Comparative Clinical Effectiveness in Skin Cancer: Lessons From HTA Decision Making in EU4, UK, and Australia
Author(s)
Ahmad Hecham Alani, PharmD1, Diana Rebeca Acosta Focil, MSc1, Hanne Ecker, MSc1, Mackenzie Mills, PhD2, Panos Kanavos, BSc, MSc, PhD3.
1HTA-Hive (Hive Health Optimum Ltd.), London, United Kingdom, 2HTA-Hive (Hive Health Optimum Limited), LONDON, United Kingdom, 3London School of Economics and Political Science, London, United Kingdom.
1HTA-Hive (Hive Health Optimum Ltd.), London, United Kingdom, 2HTA-Hive (Hive Health Optimum Limited), LONDON, United Kingdom, 3London School of Economics and Political Science, London, United Kingdom.
OBJECTIVES: Conducting head-to-head (H2H) trials in skin cancers is often challenging due to ethical concerns, particularly following the approval of novel therapies. Consequently, alternative methods are used to estimate the relative effectiveness. This study aims to explore how these comparative approaches have been assessed in skin cancer submissions, with a focus on the methodological strategies employed and the outcomes reported.
METHODS: A retrospective review of decisions was conducted using the HTA-Hive database, focusing on appraisals from the past five years. Submissions to—G-BA, HAS, AIFA, AEMPS, NICE, and PBAC—were included. Submissions containing any comparative clinical effectiveness evidence were included. Data were collected on agency assessments, methodological concerns, and decision outcomes. Statistical associations were analysed using chi-square and t-tests.
RESULTS: Forty decisions were reviewed; fourteen (35%) included comparative clinical effectiveness analyses beyond RCTs—8 using a single method, 6 multiple—yielding 25 comparisons. Methods used included naïve comparisons (24%, n=6), Bucher (20%, n=5), MAIC (16%, n=4), STC (12%, n=3), propensity score-based methods (12%, n=3), NMA (4%, n=1), and others (8%, n=2). One submission (4%) did not report its method. Submissions using indirect approaches were more likely to receive favourable outcomes, though this trend was not statistically significant. Overall, these approaches were deemed acceptable/reliable in 43% of cases, ambiguous in 36%, and insufficient in 21%. Concerns raised by agencies included adjustment techniques (29%), bias/confounding (27%), data quality/compatibility (29%), and assumptions like transitivity (15%).
CONCLUSIONS: In the absence of H2H trials, a range of indirect comparative methods are employed in submissions for skin cancer. While these approaches can support favourable assessments, their methodological robustness remains variable. Nearly half of submissions using indirect comparisons were deemed acceptable, but concerns around bias, data compatibility, and assumptions were common. These findings highlight the need for clearer guidance and standards to improve the credibility/consistency of comparative clinical evidence in decision-making.
METHODS: A retrospective review of decisions was conducted using the HTA-Hive database, focusing on appraisals from the past five years. Submissions to—G-BA, HAS, AIFA, AEMPS, NICE, and PBAC—were included. Submissions containing any comparative clinical effectiveness evidence were included. Data were collected on agency assessments, methodological concerns, and decision outcomes. Statistical associations were analysed using chi-square and t-tests.
RESULTS: Forty decisions were reviewed; fourteen (35%) included comparative clinical effectiveness analyses beyond RCTs—8 using a single method, 6 multiple—yielding 25 comparisons. Methods used included naïve comparisons (24%, n=6), Bucher (20%, n=5), MAIC (16%, n=4), STC (12%, n=3), propensity score-based methods (12%, n=3), NMA (4%, n=1), and others (8%, n=2). One submission (4%) did not report its method. Submissions using indirect approaches were more likely to receive favourable outcomes, though this trend was not statistically significant. Overall, these approaches were deemed acceptable/reliable in 43% of cases, ambiguous in 36%, and insufficient in 21%. Concerns raised by agencies included adjustment techniques (29%), bias/confounding (27%), data quality/compatibility (29%), and assumptions like transitivity (15%).
CONCLUSIONS: In the absence of H2H trials, a range of indirect comparative methods are employed in submissions for skin cancer. While these approaches can support favourable assessments, their methodological robustness remains variable. Nearly half of submissions using indirect comparisons were deemed acceptable, but concerns around bias, data compatibility, and assumptions were common. These findings highlight the need for clearer guidance and standards to improve the credibility/consistency of comparative clinical evidence in decision-making.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HTA79
Topic
Health Technology Assessment, Organizational Practices, Study Approaches
Topic Subcategory
Decision & Deliberative Processes
Disease
Oncology, Sensory System Disorders (Ear, Eye, Dental, Skin)