ReviewThe oncologist2022
Surrogacy Beyond Prognosis: The Importance of "Trial-Level" Surrogacy.
Review in The oncologist, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- Impact of Complete Response on Long-Term Survival in Patients with Relapsed or Refractory Large B-cell Lymphoma: A Center for International Blood and Marrow Transplant Research Prospective Study and Systematic Literature Review/Meta-Analysis.Transplantation and cellular therapy · 2026Pooled it
- An alternative method to validate surrogate endpoints in oncology.BMC medical research methodology · 2026Pooled it
- Evaluating surrogates for overall survival in the adjuvant treatment of bladder cancer with chemotherapy.Urologic oncology · 2025Pooled it
- Trial-level surrogacy of non-high-density and low-density lipoprotein cholesterol reduction on the clinical efficacy of statins.European heart journal. Cardiovascular pharmacotherapy · 2025Pooled it
- Pathologic Complete Response and Survival in Rectal Cancer: A Systematic Review and Meta-Analysis.JAMA network open · 2025Pooled it
- Oncological safety of reconstruction with autologous fat grafting in breast cancer patients: a systematic review and meta-analysis.International journal of clinical oncology · 2022Pooled it
- Correlation of multiple endpoints in the first-line chemotherapy of advanced gastric cancer: Pooled analysis of individual patient data from Japanese Phase III trials.Cancer medicine · 2024Trial
- Evaluating the potential of candidate surrogate endpoints for overall survival in treatment-naive metastatic melanoma treated with anti-PD-1-based regimens with or without anti-CTLA-4 therapy.Journal for immunotherapy of cancer · 2026Article
- Lower- Versus Conventional-Sodium Dialysate and Left Ventricular Mass in Patients Receiving Hemodialysis: Causal Analyses of a Randomized Clinical Trial.Kidney medicine · 2026Article
- Article
- Associations between early changes in circulating tumor DNA (ctDNA) and outcomes across randomized trials: Insights from the ctMoniTR project.The journal of liquid biopsy · 2026Article
- Moving forward from spleen response as an endpoint in randomized controlled trials in myelofibrosis.Haematologica · 2026Review
- Immune Correlates and Vaccine Immunobridging: Statistical Innovations, Challenges, and Opportunities.The Journal of infectious diseases · 2025Review
- Review
- Is pathological response an adequate surrogate marker for survival in neoadjuvant therapy with immune checkpoint inhibitors?ESMO open · 2025Review
- Surrogate endpoint metaregression: useful statistics for regulators and trialists.Journal of clinical epidemiology · 2024Article
- Autologous Fat Grafting (AFG): A Systematic Review to Evaluate Oncological Safety in Breast Cancer Patients.Journal of clinical medicine · 2024Review
- Reporting of surrogate endpoints in randomised controlled trial reports (CONSORT-Surrogate): extension checklist with explanation and elaboration.BMJ (Clinical research ed.) · 2024Article
- Reporting of surrogate endpoints in randomised controlled trial protocols (SPIRIT-Surrogate): extension checklist with explanation and elaboration.BMJ (Clinical research ed.) · 2024Article
- Intermediate clinical endpoints in early-stage breast cancer: an analysis of individual patient data from the Gruppo Italiano Mammella and Mammella Intergruppo trials.EClinicalMedicine · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many candidate surrogate endpoints are currently assessed using a 2-level statistical approach, which consists in checking whether (1) the potential surrogate is associated with the final endpoint in individual patients and (2) the effect of treatment on the surrogate can be used to reliably predict the effect of treatment on the final endpoint. In some situations, condition (1) is fulfilled but condition (2) is not. We use concepts of causal inference to explain this apparently paradoxical situation, illustrating this review with 2 contrasting examples in operable breast cancer: the example of pathological complete response (pCR) and that of disease-free survival (DFS). In a previous meta-analysis, pCR has been shown to be a strong and independent prognostic factor for event-free survival (EFS) and overall survival (OS) after neoadjuvant treatment of operable breast cancer. Yet, in randomized trials, the effects of experimental treatments on pCR have not translated into predictable effects on EFS or OS, making pCR an "individual-level" surrogate, but not a "trial-level" surrogate. In contrast, DFS has been shown to be an acceptable surrogate for OS at both the individual and trial levels in early, HER2-positive breast cancer. The distinction between the prognostic and predictive roles of a tentative surrogate, not always made in the literature, avoids unnecessary confusion and allows better understanding of what it takes to validate a surrogate endpoint that is truly able to replace a final endpoint.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.