OBJECTIVES: The economic evaluation of companion diagnostics (CDx) is complex due to their indirect impact on health and cost outcomes. This study aimed to develop guidance for incorporating CDx-related inputs into health economic models for prognostic and predictive CDx.

METHODS: This scoping review followed our published protocol and adhered to PRISMA-ScR guidelines. We conducted systematic searches in MEDLINE and Scopus databases from January 2008 to March 2023. Search terms and medical subject headings were organized into three categories: economic evaluation, companion diagnostics, and modeling methods, combined using the "AND" operator. Screening and data extraction were conducted by two independent reviewers. A descriptive analysis of the extracted data was conducted to develop guidance on health economic modeling methods for CDx evaluation.

RESULTS: The search resulted in 2,532 potentially eligible studies from which 64 economic evaluation studies were included in the final review. The results were synthesized to assess whether key methodological aspects were considered in these economic evaluations.

CONCLUSIONS: The guidance developed based on the scoping review includes six considerations:

1) Incorporating sensitivity and specificity: Use Bayesian methods to accurately reflect conditional probabilities and real-world effectiveness of the CDx.

2) Distinguishing clinical validity from clinical utility: Incorporate decision impact data to reflect actual clinical practice, considering compliance and patient/clinician preferences.

3) Pre-test probability: Ensure pre-test probability (prevalence) is incorporated in the model and it accurately represents the whole target population.

4) Impact of false predictions: Account for false positives and negatives to avoid skewed results.

5) Cut-off threshold for action: Vary cut-off thresholds to assess their impact on cost-effectiveness, and ideally, identify the optimal threshold from cost-effectiveness perspective.

6) Multifactorial decision making: Model the combined clinical utility of multiple CDx tests rather than their individual accuracies.

Our future research will focus on finalizing and disseminating the guidance.