REGULATION:
Making Sense of Drug Labeling

By Henry I. Miller

How the FDA makes medicine labels incomprehensible—and what’s good, and bad, about the newest proposals for reform. By Henry I. Miller.

Have you ever tried to read the official FDA-approved labeling for a drug? It’s tough going even for physicians who are trying to find something in a hurry, and almost impossible for nonexperts. Although there is a standard format for the subheadings, it has no rhyme or reason, and there is a lack of consistency in fonts and spacing. Both common sense and focus groups tell us that critical information such as the drug’s uses, warnings, and dosage should be up front, but instead it’s buried in the middle of the labeling—and in impenetrable small print.

Consider, for example, the antibiotic Cipro, whose labeling in the Physicians’ Desk Reference runs to five full, large pages of tiny print. The first paragraph of the first section, “Description,” contains this gem: “Ciprofloxacin hydrochloride, USP, a fluoroquinolone, is the monohydrochloride monohydrate salt of 1-cyclopropyl-t-fluoro-1, 4-dihydro-4-oxo-7-(piperazinyl)-3-quinolinecarboxylic acid. It is a faintly yellowish to light yellow crystalline substance.” Just the info you need at your fingertips! And the second section, “Pharmacology,” is equally unhelpful, discussing absorption, distribution within the body, metabolism, excretion, and so on.

It’s not until the third page that we finally get to the critical information: “Indications and Usage.” After that follows a series of discrete sections whose contents overlap significantly (and problematically): “Contraindications,” “Warnings,” “Precautions,” and “Adverse Reactions.” (Even FDA officials cannot explain what goes where.) Later still, we get to “Dosage and Administration.”

Although final product labeling results from weeks or even months of discussions between a drug’s manufacturer and the FDA (which has absolute discretion over the style and substance of labels), this incomprehensible, unwieldy format prevents efficient communication of essential information about the drug. If it had been up to drug companies, they would likely have adopted a standardized and more workable format decades ago; it appears that at last the FDA has gotten the message.

During a recent advisory committee meeting, FDA officials outlined proposed new labeling, which is expected to be published soon. Information about the drug will be organized logically and in order of importance: boxed warnings (the most forceful caution the FDA can require), what the drug is used for, and then the dosage and administration. Any major changes in the label will also be prominently featured, and the old sections on contraindications, warnings, precautions, and adverse reactions (that is, side effects) will be consolidated. There will also be, we are told, “more clarity in the adverse reaction section.” One hopes that will include information about the frequency—and therefore the likelihood—of various adverse reactions.

The FDA also intends to introduce DailyMed, “an electronic repository of . . . the most current labeling, vetted, approved, the gold standard of drug information.” I am looking forward to it; the Physicians’ Desk Reference on my office bookshelf is the 2004 edition, which means that the data were compiled at least three years ago. These initiatives will be a marked improvement over the current, antiquated system of drug labeling.

All the FDA’s innovations, however, are not so inspired. Much criticized lately for supposed deficiencies in the surveillance and reporting on the safety of drugs, the agency is implementing a wrongheaded scheme for releasing data on drugs’ adverse reactions. In May 2005, the FDA announced its new Drug Watch program, which will make “emerging safety information” publicly available. According to the FDA, this program “is intended to identify drugs for which the FDA is actively evaluating early safety signals. Drug Watch is not intended to be a list of drugs that are particularly risky or dangerous for use; listing of a drug on Drug Watch should not be construed as a statement by the FDA that the drug is dangerous or that it is inappropriate for use. Rather, inclusion on Drug Watch signifies that the FDA is attempting to assess the meaning and potential consequences of emerging safety information.”

The FDA further “clarifies” in the same document that Drug Watch is intended “to share emerging safety information before we have fully determined its significance or taken final regulatory action so that patients and healthcare professionals will have the most current information concerning the potential risks and benefits of a marketed drug product upon which to make individual treatment choices.”

If patients are to make informed, personal decisions concerning their therapies—especially about what kinds of risk/benefit trade-offs they will accept—the public availability of safety information about drugs and transparency about regulatory decisions are essential. The kind of “safety information” provided by Drug Watch might be considered a “public good”— something that cannot readily be withheld from one consumer without being withheld from all consumers, and for which the marginal cost of an additional person consuming it, once it has been produced, is zero. But that isn’t the issue; the question is at what stage the quality and integrity of the data should be considered valid and, therefore, useful. It is difficult to fathom how physicians and other health-care providers—let alone members of the public—can make good use of such preliminary data, which will be available on the agency’s website. There is a difference between indiscriminate data and useful information, and Drug Watch seems destined to provide far more of the former than the latter. Moreover, given the current fervor at the FDA for ensuring drug safety, and the difficulty of proving a negative, one wonders how a “suspect” drug could ever clear its name and get off the Drug Watch list.

As FDA Deputy Commissioner Scott Gottlieb has said, “Information that could influence clinical medical practice needs to be made available more quickly, and more widely, after it has gone through a deliberative scientific process that firms up its meaning and the magnitude and the veracity of its conclusions [italics added].”

DailyMed, which will provide up-to-the-minute labeling information, meets these criteria, whereas Drug Watch fails miserably.

Surely, it would be better to rely on what the FDA considers to be information that conforms to a “vetted, approved, gold standard” than on what Dr. Gottlieb himself has dismissed as data “still un-scrubbed by scientific rigor.”

My advice to the FDA: Take two aspirin, get a good night’s sleep, and perform a Drug Watch–ectomy in the morning.

Henry I. Miller, M.S., M.D., is a research fellow at the Hoover Institution, where his research focuses on public policy toward science and technology. It encompasses a number of areas, including pharmaceutical development, the new biotechnology, models for regulatory reform, and the emergence of new viral diseases.