Considerations and Recommendations for the Introduction of Objective Performance Criteria for Transcatheter Aortic Heart Valve Device Approval

Abstract

Abstract-In the United States, new surgical heart valves can be approved on the basis of objective performance criteria (OPC). In contrast, the US Food and Drug Administration traditionally requires stricter criteria for transcatheter heart valve (THV) approval, including randomized, clinical trials. Recent US Food and Drug Administration approval of newgeneration THVs based on single-arm studies has generated interest in alternative study approaches for THV device approval. This review evaluates whether THV device approval could follow a pathway analogous to that of surgical heart valves by incorporating OPC and provides several considerations and recommendations. Factors to be taken into account in the construction of OPC include the maturity of THV technology, variability in transcatheter aortic valve replacement practice, end points included as OPC, follow-up terms for specific OPC, patient populations to which these OPC apply, and (statistical) methods for OPC development. 4 This review provides an overview of OPC, considers the potential role of OPC for THV device approval, and discusses the challenges associated with such an approach. Several recommendations for the future implementation of OPC for THV devices are provided. Objective Performance CriteriaTraditionally, 2 methods of establishing a comparator for single-arm studies have been used: OPC and performance goals (PGs; Table 1). OPC are linearized event rates of safety end points that are derived from historical controls included in meta-analyses of available data. A PG, on the other hand, represents a single point estimate considered sufficient as a comparator. In general, the process of developing a PG is less formal than the process of developing OPC. Therefore, compared with PGs, OPC are thought to be superior because of the increased maturity of device technology and the more robust data from which the comparator is developed.5 For the FDA to allow a device to be considered for approval with OPC, it should fulfill a number of criteria: (1) The device technology should be sufficiently mature; (2) the meta-analysis from which event rates are derived should include an accumulation of studies and all relevant literature from different devices; (3) the OPC should not be developed by companies using only their own data; and (4) the OPC must be contemporary and updated regularly because technology may become obsolete over time, thereby attenuating the rigor and relevance of the OPC. OPC DevelopmentThe OPC for surgical valves were conceived, subsequently developed, and then implemented after 2 major RCTs evaluating mechanical and biological prostheses did not identify significant safety concerns.1 It was thus recognized that traditional randomized evaluations were not feasible because of the large sample sizes required to identify infrequent events. Such large RCTs would also greatly impede the timely introduction of technological advancements to the market. 7 In 1993, the FDA convened an expert workshop to consider alternative study designs for regu...

Characteristics of surgical prosthetic heart valves and problems around labeling: A document from the European Association for Cardio-Thoracic Surgery (EACTS)—The Society of Thoracic Surgeons (STS)—American Association for Thoracic Surgery (AATS) Valve Labelling Task Force

“…''ISO 5840:2015'' provides recommendations and requirements for preclinical and clinical evaluations of SHVs, 2 and it defines valve-related objective performance criteria according to linearized event rates of key safety end points (thromboembolism, valve thrombosis, hemorrhage, paravalvular leakage, and endocarditis). 2,5,6 Furthermore, ISO provides guidance on labeling by describing the information that should be available on the product labels and in the IFU, including detailed information on intended use, indications/contraindications and warnings, and physical and performance characteristics. 2…”

“…''ISO 5840:2015'' defines objective performance criteria for bleeding and thromboembolic events for the clinical evaluation of SHVs. 2,5,6 North American and European clinical practice guidelines provide recommendations on postprocedural anticoagulation after mechanical and bioprosthetic valve FIGURE 7. Pressure recovery.…”

Characteristics of Surgical Prosthetic Heart Valves and Problems Around Labelling: A Document From the European Association for Cardio-Thoracic Surgery (EACTS)–The Society of Thoracic Surgeons (STS)–American Association for Thoracic Surgery (AATS) Valve Labelling Task Force

“…The current 2015 version (ISO 5840:2015, Cardiovascular Implants-Cardiac Valve Prostheses) consists of 3 parts: 'part 1: general requirements, part 2: surgically implanted heart valve substitutes and part 3: heart valve substitutes implanted by transcatheter techniques'. 'ISO 5840:2015' provides recommendations and requirements for preclinical and clinical evaluations of SHVs [2], and it defines valve-related objective performance criteria according to linearized event rates of key safety end points (thromboembolism, valve thrombosis, haemorrhage, paravalvular leakage and endocarditis) [2,5,6]. Furthermore, ISO provides guidance on labelling by describing the information that should be available on the product labels and in the IFU, including detailed information on intended use, indications/contraindications and warnings, and physical and performance characteristics [2].…”

“…The risk of bleeding and thromboembolic events after SHV implantation depends on the type and anatomical position of the prosthesis, anticoagulation strategy and patient-related risk factors, such as haematological disorders, arrhythmias and cardiac chamber dilatation or function. 'ISO 5840:2015' defines objective performance criteria for bleeding and thromboembolic events for the clinical evaluation of SHVs [2,5,6].…”

Creation of objective performance criteria among medical devices

“…New regulatory approaches, such as the creation of objective performance criteria (OPC), which allow for the swift approval of new devices while simultaneously ensuring that all devices entering and currently on the market demonstrate a reasonable assurance of safety and effectiveness have been explored. [3][4][5][6] These numerical targets of outcomes of interest are derived from existing data and can be leveraged as comparators for the assessment of safety and efficacy. 6 Many stakeholders benefit from OPC during the premarket approval process and WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?…”