Clinical Issues

1. where the patients are Clinical Issues Andrey Bazovoy Director, Clinical Operations 29 November 2013

2. Agenda • Financial awareness for a CTA/CRA • Managing Customer expectations • SVR writing requirements • Project and staff Utilization • Start of a Project

3. + new business, salary backlog, ….

4. Easter CT CLINSTAR PRI Quality Timeliness Money saving Good recruitment Good relationship with the sites The same – Sponsor Expertize Local requirements Staff experience + knowledge English skills Competitive field

5. Budgeted hours vs spent hours => project realization • All services are against to the approved budget • Scope of work

6. Competitive Advantage What is 3 ? 1) New project 2) re-purchase business 3) See slide 4

7. Training: • ICH GCP • Helsinki declaration • FDA / EMEA • GMP ann 13 • GLP • GDP • Local requirements (GOST, MoH,…) CEC • Site’s requirement/local EC • SOP Sponsor/CrPh • Protocol/Project requirements • Communication skills/Personal/soft skills • Therapeutic knowledge CRA’s core competencies Communication ok/yes……. - ……… Verification 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) Protocol knowledge Listening skills Competence Reliability Understanding Responsiveness Credibility Site Security/Confidentiality Sponsor Access - Availability Tangibles The answer I will find out and get back to you (date) I will double check and inform you asap We are working on that. I will update you shortly ……….. Customer Courtesy (attitude)

8. >100% Project and staff Utilization Utilization • Ratio of billable hours (charged to projects) to total hours (incl. leave and sick time) • measure of amount of work performed towards Sponsor deliverables. Standard Utilization Goal for the Billable Group is

9. How to write SMV Reports_writing requirements? Annotated report to be available before each type of the visit Clear for the PM and Sponsor (обходить общих оценок, как то «все хорошо», «в центре все есть»,…..Или, например, «….the PI was not met during that MV …….хххххhave not been signed». Read before sending to PM/Sponsor Provide your feedback reg the format of a report to QM (cc your Manager) Completed reports must: be spell checked & grammatically correct be written in the third person state complete terms and titles before employing acronyms, initials or abbreviations. For example, if IP is to be used to refer to the Investigational Product, the first mention of IP must be written out and followed by the acronym in parentheses as follows: Investigational Product (IP).

10. BEFORE BEGINNING THE SVR 1. Items Needed • Copy of SVR annotation (this document, or project-specific annotations). • Previous SVR for site (To compare and confirm issue resolution.) • Copy of follow-up letter (if available) (to compare and ensure that all items match and are covered). 2. Actions To Be Taken • Check accuracy of all pre-populated information in the report header.

11. Purpose of the MVR • The SMVR should provide readers with an understanding of: • Site Performance including but not limited to integrity of study data and subject safety. • Site Issues/Problems of concern, such as compromised subject safety, protocol or regulatory compliance and IP management issues. • How the visit went overall.

12. DOCUMENTING ACTION ITEMS When a site finding is identified, the CRA must create the specific unresolved issue and action plan (section “Actions to be followed-up”) • State WHY & WHEN the deficiency occurred. • State the IMPACT the deficiency has on the study. (regulatory/subject/compliance/safety/monitoring activities) • State the ACTION PLAN that has been implemented (timelines/responsibilities).

13. Action Item Documentation Action Plan documentation must be clear and concise. • When a Site finding occurs, the CRA must create an issue to document the finding and the resulting action plan. • Action Plan show the Sponsor what happened at the Site and what CromosPh CRA is doing to fix the situation. It is important for the Sponsor to know that the CRA is working with the Site to ensure protocol/regulatory compliance. • Also, Site re-training should always be documented. Action Issue/Plan should be addressed at every visit until they are resolved. • All issues noted in the report should be carried over into the follow-up letter so that the Site staff/PI is appropriately notified of their follow-up tasks and the Monitor’s follow-up tasks.

14. SVR Review process • Site Monitoring Visit Report • Draft report to be submitted to PM/DCO -> 10 working days after the visit • Report to be reviewed and corrected with PM and approved -> 10 working days • Final report to be sent to Sponsor -> 20 working days (from the date of visit) • Day 0*             Monitoring Visit • Day 14 (or sooner)       Submission of Draft SVR & F/u letter sent to site • Day 28 (or sooner)       SVR final Approval

15. What does a site expect from the CRA/Project Team? 1)Lack of communication (btw CRA and PI) 2) Protocol knowledge 3) Fast making decision 4) Payment in time 5) English knowledge 6) Accessibility 7) help from CRA (project knowledge) 8) Accuracy 9) Pt recruitment (booster visit,….) What does a Sponsor expect from the CRA/Project Team? 1) See above

16. General issues: New CRAs in Georgia 365 MO (key docs, all correspondence) Follow up letters in Russian Upcoming absence for the long Bank Holiday in Russia (31DEC – 08Jan2014)

17. Topics for the next month: • Project Start UP • Patients’ recruitment training • Your proposal…….. • Out of Scope activity - PM