Nonrandomized studies Studies with historical controls and the
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Non-randomized studies: Studies with historical controls and the use of Objective Performance Criteria (OPCs) Jeff Cerkvenik Statistics Manager Medtronic, Inc.
Background • “If clinical data are needed, FDA and industry should consider alternatives to randomized, controlled clinical trials when potential bias associated with alternative controls can be addressed. ” • Source: “The Least Burdensome Provisions of the FDA Modernization Act of 1997: Concept and Principles; Final Guidance for FDA and Industry”, Oct. 4, 2002, CDRH ODE and CBER.
Randomized or Non-randomized Considerations • Randomization helps minimize bias. • But, what if patients can’t be blinded? – Consider amount of bias (e. g. , death vs. QOL). • Can evaluators be blinded? • Is a control group necessary for a reasonable evaluation? • Magnitude of change from existing predicate device(s).
Types of Non-randomized Trials • Trials with historical controls • Trials using objective performance criteria (OPC) • Registry trials
Definition • Objective Performance Criteria (OPC) are performance criteria based on broad sets of data from historical databases (e. g. , literature or registries) that are generally recognized as acceptable values. These criteria may be used for surrogate or clinical endpoints in demonstrating the safety or effectiveness of a device. • Source: “The Least Burdensome Provisions of the FDA Modernization Act of 1997: Concept and Principles; Final Guidance for FDA and Industry”, Oct. 4, 2002, CDRH ODE and CBER.
Historical control? • Are historical data available? • Are the populations comparable? – For the primary endpoint, not necessarily demographics.
OPC • How to determine OPC? – Past, similar, approved devices. – Use the point estimate or that study’s OPC? – Statistician’s job? • How do we balance statistical need / sample size / reasonable OPC? – E. g. , if we expect the failure rate to be 5%, should OPC be 10% (n=239) or 15% (n=76)?
