INDIRECT TREATMENT COMPARISONS IN BREAST CANCER: METHODS AND ACCEPTANCE IN NICE SUBMISSIONS
Author(s)
Jessica Amis1, Keval Haria, BA, MSc2.
1Costello Medical, Cambridge, United Kingdom, 2Costello Medical, London, United Kingdom.
1Costello Medical, Cambridge, United Kingdom, 2Costello Medical, London, United Kingdom.
OBJECTIVES: Breast cancer has a rapidly evolving competitive landscape. Since head-to-head comparative evidence for all relevant treatments is not available, indirect treatment comparisons (ITCs) are frequently required in NICE submissions. We reviewed recent NICE technology appraisals in breast cancer to describe the ITC methods applied and summarise key assessor critique.
METHODS: NICE appraisals in breast cancer with final guidance published between May 2021 and May 2026 were reviewed. Information on ITC methods and external assessment group (EAG) and committee critique were extracted and evaluated.
RESULTS: Of 14 identified submissions, seven presented ITCs, including network meta-analyses (NMAs; n=4), unanchored matching-adjusted indirect comparisons (MAICs; n=2) and a Bucher ITC (n=1). All NMAs used fixed-effects models based on assessment of model fit. Three ITCs included approaches to address proportional hazards (PH) violations, including piecewise NMA (n=1), fractional polynomial NMA (n=1) and a restricted mean survival time-based anchored ITC (n=1). EAGs raised ITC approach as a key issue in all submissions that utilised NMA, unanchored MAIC or Bucher ITC. EAGs criticised reliance on fixed-effects NMAs, noting these inadequately reflect between-study heterogeneity, potentially violating exchangeability, and underestimate uncertainty, reducing confidence in comparative estimates. Unanchored MAICs were considered appropriate when no common comparator was available, though judged to be highly uncertain. When PH were assessed, EAGs raised concerns with the validity of the PH assumption (n=1) or the adequacy of the assessment (n=1). Uncertainty in ITCs was cited among the issues in the two appraisals where technologies were initially not recommended, both of which utilised NMA, prompting revised analyses.
CONCLUSIONS: ITCs provide key clinical effectiveness data for NICE submissions in the absence of relevant direct evidence. ITC methods were a consistent focus of EAG and committee critique. Selecting an appropriate approach for the available evidence, and reporting it transparently with clear justification, is essential to support decision‑making.
METHODS: NICE appraisals in breast cancer with final guidance published between May 2021 and May 2026 were reviewed. Information on ITC methods and external assessment group (EAG) and committee critique were extracted and evaluated.
RESULTS: Of 14 identified submissions, seven presented ITCs, including network meta-analyses (NMAs; n=4), unanchored matching-adjusted indirect comparisons (MAICs; n=2) and a Bucher ITC (n=1). All NMAs used fixed-effects models based on assessment of model fit. Three ITCs included approaches to address proportional hazards (PH) violations, including piecewise NMA (n=1), fractional polynomial NMA (n=1) and a restricted mean survival time-based anchored ITC (n=1). EAGs raised ITC approach as a key issue in all submissions that utilised NMA, unanchored MAIC or Bucher ITC. EAGs criticised reliance on fixed-effects NMAs, noting these inadequately reflect between-study heterogeneity, potentially violating exchangeability, and underestimate uncertainty, reducing confidence in comparative estimates. Unanchored MAICs were considered appropriate when no common comparator was available, though judged to be highly uncertain. When PH were assessed, EAGs raised concerns with the validity of the PH assumption (n=1) or the adequacy of the assessment (n=1). Uncertainty in ITCs was cited among the issues in the two appraisals where technologies were initially not recommended, both of which utilised NMA, prompting revised analyses.
CONCLUSIONS: ITCs provide key clinical effectiveness data for NICE submissions in the absence of relevant direct evidence. ITC methods were a consistent focus of EAG and committee critique. Selecting an appropriate approach for the available evidence, and reporting it transparently with clear justification, is essential to support decision‑making.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HTA266
Topic
Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes
Disease
Oncology