When an Investigator is also a Sponsor
When investigators embark on designing, writing, and initiating the clinical trial, their responsibilities are just beginning. The FDA calls these investigators “sponsor-investigators (SIs)”. A sponsor-investigator is an individual who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. In other words, in an investigator-initiated trial, the researcher is both the investigator and the sponsor, and therefore must handle the responsibilities for both roles.
The FDA provides guidance for individual investigators planning to conduct clinical investigations of FDA regulated drug(s) or device(s) for an indication that does not appear in the approved labeling for the product. Depending on the origin of the funding for the trial (e.g. federal funding) regulations by the U.S. Department of Health and Human Services Office for Human Research Protections (OHRP), 45 CFR 46 known as The Common Rule, may also be applicable.
In most cases, institutional policies and guidance fall into two major categories: protecting human subjects and ensuring the integrity of the data from clinical investigations. This is true for all research trials.
All investigators in interventional drug studies must complete and submit FDA Form 1572 (21 CFR 312.50), which specifically outlines certain responsibilities and obligations including agreeing to personally conduct and supervise the investigation.
Investigational New Drug (IND) or IDE Applications
Some protocols may require the investigator to submit an investigational new drug (IND) or an investigational device exemption application. However, a sponsor-investigator may not be required to submit an IND for a study of a lawfully marketed drug if the criteria outlined in the FDA regulations at 21 CFR 312.2(b) for an IND exemption are met. Investigators should confirm if the protocol is exempt from this requirement by reviewing the regulations. If sponsor-investigators are uncertain if the exemption criteria are met, they should seek advice from FDA.
For trials involving medical devices, the Investigational Device Exemptions (IDE) regulation (21 CFR 812) must be considered. Under this regulation medical devices are generally categorized as significant risk or nonsignificant risk devices. Significant risk devices studies must have an IDE application approved by FDA before any research may begin.
Conduct Good Clinical Practice (GCP)
GCP is an international ethical and scientific quality standard for clinical trials with a primary objective of protecting human rights. Compliance with this standard helps to provide assurance that the rights, safety, and well-being of trial subjects are protected. FDA has adopted GCP as guidance for carrying out clinical trials. FDA regulations relating to good clinical practice and clinical trials include:
- Electronic Records; Electronic Signatures (21 CFR Part 11)
- Regulatory Hearing Before the Food and Drug Administration (21 CFR Part 16)
- Protection of Human Subjects (Informed Consent) (21 CFR Part 50)
- Financial Disclosure by Clinical Investigators (21 CFR Part 54)
- Institutional Review Boards (21 CFR Part 56)
- Good Laboratory Practice for Nonclinical Laboratory Studies (21 CFR Part 58)
- Investigational New Drug Application (21 CFR Part 312)
- Applications for FDA Approval to Market a New Drug (21 CFR Part 314)
- Bioavailability and Bioequivalence Requirements (21 CFR Part 320)
- New Animal Drugs for Investigational Use (21 CFR Part 511)
- New Animal Drug Applications (21 CFR Part 514)
- Applications for FDA Approval of a Biologic License (21 CFR Part 601)
- Investigational Device Exemptions (21 CFR Part 812)
- Premarket Approval of Medical Devices (21 CFR Part 814)
Monitoring and Reporting
Good Clinical Practice (GCP) guidelines also describe the requirements for quality management in clinical trials to further ensure the protection of participants and the reliability of trial results. Investigator-sponsors have specific responsibilities for monitoring trials to confirm the trial is conducted and the data generated, recorded, and reported are in compliance with the protocol, GCP, and the applicable regulatory requirement(s).
The methods used to assure quality should be proportionate to the risks in the trial and the importance of the information collected. Methods for monitoring clinical trials range from on-site data verification to centralized data monitoring using statistical analytics to identify areas of risk.
Investigators who do not comply with these regulations and standard operating procedures run significant risk of liability and federal investigation. The FDA has outlined a specific process for investigating non-compliant investigators that includes disqualifying investigators from further research.
The regulatory landscape is constantly shifting and can pose some challenges, particularly for new investigators. Working closely with regulatory experts through the steps, as well as taking courses on GCP, can minimize the risks, protect patients, and ensure research integrity.
Further resources
FDA Guidance for Industry: Investigator Responsibilities
https://www.fda.gov/media/77765/download
FDA Guidance for Sponsor-Investigators
https://www.fda.gov/media/92604/download
ACRP Guide to FDA Form 1572
https://acrpnet.org/2019/04/25/revisiting-the-form-fda-1572/
