Active vaccine safety surveillance utilizing administrative data: evaluating the use of open + closed claims vs. closed claims alone

Background: Moderna, Inc. is conducting active surveillance in an administrative claims database to identify and evaluate potential risks of adverse events of special interest (AESI) after administration of the mRNA-1273 COVID-19 vaccine using both open and closed claims data. Non-adjudicated open claims are sourced from providers and clearinghouses and do not include an enrollment file, whereas fully-adjudicated closed claims are sourced from the insurer during periods of enrollment. The impact of augmenting closed claims with open claims in active vaccine surveillance is unclear.

Objectives: To describe differences in inference from analyses using open and closed claims versus closed claims alone in evaluating potential safety signals after mRNA-1273 vaccination.

Methods: In an ongoing surveillance study of 43 pre-specified AESI using medical and pharmacy claims data from HealthVerity, incidence rates (IR) following mRNA-1273 administration were estimated per 100,000 person-years (PY) and compared to background rates. Where warranted, observed to expected, and self-controlled risk interval (SCRI) analyses were conducted. In primary analyses, both open and closed claims were utilized. Closed claims analyses required continuous medical and pharmacy enrollment; open and closed claims analyses required activity via ≥1 medical or pharmacy claim. For both claims source types, the study period was truncated to 3 months prior to most recent data available. The number of mRNA-1273 vaccinees and IR of several AESI following mRNA-1273 administration were compared using open and closed claims versus closed claims alone. To illustrate differences between sources, SCRI results for chilblain-like lesions (chilblain) and anosmia/ageusia (anosmia) are reported.

Results: Using closed claims identified 57.5% fewer adult mRNA-1273 vaccinees (10,055,960 vs. 23,685,805) and approximately 35% fewer chilblain and anosmia events in the 28-day risk and 42-day control window following mRNA-1273 administration (chilblain risk window: 252 via closed claims vs. 396 via open and closed claims, chilblain control window: 195 vs. 248) (anosmia risk window: 2,145 vs. 3,365, anosmia control window: 1,808 vs. 2,919). SCRI analysis using closed claims alone vs. open and closed claims led to slight attenuation of the event rate ratio (ERR) for chilblain from 1.58 (95% CI 1.35, 1.86) to 1.31 (95% CI 1.08, 1.58), however no meaningful difference was observed for anosmia/ageusia.

Conclusions: From analysis of multiple AESI, augmenting closed claims with open claims for active vaccine safety surveillance may be critical in initial evaluation and add precision valuable to assessment of rare safety events.