FDA’s new labeling rule: clinical implications


Ongoing revision of the label as information becomes outdated is a requirement, and manufacturers will be obligated to include information on whether there is a pregnancy registry for the given drug. The goal of the PLLR is thus to provide the patient and clinician with information which addresses both sides of the risk-benefit decision for a given medicine – risks of fetal drug exposure and the risk of untreated illness for the woman and baby, a factor that is not addressed at all with the current system.

Certainly, the new label system will be a charge to industry to establish, support, and encourage enrollment in well-designed pregnancy registries across therapeutic areas to provide ample amounts of good quality data that can then be used by patients along with their physicians to make the most appropriate clinical decisions.

Much of the currently available reproductive safety information on drugs is derived from spontaneous reports, where there has been inconsistent information and variable levels of scrutiny with respect to outcomes assessment, and from small, underpowered cohort studies or large administrative databases. Postmarketing surveillance efforts have been rather modest and have not been a priority for manufacturers in most cases. Hopefully, this will change as pregnancy registries become part of routine postmarketing surveillance.

The new system will not be a panacea, and I expect there will be growing pains, considering the huge challenge of reducing the available data of varying quality into distinct paragraphs. It may also be difficult to synthesize the volume of data and the nuanced differences between certain studies into a paragraph on risk assessment. The task will be simpler for some agents and more challenging for others where the data are less consistent. Questions also remain as to how data will be revised over time.

But despite these challenges, the new system represents a monumental change, and in my mind, will bring a focus to the importance of the issue of quantifying reproductive safety of medications used by women either planning to get pregnant or who are pregnant or breastfeeding, across therapeutic areas. Of particular importance, the new system will hopefully lead to more discussion between physician and patient about what is and is not known about the reproductive safety of a medication, versus a cursory reference to some previously assigned category label.

Our group has shown that when it comes to making decisions about using medication during pregnancy, even when given the same information, women will make different decisions. This is critical since people make personal decisions about the use of these medications in collaboration with their doctors on a case-by-case basis, based on personal preference, available information, and clinical conditions across a spectrum of severity.

As the FDA requirements shift from the arbitrary category label assignment to a more descriptive explanation of risk, based on available data, an important question will be what mechanism will be used by regulators collaborating with industry to update labels with the growing amounts of information on reproductive safety, particularly if there is a commitment from industry to enhance postmarketing surveillance with more pregnancy registries.

Better data can catalyze thoughtful discussions between doctor and patient regarding decisions to use or defer treatment with a given medicine. One might wonder if the new system will open a Pandora’s box. But I believe in this case, opening Pandora’s box would be welcome because it will hopefully lead to a more careful examination of the available information regarding reproductive safety and more informed decisions on the part of patients.

Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information about reproductive mental health. He has been a consultant to manufacturers of antidepressant medications and is the principal investigator of the National Pregnancy Registry for Atypical Antipsychotics, which receives support from the manufacturers of those drugs. To comment, e-mail him at [email protected]. Scan this QR code or go to to view similar columns.


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