WHAT HTA BODIES CRITICIZE IN INDIRECT TREATMENT COMPARISONS FOR ADVANCED CANCERS: A THEMATIC ANALYSIS OF RECENT HTA REPORTS IN SOLID TUMORS
Author(s)
Marissa Betts, MS1, Nicholas Parr, PhD, MPH2, Joanna Campbell, PhD3, Kyle Fahrbach, PhD4;
1ThermoFisher Scientific, Evidence Synthesis, Littleton, MA, USA, 2Thermo Fisher Scientific, Evidence Synthesis, Eugene, OR, USA, 3Thermo Fisher Scientific, Evidence Synthesis, Exeter, United Kingdom, 4Thermo Fisher Scientific, Evidence Synthesis, Waltham, MA, USA
1ThermoFisher Scientific, Evidence Synthesis, Littleton, MA, USA, 2Thermo Fisher Scientific, Evidence Synthesis, Eugene, OR, USA, 3Thermo Fisher Scientific, Evidence Synthesis, Exeter, United Kingdom, 4Thermo Fisher Scientific, Evidence Synthesis, Waltham, MA, USA
OBJECTIVES: To qualitatively characterize themes in health technology assessment (HTA) critiques of indirect treatment comparisons (ITCs) in recent oncology reimbursement submissions, focusing on advanced/metastatic NSCLC, breast cancers, and colorectal cancers.
METHODS: We performed an AI-assisted rapid review of 20 HTA reports from NICE, SMC, CDA‑AMC, and PBAC. HTA documents were randomly selected from publicly available English-language reports that included at least one ITC in the main clinical and/or economic evidence package and were published from May 2024 through November 2025. Using a prespecified extraction template and codebook, we extracted the ITC method, role in the submission, and verbatim HTA critiques. Findings were narratively synthesized by cancer type, HTA body, and ITC method.
RESULTS: Across agencies, critiques often centered on the transparency and reproducibility of ITCs, including inadequate reporting of evidence identification, risk-of-bias appraisal, covariate handling, and model specifications. Cross-trial comparability was a dominant concern, with agencies highlighting inconsistency in baseline risk, outcome definitions, subsequent therapy, and comparator regimens as threats to exchangeability. For network meta-analyses, agencies frequently cited sparse or weakly connected networks, limited ability to test inconsistency, and uncertainty related to survival modeling assumptions. For population-adjusted and real-world evidence-based comparisons, critiques frequently focused on the credibility of adjustment, particularly where key effect modifiers were unavailable or inconsistently measured. Importantly, critiques reflected both issues that could be further interrogated analytically (e.g., exploring effect modifiers, testing proportional hazards, and evaluating alternative model structures) and structural constraints that are difficult to remedy, such as thin evidence networks and rapidly changing standards of care.
CONCLUSIONS: Recent HTA feedback shows recurring, method-dependent limitations in oncology ITCs, often arising from unavoidable evidence constraints, rather than analytic approach alone. Submissions should state where assumptions are required, document steps taken to investigate and mitigate them, and report how robust conclusions remain when evidence is sparse or treatment pathways change.
METHODS: We performed an AI-assisted rapid review of 20 HTA reports from NICE, SMC, CDA‑AMC, and PBAC. HTA documents were randomly selected from publicly available English-language reports that included at least one ITC in the main clinical and/or economic evidence package and were published from May 2024 through November 2025. Using a prespecified extraction template and codebook, we extracted the ITC method, role in the submission, and verbatim HTA critiques. Findings were narratively synthesized by cancer type, HTA body, and ITC method.
RESULTS: Across agencies, critiques often centered on the transparency and reproducibility of ITCs, including inadequate reporting of evidence identification, risk-of-bias appraisal, covariate handling, and model specifications. Cross-trial comparability was a dominant concern, with agencies highlighting inconsistency in baseline risk, outcome definitions, subsequent therapy, and comparator regimens as threats to exchangeability. For network meta-analyses, agencies frequently cited sparse or weakly connected networks, limited ability to test inconsistency, and uncertainty related to survival modeling assumptions. For population-adjusted and real-world evidence-based comparisons, critiques frequently focused on the credibility of adjustment, particularly where key effect modifiers were unavailable or inconsistently measured. Importantly, critiques reflected both issues that could be further interrogated analytically (e.g., exploring effect modifiers, testing proportional hazards, and evaluating alternative model structures) and structural constraints that are difficult to remedy, such as thin evidence networks and rapidly changing standards of care.
CONCLUSIONS: Recent HTA feedback shows recurring, method-dependent limitations in oncology ITCs, often arising from unavoidable evidence constraints, rather than analytic approach alone. Submissions should state where assumptions are required, document steps taken to investigate and mitigate them, and report how robust conclusions remain when evidence is sparse or treatment pathways change.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
HTA45
Topic
Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes
Disease
SDC: Oncology