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10.1093/annonc/mdx045 http://scihub22266oqcxt.onion/10.1093/annonc/mdx045 C5834117!5834117!28200082     free     free     free Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 259.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 259.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Ann+Oncol 2017 ; 28 (7): 1427-35 Nephropedia Template TP {{tp|p=28200082|t=2017. Statistical controversies in clinical research: building the bridge to phase II?efficacy estimation in dose-expansion cohorts |pdf=|usr=}}{{28200082}} gab.com Text Statistical controversies in clinical research: building the bridge to phase II efficacy estimation in dose-expansion cohorts JO: Ann Oncol http://www.kidney.de/pget.php?&tw=1&pmid=28200082 #FOAvip Background: Regulatory agencies and others have expressed concern about the uncritical use of dose expansion cohorts (DECs) in phase I oncology trials. Nonetheless, by several metrics?prevalence, size, and number?their popularity is increasing. Although early efficacy estimation in defined populations is a common primary endpoint of DECs, the types of designs best equipped to identify efficacy signals have not been established. Methods: We conducted a simulation study of six phase I design templates with multiple DECs: three dose-assignment/adjustment mechanisms multiplied by two analytic approaches for estimating efficacy after the trial is complete. We also investigated the effect of sample size and interim futility analysis on trial performance. Identifying populations in which the treatment is efficacious (true positives) and weeding out inefficacious treatment/populations (true negatives) are competing goals in these trials. Thus, we estimated true and false positive rates for each design. Results: Adaptively updating the MTD during the DEC improved true positive rates by 8?43% compared with fixing the dose during the DEC phase while maintaining false positive rates. Inclusion of an interim futility analysis decreased the number of patients treated under inefficacious DECs without hurting performance. Conclusion: A substantial gain in efficiency is obtainable using a design template that statistically models toxicity and efficacy against dose level during expansion. Design choices for dose expansion should be motivated by and based upon expected performance. Similar to the common practice in single-arm phase II trials, cohort sample sizes should be justified with respect to their primary aim and include interim analyses to allow for early stopping. Twit Text FOAVip Statistical controversies in clinical research: building the bridge to phase II efficacy estimation in dose-expansion cohorts ????Ann Oncol http://www.kidney.de/pget.php?&tw=1&pmid=28200082 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28200082 #FOAvip English Wikipedia <ref>{{Cite pmid|28200082}}</ref> Statistical controversies in clinical research: building the bridge to phase II?efficacy estimation in dose-expansion cohorts #MMPMID28200082 Boonstra PS; Braun TM; Taylor JMG; Kidwell KM; Bellile EL; Daignault S; Zhao L; Griffith KA; Lawrence TS; Kalemkerian GP; Schipper MJ Ann Oncol 2017[Jul]; 28 (7): 1427-35 PMID28200082show ga Background: Regulatory agencies and others have expressed concern about the uncritical use of dose expansion cohorts (DECs) in phase I oncology trials. Nonetheless, by several metrics?prevalence, size, and number?their popularity is increasing. Although early efficacy estimation in defined populations is a common primary endpoint of DECs, the types of designs best equipped to identify efficacy signals have not been established. Methods: We conducted a simulation study of six phase I design templates with multiple DECs: three dose-assignment/adjustment mechanisms multiplied by two analytic approaches for estimating efficacy after the trial is complete. We also investigated the effect of sample size and interim futility analysis on trial performance. Identifying populations in which the treatment is efficacious (true positives) and weeding out inefficacious treatment/populations (true negatives) are competing goals in these trials. Thus, we estimated true and false positive rates for each design. Results: Adaptively updating the MTD during the DEC improved true positive rates by 8?43% compared with fixing the dose during the DEC phase while maintaining false positive rates. Inclusion of an interim futility analysis decreased the number of patients treated under inefficacious DECs without hurting performance. Conclusion: A substantial gain in efficiency is obtainable using a design template that statistically models toxicity and efficacy against dose level during expansion. Design choices for dose expansion should be motivated by and based upon expected performance. Similar to the common practice in single-arm phase II trials, cohort sample sizes should be justified with respect to their primary aim and include interim analyses to allow for early stopping. äStatistical controversies in clinical research: building the bridge to(epmc).pdf DeepDyve Pubget Overpricing