The prostate cancer prevention trial: design, biases and interpretation of study results.
OBJECTIVE
We describe the complexities of the study design of the PCPT and how they influenced the end point chosen, trial implementation, analysis and interpretation of the results.


METHODS
Data from the PCPT are provided to evaluate and quantify the potential biases of this trial design.


RESULTS
Six potential sources of bias, including prostate specific antigen, digital rectal examination, prostate biopsy technique, study medication nonadherence and contamination, and transurethral prostate resection are presented. These biases resulted in the need for the end of study biopsy to evaluate the trial objectives.


CONCLUSIONS
There were a large number of known and potential biases that worked for and against finasteride. Because of the trial design and inherent biases, it is imperative that interim biopsy results should be interpreted with caution. While the period prevalence end point that relied on an end of study biopsy was perhaps not the most clinically relevant, it was the only way to remove as much bias as possible and meet the study objective of determining if finasteride could decrease the risk of prostate cancer. The success of the PCPT depended on constant scrutiny by the Data and Safety Monitoring Committee to monitor these biases. The design and biopsy assumptions outlined at the inception of the trial were met, including adherence and contamination rates, the for-cause biopsy rate and the final percent of men with study end points.
Goodman
Phyllis J
PJ
Southwest Oncology Group Statistical Center, Seattle, Washington 98109-1024, USA. pgoodman@fhcrc.org
Thompson
Ian M
IM
Tangen
Catherine M
CM
Crowley
John J
JJ
Ford
Leslie G
LG
Coltman
Charles A
CA
D015982:Bias; D001706:Biopsy / Q000379:methods; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000517:prevention & control*; D012107:Research Design / Q000592:standards* / Q000706:statistics & numerical data*
D017430:Prostate-Specific Antigen