Improving the decision to pursue a phase 3 clinical trial by adjusting for patient-specific factors in evaluating phase 2 treatment efficacy data Journal Article
| Authors: | Heller, G.; Kattan, M. W.; Scher, H. I. |
| Article Title: | Improving the decision to pursue a phase 3 clinical trial by adjusting for patient-specific factors in evaluating phase 2 treatment efficacy data |
| Abstract: | Phase 2 clinical trials are undertaken to provide evidence of treatment efficacy and safety. A test statistic that accounts for individual patient risk in the patient population is proposed and applied to a phase 2 clinical trial for castrate metastatic prostate cancer. The test statistic is computed to compare, for each patient, the observed 2-year survival outcome to the predicted 2-year survival probability. A logistic regression model, developed using historical data in the same patient population, is used to adjust for patient risk in predicting the 2-year survival probability. Goodness-of-fit procedures are performed to ensure that a proper model is fit to the data. The test result is compared to the score test, the binomial exact test, and Fisher's exact test, all of which use the average 2-year survival probability in the population as the parameter of interest. The results demonstrate the benefit of risk adjustment in determining treatment efficacy in a single-arm phase 2 trial. By adjusting for patient risk, this method can provide a more precise assessment of phase 2 treatment efficacy, thereby improving the decision whether to proceed to a phase 3 clinical trial. |
| Keywords: | cancer survival; controlled study; treatment outcome; survival analysis; major clinical study; clinical trial; drug efficacy; drug safety; comparative study; antineoplastic agent; medical decision making; prostate specific antigen; controlled clinical trial; phase 2 clinical trial; statistics; logistic models; hemoglobin; prediction; risk assessment; mathematical model; prostate cancer; prostatic neoplasms; alkaline phosphatase; survival time; population research; karnofsky performance status; statistical significance; probability; models, statistical; scoring system; lactate dehydrogenase; phase 3 clinical trial; decision making; logistic regression analysis; statistical model; fisher exact test; mathematical computing; epothilones; tubulin modulators; process development; scale up; therapeutic error; analytical parameters; covariance; risk adjustment; analysis of phase 2 clinical trial data; heterogeneous patient population; model-based test statistic; clinical trials, phase ii; clinical trials, phase iii |
| Journal Title: | Medical Decision Making |
| Volume: | 27 |
| Issue: | 4 |
| ISSN: | 0272-989X |
| Publisher: | Sage Publications |
| Date Published: | 2007-07-01 |
| Start Page: | 380 |
| End Page: | 386 |
| Language: | English |
| DOI: | 10.1177/0272989x07303826 |
| PUBMED: | 17761958 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 17 November 2011" - "CODEN: MDMAD" - "Source: Scopus" |
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