The National Heart, Lung, and Blood Institute (NHLBI) hosted the Data Coordinating Centers’ Best Practices Working Group on May 24-25, 2011 to identify and create a compendium of best practices for Data Coordinating Centers (DCC) that support large clinical trial programs such as Networks or multicenter clinical studies. The compendium will serve as a resource to NHLBI Program Staff for crafting application and review criteria for RFAs/RFPs and when evaluating DCCs as part of a large clinical trial program. This document focuses upon DCCs which partner with extramural investigators through grant mechanisms and with the NHLBI through contract mechanisms, and does not address Clinical Research Organizations which contract to recruit study sites.
The DCC is often the nucleus for the success of a large clinical research program. The DCC brings expertise in clinical trial design and conduct needed to complement the clinical investigators’ content expertise, and structure and quality standards to the design and conduct of a trial. An effective DCC collaborates in protocol development and takes responsibility for statistical design including sample size calculations and data analysis strategy. The DCC provides common questionnaires, data collection forms and data management; statistical analysis; collaborates in manuscript preparation; and provides overall study training, coordination and quality assurance, including coordination of the activities of the Data and Safety Monitoring Board (DSMB), the Protocol Review Committee (PRC), the Steering Committee, and other standing committees. Additional activities may include selection and evaluation of clinical center awardees; support of ancillary study activities; procurement of services related to core labs, study drug acquisition and distribution; support of websites or online resources for the program; and commonly for NHLBI awardees, management and distribution of protocol dollars.
Since DCCs play a pivotal role in coordinating and executing large, expensive clinical trial programs, it is imperative that NHLBI identify and require best practices for DCCs funded to support these programs. Ensuring we have quality DCCs will require that we:
- Understand the current capability of DCCs.
- Identify minimum requirements for a DCC to support a large clinical program.
- Adopt best practices that all DCCs should follow.
- Understand the costs associated with specific functions or practices.
Principal Investigators and staff from DCCs with diverse business models, organizational structures and funding histories in grants versus contracts convened with NIH staff to share best practices and create a compendium. The meeting began with a discussion of the importance of effective partnerships between the Program Office, the DCC and the research teams conducting the study. Establishing effective interactions, frequent and regular communication and mutual respect were considered key elements when initiating a large clinical research program. Developing a vision for the program, clarifying expectations and roles allows each party to collaborate effectively, complementing rather than competing with one another. WG members felt that DCCs should be “enablers”, facilitating activities within the program. At the same time, they felt it necessary that NHLBI and investigators be realistic about what could or could not be done and desired a Program Office partner with experience in clinical trials who would understand the complexities and trade-offs that might be necessary.
The group then focused on best practices in four broad areas: trial operations; human subjects protection and regulatory affairs; data management and analysis; and quality control/quality assurance. This was followed by a discussion of costs associated with the activities in these areas. The group agreed that all parties must have a clear understanding of the costs involved in clinical trials, and that better ways of projecting and managing these were potential areas for improvement. Costs impacting the DCCs include federal regulations affecting clinical trials (e.g., registering trials, updating information and supplying results in ClinicalTrials.gov, FISMA); unanticipated requests from DSMBs for additional analyses; and additional requests by investigators to change a data form, support an ancillary study or to extend a trial due to poor enrollment. Costs impacting the NHLBI include unpredictability of the federal budget; restrictions on funding options; variability in costs over time; difficulties projecting actual costs; and fiscal implications of delays in enrollment. The WG felt that all parties could do a better job of being transparent by discussing these issues as projects progress and should be innovative in approaches to cost containment (e.g., utilizing already existing data forms, collecting only necessary data).
On the second day of the meeting, small break-out groups convened to identify best practices in each of the four topic areas in preparation for the development of a “Compendium of DCC Best Practices”.
While the WG was asked to focus on developing a specific product (Compendium of DCC Best Practices), members also had a number of recommendations that they felt would enhance the ability of NHLBI to procure competent, efficient DCC partners. The recommendations are not listed in any order of priority.
- NHLBI should ensure that Program Staff managing large clinical programs have the necessary knowledge and skills to do so effectively. Training opportunities can be sought in newly developed or existing courses, webinars or websites, mentoring opportunities, and working as part of a clinical project team to obtain experience. Training and mentoring opportunities should focus on identifying expectations and aligning the vision of all project stakeholders, addressing costs of running large clinical programs, task division, tips to advance the objectives of the project and clinical trial methodology and management.
- Conducting a clinical trial is clearly a team effort with every member in the study team lending different support to the various aspects of the trial. NHLBI should leverage the diverse expertise within the Institute and manage large clinical programs and network studies with internal teams. This will also ensure consistency in trial management and transfer of Institute historical knowledge as attrition increases and will facilitate mentorship opportunities for new program staff
- NHLBI staff must be proactive in establishing effective communication with all project stakeholders prior to commencement of a project. Pre-award site visits to DCCs should be mandated for each large clinical program and would allow DCC capabilities to be assessed, promote effective communication and a cross-disciplinary team approach and outline clear expectations prior to any final commitment.
- Interim analysis of DCC performance should be mandatory either through an evaluation tool, in-person site visit or both. Evaluations may include report cards and appropriate metrics.
- NHLBI should institute post-project debriefings that would include Program staff, DCC staff, clinical staff and DSMB members to assess the project’s success or failure, optimal use of funds and lessons learned which should then be shared for future project planning.
- NHLBI should undertake efforts to capture costs more effectively when proposing new projects. By analyzing data already available on NHLBI-funded studies, information could be obtained about approximate costs, additional costs needed and unexpected costs encountered. Alternatively, NHLBI might consider inviting individuals from the pharmaceutical industry with expertise in costing projects to train NHLBI staff in this area. The WG suggested that as part of a contract, proposals include a statement about whether funds are adequate or not and why. This would not be subject to review, but could help NHLBI to understand cost implications for a particular project.
- NHLBI should strongly consider funding registries (as appropriate), which can serve to identify a patient population for future research and as a platform for training clinicians to handle data and plan efficient studies with adequate numbers of eligible patients.
Publication of the “Compendium of DCC Best Practices” will be available on the NHLBI public website when completed. The WG agreed that publishing the proceedings from this meeting could be beneficial to the clinical trials community and will explore this further once the Compendium is publically available.
Day 1 meeting proceedings were recorded and may be viewed here: NIH Videocast.
Participating Institute and Organizations
This WG was sponsored by the National Heart, Lung, and Blood Institute. Individuals from each Division within NHLBI and from other NIH Institutes (National Cancer Institute, the National Institute of Allergy and Infectious Diseases, the National Institute on Drug Abuse and the National Institute of Child Health and Human Development) contributed to planning the WG.
Meeting agenda PDF (49 kb)
- Sonja McKinlay, Ph.D., President, New England Research Institutes
- Kerry Lee, Ph.D., Director, Biostatistics, Duke Clinical Research Institute
Working Group Members
- Katrina Billingsley, M.P.H., M.B.A., The GW Biostatistics Center
- Robert Byington, Ph.D., Wake Forest School of Medicine
- Jack Cahill, M.A., Westat, Inc.
- Diane Catellier, RTI International
- Stephanie D Davis, M.D., University of North Carolina
- Marsha Hasson, M.S., Westat, Inc.
- Mary Horowitz M.D., M.S., The Medical College of Wisconsin
- Sheryl Kelsey, Ph.D., University of Pittsburgh
- Selma C. Kunitz, Ph.D., KAI Research, Inc. (KAI)
- Curtis Meinert, Ph.D., Johns Hopkins University
- Marissa Miller, D.V.M., National Heart, Lung, and Blood Institute
- Michael E. Miller, Ph.D., Wake Forest School of Medicine
- Daniel Molina, PharmD., Technical Resources International, Inc.
- Sara L. Pressel, M.S. University of Texas Health Science Center
- Donald Stablein, Ph.D., The EMMES Corporation
- Elizabeth Thom, Ph.D., The George Washington University Biostatistics Center
- Bruce Thompson, Ph.D., Clinical Trials & Surveys Corporation (C-TASC)
- Foss Tighe, M.P.H., New England Research Institutes
- Elizabeth L. Wagner, M.P.H., National Heart, Lung, and Blood Institute
NHLBI Staff Contacts
- Victoria Pemberton, firstname.lastname@example.org
- Katharine Cooper-Arnold, email@example.com
- Myron Waclawiw, firstname.lastname@example.org
- Julie Bamdad, email@example.com
Last Updated August 2011