Hands-On Clinical Trials Workshop for Principal Investigators and Coordinators

National Institute on Neurological Disorders and Stroke
Hands-On Clinical Trials Workshop for Principal Investigators and Coordinators

Omni Shoreham Hotel
Washington, D.C.
July 25-26, 2006

The first NINDS Hands on Clinical Trials Workshop for Principal Investigators and Coordinators took place July 25-26, 2006. The purpose of this workshop was to bring together clinical trial PIs and study coordinators with NINDS staff to enhance the development of successful approaches to the conduct of clinical trials. The workshop focus was on solutions and successes from the perspective of PIs and coordinators.

Twenty five NINDS PI and coordinator pairs participated in the workshop, representing areas as diverse as pediatric epilepsy, MS, stroke and traumatic brain injury. The PI and coordinator pairs were either from an NINDS study chairman's office or clinical site. Efforts were made to ensure geographic, gender and ethnic diversity; see Appendix A for final list of participants.

The workshop was divided into 3 main sessions:

1. Administrative Issues to Consider for Clinical Trials - presentations in this session were from the NINDS clinical trials perspective, the NINDS grants management perspective and the PI perspective from two NINDS PIs - Fred Lublin and Gary Cutter.

2. Recruitment - the NINDS Clinical trials perspective was presented in this session, as well as the PI and coordinator perspectives from Beth Malow and Judith Spilker, respectively.

3. Strategies for Research in the HIPAA Environment and other Regulatory Issues - this session consisted of presentations from NIH and the FDA.

There were two breakout sessions - one for PIs and another one for coordinators to discuss and make recommendations on how to conduct successful clinical trials given administrative issues, recruitment challenges and regulatory concerns. After the breakouts, there was a final session to summarize and discuss the next steps.

The meeting produced feedback for NINDS leading to a series of challenges and recommendations regarding how NINDS conducts clinical trials in relation to administration, recruitment and regulatory issues.

Challenges and recommendations

Grant Administration

Changes in awards from R01s to U01s have sometimes been unexpected (no advance notice was given from NINDS); however, investigators have found that the use of the cooperative agreement mechanism has been effective.

NINDS needs to be more timely in issuances of NGAs.

NINDS

NINDS has successfully established a structure for pre-submission process, the planning grant and meeting with NINDS to discuss study design.

NINDS should increase the amount of site monitoring, so as to remove this responsibility and costs from the sites.

During the peer review process at NINDS, the review of proposed recruitment in applications should be as stringent as human subjects review to really know if the study as written can be done, i.e. must be able to show that the patients really exist.

NINDS should add a "how to" section on NINDS clinical research website - things to think about when planning a trial and a resource list - including a list of individuals to contact for specific information.

Sub-contracts

The negotiation of subcontracts continues to be a challenge as is the NINDS intent to fund trials on a per patient basis. Delays in type 5 renewals and in release of carry over of funds complicate contract negotiation. A major issue is F&A when negotiating sub-contracts. Other challenges noted are publication policy issues and difficulty finding items on the NINDS Clinical Trials website. The website is useful; however, some items are difficult to locate on the website. Foreign sites are needed but add time and additional challenges, e.g. registering the foreign IRB if it is not already registered, getting US State Dept clearances.

IRB approval may hinge on having sub-contracts in place.

NINDS should consider funding each sub-contract through its own R01 with individual PI or U10 (e.g. as in NET-PD and NETT). This approach increases ownership and responsibility and may offer incentive to recruit more patients. However, in U10 model, the parent grant institution does not get indirect costs related to the clinical sites.

Budget

NINDS should link start-up funds to milestones

NINDS should provide guidelines on how to budget for specific study activities, e.g. cost of completing a CRF for a follow-up visit - this does vary by region in US and by country

It would be helpful for NINDS or NIH to clarify what is patient care versus what is research care. Communicate to sites info about NINDS contractor and its ability to make site visits at no cost to grantees, when there are concerns about the study sites.

NIH

NIH should assemble dossier of studies that have used informed consent waivers - this would help with the IRB approval process.

Harmonization of NIH and FDA policies would make it easier to understand who requires what.

Administrative

NINDS should inform PIs and coordinators when FDA holds public hearing on a short form version of informed consent to be used in the field.

Institution IRBs do not understand HIPAA and are reluctant to give permission for patient contact. How questions are asked of IRBs is important. Universities seem to be increasing their understanding of HIPAA. Community IRBs are more problematic.

The use of the Perry Point center for drug distribution is helpful.
Drug supply problems can hold up a study, either at start-up or later on.

PIs need info on timeline from planning grant to phase III trial.

The wait for NINDS to establish a DSMB for a study can take time. In addition, often once the DSMB meets, the study is delayed due to FDA, IRBs, etc. The study PI and DSMB liaison should work together to set a timeline to get the DSMB established and set up the first DSMB meeting date.

Data sharing of test results, i.e., if a laboratory or neurological test has been done in a patient, it can be used for ? one study. This also decreases costs.

Study Site issues

NINDS should consider appointing a coordinator liaison from NINDS to facilitate communications with the study clinical coordinating center and clinical sites.

Trials could establish mentorships to help non-performing sites become high performing sites, in terms of recruitment and retention of study subjects.

NINDS should make bridge funding available for coordinators for their time in-between studies

Coordinator turnover has reached a crisis level. Coordinators are critical to the success of clinical studies. RN salaries have increased, so there is increased competition for RNs. If a study only pays for part of a coordinator, can't compete. Competing trials may be paying parts of coordinators' salaries. This is especially true for acute care studies. Recommendations:

• PIs need help with training and retaining coordinators
• Include section in MOP on how PIs will address coordinator turnover
• Can a term of award be requiring an institution to maintain appropriate staff levels?
• Create mentorships for coordinators
• Investigators should include coordinators in study protocol development for reality checks
• Coordinator to coordinator discussions
• Certification of new coordinators
• Routine communication between primary coordinator and site coordinators
• NINDS allow for some percent effort for a nurse coordinator for every trial; additional effort will be reimbursed on a per patient basis

Is a formal evaluation of successful recruitment possible, i.e. a multivariate logistic analysis to determine which study sites are likely to be successful? Sites with proven track records of successful recruitment are typically able to successfully recruit again. It is noted that the best indicator of successful recruitment is past performance. Is there a way to do this for new sites?

How to create successful recruiting sites? How to motivate sites to successfully recruit? Is money the major motivation?

Positive rewards for successful recruitment and negative consequences for non-performing sites - poorly performing sites can be dropped - does this work?

Regular communication with sites, via conference calls or other method of communication, are important. How to get site PIs to make the study a priority?

Coordinators making rounds with trauma MDs has been used as an effective way to increase interest and knowledge of on-going studies.

Concerns were raised that referring patients to a study means they are lost to the referring physician.

Incentives for MDs referring patients to studies were discussed, such as latte cards for MDs as reminders that a study is recruiting patients. These have worked successfully in Seattle.

Publications

Publications are especially important to junior investigators.

Questions regarding this workshop should be sent to Janice Cordell, RN, MPH at jc53a@nih.gov.

Appendix A

Final Participant's List

Karen Adkins, M.A., R.N., C.C.R.C.
Research Nurse Specialist III
Department of Neurology/Sleep Division
Vanderbilt University Medical Center

Athena B. Baldwin, M.S.
Physician Assistant/Clinical Coordinator
Department of Neurosurgery
Baylor College of Medicine

Nicholas M. Barbaro, M.D.
Professor
Department of Neurological Surgery
University of California, San Francisco

Marguerite Barratt, Ph.D.
Deputy Director
Clinical Research Policy Analysis and Coordination Office of Biotechnology Activities
Office of Science Policy
Office of the Director
National Institutes of Health

Alexandra I. Barsdorf, M.A.
Clinical Coordinator
Department of Neurology
Columbia University Medical Center

Richard T. Benson, M.D., Ph.D.
Program Director
Office of Minority Health Research
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Marianna J. Bledsoe, M.A.
Senior Health Science Policy Advisor
Office of Science Policy
Office of the Director
National Institutes of Health

Joseph Broderick, M.D.
Professor and Chair
Department of Neurology
University of Cincinnati Medical Center

Holly Campbell-Rosen, Ph.D.
AAAS/NIH Science Policy Fellow
Office of Science Policy and Planning
National Institute of Neurological Disorders and Stroke

Peggy O. Clark, M.S.N.
Pediatric Nurse Practitioner
Department of Neurology
Cincinnati Children's Hospital Medical Center

Stacey S. Cofield, Ph.D.
Assistant Professor
Department of Biostatistics
University of Alabama at Birmingham

Robin Conwit, M.D.
Program Director
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Janice Cordell, R.N., M.P.H.
Clinical Research Project Manager
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Gary R. Cutter, Ph.D.
Professor
Department of Biostatistics
School of Public Health
University of Alabama at Birmingham

Lisa A. Davis, R.N., M.S.N.
Senior Nurse Specialist
Stroke Branch
Section on Stroke Diagnostics and Therapeutics
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Maxine Davis-Vanlue
Acting Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Lisa de Blieck, M.P.A., C.C.R.C.
Senior Clinical Project Manager
Department of Neurology
Clinical Trials Coordination Center
University of Rochester

Sandra R. Dewar, R.N., M.Sc.
Clinical Nurse Specialist/Clinical
Director
Seizure Disaster Center
University of California, Los Angeles

Janelle R. Everett
Management Intern
Office of the Director
National Institutes of Health

Kristen M. Fowler, M.A.
Clinical Research Coordinator
Neuroendocrinology
Department of Neurology
Beth Israel Deaconess Medical Center

Jacqueline A. French, M.D.
Professor and Director
Pennsylvania Epilepsy Center
Neurological Institute
Hospital of the University of Pennsylvania

Brandy E. Fureman, Ph.D.
Science Policy Analyst
Office of Science Policy and Planning
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Julio Cesar Furlan, M.D., Ph.D.
Clinical Researcher
Division of Neurosurgery
Department of Surgery
Toronto Western Hospital

Wendy R. Galpern, M.D., Ph.D.
Program Director
Clinical Trials
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Irenita F. Gardiner, R.N., C.C.R.C.
Senior Research Coordinator
Department of Neurology
Clinical Trials Coordination Center
University of Rochester

Peter R. Gilbert, Sc.M.
Biostatistician
Clinical Trials Group
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Tracy A. Glauser, M.D.
Director
Comprehensive Epilepsy Program
Professor
Department of Pediatrics and Neurology
Cincinnati Children's Hospital Medical Center

Sara F. Goldkind, M.D., M.A.
Bioethicist
Office of Pediatric Therapeutics
Office of the Commissioner
Food and Drug Administration

Laurie Gutmann, M.D.
Program Director
Clinical Trials Group
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Claire Henchcliffe, M.D., D.Phil.
Assistant Professor
Departments of Neurology and Neuroscience
Weill Medical College
Cornell University

Andrew G. Herzog, M.D.
Director
Neuroendocrine Unit
Harvard Medical School

Carol Hess, R.N.
Project Manager
Department of Neurology
Washington University in St. Louis

Deborah Hirtz, M.D.
Program Director
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Lisa N. Hostetler
Clinical Research Coordinator
Research Services Organization
University of Minnesota

Margaret Jacobs
Program Director
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Scott Janis, Ph.D.
Clinical Research Project Manager National Institute of Neurological Disorders and Stroke
National Institutes of Health

Kate Jenkins
Program Coordinator, Transitional Pain Research
Department of Anesthesia
Brigham & Women's Hospital
Harvard Medical School

Petra Kaufmann, M.D., M.Sc.
Department of Neurology
Columbia University Medical Center

Elise P. Kayson, M.S., R.N.C.
Director, Project Coordination
Department of Neurology
Clinical Trials Coordination Center
University of Rochester

Karl Kieburtz, M.D.
Professor
Department of Neurology
University of Rochester

Aaron Kinchen
Grants Management Specialist
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Lora Kutkat, M.S., M.P.H.
Associate Director
Office of Policy, Planning, and Communications
National Institute on Mental Health

Story C. Landis, Ph.D.
Director
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Karen Lane, C.M.A., C.C.R.P.
Senior Clinical Research Coordinator
Department of Neurology
Johns Hopkins University School of Medicine

Fred D. Lublin, M.D.
Director
Corinne Goldsmith Dickinson Center for Multiple Sclerosis
Mount Sinai School of Medicine

John Kylan Lynch, D.O., M.P.H.
Program Director
Office of Minority Health and Research
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Beth A. Malow, M.D.
Associate Professor
Sleep Disorders Center
Department of Neurology
Vanderbilt University

Pam Mansfield, R.N.
Research Supervisor
Department of Neurological Surgery
University of Washington School of Medicine

Yuan Liu, PhD
Program Director
Synapses and Circuits
National Institute of Neurological Disorders and Stroke
National Institutes of Health

John R. Marler, M.D.
Associate Director for Clinical Trials
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Steven M. Marshall
Project Coordinator
Department of Neurology
New York Presbyterian Hospital

J.P. Mohr, M.D., M.S.
Daniel Sciarra Professor of Clinical Neurology
Department of Neurology
Columbia University

Lynn Morin
Program Analyst
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Claudia S. Moy, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Diane D. Murphy, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Joanne Odenkirchen
Clinical Research Project Manager
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Eugene J. Oliver, Ph. D.
Neurodegeneration Cluster
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Antonia L. Ortiz, C.H.S.
Program Administrator/Coordinator
Office of the Chancellor
NeuroAIDS Research
University of Puerto Rico

Yuko Y. Palesch, Ph.D.
Professor/Director
Data Coordination Unit
Department of Biostatistics, Bioinformatics, and Epidemiology
Medical University of South Carolina

Yuriy Petrenko, M.D.
Clinical Research Coordinator
Spinal Program
University Health Network
Department of Neurosurgery
Toronto Western Hospital

Sandy Plumb
Senior Project Coordinator
Department of Neurology
Clinical Trials Coordination Center
University of Rochester

John D. Porter, Ph.D.
Program Director
CSC Cluster
National Institute of Neurological Disorders and Stroke
National Institutes of Health

William Powers, M.D.
Professor
Department of Neurology
Principal Investigator
Carotid Occlusion Surgery Study
Washington University

Claudia Robertson, M.D.
Department of Neurosurgery
Baylor College of Medicine

Daphné A. Robinson, Ph.D.
AAAS Science Policy Fellow
Office of Science Policy and Planning
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Lynn M. Rundhaugen, M.P.H.
Program Analyst
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Christine N. Sang, M.D., M.P.H.
Director
Translational Pain Research
Department of Anesthesiology
Brigham and Women's Hospital
Harvard Medical School

Ira Shoulson, M.D.
Professor
Department of Neurology, Pharmacology and Medicine
University of Rochester

Judith A. Spilker, R.N., B.S. N.
Research Associate Professor
Department of Emergency Medicine
University of Cincinnati College of Medicine

John Stern, M.D.
Assistant Professor of Neurology
Co-Director, Seizure Disorder Center
Geffen School of Medicine
University of California, Los Angeles

Danilo A. Tagle, Ph.D.
Program Director, Neurogenetics
National Institute of Neurological Disorders and Stroke, NIH

Nancy R. Temkin, Ph.D.
Professor
Department of Neurological Surgery and Biostatistics
University of Washington

Ursula Utz, Ph.D.
Program Director
Division of Extramural Research
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Christina Vert
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Bree D. Vogelsong
Clinical Research Coordinator
Epilepsy Center
University of Pennsylvania

Kathryn R. Wagner, M.D., Ph.D.
Assistant Professor
Department of Neurology
Johns Hopkins University

Bonnie Darcy Waldman, J.D.
Project Manager
ALIAS Trial
Data Coordination Unit
Departments of Biostatistics, Bioinformatics, and Epidemiology
Medical University of South Carolina

Steven Warach, M.D., Ph.D.
Senior Investigator
Stroke Branch
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Mariann M. Ward, M.S., N.P.
Nurse Practitioner
Department of Neurological Surgery
University of California, San Francisco

Michele Weber, M.S., C.C.R.C.
Clinical Research Manager
Department of Neurology
Corrine Goldsmith Dickinson Center for Multiple Sclerosis
Mount Sinai School of Medicine

Chester B. Whitley, M.D., Ph.D.
Professor
Gene Therapy Center
Institute of Human Genetics
Department of Pediatrics
University of Minnesota

Valerie Wojna, M.D.
Professor/Principal Investigator
NeuroAIDS Research
Department of Neurology
University of Puerto Rico Medical Sciences Campus

Frances Yee, Ph.D.
Scientific Program Analyst
Clinical Trials Group
National Institute of Neurological Disorders and Stroke
National Institutes of Health