(129) Appropriate washout period for adverse events of special interest (AESI) in vaccine active surveillance utilizing an administrative claims database
Background: Moderna, Inc. is conducting active surveillance in administrative claims to identify and evaluate potential risks of adverse events of special interest (AESI) after administration of Spikevax (COVID-19 vaccine). While validated algorithms suggest a 365-day washout to estimate the incidence of most AESI, it may not exclude all prevalent cases, particularly among AESI that present as chronic illnesses.
Objectives: To evaluate the impact of variable washout lengths for AESI that are chronic in nature.
Methods: In ongoing surveillance of pre-specified AESI using HealthVerity medical and pharmacy claims data, incidence rates (IR) following Spikevax administration were estimated per 100,000 person-years (PY) and compared to background rates. Where warranted, observed to expected and self-controlled risk interval analyses were conducted. In primary analyses, a 365-day washout was applied for most AESI, including narcolepsy/cataplexy, immune thrombocytopenia (ITP), and cerebral venous sinus thrombosis (CVST). Claims profiles of patients with these AESI were reviewed, through which diagnoses were observable beyond the prior 365 days. Thus, a washout using all available data was applied; IRs were estimated and compared to IRs using a 365-day washout.
Results: After excluding patients with history of narcolepsy/cataplexy any time before vaccination, there were 883 (20%) fewer events observed following vaccination and a slightly lower IR (3,526 events, IR=19.6 per 100,000 PY all available data washout; 4,409 events, IR=24.2 per 100,000 PY 365-day washout). A lower percentage of prevalent events were excluded in analyses of ITP (9.4%) and CVST (5%) with modest but consistent decreases in observed incidence with the all available data washout (ITP: IR=22.5 per 100,000 PY all available data washout; IR=25.2 per 100,000 PY 365-day washout) (CVST: IR=2.6 per 100,000 PY all available data washout; IR=2.8 per 100,000 PY 365-day washout).
Conclusions: Given long intervals between prior claims and post-vaccination events, claims profile review indicated a 365-day washout period was not adequate for excluding prevalent events in claims-based active surveillance. Applying a washout period using all available data resulted in lower IRs for narcolepsy/cataplexy. During the COVID-19 pandemic, patterns of healthcare use changed, and some patients may not have regularly sought care, contributing to longer intervals between claims for chronic illness diagnoses. While these findings support AESI washout using all available data to ensure capture of incident events, future studies may look at variable washout lengths in study periods not affected by a global pandemic to determine the most appropriate washout.
