Partners Human Research Quality Improvement Program QUICK BITE Series

1. Partners Human Research Quality Improvement Program QUICK BITE Series More Work is Less Worry Guidance to Lessen Regulatory Concern Sarah White,QI/QA Specialist Swhite12@partners.org March 10, 2005

2. More Work is Less Worry • To work, or not to work • What are we worrying about? • Systems are the “work” • Practical Tips/Systems • Questions & Discussion

3. To work, or not to work Site A has worked hard to put systems in place to manage their hefty research study load * Versus * Site B jumped right into their research studies and took on the attitude of handling things as they come up **Both sites are very successful at enrolling and completing their subjects.

4. To work, or not to work Both Sites A and B are called by the FDA and told they will be audited. The FDA auditors will arrive at their offices at 9 a.m. the following day. Of particular interest, the FDA would like to see subject enrollment records and drug accountability records.

5. To work, or not to work Site A • PI and Study Coordinator review both the master enrollment log and drug accountability log • The site also plans to provide FDA with a delegation of responsibility log to inform FDA of study staff responsibilities

6. To work, or not to work Site B • Has not been maintaining an enrollment log • Progress notes within the subject binders track the quantity of investigational drug and date given to subject Site B is in for a long day (and night) creating an enrollment log and accounting for drug disposition of their 237 subjects!

7. What Are We Worrying About? • Notification of audit • Audit findings • IRB continuing review • Protocol noncompliance Up all night cleaning up files FDA warning letter Study deferral and/or expiration Violations/deviations subject safety/data integrity

8. Systems Are the “Work” Systems should be: • In place before the study starts • Simple, standardized, and well understood by their users • Consistent • Documented

9. Examples of Good Systems • Collective Filings • Logs • Checklists • Monitoring Plan • System to Reporting AEs and Violations • Outlook Calendar • Site Guidelines

10. Collective Filings • CVs need to be signed and dated and kept up-to-date • For those sites with large numbers of investigators and study staff: • Keep CVs in a central location • Select a ‘renewal’ date for all CVs • Mark it on your Outlook calendar

11. Study Logs • Logs that are unique to your study will help you track it’s progress • Delegation of Responsibility Log • Enrollment Log • Drug/Device Accountability Log • Adverse Event Log • Violation/Deviation Log

12. Checklist for Each Study Visit • Prevent missing procedures • A checklist for each study visit or telephone call will help you manage the visit, so you know • All procedures have been completed • Which procedures have not been completed • If any violations need to be reported

13. Monitoring Plan • Ensure your data is trouble free on a regular basis • Be realistic about your monitoring plan • Follow monitoring plan timelines • Recruit outside help

14. Adverse Event Reporting • Having an AE reporting plan can take the worry off meeting reporting requirements • Who do you report event to? • What are the reporting timelines? • What information is required? • Are you responsible for follow up?

15. Violation/Deviation Reporting • Violations do occur. • How do you deal with them? • Major vs. minor (PI determines) • Know what information is required for reporting • System to track all violations • System to prompt amending the protocol • Summarize minor violations at Continuing Review

16. Valid Consent Forms There will be unexpected consent form changes during the course of the study • Create a log that tracks consent from changes • Check in with protocol administrator for approximate review date • Dispose of all outdated consent forms as soon as new consent form has been approved

17. Continuing Review Preparation • Make the continuing review process prospective, not retrospective • Know what information is required for continuing review application • Track form specific information throughout the year (can be incorporated into your enrollment log) • # found ineligible • # lost to follow-up • # terminated due to adverse events • Mark Continuing Review dates on Outlook and set the ‘reminder’ to remind yourself

18. Use Your Outlook Calendar Don’t dismiss reminder! • Mark due dates for continuing reviews (i.e., 90, 60, 45 day reminders) • Mark deadlines for AE reporting and follow-up • Mark anticipated review/approval of amendments • Mark when consent forms expire

19. Study Site Guidelines • Develop study site specific guidelines and tools • Who is responsible for what? • Where are study medications, questionnaires, subject binders, IRB documentation stored? • What are the expectations for documentation?

20. Who should be aware of the ‘work’ • Principal Investigators • Co-Investigators • Study Staff • Other Individuals involved (e.g. open communication with Sponsor)

21. Utilize Your Resources • Partners HRC website http://healthcare.partners.org/phsirb/ • CCI for BWH • www.brighamandwomens.org/cci/ • CRP for MGH • www.mgh.harvard.edu/depts/crp/ • QI Program • http://www.partners.org/phsqi/

22. Questions? *** Systems to Share?

23. Upcoming QI QUICK BITE Lecture “Share Our Stories – Case Studies from the Field” Do you have a case study or story that you’d like to share? The QI Program is welcoming case studies to include in our next lecture. Please contact Sarah White (swhite12@partners.org / 617-424-4137) if you have a case study that will help others in the research community learn!