Surrogate endpoint: Difference between revisions
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==Examples of Surrogate Endpoints== | ==Examples of Surrogate Endpoints== | ||
Examples of surrogate markers include: | |||
*Total [[cholesterol]] | |||
*High density lipoprotein ([[HDL]]) | |||
*Low density lipoprotein ([[LDL]]) | |||
*[[c reactive protein]] ([[cRP]]) | |||
*Platelet inhibition by [[light transmittance aggregometry]] | |||
*Coronary blood flow | |||
*Minimum diameter or an artery and restenosis | |||
==References== | ==References== |
Revision as of 19:01, 31 October 2010
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In clinical trials, a surrogate endpoint is a measure of effect of a certain treatment that may correlate with a real endpoint but doesn't necessarily have a guaranteed relationship. The National Institutes of Health (USA) define surrogate endpoints as: "A biomarker intended to substitute for a clinical endpoint".[1]
The advantages of a surrogate endpoint
The assessment of "hard" primary clinical endpoints (such as death and heart attack) often requires large long-term clinical trials which can be quite expensive. The use of surrogate endpoints can allow trials to evaluate the efficacy of a new drug or device more rapidly, more efficiently and more inexpensively.
The disadvantage of surrogate endpoints
There are several potential disadvantages of a surrogate endpoint.
1. The surrogate endpoint may intuitively be hypothesized to be related to a "hard endpoint" such as death or heart attack, but may not be.
2. While a surrogate endpoint may be related to a "hard endpoint" such as death or heart attack, it is not clear that a reduction in the surrogate endpoint will lead to an improvement in the "hard endpoint" in death or heart attack. Anti-diabetic agents have been shown to reduce long term glucose (Hemoglobin A1c or HbA1C). It was hypothesized that more intense glucose control (a reduction in HbA1C) would be associated with a lower rate of death and heart attack. However, despite lowering of HbA1C, rosiglitazone or Avandia was not associated with a reduction in death and MI, but with an increase.
3. While a surrogate endpoint may be related to a "hard endpoint, it may be an acausal association (the surrogate may not lie in the causal pathway to the "hard endpoint" and changing the surrogate endpoint may not change the "hard endpoint".)
4. The agent may reduce the surrogate endpoint, but due to off target toxicity, may increase the risk of "hard endpoints" such as death or MI. Lower HDL is associated with a higher risk of adverse cardiac outcomes, Torcetrapib raises HDL and should therefore improve clinical outcomes, however, Torcetrapib administration was found to be associated with a higher rate of adverse clinical outcomes. It was felt that the potential benefit of Torcetrapib was reversed due to off target toxicity of a slight increase in blood pressure associated with Torcetrapib administration.
5. The relationship between the surrogate endpoint and the "hard endpoint" may be non-linear or may be a threshold effect. For example, in antiplatelet agent studies, it is unclear if ever greater levels of inhibition of platelet aggregation are associated with ever greater reductions in adverse outcomes, or if one must achieve just a certain "threshold" level of inhibition to improve outcomes.
Examples of Surrogate Endpoints
Examples of surrogate markers include:
- Total cholesterol
- High density lipoprotein (HDL)
- Low density lipoprotein (LDL)
- c reactive protein (cRP)
- Platelet inhibition by light transmittance aggregometry
- Coronary blood flow
- Minimum diameter or an artery and restenosis
References
- ↑ Controlled Clinical Trials 22:485–502 (2001))