Assessing outcomes in prostate cancer clinical trials: A twenty-first century tower of babel Journal Article
| Authors: | Gignac, G. A.; Morris, M. J.; Heller, G.; Schwartz, L. H.; Scher, H. I. |
| Article Title: | Assessing outcomes in prostate cancer clinical trials: A twenty-first century tower of babel |
| Abstract: | BACKGROUND. Because of the osseous distribution of prostate cancer metastases, progression is more readily identified than response in prostate cancer clinical trials. As a result, there is an increased focus on progression-free survival (PFS) as a phase 2 endpoint. PFS, however, is vulnerable to inter-study design variability. The authors sought to identify and quantify this variability and the resultant error in PFS across prostate cancer clinical trials. METHODS. The authors reviewed phase 2 clinical trials of cytotoxic agents in castration-resistant metastatic prostate cancer over 5 years to evaluate the policies determining extent of disease and the definitions of disease progression. A simulation model was created to define the degree of error in estimating PFS in 3 hypothetical cohorts (median PFS of 12, 24, and 36 weeks) when the frequency of outcome assessments varies. RESULTS. Imaging policies for trial entry were heterogeneous, as were the type, timing, and indications for outcome assessments. In the simulation, error in the reported PFS varied according to the interval between assessments. The difference between the detected and the true PFS could vary as much as 6.4 weeks per cycle, strictly resulting from the variability of assessment schedules tested. CONCLUSIONS. Outcome assessment policies are highly variable in phase 2 studies of castration-resistant prostate cancer patients, despite published guidelines designed to standardize authentication of disease progression. The estimated error in PFS can exceed 6 weeks per cycle, exclusively because of variations in the assessment schedules. Comparisons of PFS times from different studies must be made with circumspection. © 2008 American Cancer Society. |
| Keywords: | cancer chemotherapy; cancer survival; treatment outcome; disease-free survival; clinical trial; cancer growth; bone metastasis; disease free survival; research design; follow up; methodology; antineoplastic agent; prostate specific antigen; computer assisted tomography; multiple cycle treatment; phase 2 clinical trial; biological model; models, biological; antineoplastic combined chemotherapy protocols; cohort analysis; pathology; time; time factors; cancer resistance; prostate cancer; simulation; prostatic neoplasms; health care policy; standard; disease severity; evaluation; prostate tumor; bioassay; castration; taxane derivative; endpoint determination; clinical trials, phase ii as topic; analytical error; soft tissue metastasis; progression-free survival; outcome assessments; endpoints; phase 2 clinical trials |
| Journal Title: | Cancer |
| Volume: | 113 |
| Issue: | 5 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2008-09-01 |
| Start Page: | 966 |
| End Page: | 974 |
| Language: | English |
| DOI: | 10.1002/cncr.23719 |
| PUBMED: | 18661513 |
| PROVIDER: | scopus |
| PMCID: | PMC2708077 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 17 November 2011" - "CODEN: CANCA" - "Source: Scopus" |
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