THE ROLE OF SAFETY AND TOLERABILITY IN HTA VALUE ASSESSMENT: EVIDENCE REQUIREMENTS AND IMPACT ACROSS KEY EUROPEAN MARKETS
Author(s)
Carol Mao, MS, MBA1, Antoine C. El Khoury, PhD1, Nan Li, PhD2, Jochen Fleischmann, PhD2, Tetsuro Ito, MSc, MBA3, Tom Nijhuis, MSc4, Rachel Xinyun Zhu, MBA, MS4, Eduardo Ochoa, MiM4, Christoph Glaetzer, Dipl. Kfm.1;
1Johnson & Johnson, Raritan, NJ, USA, 2Johnson & Johnson, Horsham, PA, USA, 3Johnson & Johnson, High Wycombe, United Kingdom, 4IQVIA, London, United Kingdom
1Johnson & Johnson, Raritan, NJ, USA, 2Johnson & Johnson, Horsham, PA, USA, 3Johnson & Johnson, High Wycombe, United Kingdom, 4IQVIA, London, United Kingdom
OBJECTIVES: Drug safety protects patients from harmful adverse effects and supports treatment effectiveness. This study examined how safety and tolerability are valued within HTA frameworks across key European markets, assessing their role in value determination and influence on HTA outcomes.
METHODS: A multi-step approach was used: (i) secondary research on HTA methodologies and evaluation frameworks from key European HTA systems (France, Germany, England, Italy, Spain); (ii) case studies of HTA decisions 2019-2025 in France and Germany; and (iii) expert consultations to validate findings. Each system was evaluated for how safety and tolerability inform clinical benefit assessments, economic modeling, and overall value decisions.
RESULTS: All reviewed HTA frameworks incorporate safety within clinical benefit, but it generally plays a supportive rather than primary role. In Germany, improved safety can elevate HTA outcomes either alongside efficacy gains or as a differentiator when efficacy is comparable. Other markets integrate safety within broader domains rather than as a standalone criterion. Reduced adverse events can increase Quality-Adjusted Life Years (QALYs) and lower management costs, strengthening cost-effectiveness arguments. Meaningful impact typically requires robust comparative evidence, often statistically significant reductions versus appropriate comparators. Efficacy remains the dominant driver: no HTA granted a high benefit rating based solely on safety when efficacy was inferior. When efficacy advantages are unclear or absent, superior safety and tolerability may still positively influence HTA outcomes or payer negotiations, as demonstrated in G-BA’s decisions of “minor added benefit” for ibrutinib and acalabrutinib (combination with obinutuzumab in chronic lymphocytic leukemia; February 2020, June 2021 respectively), and olaparib (HER2-negative locally advanced or metastatic breast cancer; January 2020).
CONCLUSIONS: Safety and tolerability are consistently acknowledged but rarely decisive in HTA evaluations. Elevating their value in assessments, through strategic integration of these data into both clinical and economic narratives, could improve the influence of those data on HTA and reimbursement outcomes.
METHODS: A multi-step approach was used: (i) secondary research on HTA methodologies and evaluation frameworks from key European HTA systems (France, Germany, England, Italy, Spain); (ii) case studies of HTA decisions 2019-2025 in France and Germany; and (iii) expert consultations to validate findings. Each system was evaluated for how safety and tolerability inform clinical benefit assessments, economic modeling, and overall value decisions.
RESULTS: All reviewed HTA frameworks incorporate safety within clinical benefit, but it generally plays a supportive rather than primary role. In Germany, improved safety can elevate HTA outcomes either alongside efficacy gains or as a differentiator when efficacy is comparable. Other markets integrate safety within broader domains rather than as a standalone criterion. Reduced adverse events can increase Quality-Adjusted Life Years (QALYs) and lower management costs, strengthening cost-effectiveness arguments. Meaningful impact typically requires robust comparative evidence, often statistically significant reductions versus appropriate comparators. Efficacy remains the dominant driver: no HTA granted a high benefit rating based solely on safety when efficacy was inferior. When efficacy advantages are unclear or absent, superior safety and tolerability may still positively influence HTA outcomes or payer negotiations, as demonstrated in G-BA’s decisions of “minor added benefit” for ibrutinib and acalabrutinib (combination with obinutuzumab in chronic lymphocytic leukemia; February 2020, June 2021 respectively), and olaparib (HER2-negative locally advanced or metastatic breast cancer; January 2020).
CONCLUSIONS: Safety and tolerability are consistently acknowledged but rarely decisive in HTA evaluations. Elevating their value in assessments, through strategic integration of these data into both clinical and economic narratives, could improve the influence of those data on HTA and reimbursement outcomes.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
HTA14
Topic
Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes, Value Frameworks & Dossier Format
Disease
No Additional Disease & Conditions/Specialized Treatment Areas