SOP for Principal investigator

Objectives

• To provide the Investigator with general instruction to ensure that he/she understands and accepts the obligations incurred in undertaking the study.
• To ensure that the study is planned, set up, conducted, documented and reported according to the protocol, related site SOPs, Recent IEC SOPs, ICMR Guidelines, ICH GCP and applicable local regulatory requirements.
• To ensure that the rights, safety, and wellbeing of study subjects/Participants are properly protected.
• To ensure that data are generated, collected and documented with accuracy, consistency and integrity.
• To ensure that the Investigator is acquainted with the study procedures, verification procedure, audits and inspection procedures.
• To responsible for the third-party staff (Site management organization employees), whoever working in the respective clinical trials.

Co-investigators

Co-investigators are authorized healthcare professionals who work alongside the PI at a trial site, e.g. other Consultants in the department, Post Graduate Medical students). The co-investigator may conduct all or part of the PI’s duties, and must be available to act up as PI if the PI is unavailable for any length of time (e.g. annual leave) or in an emergency situation that could affect the safe conduct or oversight of the trial.

Note: PI/Co-I not affiliated to the KAHER (KLE University), those cannot be delegated in the clinical trial team.

Prior to initiation of the study

• The Investigator should:
• Be interested in the scientific aspects of the study and ensure that the study is responsive to the needs of public health within the country of the population in which it will be conducted.
• Ensure the confidentiality of the product, the protocol and trial procedures by giving a confidentiality agreement in writing to CRO/sponsoring agencies.
• Have sufficient time free from other obligations to prepare and conduct the trial.
• Clinical trials are time consuming and the Investigator should ensure that sufficient time can be dedicated to the study, including for informing and supervising study staff.
• Review Investigator’s Brochure and any up-to-date information on the investigational product.
• The Investigator must be familiar with the product, including pre-clinical toxicology, pharmacology, pharmacokinetics and up-to-date clinical data.
• Review and discuss investigators' SOPs and protocol with the Clinical Monitor
• The Investigator should clearly define: Factors that may alter the feasibility and acceptability of the trial. An adequate recruitment rate for the trial by providing retrospective data on numbers of patients who would have satisfied the proposed entrance criteria during proceeding time periods.
• Make sure that the procedures stated in the study protocol are applicable in his/her center and fully understood. The Investigator should ask the Clinical Monitor to clarify any points of possible misunderstanding.
• Make sure that there are sufficient medical, paramedical and clerical staffs to support the study and deal with foreseeable emergencies.

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Make sure that the facilities are sufficient to allow the study to be undertaken efficiently

Ensure

• Confidentiality and safety conditions for trial subjects.
• Adequate equipment/facilities for subject follow-up, examination and care.

• Adequate facilities for Investigational Medicinal Products storage
• Adequate facilities for laboratory assay of the Subjects blood parameters investigations.
• Adequate facilities for retention of trial documents, ensuring confidentiality of all information about trial subjects and information supplied by KLEs Prabhakar Kore Hospital Medical research Centre, Belagavi /sponsoring agencies.
• Make sure that the IPD trial subject should be in house in the Private Wards

Arrange archiving of trial documents according to GCP and regulatory requirements. It is important to check.

• The duration of retention of patient records with the Institution's archive. In case the Institution's archive does not ensure retention of documents for the period of time requested by sponsor.
• The Investigator must arrange for the retention of the subjects’ source documents/records for the period requested by sponsor and regulatory requirements.

If the IEC and others approve the trial, sign the final copy of the protocol and confirm in writing that he/she has read and understood, and will adhere to, the protocol, study procedures and ICH Good Clinical Practice, will collaborate with the monitor, and accords with Sponsoring agencies on publications policy.

Submit requested documents to the Site Management Office of KAHER, including:

• Signed agreement to comply with this SOP
• Approved protocol, signed and dated.
• Approved informed consent form and other subject information, advertisement (local language and English translation).
• Investigator’s and co-investigator’s curriculum vitae (CVs).
• Recent ICH-GCP training certificate
• Authorized Staff Form
• Product exportation/importation authorization.
• Laboratory certification/recent list of normal laboratory ranges, dated and signed by lab head/Investigator.
• Lab Accreditation certificate
• Final Clinical trial agreement
• Signed agreement that the product will not be used before the site Initiation Visit has been made and authorization obtained from the SMO Clinical Research Coordinator (if applicable).
• Ethics Committee accreditations
• Visit of archival facilities

During the Study

The trial can be initiated (begin screening and/or enrolment of trial subjects) only after the Clinical Monitor has satisfactorily conducted a Trial Initiation Monitoring Visit and the SMO Clinical Coordinator has given written authorization.

Delegation of duties: 

PI can delegate the CRC/Sub-I/Phlebotomist when the study is ongoing at site. PI should provide a comprehensive list of study staff members and the duties that have been delegated to them by the PI. It is applicable for both observational and interventional clinical trial studies.

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Completion of the delegation log: 

The Clinical trial delegation log provides documented evidence of the appropriate delegation of the PI’s responsibilities. The delegation log must state clearly the name of the person, their role and the activities they are delegated by the PI as well as being signed and dated by the PI prior to the activity being undertaken by the individual. All key personnel must be on the delegation log. The PI may delegate activities to a named person in a large department such as pharmacy, and the relevant trials pharmacist would then take responsibility for the conduct of that activity by the department. The dates of entries must be in chronological order and the PI must NOT presign logs (for members of the research team to add names and tasks at a later date).

Investigator’s File, Including Storage and Retention: 

On initiation of the study, the Investigator must prepare a file containing all the documents related to the trial. During the study, the Investigator is responsible for updating the File and regularly adding trial-related documents. The Investigator should keep the File in a locked cabinet, in a secure area accessible only to the Investigator and authorized study staff. The Investigator File and associated source documents should be retained for the time agreed with /sponsors. Patient identification codes should be kept for at least 15 years after completion of the trial.

Written approval from sponsors and site administrations, PI must be obtained prior to destroying records.

1. Lab kits
2. IPs
3. Study Documents (after completion of 15 years)
4. Lab kits and IPs as per sponsor requirements, during the study

The Investigator's File contains

Administrative and Regulatory Documents

1. Composition of IEC of KAHER, Belagavi
2. IEC Accreditation details
3. Lab head CV and MRC
4. Local regulatory requirements.
5. IEC and other authorities’ written approval for all documents (protocol, informed consent(s) and any written information including advertisements for recruitment of study subjects).
6. Protocol initial submission letter and initial Decision letter.
7. Correspondence with the Ethics Committee and the Authorities, including: Protocol submission. Amendment submission, if any.
8. SAE Initial, Follow Up and Final reports and SAE review report
9. Protocol modification notification, if any.
10. Interim report/written summaries of the trial, if applicable.
11. Final Report/written summaries of the trial, if applicable.
12. Product importation authorization.
13. Correspondence about product importation.
14. For studies under IND, a copy of the completed and signed Form FDA 1572 and FDA 3455
15. Investigator’s and Co/Sub-investigators’ C.V.s.
16. New Investigator and Sub-investigators’ C.V.s along with recent ICH-GCP certificate.
17. Authorized Staff Form (ASF).

Investigators/sub-Investigators qualifications and agreements

• The investigator(s) should be qualified by education, training, and experience to assume responsibility for the proper conduct of the trial, should meet all the qualifications specified by the applicable regulatory requirement(s), and should provide evidence of such qualifications through up-to-date curriculum vitae and/or other relevant documentation requested by the sponsor, the IEC, and/or the regulatory authority (ies).
• The investigator should be thoroughly familiar with the appropriate use of the investigational product(s), as described in the protocol, in the current Investigator’s Brochure, in the product information and in other information sources provided by the sponsor.

• The investigator should be aware of, and should comply with, GCP and New Drugs and Clinical Trial Rules.
• The investigator/institution should permit monitoring and auditing by the sponsor, and inspection by the appropriate regulatory authority (ies).
• The investigator should maintain a list of appropriately qualified persons to whom the investigator has delegated significant trial-related duties.
• PI should Signed confidentiality agreement
• PI should Signed agreement stating that products will not be used before the Trial Initiation.
• Monitoring Visit has been made and approval from the SMO Clinical Coordinator obtained.
• Sub investigator should be affiliated to KLES Dr. Prabhakar Kore Hospital and MRC.

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Correspondence and Monitoring

• Correspondence with sponsoring agencies (including the telephone call, E-mail etc). Notes of meetings with sponsoring agencies.
• Summary list of site visits (copy).
• Site Initiation visit Report (copy).
• Notification by Investigator to/Sponsor of serious adverse event and related reports.
• Documentation of serious adverse event reporting by/Sponsor to other investigators.
• Investigator interim report/summaries of the trial for /sponsoring agencies, if applicable.
• Investigator final report/summary of the trial for/sponsoring agencies, if applicable.
• Sponsoring agencies should inform through Mail/Telephonically Prior to Visit for site monitoring.
• Copies of the Investigator's interim report/written summaries of the trial to the IEC of KAHER and authorities.
• Monitoring visit of IEC members at site: PI/CRC should arrange/ready for the all study related documents for Monitoring. IEC secretariat will informed via mail/letter about the IEC monitoring visit. IEC members will select randomly which have approved and ongoing studies at site.
• To ensure to submit the SIV and SMV report to IEC of KAHER.

Compliance with study protocol

• The investigator/institution should conduct the trial in compliance with the protocol agreed by the sponsor and, if required, by the regulatory authority (ies) and which were given approval/favorable opinion by the IEC of KAHER. The investigator and the sponsor should sign the protocol, or an alternative contract, to confirm agreement.
• The investigator should not implement any deviation from, or changes in the protocol without agreement by the sponsor and prior review and documented approval/favorable opinion from the IEC of KAHER of an amendment, except where necessary to eliminate an immediate hazard(s) to trial subjects, or when the change(s) involves only logistical or administrative aspects of the trial (e.g., change in monitor(s), change of telephone number(s)).

• The investigator, or person designated by the investigator, should document and explain any deviation from the approved protocol.
• The investigator may implement a deviation from, or a change of, the protocol to eliminate an immediate hazard(s) to trial subjects without prior IEC of KAHER approval/favorable opinion. As soon as possible, the implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be submitted:

1. To the IEC for review and approval/favorable opinion,
2. To the sponsor for agreement and, if required,
3. To the regulatory authority (ies)

Adequate sources

• The investigator should be able to demonstrate (e.g., based on retrospective data) a potential for recruiting the required number of suitable subjects within the agreed recruitment period.
• The investigator should have sufficient time to conduct and complete the trial within the agreed trial period.
• The investigator should have available an adequate number of qualified staff and adequate facilities for the foreseen duration of the trial to conduct the trial properly and safely manner.

After Completion of the study

• The CRA has to confirm the close out visit in writing to the Investigator/study site. The letter will detail all persons expected to attend, and all administrative documents, IMP, and regulatory documents required for review at this visit. The CRA will confirm recruitment status at the end or premature end of the trial. If the site is closed prior to the end of the trial, a reason for early closure should be clearly documented.
• The CRA will ensure that all Serious Adverse Events (SAE’s) have been reported by the Investigator to the Sponsor and that the investigator is aware of any future reporting requirements and follow up on any ongoing SAEs. If applicable, a line listing of all SAEs/SUSARs that have occurred at the site should be filed in the TMF. If closing the lead site in a multi-center trial, a line listing for all the SAEs/SUSARs at each site should be filed in the TMF.
• The CRA will ensure that all outstanding data queries are resolved at the time of the close out visit.
• All outstanding issues from previous monitoring visits will be resolved or appropriately documented.
• The CRA will verify that final drug accountability is complete
• If applicable, the CRA will ensure that Sponsor authorization for IMP destruction has been obtained and that the destruction or return of unused or partially used IMP is appropriately commented and documented in the Pharmacy file.
• PI along with the study CRA review the all study related documents in study close out visit. After completion of the study, all the study documents should be archived.

Annexure

Nil

Revision History

Nil

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