The difference between sponsors and investigators
By J. Mark Waxman, JD
General Counsel
CareGroup Healthcare System, Boston
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IRB administrators and committee members may use the words sponsor and investigator interchangeably, but it’s important to know the difference between the two. A sponsor is the entity or person who takes the responsibility for a clinical investigation. The sponsor may be, but is not required to be the investigator — the individual who actually conducts the clinical investigation.
According to the U.S. Food and Drug Administration (FDA), a clinical investigation means any experiment that involves a test article that either is subject to the prior submission requirements of the FDA (found in sections 505 or 520 of the FDC Act), or is not subject to submission, but the results of which are intended to be submitted later or held for inspection as part of an application for a research or marketing permit (21 CFR section 50.3c). In general, any clinical investigation that must meet the requirements for prior submission is subject to IRB review. An experiment is any use of a drug except for the use of a marketed drug in the course of medical practice.
Finally, it is interesting to note that the actual definition of research itself is defined elsewhere to mean a systematic investigation develop to defeat or contribute to generalizable knowledge (45 CFR section 46.102d).
Responsibilities all around
Both sponsors and investigators have an extensive series of responsibilities defined by federal law, and in particular under the Food, Drug and Cosmetic Act. These responsibilities are wide ranging and must be carefully understood by both investigators and sponsors. A deliberate or repeated failure to comply with these responsibilities can, in addition to other potential sanctions, lead to a disqualification.
Sponsors have four responsibilities
Representative of the general responsibilities of a sponsor are:
1. Selection of qualified investigators — those documented to be qualified by training and experience. The information to be furnished in this regard includes mandated financial disclosure information.
2. Provision of adequate information to properly conduct the investigation, including keeping each participating investigator informed of new observations discovered by or reported to the sponsor.
3. Proper monitoring of the investigation through ongoing review of the progress of the investigation. A sponsor must select a qualified monitor to assist in this process. A sponsor who discovers noncompliance is required to act to secure compliance or potentially end the investigation. Further, the sponsor must be vigilant to allow it to determine if the investigational drug presents an unreasonable and significant risk to the subject. If that is the case, it must notify the FDA, all relevant IRBs, and the investigators. The sponsor also must discontinue the investigation no later than five working days after making the determination.
4. Maintenance of adequate records relating to the drugs and its disposition and the financial interest of investigators.
Investigators share responsibilities
At the inception of the investigator’s role, a signed investigator statement is required. The statement contains a series of important commitments by the investigator. The statement includes commitments that the investigator will:
- Conduct the study in accordance with the protocol and make no changes (unless safety requires it) in a protocol until the sponsor is notified.
- Personally conduct or supervise the described investigation.
- Properly inform potential subjects that the drugs are being used for investigational purposes.
- Ensure that requirements relating to obtaining informal consents and IRB approval are met.
- Report adverse experiences.
- Ensure that all associates and others assisting in the conduct of the investigation are informed about their obligations in meeting these commitments.
Separate and apart from the direct obligations to the sponsor, the investigator must also commit to promptly report all changes in the research activity and all unanticipated problems to the IRB. Similarly, no changes (absent a need to protect a subject) can be made to be research without IRB approval. (21 CFR 312.53).
These commitments are supplemented by a series of regulatory mandates. First, the drug may only be administered under the personal supervision of the investigator or a subinvestigator responsible to the investigator. A subinvestigator is a member of the investigator’s team. Investigational drugs may only be given to those specifically authorized to receive it, and detailed records of drug disposition must be maintained and available for inspection at all times.
Second, record-keeping requirements are critical. Case histories in particular are mandated with the appropriate documentation of the receipt of informed consent.
Third, a series of investigator reports are specified — progress reports, safety reports, a final report shortly’ after the investigator’s participation is completed, and financial disclosure reports. All such reports and any other required records must be maintained for a period of two years following the date a marketing application is approved or two years after the investigation is discontinued and the FDA is notified.
Compliance and liability
Compliance with sponsor and investigator responsibilities is time and effort consuming, but critical nonetheless. From the research enterprise perspective, worst case, as recently occurred with Johns Hopkins, is suspension (or even termination) of the programs for individuals and the institution. In addition, a failure to comply with the mandate may lead to reimbursement claims on the FDA which are not supportable and deemed false claims by the government.
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