Cardiovascular disease A commonly used example is
cholesterol. 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. "Death from heart disease" is the endpoint of interest, but "cholesterol" is the surrogate marker. A clinical trial may show that a particular drug (for example,
simvastatin (Zocor)) is effective in reducing cholesterol, without showing directly that simvastatin prevents death. Proof of Zocor's efficacy in reducing cardiovascular disease was only presented five years after its original introduction, and then only for
secondary prevention. In another case,
AstraZeneca was accused of marketing
rosuvastatin (Crestor) without providing hard endpoint data, relying instead on surrogate endpoints. The company countered that rosuvastatin 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.
Cancer Progression Free Survival is a prominent example in
Oncology contexts. There are examples of cancer drugs approved on the basis of progression-free survival failed to show subsequent improvements in overall survival in subsequent studies. In breast cancer,
Bevacizumab (Avastin) initially gained approval from the
Food and Drug Administration, but subsequently had its license revoked. More patient focused surrogate endpoints may offer a more meaningful alternative such as
Overall Treatment Utility.
Infectious disease In HIV/AIDS medicine, CD4 counts and viral loads are used as surrogate markers for drug approval for clinical trials. In hepatitis C medicine, the surrogate endpoint "Sustained Virological Response" has been used for the approval of expensive drugs known as
Direct Acting Antivirals. The validity of this surrogate endpoint for predicting clinical outcomes has been challenged. For several vaccines (anthrax, hepatitis A, etc), the induction of detectable antibodies in blood is used as a surrogate marker for vaccine effectiveness, as exposure of individuals to an actual pathogen is considered unethical.
Alzheimer's disease A recent study showed that plasma biomarkers have the potential to be used as surrogate biomarkers in
Alzheimer's disease (AD) clinical trials. More specifically, this study demonstrated that plasma p-tau181 could potentially be used to monitor large-scale population interventions targeting preclinical AD individuals. ==Criticism==