Although biologic therapy offer much hope for reducing morbidity in many chronic inflammatory diseases, it is critical to better understand whether they cause Serious Adverse Events (SAEs) and to identify if there are patient populations for which these risks are particularly high. This study is intended to help the AHRQ, the FDA, drug manufacturers, physicians, and patients identify those patient groups who are at increased risk for SAEs with biologic therapy.
The specific aims are: ? 1) To estimate the incidence rates (IR) of SAEs associated with each of eight specific biologic agents among users and comparable nonusers, and to estimate the standardized incidence rate ratio (SIRR) comparing users to nonusers after considering time since first use, duration of use, concomitant drug use and relevant comorbidities. ? The ten SAEs and one outcome potentially inversely associated with biological exposure (protective event) listed explicitly in the funding opportunity announcement (FOA) will be evaluated. Analyses will include disease specific comparator groups. ? 2) To estimate IR and SIRR of SAE's in 8 vulnerable populations specified in the FOA. ? 3) To develop generalizable specifications to combine health-care databases using a previously used distributed data model. We propose a collaboration of 4 CERTs and one DeCIDE center that will use 5 national databases. For our retrospective cohort studies we have preliminarily identified 106,783 anti-TNF users and at least 858 users of other biologic agents. These include 60,721 users with RA, 13,322 with Crohn's Disease (CD), 6,287 with PsA, and smaller numbers with other indications. In addition, ? we have data for 1,191 children, 15,629 elders, and 48 infants exposed to biologics in utero. Our proposed large-scale, community based study is designed to overcome the limitations posed by previous studies. We will use large databases that are particularly focused on vulnerable persons with some databases having been linked to State birth certificates or registries or containing detailed clinical information such as test results and diagnostic findings. Our research team has demonstrated clinical and methodological expertise in the investigation of biological therapies, drug safety, and the validation of adverse events that predicts high success for this multi-disciplinary collaborative endeavor. ? ? ?
Although biological therapeutics have excellent efficacy for many chronic inflammatory diseases, a number of safety considerations persist. A collaboration of four CERTs and one DECiDE Center will seek to gain an improved understanding of biological safety by evaluating data from five national databases involving over 100,000 users of biological therapies.
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