(C-148) Beyond Comparison: Target Trial Emulation (TTE) Principles Strengthen Observational Single-Arm (SA) Effectiveness Studies

Background: Observational SA effectiveness studies (no comparator group) are often used to support a drug’s value story by providing real-world evidence of clinical impact in broad patient populations. Patient registries are valuable for SA effectiveness studies as they often collect elements like clinician and patient reported outcomes (ClinROs/PROs) that are not available in other data sources (e.g., claims, EHR). Applying TTE principles in SA effectiveness studies using registry data can help mitigate threats to validity and strengthen conclusions.

Objectives: Describe implementation of TTE principles for SA effectiveness studies based on registry data.

Methods: Examples of how several TTE elements may be applied to SA effectiveness studies of immunomodulator medications are described. Applications are based on using data from the observational CorEvitas registries of patients with autoimmune/neurological disease evaluated at routine clinical visits using standardized questionnaires.

Results: Eligibility: Comprehensive registry information on patient characteristics, disease activity and medication use (e.g., start dates, prior therapy use) ensures that: 1) the study cohort is defined using information up to time zero and not beyond; and 2) that time zero coincides with drug start

Treatment strategy: Data ascertained by the registry including concomitant therapies, drug dose and frequency, and discontinuations and switches (as well as their reasons) may be used to specify relevant treatment protocol and identify deviations.

Follow-up period: Particularly in immunology/neurology settings, clinically meaningful effectiveness typically focuses on response at a specific time point (e.g., 6-months). Because CorEvitas registries are observational and clinic visits may not occur at a consistent cadence, follow-up can be based on visits occurring within windows around the time-point of interest (e.g., 5-9 months for a 6-month follow-up).

Outcome: ClinRO/PRO data includes validated measures used in randomized trials and may be used to clearly define outcomes, typically as a response or change from time zero at the specified time point.

Causal contrast: While there are no causal contrasts in a SA study, an ITT or per protocol approach may be specified for analysis of all initiators or only persistent users, respectively.

Analysis: The analytic plan may include descriptions of how missing data and loss to follow-up (e.g., NRI, IPCW) or time-varying confounding (e.g., IPTW, MSM) are handled.

Conclusions: When comprehensive, granular registry data are available, application of TTE principles can help produce scientifically robust and clinically informative SA effectiveness studies.