Participating Clinics in Multicenter Clinical Trials

Policy and General Information

The National Eye Institute (NEI) supports investigator-initiated multicenter clinical trials using cooperative agreement awards. This mechanism of support is used because NEI staff will be substantially involved with the investigators during the conduct of the clinical trial. Therefore, the organizers of a proposed clinical trial should contact NEI as soon as possible when contemplating submission of an application. Investigators at potential participating clinics should contact the Chairperson of the proposed trial for the submission schedule, logistical arrangements, and for trial-specific information and guidance. The following sections provide generic information regarding the preparation, submission, peer review, and award of applications from potential participating clinics.

Application Procedures

Submit applications using form PHS 398 (Rev. 5/2001) which is available in an interactive electronic format at http://grants.nih.gov/grants/funding/phs398/phs398.html. Follow the instructions supplied with this form, and the specific instructions given below. An investigator submitting an application for support for a participating clinic should check with the study Chairperson and/or NEI staff regarding submission procedures. The study Chairperson will usually collect all applications associated with the study and send them to NIH in a single package. Whether submitted by the study Chairperson or the participating clinic investigator, the original application and FOUR exact copies of the application must be sent to:

Center for Scientific Review
National Institutes of Health
Suite 1040
6701 Rockledge Drive MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817-7710 (for express mail or courier service)

In order to expedite the review of the application, at the same time, please mail or deliver ONE additional complete copy of the application to:

Samuel C. Rawlings, Ph.D.
Chief, Scientific Review Branch
National Eye Institute
Division of Extramural Research
Suite 1300
5635 Fishers Lane, MSC 9300
Bethesda, MD 20892-9300

Peer Review

Applications assigned to the NEI will be reviewed for scientific merit by an initial review group convened by staff of the Scientific Review Branch, NEI. Second level program and policy review for applications assigned to NEI will be conducted by the National Advisory Eye Council.

Review Criteria

All applications will be reviewed using the general NIH review criteria, with special emphasis on the following:

• Experimental Design - adequacy of the participating clinic's procedures for: patient recruitment and patient retention and follow-up, data collection and data management, quality control of clinical examinations, training and certification of personnel, testing and monitoring of study procedures;
• Personnel - qualifications of all key personnel (whether compensated or not), including their experience and track record in clinical trials (NEI-supported and other);
• Resources and Facilities - adequacy of the potential sources and numbers of fully-eligible patients and the documentation of any proposed collaborations; the clinic's recruitment and retention track record in clinical trials; the physical facilities and equipment available for the study; and,
• Budget - appropriateness and reasonableness of all items requested relative to the clinic's potential for patient recruitment, and to the overall scope of the clinic's proposed activities.

Specific Instructions

Enter the code U10 in item 2 on the face page of the application.

Applications should be written with the principal purpose of demonstrating that the clinic will be able to deliver sufficient high-quality data to make its participation desirable and cost-effective. An application should include information that, at a minimum, addresses the peer review criteria, and the NIH policies on the welfare of human subjects, the inclusion of children, and the inclusion of women and minorities in study populations.

Specific information that is pertinent includes the following:

Personnel.

• clinical-trial experience (with specific roles) of all key personnel including clinic coordinators and technical staff (whether compensated or not);
• for clinical trials in which key personnel participated previously as the principal investigator of a participating clinic or satellite center, the recruitment goals, numbers recruited, and recruitment period;
• relevant experience and training of clinic coordinators, testers, technicians, and also of clinicians in any procedures required by the protocol;
• criteria for selecting key personnel who are yet to be identified; size of the local pool of such personnel; and procedures for the search.

Resources and Facilities. The specific information presented should demonstrate access to patients and physical facilities such that the clinic will be able to recruit, examine/test, treat, and follow a sufficient number of patients who meet all study eligibility criteria and who would be willing to participate. Thus, the specific information presented should include:

• size, and geographic and demographic characteristics (including racial/ethnic identity, age and gender) of the clinic's referral base;
• data (prospectively-collected, if possible) for a one-year (or other specified) period on the number of fully eligible patients seen at the clinic and at each collaborating site;
• documentation of the agreement of satellite centers and individual clinicians to provide patients for the study;
• the specific equipment and space available for examining, testing, and or providing protocol treatment of patients; and,
• track record of recruitment and retention in other clinical trials.

Budget. This section should fully explain and justify all requested items, especially:

• the duties and responsibilities of each of the key personnel, clinic coordinators, photographers, readers/examiners, and clerical staff;
• the need for consultant services, the number of hours or days per consultant, and the basis for calculating the compensation;
• the intended use of any equipment requested, the rationale for the model chosen, e.g., price competitiveness, and the percent of time it will be used for the study;
• the details of travel requests, i.e., the purpose of each trip; the number and positions of travelers; and the per person cost of airfare, lodging, per diem expenditures and mileage costs for local travel; and,
• the specifics of patient-care costs not covered by third-party payments, i.e., number of patients; test or procedure to be performed; number of visits; average cost per visit; and basis for calculating charges;

Experimental Design. The specific information that should be provided in the Research Plan section of Form 398 should not repeat the Manual of Procedures for the overall study. But, it should make clear that the investigators at the participating clinic understand the study design and that sufficient thought has been given to how the protocol will be carried out on a day-to-day basis at the clinic. Thus, the following should be addressed:

• mechanisms for identifying and recruiting potential study patients;
• procedures for scheduling potential study patients for the eligibility and follow-up examinations, and how study and nonstudy patients will be examined (i.e., seen at the same time or a dedicated time for study patients);
• provisions for any testing needed as part of the study (e.g., scheduled or first-come, first-served);
• mechanisms for retaining patients enrolled in the study;
• interactions among clinic coordinator, principal investigator, and other key study personnel, including provisions for formal meetings, review of study procedures, protocol monitoring, handling communications from the study coordinating center;
• where satellites to the clinic will be recruiting and/or treating study patients, procedures for coordination and monitoring of satellite performance by the main clinic;
• arrangements for backup coverage for the principal investigator, clinic coordinator, and other key personnel; and,
• security procedures for storage of study supplies (including drugs), equipment, patient records (paper and/or electronic), and other study materials.

Human Subjects. As part of the peer review process, the peer review group carefully considers protections from research risk. The reviewers will assess the adequacy of safeguards of the rights and welfare of research participants based on the information in the application. NIH no longer requires IRB approval and certification of the proposed research prior to NIH peer review of an application. If the application is to be funded, NEI grants management staff will contact the institution for the certification of IRB approval. Please refer to the PHS 398 application kit for further information and guidance on human subject issues.

Inclusion of Children and of Women and Minorities in Study Populations. NIH-funded projects that involve human subjects are required to include children, minorities and both genders in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder, or condition under study. Special emphasis should be placed on the need for inclusion of children, women and minorities in studies of the diseases, disorders, and conditions that affect them disproportionately. Further information on this policy appears in the Form 398 application kit. Peer reviewers will address specifically whether the research plan conforms to these policies. If the representation of children, women or minorities is inadequate to answer the scientific question(s) addressed and the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in the recommendation to further consider the application and in the priority score assigned to the application. NIH funding components will not award grants or cooperative agreements that do not comply with this policy.

For multicenter clinical trials, the Chairperson's application must discuss these issues for the study as a whole. Applications from participating clinics, as indicated in Resources above, should address the age, gender and racial/ethnic composition of their referral base, eligible patient pool, and likely enrollment of patients.

Inquiries

Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcomed.

For further information regarding the initial scientific review, prospective applicants should contact Dr. Rawlings at (301) 451-2020.

For inquiries about the programmatic aspects of this announcement, applicants should contact: Maryann Redford, D.D.S., M.P.H., Päivi H. Miskala, M.S.P.H., Ph.D., Natalie Kurinij, Ph.D., or Donald Everett, M.A., Collaborative Clinical Research, NEI, at:

National Eye Institute
Division of Extramural Research
Suite 1300
5635 Fishers Lane, MSC 9300
Bethesda, MD 20892-9300
Telephone: (301) 451-2020

For grants administration information, applicants should contact:

William W. Darby
National Eye Institute
Division of Extramural Research
Suite 1300
5635 Fishers Lane, MSC 9300
Bethesda, MD 20892-9300
Telephone: (301) 451-2020
Fax: (301) 496-9997
Email: wwd@nei.nih.gov

Authority and Regulations

This program is described in the Catalogue of Federal Domestic Assistance No. 93.867, Vision Research. Awards made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review.