1. Provider Adherence to Oral Chemotherapy Dose Adjustment Guidelines UT Clinical Safety & Effectiveness Conference San Antonio, TX October 27-28, 2011 Amy Fowler, MD Alexis Kennedy, CPNP Naomi Winick, MD

2. The Team Team Members CS&E Participants Amy Fowler, MD, Project Leader Alexis Kennedy, CPNP, Project Champion Team Members Naomi Winick, MD, Physician Champion Gretchen Hirschey, RN, Nursing Champion Jessica Rajian, RN, EPIC Champion Christian Tellinghuisen, Database support All the pediatric hematology/oncology fellows Facilitator - Pat Griffith, BS, MT, MBA

3. Childhood Acute Lymphoblastic Leukemia (ALL) Most common malignancy of childhood –50-60 new cases annually in Dallas –About 150 children treated for ALL at any given time Current survival rates vastly improved Oral chemotherapy – Important component of therapy –6-mercaptopurine (6MP) and methotrexate (MTX) –Given daily, at home, for ~ 2-3 years –Dosed based on degree of bone marrow suppression Published dosing guidelines for providers Specific rules for when to hold doses or dose escalate Target absolute neutrophil count (ANC): 500 – 1,500/μL

4. Clinical importance of dosing guidelines Degree of bone marrow suppression –Lower ANC  Improved survival Dose intensity of oral chemotherapy –Greater dose intensity  Improved survival Problem with excessive neutropenia (ANC <500) Risk of serious infections increases Results in held doses (chemo interruptions) Decreases dose intensity due to breaks in therapy Dose interruptions –Greater dose interruptions  Inferior survival Provider adherence impacts all of the above

5. Dose Adjustment Guidelines Dose Escalations Dose escalation when current dose is ≥ 100% –When ANC > 1,500 on 3 CBC over 6 weeks OR 2 successive monthly CBCs –Alternate 6MP/MTX, and increase by 25% each time Dose escalation when current dose is <100% –When ANC remains > 750 and platelets > 75K –Increase doses by 25% every 2-4 weeks –May increase both drugs simultaneously

6. Dose Adjustment Guidelines Holding for Neutropenia When ANC < 500 or platelets < 50K –Hold doses of both 6MP & MTX Restart both 6MP & MTX – After 1 st drop Resume when ANC > 500 and platelets > 50K Restart at 100% prior dose –After ≥ 2 nd drop Resume when ANC >750 and platelets >75K Restart at 50% most recent dose 6

7. Background Data Overall ANC results from retrospective review 2006-2010 7 Average ANC

8. Background Data Percentage of time providers adherent to indicated dose increases 8

9. Aim Statement Improve percentage of time that providers modify chemotherapy doses as indicated by protocol guidelines in children with ALL from 39% to over 75% –From January 1, 2011 to May 31, 2011.

10. 10 Measures of Success Provider adherence –Proportion of times dose escalation made when indicated by the guidelines. –Followed specific rules based on guidelines Used consistent and trained set of providers to make decision on appropriateness of dose escalations Goal to minimize variation in interpretation Goal to improve from 39% to >75%

11. Pareto Chart - Provider Survey Results Most common reason why providers neglect indicated dose escalations

12. Targets for Intervention Provider and nursing education –Awareness of the clinical importance –Review of guideline content Created flow-sheet –Easy access to pertinent labs and dosing Posters with guidelines placed in provider work areas Change in process of clinic flow –Timing of lab draws –Results return prior to patient leaving clinic

14. Flow chart of clinic flow

15. Quality Improvement Timeline 10/29/2 010 Brainst orming session 12/8/20 10 Nursing and Provide r Survey 12/15/20 10 Clinic flow change & dosing guidelin es posted 12/29/ 2010 Flow- sheet introdu ced into medic al record 12/29/2 010- 1/5/201 1 Educati onal sessio ns 1/1/20 11 Data collec tion initiat ed

16. Percent adherence per month compared to pre-intervention

17. Absolute neutrophil count Episodes of neutropenia per patient per month

18. Conclusions Exceeded goal with 90% adherence Increased bone marrow suppression (ANC) No change in frequency of neutropenic episodes May increase length of dose interruptions Longer dose interruptions  Theoretical risk of negative influence on survival rates Must weigh risks and benefits of improved adherence Universal buy-in Nursing staff Families Administration Providers (Mid-level and physician)

19. Challenges Data collection –Very labor and time intensive –Complex spreadsheets –Clinical expertise needed for data evaluation Commitment from providers “set in their ways” Guidelines leaving room for interpretation Difficult to put $$ value on results

20. Next Steps Clinic to continue the interventions Continued monitoring Quarterly chart audits Introduce into EMR system Build reminders and flow sheets electronically Large scale, multi-institution collaborative Need to look at effect on survival rates Publish results Influence the Children’s Oncology Group, organization creating new versions of guidelines