Yago Garitaonaindía, Professor at University of Copenhagen (Københavns Universitet), shared a post on LinkedIn:
“Quantifying the efficacy-effectiveness gap: a framework for any drug with a national registry
(Garitaonaindia et al., J Natl Canc Inst, June 2026). Subscription access.
Approval and reimbursement rest on trial efficacy. What a drug then delivers in the population actually treated is rarely re-measured. In our new JNCI Oxford University Press paper we set out a framework to quantify that gap, and demonstrate it in first-line metastatic melanoma.
The framework (not disease-specific):
- Start from a near-complete national registry (here Danish Metastatic Melanoma Database (DAMMED), >95% capture, 1909 patients).
- Reconstruct pseudo-IPD from the pivotal-trial Kaplan-Meier curves and treat them as regulatory efficacy benchmarks.
- Stratify the real-world cohort by trial eligibility, using the pivotal exclusion criteria.
- Report effectiveness as benchmark-deviation HRs, population by population.
The output is a number a payer can act on: how far, and for whom, routine outcomes depart from the efficacy that justified approval.
Why it generalizes: nothing in the method is melanoma-specific. Any disease with pivotal trials and a national registry can be benchmarked this way. Deviations should be larger in tumours with lower trial eligibility, such as NSCLC.
The engine: pseudo-IPD reconstruction from digitized KM curves preserves the full survival distribution and avoids the distortions of median and snapshot comparisons under non-proportional hazards.
What melanoma showed: the gap was eligibility-conditioned and drug-class dependent. Immunotherapy matched the benchmark in trial-eligible patients and deviated only in the ineligible (anti-PD-1 OS HR 1.61, 95% CI 1.39-1.86); BRAF/MEKi deviated even in eligible patients (OS HR 2.03, 1.60-2.56), mostly indication bias. These are benchmark-deviation HRs, not causal effects.
Call for high-quality national registries that can monitor and benchmark how these new drugs actually perform in the populations we treat.
Companion post with the full melanoma data by senior author Marco Donia (link in first comment).
Grateful to all co-authors and to senior authors Eva Ellebæk and Marco Donia (corresponding), and to Sociedad Española de Oncología Médica (SEOM) and the Fundación Alfonso Martín Escudero for supporting this work.”
Title: Quantifying the efficacy-effectiveness gap in first line treatment of metastatic melanoma
Authors: Yago Garitaonaindia, Adam A Luczak, Christina H Ruhlmann, Søren Kjær Petersen, Rasmus Blechingberg Friis, Troels H Borch, Louise M Guldbrandt, Inge Marie Svane, Henrik Schmidt, Lars Bastholt, Eva Ellebaek, Marco Donia
Read the Full Article.
Other articles featuring Yago Garitaonaindía on OncoDaily.