International Center for Health Outcomes and Innovation Research (InCHOIR) is a clinical and data coordinating center with an interdisciplinary faculty. InCHOIR faculty are expert in study design, clinical coordination, regulatory approval and management, endpoint and event adjudication and Data Safety and Monitoring Board management. In addition, faculty has expertise in data management, statistical analysis, health economics, and FDA-compliant web-based electronic data capture systems.
The trials that InCHOIR faculty have conducted over more than a decade past, beginning with the REMATCH trial that established LVADs as destination therapy for advanced heart failure patients, have shaped treatment paradigms. Our recent research in the surgical treatment of ischemic mitral valve disease and atrial fibrillation which was recently published in a series of papers in The New England Journal of Medicine, is changing recommendations for the use of these interventions. Since 2008, the Center has been awarded over $91 million in federal and industry funding.
Translational Clinical Trial Capabilities
InCHOIR has substantial expertise in first-in-human trials and other early phase investigations. The Center successfully competed to become the Data and Statistical Coordinating Center for an NIH-funded Specialized Clinical Center of Research (SCCOR) grant, which focused on bringing basic scientists and clinical investigators together in the development of treatments for patients with advanced heart failure. The Center has conducted early phase trials with novel mechanical circulatory assist devices, mesenchymal precursor stem cells and gene therapy for cardiac regeneration. Our faculty participates in the Spotrias National Network, which performs early phase clinical studies of new approaches for acute stroke.
Confirmatory and Comparative Effectiveness Trials
The Center has an extensive research portfolio of confirmatory and comparative effectiveness trials (see Table 1). InCHOIR, for example, was the coordinating center for the National Heart, Lung, and Blood Institute (NHLBI) that sponsored the REMATCH trial which established the value of left ventricular assist devices (LVADs) as long-term treatment, or destination therapy for advanced heart failure.
InCHOIR was also the coordinating center for a randomized trial comparing conservative management to prophylactic eradication of unbled brain arteriovenous malformations in Europe, Australia, North and South America, and Asia. As a result, one new development has been the formation of large clinical trial networks which address a shortcoming in the clinical trial enterprise that were often one-off investigations where the infrastructure was dismantled after the trial ended. By contrast, the resulting new federally funded Networks provide an infrastructure with a coordinating center and multiple core and consortium sites to conduct multiple trials over 5-year periods. These trials offer the opportunity for renewal.
Modeling this new trial structure, InCHOIR is currently the Data and Clinical Coordinating Center for the renewed NIH- and CIHR-funded Cardiothoracic Surgical Trials Network which conducts trials of common procedures for which the evidence base is weak. The Center developed particular platforms of expertise such as research on valve disease (including ischemic mitral valve disease, aortic valve disease, and tricuspid regurgitation), and atrial fibrillation (including surgical ablation for AF, and management of postoperative atrial fibrillation).
Expertise in Design, Conduct, and Analysis of Novel Trials
The Center’s analytical expertise includes survival analysis, analysis of composite endpoints (such as MACCE), development and validation of risk scores, the analysis of imaging data and biomarkers, and economic analysis, including cost-effectiveness analysis.
The Center contributes actively to the methodology of design and analysis of clinical trials, including novel adaptive trial designs, combining information from randomized and nonrandomized observations (using both classical and Bayesian methods), the use of Bayesian methods to interpret the uncertainty associated with cost-effectiveness ratios, and adaptation of longitudinal methods for analyzing quality of life. The Center was an early innovator in the use of remote, electronic data capture during the 1990s, and has developed proprietary electronic data capture software with features and functionality that facilitate large scale international trials. In addition to compliance with federal regulations (FISMA) the system provides specimen tracking, clinical imaging management, task management, and committee management (DSMB, Adjudication) among other features. The screenshot above, from the ARUBA trial, demonstrates an image-reading assessment tool.
In recent years, concerns have risen about the inefficiency and high cost of the clinical trial enterprise. On the forefront of efforts to address these concerns, the Center has substantially reduced the costs of trial monitoring by obtaining direct, remote access to the electronic health record of its participating clinical centers, obviating the need for on-site monitoring visits and document transfer. It has also developed registry-based trials, which promise to substantially reduce the cost of conducting trials while maintaining their rigor. We have, for example, been funded by NHLBI for a pragmatic trial of hybrid coronary revascularization (PCI plus CABG), which utilizes data from the existing STS and ACC-CDRN clinical registries and other sources.
Large Dataset Unit
To respond to renewed interest in using large-scale administrative datasets coupled with clinical databases to conduct clinical evaluative research, the Center has developed an extensive library of administrative and clinical datasets and experience in analyzing claims and survey data that include Medicare, Medicaid, private payers, Premier, University Hospital Consortium, statewide discharge databases, NIS and NHDS. These databases, available to clinical investigators throughout the medical center, offer a mechanism to:
- Provide a real-time look at changes in utilization rates of clinical interventions and geographical variations in their use, which can be used to generate new hypotheses
- Provide supplementary claims data for economic analysis in clinical trials
- Extrapolate the potential impact of clinical trials findings to the national level
- Undertake comparative effectiveness research.
In papers published in leading journals (such as JAMA), the Large Dataset Unit has addressed important clinical issues, in domains such as the quality of obstetrical care, bioprosthetic versus mechanical valves in younger patients, and cancer care. The department analyzes these data in collaboration with a broad range of clinical investigators from the Mount Sinai Health System.