# Surrogate end points in clinical research: hazardous to your health.

@article{Grimes2005SurrogateEP,
title={Surrogate end points in clinical research: hazardous to your health.},
author={David A. Grimes and Kenneth F. Schulz},
journal={Obstetrics and gynecology},
year={2005},
volume={105 5 Pt 1},
pages={
1114-8
}
}
• Published 1 May 2005
• Medicine
• Obstetrics and gynecology
Surrogate end points in clinical research pose real danger. A surrogate end point is an outcome measure, commonly a laboratory test, that substitutes for a clinical event of true importance. Resistance to activated protein C, for example, has been used as a surrogate for venous thrombosis in women using oral contraceptives. Other examples of inappropriate surrogate end points in contraception include the postcoital test instead of pregnancy to evaluate new spermicides, breakage and slippage… Expand

#### Paper Mentions

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Adoption and use of surrogate end points lacking validation, especially in cardiovascular medicine, have caused thousands of patients' deaths, a serious violation of the ethical principle of beneficence. Expand
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#### References

SHOWING 1-10 OF 43 REFERENCES
Surrogate End Points in Clinical Trials: Are We Being Misled?
• Medicine
• Annals of Internal Medicine
• 1996
Surrogate end points are rarely, if ever, adequate substitutes for the definitive clinical outcome in phase 3 trials and proper justification for such replacement requires that the effect of the intervention on the surrogate end point predicts the effect on the clinical outcome. Expand
Clinical trial end points: on the road to nowhere?
• Medicine
• Neurology
• 2002
The authors hypothesize that lingering therapeutic uncertainty exists because many of the clinical trial end points have been surrogate outcome measures rather than end points with clear and convincing value to patients. Expand
Surrogate endpoints in clinical trials: definition and operational criteria.
A rather restrictive criterion is proposed for use of the adjective 'surrogate' - it is proposed that a surrogate for a true endpoint yield a valid test of the null hypothesis of no association between treatment and the true response. Expand
The promise and peril of surrogate end points in cancer research
• Medicine
• Nature Reviews Cancer
• 2002
Both experimental and observational studies of cancer need to have an end point. Traditionally, in aetiological and prevention studies, that end point has been the incidence of cancer itself, whereasExpand
A perfect correlate does not a surrogate make
• Medicine, Psychology
• BMC medical research methodology
• 2003
Perfect correlation between potential surrogate and unobserved true outcomes within randomized groups does not guarantee correct inference based on a potential surrogate endpoint and even in early phase trials, investigators should not base conclusions on potential surrogate endpoints. Expand
Statistical issues for HIV surrogate endpoints: point/counterpoint. An NIAID workshop.
This paper summarizes the proceedings of an NIAID-sponsored workshop on statistical issues for HIV surrogate endpoints and provides the position statements from the two debaters on each issue. Expand
Oral contraceptives and blood coagulation: a critical review.
• E. Mammen
• Medicine
• American journal of obstetrics and gynecology
• 1982
There seems to be no test procedure or even combination of tests that will reliably predict which patient might develop a thromboembolic episode in association with oral contraceptives or in combination with any other condition recognized as being a risk factor. Expand
Sex hormone--binding globulin--a surrogate marker for the prothrombotic effects of combined oral contraceptives.
• Medicine
• American journal of obstetrics and gynecology
• 2004
The correlation between SHBG and the well-established risk factor APCr might indicate the usefulness of SHBG as a risk marker for VTE during COC treatment. Expand
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial
Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD. Expand
Effects of contraceptive steroids on serum lipoproteins and cardiovascular disease scrutinized at workshop in Bethesda.
• Medicine
• Contraception
• 1980
It was agreed that at least some OC pills do lower serum HDL levels, and the apparent association between HDL levels and the incidence of cardiovascular disease dictates the need for vigorous research. Expand