predictors of non-adherence to oral chemotherapy in children with acute lymphoblastic leukemia a ...

231 Pages·2010·4.64 MB·English

PREDICTORS OF NON-ADHERENCE TO ORAL CHEMOTHERAPY IN
CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

A DISSERTATION SUBMITTED TO THE GRADUATE DIVISION OF THE
UNIVERSITY OF HAWAI'I AT MĀNOA IN PARTIAL FULFILLMENT OF THE
REQUIREMENTS FOR THE DEGREE OF

DOCTOR OF PHILOSOPHY
IN
NURSING
December 2010
By
Wendy Landier

Dissertation Committee:
Sandra A. LeVasseur, Chairperson
Smita Bhatia
Francisco A. Conde
Joe Mobley
Patricia W. Nishimoto
Randal K. Wada

Keywords: childhood acute lymphoblastic leukemia, oral chemotherapy, adherence
UMI Number: 3448679

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ii

Unpublished Work
Copyright (2010) by Wendy Landier
All Rights Reserved
iii
Acknowledgments
This dissertation is the product of an extraordinary journey, throughout which I
have been blessed with outstanding guidance, mentorship, and support. I was particularly
fortunate to be granted access to a rich data set from which I have learned so much, and
for that I am extremely grateful to Smita Bhatia, MD, MPH, Principal Investigator of the
Children’s Oncology Group (COG) study from which the data were drawn, as well as to
the 86 COG institutions that collected the data, and to the patients and their parents who
so selflessly participated in order that we could learn from them what might benefit future
patients. In addition to providing access to the data, Smita Bhatia also served as an
exemplary mentor, overseeing my analysis throughout all its phases and providing expert
guidance at each step along the way. I will always be incredibly grateful to her for her
kindness and generosity in sharing both her time and expertise with me.
I have also been very fortunate to have received outstanding mentorship from the
faculty of the School of Nursing at the University of Hawai'i at Mānoa. Sandra A.
LeVasseur, PhD, RN, chair of my Dissertation Committee, provided exceptional
guidance and support as I progressed through each academic requirement, and always
offered thoughtful insight and direction at every juncture. Her remarkable leadership in
directing a PhD program that harnesses technology in order to provide the high level of
academics and mentoring that I received across the thousands of miles physically
separating me from the faculty and university is truly extraordinary, and is what made
pursuit of doctoral education possible for me. I will always be indebted for her for
providing this incredible learning opportunity.
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Francisco A. Conde APRN, PhD, AOCNS, and Joe Mobley, PhD, MA, both
members of my Dissertation Committee, are also outstanding educators who provided me
with the foundation in statistical analysis during my coursework that was so necessary for
completion of this work. Patricia Nishimoto, RN, DNS, and Randal K. Wada, MD, also
key members of my Dissertation Committee, supplied insight and guidance that were
extremely helpful in provoking additional thought regarding data interpretation. I will
always remember and appreciate the kind assistance that I received from all of my
committee members in selflessly sharing their time and insights with me.
In addition to the University of Hawai'i faculty, two School of Nursing staff
members also provided outstanding support across the years. Aeza Hafalia-Bobo tracked
and coordinated all the details necessary for successful defense of both my
Comprehensive Exam/Dissertation Proposal and my Dissertation, and James Callahan
lent his expertise in providing the audio and video links that allowed on-line participation
for those unable to attend in person. In addition to facilitating these events specifically
on my behalf, Aeza and James also provided outstanding support throughout my entire
experience in the PhD program. I am also incredibly appreciative of the support and
kindness of my fellow PhD students throughout this journey – I have many treasured
memories and new friendships as a result.
I would also like to acknowledge the outstanding guidance that I received from F.
Lennie Wong, PhD, statistician at City of Hope, who provided expert statistical guidance
and technical review of my analysis, and would like to extend sincere thanks to Lindsey
Hageman, MPH, coordinator of the COG study, for her incredible organizational skills in
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transforming a massive amount of raw data into a well-annotated data set, and for her
persistence in tracking down missing pieces of data from the COG institutions.
Additionally, the support received from the American Cancer Society in the form of a
Doctoral Scholarship in Cancer Nursing (#DSCN-09-138-01), is also gratefully
acknowledged.
Finally, I would like to extend heartfelt thanks to my family for their support,
patience, and understanding over these past three years. To my husband David – thank
you from the bottom of my heart for giving me the time, space, and encouragement that I
needed to pursue this dream. The sacrifices that you made were enormous, and I will
never forget them. To my sons, Michael and Bryce, and to my sister, Patty – your
thoughtfulness and encouragement (and occasional help with statistics) were so very
much appreciated. And to Mom and Dad, who fostered in me a love of learning and the
belief that I could be anything that I wanted to be – I only wish that I could have shared a
bit of this extraordinary journey with you. It is in your honor that I dedicate this work.
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Abstract
Overall survival for pediatric patients with acute lymphoblastic leukemia (A.L.L.)
treated with contemporary therapy now exceeds 85%; however, approximately 20% will
experience relapse. Since A.L.L. is the most common malignancy in children, relapsed
patients comprise a large proportion of the total number of children with cancer. The
prognosis for long-term survival following relapse is generally poor; thus, relapsed
A.L.L. is a significant contributor to cancer-related mortality in children.
Poor adherence to oral medication is a substantial problem in contemporary health
care and may contribute to unexplained relapses in children with A.L.L. Therapy for
pediatric A.L.L. includes a prolonged “maintenance” phase that requires daily 6-
mercaptopurine (6MP), a self- or parent/caregiver-administered oral chemotherapy agent
given for approximately two years. 6MP has been shown to be a critical component of
the curative regimen for A.L.L.; thus, children with A.L.L. who fail to adhere to oral
6MP chemotherapy as prescribed may be at increased risk of leukemia relapse.
This study used extant questionnaire data from a cohort of children with A.L.L
enrolled on a Children’s Oncology Group study (AALL03N1) to determine the
prevalence of self/parent-reported non-adherence to oral 6MP during the maintenance
phase of A.L.L. therapy, and to identify sociodemographic and behavioral predictors of
non-adherence to oral 6MP.
Twenty-two percent of children in the cohort were non-adherent to oral
chemotherapy, defined as missing more than one dose of 6MP for non-medical reasons
over the 112-day observation period. The risk of non-adherence was significantly
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increased for those who failed to perceive the severity of the child’s illness (Odds ratio
[OR] 1.89, 95% Confidence Interval [CI] 1.00-3.55, P=0.049) or the benefits of treatment
with oral 6MP (OR 1.78, 95%CI 1.07-2.94, P=0.025). Vulnerable subgroups included
Hispanic ethnicity (OR 2.25, 95%CI 1.30-3.90, P=0.004) and older age (OR 1.07 per
year, 95%CI 1.02-1.12, P=0.005).
Study findings suggest that even occasional reports of missed 6MP doses may
herald a significant adherence problem; that patients and their parents may need ongoing
reminders regarding the subclinical and asymptomatic nature of leukemia in remission;
and that frequent review with families regarding the purpose, function, and proper
administration of oral 6MP is imperative.
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Table of Contents
COPYRIGHT...............................................................................................................................................ii
ACKNOWLEDGMENTS...........................................................................................................................iii
ABSTRACT..................................................................................................................................................viii
LIST OF TABLES.......................................................................................................................................xi
LIST OF FIGURES...................................................................................................................................xii
LIST OF ABBREVIATIONS...................................................................................................................xiii
CHAPTER 1: INTRODUCTION................................................................................................................1
1.1. CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA (A.L.L.).................................................................1
1.2. RELAPSE IN CHILDHOOD A.L.L...........................................................................................................1
1.3. TREATMENT OF CHILDHOOD A.L.L.....................................................................................................2
1.4. ADHERENCE TO MEDICATION..............................................................................................................8
1.5. THEORETICAL FRAMEWORK..............................................................................................................12
CHAPTER 2: REVIEW OF LITERATURE............................................................................................17
2.1. ADHERENCE DEFINED........................................................................................................................17
2.2. SIGNIFICANCE OF ADHERENCE..........................................................................................................19
2.3. MEASURING ADHERENCE IN CHILDHOOD A.L.L...............................................................................20
2.4. ADHERENCE IN PEDIATRIC ONCOLOGY.............................................................................................23
2.5. DETERMINANTS OF ADHERENCE........................................................................................................28
2.6. CONCLUSIONS: ADHERENCE IN CHILDHOOD A.L.L...........................................................................38
CHAPTER 3: METHODOLOGY.............................................................................................................41
3.1. BACKGROUND...................................................................................................................................41
3.2. PURPOSE AND SPECIFIC AIMS............................................................................................................46
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3.3. SIGNIFICANCE....................................................................................................................................48
3.4. STUDY DESIGN..................................................................................................................................49
3.5. SAMPLE.............................................................................................................................................51
3.6. POWER ANALYSIS..............................................................................................................................51
3.7. HUMAN SUBJECTS PROTECTION........................................................................................................52
3.8. STUDY INSTRUMENTS........................................................................................................................52
3.9. DATA ANALYSIS PROCEDURES..........................................................................................................57
CHAPTER 4: RESULTS............................................................................................................................76
4.1. PARTICIPANT CHARACTERISTICS.......................................................................................................76
4.2. PARTICIPANT CHARACTERISTICS RELEVANT TO SELF-REPORT QUESTIONNAIRE.................................79
4.3. SPECIFIC AIM 1: FINDINGS.................................................................................................................85
4.4. SPECIFIC AIM 1A: FINDINGS..............................................................................................................88
4.5. CONCORDANCE OF PATIENT AND PARENT/CAREGIVER REPORTS: FINDINGS.......................................98
4.6. SPECIFIC AIM 1B: FINDINGS...............................................................................................................99
4.7. SPECIFIC AIM 2: FINDINGS...............................................................................................................102
4.8. FINDINGS IN THE CONTEXT OF STUDY HYPOTHESES.........................................................................110
4.9. SUMMARY OF FINDINGS...................................................................................................................111
CHAPTER 5: DISCUSSION, LIMITATIONS, AND CONCLUSION................................................113
5.1 OVERVIEW........................................................................................................................................113
5.2. DISCUSSION OF FINDINGS IN THE CONTEXT OF THE STUDY’S RESEARCH QUESTIONS........................113
5.3. LIMITATIONS...................................................................................................................................128
5.4. CONCLUSION...................................................................................................................................129
APPENDICES...........................................................................................................................................132