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impact subject safety and data integrity. If monitoring or audit observations reflect serious or persistent noncompliance on the part of an investigator/institution then the sponsor should terminate the investigator's/institution's participation in the investigation and promptly notify the regulatory authority(ies). (ICH E6(R2) 5.20 Noncompliance, Chapter 25 Investigator/Institution Interim Monitoring, Chapter 33 Quality Assurance Components, Chapter 34 Regulatory Authority Inspections, Chapter 31 Quality Responsibilities).

      9.2.2.3 After Completion or Termination of the Trial

       9.2.2.3.1 The Investigator

       Submits reports of final trial status and outcome to IRB/IEC and regulatory authority(ies) as required (ICH E6(R2) 4.13 Final Report(s) by Investigator; Chapter 29 Essential Documents; Chapter 26 Investigator/Institution Close‐out; Chapter 8 IRB/IEC Roles and Responsibilities).

       In the event of premature termination or suspension of a trial, promptly informs the trial subject, arranges for appropriate medical care follow‐up for the subject, and informs the sponsor, IRB/IEC, and/or regulatory authority(ies) as applicable, (ICH E6(R2) 4.12 Premature Termination or Suspension of a Trial; Chapter 29 Essential Documents; Chapter 26 Investigator/Institution Close‐out; Chapter 8 IRB/IEC Roles and Responsibilities).

       Permits audits/inspections by Sponsor, IRB, and Regulatory Authority(ies) at ANY time! (ICH E6(R2) 4.1 Investigator's Qualifications and Agreements; Chapter 24 Investigator/Institution Initiation)

       9.2.2.3.2 The Sponsor

       In the event of premature termination or suspension of a trial, promptly informs the investigator(s), the regulatory authority(ies), and IRB/IEC as applicable, of the termination or suspension and the reason(s) for termination or suspension (ICH E6(R2) 5.21 Premature Termination or Suspension of a Trial; Chapter 18 Clinical Trial Protocol and Amendments; Chapter 26 Investigator/Institution Close‐out; Chapter 8 IRB/IEC Roles and Responsibilities).

       Closes trial sites upon study completion (Chapter 26 Investigator/Institution Close‐out).

       Prepares and submits clinical trial/study reports of trial results to the regulatory authority(ies) whether the trial is completed or prematurely terminated as required by the regulatory requirements. The clinical trial reports in marketing applications will meet the standards of the ICH E3 Guideline for Structure and Content of Clinical Study Reports [3,4]. (ICH E6(R2) 5.22 Clinical Trial/Study Reports; Chapter 28).

       Permits audits/inspections by Regulatory Authority(ies) at ANY time! (ICH E6(R2) 5.1 Quality Assurance and Quality Control; Chapter 31 Quality Responsibilities).

       9.2.2.3.3 The Sponsor and Investigator

      Maintain and archive records (evidence of trial conduct). Maintain records that demonstrate the conduct of the trial. Archive records so that they are retrievable and for the duration required by applicable regulations. The investigator will have access to trial data at all times. (ICH E6(R2) 4.9 Records and Reports, 5.5 Trial Management, Data Handling, and Record Keeping, Chapter 29 Essential Documents).

      

      Knowledge Check Questions

      1 What is the role of the sponsor?

      2 What other individuals or parties may assist the sponsor with trial‐related duties, and under what conditions?

      3 What is the role of the investigator?

      4 What other individuals or parties may assist the investigator with trial‐related duties, and under what conditions?

      5 What are the sponsor's responsibilities before the trial commences, during the conduct of the trial, and after completion or termination of a trial?

      6 What are the investigator's responsibilities before the trial commences, during the conduct of the trial, and after completion or termination of a trial?

      7 Overheard:“We should have ethics committee approval of the protocol tomorrow so we will enroll the patient the following day. We can then submit to the study to the regulatory authority.”Physician at a clinic who received donated study drug from a manufacturer to conduct their own clinical trial. This physician will otherwise wholly finance and resource the study.Comment and discuss:What are the GCP and regulatory responsibilities of this “investigator”?Is the investigator violating any GCP requirement? If yes, which?

      1 1 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Integrated Addendum to ICH E6(R2):Guideline for Good Clinical Practice, E6(R2) (2016). Current Step 4 version dated 9 November 2016. https://www.ich.org/page/efficacy‐guidelines

      2 2 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting E2A (1994) Current Step 4 version dated 27 October 1994. https://www.ich.org/page/efficacy‐guidelines

      3 3 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Guideline for Structure and Content of Clinical

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