Essential documents

In any work or process documents that are needed before initiation, Between or generally the end of the process just like in a clinical trial those “Documents which permit evaluation of the conduct of a trial and the quality of the data produced. It is given in the 8th section of the ICH-GCP.

1. Essential Documents For The Conduct of A Clinical Trial (ICH-GCP) Rajeev Sahai B.Sc , M.Pharm (Pharmacology)

2. INTRODUCTION Essential documents are those documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced. In any work or process documents that are needed before initiation, Between or generally end of the process just like in a clinical trial those “Documents which permit evaluation of the conduct of a trial and the quality of the data produced. It is given in 8th section of the ICH-GCP. 1

3. IMPORTANCE OF THE ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A CLINICAL TRIAL Essential documents are important for: Evaluation of the conduct of a trial and the quality of data produced Successful management of the trial by the investigator, sponsor and monitor Validation by regulatory authority( ies ) and sponsor’s audits Depending on the stage of the trial, essential documents are grouped in three sections according to the stage of the trial: Before the start of clinical trial – It contains 20 documents. During the conduct of the trial- It contains 25 documents that are necessary during the trial/study. After the completion or termination of the trial – It contains 8 documents. 2

4. TRIAL MASTER FILE (TMF) Guideline E6 (2) states that trial master file should be established at the beginning of the trial, both at the investigator/institution site and at the sponsor office. A final close – out of a trial only be done when the monitor has reviewed both the investigator/institution and sponsor files and confirm that all necessary documents are in the appropriate files. The file maintained at the site is often called, “THE SITE MASTER FILE” 3

5. ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS Before the Trial: The following documents should be generated and compiled in file before the trial. INVESTIGATOR’S BROCHURE:- To document that relevant and current scientific information about the investigational product has been provided to the investigator. SIGNED PROTOCOL OR RESEARCH PROPOSAL: The protocol demonstrates the guidelines for conducting the trial. It illustrates what will be made in the study by explaining each essential part of it and how it is carried out. It also describes the eligibility of the participants, the length of the study, the medications and the related tests. PATIENT INFORMATION SHEET (BLANK): The written information of the research to the patient. 4

6. Cont … PATIENT CONSENT FORM (BLANK): A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject's decision to participate. Informed consent is documented by means of a written, signed and dated informed consent form. ETHICS APPROVAL DOCUMENTATIONS: E thics approval is needed for any research that involves human participants, their tissue and /or data to ensure the dignity, right , safety and well-being of all participants are the primary consideration of the research project. some of documents that needs to be approval from ethics committee before initiating trial are follows- current Protocol, ICD, Translated ICD of vulnerable language, translation certificate, back translation certificate, Insurance, CRF, advertisement (if any). CVs OF ALL TEAM INVOLVED: Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s) (as per GCP principle). 5

7. Cont … SIGNATURE AND DELEGATION LOG: Information entered in all sections of the log should be legible and correct. The Principal Investigator and site staff who have been delegated duties/tasks should use the same signature and initials, as provided on the site signature and delegation of responsibility log, when signing and initialing patient records and any study related documents. CLINICAL TRIAL AGREEMENT: A clinical trials agreement should describe and acknowledge responsibilities, terms of collaboration, requirements for payment and reimbursement, publication and intellectual property term and insurance, subject injury coverage, guidelines for dispute resolution, grounds for termination of contract, and possibility of amending contract terms in the future. NORMAL VALUES FOR MEDICAL/LABORATORY PROCEDURES AND TESTS According to the Food and Drug Administration (FDA), normal lab test values are a set of upper and lower limits generally given as a range since normal values vary from person to person.  6

8. Cont … INSTRUCTIONS AND DOCUMENTATION FOR HANDLING / TRANSPORTING OF ANY TRIAL MEDICATION AND RELATED MATERIALS: The investigational product(s) should be packaged to prevent contamination and unacceptable deterioration during transport and storage. STANDARD OPERATING PROCEDURES (SOPs): A standard operating procedure (SOP) is a set of step-by-step instructions compiled by an organization to help workers carry out complex routine operations. SOPs aim to achieve efficiency, quality output and uniformity of performance, while reducing miscommunication and failure to comply with industry regulations. MASTER RANDOMIZATION LIST: Documents that describes the method for randomization of trial population. The randomization schedule of a clinical trial documents the random allocation of treatments (IPs) to subjects. Different trial designs will require different procedures for generating randomization schedules. 7

9. Cont … CASE RECORD / REPORT FORM (CRF) CRF is a paper or electronic document designed to record all the information for an individual study subject required by the study protocol. All CRF’s should include the following data: Study title and number; Investigator’s name study subject/patient ID (Number and Initials) Inclusion / exclusion criteria; Demographic data; Detailed description of dosage regimens of investigation drug; Concomitant treatment; Adverse events (side effects and intercurrent disease) Conclusion on subject’s health Investigator’s signature and date Lab reports details (If applicable) 8

10. ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS During the Trial: In addition to having on file the above documents, the following should be added to the files during the trial as evidence that all new relevant information is documented as it becomes available ANY PROTOCOL AMENDMENTS: If any amendments in the protocol it should be notify to the Ethics committee and get approval. ANY UPDATES IN “IB”: To document that investigator is informed in a timely manner of relevant information as it becomes available DATED, DOCUMENTED APPROVAL/FAVORABLE OPONION OF IRB/IEC OF THE FOLLOWING: To documents that the amendment(s) and/or revision(s) have been subject to IRB/IEC reviewed and were given approval/favorable opinion. To identify the version number and date of the documents. 9

11. ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS Protocol amendment Revision of: Informed consent form Any other written information to be provided to the subject Advertisement for subject recruitment (If used) Any other documents given approval / favorable opinion Continuing review of trial (When required) NOTIFICATION OF SERIOUS ADVERSE EVENTS / ADVERSE EVENTS: Notification by sponsor and/or investigator, where applicable, to regulatory authorities and IRB(s)/IEC(s) of serious adverse events/ adverse events. SUBJECT IDENTIFICATION AND ENROLMENT LOG: Confidential for researcher only (each patient’s address, date of birth, hospital number) To document that investigator/institution keeps a confidential list of names of all subjects allocated to trial numbers on enrolling in the trial. Allows investigator/institution to reveal identity of any subject. Subject identification log complied only site master file. 10

12. Cont … INSTRUCTIONS FOR HANDLING OF INVESTIGATIONAL PRODUCT(S) AND TRIAL-RELATED MATERIALS (if not included in protocol or Investigator’s Brochure) To document instructions needed to ensure proper storage, packaging, dispensing and disposition of investigational products and trial-related materials SIGNATURE SHEET: To document signatures and initials of all persons authorized to make entries and/or corrections on CRFs INTERIM OR ANNUAL REPORTS TO IRB/IEC AND AUTHORITY(IES): Interim or annual reports provided to IRB/IEC in accordance with 4.10 and to authority( ies ) in accordance with 5.17.3 11

13. ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS After completion of the Trial: After completion or termination of the trial, all of the documents identified in Sections 8.2 and 8.3 should be in the TMF together with the following. INVESTIGATIONAL PRODUCT(S) ACCOUNTABILITY AT SITE: To document that the investigational product(s) have been used according to the protocol. To documents the final accounting of investigational product(s) received at the site, dispensed to subjects, returned by the subjects, and returned to sponsor. DOCUMENTATION OF INVESTIGATIONAL PRODUCT DESTRUCTION: To document destruction of unused investigational products by sponsor or at site as per regulatory guidelines. 12

14. ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS COMPLETED SUBJECT IDENTIFICATION CODE LIST: To permit identification of all subjects enrolled in the trial in case follow-up is required. List should be kept in a confidential manner and for agreed upon time. AUDIT CERTIFICATE (if available): To document that audit was performed at the site. It is located only site file. FINAL TRIAL CLOSE-OUT MONITORING REPORT: To document that all activities required for trial close-out are completed, and copies of essential documents are held in the appropriate files. TREATMENT ALLOCATION AND DECODING DOCUMENTATION: In case of an emergency, identity of blinded investigational product can be revealed without breaking the blind for the remaining subjects’ treatment. 13

15. ESSENTIAL DOCUMENTS FOR CLINICAL TRIALS F INAL REPORT BY INVESTIGATOR TO IRB/IEC WHERE REQUIRED, AND WHERE APPLICABLE, TO THE REGULATORY AUTHORITY(IES): CLINICAL STUDY REPORT: The clinical and statistical description, presentations, and analyses are fully integrated into a single report. AND FINALLY: If it is not written down, it did not happen !! If it is not documented, it does not exist !! 14

16. 15 Thank You