Guidance for Industry: Investigator Responsibilities –Protecting the Rights, Safety, and Welfare of Study Subjects

This guidance was released as a final guidance in October 2009. It can be found online at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM187772.pdf

TARGET AUDIENCE

• The sponsor of the clinical trial: the sponsor is usually a pharmaceutical company who develops prescription drugs, including biological drug products.
• The clinical investigator: the clinical investigator is generally a physician contracted by the sponsor to recruit trial subjects and conduct procedures outlined in a clinical protocol.

FDA LAWS AND REGULATIONS REFERENCED

• Title 21 of the Code of Federal Regulations, Part 11 (Electronic Records; Electronic Signatures Validation); referred to as 21 CFR Part 11; http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm124946.pdf
• Title 21 of the Code of Federal Regulations, Part 50 (Protection of Human Subjects); referred to as 21 CFR Part 50; http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=50
• Title 21 of the Code of Federal Regulations, Part 54 (Financial Disclosure by Clinical Investigators); referred to as 21 CFR Part 54; http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=54
• Title 21 of the Code of Federal Regulations, Part 56 (Institutional Review Boards); referred to as 21 CFR Part 56; http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=312&showFR=1&subpartNode=21:5.0.1.1.3.4
• Title 21 of the Code of Federal Regulations, part 312 (Investigational New Drug Application [IND]); referred to as 21 CFR Part 312; http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=312
• Title 21 of the Code of Federal Regulations, part 812 (Investigational Device Exemptions [IDE]); referred to as 21 CFR Part 812; http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?cfrpart=812
  

OTHER GUIDANCES REFERENCED

Guidance for Industry: E6 Good Clinical practice: Consolidation Guidance (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073122.pdf)

RATIONALE

Within this guidance are the FDA’s thoughts regarding the investigator’s supervisory role during the conduct of a drug, biologic, or device clinical trial at his or her clinical site. It also addresses the investigator’s role in protecting the rights, welfare and safety of the human subject. The description of the responsibilities is high level; the guidance directs the investigator and sponsor to 21 CFR 312 and 21 CFR 812 for more detailed descriptions of the investigator responsibilities during the conduct of a drug/biologic or device clinical trial, respectively.

RECOMMENDATIONS

Supervision of Trial Conduct:

• Only 1 person at a site should have supervisory responsibilities and this person is the primary investigator. Responsibilities include developing an investigative plan and monitoring all trial activities.
• The investigator may delegate trial-related tasks to others. The investigator must keep an accurate record of who the responsibility is assigned to and their qualifications.
• The investigator must ensure those performing the trial-related tasks are (1) trained to perform the tasks (2) understand the purpose of the trial, (2) understand the protocol and specific details within the protocol, (3) be aware of changes to the protocol during the conduct of the trial, and (4) understand the regulatory requirements of conducting a clinical trial in human subjects.
• In some cases the site staff may not be directly employed by the investigator (ie, they are employed by a site management organization hired to perform trial-related procedures). In these cases the investigator is still responsible for ensuring the staff is qualified. If issues arise that the investigator cannot quickly resolve, it is the investigator’s responsibility to notify the sponsor.

Study Subject Protection

• Many of a protocols inclusion and exclusion criteria are there for the protection of the human subject (ie, pregnant women are excluded from the study; subjects with a medical history of Sjogren's Syndrome must not be enrolled). The investigator is responsible for making sure a person meets the protocol-defined inclusion and exclusion criteria.
• If the subject agrees, the investigator should let the subject’s primary care physician know that the person if participating in a clinical trial.
• The investigator is responsible for ensuring the subject receives reasonable medical care for any trial related adverse events.
• The investigator must be available to the trial subject to discuss trial-related procedures and concerns.

IMPACT

Overall this guidance is helpful for giving the investigator and the sponsor a high level description of the investigators’ clinical trial responsibilities. However, I found the title of this guidance misleading since based on the title this guidance is for industry. Within this guidance it specifically states the purpose is to help the investigator understand their responsibilities. If one were to only read the title this guidance would not be read by the appropriate target audience.