The Cytel blog keeps you up to speed with the latest developments in biostatistics and clinical biometrics.
Cytel has published a new whitepaper on Monte Carlo Simulations for Patient Recruitment, which illustrates how a technique already popular within industrial and business environments is now changing the game of data-driven patient enrollment forecasting.
According to a recent Impact Report from the Tufts Center for the Study of Drug Development, 21% of active clinical trials improve trial success rates and cut operating costs by designing trials with simple adaptive elements like sample size re-estimation and opportunities for early stopping.
Cytel Senior Biostatistician Zoran Antonjevic, who also chairs the DIA’s Adaptive Design Scientific Working Group (ADSWG), says the CSDD's findings come very close to the numbers reported by the ADSWG. The ADSWG recently updated its published findings in a Therapeutic Innovation & Regulatory Science article entitled, ‘Adaptive Design: Results of 2012 Survey on Perception and Use.’ The Survey team, led by Cytel statistician and Senior Director Caroline Morgan, used a variety of source material to report on adaptive designs in clinical trials between 1996 and 2012.
The core methodological problem that would eventually spur the development of Cytel’s StatXact software was first posed by Harvard’s Marvin Zelen at a computational seminar in the late 1970s. Zelen, a distinguished professor of statistical sciences and head of the Department of Biostatistics at Harvard University, was also serving as the Director of the Dana Farber Cancer Institute.
The analysis of serious adverse events from cytotoxic agents in oncology trials were heavily dependent on an imprecise Cochran rule to measure the signifincance of small sample categorical data. The crude calculation meant that estimations of p-values were wide off the mark. Zelen challenged his students to find ways to expand Fisher’s exact test to r x c contingency tables, and by doing so to seal the promise of more effective development and delivery of urgent cancer treatments.
Cyrus Mehta and Nitin Patel took up Zelen’s challenge, publishing a series of papers on exact significance testing throughout the 1980s. Despite offering novel statistical solutions to persisting problems, the implementation of such solutions clearly required assistance from software. Unfortunately, few venture capitalists were willing to invest in a package of arcane statistical tests that were largely still in development.
Cytel was created with a grant from the National Cancer Institute, with a view to developing software that would make newer exact tests widely available for clinical studies. Its first software package, StatXact, is now used for exact testing in oncology, as well as environmental studies, public health, demography, law, and several areas of medicine and clinical development. The widespread use of exact tests has led to an array of intriguing research questions involving the power of various exact tests. Below we present a favorite finding, on the power of conditional versus unconditional exact tests: