Sample Size Requirements For Clinical Trials Of Transcatheter Valve Replacement And Valve Repair Devices

Objectives: To provide the scientific basis for the sample size required for clinical trials of new transcatheter replacement valves and valve repair devices.Background: For regulatory approval of surgically implanted valves, linearized rates of individual types of adverse events with a new valve are compared to the average rates of the same events with previously approved valves, known as objective performance criteria (OPC). OPC are used to calculate the sample sizes necessary for regulatory submission.Methods and recommendations: OPC do not exist for transcatheter valves and valve repair devices because average adverse event rates have not yet been determined. Therefore an alternative approach was devised without the benefit of historical OPC, by calculating the number of patient-years necessary to detect adverse event rates within an "acceptable" range. For example, 400 patient-years of follow-up would detect an adverse event rate of 2.4%/patient year. For consistency with the ISO standard for surgical valves, a minimum sample size of 150 patients followed for at least 1 year and a minimum follow-up of 400 patient-years is recommended unless the manufacturer can adequately justify (using the table provided) a smaller number of follow-up years based on the expectation of a higher adverse event rate in a high risk population.Conclusions: It is hoped that the calculated sample size requirements already incorporated into ISO 5910:2018 (valve repair devices) will also be incorporated into forthcoming revision of ISO 5840-3 (transcatheter valve replacement devices), and that they should facilitate regulatory assessment.