ACCOUNTING FOR HIGH PLACEBO RESPONSE IN HEALTH TECHNOLOGY ASSESSMENT: EVIDENCE FROM NICE TECHNOLOGY APPRAISALS AND LESSONS FOR RCTS AND ECONOMIC MODELING FOR SJOGREN'S DISEASE
Author(s)
Anastasiia Motrunich, MSc, PhD1, Katarzyna Jablonska, MSc2, Zuzanna Lukowicz, MSc2, David Collomb, MS, PharmD3, Tove Ragna Reksten, PharmD, PhD4, Isabelle Lundqvist, MSc5, Clement Francois, MSc, PhD6, Michele Bombardieri, MD, PhD7.
1Inizio Ignite Putnam, Rotterdam, Netherlands, 2Inizio Ignite Putnam, Krakow, Poland, 3Novartis, Maidenhead, United Kingdom, 4Novartis, Oslo, Norway, 5Novartis, Kista, Sweden, 6Inizio Ignite Putnam, Paris, France, 7William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
1Inizio Ignite Putnam, Rotterdam, Netherlands, 2Inizio Ignite Putnam, Krakow, Poland, 3Novartis, Maidenhead, United Kingdom, 4Novartis, Oslo, Norway, 5Novartis, Kista, Sweden, 6Inizio Ignite Putnam, Paris, France, 7William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
OBJECTIVES: High placebo response is consistently observed in Sjögren’s disease (SjD) randomised controlled trials (RCTs) and increases uncertainty in the interpretation of treatment benefit and its impact within health technology assessment (HTA). This study explored how the National Institute for Health and Care Excellence (NICE) has accounted for placebo response mechanisms in their technology appraisals (TAs), and analysed the relevance of these approaches for interpretation of clinical and cost-effectiveness evidence in SjD.
METHODS: A targeted methodological review was conducted on NICE TAs that explicitly discussed placebo response in RCTs, its different contributing mechanisms, and implications for economic modelling. Additional published evidence describing placebo improvements and challenges in demonstrating treatment benefit in SjD trials were reviewed.
RESULTS: A targeted review identified 28 TAs, of which 12 explicitly discussed placebo response mechanisms and their implications for economic modelling. NICE recognized multiple overlapping mechanisms contributing to placebo improvements, including true placebo effects, Hawthorne effects, and regression to the mean. They considered their implications in interpreting treatment benefit and economic modelling. Alternative approaches and scenario analyses were discussed. Placebo adjustment was accepted as base-case scenario in one TA. Other TAs explored uncertainty through scenario analyses by varying the contributions of different placebo mechanisms. Treatment-waning assumptions and alternative extrapolation approaches were also described. Published SjD literature confirmed persistent challenges linked to high placebo response. Although no SjD-specific TAs were identified, approaches described in other diseases may be applicable to SjD.
CONCLUSIONS: Although NICE has included high placebo response as a consideration in economic modelling in several TAs, formal HTA guidance remains limited. These challenges may be especially relevant in SjD, where heterogeneity, fluctuating disease activity, high unmet need, and limitation of current semi-objective endpoints may amplify placebo effects and complicate assessment of treatment benefit. Further methodological guidance on placebo response may help improve cost-effectiveness understanding of treatments of SjD.
METHODS: A targeted methodological review was conducted on NICE TAs that explicitly discussed placebo response in RCTs, its different contributing mechanisms, and implications for economic modelling. Additional published evidence describing placebo improvements and challenges in demonstrating treatment benefit in SjD trials were reviewed.
RESULTS: A targeted review identified 28 TAs, of which 12 explicitly discussed placebo response mechanisms and their implications for economic modelling. NICE recognized multiple overlapping mechanisms contributing to placebo improvements, including true placebo effects, Hawthorne effects, and regression to the mean. They considered their implications in interpreting treatment benefit and economic modelling. Alternative approaches and scenario analyses were discussed. Placebo adjustment was accepted as base-case scenario in one TA. Other TAs explored uncertainty through scenario analyses by varying the contributions of different placebo mechanisms. Treatment-waning assumptions and alternative extrapolation approaches were also described. Published SjD literature confirmed persistent challenges linked to high placebo response. Although no SjD-specific TAs were identified, approaches described in other diseases may be applicable to SjD.
CONCLUSIONS: Although NICE has included high placebo response as a consideration in economic modelling in several TAs, formal HTA guidance remains limited. These challenges may be especially relevant in SjD, where heterogeneity, fluctuating disease activity, high unmet need, and limitation of current semi-objective endpoints may amplify placebo effects and complicate assessment of treatment benefit. Further methodological guidance on placebo response may help improve cost-effectiveness understanding of treatments of SjD.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
EE431
Topic
Economic Evaluation
Topic Subcategory
Trial-Based Economic Evaluation
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)