Surrogate endpoint
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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. 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".)
is that it may be associated with a "hard" outcome such as death or a heart attack. It is a major issue in testing the efficacy of medication. For example, most cholesterol-lowering drugs (e.g. the statins) are used to control cardiovascular disease, yet they were introduced with only information on their capacity to decrease cholesterol levels. While elevated cholesterol levels increase the likelihood for heart disease, the relationship is not linear - many people with normal cholesterol develop heart disease, and many with high cholesterol do not. In the case of simvastatin (Zocor®), proof of its efficacy in reducing cardiovascular disease was only presented five years after its original introduction, and then only for secondary prevention. In another case, AstraZeneca has been accused of marketing rosuvastatin (Crestor®) without providing hard endpoint data, relying instead on surrogate endpoints. The company counters that it had been tested on larger groups of patients than any other drug in the class, and that its effects should be comparable to the other statins.
References
- ↑ Controlled Clinical Trials 22:485–502 (2001))