abstract: Assumptions of Expected Benefits in Randomized Phase III Trials Evaluating Systemic Treatments for Cancer

Assumptions of Expected Benefits in Randomized Phase III Trials Evaluating Systemic Treatments for Cancer

Background In designing phase III randomized clinical trials (RCTs), the expected magnitude of the benefit of the experimental therapy (δ) determines the number of patients required and the number of person-years of follow-up. We conducted a systematic review to evaluate how reliably δ approximates the observed benefit (B) in RCTs that evaluated cancer treatment. 

Conclusions Investigators consistently make overly optimistic assumptions regarding treatment benefits when designing RCTs. Attempts to reduce the number of negative RCTs should focus on more realistic estimations of δ. Increased use of interim analyses, certain adaptive trial designs, and better biological characterization of patients are potential ways of mitigating this problem.

Now's the time to find biomarkers on purpose -- Annals of Oncology

"Studies need to be conducted to determine the optimal design for using genome-wide profiling to identify putative biomarkers of drug response. To date, most biomarkers of drug response identified through genome-wide profiling have occurred through retrospective analysis of available tissue. To really progress this field, realistic planning for biomarker discovery and validation in clinical trials needs to be conducted. We, as clinical scientists, need to progress from only using convenient clinical cohorts to identify biomarkers to actually planning and following through with prospective clinical trials whose aims are to discover and/or validate putative biomarkers of drug response. To initiate a study without a realistic plan for discovery and validation reflects a lack of serious desire to find robust clinical predictors.^.... Until this becomes more commonplace, the genomic revolution will be focused on manuscript generation and investigator career development, leaving the benefit to patients nothing more than an unrealized dream."

Trial design for evaluation of novel targeted therapies

"Conclusions:Alternatives to traditional phase II trial design including alternative end points, randomized designs, biomarkers, and imaging tools should allow ineffective agents to be discarded and promising agents to undergo further investigation."