Person:

Hernandez-Diaz, Sonia

Background: In the absence of clinical trial data, large post-marketing observational studies are essential to evaluate the safety and effectiveness of medications during pregnancy. We identified a cohort of pregnancies ending in live birth within the 2000–2007 Medicaid Analytic eXtract (MAX). Herein, we provide a blueprint to guide investigators who wish to create similar cohorts from healthcare utilization data and we describe the limitations in detail. Methods: Among females ages 12–55, we identified pregnancies using delivery-related codes from healthcare utilization claims. We linked women with pregnancies to their offspring by state, Medicaid Case Number (family identifier) and delivery/birth dates. Then we removed inaccurate linkages and duplicate records and implemented cohort eligibility criteria (i.e., continuous and appropriate enrollment type, no private insurance, no restricted benefits) for claim information completeness. Results: From 13,460,273 deliveries and 22,408,810 child observations, 6,107,572 pregnancies ending in live birth were available after linkage, cleaning, and removal of duplicate records. The percentage of linked deliveries varied greatly by state, from 0 to 96%. The cohort size was reduced to 1,248,875 pregnancies after requiring maternal eligibility criteria throughout pregnancy and to 1,173,280 pregnancies after further applying infant eligibility criteria. Ninety-one percent of women were dispensed at least one medication during pregnancy. Conclusions: Mother-infant linkage is feasible and yields a large pregnancy cohort, although the size decreases with increasing eligibility requirements. MAX is a useful resource for studying medications in pregnancy and a spectrum of maternal and infant outcomes within the indigent population of women and their infants enrolled in Medicaid. It may also be used to study maternal characteristics, the impact of Medicaid policy, and healthcare utilization during pregnancy. However, careful attention to the limitations of these data is necessary to reduce biases.

Purpose: To examine indications for, duration of use, and rate of adverse drug events (ADE) attributable to anticonvulsant initiation, as adjudicated by expert review of electronic health records (EHR) of older adults. Methods: We identified a cohort of community-dwelling Medicare beneficiaries with linked EHR (aged 65+, continuously enrolled with a large health system/until death between 2012-2014, n=20,945) and drew a stratified EHR review sample (n=1,534). An expert reviewed all records to adjudicate anticonvulsant use, years of use, indication for use, and evidence of ADEs attributable to anticonvulsant initiation. After excluding patients with insufficient EHR data (n=37; 2%), we reconstructed the cohort using inverse probability weights to resemble the original cohort of eligible beneficiaries (n=20,380). Among incident users of a single anticonvulsant, we estimated the rate of ADEs and described the type and severity of ADEs. Results: Overall, 12% (n=2,469) of eligible beneficiaries used at least one anticonvulsant in the 2012-2014 period (4% [n=757] incident users, 8% [n=1,712] prevalent users). Incident users were most frequently prescribed gabapentin (n=461/757, 61%), benzodiazepines (n=122/757, 16%), and levetiracetam (n=74/757, 10%); the most common indication was pain relief (n=214; 28%) followed by epilepsy (n=53; 7%). Among incident users, the overall ADE rate was 10/100 person-years (95% CI 4-20/100 person-years), of which 29% (n=28/97) were life-threatening (e.g., somnolence). Most ADEs among incident monotherapy users were nervous-system related (68%, n=66/97). Conclusions: Many older adult community-dwelling Traditional Medicare beneficiaries had clinically significant ADEs likely attributable to the initiation of anticonvulsant therapy, which was begun for a range of indications.