Introduction

It will be pleasant news to some that University approval to perform clinical trials can be obtained without great effort and emotion. While the administrative review and approval of most grant applications is accomplished in a relatively smooth flow, proposals to establish agreements with industry sponsors for clinical trials have often presented problems and encountered delays, thus bringing frustration to proponents and administrators alike. The purpose of this guide is to clear-up the mystery shrouding this category of sponsored research and to describe a process that can prevent most problems and delays from occurring. This treatment is meant as a handbook of low complexity and high utility. It is not intended to be an official policy document and it does not introduce new policy. This guide shows the short path to establish a Clinical Trial Agreement at this University and it describes the administrative services available to the clinical investigator.

The Elements

A proposed Clinical Trial Agreement (CTA) normally consists of the following essential elements of particular interest to Medical School and University research administration:

1 - Protocol
2 - Investigator Agreement (sometimes called the Clinical Trial Agreement)
3 - Clinical Trial Budget
4 - Evidence of Institutional Review Board Approval
5 - University of Wisconsin Transmittal Form

The first three elements can be presented as separate documents or they can be combined into one document. The appended suggested format is an example of the three elements forming one agreement.

University of Wisconsin Policy

It is required that the five essential elements of a proposed CTA be reviewed and approved by the Principal Investigator's Department Chair, the Medical School Extramural Support Office, and the University office of Research and Sponsored Programs before a CTA can be said to exist and before work can begin on the project.

Comments on the Elements

The Protocol delineates the work to be performed and is therefore part of the CTA that must be approved by University administration before the project is begun. Frequently, the protocol contains terms and conditions that must be reviewed and modified to conform with University policy. While it often requires the signature of the Principal Investigator, the protocol should never be signed by the Principal Investigator and delivered directly to the sponsor which could falsely signal them that they have reached an agreement with the University. It must be routed with the other CTA elements.

The Investigator Agreement should be signed by the Principal Investigator, but like the protocol, it should never be returned directly to the sponsor. It must be reviewed and signed by an authorized institutional official in order to have any legal stature at the University. This element of the total CTA usually contains terms and conditions affecting proprietary information, data rights, publication rights, inventions and patents, payment schedules and conditions, as well as other matters that can be agreed to only by an authorized University official.

The Clinical Trial Budget provides a reasonable degree of detail for the major costs of performing the protocol. Both direct and indirect costs are shown and a cost per patient studied is established. Unlike the cost reimbursement budgets we prepare for federal granting agencies, the CTA budget itemization is usually stated in terms of procedures and tests performed. The easiest way to understand this difference is to review the sample budget shown in the Appendix.

The budget is subject to review and approval at the several administrative levels and these reviews are required before the budget is delivered to the sponsor.

Clinical trials performed at the Medical School with support from for-profit entities pay indirect costs at the rate of 20% of total direct costs. Approval by the University for this reduced rate was conditioned on its consistent application to these projects. This policy enjoys broad acceptance because it is reasonable and consistently applied.

Evidence of Institutional Review Board (IRB) Approval must be furnished to Medical School and University researches administration before a fund-account number is requested and before work with human subjects begins. It is not necessary to have IRB approval in hand before administrative processing of the other CTA elements.

Procedures for the UW Transmittal Form are the same as those for all proposals for extramural support. Persons experienced in completing these are available at the departmental level.

Payment Schedule

Each CTA must include a payment schedule which should appear in the written agreement or be incorporated in the budget presentation. To be acceptable to the University, the payment schedule must provide for receipt of payments in advance of costs incurred in performing the study. The University will not finance clinical studies in anticipation of later payment. After an initial start-up payment of 30% or more, increments may be scheduled by payment dates or upon submission of completed case reports or by some other acceptable measure of contract performance.

Procedural Requirements and Timing

As previously suggested, pursuit of IRB approval of the protocol and University administrative approval of the other four elements can occur simultaneously and this is strongly encouraged. Many sponsors will provide the format for the first three elements of the CTA and require their use. In addition, the Medical School has a CTA format designed for use with both a scope of work (the protocol) and a budget as attachments. Use of the Medical School prescribed format (see the Appendix) is encouraged as it facilitates University review and approval.

As soon as possible following preliminary negotiations with the sponsor, the Principal Investigator should gather, complete, and sign the documents identified as the five elements and start their routing, beginning at the department office. Because of the fact that for-profit sponsors frequently propose contract provisions that are more restrictive than the University can accept or that contradict University policy, a reasonable time period must be anticipated to allow University administrators and legal staff to negotiate contract changes with authorized executives of the sponsor. University faculty normally do not take part in the final negotiation of agreements with sponsors but Principal Investigators will be kept informed and asked for concurrence at appropriate times.

The Office of Clinical Trials

Because CTA's are remarkably different from the more common research proposals and are highly variable in content and format among themselves, the Office of Clinical Trials has been established to assist clinical investigators with all administrative aspects of clinical trials. Located in rooms H6/122-H6/132 of the Clinical Science Center, the Office of Clinical Trials provides a full range of administrative services including protocol and contract review, budget preparation, IRB applications and consent forms, and a number of coordinating functions. The facilitative role of the Office is most effective when a prospective clinical study project is brought to them in its early stages. For more information, contact Clinical Trials Staff at 263-0383.

Responsibility at the Department Level

Because all extramurally supported projects have administrative impacts at the Department level in such areas as space, personnel, payroll, accounting, and certainly others, it is essential for the Principal Investigator to seek the advice and approval of the Chair and other appropriate persons in his/her departmental office and to keep those persons informed as developments occur with the proposed CTA. The help, advice, and services available at the Office of Clinical Trials and other University offices are additional services that do not replace the relationship between the faculty member and the Department Chair's office. The Chair's office is the point of entry for University review and approval of all sponsored projects and it needs to be involved in their development.

Additional Help

Another resource for advice and assistance is Jack Graham, (Medical School) Administrative Officer for Extramural Support and writer of this guide. He may be contacted with questions and problems concerning the policies and procedures described herein that cannot be easily resolved at the department level. Jack can be reached at 263-4940.

For additional information concerning the administration of sponsored projects, please request the booklet "University of Wisconsin-Madison Policies Concerning Research Sponsored by Industry" available from the Office of Clinical Trials and most departmental and extramural support offices.

Reasonable Expectations

Experience shows that issues will occasionally arise involving significant differences between established University policy and the initial requirements of sponsors, particularly in areas such as data rights, publication rights and confidentiality. Since University Research Administration and Legal Services do not alone control the pace at which such issues are resolved, Principal Investigator patience may at times be tried. The Principal Investigator can lessen the seriousness of any last stage delay by routing his/her CTA elements for the required approvals well in advance of a planned start date.

Finally

The Medical School suggested format for a CTA is appended. The last page of the CTA format shows a sample budget. Additional copies of the agreement form are available at the Office of Clinical Trials and many department offices.

                                                       (August 1999)