Evaluation of Medication-mediated Effects in Pharmacoepidemiology

Medical conditions such as epilepsy or infection with human immunodeficiency virus (HIV) are known to be associated with a spectrum of adverse health outcomes if not appropriately managed by efficacious treatment and care. Medications for such conditions can be potent, and their use might sometimes have unintended health consequences. Prominent examples have emerged in HIV perinatal research in which use of antiretroviral treatment during pregnancy to treat maternal HIV infection and prevent transmission of the virus to the fetus have been shown to be associated with adverse birth outcomes. Likewise, use of antiepileptic drugs during pregnancy to treat maternal epilepsy has been shown to increase the risk of birth defects. Pharmacoepidemiology studies routinely aim to quantify the extent to which, in such settings, an observed association between an underlying medical condition and certain health outcomes can be attributed to the natural progression of the disease, and the extent to which it might be mediated by medication used to slow disease progression. We describe a simple yet principled methodology to quantify medication-mediated effects to address these types of queries. While methods for causal mediation analysis abound, there also has been much criticism of these methods as relying on untestable and sometimes unrealistic assumptions. In contrast, here we show that when the disease-free control group is also medication-free, mediated effects of the type described above are nonparametrically identified under standard no-unobserved confounding conditions, thus establishing that such effects are in a sense immune to recent criticism leveled at causal mediation methodology

Identification of pregnancies and infants within a United States commercial healthcare administrative claims database

PURPOSE: Health care insurance claims databases are becoming a more common data source for studies of medication safety during pregnancy. While pregnancies have historically been identified in such databases by pregnancy outcomes, International Classification of Diseases, 10 revision Clinical Modification (ICD-10-CM) Z3A codes denoting weeks of gestation provide more granular information on pregnancies and pregnancy periods (i.e. start and end dates). The purpose of this study was to develop a process that uses Z3A codes to identify pregnancies, pregnancy periods, and links infants within a commercial health insurance claims database. METHODS: We identified pregnancies, gestation periods, pregnancy outcomes, and linked infants within the United States (US)-based Optum Research Database (ORD) between 2015 and 2020 via a series of algorithms utilizing diagnosis and procedure codes on claims. The diagnosis and procedure codes included ICD-10-CM codes, Current Procedural Terminology (CPT) codes, and Healthcare Common Procedure Coding System (HCPCS) codes. RESULTS: We identified 1,030,874 pregnancies among 841,196 women of reproductive age. Of pregnancies with livebirth outcomes, 84% were successfully linked to infants. The prevalence of pregnancy outcomes (livebirth, stillbirth, ectopic, molar, abortion) was similar to national estimates. CONCLUSIONS: This process provides an opportunity to study drug safety and care patterns during pregnancy and may be replicated in other claims databases containing ICD-10-CM, CPT, and HCPCS codes. Work is underway to validate and refine the various algorithms. This article is protected by copyright. All rights reserved

Real‐world treatment patterns and clinical outcomes after introduction of immune checkpoint inhibitors: Results from a retrospective chart review of patients with advanced/metastatic non‐small cell lung cancer in the EU5

Abstract Background Real‐world evidence is increasingly used to guide treatment and regulatory decisions for non‐small cell lung cancer (NSCLC). Real‐world treatment patterns and clinical outcomes among patients with advanced/metastatic NSCLC in France, Germany, Italy, Spain, and the UK (EU5) were assessed. Methods This retrospective physician‐completed patient chart review assessed treatment patterns (regimen, duration of treatment [DOT], time to discontinuation), and clinical outcomes (duration of response [DOR], progression‐free survival [PFS], and overall survival [OS]) of patients with stage IIIB/C or IV NSCLC who received pembrolizumab‐based first‐line induction chemotherapy. Results Overall, 322 patients were included; at first‐line maintenance (1LM), 92% had stage IV NSCLC, 68% had nonsquamous histology, and 89% had no central nervous system (CNS)/brain metastasis. The two most common 1LM regimens were pembrolizumab monotherapy (76% overall) and pembrolizumab + pemetrexed (21% overall). Docetaxel monotherapy was the most common second‐line regimen in all countries except Germany (54% overall). For 1LM therapy, the overall median DOT and DOR were 5 and 10 months, respectively; PFS was 7 months and OS was 8 months. Germany had a longer duration of each outcome except for DOR which was longer in Spain. Clinical outcomes were generally poorer for patients with squamous histology and CNS/brain metastases. Conclusions This study demonstrated differences in treatment patterns and clinical outcomes in NSCLC across the EU5 and patient subgroups. Improved survival was generally associated with response to first‐line therapy, nonsquamous histology, and CNS/brain metastases absence. These real‐world data provide valuable insights which may aid treatment decision‐making and clinical trial design

First Trimester Exposure to Antiretroviral Therapy and Risk of Birth Defects

South lateral curved wing, view of the interior; Syon Park borders the Thames, looking across the river to Kew Gardens, and near its banks is a tidal meadow flooded twice a day by the river. It contains more than 200 species of rare trees. Although the park and lake were designed by Capability Brown in 1760, their character today is nineteenth century. The circular pool has a copy of Giambologna's Mercury. The Great Conservatory in the gardens, designed by Charles Fowler in 1826 and completed in 1830, was the first conservatory to be built from metal and glass on a large scale. It was originally designed to act as a show house for the Duke's exotic plants and inspired Joseph Paxton in his designs for the Crystal Palace. Source: Wikipedia; http://en.wikipedia.org/wiki/Main_Page (accessed 6/15/2009