Article type
Year
Abstract
Background: Conducting randomized controlled studies inpopula- tions with rare diseases is challengingbecause of difficulties in participant recruitment. There are far fewer challenges in conducting uncontrolled studies in these populations, even if participant numbers are relatively small.
Objectives: To investigate if indirect meta-analysis of uncontrolled studies in two independent regimeswas possible and whether the results werecredible.
Methods: Systematic searches were performed in PubMed, The Cochrane Library, EMBASE and ISI Web of Knowledge to identify randomized controlled trials (RCTs) in gemcitabine-cisplatin compared with gemcitabine alone for advanced biliary tract cancer (BTC), or phase II trials reporting on the efficacy detected in gemcitabine alone or in combination with cisplatin for advanced BTC. The pooled results for each outcome of each regime were calculated, and compared using Chi2 analysis. Direct comparisons were also conducted to compare gemcitabine-cisplatin with gemcitabine.
Results: The pooled overall response rate (ORR), T-cell receptor (TCR), mean progression-free survival (PFS) and overall survival (OS) of 10 phase II studies (330 patients) in gemcitabine-cisplatin for BTC was 25.45% (95% CI 20.75% to 30.15%), 52.12% (95% CI 46.73% to57.51%); 9.02 months, 13.65 months, respectively. The pooled ORR, TCR, mean PFS and OS of eight phase II studies (208 patients) in gemcitabine for BTC was 20.19% (95% CI 14.74% to 25.65%), 55.77% (95% CI 49.02% to 62.52%); 5.94months, 4.98 months, respectively. Results of indirect comparison from 18 uncontrolled studies (538 patients) showed that there were no significant differences in efficacy (ORR, TCR, PFS and OS) between the groups. Results of direct comparison from three controlled studies (579 patients) showed gemcitabine-cisplatin combination prolonged the median time to progression, substantially increased the OS and produced a statistically significant increase in TCR compared with gemcitabine alone.
Conclusions: From this case report, discrepancies between indirect and direct meta-analysis were found. Although indirect meta-analysis might be possible, we must be cautious about the results produced.
Objectives: To investigate if indirect meta-analysis of uncontrolled studies in two independent regimeswas possible and whether the results werecredible.
Methods: Systematic searches were performed in PubMed, The Cochrane Library, EMBASE and ISI Web of Knowledge to identify randomized controlled trials (RCTs) in gemcitabine-cisplatin compared with gemcitabine alone for advanced biliary tract cancer (BTC), or phase II trials reporting on the efficacy detected in gemcitabine alone or in combination with cisplatin for advanced BTC. The pooled results for each outcome of each regime were calculated, and compared using Chi2 analysis. Direct comparisons were also conducted to compare gemcitabine-cisplatin with gemcitabine.
Results: The pooled overall response rate (ORR), T-cell receptor (TCR), mean progression-free survival (PFS) and overall survival (OS) of 10 phase II studies (330 patients) in gemcitabine-cisplatin for BTC was 25.45% (95% CI 20.75% to 30.15%), 52.12% (95% CI 46.73% to57.51%); 9.02 months, 13.65 months, respectively. The pooled ORR, TCR, mean PFS and OS of eight phase II studies (208 patients) in gemcitabine for BTC was 20.19% (95% CI 14.74% to 25.65%), 55.77% (95% CI 49.02% to 62.52%); 5.94months, 4.98 months, respectively. Results of indirect comparison from 18 uncontrolled studies (538 patients) showed that there were no significant differences in efficacy (ORR, TCR, PFS and OS) between the groups. Results of direct comparison from three controlled studies (579 patients) showed gemcitabine-cisplatin combination prolonged the median time to progression, substantially increased the OS and produced a statistically significant increase in TCR compared with gemcitabine alone.
Conclusions: From this case report, discrepancies between indirect and direct meta-analysis were found. Although indirect meta-analysis might be possible, we must be cautious about the results produced.