In clinical trials, the surrogate endpoint (or marker ) is a measure of the effect of a specific treatment that may be correlated with a clinical end point real > but not always have a guaranteed relationship. The National Institutes of Health (USA) defines a replacement endpoint as a "biomarker intended to replace clinical endpoints".
The replacement marker is used when the primary endpoint is undesirable (eg, death), or when the number of occurrences is very small, making it impractical to conduct a clinical trial to collect a significant number of statistically significant end points. The FDA and other regulatory bodies will often receive evidence from clinical trials that demonstrate a direct clinical benefit for substitute markers.
Endpoint replacements can be obtained from different modalities, such as, behavioral or cognitive scores, or biomarkers of electroencephalography (qEEG), MRI, PET, or biochemical biomarkers.
Correlation does not make a substitute. It is a common misconception that if results are correlated (ie, correlated with correct clinical outcomes) it can be used as a valid replacement endpoint (that is, a substitute for a correct clinical outcome). However, the correct justification for such reimbursement requires that the effects of intervention on the replacement endpoint predict the effect on clinical outcomes - conditions much stronger than correlations.
The term "surrogate" should not be used in describing the end point. In contrast, the description of results and interpretations should be formulated in terms of the specific nature and category of the assessed variables.
The surrogate endpoint of clinical trials is a laboratory or physical marker measurement used as a substitute for clinically meaningful end points that directly measure how the patient feels, functions, or endures. Changes caused by therapy at the replacement endpoint will reflect changes in clinically meaningful end points.
Commonly used example is cholesterol. While high cholesterol levels increase the likelihood of heart disease, the relationship is not linear - many people with normal cholesterol develop heart disease, and many with high cholesterol do not. "Death due to heart disease" is the end point of interest, but "cholesterol" is a surrogate marker. A clinical trial may show that certain drugs (eg, simvastatin (Zocor)) are effective in reducing cholesterol, without directly showing that simvastatin prevents death. Proof of Zocor's efficacy in reducing cardiovascular disease is presented only five years after its original introduction, and then only for secondary prevention. In other cases, AstraZeneca has been accused of marketing rosuvastatin (Crestor) without providing strong endpoint data, relying solely on replacement endpoints. The company claims that it has been tested in a larger group of patients than other drugs in the class, and that the effect should be comparable with other statins.
Video Surrogate endpoint
Criticism
There are a number of instances when research using replacement markers has been used to demonstrate the benefits of certain treatments, but then, re-studies that look at the endpoints do not show any benefit, or even show harm.
Maps Surrogate endpoint
See also
- The FDA Accelerated Approval program is based on a substitute endpoint
References
Source of the article : Wikipedia
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