The Landscape of Current Policy and Health Authority Positions on Intermediate Endpoints (IEs) for Clinical Outcomes in Oncology
Author(s)
Uwe Siebert, MPH, MSc, ScD, MD1, Francesco De Solda, MBA, PharmD2, Kimberly Hofer, BSc3, Otto Lam, PhD3, James McCallion, BA, MSc2, Sharon A. McCarthy, BPharm2, Suneel Mundle, PhD2, Mir-Masoud Pourrahmat, MSc3, Beate Jahn, Dipl.-Math. oec., Dr.rer.soc.oec.1;
1UMIT TIROL – University for Health Sciences and Technology, Hall in Tirol, Austria, 2Johnson & Johnson, New Brunswick, NJ, USA, 3Evidinno Outcomes Research Inc., Vancouver, BC, Canada
1UMIT TIROL – University for Health Sciences and Technology, Hall in Tirol, Austria, 2Johnson & Johnson, New Brunswick, NJ, USA, 3Evidinno Outcomes Research Inc., Vancouver, BC, Canada
OBJECTIVES: While rates of new drug approvals based on IEs have increased recently, approaches for IE validation are inconsistent. This study reviewed the current landscape of guidance from regulatory bodies, health technology assessment (HTA) agencies, payers, and other policy-makers on IEs in oncology.
METHODS: We conducted a literature search using Embase (1974 to 10-29-2024), supplemented by manual searches of prespecified organizations in the Americas, Europe, and Asia-Pacific regions, for guidance or policy on IEs.
RESULTS: We identified guidance from >40 organizations on IE use and/or surrogacy validation. Other relevant documents pertained to approval trends. Regulatory bodies lacked detailed guidance on IE validation methods. Most HTA agencies only minimally referenced the need for significant/established relationships between IEs and target clinical outcomes, while a few agencies provided more detailed guidance. The National Institute for Health and Care Excellence (NICE; UK) recommended a Bayesian meta-analytic approach with take-one-out cross-validation. The Institute for Quality and Efficiency in Health Care (IQWiG; Germany) provided guidance for IE validation, which was adapted for a validation framework by the National Authority of Medicines and Health Products (INFARMED; Portugal). Some HTA agencies only cited other organizations, such as the European Network for Health Technology Assessment (EUnetHTA), which reported a 3-level hierarchy of evidence. Specific correlation thresholds for IE validation were noted by IQWiG, EUnetHTA, European Commission, and INFARMED.
CONCLUSIONS: Detailed guidance on IE validation is insufficient and inconsistent across most organizations. A minority of HTA agencies, including IQWiG and NICE, provide more comprehensive frameworks. Nevertheless, the majority of guidance is limited and not disease-specific. Recommendations on validation criteria remain limited, and thresholds for correlations between IEs and specific clinical outcomes are often stringent or undefined. To enhance decision-making, it is crucial to align on robust validation approaches and use correlation thresholds that consider tumor type, disease context, and clinical consequences for patients.
METHODS: We conducted a literature search using Embase (1974 to 10-29-2024), supplemented by manual searches of prespecified organizations in the Americas, Europe, and Asia-Pacific regions, for guidance or policy on IEs.
RESULTS: We identified guidance from >40 organizations on IE use and/or surrogacy validation. Other relevant documents pertained to approval trends. Regulatory bodies lacked detailed guidance on IE validation methods. Most HTA agencies only minimally referenced the need for significant/established relationships between IEs and target clinical outcomes, while a few agencies provided more detailed guidance. The National Institute for Health and Care Excellence (NICE; UK) recommended a Bayesian meta-analytic approach with take-one-out cross-validation. The Institute for Quality and Efficiency in Health Care (IQWiG; Germany) provided guidance for IE validation, which was adapted for a validation framework by the National Authority of Medicines and Health Products (INFARMED; Portugal). Some HTA agencies only cited other organizations, such as the European Network for Health Technology Assessment (EUnetHTA), which reported a 3-level hierarchy of evidence. Specific correlation thresholds for IE validation were noted by IQWiG, EUnetHTA, European Commission, and INFARMED.
CONCLUSIONS: Detailed guidance on IE validation is insufficient and inconsistent across most organizations. A minority of HTA agencies, including IQWiG and NICE, provide more comprehensive frameworks. Nevertheless, the majority of guidance is limited and not disease-specific. Recommendations on validation criteria remain limited, and thresholds for correlations between IEs and specific clinical outcomes are often stringent or undefined. To enhance decision-making, it is crucial to align on robust validation approaches and use correlation thresholds that consider tumor type, disease context, and clinical consequences for patients.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
P11
Topic
Clinical Outcomes
Topic Subcategory
Relating Intermediate to Long-term Outcomes
Disease
SDC: Oncology