Advertisement

Improving pregnancy drug warnings to promote patient comprehension

Published:February 14, 2011DOI:https://doi.org/10.1016/j.ajog.2010.12.040

      Objective

      We sought to evaluate the effectiveness of a pharmaceutical labeling strategy intended to improve comprehension of a teratogen warning.

      Study design

      This is a secondary analysis that evaluated women of childbearing age who were assigned prescription containers with the current teratogen warning, a label with simplified text, or a label with simplified text and icons. The association between label type and understanding of label instructions was assessed.

      Results

      A total of 132 women were interviewed. Comprehension of the icon label (94%) was higher than for the standard and enhanced text-only labels (76% and 79%), respectively (P < .05). Adjustment for age, race/ethnicity, education, literacy, and number of current medications revealed that the label with the enhanced text and icon yielded superior comprehension (risk ratio vs standard, 1.26; 95% confidence interval, 1.04–1.53; risk ratio vs enhanced, 1.22; 95% confidence interval, 1.02–1.46).

      Conclusion

      In our study, a teratogen warning label that had easy-to-read messages with icons significantly improved comprehension.

      Key words

      The use of medications during the preconceptional period of pregnancy is a frequent occurrence. Andrade et al
      • Andrade S.E.
      • Gurwitz J.H.
      • Davis R.L.
      • et al.
      Prescription drug use in pregnancy.
      reported that 64% of pregnant women are prescribed a drug (other than a vitamin or mineral) during their pregnancy and nearly 5% of women may be taking a class X medication at the time of conception. Similarly, a large retrospective study by Schwarz et al
      • Schwarz E.B.
      • Postlethwaite D.A.
      • Hung Y.Y.
      • Armstrong M.A.
      Documentation of contraception and pregnancy when prescribing potentially teratogenic medications for reproductive-age women.
      found that 1 in 6 women of reproductive age filled a prescription for a class D or X medication over the course of a year. These classes of medications are of particular importance as they have the potential to cause harm to the developing fetus and should either be avoided completely or used only when the benefits of the treatment outweigh the risks. Specific examples include valproic acid, phenytoin, and warfarin.
      See related editorial, page 281
      For Editors' Commentary, see Table of Contents
      Because the use of teratogenic medications among reproductive-age women increases the risk of congenital anomalies, it is important that women taking these medications understand the risks such therapy may incur. One method toward understanding these risks is through physician counseling. Yet, because approximately 50% of pregnancies in the United States are not planned, a preconceptional consultation often does not occur.
      • Finer L.B.
      • Henshaw S.K.
      Disparities in rates of unintended pregnancy in the United States, 1994 and 2001.
      Moreover, many women never receive contraceptive counseling when their medication is prescribed. In the study by Schwarz et al,
      • Schwarz E.B.
      • Postlethwaite D.A.
      • Hung Y.Y.
      • Armstrong M.A.
      Documentation of contraception and pregnancy when prescribing potentially teratogenic medications for reproductive-age women.
      up to half of patients taking class D or X medications did not have documented contraceptive counseling or were not actively using contraception.
      • Schwarz E.B.
      • Postlethwaite D.A.
      • Hung Y.Y.
      • Armstrong M.A.
      Documentation of contraception and pregnancy when prescribing potentially teratogenic medications for reproductive-age women.
      Consequently, warnings conveyed on medication labels are often the only way many women are informed of the potential danger of a medication in the context of pregnancy. This fact emphasizes the importance these labels have in conveying the potential reproductive consequences of medication use.
      Despite the importance of clear labeling, prior studies have suggested that warning symbols are often misinterpreted by individuals, especially those with limited literacy. Recognizing this tendency toward misinterpretation, the Food and Drug Administration along with numerous medical, pharmaceutical, and public health organizations have directed greater attention to the quality of prescription drug labeling.
      Institute of Medicine
      Standardizing medication labels: confusing patients less, workshop summary.

      American Pharmaceutical Association. Committee policy report on health literacy 2001-2002.

      American Society of Health-System Pharmacists. ASHP guidelines on pharmacist-conducted patient education and counseling. Am J HealthSyst Pharm 1997;54:431-4.

      Schwartzberg J. Health literacy and patient safety: help patients understand. Reducing the risk by designing a safer, shame-free health care environment, 2008. POGOe—Portal of Geriatric Online Education; 2009. Available at: http://www.pogoe.org/productid/20398. Accessed Feb. 1, 2011.

      To date, though, little progress has been made by these organizations in improving or standardizing warning labels for prescription drug containers.
      We recently developed and pilot tested an “enhanced” prescription drug warning label strategy that we hypothesized would be more easily understood by a diverse set of individuals, including those with limited literacy.
      • Webb J.
      • Davis T.C.
      • Bernadella P.
      • et al.
      Patient-centered approach for improving prescription drug warning labels.
      The objective of the current study was to evaluate the effectiveness of the enhanced labeling strategy to improve comprehension of a pregnancy warning label among women of childbearing age.

      Materials and methods

      This is a secondary analysis of a 3-arm clinical trial testing the efficacy of different approaches to pharmaceutical labeling. In the main study, multiple types of warning labels were tested in a population of men and women of varying ages.
      • Wolf M.S.
      • Davis T.C.
      • Bass P.F.
      • et al.
      Improving prescription drug warnings to promote patient comprehension.
      The present secondary analysis concerns only those labels that were designed to be precautionary for a pregnant and/or breast-feeding population and only the subjects (ie, reproductive-age females) for whom those labels are primarily intended.
      The specific protocol used in the original study has been described previously.
      • Wolf M.S.
      • Davis T.C.
      • Bass P.F.
      • et al.
      Improving prescription drug warnings to promote patient comprehension.
      Briefly, a convenience sample of adult patients who attended 1 of 4 outpatient primary care clinics was recruited in 2 cities (Shreveport, LA, and Chicago, IL) from June through August 2007. Patients were considered eligible for the study if they were English speaking and ≥18 years of age, and ineligible if they had severely impaired vision or hearing. Institutional review boards at both locations approved the study. A total of 562 patients were approached in the order they arrived at the clinics and prior to the medical encounter. Of the 500 (89%) patients who were eligible and consented to the larger study, 132 were women of childbearing age (18-44 years of age) and included in the present analysis.
      In each of the participating clinics patients reviewed: (1) the current standard drug warning label for prescription containers (standard); (2) an “enhanced” drug warning with text rewritten in plain language (enhanced text); or (3) the enhanced language and an icon developed with patient feedback to support the text message (enhanced text + icon). The label they reviewed was varied based on a systematic rotation. The text and icons (Figure) on the labels were designed based on patient feedback and pilot testing.
      • Webb J.
      • Davis T.C.
      • Bernadella P.
      • et al.
      Patient-centered approach for improving prescription drug warning labels.
      Additionally, guidelines established by the International Organization for Standardization for the development and testing of universal icons were followed.

      International Standard. ISO 7001, public information symbols. International Organization for Standardization, 1990.

      Other design elements were also implemented, including removal of color and optimizing of font size.
      Figure thumbnail gr1
      FIGUREWarning label by type
      Improving Pregnancy Drug Warnings
      You. Improving pregnancy drug warnings. Am J Obstet Gynecol 2011.
      A structured “cognitive” interview protocol was developed to assess patient understanding of the drug labels, as previously described by our research team.
      • Davis T.C.
      • Wolf M.S.
      • Bass III, P.F.
      • et al.
      Literacy and misunderstanding prescription drug labels.
      • Wolf M.S.
      • Davis T.C.
      • Shrank W.
      • et al.
      To err is human: patient misinterpretations of prescription drug label instructions.
      • Davis T.C.
      • Wolf M.S.
      • Bass III, P.F.
      • et al.
      Low literacy impairs comprehension of prescription drug warning labels.
      • Davis T.C.
      • Federman A.D.
      • Bass III, P.F.
      • et al.
      Improving patient understanding of prescription drug label instructions.
      In summary, after patients consented to the study, a trained research assistant obtained demographic information (age, sex, race/ethnicity, education, number of prescription medications currently taken daily) and administered the structured interview. Actual prescription pill bottle containers with the attached drug warning labels were then shown to all of the patients for review. During this interview, the research assistant would direct patients to the back of 1 of 3 prescription vials, and ask: “In your own words, what does this mean to you?” The patient's verbatim responses were documented on a separate form. Once the patient provided their interpretations, the research assistant administered the Rapid Estimate of Adult Literacy in Medicine (REALM), a reading recognition test comprised of 66 health-related words. Based on REALM scores, participants were classified as having limited (≤6th-grade reading level; REALM = 0-44), marginal (7th- to 8th-grade reading level; REALM = 45-60), or adequate (≥9th-grade reading level; REALM = 61-66) health literacy skills. The REALM is the most commonly used test of patient literacy in medical settings.
      • Davis T.C.
      • Long S.W.
      • Jackson R.H.
      • et al.
      Rapid estimate of adult literacy in medicine: a shortened screening instrument.
      It is highly correlated with standardized reading tests and the Test of Functional Health Literacy in Adults.
      • Parker R.M.
      • Baker D.W.
      • Williams M.V.
      • Nurss J.R.
      The test of functional health literacy in adults: a new instrument for measuring patients' literacy skills.
      • Davis T.C.
      • Marin E.
      • Gazmararian J.
      • Williams M.
      Literacy testing in health care research.
      Responses regarding the prescription label were then independently rated as either correct or incorrect by 3 attending physicians from 3 different academic medical centers. Each physician rater was blinded to all patient information and was trained to follow stringent coding guidelines agreed upon previously by the research team. Specifically, correct scores were to be given only if the patient's response included all aspects of the label's message. Responses were given an incorrect score if they were inaccurate, or if they did not contain all aspects of the warning. If a consensus decision was not obtained the final score was assigned through majority rule. Cohen kappa was calculated to assess interrater agreement.
      Frequencies were calculated and Fisher's exact tests were used to evaluate the association among label type (current standard vs enhanced text vs enhanced text + icon), literacy level (low, marginal, adequate), and patient understanding of the label instructions (correct, incorrect). A generalized linear model with a Poisson distribution and log link function was used to estimate the risk ratio (RR) and corresponding 95% confidence intervals (CIs) of correct interpretation of warning label instructions for covariates in the model compared to each referent condition. Robust error estimation was used to correct for overestimation of variance resulting from using the Poisson distribution for a binomial outcome.
      • Zou G.
      A modified Poisson regression approach to prospective studies with binary data.
      In addition to the primary independent variable of interest (label type), the final multivariable model included the potential confounding variables of age, sex, race (African American vs white), low literacy, education, and number of daily medications currently taken. While educational attainment is associated with literacy, it was included in the final model to present conservative estimates of the effect of literacy on rates of understanding.
      • Wolf M.S.
      • Gazmararian J.A.
      • Baker D.W.
      Health literacy and functional health status among older adults.
      Study site was also entered into the model to adjust for any potential differences across study locations. All statistical analyses were performed using software (STATA, version 10.1; StataCorp, College Station, TX).

      Results

      The demographic characteristics of the study sample (n = 132) are presented in Table 1. Briefly, the women who were evaluated were mostly African American, and many had relatively low educational attainment (59.9% high school level of education or less) and limited literacy skills. These women were taking on average 2.1 prescription medications daily (SD = 2.5). As noted, there were no differences in characteristics of the women with relation to the type of label that they visualized.
      TABLE 1Characteristics of study sample
      VariablenSummary valueLabel typeP value
      Standard (n = 50)Enhanced (n = 49)Enhanced + icon (n = 33)
      Age, y13231.9 (7.7)31.6 (7.3)31.9 (8.3)32.2 (7.6).94
      Race.47
       African American10277.380.077.572.7
       White2518.914.018.427.3
       Other53.86.04.10.0
      Education, y.60
       <123627.324.030.627.3
       124332.638.022.539.4
       13-153425.824.032.618.2
       16-201914.414.014.315.1
      Health literacy.64
       Low2418.220.014.321.2
       Marginal5239.444.040.830.3
       Adequate5642.436.044.948.5
       Medications taken daily1322.1 (2.5)1.8 (2.1)2.3 (2.9)2.3 (2.6).45
      Study location.88
       Chicago, IL9571.974.069.472.7
       Shreveport, LA3728.026.030.627.3
      All data presented as n (%) or mean (SD).
      You. Improving pregnancy drug warnings. Am J Obstet Gynecol 2011.
      Interrater agreement among the 3 physicians coding the patient responses was high (kappa = 0.87). Univariable analysis revealed that comprehension of the enhanced text + icon label (94%) was significantly higher than of the standard and enhanced text-only labels (76% and 79%), respectively (P < .05). After adjusting for age, race/ethnicity, education, literacy, number of medications currently taken, and study site, comprehension of the enhanced text + icon label remained significantly higher compared to both standard and enhanced text-only labels (icon vs standard: RR, 1.26; 95% CI, 1.04–1.53; icon vs enhanced text: RR, 1.22; 95% CI, 1.02–1.46). Limited literacy was not found to be an independent predictor of comprehension, nor was any other patient characteristic included in the model (Table 2). Interactions among literacy, education, and label type also were tested but were not found to be significant.
      TABLE 2Correct interpretation of prescription drug warning labels
      VariableCorrect interpretation of warning
      RR95% CIP value
      Label type
       Standard1.00
       Enhanced text1.03(0.84–1.26).763
       Enhanced text + icon
      Enhanced text + icon vs enhanced text only RR, 1.22; 95% CI, 1.02–1.46; P = .027.
      1.26(1.04–1.53).017
      Literacy level
       Adequate1.00
       Marginal1.02(0.85–1.22).856
       Low0.80(0.59–1.11).181
       Age0.99(0.98–1.00).158
      Race
       White1.00
       African American1.06(0.79–1.42).691
      Education, y
       16-201.00
       13-151.14(0.77–1.69).505
       121.10(0.75–1.61).623
       <121.05(0.70–1.59).809
      No. of medications taken daily
       None1.00
       1-21.10(0.89–1.37).383
       3-40.99(0.71–1.40).976
       ≥51.27(0.97–1.66).079
      Clinic
       Shreveport, LA1.00
       Chicago, IL0.87(0.73–1.03).097
      Interactions among literacy, education, and label type were not significant.
      CI, confidence interval; RR, risk ratio adjusted for all variables shown.
      You. Improving pregnancy drug warnings. Am J Obstet Gynecol 2011.
      a Enhanced text + icon vs enhanced text only RR, 1.22; 95% CI, 1.02–1.46; P = .027.

      Comment

      In our study, a teratogen warning label developed from patient feedback that had an explicit, easy-to-read message in conjunction with icons was found to significantly improve comprehension among women of childbearing age. The finding that enhanced text with icons significantly improves comprehension is consistent with that of previous studies, although those labels were unrelated to reproduction.
      • Davis T.C.
      • Federman A.D.
      • Bass III, P.F.
      • et al.
      Improving patient understanding of prescription drug label instructions.
      • Dowse R.
      • Ehlers M.S.
      The evaluation of pharmaceutical pictograms in a low-literate South African population.
      • Doak C.C.
      • Doak L.G.
      • Root J.H.
      Teaching patients with low-literacy skills, 2nd ed.
      • Morrow D.
      • Leirer V.O.
      Designing medication instructions for older adults.
      • Shrank W.H.
      • Avorn J.
      • Rolón C.
      • Shekelle P.
      The effect of the content and format of prescription drug labels on readability, understanding and medication use: a systematic review.
      A major strength of this study is that patient input was used to develop the enhanced label. Additionally, we controlled for literacy, which has been shown in previous studies to affect the ability of a patient to accurately interpret a drug label.
      • Davis T.C.
      • Wolf M.S.
      • Bass III, P.F.
      • et al.
      Literacy and misunderstanding prescription drug labels.
      • Davis T.C.
      • Wolf M.S.
      • Bass III, P.F.
      • et al.
      Low literacy impairs comprehension of prescription drug warning labels.
      The use of 3 physician raters to determine whether a given response was correct or incorrect strengthens the validity of these results as well.
      There are several limitations to our study that should be recognized. We investigated whether the language and icons would support understanding of important concepts, but cannot know whether this understanding translates into fewer medication errors or undesired exposures. We also did not study patients' conceptions related to their own prescription medicines. Patients' motivation, concentration, and comprehension might have been greater if they were reporting on their own medicine given by their physician for conditions they actually had.
      • Morrow D.
      • Leirer V.
      • Sheikh J.
      Adherence and medication instructions: review and recommendations.
      • Rice G.E.
      • Okun M.A.
      Older readers' processing of medical information that contradicts their beliefs.
      • Metlay J.P.
      Medication comprehension and safety in older adults.
      Since the study design did not include a chart review, we also did not have information on patients' health, and in particular whether they had actual experience with medication use. Finally, the generalizability of our findings is limited by the fact that patients were predominantly African American and that participation was limited to patients who spoke English. This was due in part to criteria for using the REALM as our literacy assessment. The findings of this study may not be relevant for over the counter (OTC) medications as these containers have a different (and rather diverse) appearance as compared to prescription containers. Additionally, patient may have a different level of concern with regard to OTC medications and consequently may respond differently to a label placed on such a container than they would to a prescription container. OTC medications are an important topic and warrant further study.
      Prescription warnings placed on the container label may be particularly valuable to patients as the most tangible source of medication information. Presently, there are several companies, including pharmacies themselves, that produce auxiliary warning labels (as part of a software package or as container stickers) for use by community pharmacies. As a result, different messages and icons may be used to convey similar messages regarding medication administration. A large number of these instructions and precautions remain unnecessarily complex, and are seldom tested for comprehension among consumers to include their feedback in the development process.
      We offer further evidence for setting forth best practices in the design and development of patient-centered prescription drug warnings for use on container labels. This evidence is of particular relevance for reproductive-age women who use prescription medications as many may become pregnant without a full understanding of the teratogenic potential of their treatment.

      References

        • Andrade S.E.
        • Gurwitz J.H.
        • Davis R.L.
        • et al.
        Prescription drug use in pregnancy.
        Am J Obstet Gynecol. 2004; 191: 398-407
        • Schwarz E.B.
        • Postlethwaite D.A.
        • Hung Y.Y.
        • Armstrong M.A.
        Documentation of contraception and pregnancy when prescribing potentially teratogenic medications for reproductive-age women.
        Ann Intern Med. 2007; 147: 370-376
        • Finer L.B.
        • Henshaw S.K.
        Disparities in rates of unintended pregnancy in the United States, 1994 and 2001.
        Perspect Sex Reprod Health. 2006; 38: 90-96
        • Institute of Medicine
        Standardizing medication labels: confusing patients less, workshop summary.
        in: Hernandez L.M. National Academies Press, Washington, DC2008
      1. American Pharmaceutical Association. Committee policy report on health literacy 2001-2002.

      2. American Society of Health-System Pharmacists. ASHP guidelines on pharmacist-conducted patient education and counseling. Am J HealthSyst Pharm 1997;54:431-4.

      3. Schwartzberg J. Health literacy and patient safety: help patients understand. Reducing the risk by designing a safer, shame-free health care environment, 2008. POGOe—Portal of Geriatric Online Education; 2009. Available at: http://www.pogoe.org/productid/20398. Accessed Feb. 1, 2011.

        • Webb J.
        • Davis T.C.
        • Bernadella P.
        • et al.
        Patient-centered approach for improving prescription drug warning labels.
        Patient Educ Couns. 2008; 72: 443-449
        • Wolf M.S.
        • Davis T.C.
        • Bass P.F.
        • et al.
        Improving prescription drug warnings to promote patient comprehension.
        Arch Intern Med. 2010; 170: 50-56
      4. International Standard. ISO 7001, public information symbols. International Organization for Standardization, 1990.

        • Davis T.C.
        • Wolf M.S.
        • Bass III, P.F.
        • et al.
        Literacy and misunderstanding prescription drug labels.
        Ann Intern Med. 2006; 145: 887-894
        • Wolf M.S.
        • Davis T.C.
        • Shrank W.
        • et al.
        To err is human: patient misinterpretations of prescription drug label instructions.
        Patient Educ Couns. 2007; 67: 293-300
        • Davis T.C.
        • Wolf M.S.
        • Bass III, P.F.
        • et al.
        Low literacy impairs comprehension of prescription drug warning labels.
        J Gen Intern Med. 2006; 21: 847-851
        • Davis T.C.
        • Federman A.D.
        • Bass III, P.F.
        • et al.
        Improving patient understanding of prescription drug label instructions.
        J Gen Intern Med. 2009; 24: 57-62
        • Davis T.C.
        • Long S.W.
        • Jackson R.H.
        • et al.
        Rapid estimate of adult literacy in medicine: a shortened screening instrument.
        Fam Med. 1993; 25: 391-395
        • Parker R.M.
        • Baker D.W.
        • Williams M.V.
        • Nurss J.R.
        The test of functional health literacy in adults: a new instrument for measuring patients' literacy skills.
        J Gen Intern Med. 1995; 10: 537-541
        • Davis T.C.
        • Marin E.
        • Gazmararian J.
        • Williams M.
        Literacy testing in health care research.
        in: Schwartzberg J.G. VanGeest J.B. Wang C.C. Understanding health literacy: implications for medicine and public health. American Medical Association Press, Chicago2005: 157-179
        • Zou G.
        A modified Poisson regression approach to prospective studies with binary data.
        Am J Epidemiol. 2004; 159: 702-706
        • Wolf M.S.
        • Gazmararian J.A.
        • Baker D.W.
        Health literacy and functional health status among older adults.
        Arch Intern Med. 2005; 165: 1946-1952
        • Dowse R.
        • Ehlers M.S.
        The evaluation of pharmaceutical pictograms in a low-literate South African population.
        Patient Educ Couns. 2001; 45: 87-99
        • Doak C.C.
        • Doak L.G.
        • Root J.H.
        Teaching patients with low-literacy skills, 2nd ed.
        JB Lippincott, Philadelphia, PA1996
        • Morrow D.
        • Leirer V.O.
        Designing medication instructions for older adults.
        in: Park D.C. Morrell R.W. Shifren K. Processing of medical information in aging patients: cognitive and human factors perspectives. Lawrence Erlbaum Associates Publishers, Mahwah, NJ1999: 249-266
        • Shrank W.H.
        • Avorn J.
        • Rolón C.
        • Shekelle P.
        The effect of the content and format of prescription drug labels on readability, understanding and medication use: a systematic review.
        Ann Pharmacother. 2007; 41: 783-801
        • Morrow D.
        • Leirer V.
        • Sheikh J.
        Adherence and medication instructions: review and recommendations.
        J Am Geriatr Soc. 1988; 36: 1147-1160
        • Rice G.E.
        • Okun M.A.
        Older readers' processing of medical information that contradicts their beliefs.
        J Gerontol. 1994; 49: P119-P128
        • Metlay J.P.
        Medication comprehension and safety in older adults.
        LDI Issue Brief. 2008; 14: 1-4