NCHR Comments at the Risk Communication Advisory Committee on Pregnancy and Lactation Labeling Rule

Thank you for the opportunity to speak today. I am Dr. Danielle Shapiro, I am a physician and senior fellow at the National Center for Health Research. Our research center scrutinizes scientific and medical data and provides objective health information to patients, providers and policy makers. Those are the perspectives I bring with me today. We do not accept funding from the pharmaceutical industry and therefore I have no conflicts of interest.
We offer the following comments to the discussion questions:
#1- What factors are meaningful to interpretation of risk messages?
Pregnancy/postpartum represent critical periods for counseling, health promotion, and health maintenance. Providers and patients must engage in informed discussions of benefits, risks, and alternatives in order to achieve shared-decision making. However, uncertainty of drug harms present a unique challenge in the overall picture of risks and benefits. Although about 1% of adverse birth outcomes are due to drug use during pregnancy, women misperceive those risks to be much higher1.
A Dutch study2 (published in 2017) found that 35% of pregnant women were concerned about birth defects, and 35% about miscarriage. The majority of women responding to the survey/questionnaire, however, took medications during pregnancy, with acetaminophen being the most common. Women were most likely to perceive harm for antidepressants, sedatives/anxiolytics, and NSAIDs. Women were most likely to believe the benefits outweighed the harms for antibiotics, antifungal medication, and antacids. Importantly, the study identified pregnancy trimester, parity, marital status, smoking status, and family history as important factors in women’s interpretation of treatment risks and benefits.
#2-How effective are the communications provided in product labeling under PLLR to date?
We don’t yet know how effective PLLR has been in increasing provider knowledge or changing clinical practice. Based on the FDA’s 2009 mental models study3 of 54 providers, drug labels are not providers’ first source for pregnancy/lactation prescribing information (rather providers utilize secondary point-of-care websites or smart phone applications) . Perhaps the old lettering system was too simplistic and did not provide sufficient or useful information. The study found that provider confidence in treatment decisions increases when quality data on human use are available. However, when those quality data are not available, interpreting and/or extrapolating data from animal models is likely to increase confusion. Based on the mental models study, providers want simple, yet clear information in order to meaningfully and effectively communicate treatment risks and benefits to patients.
#3- What are the best-practice approaches to effectively communicate risk in a manner helpful to prescribers and pregnant women?
There are many approaches to effectively communicate risk in a manner that helps, rather than hurts, decision-making: 1: Frame risk as a positive vs. negative. 2: Emphasize beneficial outcomes of treating a condition in a pregnant or lactating woman vs. low probability of harmful outcomes. 3: Communicate risk in absolute terms, rather than relative terms. 4: Use visual aids (icon arrays e.g., 100 face Cates Plot, bar graphs, charts, etc.). For example, in one survey of pregnant women with urinary infections, 30% reported not taking treatments for those infections4. To help women make informed decisions, we need to emphasize that while the chances of a common antibiotic causing an adverse fetal event are less than 1%, the absolute risk of preterm birth (before 37 weeks gestation) and low birth weight (weight less than 2,500 g) in women with untreated urinary infections are 16% and 12%, respectively5,6. Unfortunately, studies show that patients and providers alike have difficulties with numeracy, especially around understanding and communicating risk7. This makes it difficult for patients and their healthcare providers to make informed decisions about treatment. Using icon arrays to demonstrate both baseline risk and incremental risk increases could help to illustrate numerical concepts, which will enable patients and providers to reach well-informed treatment decisions.
In addition, approaches that create a central information resource are likely to be effective. The question/answer service offered by Norwegian Regional Medicines and Pharmacovigilance Centres in Norway (RELIS) database serves as a good example. A study of 45 providers using RELIS found that it increased provider confidence and re-framed risk perceptions8. A free, independently run information service in the U.S. is likely to help patient and providers individualize treatment decisions and balance risks and benefits for patients and their families.
Thank you for the opportunity to share our perspective.
1. Widnes SF and Schjott J. Risk perception regarding drug use in pregnancy. American Journal of Obstetrics and Gynecology. 2017;216(4):375-378.
2. Mulder B, Bijlsma MJ, Schuiling-Veninga CC, et al. Risks versus benefits of medication use during pregnancy: what do women perceive? Patient preference and adherence. 2018;12:1-8. doi:10.2147/PPA.S146091.
3. U.S. FDA. Content and Format of Labeling for Human Prescription Drug and Biological Products;Requirements for Pregnancy and Lactation Labeling;Final Rule. 2011.Available online:
4.Twigg, M.J., Lupattelli, A. & Nordeng, H.Women’s beliefs about medication use during their pregnancy: a UK perspective. Int J Clin Pharm (2016) 38: 968. 
6.Delzell JE, et al. Urinary Tract Infections During Pregnancy. Am Fam Physician. 2000 Feb 1;61(3):713-720.
7. Anderson B, et al. Numerical Reasoning in Judgements and Decision Making about Health. Cambridge University Press. 2014. Available online:
8.Bakkebø T, et al.  Physicians’ Perception of Teratogenic Risk and Confidence in Prescribing Drugs in Pregnancy-Influence of Norwegian Drug Information Centers. Clin Ther. 2016;38(5):1102-8. doi: 10.1016/j.clinthera.2016.02.018.