Enhancing Research Efficiency: Less Worry, More Work in Quality Improvement Programs

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!