Clinical Coordinating Center

Part of the Cardiovascular Clinical Research Center, NYU School of Medicine

The Clinical Coordinating Center (CCC) within the Cardiovascular Clinical Research Center at NYU School of Medicine is directed by Dr. Judith Hochman with Dr. Harmony Reynolds serving as Associate Director. The CCC will work closely together with all parties to assure a consistent and accessible, (i.e., 24 hours a day, 365 days a year) team and will facilitate communication with the NHLBI, the SDCC, ICC, EQOLCC, other Core Labs, and the enrolling clinical sites through email, shared internet-based databases, webinar, and videoconference services. Advances in technology permit the successful execution of studies by geographically disparate leadership. We have used this model in prior NHLBI-funded trials, SHOCK and OAT.

The CCC functions as a clinical trial center and is responsible for all aspects of conducting trials, including clinical operations; oversight of all committees and working groups; development of the protocol, consent, manual of operations and all amendments; oversight of core laboratories; monitoring of study progress; leadership in data analysis, presentations, and publications. In regards to sites, the CCC will be responsible for site identification and start-up, maintenance of regulatory documents, certification of personnel, recruitment, education, and retention; quality control; site management and monitoring; site reimbursement; data quality and enrollment by country and site; and staffing a 24 hour HelpLine for questions from clinical sites and prevention of crossovers.

Clinical Operations is the critical functional component of the CCC. Members of this team assigned to your study will provide project management; development and preparation of study materials; site management and monitoring; education of all site-based personnel on the rationale, design, and execution of the trial study; oversight of a 24-hr helpline, including documentation and generation of frequently asked questions; and assistance with preparation of manuscripts and publications. The CCC will be responsible for resolution of queries received from the SDCC for missing and questionable data and the identification of trends in data fields that may require additional clarification and training.  

The CCC will be the primary day-to-day contact for sites. CCC staff will develop and implement educational and training plans, communication initiatives including phone and email contact, conference calls, newsletters, website, and social networking media. The CCC staff will collaborate with the sites to assure their understanding of the protocol, the operationalization of the protocol, and the successful identification of eligible patients for screening and enrollment. These project team members bring to the trial substantial operational experience from working on many other multicenter randomized controlled studies. The CCC expects that our efforts to significantly vet sites for interest and capabilities, to extensively educate sites, and to carefully and clearly state the expectations for sites will minimize problems with sites’ performance. For the most part, CCC staff will execute all calls to sites regarding quality or other issues noted by any center or core lab. Exceptions are noted (e.g., imaging technician training). CCC staff will conduct site monitoring centrally by review of copies of source documents. However, when site problems arise that cannot be handled by phone and email, CCC will coordinate with SDCC staff to conduct site visits together.

An important asset to the site management component of the CCC will be the utilization of a project management web-based application that will provide CCC and SDCC project teams with direct access to trial data and can be used to manage various aspects of the study, including: protocols, accounts, contracts, sites, site monitoring, and subject management.  Using this centralized system will ensure an integrated approach to handling trial information and will help the CCC and the SDCC work together seamlessly. 

Detailed Description of Featured CCC Responsibilities

  1. Site Preparation, Start-up, Development of Study Documents, Training, and Education: The CCC will be responsible for working with investigators, the SDCC, ICC, EQOLCC, core laboratories, NHLBI and the NHLBI-appointed DSMB to finalize the study protocol and template consent forms.  The CCC will be responsible for the development, distribution, storage, and submission of all regulatory materials. The CCC will assure that study personnel are trained on the required regulations and documentation for your trial.

     

    The CCC will be responsible for all educational and site communication efforts:  design, production, and implementation of in-person and web-based Investigator and Coordinator training; development and distribution of PowerPoint slide set describing rationale and design of the trial; production of multimedia newsletters; ongoing training through conference calls and web sessions with coordinators; in-person training and annual study meetings and individual meetings with investigators and coordinators attending cardiology professional society meetings; materials to facilitate enrollment of eligible patients, and patient education materials.

  2. Evaluation of Sites Prior to Study Initiation: Sites have completed a survey of their capabilities for patient recruitment, imaging, and intervention, and of the sites’ procedural volumes (stress imaging, CCTA, cardiac catheterization, percutaneous and surgical revascularization). Additional review of sites’ personnel, ability to collaborate across specialties, and availability of technologies to assure seamless transmission of images will occur before study initiation. In addition, we will reaffirm commitment to the trial and will recruit additional sites before study initiation. This will take place in year one prior to site IRB review or contracting. CCC staff will also review procedural outcome data and volumes for individual site operators—interventional cardiologists and cardiac surgeons who will perform procedures on trial-enrolled patients. They must be trial-certified according to criteria which will be finalized before study start-up.
  3. Site Management and Monitoring: The CCC will oversee activities at all sites with the assistance of country and regional leaders. In the US, the CCC will monitor a percentage of patients’ source documents at the time of enrollment; monitoring site visits in the US will be performed by the SDCC.  In general, country/regional leaders will conduct on-site monitoring visits for international sites. Central review of source documents for international sites will be performed either by the country leader’s   staff (in the native language) or at NYU.  When a country leader is not identified within a country, a regional leader’s staff will assist with those sites. Country/regional leader staff will be paid according to formulas based on tasks performed.
  4. Training Meetings: Sites will send a coordinator for training at an in-person Coordinators’ Training Meetings. Selected countries will have investigators attend these in-person training meetings. All other investigators (noninvasive cardiologists, interventionalists and surgeons, stress imaging and CCTA technicians and staff) will be trained initially by webinar meetings. All study staff are required to be trained before site initiation. These meetings will be archived through the trial website and web-based meetings to be conducted as needed for new site training or re-training. Two meetings will be held in North America to accommodate sites from different time zones. Training meetings outside of North America will be held in locations that are cost efficient to support regional education on the trial.  In countries where sites prefer a web-based forum for investigators, we will accommodate this request while still holding an in-person coordinators’ meeting. Sites that are unable to attend an in-person meeting, e.g., they join the trial after the initial start-up phase, will also be trained by webinar, and will be supplemented by a start-up teleconference, and/or by Internet-based technology that allows video and audio conferencing. 
  5. Committees/Organization
    a. Steering and Executive Committee Meetings (held back to back in the same venue):  The CCC will be responsible for planning, organization, execution, and minutes of the Steering Committee meetings. In addition, there will be regular conference calls for the Steering Committee.
  6. Other Web-based Meetings:  The CCC will develop and host 2 webinar meetings per year to update sites/investigators and coordinators who are not able to attend one of the Investigators’/Coordinators’ meetings that will be held at professional society meetings. These have special capability to be archived for the website and accessed by staff who could not attend the scheduled session. In addition, any protocol amendments will be reviewed on webinar meetings.
  7. Website Design:  The CCC will be responsible for creative direction, oversight, and development of content based on the communication and educational needs of the site personnel. The website will support at least 2,000 (2 investigators/site, 1 coordinator/site, Steering Committee, DSMB, CCC/SDCC staff) users and will be regularly updated with study news including enrollment, peer reviewed literature supporting the optimal medical therapy study drugs, new techniques in PCI/CABG, enrollment tips, reminders for those completing case report forms, and other documentation.  The website will contain archived meetings, study documents, publications and references for study rationale, meeting minutes, educational materials, calendars, reminders, and newsletters.  While there will be publicly available information on the trial website with a link to www.clinicaltrials.gov, there will be password protected information, study-related documents, minutes of and recorded calls of key meetings, videos of the training meetings, and educational information. The website will also provide a link into the e-CRF portal for CRF completion.  
  8. Site Administrative Payments and IRB Fees: Funding is allocated per site to cover costs associated with study start-up activities. These funds are to support study coordinator work associated with regulatory documentation, team meetings to review processes and procedures related to the trial, and contacts with the CCC.  IRBs in the United States are expected to waive the IRB fee for NIH-funded studies. The CCC will contract with a central IRB to assist sites that do not have a local IRB. The administrative payment also covers work associated with close out.
  9. Per Patient Site Payments: The trial per patient payment to sites includes funding for coordinator time spent in screening, enrollment, arranging procedures, transfer of imaging studies to the image processing center for interpretation, follow-up, completion of case report forms, resolution of data queries, and collection and reporting of events and crossovers. The per patient payment to the sites is structured to include work associated with patients who are screened, enrolled, and had the stress imaging study uploaded for core lab review and/or complete the CCTA and upload for core lab review, but who are found to be ineligible and therefore not randomized. These CCTAs will be reimbursed by the study. A payment is also provided for coordinator work to enroll patients in the Registry. See “Payments to Sites” for details of the structure of per-case reimbursements. 
  10. Tests and Procedures: Tests that are not part of standard of care (CCTA) will be reimbursed by the study. Procedures that are part of standard of care (medical therapy, invasive coronary angiography and revascularization) will not be reimbursed by the study.
  11. Site Contracts and Payments: The trial account manager will be responsible for site payments throughout the trial to sites and to the country/regional leaders. We will pay funds to a few country leaders to issue payments to their sites for per case reimbursement, startup costs and reimbursement for CCTA acquisition, and oversee these activities.
  12. Oversight of resupply of donated products and troubleshooting if site problems are encountered.
  13. Manuscript Preparation:  The CCC Publications team will be primarily responsible for assignment of lead authors and co-authors for all manuscripts and presentations deriving from trial results. The CCC publication team will oversee manuscript preparation from the data request stage through writing of the paper, incorporation of comments from co-authors and the publications committee and preparation for journal submission and re-submission, as needed. The CCC will liaise between lead authors and the SDCC, which will prepare tables and graphical summaries, assist in the interpretation of the results, and summarize the statistical methods for the final manuscripts. 

Management of Regions
Management of U.S. Sites

Depending on the number of enrolling centers, management of sites will be more effective if divided into regions, which co-investigators will be responsible for site management and monitoring by the CCC. A team of a clinical research associate, clinical trial assistant and other staff, and a CCC investigator will manage each region. This structure will foster development of a strong relationship between the CCC and site research staff. Each team will review site screening logs, enrollment and protocol compliance performance reports, quality of studies sent to core labs, data quality, and protocol-specified severe adverse event summaries for sites in their region. The team will be responsible for all site contact within each region. The Principal Investigator will oversee this as well as advise the Study Chair of all regions and sites that should participate. This model has been effective in numerous trials the study leadership has led.

Structure of Enrolling Centers
The optimal approach for trial success involves a multidisciplinary team, with support from primary care MDs, noninvasive cardiologists, interventionalists and cardiac surgeons. The primary point of patient identification will most often be the stress imaging labs and training study investigators in imaging criteria is important; therefore, at least one noninvasive cardiologist will play a lead role at each site. Interventional cardiologists are often contacted with referrals and need to be engaged and supportive, and high quality PCI must be ensured; therefore a lead interventionalist will be designated. One of these individuals will serve as site principal investigator and will take responsibility for regulatory documentation and completion of data forms and the other usual duties of site principal investigators, including protection of human subjects. A lead cardiovascular surgeon will be identified at sites where cardiac surgery will be performed to ensure trial certification of surgeons who perform high quality surgery.

Participating Country Coordination depending on study protocol and trial study

Country Leaders
The CCC maintains responsibility for the conduct of the study, site management, and site monitoring in North America and Europe. The CCC will review reports generated by the SDCC with country leaders at least quarterly to provide information regarding performance in enrollment, including enrollment of women and minorities, data completeness and quality, protocol violations, patient withdrawals of concern (e.g., after CCTA when the CT core laboratory approved the patient for enrollment), appropriate selection and completeness of revascularization, and status of regulatory documents. The CCC and country leaders will work together to formulate corrective action plans as needed for concerns in any of these areas. CCC will take the lead in implementation of such action plans with assistance from the Country leaders as needed.

The CCC team can brings together an extremely experienced and committed group of international thought leaders in cardiology who will lead sites in their respective countries. They have assisted with and will assist with site selection, site education, enrollment of patients, retention of patients, assurance of high quality imaging, PCI and CABG, and the procurement of high-quality data.