A Vaccine Study Design Selection Framework for the Postlicensure Rapid Immunization Safety Monitoring Program

Abstract

The Postlicensure Rapid Immunization Safety Monitoring Program, the vaccination safety monitoring component of the US Food and Drug Administration's Mini-Sentinel project, is currently the largest cohort in the US general population for vaccine safety surveillance. We developed a study design selection framework to provide a roadmap and description of methods that may be utilized to evaluate potential associations between vaccines and health outcomes of interest in the Postlicensure Rapid Immunization Safety Monitoring Program and other systems using administrative data. The strengths and weaknesses of designs for vaccine safety monitoring, including the cohort design, the case-centered design, the risk interval design, the case-control design, the self-controlled risk interval design, the self-controlled case series method, and the case-crossover design, are described and summarized in tabular form. A structured decision table is provided to aid in planning of future vaccine safety monitoring activities, and the data components comprising the structured decision table are delineated. The study design selection framework provides a starting point for planning vaccine safety evaluations using claims-based data sources.

Self‐controlled case series studies: Just how rare does a rare non‐recurrent outcome need to be?

“…Thus, a set up for an SCCS model with an age-defined observation period is illustrated in Figure 1 , panel (a) An alternative is to ascertain exposure histories, and define observation periods in relation to exposure, thus cutting down observation time used and altogether dropping cases whose outcomes arose further in time from exposure. This approach is taken for the self-controlled risk interval (SCRI) design (Baker et al, 2015;Tse, Fu Tseng, Greene, Vellozzi, & Lee, 2012), a special case of an SCCS design. In a typical SCRI design, a single exposure risk window is defined, along with either one or two reference or control windows, before and after the exposure risk window or following the exposure risk window.…”

A simulation study of the statistical power and signaling characteristics of an early season sequential test for influenza vaccine safety

“…While USPRT has proven useful for rapid detection of highly elevated GBS risk after vaccination, it is limited by its use of historical comparator, which does not control for confounding as robustly as other sequential methods used for real‐time vaccine surveillance such as the binomial MaxSPRT . Thus, we have complemented the use of USPRT with self‐controlled risk interval (SCRI) analyses, which provide less biased and more precise estimates of the GBS risk attributable to influenza vaccines by at least adjusting for time‐invariant confounders if not for time‐varying confounders such as influenza circulation . These two systems together with a descriptive analysis conducted during and after USPRT testing have constituted the active surveillance components of the FDA‐CMS multilayered surveillance system …”

Development and Application of Two Semi-Automated Tools for Targeted Medical Product Surveillance in a Distributed Data Network

“…However, both types of self-controlled designs control for all time-invariant confounding so most complicating factors in self-controlled designs involve adding additional model terms to account for time-varying confounding [47]. While the self-controlled case series design has been used extensively in epidemiological research [48–51], the self-controlled risk interval design was first used in the VSD and the Post-licensure Immunization Safety Monitoring system [52] for vaccine safety studies [53–60]. In this design, an exposed person acts as his or her own control and the comparison occurs between a period when the person is thought to be at heightened risk for experiencing a health outcome of interest (i.e., the risk window) and a period without heightened risk (i.e., the comparison window).…”