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| Investigator's Handbook A Manual for Participants in Clinical Trials of Investigational Agents Sponsored by DCTD, NCI
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3. The Research Base and the Investigator
3.1 Definition and Purpose of a Research Base for Clinical Trials
A research base is an entity that assumes a broad range of responsibilities and functions for the support of clinical trials conducted under its name. Examples of research bases include Cancer Centers and Cooperative Groups. The research base supports the investigator in developing, organizing, implementing, and analyzing clinical trials. It assumes responsibility for the quality of the research, both in concept and execution, and has an important role in assuring patient safety.
An effective research base enhances the investigator's research in several specific ways. It provides assistance in developing protocols and obtaining approval by sponsoring agencies. It often offers centralized data management and statistical consultation. An effective research base should also provide the opportunity for internal peer review and quality assurance.
Obviously, the research base enhances its own scientific credibility by assuming responsibility for the quality of the scientific ideas and the care with which they are tested. These activities may also be an economical way of supporting multiple clinical investigations simultaneously.
In short, a research base provides an institutional source of support and assistance for the activities of protocol chairs and investigators. Clinical Cooperative Groups are examples of research bases whose functions are described in this section. Many of the same considerations about organization for support of clinical research apply to any Cancer Center or single institution.
3.2 Activities of the Research Base
The research base may assist the clinical investigator in many activities and may assume primary responsibility in several.
3.2.1 Protocol Development
3.2.1.1 Scientific Review
Many research bases have procedures for review of the science of a clinical trial, either at the concept stage or at the time a protocol is written. This review is distinct from the task of the Institutional Review Board (IRB) which may or may not view as part of its charge a critical scientific review. Ideally, a scientific review assists the investigator in focusing his or her ideas and perhaps in identifying other useful scientific resources within the research base. This process should facilitate research and assist in the testing of new ideas. Careful review may be particularly important for Phase 3 trials, because of the very substantial commitment of time, patients, and resources involved.
3.2.1.2 Biostatistical Consultation
The design of any clinical trial should be based on sound statistical principles. Issues such as sample size, stopping rules, endpoints, and the feasibility of relating endpoints to objectives are pivotal to a successful trial. Statistical expertise should be provided by a research base.
3.2.2 Protocol Administration
Since most protocols require multiple levels of approval, and since policies of the various sponsoring agencies may differ and change with time, a research base can provide valuable assistance to the investigator in obtaining these approvals. Establishment of a centralized mechanism for submitting and tracking a protocol through the necessary approvals, including the IRB, saves individual investigators a very large expenditure of time and effort that is much better directed elsewhere. A research base with multiple CTEP-sponsored protocols could efficiently assume the responsibility for communicating status changes, amendments, results reports, publications, and other pertinent protocol administration information to CTEP.
3.2.3 Establishment of an Affiliate Program
The participation of affiliate investigators often contributes to the success of cancer clinical trials. The research base must be as concerned about the quality of research performed by its affiliate investigators as that of its own staff.
CTEP has established a set of guidelines to assist research bases in developing a policy toward affiliate investigators (see Section 13). Each research base participating in investigational agent trials sponsored by DCTD should develop its own affiliate policy in accord with these guidelines.
The most important components of these guidelines are that the research base should, (a) define qualifications necessary for affiliate investigators and (b) periodically review their performance. Such review of performance should include site visits by investigators from the research base.
3.2.4 Agent Accountability and Storage
Although FDA regulation places the responsibility for maintaining accountability for the use of investigational agents with the investigator, an institution may assume these responsibilities for the investigators on its staff and assure itself of compliance with Federal requirements. (see Section 15).
3.2.5 Reporting of Results to CTEP
The results of trials involving IND agents must be reported to the sponsor. The Cooperative Groups, as research bases, inform CTEP directly of their results. In all other cases, such reporting is the responsibility of the protocol chair (see Section 10).
3.2.6 Data Management and Statistics
Since most cancer clinical trials involve professional staff other than the protocol chair, adequate collection of clinical data is a complex task that must be integrated into the medical practices of the institution. Furthermore, data collection is best done as data are generated; this practice promotes protocol compliance and permits the protocol chair to monitor the study's progress. For these reasons, data management organized and supported at the department or institution level is usually more efficient and reliable than that which is left to the individual investigator. Centralized data management is obviously not required of institutions performing NCI-supported trials, but its advantages seem clear. In the experience of CTEP's site visit monitoring program (see Section 16) the quality of execution of clinical trials is better in institutions that provide central support for data management.
3.2.7 Quality Assurance
This term, as discussed in detail in Section 16, applies to three features of the conduct of clinical trials.
A quality assurance program permits the research base to satisfy itself that each participating investigator is fulfilling his/her responsibilities. It also provides the research base with data about the quality of execution of its clinical research, and it provides the investigator an opportunity to learn from an external evaluation of his/her performance. In its most constructive form, this process constitutes a peer review of performance and improves the quality of clinical research.
The implementation of these activities takes many forms. Section 16 describes the existing procedures of the Cooperative Groups and CTEP for quality assurance. Although CTEP does not require single institutions to establish internal quality assurance programs, inclusion of this subject in this section is intended to draw attention to the potential value of this activity for any research base. CTEP staff will assist any research base that desires assistance and advice in developing these programs.
| Table of Contents |
Part A 1 2 3 |
Part B 4 5 6 |
Part C 7 8 9 10 11 |
Part D 12 13 14 15 16 |
Part E 17 18 19 |
Appendices |
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