Surrogate End Points in Clinical Trials¶
Fleming, T. R., & DeMets, D. L. (1996). Surrogate End Points in Clinical Trials: Are We Being Misled?. Annals of Internal Medicine, 125(7), 605-613.
Cited by¶
5 citations across 5 artifacts.
Each citation links to the sentence it supports in the citing article.
Primes¶
- Construct Validity
- And in clinical measurement, the question is whether a marker measures the disease or a correlated downstream effect that can respond to treatment without the disease responding — the structure behind many surrogate-endpoint failures.
This sourceShows surrogate endpoints can move while the underlying clinical construct does not, the canonical surrogate-endpoint failure.
- And in clinical measurement, the question is whether a marker measures the disease or a correlated downstream effect that can respond to treatment without the disease responding — the structure behind many surrogate-endpoint failures.
- Proxy-Target Divergence
- In medicine, surrogate-endpoint failures occur when a treatment improves a proxy outcome (LDL, HbA1c, tumour response) but fails to improve, or worsens, the patient outcome the proxy was meant to represent.
This sourceCatalogs cases where a treatment improved a surrogate (LDL, arrhythmia suppression) while failing to improve, or worsening, clinical outcomes.
- In medicine, surrogate-endpoint failures occur when a treatment improves a proxy outcome (LDL, HbA1c, tumour response) but fails to improve, or worsens, the patient outcome the proxy was meant to represent.
- Proxy–Target Fidelity
- In medicine, surrogate endpoints are proxies for clinical outcomes: a drug that lowers a biomarker (blood pressure, viral load, tumor size, LDL cholesterol) is assumed to improve the outcome the biomarker stands in for (stroke, mortality, survival), and the surrogate-validity literature is a sustained reckoning with cases where the proxy moved but the outcome did not — drugs that improved the biomarker while harming patients.
This sourceDocuments surrogate endpoints (biomarkers) that moved favorably while clinical outcomes did not, sometimes worsening.
- In medicine, surrogate endpoints are proxies for clinical outcomes: a drug that lowers a biomarker (blood pressure, viral load, tumor size, LDL cholesterol) is assumed to improve the outcome the biomarker stands in for (stroke, mortality, survival), and the surrogate-validity literature is a sustained reckoning with cases where the proxy moved but the outcome did not — drugs that improved the biomarker while harming patients.
- Relevance Substitution
- The same pattern recurs in heuristic substitution (a complex statistical question answered as "does this make me feel comfortable?"), shortcut learning (a model "taking itself" to detect pneumonia while its inference runs through a scanner artefact), surrogate-endpoint substitution (a physician updating on LDL reduction as if it were evidence about cardiovascular mortality),
This sourceShows surrogate endpoints substituted for clinical outcomes can mislead, the medical instance of relevance substitution.
- The same pattern recurs in heuristic substitution (a complex statistical question answered as "does this make me feel comfortable?"), shortcut learning (a model "taking itself" to detect pneumonia while its inference runs through a scanner artefact), surrogate-endpoint substitution (a physician updating on LDL reduction as if it were evidence about cardiovascular mortality),
Mechanisms¶
- Biomarker Monitoring
- The classic misuse is promoting a candidate surrogate to a decision rule before it is validated — trusting that moving the marker means helping the patient, when a therapy can shift the number without touching the outcome.
This sourceShows why an intervention-induced biomarker change cannot stand in for patient benefit until the surrogate is rigorously validated.
- The classic misuse is promoting a candidate surrogate to a decision rule before it is validated — trusting that moving the marker means helping the patient, when a therapy can shift the number without touching the outcome.
Verification¶
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