Introduction to Clinical Protocol

1. Introduction to Clinical Protocol Qtech Solutions Inc., NJ USA

2. Topics To be Covered • What is Protocol • Protocol Outline • Protocol Design • Study Procedure • Informed Consent process • Subject Confidentially • Data Recording • GCDMP • Data Management Plan • Data Capture • Data Quality Assurance • Data Validation • Query Management Plan • Best Practice for CRF • Statistical Analysis • Data Locking • Appendices / Supplements • Conclusion Qtech Solutions Inc., NJ USA

3. Protocol • A protocol is a document that states the reasoning behind and structure of a research project • Protocol also defined as a document that describes the background, rationale, objectives, design, methodology, statistical consideration and organization of trial • The Study protocol can be viewed as a written agreement between the investigator , the participants and the scientific community Qtech Solutions Inc., NJ USA

4. ProtocolOutline • A typical protocol has the following elements: • Title Page • Objectives • Signature Page • Study Design • Background Information and scientific rationale • Study Population Qtech Solutions Inc., NJ USA

5. Protocol Design • Study Procedure • Informed Consent process • Statistical Considerations • Literature References • Subject Confidentiality • Supplements / Appendices Qtech Solutions Inc., NJ USA

6. TitlePage • Title pages introduce the document, their title, precise number, sponsor and author to the reader • Protocol title, protocol identifying number, and date • Any amendments should also bear the amendment number and date • The protocol number must clearly indicate the version number, whether it is final or draft and date of this version Qtech Solutions Inc., NJ USA

7. Continue…Elements Full title should include: Summary study design Medicinal products Nature of the treatment (ex: treatment, prophylaxis and diagnosis) Comparator Placebo Indication Patient population Setting (ex: in-patient, outpatient) Randomized Double Blind Multiple Studies Qtech Solutions Inc., NJ USA

8. Continue… 2.Name and address of the sponsor and monitor. Sponsor names and list of responsibilities with agreed allocations 3. Name and title of the person authorized to sign the protocol and the protocol amendments for the sponsor. Generally, Chief Investigator for multiple center trials or Principal Investigator for single center trials 4. Name, title, address and telephone number of the sponsor medical expert for the trial Qtech Solutions Inc., NJ USA

9. Continue… • 5. Name and title of the investigator who is responsible for conducting the trial, and the address and telephone numbers of the trial site • 6. Name, title , address and telephone number of the qualified physician who is responsible for all trial site related medical decisions • Name and address of the clinical laboratory and other medical and /or technical department and /or institution involved in the trial Qtech Solutions Inc., NJ USA

10. Protocol Summary/Synopsis • This summary should be only one to two pages long • It should give the reader sufficient information to understand the rationale for the trial, its objective and the methods that will be used to achieve these objectives Qtech Solutions Inc., NJ USA

11. Study Objective/Aims • A clinical trial often has both primary and secondary objective, and these should be identified as such in the protocol • Ideally, no more than 1 or 2 of each should be included in a clinical trial Qtech Solutions Inc., NJ USA

12. Signature Page • Signature page of the healthcare professional in the trial including contact details of participating site, sponsor and sponsor medical advisor if not already given above. Qtech Solutions Inc., NJ USA

13. Content Page • This helps navigating through the document by large number of different people that will be needed throughout the life of the trial Qtech Solutions Inc., NJ USA

14. Study Design • A description of the trial design should include: • A description of the design of trial to be conducted • ex: double blind, placebo controlled, parallel design • 2) A description of the measure taken to minimize/ • avoid bias • A) Randomization • B) Blinding Qtech Solutions Inc., NJ USA

15. Continue… • A description of the trial treatment and the dosage • and dosage regimen of the IP. Also, include a • description of the dosage form, packaging and • labeling of the IP • 4) The expected duration of subject participation , and • description of the sequence and duration of all trial • periods, including follow up any. • 5) A description of “stopping rile” or “Discontinuation Criteria” Qtech Solutions Inc., NJ USA

16. List of Abbreviation • All abbreviations used should be listed and defined • Accepted international medical abbreviations should be used • Project specific abbreviations should be standardized with each project Qtech Solutions Inc., NJ USA

17. Compliance Statement • The protocol should include a trial statement with the protocol, GCP and the applicable regulatory requirements Qtech Solutions Inc., NJ USA

18. Background Information • Name and description of the investigational product • A summary of finding from nonclinical studies that potentially have clinical significance and form clinical trials that are relevant to the trial • Summary of the known and potential risks and benefits, if any, to human subjects • Description and justification for the route of administration, dosage, dosage regimen and treatment period Qtech Solutions Inc., NJ USA

19. Continue… • Description of the population to be studied • In short, the data in this background information should be able to justify the need for this study Qtech Solutions Inc., NJ USA

20. Selection and Withdrawal of Subjects Subject Inclusion Criteria Subject Exclusion Criteria Subject Withdrawal Criteria Qtech Solutions Inc., NJ USA

21. Treatment of Subjects • The treatment to be administered, including the name of all the products, dose, the dosing schedule, the route/mode of administration and the treatment period • ii) Medication/ treatment permitted and not permitted before and/ or during the trial. • iii) Procedure for monitoring subject compliance Qtech Solutions Inc., NJ USA

22. Assessment of Safety • Specification of safety parameters • ii) The methods and timing for assessing, recording, • and analyzing safety parameters • iii) Procedure for eliciting reports of and recording and • reporting adverse event and inter current illnesses Qtech Solutions Inc., NJ USA

23. Direct Access to Source Data Document • Sponsor ensures that it is specified in the protocol or other written agreement that the investigator will permit trial related monitoring, audits, IEC review, and regulatory inspection by providing direct access to source data/documents Qtech Solutions Inc., NJ USA

24. Informed Consent • Defined as: a patient is being given adequate information about a clinical trial; understanding and voluntarily accepting the terms of a clinical trials and agreeing to cooperate in its conduct Qtech Solutions Inc., NJ USA

25. The following slides are the key concepts to be considered while designing the protocol, which impact the Clinical Data Management • Data Recording • Data Quality Assurance • Statistical Analysis Plan Qtech Solutions Inc., NJ USA

26. Data Handling and Record Keeping • Indicate how data will be collected. If detailed instructions have been prepared, specify their location (study manual, appendix) • Discuss the use and management of source documents • Discuss the procedure for correcting errors • GCDMP • Data Management Plan • Data Capture • CRF Qtech Solutions Inc., NJ USA

27. Data Handling and Record Keeping • Good Clinical Data Management Practices • Provides assistance to clinical data managers in their implementation of high quality Clinical Data Management processes • Used as a reference tool for clinical data managers • Review and approval of new medications or medical devices • Clinical and laboratory information must be collected and converted to digital form for analysis and reporting purposes Qtech Solutions, Inc., NJ, USA

28. Data Handling and Record Keeping 2. Data Management Plan • Record all the most important information on how data management was carried out for a study • The documents are more accurate when written at the start of the study • Provides a focus for identifying the work to be performed, who will perform the work, and what is to be produced as documentation of the work Qtech Solutions, Inc., NJ, USA

29. Data Handling and Record Keeping • Data Management Plan Continued… • Touches the elements of the data management process for the study in question • Becomes an approximate table of contents • Used as a source document for internal quality assurance audits Qtech Solutions, Inc., NJ, USA

30. Data Handling and Record Keeping 3. Data Capture • Electronic Data Capture • EDC systems deliver clinical trial data from the investigation sites to the sponsor • Eliminates the need for double-key data entry • Data management planning and implementation are completed even before data entry is initiated • EDC systems are improved for site activities during a clinical trial Qtech Solutions, Inc., NJ, USA

31. Data Handling and Record Keeping • Best Practice for CRF • A tool used to collect pre- defined data from a subject in a clinical trial • Design the CRF along with protocol • Keep questions, prompts and instructions clear and concise • Design the CRF to follow the data flow from the perspective of the person completing it • Avoid referential and redundant data points within the CRF • Design the CRF with the primary safety and efficacy endpoints in mind • Establish and maintain a library of standard forms • Make the CRF available for review at the clinical site prior to approval Qtech Solutions, Inc., NJ, USA

32. Data Quality Assurance • Describe procedures for assessing subject compliance • Discuss source document review • Provide assurance on good clinical practice, quality of data collection and refer to monitor and their role • Data Validation • Query Management Qtech Solutions Inc., NJ USA

33. Data Quality Assurance • Data Validation • Important role within the drug development program involving many people, multiple systems, and several data transfers • Automated and manual procedures to detect missing entries, illogical data • Ensures Data accuracy and Completeness • Helps to inform Data Managers about data issues in timely fashion • Once data validation is completed it is time for Data Treatment stage Qtech Solutions, Inc., NJ, USA

34. Data Quality Assurance • Data Validation Continued… • Factors affecting the quality of data • CRF design • Field Monitoring Guidelines • Source data verification • Missing data/ CRF pages • Data conventions • Electronic laboratory data Qtech Solutions, Inc., NJ, USA

35. Data Quality Assurance 2. Query Management • Performance metrics are tracked routinely and analyzed periodically to ensure maintenance of the highest data management quality standards • All discrepancies are identified automatically by the system that are reviewed by a data manager • These are resolved internally through inspection of the CRF Qtech Solutions, Inc., NJ, USA

36. Data Quality Assurance • Query Management Continued… • Following actions can be taken based on project specific guidelines • Closing discrepancy per internal connection • Generating a query to the investigator • Creating queries • Sending queries • Tracking queries • Resolving queries • Re-quering Qtech Solutions, Inc., NJ, USA

37. Data Quality Assurance • Query Management Continued… • Turning a discrepancy into a query • Resolving queries • Applying the Resolution • Quality assurance and control Qtech Solutions, Inc., NJ, USA

38. Statistical Analysis Plan • It is critical to specify in the protocol the precise definition of the primary variable as it will be used in the statistical analysis. • Oversees the processes that group, summarize, analyze, and otherwise present trial data for clinical interpretation • Statement of the planned sample size • Classification of the study variables • Information about the timing and purpose of any planned interim analysis • Handling of missing or non- evaluable data Qtech Solutions, Inc., NJ, USA

39. Statistical Analysis Plan • Data Locking • Once the patient’s data has been collected, the study needs to be locked in an expeditious manner • The list involves many steps: • Collecting final data • Resolving outstanding queries • Reconciling against other databases • Performing final QC • After these tasks are done, data manager reviews with the clinical group and the study is considered locked- no data will be changed, from the first patient in through to database lock Qtech Solutions, Inc., NJ, USA

40. Appendices • Based on the protocol, relevant appendices as elaborated should be attached: • Summary of Product characteristics, data sheer for IP • Measurement tools and their validation • Pharmacy information, shelf lives, dispensing procedure • Methods for collecting patient samples, their storage, • dispatch and handling conditions Qtech Solutions Inc., NJ USA

41. Continue… • Clinical labs and tests • Adverse reaction grading systems for particular safety parameters • Scoring systems of efficiency parameters • Analysis diagram • Declaration of Helsinki • Patients and parent/legal guardian consent form • Subject information sheet for informed consent • Method of recruitment of patients/subjects to the trial Qtech Solutions Inc., NJ USA

42. Conclusion • Protocol is a blue print for a study. It contains all the information necessary • Certain Information is required by regulation to be into protocol • The following are the key points that follow Data Management Protocol: • Data Recording • GCDMP • DMP • Data Capture • CRF Practices • Quality Assurance • Data Validation • Query Management • Statistical Analysis • Data Locking Qtech Solutions Inc., NJ USA

43. Thank You For queries or questions, please email at info@qtech-solutions.com Qtech Solutions, Inc., NJ, USA