"The three-month PSA measurement may augment clinical decision making and holds promise as a potential surrogate end point
in clinical trials," the authors write.
Instituted in 1992, the accelerated approval program was designed to approve drugs to treat serious conditions on the basis of a surrogate end point
. As part of this pathway, pharmaceutical companies are required to complete phase 4 confirmatory studies, and if such trials turn out negative, the FDA has regulations in place to remove the drug from the market, fn contrast, Amgen would not be required to show a positive effect on cardiovascular outcomes if evolocumab were approved on the basis of changes in LDL cholesterol." (4)
In order to use a biomarker as a surrogate end point
in a regulatory submission, researchers must evaluate the method for sensitivity, specificity, reproducibility, interobserver reliability, variability and bias (REF6).
CD4 cell count as a surrogate end point
in HIV clinical trial, a meta analysis of studies of the AIDS clinical trials group.
Atherosclerotic changes can be measured by carotid intima-media thickness by B-mode ultrasound is surrogate end point
in cardiovascular outcomes in clinical trials.5 Carotid intima-media thickness has been measured to determine risk of atheroscle-rosis.6-12 Studies have shown that increased carotid intima-media thickness is high risk for cardiovas-cular diseases.13-15 B-mode ultrasound imaging (Carotid Doppler) can visualize noninvasively the superficial arteries in every stage of arthrosclerosis.
Yet, they write, "no systematic assessment of PFS as a surrogate end point
in NSCLC has been reported to date" (Soria 2010).
But early endoscopic findings suggest that the added aspirin helps promote the appearance of new squamous epithelial islands in areas previously showing Barrett metaplasia, a promising surrogate end point
, according to Dr.
The primary surrogate end point
for response was RITS at surgery.
As the early data are validated by additional clinical trials, CTCs may become a surrogate end point
for disease status, as opposed to waiting many months or years for end points such as disease progression and survival data.
These approvals can be based on a surrogate end point
that is considered "reasonably likely" to predict clinical benefit, or on an effect on a clinical end point "other than survival or irreversible morbidity." Since 1995, the FDA has approved 49 new oncology indications for 37 products as accelerated approvals.
Midodrine received accelerated approval as ProAmatine in 1996 based on the surrogate end point
of increase in 1minute standing systolic blood pressure.
While not endorsing HBV DNA as a reliable surrogate end point
for long-term clinical outcomes, the panel did conclude that elevated HBV DNA is the "most important predictor" of cirrhosis or hepatocellular carcinoma in patients with chronic HBV infection.