SBIR-STTR Award

Often sample sizes for randomized clinical trials (RCT) are too small because prior estimates of design parameters are inaccurate. Therefore, a computerized approach to increasing sample size during a RCT without increasing a-level has important commercial applications for organizations that perform RCTS. This project describes a new class of designs for an RCT. The new design designates a portion of the main clinical trial as the internal pilot (IP) study. The sample size may be recalculated based on data from the IP. The final analysis includes data collected during the IP. The project will develop prototype software programs for IP designs. Phase I has three aims:(1) To investigate operating characteristics of a binomial test for a IP trial. The binomial represents distributions with nonindependent sample mean and variance. Numerical integration, checked for accuracy by simulation, will calculate size and power for several types of IP's.(2) To determine by numerical integration for normal distributions the optimal proportion of the planned sample to include in the IP phase.(3) To write a demonstration computer program that designs an IP-RCT using a variety of inputs (e. g. parameters to be recalculated and maximum allowable sample size). Applications to cardiovascular disease will be stressed.Awardee's statement of the potential commercial applications of the research:The research aims ultimately to introduce "plug-in" computer programs to design internal pilot studies for randomized clinical trials. The modules will be add-ons to commonly used computer statistical packages. They will be marketed to drug companies and other organizations conducting clinical trials. Several organizations have expressed interest in such programs.

Thesaurus Terms:
computer processing of clinical data, computer program /software, computer system design /evaluation, statistics /biometry computer simulation, mathematics computer system hardware National Center for Research Resources (NCRR)

Designing a randomized clinical trial (RCT) that incorporates flexible approaches to sample size calculation, data monitoring, early stopping, multiple endpoints, and changing sample size during the trial all while still preserving the stated a-level is computational difficult. Therefore, a computerized approach to the design of an RCT has important commercial application to pharmaceutical companies, both domestic and foreign, and other organizations that perform clinical trials.Phase I studied a new class of designs for an RCT. The new design designates a portion of the main clinical trial as an internal pilot (IP) study. The sample size recalculated the basis of data from the IP. Phase II will continue the work of Phase I in investigating the operating characteristics of IPs for the normal, the binomial, and the log-rank statistics. It will develop a computer program that implements IP studies incorporating the Lakatos method of sample size calculation, the Lan-DeMets a-spending approach to data monitoring, stochastic curtailing, and Bonferroni correction for multiple endpoints.The research component of Phase II will focus on statistical methods for combining the approaches while still maintaining control over alpha and power.Awardee's statement of the potential commercial applieations of the research:The research aims ultimately to introduce a computer program to design randomized clinical trials. The program will be available in two forms. One version will be a stand-arone package while the other will be a module compatible with a clinical database software package currently under development. The program will be marketed to drug companies and other organizations conducting clinical trials.

Thesaurus Terms:
clinical trial, computer assisted medical decision making, method development computer processing of clinical data, health science research analysis /evaluation, longitudinal human study, statistics /biometry computer human interaction, handbook National Institute for Research Resources (NCRR)