Surrogate markers, clinical trial

Andersson et al. (2002) have shown in a randomized clinical trial that raloxifene does not affect insulin sensitivity or glycemic control in postmenopausal women with type-2 diabetes mellitus. It has favorable or neutral effects on selected surrogate markers of cardiovascular risk while decreasing hyperan-drogenicity in these patients. 

As a surrogate or clinical marker of efficacy during all phases of human clinical trials... 

In clinical trials, biomarkers are used to indicate a particular disease state and its progression. They may be used as surrogate markers in the evaluation of the effectiveness of a drug as representative of the natural endpoint such as survival rate or irreversible morbidity. 

Delavirdine tablets are indicated for the treatment of HIV-1 infection in combination with appropriate antiretroviral agents when therapy is warranted. This indication is based on surrogate marker changes in clinical studies. Clinical benefit was not demonstrated for delavirdine based on survival or incidence of AIDS-defining clinical events in a completed trial comparing delavirdine plus didanosine with didanosine monotherapy. 

Lockhart AC, Braun RD, DewhirstMW, KlitzmanB, Humphrey JS, Yuan F, etal. Wound angiogenesis as a potential surrogate marker for anti-angiogenesis clinical trials. Proc Am Assoc Cancer Res 2000 41 168 (abstract). 

Twelve month studies may be more appropriate for chronically used drugs to be approved on the basis of short-term clinical trials employing efficacy surrogate markers where safety data from humans are limited to short-term exposure, such as some acquired immunodeficiency (AIDS) therapies. 

MELD/PELD/Child-Pugh scores are not designed to provide information on likely drug handling in a patient, but they are often used as surrogate markers in clinical trials. If available, they may give an indication of how far advanced the liver disease is overall. 

Lotterer, E., Hogel, J., Gaus, W., Fleig, W.E., Bircher, J. Quantitative liver function tests as surrogate markers for end-points in controlled clinical trials a retrospective feasibility study. Hepatology 1997 26 1426-1433... 

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