Good Practices Recommendations Aim to Strengthen
Health Technology Assessment Decision Making Worldwide

Lawrenceville, NJ, USA—May 28, 2026—Value in Health, the official journal of ISPOR—The Professional Society for Health Economics and Outcomes Research, announced today the publication of an ISPOR Good Practices Report providing guidance on the use of surrogate endpoint evaluation methods in health technology assessment (HTA) decision making. The report, “Methods for Evaluation of Surrogate Endpoints for HTA Decision Making: A Good Practices Report of an ISPOR Task Force,” was published in the May 2026 issue of Value in Health.

Surrogate endpoints are widely used as primary outcomes in clinical trials, and their use is growing. Rather than measuring clinical benefit directly, a surrogate endpoint is expected to predict clinical benefit or harm based on epidemiologic, therapeutic, pathophysiologic, statistical, or other scientific evidence. In statin trials, for example, LDL-C reduction serves as the surrogate endpoint while the true target outcome is all-cause mortality or cardiovascular disease death. This approach can reduce both the sample size and duration of clinical trials—but only delivers reliable results when the surrogate endpoint has been properly validated for its ability to predict clinical benefit.

"Approximately 60% of new drugs and biologics approved by the US Food and Drug Administration (FDA) in the last 2 decades are based on surrogate endpoints," said Oriana Ciani, PhD, Center for Research on Health and Social Care Management, SDA Bocconi School of Management, Milan, Italy and one of the 4 task force co-chairs. “However, recent studies found that most surrogate endpoints used to support FDA approval of drugs lacked high-level evidence of validation.” This lack of validation increases uncertainty in the decision-making process of regulatory bodies, HTA agencies, and payers, said task force co-chair, Bart Heeg, PhD, Senior Advisor Zorginstituut Nederland, Diemen, The Netherlands.

This Good Practices Report addresses the gap by describing how surrogate endpoints can be statistically evaluated and used in HTA decision making. It provides integrated recommendations spanning both surrogate endpoint validation and health economic modeling, considering 3 levels of evidence: biological plausibility, individual-level, trial-level surrogacy.

The Task Force recommendations fall into 2 categories.

For statistical evaluation, the report calls for:

• Robust meta-analytic approaches—ideally using individual participant data across multiple relevant randomized controlled trials—that account for measurement error and within-study correlation
• Bayesian methods when data are limited and information needs to be borrowed across treatment classes or indications
• Real-world data to supplement, but not replace, randomized controlled trial evidence

For health economic modeling, the report recommends that:

• Disease progression models used for surrogate evaluation should be aligned with the conceptual models informing health economic models
• Cost-effectiveness models should be assessed for clinical and biological plausibility, with transparent reporting of modeled outcomes over time
• Uncertainty in the surrogate relationship should be thoroughly explored through probabilistic sensitivity analyses, scenario analyses, and threshold analysis techniques
• For rare and orphan diseases where both trial data and validated surrogate relationships are scarce, a totality-of-evidence approach should be used, integrating biological rationale, available evidence, and expert opinion, with early engagement of clinicians and HTA bodies

Across both categories, the Task Force emphasizes transparency, rigor, and the need for models to be future-proofed to incorporate new evidence efficiently as it becomes available.

"This ISPOR task force recommends transparent, evidence-based use of surrogate endpoints in HTA by aligning levels of evidence for surrogate endpoint validation with model-based cost-effectiveness to enhance consistency and credibility in healthcare decision making,” noted task force co-chair, Sylwia Bujkiewicz, MSc, PhD, Professor of Biostatistics, University of Leicester, Leicester, England, United Kingdom. “An openly accessible repository of high-quality surrogate endpoint validation studies, systematically organized by treatment, therapeutic class, indication, and substituted target outcome, would represent a valuable resource for researchers, clinicians, industry representatives and decision makers," added Mario Ouwens, PhD, Group Director, Medical and Payer Evidence Statistics, AstraZeneca, Mölndal, Sweden and task force co-chair.

About ISPOR’s Task Force on Surrogate Endpoint Statistical Evaluation for HTA Decision Making
Objective: To provide guidance on emerging good practices for surrogacy evaluation and validation of the relationship between outcomes quantitatively informing HTA. The report will outline different methods to deal with the use of surrogate evidence and how to make appropriate decisions when the relationship between outcomes and their associated treatment effects are used.

Rationale: The task force addresses a gap in guidance in an increasingly important area. This task force will discuss how data can qualitatively and quantitatively be used for HTA purposes to obtain evidence of implicitly or explicitly used relationships, where in some situations sufficient evidence is collected and in other situations only supportive evidence is obtained. Although surrogacy is only 1 element of multidimensional decision making, creating principles for establishing and understanding surrogacy can help reduce variability in this aspect of decision making.

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ABOUT ISPOR 
ISPOR—The Professional Society for Health Economics and Outcomes Research (HEOR), is an international, multistakeholder, nonprofit dedicated to advancing HEOR excellence to improve decision making for health globally. The Society is the leading source for scientific conferences, peer-reviewed and MEDLINE^®-indexed publications, good practices guidance, education, collaboration, and tools/resources in the field. 
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ABOUT VALUE IN HEALTH 
Value in Health (ISSN 1098-3015) is an international, indexed journal that publishes original research and health policy articles that advance the field of health economics and outcomes research to help healthcare leaders make evidence-based decisions. The journal’s current impact factor score is 6.0 and its 5-year impact factor score is 5.7. Value in Health is ranked 5th of 124 journals in Health Policy and Services, 12th of 185 journals in Health Care Sciences & Services, and 37th of 617 journals in Economics. Value in Health is a monthly publication that circulates to more than 55,000 readers around the world. 
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ABOUT ISPOR GOOD PRACTICES REPORTS ISPOR has earned an international reputation for research excellence based, in part, on its Good Practices Reports. These highly cited reports are expert consensus recommendations on good practice standards for outcomes research (clinical, economic, and patient-reported outcomes) and on the use of this research in healthcare decision making. ISPOR Task Forces comprise subject matter experts representing different stakeholders from diverse work environments (ie, regulators, payers, manufacturers, technology assessors, etc from research, government, academic, and industry sectors around the world). All ISPOR Good Practices Reports are published in the Society’s scientific journal, Value in Health, and are made freely available as part of the Society’s mission. The Society’s Good Practices Reports have been recognized with an ASAE “Power of A” award that acknowledges innovative, effective, and broad-reaching programs that have a positive impact on the world.