CLINICAL TRIAL DOCUMENTATION ASHWIN.pptx

clinical research

1. 15-12-2021 CRPV 1 Presented by, ASHWIN RAM R Master of pharmacy Pharmacology Department KMCH COLLEGE OF PHARMACY CLINICAL TRIAL DOCUMENTATION CLINICAL RESEARCH AND PHARMACOVIGILANCE

2. CONTENTS INTRODUCTION ESSENTIAL DOCUMENTS FOR THE CONDUCT OF CLINICAL TRIAL TRAIL MASTER FILE(TRF). GOOD DOCUMENTATION PRACTICE. CONCLUSION. REFERENCES.

3.  All records , in any form ( including, but not limited to, written, electronic, magnetic, and optical records, and scans, x-rays, and electrocardiograms ) that describe or record the methods, conduct and/or results of a trial, the factors affecting a trial and the actions taken. Such a record is known as, “ Document ” and process is “ Documentation ”  INTRODUCTION

4. Essential Documents are those documents which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. These documents serve to demonstrate the compliance ( following the order or rule ) of the investigator, sponsor and monitor with the standards of Good Clinical Practice and with all applicable regulatory requirements. ESSENTIAL DOCUMENTS FOR THE CONDUCT OF CLINICAL TRIAL

5. Filing essential documents at the investigator/institution and sponsor sites in a timely manner can greatly assist in the successful management of a trial. These documents are also the ones which are usually audited by the sponsor's independent audit function and inspected by the regulatory authority( ies ) as part of the process to confirm the validity of the trial conduct and the integrity of data collected.

6. The various documents are grouped in three sections according to the stage of the trial during which they will normally be generated: BEFORE THE CLINICAL PHASE OF THE TRIAL COMMENCES. DURING THE CLINICAL CONDUCT OF THE TRIAL. AFTER COMPLETION OR TERMINATION OF THE TRIAL.

7. PREPARATION OF PROTOCOL. INVESTIGATOR BROUCHURE. CASE REPORT FORM (CRF). CLINICAL STUDY REPORT. SAFETY MONITERING IN THE CLINICAL TRIAL. ESSENTIAL DOCUMENTS

8. Guideline E6 states that trail master file should be established at the beginning of the trail , both at the investigator/institution site and at the sponsors office . A final close-out of a trail 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 . The file is generally the responsibility of a designated member of the investigating team at the site of the monitor at the sponsors office.  TRIAL MASTER FILE (TMF)

9. The sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents . The storage system used during the trial and for archiving (irrespective of the type of media used) should provide for document identification, version history, search, and retrieval . Essential documents for the trial should be supplemented or may be reduced where justified (in advance of trial initiation) based on the importance and relevance of the specific documents to the trial. MANAGING OF DOCUMENTS

10. The importance of good documentation practice needs to be emphasized to investigator sites to ensure that the study results are built on the foundation of credible and valid data . GOOD DOCUMENTATION PRACTICE

11. PRINCIPLES OF GOOD DOCUMENTATION PRACTICE Any basic training in clinical research will definitely include these phrases: ‘What is not documented is not done!’ ‘Document what is done as well as what is not done!’ Roots of good documentation principles are in the ICH-GCP where source data and source document is first defined.

12. SOURCE DOCUMENTS AND SOURCE DATA SOURCE DOCUMENTS: Original documents , data and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, X-rays, subject files, and records kept at the pharmacy, at the laboratories and at medico-technical departments involved in the clinical trial)  SOURCE DATA: All the information in the source document are said to be the source data .

13. Key attributes for good documentation were first described by US-FDA in the form of ALCOA-C. These are also adapted by World Health Organization (WHO) .

14. Let‘s look at these attributes described by different authorities collectively. ATTRIBUTABLE It should be clear who has documented the data. LEGIBLE Readable and signatures identifiable. CONTEMPORANEOUS The information should be documented in the correct time frame along with the flow of events. If a clinical observation cannot be entered when made, chronology should be recorded. Acceptable amount of delay should be defined and justified. ORIGINAL Original, if not original should be exact copy; the first record made by the appropriate person. The investigator should have the original source document. ACCURATE Accurate, consistent and real representation of facts.

15. HOW CAN THE DOCUMENTATION BE IMPROVED? PI( principle investigator ) should delegate responsibilities to staff adequately trained in protocol and GCP. PI should commit for i nvolvement , and supervision throughout the entire duration of the study. Site should develop a SOP for good documentation . This SOP should be shared with the sponsor/CRO and agreed upon before the start of the trial .  Before the trial commences all technical aspects such as for e-CRFs, fax, printers, etc. should be clarified and issues resolved . In case of any difficulties during the trial, sponsor should be informed and back-up plans agreed upon till the issue is resolved. Sponsor/CRO also plays an important role in ensuring quality of source documentation. Sponsor/CRO should ensure PI’s commitme nt and involvement throughout the study.

16. Source documentation should demonstrate the ALCOA and other attributes as described by regulatory authorities and GCP. Source documentation related findings are the most commonly cited during inspections and audits . PI’s commitment and involvement in the trial makes a huge difference. Efforts to train the sites, understand the sites practices right from the pre-study visit and continuous monitoring and training would definitely help in improving and maintaining the quality of site source documentation practices. Ultimately the source document should speak for itself. It should narrate the medical journey of the patient as it happened to an independent observer-an auditor or inspector and thus form a strong foundation for a good clinical research . CONCLUSION

17. INTEGRATED ADDENDUM TO ICH E6(R1): GUIDELINE FOR GOOD CLINICAL PRACTICE E6(R2) (CHAPTER 8). GOOD DOCUMENTATION PRACTICE IN CLINICAL RESEARCH CHITRA BARGAJE . IMAGES FROM GOOGLE. REFERENCES