NHLBI Workshop
Clinical Research United in Successful Enrollment (CRUiSE)

December 7-8, 2010

The National Heart, Lung, and Blood Institute (NHLBI) and co-sponsors convened a two-day workshop on December 7 and 8, 2010 in Bethesda, MD, to address successful recruitment and retention in Phase III & IV clinical trials. Three key areas were addressed: 1) public and professional awareness and acceptance of clinical trials; 2) human subject research policies, guidelines, and reimbursement; and 3) clinical trial enrollment experience and practice. Seventy-five participants including invited speakers representing clinical researchers, private advocacy groups, federal sponsors and regulatory agencies, and industry attended.

Discussion

The ability of the current domestic clinical trial infrastructure to carry out clinical trials appears to be in jeopardy. Current initiatives [e.g., the Clinical Trials Transformation Initiative (CTTI) and the proposed new National Center for Advancing Translational Sciences] and the recent Institute of Medicine report on cancer clinical trial networks each recognize that successful recruitment and retention in clinical trials is critical to improving the efficiency and effectiveness of Phase III/IV clinical trials and that action to insure enrollment success is urgently needed. Too often, despite careful planning, trial enrollment fails.

Workshop participants identified several critical barriers to successful recruitment. First, health care providers are gatekeepers for trial participation, yet many providers are either not aware of active trials or do not refer their patients to trials. Likewise, patients lack knowledge of clinical trials for which they may be eligible and often view clinical research with uncertainty or suspicion. Second, the administrative burden and regulatory requirements combined with underestimation of infrastructure, reimbursement and resource costs associated with recruitment and retention present unprecedented challenges, even for experienced trialists. Third, the financial realities of funding clinical trials must be recognized and met. The unplanned expansion of time and resources often required to reach target enrollment is a major threat to the continued commitment of any sponsor. Fourth, institutional policies that govern clinical investigation often create barriers for clinician investigators rather than encouraging their participation in clinical research.

Many important complicating issues were also identified and discussed. For example, adverse pressure on trial enrollment is an unintended consequence of the requirement to include all populations in clinical studies. Minorities and women, who are often underserved and under- or uninsured, are harder and more costly to recruit and retain in trials. Added costs required to enroll and retain diverse populations compete for available funds in a fiscal climate in which cost containment is encouraged. Finally, how indirect costs awarded to institutions conducting federally sponsored trials might better be used to aid clinical trial conduct was also discussed.

Despite the multiple problems identified, workshop attendees recognized that clinical trials are an essential means to evaluate new therapy and improve health care and that successful enrollment is pivotal for the success of every trial. Specific strategies to enhance awareness of the importance of participation in clinical research and to facilitate the execution of trials through successful enrollment are outlined below (the order of recommendations does not imply relative priority or sequence for implementation):

Recommendations

Foster an engaged and informed clinical research culture. NHLBI should take a leadership role in programs that foster long-term engagement of all stakeholders and increased awareness of the importance of clinical trials. Specific areas where NHLBI should build on existing relationships and encourage public-private initiatives include:
1. Collaborations with academic centers, professional societies, and patient advocacy organizations to promote effective education among health professionals and the general public about the role of clinical research and to establish clinical trial participation as a valued contribution to the general public and the scientific community.
2. Specific funding opportunities to examine clinician recruitment behavior, develop methods for educating healthcare providers about clinical research, and expand racial and ethnic diversity among researchers;
3. Targeted communication strategies aimed at developing an NIH-wide National Campaign to increase public awareness and participation in clinical trials using conventional media and social networking approaches to highlight research participation and outcomes in terms that health consumers understand; and
4. Community engagement programs to develop a cadre of community ambassadors and speakers, including investigators, health care providers, and participants, on clinical research topics (CTSAs should be engaged for these activities).
Establish a Federal Partners Working Group. NHLBI should take the lead to establish a Federal Partners Working Group (FPWG) to facilitate translational science by harmonizing and promoting best regulatory and oversight practices: The FPWG should include FDA, CMS, NIH and OHRP representatives to address such issues as:
- Overextended institutional review boards (IRB). The FPWG could identify methods and encourage IRBs to, as examples: 1) focus on the high priorities of patient safety and accurate, lucid informed consent in trials; 2) use central IRBs, and 3) simplify the informed consent process, and appropriately use staged informed consent, or waiver of informed consent.

Independent collection and interpretation of clinical trial data by NHLBI, FDA, and CMS. The FPWG could develop and recommend standard definitions and procedures to promote data-sharing and dialogue among federal partners. A transparent process and standard procedures would allow investigators to more efficiently address safety and outcomes reporting requirements.

Investigational devices, drugs, or clinical interventions under evaluation that are widely available outside a trial. The FPWG could develop reimbursement agreements to cover appropriate expenses and thus promote clinical trial participation.

Develop programs to facilitate recruitment into NHLBI trials. NHLBI should implement programs to 1) assist investigators meet the challenges of conducting clinical trials and 2) enhance awareness of and participation in NHLBI-sponsored clinical trials. Suggested strategies include:

Supporting collaboration with academic medical centers and CTSAs to encourage community and private practice-based recruitment in clinical trials;

Partnering with AccrualNet (http://accrualnet.acscreativeclients.com/) to add NHLBI-specific content to this central repository of successful recruitment strategies;

Placing emphasis on including metric-driven recruitment strategies with clear measures of recruitment, retention, and adherence in research protocols;

Developing a budget “tool” that can be used by the research community to accurately estimate trial costs;

Ensuring that all NHLBI-funded studies outline and adhere to acceptable and appropriate strategies for notifying study participants of study results in the dissemination plan;

Encouraging the use of electronic health records to facilitate study screening, enrollment and data capture; and
Collaboration among trials addressing similar research questions to reduce competition for patients, and encourage potential sponsors to cost-share.

Publication Plans

The Workshop participants will submit a commentary to JAMA and will develop a more detailed report of the discussion for publication in an appropriate peer reviewed journal.

NHLBI Contacts

Patrice Desvigne-Nickens, MD; desvignp@mail.nih.gov
Debra Egan, MSc, MPH; debrae@mail.nih.gov
Victoria Pemberton, RNC, MS, CCRC; pembertonv@mail.nih.gov
Lynn Rundhaugen, MPH; rundhaul@nhlbi.nih.gov

Co-Chairs

Robert Frye, MD, Mayo Clinic
Jeffrey Probstfield, MD, University of Washington

Speakers and Discussants:

C. Noel Bairey-Merz, MD, Cedars-Sinai Medical Center
Deepak Bhatt, MD, MPH, VA Boston Health Care System, Brigham and Women’s Hospital
Jackie Bosch, MSc, McMaster University
Robin Roberts Bostic, Thoratec Corporation
Donald Brautigam, MD, Great Lakes Medical Research
Bonnie Brescia, BBK Worldwide
Janet Brody, PhD, Oregon Research Institute
Thomas Brott, MD, Mayo Clinic
Robert Califf, MD, Duke University
Peter Carson, MD, VAMC
Elise Cook, MD, The University of Texas MD Anderson Cancer Center
Giselle Corbie-Smith, MD, MSc, University of North Carolina
Lawrence Friedman, MD, Consultant
Ken Getz, MBA, Tufts University
Anthony Hayward, MD, PhD, NCRR
Martha Hill, PhD, RN. Johns Hopkins School of Nursing
Louis Jacques, MD, CMS
Constance Lewin, MD, MPH, FDA
Ruth McBride, ScB, Axio Research
Yale Mitchel, MD, Merck Research Laboratories
Linda Parreco, RN, MS, NCI
Vivian Pinn, MD, ORWH
Sara Pressel, MS, University of Texas at Houston
Diane Simmons, Center for Information & Study on Clinical Research Participants
Coard Simpler, patient representative
Sidney Smith, MD, University of North Carolina
Darby Steadman, patient representative
James Stolzenbach, PhD, Abbott
Armin Weinberg, PhD, Baylor College of Medicine
Mary Woolley, MA, Research America
Freda Yoder, MA, OHRP
Bram Zuckerman, MD, FDA