Safety and quality of AI chatbots for drug-related inquiries: A real-world comparison with licensed pharmacists.

Introduction: Pharmacists play a pivotal role in ensuring patients are administered safe and effective medications; however, they encounter obstacles such as elevated workloads and a scarcity of qualified professionals. Despite the prospective utility of large language models (LLMs), such as Generative Pre-trained Transformers (GPTs), in addressing pharmaceutical inquiries, their applicability in real-world cases remains unexplored. Objective: To evaluate GPT-based chatbots' accuracy in real-world drug-related inquiries, comparing their performance to licensed pharmacists. Methods: In this cross-sectional study, authors analyzed real-world drug inquiries from a Drug Information Inquiry Database. Two independent pharmacists evaluated the performance of GPT-based chatbots (GPT-3, GPT-3.5, GPT-4) against human pharmacists using accuracy, detail, and risk of harm criteria. Descriptive statistics described inquiry characteristics. Absolute proportion comparative analyses assessed accuracy, detail, and risk of harm. Stratified analyses were performed for different inquiry types. Results: Seventy inquiries were included. Most inquiries were received from physicians (41%) and pharmacists (44%). Inquiries type included dosage/administration (34.2%), drug interaction (12.8%) and pregnancy/lactation (15.7%). Majority of inquires included adults (83%) and female patients (54.3%). GPT-4 had 64.3% completely accurate responses, comparable to human pharmacists. GPT-4 and human pharmacists provided sufficiently detailed responses, with GPT-4 offering additional relevant details. Both GPT-4 and human pharmacists delivered 95% safe responses; however, GPT-4 provided proactive risk mitigation information in 70% of the instances, whereas similar information was included in 25.7% of human pharmacists' responses. Conclusion: Our study showcased GPT-4's potential in addressing drug-related inquiries accurately and safely, comparable to human pharmacists. Current GPT-4-based chatbots could support healthcare professionals and foster global health improvements.

Comparing pregnancy and pregnancy outcome rates between adolescents with and without pre-existing mental disorders.

BACKGROUND: There are limited population-based data on the role of mental disorders in adolescent pregnancy, despite the presence of mental disorders that may affect adolescents' desires and decisions to become pregnant. OBJECTIVE: This study aimed to examine the relationship between specific types of mental disorders and pregnancy rates and outcome types among adolescents aged 13-19 years, using single-year age groups. METHODS: We conducted a retrospective cohort study using data from the Merative™ MarketScan Research Databases. The study population consisted of females aged 13-19 years with continuous insurance enrollment for three consecutive calendar years between 2005 and 2015. Pregnancy incidence rates were calculated both overall and within the different categories of mental disorders. The presence of mental disorders, identified through diagnosis codes, was classified into 15 categories. Pregnancy and pregnancy outcome types were determined using diagnosis and procedure codes indicating the pregnancy status or outcome. To address potential over- or underestimations of mental disorder-specific pregnancy rates resulting from variations in age distribution across different mental disorder types, we applied age standardization using 2010 U.S. Census data. Finally, multivariable logistic regression models were used to examine the relationships between 15 specific types of mental disorders and pregnancy incidence rates, stratified by age. RESULTS: The age-standardized pregnancy rate among adolescents diagnosed with at least one mental disorder was 15.4 per 1,000 person-years, compared to 8.5 per 1,000 person-years among adolescents without a mental disorder diagnosis. Compared to pregnant adolescents without a mental disorder diagnosis, those with a mental disorder diagnosis had a slightly but significantly higher abortion rate (26.7% vs 23.8%, P-value < 0.001). Multivariable logistic regression models showed that substance use-related disorders had the highest odds ratios (ORs) for pregnancy incidence, ranging from 2.4 [95% confidence interval (CI): 2.1-2.7] to 4.5 [95% CI:2.1-9.5] across different age groups. Overall, bipolar disorders (OR range: 1.6 [95% CI:1.4-1.9]- 1.8 [95% CI: 1.7-2.0]), depressive disorders (OR range: 1.4 [95% CI: 1.3-1.5]- 2.7 [95% CI: 2.3-3.1]), alcohol-related disorders (OR range: 1.2 [95% CI: 1.1-1.4]- 14.5 [95% CI: 1.2-178.6]), and attention-deficit/conduct/disruptive behavior disorders (OR range: 1.1 [95% CI: 1.0-1.1]- 1.8 [95% CI: 1.1-3.0]) were also significantly associated with adolescent pregnancy, compared to adolescents without diagnosed mental disorders of the same age. CONCLUSION: This study emphasizes the elevated rates of pregnancy and pregnancy ending in abortion among adolescents diagnosed with mental disorders, and identifies the particular mental disorders associated with higher pregnancy rates.

The effectiveness of single and two-dose Pfizer-BioNTech vaccine against SARS-COV-2: A real-world evidence from Saudi Arabia.

BACKGROUND: Several studies proved the effectiveness of Severe Acute Respiratory Syndrome Corona Virus (SARS-CoV-2) vaccines; however, the number of doses and the period between doses that warrant the highest protection remain unclear. This study aims to assess the effectiveness of the Pfizer-BioNTech vaccine and to evaluate the effectiveness of early and delayed second-dose administration of the vaccine. METHODS: This is a retrospective cohort study that was conducted using the data from March 1st, 2021, to August 31st, 2021. Data regarding vaccination coverage and confirmed SARS-CoV-2 infection were obtained using academic hospitals databases and Health Electronic Surveillance Network (HESN) platform. The vaccination status of the participants were categorized as: unvaccinated, vaccinated 1st dose, and vaccinated 2nd dose of Pfizer-BioNTech vaccine. The outcome of interest was positive polymerase chain reaction test for SARS-CoV-2. Generalized linear model with a Poisson distribution was used to estimate the incidence of the infection. FINDINGS: Among 66,775 participants included, 2615 SARS-CoV-2 infections were observed. The sample was relatively young with median age of 22 years and 43% female. A single dose of Pfizer-BioNTech vaccine had 40 % effectiveness. The effectiveness of the vaccine was doubled after the second dose of Pfizer-BioNTech (80 %). The time between the first and the second dose appears to be crucial after observing 75 %, 90 % and 85 % effectiveness with early vaccination, on-time vaccination, and delayed vaccination, respectively. CONCLUSION: For Pfizer-BioNTech vaccine recipients in Saudi Arabia, particularly among a predominantly young population, higher effectiveness against SARS-CoV-2 was observed with two doses of the vaccine. The timing of the second dose appears crucial for the extent of protection against SARS-CoV-2. However, potential residual confounding cannot be discounted, and further studies are needed to validate these findings and improve generalizability.

Reproducible variability: assessing investigator discordance across 9 research teams attempting to reproduce the same observational study.

OBJECTIVE: Observational studies can impact patient care but must be robust and reproducible. Nonreproducibility is primarily caused by unclear reporting of design choices and analytic procedures. This study aimed to: (1) assess how the study logic described in an observational study could be interpreted by independent researchers and (2) quantify the impact of interpretations' variability on patient characteristics. MATERIALS AND METHODS: Nine teams of highly qualified researchers reproduced a cohort from a study by Albogami et al. The teams were provided the clinical codes and access to the tools to create cohort definitions such that the only variable part was their logic choices. We executed teams' cohort definitions against the database and compared the number of subjects, patient overlap, and patient characteristics. RESULTS: On average, the teams' interpretations fully aligned with the master implementation in 4 out of 10 inclusion criteria with at least 4 deviations per team. Cohorts' size varied from one-third of the master cohort size to 10 times the cohort size (2159-63 619 subjects compared to 6196 subjects). Median agreement was 9.4% (interquartile range 15.3-16.2%). The teams' cohorts significantly differed from the master implementation by at least 2 baseline characteristics, and most of the teams differed by at least 5. CONCLUSIONS: Independent research teams attempting to reproduce the study based on its free-text description alone produce different implementations that vary in the population size and composition. Sharing analytical code supported by a common data model and open-source tools allows reproducing a study unambiguously thereby preserving initial design choices.

Concordance of neonatal critical condition data between secondary databases: Florida and Texas birth certificate Linkage with medicaid analytic extract.

BACKGROUND: Limited information is available about neonates' critical conditions data quality. The study aim was to measure the agreement regarding presence of neonatal critical conditions between Medicaid Analytic eXtract claims data and Birth Certificate (BC) records. METHODS: Claims data files of neonates born between 1999-2010 and their mothers were linked to birth certificates in the states of Texas and Florida. In claims data, neonatal critical conditions were identified using medical encounter claims records within the first 30 days postpartum, while in birth certificates, the conditions were identified based on predetermined variables. We calculated the prevalence of cases within each data source that were identified by its comparator, in addition to calculating overall agreement and kappa statistics. RESULTS: The sample included 558,224 and 981,120 neonates in Florida and Texas, respectively. Kappa values show poor agreement (< 20%) for all critical conditions except neonatal intensive care unit (NICU) admission, which showed moderate (> 50%) and substantial (> 60%) agreement in Florida and Texas, respectively. claims data resulted in higher prevalences and capture of a larger proportion of cases than the BC, except for assisted ventilation. CONCLUSIONS: Claims data and BC showed low agreement on neonatal critical conditions except for NICU admission. Each data source identified cases most of which the comparator failed to capture, with higher prevalences estimated within claims data except for assisted ventilation.

Prenatal exposure to teratogenic medications in the era of Risk Evaluation and Mitigation Strategies.

BACKGROUND: Prevention of prenatal exposures to teratogenic drugs is a significant clinical and public health concern. With the enactment of the US Food and Drug Administration Amendments Act in 2007, the US Food and Drug Administration has begun to require manufacturers to implement Risk Evaluation and Mitigation Strategies to prevent prenatal exposures. Among 12 risk evaluation and mitigation strategy drugs, several had predecessor risk mitigation plans (eg, isotretinoin) and some were newly required (eg, mycophenolate). Only a small proportion of teratogenic drugs are currently subject to Risk Evaluation and Mitigation Strategies, and the extent of prenatal exposure to the universe of teratogenic drugs compared with drugs subject to Risk Evaluation and Mitigation Strategies is unknown. Moreover, the effectiveness of such advanced risk mitigation programs in preventing prenatal exposure is not clear. OBJECTIVE: This study aimed to characterize the epidemiology of prenatal exposures to definite and potential teratogens during the risk evaluation and mitigation strategy era. STUDY DESIGN: We constructed a time-series of pregnancies identified from a national private insurance claims database (IBM MarketScan) to estimate prenatal exposures to teratogenic drugs (2006-2017). Pregnancy outcomes, gestational age, and the onset of pregnancy were determined with previously validated algorithms. The Teratology Information Service and Clinical Pharmacology databases were used to identify drugs with definite (n=141) or potential (n=65) teratogenic effects, and drugs with debatable risks such as benzodiazepines, statins, tetracyclines, sex hormones, infertility treatments, and gonadotropin-releasing hormone analogs were excluded. We defined prenatal exposure as ≥1 prescription fill or medical encounter involving administration of drugs with a definite teratogenic risk (including 12 for which there is a "current or discontinued" risk evaluation and mitigation strategy) or a potential teratogenic risk. We evaluated secular trends and modeled the effects of age, preconception exposure, and state healthcare quality rankings on prenatal exposure, adjusting for demographic factors and clinical conditions. RESULTS: The cohort included 3,445,612 pregnancies (2,532,444 live deliveries). Prenatal exposures to definite teratogens decreased slightly during the study years from 1.86 to 1.24 per 100 pregnancies between 2006 and 2017, whereas exposure increased for potential teratogens from 3.40% to 5.33%. Prenatal exposure prevalences were higher during the first trimester and for pregnancies that ended in nonlive outcomes. Drugs subject to Risk Evaluation and Mitigation Strategies had low background utilization and contributed to a small proportion of prenatal exposures (15.1 per 100,000 pregnancies). We also observed fewer prenatal exposures to risk evaluation and mitigation strategy drugs among women of childbearing age who used these treatments (0.14% vs 0.36% for any definite teratogen). Age extremes and low state-level healthcare quality rankings were independent predictors of prenatal exposure. CONCLUSION: Fetuses in more than 1 in 16 pregnancies continued to be exposed to teratogenic drugs during the past decade. Drugs with Risk Evaluation and Mitigation Strategies imposed a small burden of prenatal exposure because of the low background utilization rates and lower pregnancy prevalence among women of childbearing age who used these drugs. Although the declining exposure rates to teratogenic drugs with definite risk are encouraging, the rising prenatal exposure to drugs with potential risk calls for more assessments. Future research is needed to elucidate the health outcomes of fetuses exposed to potential risk drugs, understand the effectiveness of risk evaluation and mitigation strategy programs, and prioritize teratogenic drugs for advanced risk mitigation.

Generalizability and accuracy of IBM MarketScan health risk assessment instrument data for augmentation of commercial claims data.

PURPOSE: We evaluated the generalizability and accuracy of the IBM® MarketScan® Health Risk Assessment (HRA) data to assess its suitability as supplement to linked claims data. METHODS: We identified adult private insurance enrollees in the IBM® MarketScan® Commercial Claims & Encounters (CC&E) and HRA databases between 2012 and 2017. In the claims data, for each enrollee, we sampled the first calendar year with continuous enrollment indicating full capture of claims data and extracted linked HRA survey data if available. We compared HRA participants and non-participants considering demographics, prevalences of chronic conditions, and healthcare utilization. Including the subsample with HRA data only, we estimated the negative predictive value (NPV) of obesity and smoking reported in the HRA against diagnosis code in the claims data. RESULTS: Between 2012 and 2017, 2 693 444 and 31 450 000 of HRA and non-HRA participants were included in the study, respectively. Chronic diseases were similarly distributed between the two populations, with hypertension and hyperlipidemia representing the highest prevalence difference (1.4%). The two samples showed similar healthcare utilization. The proportion of false-negatives for obesity and smoking information when relying on the HRA data compared to patients with positive diagnosis based on claims data was low (<1%). Prevalence estimates of both variables were similar to national estimates. CONCLUSION: Our findings suggest that the overall HRA population may represent the overall claims population and HRA provides certain data elements with satisfactory accuracy.

Covid-19 Vaccine Surveillance in Saudi Arabia: Opportunities for Real-time Assessment.

After months of confronting COVID-19 pandemic, several countries, including Saudi Arabia, have recently approved newly developed vaccines to prevent COVID-19 infection. With the new technology utilized to develop some vaccines, questions arise about their long-term safety. To provide rapid response to emerging safety issues, robust surveillance programs that provide near real-time analysis of vaccines effects are required. Saudi Arabia has a well-established passive pharmacovigilance system that monitors drugs and vaccines safety. However, recent development in health digitalization in Saudi Arabia may provide a unique opportunity to harvest existing resources to generate high-quality evidence. This commentary provides an overview of the available systems that can be utilized to monitor the COVID-19 vaccines' safety and discusses opportunities for data integration to improve data quality and generate real-world evidence on COVID-19 vaccine safety.

Glucagon-Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory Disease Exacerbations Among Patients With Type 2 Diabetes.

OBJECTIVE: Emerging data from animal and human pilot studies suggest potential benefits of glucagon-like peptide 1 receptor agonists (GLP-1RA) on lung function. We aimed to assess the association of GLP-1RA and chronic lower respiratory disease (CLRD) exacerbation in a population with comorbid type 2 diabetes (T2D) and CLRD. RESEARCH DESIGN AND METHODS: A new-user active-comparator analysis was conducted with use of a national claims database of beneficiaries with employer-sponsored health insurance spanning 2005-2017. We included adults with T2D and CLRD who initiated GLP-1RA or dipeptidyl peptidase 4 inhibitors (DPP-4I) as an add-on therapy to their antidiabetes regimen. The primary outcome was time to first hospital admission for CLRD. The secondary outcome was a count of any CLRD exacerbation associated with an inpatient or outpatient visit. We estimated incidence rates using inverse probability of treatment weighting for each study group and compared via risk ratios. RESULTS: The study sample consisted of 4,150 GLP-1RA and 12,540 DPP-4I new users with comorbid T2D and CLRD. The adjusted incidence rate of first CLRD admission during follow-up was 10.7 and 20.3 per 1,000 person-years for GLP-1RA and DPP-4I users, respectively, resulting in an adjusted hazard ratio of 0.52 (95% CI 0.32-0.85). For the secondary outcome, the adjusted incidence rate ratio was 0.70 (95% CI 0.57-0.87). CONCLUSIONS: GLP-1RA users had fewer CLRD exacerbations in comparison with DPP-4I users. Considering both plausible mechanistic pathways and this real-world evidence, potential beneficial effects of GLP-1RA may be considered in selection of an antidiabetes treatment regimen. Randomized clinical trials are warranted to confirm our findings.

Real-World Fetal Exposure to Acne Treatments in the United States: A Retrospective Analysis from 2006 to 2015.

INTRODUCTION: Several studies have evaluated the effects of changes in isotretinoin risk mitigation programs, but little is known about actual fetal exposure rates in the context of other acne treatments. OBJECTIVE: Our objective was to quantify fetal exposure rates during the use of common acne treatments. METHODS: Employing the insurance claims data of > 100,000 acne treatment users between 2006 and 2015, we created three user cohorts: (1) isotretinoin (strong teratogen/mandatory risk mitigation program), (2) doxycycline/minocycline (mild teratogen, label warning), and (3) topical clindamycin/erythromycin (no fetal risk). Fetal exposure rates overall and stratified by age were compared after adjusting for potential confounders. RESULTS: Contraceptive use during acne treatment was < 50% in isotretinoin users and < 30% in the other study groups. Long-acting contraceptives contributed to 1% of all contraceptives used, with 90% being oral contraceptives. Isotretinoin users had 19.2 (95% confidence interval [CI] 20.3 to 17.9) fewer fetal exposures per 1000 person-years of use compared with doxycycline/minocycline users, which in turn had 28.8 (95% CI 31.2 to 26.3) fewer pregnancies compared with clindamycin/erythromycin users. Stratification by age showed attenuated differences in fetal exposure among acne treatment groups for teenagers. CONCLUSION: Fetal exposure to acne treatments varied according to levels of teratogenicity, with reduced rates among users of isotretinoin and to a lesser extent doxycycline/minocycline. Teenagers had low pregnancy rates but less pronounced differences in fetal exposure across acne treatments.

Evaluation of statin discontinuation stratified by primary versus secondary prevention following bariatric surgery: a retrospective cohort study.

BACKGROUND: Bariatric surgery leads to an improvement in hyperlipidemia and a subsequent decline in the use of hyperlipidemia-related medications, including statins. In patients with a history of atherosclerotic cardiovascular disease (ASCVD), it is recommended to continue statins; however, it is unknown whether there is a differential risk for statin discontinuation in patients with and without a history of ASCVD. OBJECTIVES: To estimate the rates and factors associated with statin discontinuation following bariatric surgery. SETTING: Large U.S. administrative claims database of privately insured beneficiaries, January 2005 through December 2017. METHODS: We identified patients aged ≥19 years who were statin users at the time of bariatric surgery. Patients were stratified into primary prevention and secondary prevention (patients with a history of ASCVD) groups. Time to statin discontinuation was defined as the first 90-day gap after exhausting the last day's supply of the last statin prescription. Factors associated with statin discontinuation were assessed using the Cox proportional hazards regression model. RESULTS: We identified 19,332 statin users at the time of bariatric surgery, of whom 84% (16,221) used statins for primary prevention. At 6 months, 62% and 53% of patients in the primary and the secondary prevention treatment groups, respectively, discontinued statin use. Patients in the primary prevention treatment group were 18% more likely to discontinue statin therapy compared with the patients in the secondary prevention treatment group (hazard ratio, 1.18; 95% confidence interval, 1.13-1.24) according to a multivariable analysis. CONCLUSIONS: Our findings suggest that the rate of discontinuation of statin therapy after bariatric surgery was more pronounced in the primary versus secondary prevention treatment group.

Impact of the Transition from ICD-9-CM to ICD-10-CM on the Identification of Pregnancy Episodes in US Health Insurance Claims Data.

BACKGROUND: Before October 2015, pregnancy cohorts assembled from US health insurance claims have relied on medical encounters with International Classification of Diseases-ninth revision-clinical modification (ICD-9-CM) codes. We aimed to extend existing pregnancy identification algorithms into the ICD-10-CM era and evaluate performance. METHODS: We used national private insurance claims data (2005-2018) to develop and test a pregnancy identification algorithm. We considered validated ICD-9-CM diagnosis and procedure codes that identify medical encounters for live birth, stillbirth, ectopic pregnancy, abortions, and prenatal screening to identify pregnancies. We then mapped these codes to the ICD-10-CM system using general equivalent mapping tools and reconciled outputs with literature and expert opinion. Both versions were applied to the respective coding period to identify pregnancies. We required 45 weeks of health plan enrollment from estimated conception to ensure the capture of all pregnancy endpoints. RESULTS: We identified 7,060,675 pregnancy episodes, of which 50.1% met insurance enrollment requirements. Live-born deliveries comprised the majority (76.5%) of episodes, followed by abortions (20.3%). The annual prevalence for all pregnancy types was stable across the ICD transition period except for postterm pregnancies, which increased from 0.5% to 3.4%. We observed that ICD codes indicating gestational age were available for 86.8% of live-born deliveries in the ICD-10 era compared to 23.5% in the ICD-9 era. Patterns of prenatal tests remained stable across the transition period. CONCLUSION: Translation of existing ICD-9-CM pregnancy algorithms into ICD-10-CM codes provided reasonable consistency in identifying pregnancy episodes across the ICD transition period. New codes for gestational age can potentially improve the precision of conception estimates and minimize measurement biases.

Validation of algorithms to estimate gestational age at birth in the Medicaid Analytic eXtract-Quantifying the misclassification of maternal drug exposure during pregnancy.

PURPOSE: Accurate ascertainment of gestational age (GA) has been a challenge in perinatal epidemiologic research. To date, no study has validated GA algorithms in Medicaid Analytic eXtract (MAX). METHODS: We linked livebirths of mothers enrolled in Medicaid ≥30 days after delivery in 1999-2010 MAX to state birth certificates. We used clinical/obstetric estimate of gestation on the birth certificates as gold standard to validate claims-based GA algorithms. We calculated the proportions of deliveries with algorithm-estimated GA within 1-/2-weeks of the gold standard, the sensitivity, specificity, and positive/negative predictive value (PPV/NPV) of exposure to select medications during specific gestation windows, and quantified the impact of exposure misclassification on hypothetical relative risk (RR) estimates. RESULTS: We linked 1 336 495 eligible deliveries. Within 1-week agreement was 77%-80% overall and 47%-56% for preterm deliveries. The trimester-specific drug exposure status had high sensitivities and PPVs (88.5%-98.5%), and specificities and NPVs (>99.0%). Assuming a hypothetical RR of 2.0, bias associated with exposure misclassification during first trimester ranged from 10% to 40% under non-differential/differential misclassification assumptions. CONCLUSIONS: Claims-based GA algorithms had good agreement with the gold standard overall, but lower agreement among preterm deliveries, potentially resulting in biased risk estimated for pregnancy exposure evaluations.

Risk of pregnancy loss in patients exposed to mycophenolate compared to azathioprine: A retrospective cohort study.

PURPOSE: To evaluate the relative risk of pregnancy loss associated with mycophenolate (MPA) vs azathioprine (AZA) use. METHODS: We conducted a retrospective cohort study using the IBM MarketScan Research Databases (2005-2015). Patients with ≥1 MPA or AZA prescription claim during the first trimester were included. The study outcome was pregnancy loss (spontaneous abortion or stillbirth). Potential confounders included age, drug indications, comorbidities, other teratogenic medication use, and gestational age at first MPA or AZA prescription fill. The risk for pregnancy loss was estimated using a generalized estimating equation model with stabilized inverse probability of treatment weighting. In sensitivity analyses, we varied the exposure definition, outcome definition, and the analytical method. RESULTS: Among 111 pregnancies exposed to MPA, 55 resulted in pregnancy loss (49.5%). Among 471 pregnancies exposed to AZA, 113 had pregnancy loss (24.0%). The unadjusted relative risk for pregnancy loss was 2.0 (95% CI 1.6, 2.6), and the adjusted relative risk was 1.9 (95% CI, 1.6, 2.3) compared to AZA. Relative risk estimates were stable in all sensitivity analyses. CONCLUSION: Exposure to MPA during early pregnancy was associated with a 2-fold increase in pregnancy loss risk.

Comparative effectiveness of risk mitigation strategies to prevent fetal exposure to mycophenolate.

BACKGROUND: In 2012, the US Food and Drug Administration approved a Risk Evaluation and Mitigation Strategy (REMS) programme including mandatory prescriber training and a patient/provider acknowledgement form to prevent fetal exposure to mycophenolate. Prior to the REMS, the teratogenic risk was solely mitigated via written information (black box warning, medication guide (MG period)). To date, there is no evidence on the effectiveness of the REMS. METHODS: We used a national private health insurance claims database to identify women aged 15-44 who filled ≥1 mycophenolate prescription. To compare fetal exposure during REMS with the MG period, we estimated the prevalence of pregnancy at treatment initiation in a pre/post comparison (analysis 1) and the rate of conception during treatment in a retrospective cohort study (analysis 2). Pregnancy episodes were measured based on diagnosis and procedure codes for pregnancy outcomes or prenatal screening. We used generalised estimating equation models with inverse probability of treatment weighting to calculate risk estimates. RESULTS: The adjusted proportion of existing pregnancy per 1000 treatment initiations was 1.7 (95% CI 1.0 to 2.9) vs 4.1 (95% CI 3.2 to 5.4) during the REMS and MG period. The adjusted prevalence ratio and prevalence difference were 0.42 (95% CI 0.24 to 0.74) and -2.4 (95% CI -3.8 to -1.0), respectively. In analysis 2, the adjusted rate of conception was 12.5 (95% CI 8.9 to 17.6) vs 12.9 (95% CI 9.9 to 16.9) per 1000 years of mycophenolate exposure time in the REMS versus MG periods. The adjusted risk ratio and risk difference were 0.97 (95% CI 0.63 to 1.49) and -0.4 (95% CI -5.9 to 5.0), respectively. Sensitivity analyses on the estimated conception date demonstrated robustness of our findings. CONCLUSION: While the REMS programme achieved less pregnancies at treatment initiation, it failed to prevent the onset of pregnancy during treatment. Enhanced approaches to ensure effective contraception during treatment should be considered.

Public awareness and perception toward Adverse Drug Reactions reporting in Riyadh, Saudi Arabia.

Purpose: To assess the general public awareness and perception about Adverse Drug Reactions (ADRs) reporting and pharmacovigilance. Method: A cross-sectional study conducted on June 2012 during awareness campaign held in two malls in Riyadh city for two days. A self-administered questionnaire consisting of three parts was distributed to the attendees who accepted to participate in the study. Results: A total of 204 questionnaires were collected with a response rate of 68%. Twenty-three percent could correctly define ADRs. Only 13(15.7%) of responders were familiar with the term "Pharmacovigilance" and only 78.6% were aware about the Saudi Pharmacovigilance Center. Sixty-seventy percent indicated that their physicians or pharmacists don't actively encourage them to report ADRs that may occur when they take their medications. The majority of responders (73.2%) believed that the medical team, rather than consumers, should report ADRs. When asked why patients do not report ADRs, 19.1(48.5%) believed that patients do not know whether the ADR is from the medication or not, 18.1(46.1%) stated that the reason was because patients don't know about the Pharmacovigilance Center, 16(40.7%) think that patients don't know about the importance of ADRs reporting, and 14(36.3%) responded that patients probably don't know how to report ADRs. Conclusion: The general public in Saudi Arabia are not aware about ADRs reporting and the pharmacovigilance system. The Saudi Food and Drug Authorities (FDA) need to put more efforts to increasing public awareness about the importance of ADRs reporting process and the importance of pharmacovigilance system in promoting patient safety.

The safety of H1N1 vaccine in children in Saudi Arabia: a cohort study using modern technology in a developing country.

BACKGROUND: With its rapid introduction in 2009, concerns about the safety of the H1N1 vaccines have been raised. Data were especially limited on the pediatric safety of H1N1 vaccine in Saudi Arabia. OBJECTIVES: The objectives of this study were to investigate the safety of the H1N1 vaccine (Pandemrix(®)) in children and examine the feasibility of obtaining information on possibly associated adverse reactions using mobile telephone contact with child caregivers. METHODS: A cohort study was conducted in Riyadh, Saudi Arabia. Patients were included if they were aged between 6 and 18 years and had received one dose of the H1N1 vaccine. A control group involved children from the same school system who had not received the vaccine. Six months following vaccination, a clinical pharmacist called the caregiver of the child to ask about hospitalization, emergency room visits and events related to H1N1 vaccine administration using a standardized questionnaire. RESULTS: Caregivers of 372 school-age children were contacted. The response rate was 97% (n = 359). A total of 169 children who received at least one dose of the H1N1 vaccine were compared with 190 children in the control group who had not received the vaccine. Controlling for age, sex, education and use of medications, the odds ratio (OR) of hospitalization or emergency room visits for children within the 6 months after vaccination relative to the unvaccinated children was 1.25 (95% CI 0.47, 3.35). The risk of influenza-like symptoms was significantly reduced in vaccinated children compared with unvaccinated children (OR 0.63; 95% CI 0.41, 0.99). CONCLUSION: School-age children in Saudi Arabia who received the H1N1 vaccine did not have an increased risk of hospitalization or emergency room visits. Larger studies are needed to confirm these results. Proactive pharmacovigilance is important in assessing the safety of vaccines and other medications. It is feasible to collect information on adverse drug reactions using mobile telephones, a method that can be of benefit in both developed and developing countries.