***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Investigations using intermediate end points as cancer surrogates are quicker , smaller , and less expensive than studies that use malignancy as the end point . We present a strategy for determining whether a given biomarker is a valid intermediate end point between an exposure and incidence of cancer . C and i date intermediate end points may be selected from case series , ecologic studies , and animal experiments . Prospect i ve cohort and sometimes case-control studies may be used to quantify the intermediate end point-cancer association . The most appropriate measure of this association is the attributable proportion . The intermediate end point is a valid cancer surrogate if the attributable proportion is close to 1.0 , but not if it is close to 0 . Usually , the attributable proportion is close to neither 1.0 nor 0 ; in this case , valid surrogacy requires that the intermediate end point mediate an established exposure-cancer relation . This would in turn imply that the exposure effect would vanish if adjusted for the intermediate end point . We discuss the relative advantages of intervention and observational studies for the validation of intermediate end points . This validation strategy also may be applied to intermediate end points for adverse reproductive outcomes and chronic diseases other than cancer 
    Output:
    
The use of biomarkers in phase I trials has increased over the period from 1991 to 2002 .
To date , biomarker utilization has made a limited and primarily supportive contribution to dose selection , the primary end point of phase I studies .