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Medication use in pregnancy has increased over time while the use of medications during pregnancy that have a suspected or known teratogenic or fetotoxic risk has been reported. Although the new Pregnancy and Lactation Labeling Rule (PLLR) addresses additional drug’s safety requirements during pregnancy, research efforts that examine its impact need to be further explored.
To develop a web-based intervention to increase knowledge of medication safety in pregnancy and lactation among women of reproductive age and an assessment of knowledge and application of the Pregnancy and Lactation Labeling Rule (PLLR) among pharmacists and physicians.
This study utilized two study designs for the two groups of study participants (Women and Healthcare Providers). To test the effectiveness of a web-based educational intervention about gestational and lactational medication safety practices for pregnant and non-pregnant women of reproductive age a quasi-experimental study was used. The primary outcome of this study was knowledge. To evaluate pharmacists’ and physicians’ knowledge and attitudes related to the FDA PLLR a cross sectional study design was used. The primary outcome for this study was PLLR knowledge. A total of 210 women participated in the Women’s study and a total of 181 providers participated in the Provider study. Descriptive statistics of all study variables were estimated including means for continuous and percentages for categorical variables. For the Women’s study, a paired t-test was conducted to determine differences in mean knowledge scores before and after the intervention. Also, a McNemar’s test was conducted to determine differences in the proportion of women who preferably agreed that natural remedies should preferably be used during pregnancy. In the Provider study, a linear regression was conducted to determine potential predictive factors for knowledge. SPSS version 25 was utilized as the Statistical Analysis Software for this study, and all analyses were conducted at an alpha value of 0.05.
In the women study, there were 210 females residing in the United States between 18-44 years. Of the 210 female, (N=62;29.5%), were currently pregnant, (N=61;29%) had a child one year old or younger, and (N=6;2.9 %) were both, currently pregnant and had a child one year old or younger. The mean age of the respondents was 32.4 years (±6.5). Majority of the respondents were White (N=146;69.5%), lived in rural region (N=111;52.9%), were married (N=129;61.4%), had incomes below $50,000 (N=119;56.7%), and completed high school (N=126;60.0%). Most of the respondents had health insurance, (N=97;46.2%) private health insurance, and (N=94;44.8%) public health insurance. The overall knowledge level in this population was 49.72%. For the primary outcome, a paired-samples t-test was conducted to compare knowledge scores before and after intervention. There was a significant difference in the knowledge scores before intervention (M=5.47, SD=2.12) and after intervention (M=9.19, SD=2.96), (P = 0.000). For the secondary outcome of natural remedies belief, a McNemar’s test was conducted. There was a significant decrease in the proportion of women who agreed that natural remedies should preferably be used during pregnancy (P=0.000).
In the provider study, there were 181 respondents in the sample. Most respondents were pharmacist (N=131, 78.4%), while (N=36, 21.6%) were physician. The mean age of the respondents was 38.60 years (SD=12.24 years). The majority were female (N=102, 61.1%), African American (N=106, 63.5%), and were actively licensed (N=152, 91.6%). The overall PLLR knowledge level in this population was 44.14 %. Findings from multivariable analysis showed that gender was the only significant predictor of PLLR knowledge, female have a mean PLLR knowledge score that is 1.356 higher than male, adjusting for the other factors (P=0.000, 95% CI, 0.61-2.09).
This study was able to demonstrate that a web-based intervention of medication safety in pregnancy and lactation among women of reproductive age is feasible and effective. There was a positive correlation between educational web-based intervention and knowledge score among women of reproductive age. Hence, the developed educational web-based intervention has positively influenced knowledge scores among women of reproductive age. An educational gap, on the other hand, was concluded from the assessment of knowledge and application of the pregnancy and lactation labeling rule among pharmacists and physicians. There is a need to increase healthcare professionals’ interdisciplinary comprehension of the new PLLR. Hence, this study provides a baseline for additional interventions to reduce the knowledge gap about the new pregnancy labeling rule among healthcare professionals.
Safety and effectiveness of medication use during pregnancy are crucial aspects for disease state management to provide health benefits and minimize the risk to the fetus and the mother 1. Statistics show increased usage of medications during pregnancy as well as an increased trend over time. Specifically, a study by Mitchell et. al showed a 68% increase in medication use in pregnancy from 1976 and 2008 (from an average 2.5 medications to 4.2 medications), and almost nearly 90% of pregnant women take at least one medication during their pregnancy, with more than half report using at least one prescribed medication during the first trimester 2.
The U.S. Food and Drug Administration (FDA) has a significant role in addressing drug safety. It aims to create a consistent and reliable format for providing information about the risks and benefits of prescription drug use as well as biological products 3. Efforts toward achieving this aim has progressed over the years. In 1979, the FDA introduced a simple pregnancy labeling system for medications that consists of five letter categories (A, B, C, D, X) where each letter corresponds to the associated risk level 4. It has since been regarded as generalized, incomplete and, also became repetitive and difficult to use over time 4.
In an effort to improve medication safety in pregnancy, a new labeling system was published on December 4th, 2014 with the intention of providing patients and healthcare providers with clear and detailed information on medication risk during pregnancy 5. Effective June 30th, 2015 the new Pregnancy and Lactation Labeling Rule (PLLR) is now considered more comprehensive because it addresses the safety requirements of drugs for both women and men in reproductive age, currently pregnant women, and women who are lactating 5. Based upon this, the new system is believed to improve the assessment of medication risk and benefit for pregnant and nursing mothers. Drug safety interpretation and prescribing practices will be impacted from this new labeling system concerning pregnancy and lactation safety. While these changes involve providing healthcare professionals with more detailed information, they also imply more responsibility on them to ensure the safety of their patients 1.
Considering the recent launch of the new labeling system in June 30, 2015, there have been no studies thus far among physicians and pharmacists that have examined the impact of the PLLR and knowledge of its use. Furthermore, more patients’ education is needed to educate women of reproductive age on medication safety during pregnancy. As a result of these previously mentioned gaps in knowledge, this study developed a web-based intervention to increase knowledge of medication safety in pregnancy and lactation among women of reproductive age and assessed the knowledge and application of the Pregnancy and Lactation Labeling rules among pharmacists and physicians.
Medication use among women during pregnancy and lactation is very common. A study published in 2011 estimated that 94% of women take at least one medication during pregnancy or lactation, with almost 70% taking a medication during organogenesis in the first trimester of pregnancy 2. Although many medications are safe to use during pregnancy, there is a risk of taking a medication that could potentially harm the fetus and eventually cause a pregnancy loss 6. Usage rates of prescription and over-the-counter (OTC) medication use during pregnancy to range from 50 percent to 80 percent 7,8. An incremental trend of these usage rates is expected as women delay pregnancy until later in their reproductive lives when the rate of illnesses that require medication increases 9. Accordingly, medication safety needs to be addressed as medication use and mean age of first pregnancy will increase among women of reproductive age. Although little is known about women’s awareness of medication safety during pregnancy and lactation, there has been no intervention program, to date, addressing medication safety for women of reproductive age.
Women safe use of medication during their pregnancy and lactation is an area of concern for them as well as for their healthcare providers. In December 2014, the U.S. Food and Drug Administration (FDA) issued a final rule on new labeling changes, which went into effect in June 2015 and eliminated the letter system of A-D, X. The new labeling includes a summary of risks to using the medication during pregnancy and lactation, and supporting data and relevant information to assist health care providers in counseling pregnant and lactating women 6.
During the implementation period thus far, there has not been any documented assessment of the transformation to the new labeling system. Adoption of this new system implies more responsibility on clinicians to read a potentially lengthy label compared to the verbal shortcut of the older ABCDX categories. In addition, it requires healthcare professionals to share the medication information with the women for whom a potential prescription is being considered. Few research studies have investigated the awareness about the newly implemented system among physicians and pharmacists. Hence, missing assessment efforts of the new system impact after three years of implementation represent a knowledge gap that needs to be addressed toward further enhancements.
As aforementioned, the purpose of this study is to develop a web-based intervention to increase knowledge of medication safety in pregnancy and lactation among women of reproductive age and to assess the knowledge of the pregnancy and lactation labeling rule among pharmacists and physicians. The developed intervention will help improve the knowledge of medication safety and to introduce a positive change among reproductive age women. The developed intervention will also provide a platform for future studies to further enhance women knowledge about medication safety during pregnancy and lactation. The results of this study will help healthcare providers and researchers to understand the types of beliefs that affect women of reproductive age toward safe medication use.
The results from this exploratory study will also address significant predictors of healthcare provider knowledge towards the new PLLR to provide guidance in the selection of intervention strategies.
Primary Hypothesis H1 will determine whether women of reproductive age who have a web-based educational intervention will increase their knowledge of medication safety. It is hypothesized that the knowledge of medication safety in pregnancy and lactation among women of reproductive age will increase after the web-based intervention. This hypothesis is consistent with a study by Walker et. al., which showed that web-based educational intervention improved maternal knowledge of placental complications of pregnancy and reduce maternal anxiety in high risk-pregnancies 10. Hypothesis H2 will assess women’s belief of natural remedies after the intervention. it is hypothesized that the proportion of women who falsely believe that herbal medications should be preferred to conventional medicines will decrease after the intervention. Previous studies have shown improvements in women’s belief post the intervention 11. Primary Hypothesis H3 will evaluate whether providing a direct patient care to pregnant or reproductive age women is a predictive factor of their knowledge related to the pregnancy and lactation labeling rule. It is hypothesized that providing direct patient care to women who are pregnant or of reproductive age will have a higher knowledge scores compared to those who do not have direct patient care to women who are pregnant or of reproductive age adjusting for other factors. This hypothesis is based on a study’s finding that obstetrician–gynecologists had better knowledge of imaging in pregnancy than emergency medicine physicians 12. Hypothesis H4 will compare pharmacists’ and physicians’ knowledge about the new PLLR. It is hypothesized that pharmacists’ will have a higher knowledge scores compared to physicians’, adjusting for other factors. This hypothesis is consistent with a study by Staicu et.al., (2017) which showed that pharmacists had a better understanding of the natural history of penicillin allergy and antibiotic cross-reactivity compared to other healthcare practitioners 13.
Although ongoing medications for women is established regardless of their maternity status, pregnancy could worsen this dependency due to associated biological and psychological changes 14. Many symptoms can result from these changes such as nausea and vomiting, which are estimated to affect 75% of pregnant women, heartburn, headache or pelvic girdle pain 14. A diagnose of urinary tract infections (UTIs) is expected to complicate 7% to 10% of pregnancies as the biological changes during pregnancy increase women’s susceptibly to UTIs 15. Moreover, pregnant women with preexisting conditions can neither stop their medications nor give up childbearing. The risk of developing obstetrical complications such as gestational diabetes, preeclampsia, or hypertension increases with delayed pregnancy 14. Accordingly, pharmacotherapy during pregnancy is crucial for the health and safety of both the mother and the fetus.
Drug utilization studies have indicated that the use of medication is common during pregnancy. A systematic review of all studies about drug utilization during pregnancy in developed countries reveled that France and Germany were highest in prescribed medication use during pregnancy (93% and 85% respectively), whereas Northern Europe nations ranged lowest (44% to 47%) 15. Different estimates of prescribed medication use were identified in individual studies for each country among which: Serbia 27%, Finland 46%, Italy 48%, Norway 57%, The Netherlands 79%, and France 93% 16–23. In the US, according to Mitchel et al 2, occurrence of prescribed and over-the-counter medication use in all pregnancies was 89%.
While paracetamol is the most common type of medicine used in pregnancy, medications for the alimentary tract and metabolism, antibiotics, anti-asthmatics and psychotropics are commonly used as well 7,22,24,25.
Contraindicated medicines are evidently used as well in pregnancy as measured rates of their use during pregnancy in Denmark and USA, were 0.9% and 4.6% respectively 15. In a study that examined filled prescriptions in the US, it was revealed that 4.6% of pregnant women filled a prescription of at least one contraindicated medicines or category X as rated by the FDA, while 4.8% filled a prescription of at least one drug that has positive evidence of risk in pregnancy or category D as rated by the FDA 7.
While studies on prescribed medication use in pregnancy is abundant due to availability of prescription-only medications databases, analysis of OTC medication use during pregnancy is limited. The use of OTC in pregnancy, however, is common as Werler et al 26 reported the paracetamol use among pregnant women was 65%, whereas ibuprofen and pseudoephedrine use were 18% and 15% respectively. Analysis of OTC use by race reveled that self-reported usage rate of OTC during pregnancy among Hispanic women in the US was 23% 27. On the other hand, Refuerzo et al 28 reported higher estimates of OTC medication use during pregnancy (63%) in the same group with paracetamol, antacids, and ibuprofen being the most commonly reported OTCs (37%, 26%, and 10%, respectively) 28.
Use of herbal medicines during pregnancy varies among the Western countries. In Australia and the United Kingdom, prevalence estimates of using herbal medicines during pregnancy range from 52% to 58%, while they range from 40% to 48% in Norway and Italy 29–32. A lower prevalence estimates range of using herbal medicines during pregnancy was reported in the United States (4.1%-9.4%) 33–35. However, a recent multinational study indicated that 28.9% was the overall usage of herbal medicines during pregnancy across different countries while it was 29% in the U.S. 36.
Medications with potential risk for complicating pregnancy are hard to examine on human subjects. Attempts, however, have been made toward estimating the prevalence use of these medications among pregnant women. Andrade et al 37 have successfully made an attempt to unravel teratogenic medication exposure among pregnant women. The resulted study found that 1.1% of women in the US were exposed to a teratogenic medication during pregnancy. According to the same study, this finding was “based on the assessment of clinical teratologists, most commonly fluconazole, carbamazepine, prophylthiouracil and tetracycline.” 37. Another study that examined the prevalence and fetal risks during the first trimester found that 54 medications were used by more than half percent of pregnant women 38. While the majority of these medications had low data availability rating (limited to fair) for assessing their teratogenic risks in human pregnancy according to the Teratology Information System (TERIS), promethazine and doxylamine were the only two medications that had high rating (good to excellent) 38.
General online education has rapidly grown in recent years. Educators are continuously utilizing the web platform to reach a bigger audience and widely spread their contents. Health sector is not excluded from this phenomenon as the application of e-health is evolving. Cook et al 39 has indicated that e-health has expanded through web-based education 39. Online educational interventions, via Internet or local intranet, constitute web-based learning 39. According to a systematic review of research into web-based health education, knowledge gain and behavioral change are among the factors for web-surfing 40,41. Informing patients through health educational video intervention is effective as studies indicated. A study have positively influenced vaccination health beliefs without impacting vaccination rates through a video education on influenza vaccination in pregnancy 11. Another study that developed an RCT web-based intervention has helped to improve knowledge of healthy diet and lifestyle among reproductive age women with Gestational Diabetes Mellitus 42. In a project that adapted an existing web-based program to reduce alcohol consumption among women of reproductive potential, risky alcohol consumption has been reduced following the web-based feedback intervention 43. A disease-targeted web-based educational intervention for placental complications of pregnancy has significantly improved knowledge of women patients and reduced their maternal anxiety 10. In a recent pilot study to determine the impact of a customized educational video, Robinson et al 44 found that the video intervention has increased participation of African American breast cancer patients in therapeutic trials 44.
While pregnancy is mostly perceived as good news toward motherhood, it could be associated with health concerns. Pregnant women struggle with decisions related to their ongoing medications and whether taking medication during pregnancy is safe to the fetus. This fear for safety is justified due to many factors involving all parties in the healthcare system. The caution treatment approach of healthcare providers toward prescribing needed medication to pregnant women is a contributing factor in the stated medication fear. Other factors include medication labeling, missing evidence-based teratogenic counseling, recommendation variance among sources, and the significant lack of safety profile for most marketed pregnancy medications. 45–49
Historically, the “thalidomide disaster” during the early 60’s, where more than 10,000 children had been born with major thalidomide-related malformations, has shaped the current fear of harming the fetus due to medication exposure during pregnancy 50. Prior to this tragedy, there was a common belief about the placenta being a natural barrier through which nothing harmful could cross to the fetus 50. Thalidomide, a sedative and anti-nausea medication, destroyed this perception as Dr. McBride and Dr. Lenz independently examined utero exposure to thalidomide and reported an increase in severe congenital anomalies among infants 51,52. Accordingly, the medicine was withdrawn from the market following these astonishing finding in the early 60’s 50. The chance of giving birth to a child with congenital anomalies, mainly Amelia or phocomelia of extremities, due to thalidomide exposure during the first trimester was approximately one out of three 53,54. The frequency of intake was insignificant as single or repeated use of thalidomide during the critical period between 27th to 40th day of gestation would still result in these congenital anomalies 54.
As thalidomide became a teratogen, the FDA stepped up its regulations efforts and issued new procedures of all investigational medications by the mid 60’s where it mandated animal studies prior to testing in human subjects 55. Moreover, the new FDA regulations required collection of reproductive and fertility data and investigation of teratogenic effects studies in two different animal species prior to approval for reproductive age women 55,56. Eventually, medication labeling was subject to many proposed changes following the thalidomide historical event 55–57.
The Food and Drug Administration (FDA) has a significant role in addressing drug safety. It aims to create a consistent and reliable format for providing information about the risks and benefits of prescription drug use as well as biological products 3. Efforts toward achieving this aim has progressed over the years. In 1979, the FDA introduced a simple pregnancy labeling system for medications and continued to be in effect for over 35 years 56,57. The simple system consisted of five letter categories (A, B, C, D, X) where each letter corresponds to the associated pregnancy risk and teratogenic potential in compliance to the consistent and uniform regulations 4. The general safety indication for using a drug during pregnancy or lactation, which eventually became part of labels, was based on available data. Table 2 5 details the alphabet system and describes the clinical implications along with the major shortcomings as identified by researchers since its implementation 55,58,59.
Examining the attached table reveals that definition clarity and clinical relevance recommendations were only available for category A and X (safe to use and contraindicated respectively). On the contrary, information about other categories (i.e. B, C, and D), which have been used broadly, were ambiguous and safety could not be assessed. While this unclarity was possible to assess after more than three decades of implementation, clinicians’ awareness may have been missing at the time of adoption to interpretation and misinterpretation 55.
While the system objective was to provide more clarification about medications to healthcare providers and patients, it did not fully achieve this objective as categories ambiguity was resulted. According to Doering et al. 55, and Ramoz & Patel-Shori 56, the system has rigid categories and hence, it was not able to provide clarity about medications risk versus benefits. Besides the missing information about medication use during labor, birth, and lactation along with exposure, users of the letter system couldn’t interpret the categories’ actual meaning relative to teratogenicity 55,56. As a result, the system has since been regarded as generalized, incomplete and, also became repetitive and difficult to use over time 4.
Adding to the categories’ ambiguity, drug labeling was problematic due to limited information. For instance, certain usage information of the drug agent during preconception, intrapartum or postpartum, and lactating periods were not included. To the contrary of the common misconception about FDA awarding category, pharmaceutical companies are the one assigning their drugs to the letter categories while FDA plays a regulatory role of approving drugs. Although scientists have different opinions about drug’s category based on the clinical information, manufacturers perform actual labeling of their drugs. The resulting differences cause confusion among researchers and clinicians. 53
In an effort that started in 2008 with a proposal to improve medication safety in pregnancy, a new pregnancy labeling system was accepted on December 4th, 2014 with the intention of providing patients and healthcare providers with clear and detailed information on medication risk during pregnancy 5,60. The new Pregnancy and Lactation Labeling Rule (PLLR) was effective on June 30th, 2015 and is considered now more comprehensive. It is mandated for all FDA approved drugs on both brand names and generics excluding over-the-counter after June 30, 2001 61. Moreover, updated information will be reflected on the package insert as they become available 61. While the new labeling is not required for approved drugs before June of 2001, old labeling references must be removed by 2018 61. However, there is neither update recommendation for these old drugs nor a substitute mandate for certain information and hence, clinicians may struggle with the information lack. The new system addresses the safety requirements of drugs for both women and men in reproductive age, currently pregnant women, and women who are lactating 4. Based upon this, the new system is believed to improve the assessment of medication risk and benefit through a consistent format for pregnant and nursing mothers 4. Drug safety interpretation and prescribing practices will be impacted from this new labeling system concerning pregnancy and lactation safety. 5
The 8th section of the federal drug labeling rules titled Labeling for Human Prescription Drug and Biological Products was expanded in the new PLLR system. More specifically, the Special Populations part of the drug label has now three new sections addressing: 8.1) pregnancy and intrapartum, 8.2) lactation, and 8.3) reproductive capable women and men use of drugs 4,62. For each section, there are further subsections addressing three areas: 1) risk information, 2) clinical considerations, and 3) background data collected from different sources. The first area provides the potential risks of not treating the condition along with associated risk of taking the drug. The clinical consideration subsection provides drug doses variation if used by a pregnant woman. Drug manufacturers must share all clinical trial data in the third subsection with separate listing of animal and human studies. 4,62; further details about these subsections are included in Table 3 5.
While the use of drugs during the prenatal period, with the possibility of including some information about intrapartum or breastfeeding, was the focus of the old category system, the new PLLR system has narrative summaries. Comparison between the old ABCDX category system and the new PLLR labeling appears in figure 1 62.
The new PLLR system included the previously combined section of labor and delivery in the pregnancy section. The pregnancy section of the new system provides a summary of related antepartum and intrapartum risks as shown in the early presented Table 3 (page 15) 5. Pregnancy Exposure Registry is an important clinical addition to the pregnancy section as it provides, if exists, contact information for a pregnancy registry. 4,62
Pregnancy registries are observational studies that can be perceived as a follow-up of women exposed to medication during pregnancy. They contain a collection of uniform data toward evaluating outcomes for a given population defined by a specific exposure of pregnant women. The exposure can be either based on a common exposure to a medication or on a common outcome of the pregnancy such as congenital or anomalies. Significance of these registries comes from supporting post-marketing information about the drug usage 63. Thus, optimum utilization of these registries depends on full inclusion of all exposed women. Information of pregnancy exposure listed in these registries have existed long ago and resemble contributions of drug makers and promotors.
Administration of current ongoing registries is handled by pharmaceutical industries, general hospitals, and non-profit organizations. While FDA does not administer these registries, it may recommend or require their establishment by the pharmaceutical company based on the new PLLR system. GlaxoSmithKline, for example, runs the Seasonal Influenza Vaccine Pregnancy Registry while the Center for Women’s Mental Health at Massachusetts General Hospital manages the National Pregnancy Registry for Atypical Antipsychotics. Non-profit organizations such as the Organization of Teratology Information Specialists (OTIS) and the European Network of Teratology Information Services (ENTIS) administers the OTIS Autoimmune Diseases Study and the prospective multicenter observational study on safety of TNF-alpha inhibitors in pregnancy respectively. 64
As these registries are in effect observational studies, it requires the contribution of drug users or clinicians who note an adverse outcome through prompt reporting toward facilitating early detection. Hence, the two main contributors of the pregnancy registry are physicians and pregnant women. Exposure to specific medications can be identified through physicians who enroll their patients on pregnant medications into corresponding registries. In addition, pregnant women can voluntarily perform self-enrollment into pregnancy registry through phone by calling teratology information or online by visiting the service webpage 65. While early identification of medication exposure before knowing the pregnancy outcome is an upside of this enrollment, the downsides for these studies include: referral bias, missing follow-up, and suitable selection of a control group. Overall, pregnancy registries is considered a source population and hence, can be used for cohort or case control studies 66.
While pregnancy main section in the new PLLR system has the exception of including a registry subsection, there are consistently three subsections appears for each main PLLR section: risk information, clinical considerations, and background data. Having detailed the exceptional pregnancy subsection of registry, the following contents describe the remaining subsections.
As indicated previously, the fetal risk subsection is a summary that provides the potential risks of not treating the condition along with associated risk of taking all drugs absorbed systemically. This summary contains data from human, animal, and pharmacologic sources about embryocidal, teratogenic, and/or fetotoxic risks.
The clinical consideration subsection provides drug doses adjustments during antepartum and/or intrapartum periods. It also provides information about adverse effects of drug use that is unique along with any dosing base, time base, or duration of exposure base effects. In addition, drug effects during labor or birth, possible effects on the newborn, and intervention recommendation are included in this section. While known risks after inadvertent exposure in included in the clinical consideration subsection, a statement indicating no data about risks is provided if unknown. Drug manufacturers must share all clinical trial data in the third subsection with separate listing of animal and human studies.
Finally, the background section includes shared clinical trial data by drug manufacturers while maintaining separate listing of human studies and animal studies respectively. While the former studies have positive and negative findings, subjects count, and duration, the latter point the species involved and equivalent human dosages, if possible, for comparison. The summarized information in this section generally includes study type, exposure, and any fetal abnormality or other adverse effects identified.
The second main section of the new PLLR system is lactation or post-delivery phase of breastfeeding. Although, safety data is available, requiring a drug during nursery usually jeopardize breastfeeding as safety uncertainty is associated 67. Accordingly, lactation section in the new labeling system include summary of risk subsection, if available, or indicate data lacking. It lays out the effect of the intended drug on production of breast milk, its concentration in the breast milk, relative infant dosage, and known effect over short or long terms on the breastfeeding child 68. The risk subsections conclude with a risk-benefit statement indicating the drug compatibility with breastfeeding if no adverse effect on production of breast milk or the infant is found.
As in the pregnancy section of the new labeling, clinical consideration within lactation include dosing adjustments, recommendations to minimize exposure to the infant such as pumping out and discarding breast milk during short term use of a specific drug agent, and adverse effects interventions. The last subsection of background data has the same information structure described in the pregnancy section. Table 3 (page 15) 5 provides a summary of the lactation information.
Due to the lack of information about preconception counseling concerning a specific drug, clinician’s comments inspired the creation of reproductive potential section within the new PLLR system. Dedicating this labeling section enables standard placement of drug information that could have been found anywhere. While pregnancy is a female notion, expanding the focus to male partners whom their reproductive capability could be harmed was essential. Accordingly, this section is only mandated upon availability of human or animal data that indicates a fertility risk associated with drugs in which contraception is recommended before, during, or after treatment.
Unlike pregnancy and lactation sections, reproductive potential section is brief and include three distinct subsections: pregnancy testing, contraception, and infertility. The significance of this section can be realized from the fact that almost half of all pregnancies are unplanned ones and hence, the contained information is critical to identify pregnancy risks for male and female alike.
Table 3 (page 15) 5 provides a summary for the required information of this section. A practical example of a known drug can improve the abstract understanding of this section: pomalidomide or Pomalyst. This drug is a thalidomide analogue that treats individuals with multiplemyeloma and can be found in male’s sperm for several weeks of intake. Accordingly, a birth control such as condom is recommended not less than four weeks after drug discontinuation 69.
A quasi-experimental study was designed to increase knowledge of medication safety in pregnancy and lactation among women of reproductive age.This study included adult women of reproductive age (18 – 44) 70. Women were recruited via the internet and were provided an incentive of $8.00. Qualtrics Inc. (www.qualtrics.com), an independent vendor that provides online survey services, was contracted to draw the sample and collect the data according to the proposed research specifications. Data were collected at the same point in time using items that have been adapted from Slone Epidemiology Center’s Birth Defect Study 71 and from the Multinational Medication Use in Pregnancy Study 72. These surveys have been widely used to study medication use behavior in women and will be detailed in a separate section on survey development. The inclusion criteria for the Women’s study included reproductive age women (18-44) who were pregnant at the time of the study, have had a child within the past year, or were non-pregnant. The exclusion criteria, were women who had difficulty understanding the English language at the time of the study.
A “priori power analysis” was conducted to determine the required sample size to achieve the goals of the study. The G*Power version 184.108.40.206 software was used 73. In this analysis, the following parameters were needed to calculate the sample size (N): the power level (1-β), the pre-specified significance level (α), and the population effect size 73. The power for this study was set at 80%, the alpha level at 0.05, the effect size at 0.2, for a one-tailed paired t-test was chosen. As a result, a sample size of at least 156 was required for this study (See Appendix A).
For the Women’s study, the study survey and the web-based intervention were deployed in Qualtrics. The intended video intervention was uploaded to YouTube public host services and then, an embedded URL link was provided to participants on the survey. Upon signing a consent form, participants first responded to baseline questions (pre-survey). After completing the pre-survey, respondents watched the web-based educational video presentation by an actor posing as a pharmacist. Immediately afterward, respondents completed the post-survey, which include only the knowledge and attitude domain questions of the pre-survey but asked respondents to answer based upon their knowledge of the importance of medication safety use during pregnancy and lactation after viewing the video presentation. As watching the video intervention is critical for the intended assessment, three verification measures were implemented to ensure that respondents would not be able to resume the survey before finishing watching the video: 1) a watching commitment statement, 2) an auto-play feature to start the presentation if participant did not resume, and 3) a timer was set on the video.
The proposed survey for the Women’s study used items on medication use behavior adapted from existing surveys used in the Slone Epidemiology Center’s Birth Defect Study 71, and the multinational medication use in pregnancy study 72. Both instruments were modified to suit this study population and subject matter (See Appendix B). To collect data on knowledge, questions were created based on actual information found on the FDA website 74. A total of eleven knowledge- related items were included in the questionnaire. Additionally, attitude questions were adapted from the multinational medication use in pregnancy study 72 and Zaki et.al. study 75. There were ten attitude questions to test respondents’ attitude on medication safety use during pregnancy and lactation. Moreover, there were six questions assessing participants’ normative belief 76. Post-survey questions that include the same knowledge and attitude questions were inquired immediately afterward. In addition, questions adapted from Gupta et. al. 77, were used to examine the effectiveness of the intervention toward increasing participants’ knowledge of medication safety, the likelihood of sharing the content information with others, and using the presented resources in the video.
A pilot study with 10% of the population was used to assess the face-validity and content validity of the knowledge items only as the other items for medication use and attitudes have been used from existing surveys. The sample size of the pilot study was determined to be sufficient based on extant literature suggests that a pilot study sample size should be between 10 – 30 78–80.
Accordingly, a survey of two parts was created: 1) online questionnaires that composed of items related to sociodemographic, knowledge and attitude of medication safety use during pregnancy and lactation, and 2) post intervention questions. Acceptability testing is a post procedure following the survey completion where respondents had additional questions. These questions are survey characteristics to determine their difficulties to participants, and other questions related to the language, wording, clarity, and appropriateness of responses.
Content validity was assessed for this study through expert faculty members of Howard University Pharmacy College. They reviewed the final items after survey creation and assessed the suitability of the questions in assessing knowledge and perceptions of safe medication use.
As aforementioned, the primary outcome of this study is to increase the knowledge of medication safety in pregnancy and lactation among women of reproductive age. Study covariates included: age, education level, parity, marital status, and work situation.
Operational definitions were created for knowledge and Likert scale responses for TRA constructs in this study. Knowledge level was operationally defined as true, and falsebased upon the actual survey responses options for “True”, “False” and “Don’t Know”. Four-point Likert-style survey was used to measure attitude, while five-point Likert-style survey was used to measure normative belief.
Women of reproductive age who were pregnant or non-pregnant at the time of the study were recruited from an online sample using Qualtrics-a contracted online company that acquires web-based samples. Potential survey respondents were sent an email invitation informing them that the survey is for research purposes only, how long the survey is expected to take and what incentives are available. Based upon our proposed sample of 156, this study provided an incentive of $8.00. To avoid self-selection bias, the survey invitation did not include specific details about the contents of the survey.
A web-based online educational intervention was developed for use in the women of reproductive age group (pregnant or non-pregnant) as a pre-post study design. A short demonstration video on medication safety that lasts for about 10 minutes was produced and posted online as a web-based intervention after being reviewed from the clinical co-investigator.
The source content of the video was developed from publicly available medication safety materials created by the FDA (See Appendix C). The flow of the video information was framed under the four learning tips. First was “Ask questions”, second was “Reading the label”, third was “How to be smart online” and fourth was “Reporting Problems”. Information on pregnancy registry exposure was also provided. The video was embedded in the Qualtrics survey system as a YouTube video link in the appropriate format. Table 4 below summarizes the detailed content and format of each section.
This study adopted the Theory of Planned Behavior (TPB) as the conceptual framework. The theory started in 1980 as the Theory of Reasoned Action to predict an individual’s intention to engage in a behavior at a specific time and place 81. The intention was to explain all behaviors over which people have the ability to exert self-control and hence, behavioral intent is the key component 81. There are factors influencing the behavioral intentions: 1) the attitude about the possibility that the behavior will have the expected outcome, and 2) the subjective evaluation of the risks and benefits of that outcome 81.
Historically, Ajzen 82 proposed the theory of planned behavior (TPB) in 1985 to explain briefly and concisely how humans were perceived to perform various behaviors under the influence of intention. According to the theory, intention is the immediate antecedent, while perceived behavioral control is an additional factor that differs from the theory of reasoned action 83. There are three main beliefs identified in this theory: 1) behavioral, 2) normative, and 3) control. Figure 2 below provides a demonstration of the schematic presentation of this theory.
First, behavioral beliefs are personal assessment that formulate individual’s attitude toward executing the behavior. Thus, self-evaluations of the behavior’s benefits and drawbacks shape an individual’s attitude and consequently the possibility of performing the behavior. Second, normative beliefs can be formed into two types: a) injunctive beliefs that are formed based on the degree to which important people in our life would support our decision to execute the behavior, or b) descriptive beliefs that are formed based on the degree to which these important people personally perform a particular behavior. The two normative types combined form the perceived norm by which an individual has the sense of peer and social pressure to either perform the behavior or not. Third, control beliefs resemble the impact of personal and environmental factors that either ease or hinder our ability to carry out a behavior. Accordingly, a perception of low or high self-efficacy results from these control beliefs. 83
People’s willingness to perform a behavior or our behavioral intention are the combination of three factors: their attitudes, perceived norms, and perceived behavioral control. The direct predictors of behavior are both intentions and perceived behavioral control. With the absence of external constraints while having the right skills and qualities, a stronger intention implies higher possibility of performing a behavior. Hence, intention is an immediate behavior determinant. 83
This study adopted attitude and normative belief areas of the theory of planned behavior as the aim of this study is to build intention through knowledge. Accordingly, increasing knowledge will indirectly affect attitude and normative belief. The control belief, on the other hand, was not addressed since it’s behavior is out of individual’s control and hence, beyond the scope of this study. The adopted areas of importance designated by the FDA were mapped. The following Table 5 provides this study’s application of the theory.
Following the completion of the data collection phase, descriptive statistics of all study variables were estimated including means for continuous and percentages for categorical variables. Simple descriptive statistics were conducted for all variables to detect extremes values by examining frequency tables, mean and standard deviation, histograms, correlations and plots.
A paired t-test was conducted to determine knowledge and attitude before and after intervention. All analysis were conducted using SPSS version 25 at an alpha value of 0.05.
This study adopted a cross-sectional study design using a survey method. An online questionnaire was developed using Qualtrics (http://www.qualtrics.com/) – an online survey software program – in order to collect data on users’ characteristics and their knowledge and attitude of pregnancy lactation labeling rule. Participants were recruited using a mass e-mailing service.
A “priori power analysis” was conducted to determine the required sample size to achieve the goals of the study. The G*Power version 220.127.116.11 software was used 73. In this analysis, the following parameters were needed to calculate the sample size (N): the power level (1-β), the pre-specified significance level (α), the population effect size, and the numbers of predictors 73. The power for this study was set at 80%, the alpha level at 0.05, the effect size at 0.15, and the number of predictors = 8. As a result, a sample size of at least 109 was required for this study (See Appendix D).
Online surveys are usually associated with low response rates. Several studies that examined web-based surveys have reported a response rate range from 7% to 81% 84–89. In a systematic review conducted by Braithwaite D et al (2003), of 17 Internet-based surveys of health professionals 90. Twelve studies reported response rates, which ranged from 9% to 94% 90. However, an increase in the response rate of electronic surveys for healthcare professionals has been found following reminders 90.
Accordingly, having an initial distribution list of about 1,000 healthcare providers for this study was to account for non-response rate.
For the Provider study, the electronic study survey was deployed in Qualtrics. An existing email distribution list of physicians and pharmacists was utilized. Potential survey respondents were sent an email invitation containing a brief description of the study along with a link for the survey. Based upon our proposed sample of 109, this study provided no incentive for the physicians and pharmacists.
The content of the email invitation included information about the study’s objectives, purposes, and importance. Once visiting the electronic survey link, a required consent form appeared first. Upon signing that form, participants were able to proceed with the survey questions. Follow-up reminder emails were sent at varying time intervals. The reminder e-mails also included the link for the survey. Respondents viewed a “thank you” note upon completing the survey.
The proposed survey for the provider study was created from three different sources with items aggregated to allow for assessment of knowledge and attitude. To collect data on knowledge, questions were created based on the information found in NIH and FDA websites 62,91. From these knowledge surveys, a total of 14 knowledge related items were included in the questionnaire. These knowledge items were equally divided between PLLR and Pregnancy Letter Category. Additionally, attitude questions were adapted from a study by Lugtenberg et al 92, and were modified to suit our study population and subject matter. There were 8 attitude questions to test respondents’ attitude for the old category system and the new labeling rule (See Appendix E).
As aforementioned, the primary outcome of this study is to assess physicians and pharmacists’ current knowledge and attitude of the Food and Drug Administration’s pregnancy and lactation labeling rule. Study covariates included: gender, age, race, and practice setting.
Operational definitions were created for knowledge and Likert scale responses. Knowledge level was operationally defined as true, and falsebased upon the actual survey responses options for “True”, “False” and “Don’t Know”. Five-point Likert-style survey was used to measure attitude toward the old category system and the new labeling rule.
Physicians and pharmacists were recruited from existing email distribution list. Potential survey respondents were sent an email invitation informing them that the survey is for research purposes only, how long the survey is expected to take and what incentives are available. Based upon our proposed sample size of 109, this study provided no incentive for the physicians and pharmacists.
Following the completion of the data collection phase, descriptive statistics of all study variables were estimated including means for continuous and percentages for categorical variables. Simple descriptive statistics were conducted for all variables to detect extremes values by examining frequency tables, mean and standard deviation, histograms, correlations and plots. A multivariate linear regression was conducted to determine predictive factors of knowledge. All analysis was conducted using SPSS version 25 at an alpha value of 0.05.
The fact that this study relied on online survey, data were aggregated by website, not by investigator, it required no human contact during the data collection phase. This study obtained participant consent prior to the intended survey participation. Upon completion of the survey, personal data of participants were de-identified before they became available. Accordingly, a “Certified Exempt” was obtained from Howard University Institutional Review Board (IRB); such exempt grants permission toward proceeding with this research.
This study examined sources of information women generally used to know about medication safety. Although women used multiple information sources, healthcare professionals among whom physicians were the most common source. This finding is in consistent with previous studies that reported healthcare professionals being the primary source of information 25,93. Internet was also a widely used source of information (47.1%) for women to obtain information about medication safety. This is consistent with previous studies 25,93–95. Hence, this study recommends that healthcare providers should incorporate this into their practice through discussion with their reproductive age women patients about obtaining online information, validate its accuracy, and offer clarification about any related questions. Moreover, education for healthcare professionals should be updated to include reliable online information sources and how such information should be discussed with their patients.
Moreover, this study evaluated the need for information during pregnancy and breastfeeding. Over half of the pregnant women who responded to this study’s online survey indicated a need for information related to medication safety during pregnancy and breastfeeding. Similarly, a multinational study found that 54% of pregnant women participants in the U.S. need information during pregnancy 49. Reexamining sources of information during pregnancy and breastfeeding for participants who were currently pregnant or had one year or less child reveled a lower dependence on the Internet (27.1%). This can be contributed to the special time of maternity during which women become more cautious and concerned about their babies’ health. Accordingly, these women weighed their Gynecologist more as the primary source of information about medication safety (55%).
As the study surveyed women about taking prescription medications while pregnant, (41.1%) confirmed that with a majority reading leaflet accompany their prescription medications (83.1%). Taking non-prescription medications, on the other hand, were higher (44.2%) while reading medication information leaflets accompany their non-prescription medications were 78.9%. This slight rise in consumption could signal a safety misperception; ease of access and availability of non-prescription medications could lower pregnant women’s guard concerning their health. Hence, this study recommends physicians to verify this misperception with their pregnant women patients and convey any consumption concerns.
In relevance, this study asked women about their interaction with healthcare professionals regarding complete information of prescribed drugs. For women who were pregnant or have one year or less child, Gynecologists were the primary source of complete information (79.8%), followed by pharmacist (76%) and doctors (63.6%). This result supports the significant role of pharmacists who can provide effective counseling and enhance patient care. Pharmacists can educate patients when dispensing prescription medications and hence, doctors can redirect extensive counseling to them.
Among several disorders, depression was the highest reported one in this study’s survey. While (36.4%) of women participants indicated a depression disorder, interestingly (42.6%) did not use any medication during their pregnancy. This finding can be contributed to health concerns about potential adverse effects of the treatment during pregnancy. However, it is recommended that benefits and risks of using anti-depressant medications should be carefully weighed during pregnancy toward avoiding potential risk of non-treatment.
This study also examined Over-the-Counter medication use among pregnant women or had one year or less child. Aspirin and Ibuprofen (containing medications) were medicines used for common cold (20% and 22.2% respectively). In addition, Ibuprofen, as a pain killer, was frequently chosen under different names: Ibuprofen (22.5%), Advil (10.9%), and Motrin (7%). Aspirin and Ibuprofen were both not the drug of choice to take during pregnancy due to their side effect specially during the third trimester. Hence, this study recommends that physicians should caution their pregnant patients about using OTC for pain relief.
The result of this study indicated that herbal preparation usage among women during their pregnancy was 24.8%. This percentage is slightly different from the 29% reported in a multinational study for the U.S. 36, while significantly higher than the 5.8% and 4.1% reported by Louik et al 33 and Refuerzo et al 34 respectively. These differences are contributed to the way each study defines herbal products; while some studies consider all forms of nutritional supplement as herbal, other apply more restrictions. Moreover, another study in the U.S. about the usage of herbal preparation reveled that only a minority of women (9.4%) used herbal preparation during their pregnancy 96. It is important to note, however, that the use of herbal medicines could go unreported as one qualitative study disclosed. Vickers et al 97 indicated that a large majority of women did not inform their doctors about their use of herbal medicines. It contributed that partly on the physicians’ side due to lack of inquiry, and on women’s side due to misperception of importance and avoiding a negative response 97. Hence, this study agrees with Vickers et al 97 recommendation to healthcare providers to routinely inquire about herbal use while informing their patients about the known low risk of using herbal products.
The developed intervention for this study is considered one of the first attempt to develop an effective web-based intervention for the improvement of knowledge about medication safety use among women of reproductive age in the United States. The findings of this study disclosed a significant knowledge gap in medication safety use among reproductive age women. The survey incorporated questions regarding women’s knowledge in the following eight aspects before and after the intervention: impact of becoming pregnant on medication use, the role of folic acid, conception about medicines passing breast milk during nursing, use of products labeled “natural”, the creation of reproductive potential section within the new PLLR system, use of MedWatch form to report problems, online sources of information, and pregnancy exposure registries.
Overall, knowledge score level was less than 50%. Participants showed significant increase in most examined aspects of knowledge after receiving the intervention compared to their responses prior to the exposure. The percent of knowledge score after intervention significantly increased by (33.82%). Hence, the intervention has improved participants’ knowledge in particularly four aspects: 1) products labeled “natural”, 2) MedWatch form, and 3) the creation of reproductive potential section within the new PLLR system, and 4) online sources of information.
Improvement due to the intervention exposure was significant in the aspect of products labeled “natural”. While (53.3%) of women participants indicated that products that says “natural” were not safe to use during pregnancy, the percentage has improved post the intervention to become (75.7%). The effective intervention has also improved the knowledge of women participants about MedWatch forms; (87.1%) of women participants correctly indicated after the intervention that a MedWatch form can be used by consumers to report problems with medications during pregnancy or breastfeeding compared to (41.4%) before the intervention. Similarly, the percentage of women participants who become aware post the intervention about the new FDA requirement of newly approved drugs (i.e. to have information about the need for pregnancy testing, birth control, and the effect of medications on fertility) was (84.8%) compared to (56.7%) prior to the intervention. The designed survey of this study also examined participants’ knowledge of valid online sources of information about safe medication use during pregnancy and breastfeeding. There are four FDA recommended online sources for pregnant women: 1) Mother to baby, 2) CDC, 3) Text 4 baby, and 4) March of dimes. All four were introduced in the intervention for participants as websites that provide valid information about drug safety use during pregnancy and breastfeeding. Post intervention results showed a major percentage increase of women who correctly selected these websites: Mother to baby (28.1% vs 53.3%), CDC (39.5% vs 62.9%), Text 4 baby (8.6% vs 42.9%), March of dimes (20% vs 45.7%). These results confirmed the significance of online sources about medication safety.
Although the pregnancy exposure registries area was among the improved knowledge aspect post the intervention, it involved a couple of confusion elements: administration of the pregnancy exposure registries, and enrollment requirement of experimenting a new medicine; findings indicate that women participants made false selection about these two elements post the intervention. Hence, this study recommends that further clarification concerning the pregnancy exposure registries should be addressed.
On the other hand, a couple of incorporated knowledge aspects in the study’s survey were not significantly improved post the intervention due to participants prior knowledge. Interestingly, more than 90% of women were already aware prior to the intervention that medicines could affect their babies through their breast milk during nursing. In addition, more than 70% were also aware before the intervention about the folic acid role in prevent birth defects of the baby’s brain or spine during pregnancy. This finding is consistent with the findings of two other studies: a pilot study assessing knowledge and use of folic acid among college women (78.1%) 98, and a study on the knowledge of using folic acid among reproductive age women (61.8%) 99. This prior knowledge found in our study justifies the higher percentage (82.2%) of women who used folic acid either before they become pregnant, before and during their pregnancy, or only during their pregnancy.
The finding of this study significantly indicated that more women placed importance after the intervention in three aspects: 1) taking their medications during pregnancy, 2) changing their belief against doctor prescribing too many medicines, and 3) using of natural remedies.
Prior to the intervention, more than two thirds of participants (70%) in this study confirmed that using medicines during pregnancy is better for the health of fetus rather than not treating their illnesses. Improvement post the intervention in this study was consistent with Eldalo’s 100 finding as (87.2%) of women participants confirmed that untreated illness during pregnancy could be more harmful than the medication itself.
As for the aspect of women’s belief about doctor prescribing too many medicines, less than half (40.5%) agreed. In another study 101, one third of participants (33.4%) agreed that doctors prescribed to many medicines, while almost the double (68.1%) was reported in Nordeng et al 25 study. This belief has improved post the intervention as (27.6%) agreed about doctor prescribing too many medicines.
The use of natural remedies during pregnancy was the third belief aspect examined in this study. More than two thirds of women agreed with two statements of pregnant women using natural remedies; (76.2%) on “natural remedies can generally be used by pregnant women” statement, and (74.8%) on “pregnant women should preferably use natural remedies” statement. Following the intervention, on the other hand, there was a significant change in women’s opinions about the use of natural remedies during pregnancy. Most women in this study who previously agreed to the use of natural remedies during pregnancy, disagreed after the intervention; (49%) on “natural remedies can generally be used by pregnant women” statement, and (38.5%) on “pregnant women should preferably use natural remedies” statement. These findings are still relatively high compared to other studies that examined the natural remedies belief without exposing participants to interventions. Nordeng et al 25 study reported that (22.9%) of women agreed about the use natural remedies by pregnant women, while (31.6%) agreement was reported in Eldalo 100 study. Similarly, Twigg et al 101 found that (19.6%) of women believed that natural remedies are safer than medicines. Accordingly, the area of natural remedies should be addressed in further education to rectify its belief among pregnant and reproductive age women.
This study aimed at examining pharmacist and physician knowledge about the new Pregnancy and Lactation Labeling Rule. Overall, findings reveled a low knowledge score (44.1%). This can be contributed to the perception that the old category system might still be in use as the result showed that more than half affirmed this or were unsure about it. In addition, (40%) of respondents were unsure about the new “Females and Males of Reproductive Potential” and “Pregnancy” subsections within the PLLR. Implementation details for the new PLLR were a vague area for most healthcare providers who participated in this study. For instance, more than half were unsure about the implementation requirements concerning drugs prior to June 30, 2001. Moreover, almost half of the providers who participated in this study were unsure about PLLR effect on OTC medicines (47.3%) while (34.7%) of responses had incorrect answer. This is a concern because the new rule has been effective since 2015 as it proves the asserted knowledge gap among healthcare professionals. In addition, healthcare providers were the primary source of information for reproductive age women as shown in the women’s study.
On the other hand, knowledge about the old letter category system was better when compared against the new PLLR (81.1%). As this study examined knowledge responses about the Pregnancy Letter Category System, majority of provider’s who participated correctly confirmed statements about all the system’s categories (A, B, C, D, and X). However, (17.5%) still thought that the use of ibuprofen during pregnancy is safe. While studies have indicated no teratogenic effects during first trimester, positive risk association in late pregnancy was established through a significant increase of premature ductal closure 102. Hence, this study recommends that providers should be cautious when prescribing NSAIDs to pregnant women; benefits and risks of using prescription and OTC pain medicines should be carefully weighed during pregnancy.
In addition to the above educational gap assessment, this study indicated that 94.2% of respondents need to learn more about the new PLLR. This percentage was even higher than the one reported in another assessment study of the PLLR on pharmacists (87%). Hence, this study recommends additional training for healthcare providers on the new pregnancy label updates 103.
Overall, most providers who participated in this study were not resistant to use the new PLLR (51.1%). In addition, most respondents agreed about the usefulness of the new PLLR (53.3%), and (47.5%) affirmed it will improve patient care. Almost a quarter of respondents admitted their lack of knowledge about the new PLLR, and about (29%) were unfamiliar with it. These results indicate that more knowledge about the new PLLR would lead to a better understanding and effective implementation.
On the other hand, examining the old category labeling system reveled that (80.3%) of respondents were not resistant to using it. In addition, most respondents agreed about the usefulness of the old system (78.1%), and (75.9%) affirmed it will improve patient care. There were (27.8%) of respondents who admitted their lack of knowledge about the old labeling system. Compared with the responses about the new system, these higher results indicate more familiarity with the old category system due to its long implementation.
The findings from this study showed that providing direct patient care to pregnant women or reproductive age women had an insignificant effect on PLLR knowledge score among pharmacists and physicians (β=-0.142, 95% CI: -0.95,0.66), (P=0.730). This can be justified with pharmacists being uncomfortable providing direct patient care to pregnant women. According to a couple of U.S. studies, findings indicated that pharmacists did not feel comfortable providing such care to pregnant patients 104,105. Moreover, confident pharmacists about their qualifications making over-the-counter medication recommendation were uncomfortable providing such recommendation to pregnant and breastfeeding women 104,105. Another contributing factor for the insignificance effect of direct patient care to pregnant or reproductive age women on PLLR knowledge could be providers’ education. The same two studies found that pharmacists’ formal education involved insufficient training on the area of maternal-fetal medicine to provide direct patient care to pregnant and breastfeeding women 104,105. Accordingly, due to the significance of their role, this study recommends filling the educational gap for pharmacists through continuing education in the maternal-fetal medicine area.
Our research showed that pharmacists had a higher mean PLLR knowledge scores compared to physician (3.35 vs 2.03 out of a maximum of 7). However, being a pharmacist was not a significant predictor of PLLR knowledge scores (β=0.709, 95% CI: -0.28,1.70), (P=0.160). This finding of the pharmacists’ higher knowledge mean is consistent with previous studies that found pharmacy students had a better knowledge of drug-drug interactions and basic pharmacology than medical students 106,107.
Gender was the only significant predictor that was not part of the study hypotheses. Female were shown to have a higher mean PLLR knowledge score compared to male (β=1.356, 95% CI: 0.61,2.09), (P=0.000). This was a surprising significant predictor of PLLR knowledge score among pharmacists and physicians because it showed a very strong effect. This can be contributed to the study female specific topic. A study investigating the existence of gender difference found that female students outperformed their male encounter in the obstetrics and gynecology clerkship 108. Another study examining gender performance in sex-specific clinical knowledge found that female subjects performed better than the male 109.
Primary data usually involve limitations associated with survey data collection method and hence, this study has a couple of general limitations. First, self-report responses is a limitation as obtained information are not confirmed by other objective measures. Second, selection bias is another limitation of this study since non-random sampling were used and participation was voluntary.
For the women study, the following limitations are worthy to note. First, the study was limited to participants who understand English language and hence, minorities were excluded. Second, missing follow-up to examine the effect of the intervention is another limitation as pre post-testing of the survey and the intervention were carried at the same point in time. Third, the lack of control group precluded the ability to assess if the change in knowledge of medication safety is confounded by external factors not accounted for in this study. Fourth, participants won’t be re-contacted in the future to measure/ confirm actual behavior. Lastly, the results of this study cannot be generalized as most participants were White.
The provider study, on the other hand, has the following limitations. First, the study design was cross-sectional and hence, no inference on causality can be made. Second, low response rate of online survey is a limitation compared to other data collection methods as mail survey and face-to-face interview. Third, the results from this study cannot be generalized due to participants’ affiliation with Howard University.
The video presentation has proved to be informative, easy to understand, and useful for use among reproductive age women. It has a positive impact on women’s knowledge and attitude. This video presentation can be used in the clinical setting because it is simple, efficient, and cost-effective. The video can also be used within the waiting areas of OBGYN clinics/ physicians’ offices to educate pregnant women and women of reproductive age about safe medication use during their routine visits.
An educational gap, however, was concluded. Predictors of PLLR knowledge among pharmacists and physicians were also assessed. Gender was the only significant predictor of PLLR knowledge. Addressing the significant predictor of PLLR will provide guidance in the selection of future intervention strategies for the population studied. Hence, this study provides a baseline for additional interventions to reduce the knowledge gap about the new pregnancy labeling rule among healthcare professionals.
Developing interventions specifically for pregnancy exposure registry would further improve the knowledge of pregnant and women of reproductive age. In addition, developing a targeted-intervention for healthcare providers is needed to fill their knowledge gap about the new PLLR. Translation of the developed intervention for this study into different languages would expand the knowledge across minorities. Similar studies can be performed in a larger sample size in different settings around the US. As other new factors affecting healthcare provider PLLR knowledge may also be evaluated. Having knowledge about additional factors that impact PLLR knowledge among healthcare providers would also provide guidance in the selection of future intervention strategies.