that ushered in the modern era of drug regulation by requiring pharmaceutical companies to demonstrate that their drugs are not only safe but also effective in treating patients as claimed. To do this, companies must show through carefully designed clinical studies that the drug works to treat a disease or condition. These studies are expensive to conduct, but they are worth the investment: FDA approval means that the world’s premier drug-regulatory agency has determined a drug will work as advertised.
Lawmakers knew when they created these standards that unless pharmaceutical companies had to prove efficacy for all of their drugs’ marketed uses, companies would simply obtain approval for a drug under a narrow use but then market it more broadly with no FDA review.
Pharmaceutical companies generally support FDA regulation for drugs first entering the market, especially the safety and efficacy requirement. But some major companies argue that once a drug has been approved for the first use (treating a skin rash, for example), the First Amendment’s free-speech clause should allow companies to market it for a second use (skin cancer, for example), even if that use is supported by only a small study that would never survive FDA review. These companies claim that, as long as what is said is truthful and not misleading, they have a constitutional right to market a drug without ever showing it works for that particular condition.
The problem with this approach — as everyone who has worked with clinical studies knows — is that early tests on a small number of patients can suggest great promise, but subsequent, more robust studies often disappoint. This is why the FDA generally requires two clinical studies to demonstrate efficacy and that the studies be large enough that their results are unlikely to be due to chance.
Under the law, the FDA considers efficacy in the context of the risk that a drug may cause harm so that it can determine whether the drug’s benefits are greater than its risks. To understand how this works, consider the drug OxyContin. The FDA approved OxyContin as a powerful opioid to treat severe pain, such as the pain experienced by terminal cancer patients. Its most serious side effect is addiction. For terminal cancer patients and others in severe pain, the benefits of the drug outweigh its risks.
But what about patients with mild pain? For them, the risk-benefit balance tilts in the other direction. The FDA has determined that addiction is too great a price to pay, and it is illegal for a drug company to market OxyContin for mild pain. Yet advertising OxyContin for mild pain would be truthful, and the pharmaceutical companies apparently believe they have a constitutional right to do so, without any FDA review or approval.
The most serious problem with reducing the efficacy standard is that we might never find out whether a drug being used to treat a disease actually works. If pharmaceutical companies are permitted to talk about promising test results of their drugs, many companies will forgo the expensive, rigorous studies necessary to validate the hope of the early results. Drug manufacturers typically propose reducing the efficacy standard only for the second use of a drug, which is not as extreme as the wholesale elimination of the standard. But such a policy change would still severely impair the ability of physicians to provide the highest quality health care to patients.
Other candidates considered for the FDA commissioner position had publicly advocated eliminating the efficacy standard for drugs altogether. Fortunately, Gottlieb has never taken such an extreme position. Still, the pharmaceutical companies’ proposal under consideration will test his and the agency’s commitment to the basic tenets of drug regulation in the United States.