Critical Examination of Modeling Approaches Used in Economic Evaluations of First-Line Treatments for Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations: A Systematic Literature Review

Abstract

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with up to 32% of patients with NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. NSCLC harboring an EGFR mutation has a dedicated treatment pathway, with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy often being the therapy of choice.

Objective: The aim of this study was to systemically review and summarize economic models of first-line treatments used for locally advanced or metastatic NSCLC harboring EGFR mutations, as well as to identify areas for improvement for future models.

Methods: Literature searches were conducted via Ovid in PubMed, MEDLINE, MEDLINE In-Process, Embase, Evidence-Based Medicine Reviews: Health Technology Assessment, Evidence-Based Medicine Reviews: National Health Service Economic Evaluation Database, and EconLit. An initial search was conducted on 19 December 2022 and updated on 11 April 2023. Studies were selected according to predefined criteria using the Population, Intervention, Comparator, Outcome and Study design (PICOS) framework.

Results: Sixty-seven articles were included in the review, representing 59 unique studies. The majority of included models were cost-utility analyses (n = 52), with the remaining studies being cost-effectiveness analyses (n = 4) and a cost-minimization analysis (n = 1). Two studies incorporated both a cost-utility and cost-minimization analysis. Although the model structure across studies was consistently reported, justification for this choice was often lacking.

Conclusions: Although the reporting of economic models in NSCLC harboring EGFR mutations is generally good, many of these studies lacked sufficient reporting of justification for structural choices, performing extensive sensitivity analyses and validation in economic evaluations. In resolving such gaps, the validity of future models can be increased to guide healthcare decision making in rare indications.

Fig. 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. *These conferences were searched as part of the original SLR. **Not an HTA body. ^†Search by intervention (brand and generic name) since it is not possible to search by indication. AACR American Association for Cancer Research, ASCO American Society of Clinical Oncology, BTOG British Thoracic Oncology Group, CADTH Canadian Agency for Drugs and Technologies in Health, ELCC European Lung Cancer Congress, ESMO European Society for Medical Oncology, EU European Union, HAS French National Health Authority (Haute Autorité de Santé), HTA health technology assessment, IASLC International Association for the Study of Lung Cancer, ICER Institute for Clinical and Economic Review, IQWiG Federal Joint Committee (Gemeinsamer Bundesausschuss/Institute for Quality and Efficiency in Health Care), ISPOR The Professional Society for Health Economics and Outcomes Research, NHS EED National Health Service Economic Evaluations Database, NICE National Institute for Health and Care Excellence, PBAC Pharmaceutical Benefits Advisory Committee, SLR systematic literature review, SMC Scottish Medicines Consortium, TAT targeted anticancer therapies, TLV Dental and Pharmaceutical Benefits Agency (Tandvårds-och läkemedelsförmånsverket), ZIN National Health Care Institute (Zorginstituut Nederland)

Fig. 2

World map of economic evaluations in patients with non-small cell lung cancer harboring epidermal growth factor receptor mutations

Fig. 3

Evolving comparator landscape among health technology assessment and/or value Assessments. CADTH Canadian Agency for Drugs and Technologies in Health, ICER Institute for Clinical and Economic Review, NICE National Institute for Health and Care Excellence, PBAC Pharmaceutical Benefits Advisory Committee, SMC Scottish Medicines Consortium, TLV Dental and Pharmaceutical Benefits Agency (Tandvårds-och läkemedelsförmånsverket), ZIN National Health Care Institute (Zorginstituut Nederland)

Fig. 4

Uncertainty parameters tested in scenario analysis. External survival estimates refers to the use of an external clinical trial to estimate the survival probability of patients in the chemotherapy arm. FPNMA fractional polynomial network meta-analysis

Fig. 5

Model validation

Fig. 6.

Reported sponsors. NR, not reported