According to section 4 of the International Conference on Harmonisation – Good Clinical Practice (ICH-GCP), the Principal Investigator (PI) is responsible for the conduct of the clinical trial at a trial site, i.e.:
1. Investigator’s Qualifications and Agreements:
the PI and the study team should be qualified by education, training, and experience, should meet all the qualifications specified by the applicable regulatory requirement(s), and should comply with GCP. Up-to-date CVs, GCP certificates (maximum 3 years old) and training of study team should be well documented at the trial site;
2. Adequate Resources:
the PI and the study team should be educated and trained in the protocol and the Investigational Product(s) (if applicable) and all persons assisting with the trial should be adequately informed about their trial-related duties and functions;
3. Medical Care of Trial Subjects:
the PI should have a qualified physician (or dentist, when appropriate) in the study team who should be responsible for all trial-related medical (or dental) decisions;
4. Communication with (central) Ethics Committee:
the PI should before initiating a trial, as well as for substantial changes to documents during the study, have written and dated approval from the (central) Ethics Committee for the protocol, documentation related to the Investigational Product(s) (if applicable), written informed consent form(s), subject recruitment procedures, and any other written information to be provided to subjects;
5. Compliance with Protocol:
the PI and the study team should conduct the trial in compliance with the protocol agreed to by the sponsor and, if required, by the regulatory authority(ies) and which was given approval by the (central) Ethics Committee;
6. Investigational Product(s) (if applicable):
the PI should take responsibility for Investigational Product(s) accountability at the trial site(s). Where necessary, some or all duties for Investigational Product(s) accountability at the trial site(s) should be assigned to an appropriate pharmacist or another appropriate individual who is under the supervision of the PI. The Investigational Product(s) should be stored and used in accordance with applicable regulatory requirement(s) and with the approved protocol;
7. Randomization Procedures and Unblinding (if applicable):
the PI should follow the trial’s randomization procedures, if any, and should ensure that the code is broken only in accordance with the protocol. If the trial is blinded, the PI should promptly document and explain to the sponsor any premature unblinding of the Investigational Product(s);
8. Informed Consent of Trial Subjects:
the PI should comply with the applicable regulatory requirement(s), and should adhere to GCP and to the ethical principles that have their origin in the Declaration of Helsinki. The written informed consent form and any other written information to be provided to subjects should be revised whenever important new information becomes available that may be relevant to the subject’s consent. Any revised written informed consent form and written information should receive the (central) Ethics Committee’s approval in advance of use. The subject or the subject’s legally acceptable representative (if applicable) should be informed of all pertinent aspects of the trial;
9. Records and Reports:
the PI should ensure the accuracy, completeness, legibility, and timeliness of the data reported to the sponsor in the CRFs and in all required reports. Any change or correction to a CRF should be documented correctly (i.e. an audit trail should be maintained). The PI should maintain the trial documents as specified in Essential Documents for the Conduct of a Clinical Trial (see section 8 of ICH-GCP) and as required by the applicable regulatory requirement(s);
10. Progress Reports:
the PI should submit written summaries of the trial status to the (central) Ethics Committee annually, or more frequently, if requested by the (central) Ethics Committee. The PI should promptly provide written reports to the sponsor, the (central) Ethics Committee and, where applicable, the institution on any changes significantly affecting the conduct of the trial, and/or increasing the risk to subjects;
11. Safety Reporting:
the PI should report all serious adverse events (SAEs) immediately to the sponsor except for those SAEs that the protocol or other document (e.g. Investigator’s Brochure) identifies as not needing immediate reporting. The PI should comply with the applicable regulatory requirement(s) related to the reporting of unexpected serious adverse drug reactions to the regulatory authority(ies) and the (central) Ethics Committee. Adverse events and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the sponsor according to the reporting requirements and within the time periods specified by the sponsor in the protocol;
12. Premature Termination or Suspension of a Trial:
the PI should promptly inform the trial subjects if the trial is prematurely terminated or suspended for any reason, should assure appropriate therapy and follow-up for the subjects, and, where required by the applicable regulatory requirement(s), should inform the regulatory authority(ies). If the PI terminates or suspends a trial without prior agreement of the sponsor, the PI should inform the study team, the sponsor and the (central) Ethics Committee and should provide a detailed written explanation of the termination or suspension;
13. Final Report(s) by Investigator:
the PI should inform the institution when the trial is completed. The PI should provide the (central) Ethics Committee with a summary of the trial’s outcome, and the regulatory authority(ies) with any reports required.