O. CSP Study Files

E..

Change in Funding Support

F.

Data Collection, Editing and Patient Entry Policy

K.

L.

Putting a Medical Center on Probation

N. CSEC Reviews of Ongoing Studies

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Replacement of a PI or Study Chairperson During the Course of a Study

M. Early Termination of a Medical Center

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Q. Collaboration with Industry

VI. CONCLUDING A CSP STUDY

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1. INTRODUCTION

The purpose of this manual is to describe practices and procedures for the organization and operation of Cooperative Studies Program (CSP) studies in the Veterans Health Administration (VHA). Cooperative studies are those in which investigators from two or more VA medical centers agree to study collectively a selected problem in a uniform manner, using a common protocol with central coordination.

Although cooperative studies are generally not appropriate for the early development and refinement of new therapeutic techniques, they are particularly advantageous in the later stages of evaluation of safety, efficacy and cost effectiveness of health care interventions that have already had the necessary preliminary trials in humans. Clinical trials and health services research studies of this type as well as some epidemiologic studies can benefit from a multicenter approach that facilitates the accumulation of patient samples that are:

Sufficiently large to provide a definitive answer to the research questions. For medical conditions
that are relatively rare, cooperative studies may be the only feasible approach, but even in more
common conditions, knowledge can be accumulated more rapidly by pooling the observations
made in several facilities.

The large number of medical centers within the VA presents an ideal environment for conducting multicenter cooperative studies. The VA has a large and relatively uniform patient base; this is especially appropriate for research that addresses medical problems and diseases prevalent in the veteran population. These characteristics facilitate the conduct of multicenter studies that require strict adherence to a common protocol. In this setting, it is more likely that the essential patient follow-up will be completed.

Successful cooperative studies require central administration to ensure uniformity of research methodology as well as fiscal control. The administrative structure of the VA contributes to this kind of coordination.

The Cooperative Studies Program, a division of the Department of Veterans Affairs Office of Research and Development, was established to provide coordination and support for multicenter research studies that fall within the purview of the VA. When appropriate, CSP works with other divisions of the VA to promote cooperative studies.

CSP has five coordinating centers (see figure 1): four statistical/administrative coordinating centers and one pharmacy coordinating center. The four Cooperative Studies Program Coordinating Centers (CSPCCs), located at the VA Medical Centers in Hines, IL, Palo Alto, CA, Perry Point, MD, and West Haven, CT, provide biostatistical and data processing assistance for CSP studies and also ensure their compliance with Cooperative Studies Program guidelines. There is a Human Rights Committee established at each Coordinating Center that reviews the ethical aspects of proposed studies.

The fifth center, unique to CSP, is the Cooperative Studies Program Clinical Research Pharmacy Coordinating Center (CSPCRPCC), affiliated with the VAMC in Albuquerque, NM. CSPCRPCC was established to provide additional resources for all CSP studies that involve drugs or devices. Personnel from this center help in the planning and development of the study, participate in monitoring the study, serve as liaison between the pharmaceutical industry or manufacturer and the CSP, provide guidance and information on Food and Drug Administration regulations, and centrally control and distribute study drugs and devices.

In a cooperative study, certain persons and groups have specific responsibilities. These Guidelines attempt to identify the most important tasks and responsibilities. A successful cooperative study requires communication, cooperation, and a willingness to pursue a common goal. We recommend that those interested in proposing a CSP study communicate with the CSP office in VA Headquarters if additional information is needed.

FIGURE 1. Organization of Cooperative Studies Program (CSP)

See Appendix A for names, addresses and FTS numbers relevant to the Cooperative Studies Program.

II. DEVELOPING A CSP STUDY

A. Submission and Review of Planning Request

A CSP study begins with the submission of a planning request by a VA investigator to the Chief Research and Development Officer (CRDO) in VA Headquarters. The investigator is designated as the Principal Proponent. A Co-Principal Proponent is named only when a clear and justifiable need exists; in general, the practice is discouraged. No more than two Principal Proponents may be named. A planning request should be no longer than 10 pages, and contain the following information:

Justification of the need for a multi-site study and why it is feasible to conduct the study within the
VA.

Summary statement that the necessary preliminary research has been accomplished and that a large-scale evaluation should follow.

Acknowledgment of VA policy to include women and minorities in clinical research.

Description of the contemplated study design. Include the following items in the description as appropriate:

Other documents must accompany the planning request but are not included in the 10 page restriction:

Statement of disclosure. A formal statement is required indicating that no financial or contractual relationship exists between the Principal Proponent and any organization involved in the trial that may constitute a real or apparent conflict of interest. If such a relationship or contract does exist, or appears to exist, full disclosure must be provided by the Principal Proponent. (See Appendix D.)

Statement of eligibility. To be eligible for planning support, the Principal Proponent must either have, at minimum, a 5/8th's VA appointment or have applied for and received approval from the Eligibility Panel in VA Headquarters (Circular 10-88-95) within the previous nine months. In the latter case, a copy of the letter establishing eligibility to receive funds should be attached to the request.

Cover letter from the Director and the ACOS for Research and Development at the Principal
Proponent's Medical Center acknowledging and approving the submission.

Curriculum Vitae (CV) of the Principal Proponent with address, telephone and fax number(s). (not to exceed 10 pages).

Names, addresses, and telephone numbers of five to seven unbiased experts in the field who might be suitable to review the proposal. Planning requests will not be processed unless these names are included.

Seven copies of the request and CVs should be submitted.

A preliminary protocol outline and other relevant background materials including reprints and references may be appended to this request. However, only a portion of the submitted material may be distributed to the reviewers.

Investigators who have questions about submission of a planning request are encouraged to contact the CRDO. When it appears advantageous, the CRDO may suggest a consultation with the staff of one of the four CSPCCs. Similar support is available in the areas of cost effectiveness and decision analysis.

Planning requests are sent to four or more reviewers to evaluate the merit of the proposal. The decision to fund the study for planning will be made by the CRDO on the basis of the consultants' recommendations, together with other relevant considerations. Turnaround time for responses to planning requests is six to eight weeks unless additional information is requested from the Principal Proponent.

Although most CSP studies are supported by CSP funds appropriated by VHA, occasionally studies are funded from other VA sources or by outside sources such as the National Institutes of Health or the pharmaceutical industry. Regardless of funding support, all VA and CSP rules and regulations must be followed both in the development of the protocol and the conduct of the study unless specifically waived by the CRDO. If industry support is anticipated, industry representatives may be included in the planning process (see Section V.Q.).

B. Administrative Approval

A limited number of proposals may be evaluated and approved by the CRDO. Such proposals are defined by the length of the research - less than two years, and the budget - less than $25,000. If approved, these proposals are assigned to a Coordinating Center and administratively reviewed midway through the course of the study. The planning and review process varies from that for a conventional CSP study in ways that are unique to each research plan.

When a study is funded for planning, the Principal Proponent is notified in writing by the CRDO, and informed as to which CSPCC the study will be assigned. The Director and the ACOS for Research and Development at the Principal Proponent's medical center are notified as well. The Chief of the CSPCC will identify the Study Biostatistician with whom the Principal Proponent will work. If the study involves drugs or devices, the Chief, CSPCRPCC will also be notified, and a Clinical Research Pharmacist (CRP) will be assigned to the study.

At the time a study is approved for planning, a TWX is distributed by Office of R&D, VA Headquarters inviting expressions of interest in participation. Interested investigators are encouraged to contact the Principal Proponent or the Study Biostatistician.

D. Planning a CSP Study: Participants

Planning and developing a CSP study requires close cooperation among several groups and individuals: the Principal Proponent, the CSPCC (represented primarily by the Study Biostatistician), the CSPCRPCC (represented primarily by the Study CRP), and the other members of the Planning Committee.

1. Principal Proponent

The Principal Proponent provides leadership in the planning process with support from CSPCC and CSPCRPCC personnel. Working closely with the Study Biostatistician, the Principal Proponent will: