Clinical trial process

1. Clinical Trial Process Sunitha P. 1

2. Contents 2 Introduction to clinical trial process Study Plan Study Implementation Analysis Conclusion

3. introduction Clinical trial process involves planning, implementing and analyzing clinical study 3 Study Plan Implementation Analysis

4. Study plan 4

5. Protocol development Protocol development and finalization: Protocol is a document that describes the objectives, design, methodology and statistical considerations of a clinical trial An outline protocol to describe the basic details of the trial is initially prepared Written according to GCP standards After number of discussions and meetings, the protocol is finalized 5

6. Informed consent form Informed consent form is the learning the key facts about a trial before deciding whether to participate. Research study purpose Risks/Benefits Alternative treatments Confidentiality of records Medical treatment available if injury occurs Whom to contact for answers to questions Statement that participation is voluntary Informed consent form is finalized before submitting to the IRB approval 6

7. Case report form Case report form is a data capture tool used in obtaining data about the subjects CRF is designed and finalized according to the protocol CRF can be paper based or electronic Data recorded on the CRFs is used to analyze the data according to statistical plan and interpret the results One study can have one or more number of case report forms 7

8. Database design and finalization Clinical data management encompasses the entry, verification, validation and quality control of data gathered during the conduct of the trial. The database is designed, tested and finalized before the initiation of the trial CSV(Computer system validation): All computer systems used in processing and management are validated CDISC (Clinical Data Interchange Standards Consortium) leads the development of global system independent data standards 8

9. Site selection process Site selection is based on Access to patient geographic distribution Past performance of site team Capability to recruit anticipated number of enrollment Availability of required equipment or specialized staff Confidential Disclosure Agreement (CDA) is sent to the sites Site Feasibility Questionnaire (SFQ)is sent to the site 9

10. IRB/IEC Approval IRB/IEC is an independent body constituted of medical, scientific and nonscientific members This committee has been designated to approve, monitor, and review biomedical and behavioral research involving humans with the aim to protect the rights and well-being of the subjects All clinical trials require favorable opinion from Ethics committee before site initiation 10 INITIATION

11. Study drug supply finalization Before the initiation drug supply plan is finalized Matching placebo is also ready Shipment of drug Primary, secondary packing and labeling is ready Blindedness testing, stability testing Storage requirements Site SOP for the inventory, usage and return/disposal is ready 11

12. Study implementation 12

13. Site activation Conduct investigator meeting Contract negotiations/agreements Prepare regulatory documents FDA form 1572, CVs, financial disclosure etc. Provide sites with clinical supplies Lab kits, drug supply etc. 13 Ready ACTIVATION

14. Initial patient screening Patients are selected on the basis of inclusion and exclusion criteria I/E criteria is a screening questionnaire that evaluates the subject’s eligibility to participate in the study Informed consent form is signed by the subject after the screening questionnaire 14 Meets Criteria

15. Informed consent Eligible subjects are informed about the required information about the study Informed consent is signed by the subjects after decision 15

16. Baseline exam and enrollment Baseline examination is the assessment taken before the subject is given any treatment Demographic data Physical examination data Clinical data Lab data etc. The subject is enrolled and randomized into the study after the baseline parameters are taken The enrolled subject is given the treatment assigned to the study group. 16

17. DATA acquision and data entry Data comes from various source documents From Subject - Diaries, self report, questionnaire Investigators - clinical findings Lab test reports – Urine, blood test, ECG etc. Other sources – previous medical records etc. Data from the source document is entered into the case report forms Events are coded using standard medical dictionaries 17

18. Data validation Data validation plays key role in discrepancy management Validation is checking the data for discrepancies and outlier values Objective for data validation is to assure the validity and accuracy of the data In case of discrepancy, a DCF (Data Clarification Form) is raised and sent to the investigator 18 DCF

19. Data cleaning and Quality control After the queries are resolved, the database is updated The updated database is now ready for the quality check Quality control procedure is run to assure that the database is clean with no discrepancies Data listings are reconciled with DCF and CRF Safety data is reconciled with pharmacovigilance SAE data 19 Quality

20. Database lock The database is locked after all corrections are done A locked database means All discrepancies closed DCFs received and updated coding complete SAE Reconciliation complete The data is ready to be submitted for analysis 20

21. Statistical analysis 21

22. Statistical Analysis and regulatory submission Import study data for analysis Statistical analysis is done by SAP (Statistical Analysis Plan) Primary and secondary outcome measures are calculated using statistical analysis methods Eg : Mean, t-test and chi-square test etc. After the statistical analysis, the tables, listings and figures are published Clinical Study reports are generated for the regulatory submission 22

23. Conclusion Clinical trial process involves careful planning, implementing and analyzing a clinical trial with good practices A clinical trial must be planned in such a way that the prerequisites are ready in time After careful planning, the study must be implemented and data must be maintained with high accuracy for the subsequent analysis Unambiguous conclusion regarding the clinical outcome of the test treatment/device is ideal One must always strive for the ideal, but in most cases have to settle for the best comprise 23

24. Questions ? Thank You 24