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Short Report
Hydroxyurea therapy for children with sickle cell disease: describing how caregivers make this decision
Susan Creary*, Susan Zickmund, Diana Ross, Lakshmanan Krishnamurti and Debra L. Bogen
Corresponding author:
Division of Hematology-Oncology, Nationwide Children’s Hospital, The Ohio State University, 700 Children’s Drive Columbus, Columbus 43205, OH, USA
Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Division of Hematology/Oncology/BMT, Emory University School of Medicine, Atlanta 30322, GA, USA
Division of General Academic Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, USA
For all author emails, please .
BMC Research Notes 2015, 8:372&
doi:10.-015-1344-0
The electronic version of this article is the complete one and can be found online at:
Received:29 May 2015
Accepted:12 August 2015
Published:25 August 2015
& 2015 Creary et al.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Background
Hydroxyurea (HU) is underutilized in children with sickle cell disease (SCD) because
caregivers frequently decline HU when it is offered. This study explores what impacts
this decision.
Caregivers of children with clinically severe SCD whose children were offered HU previously
were interviewed. We used a qualitative analytical approach to analyze their telephone
interview transcripts. Caregivers who chose HU (n&=&9) reported their children had
severe SCD, sought detailed information about HU, and accepted HU as a preventative
therapy. In contrast, caregivers who did not choose HU (n&=&10) did not perceive their
children as having severe SCD and did not question their child’s provider about HU.
Conclusions
This study identifies specific areas that providers should address to when they discuss
HU with families so that they can make informed decisions. Our study also uncovered
factors that are important to consider when designing future interventions to improve
hydroxyurea acceptance and when developing decision-aid tools to assist caregivers
of children with SCD who are considering disease modifying therapies.
Keywords: H S D Qualitative researchBackground
Sickle cell disease (SCD) is an inherited red blood cell disorder that leads to early
morbidity and mortality [], []. Hydroxyurea (HU) is the only available disease-modifying medication for patients
with SCD []. Clinical trials show that HU decreases vaso-occlusive pain (VOC), acute chest syndromes
(ACS), hospitalizations, and transfusions in both pediatric and adult patients [], [], and current guidelines are to offer HU therapy to all pediatric patients with Hemoglobin
SS and Sβ
SCD to reduce and prevent SCD complications [].
HU is underutilized in clinical practice, and this results in worse clinical outcomes
in pediatric patients with SCD. A major barrier to prescribing HU therapy is that
20&% of patients do not accept HU as a therapeutic option when it is offered []. Surveyed adult hematologists believe that this is because patients are fearful of
side effects [], whereas adult patients suggest that this is because patients lack knowledge about
HU therapy and have unrealistic expectations about the time to effect with HU therapy
[]. For pediatric patients with SCD, caregivers are the primary decision makers but
little is known about the factors that influence their decision about HU. Findings
from caregiver surveys suggest that caregivers are concerned about HU’s side effects
but also may not identify their child as sufficiently symptomatic to warrant HU therapy
[]. However, in-depth studies of caregivers that may identify significant, but unrecognized
caregiver barriers do not exist. Fully understanding the caregiver perspective may
help clinicians provide better education, counseling, and expectations to families
about HU so that caregivers can make informed decisions for their children. It may
also impact the design of future interventions to improve HU acceptance and decision-aid
tools to assist caregivers who are considering other disease modifying therapies for
SCD, such as chronic transfusion therapy and stem cell transplant. In this study we
aim to explore what impacts caregivers’ decision to choose HU or not choose HU therapy
for their children with SCD.
Participant identification
This study was approved by the University of Pittsburgh Institutional Review Board.
The pediatric SCD team at Children’s Hospital of Pittsburgh (CHP) identified pediatric
patients who were offered HU therapy for clinically severe SCD prior to March 2012.
Caregivers were eligible to participate if they were ≥18&years of age and their child’s
medical record confirmed that a SCD provider had offered HU at least once prior to
enrollment. We mailed prospective caregivers recruitment letters that stated the purpose
of the study. All caregivers who contacted the research team after receiving the letter
were interviewed. We then attempted to contact the remaining prospective caregivers
sequentially until thematic saturation was achieved. Caregivers received a $20 gift
card for participating in this study.
Qualitative interviews
The qualitative interviews followed a semi-structured interview guide. (Fig. ) The interview guide was multidimensional, allowing the interviewer to explore different
topical pathways, depending on how respondents answered prior questions. The specific
categories that were chosen were based on a literature review of both HU and medical
decision making []–[], []. The initial interview guide was pilot tested on volunteers without SCD and the study’s
qualitative expert (SZ) and then adjusted to improve the clarity and flow of the questions.
The interviewer (SC) conducted all of the interviews over the telephone from March
to October 2012. SZ trained SC to listen carefully to each interviewee’s responses
to guide the interview spontaneously, avoid repetition, and probe interesting comments
to investigate how caregivers made their decision to choose or not choose HU therapy
when their child’s provider offered it. At the end of the interview, caregivers completed
a short, verbal, demographic survey. A medical transcriptionist transcribed the digitally
recorded interviews verbatim for analysis. SC reviewed these transcripts prior to
the analysis for transcription accuracy.
The semi-structured interview guide
Codebook construction
Two trained coders (SC and DR) read the transcripts iteratively to develop a qualitative
codebook of themes, using the qualitative editing style developed by Miller and Crabtree
[]. All transcripts were double coded and the coders met regularly to resolve any coding
discrepancies.
Medical record review
We used a standardized data collection form to record patients’ demographic information
and the provider-documented indication for HU therapy within the medical record. We
used descriptive statistics to describe demographic data.
We identified 52 patients with SCD at CHP who were offered HU for clinically severe
SCD before March 2012. Nineteen caregivers of 16 patients completed the interview.
Two caregivers contacted the research team after receiving the recruitment letter
and then we consecutively contacted the remaining caregivers (n&=&17) by telephone
until thematic saturation was achieved. Each caregiver we contacted agreed to participate
in the study. Approximately half (n&=&9) of the interviewed caregivers chose HU for
their children with SCD (Table&). The interviews lasted 18–54&min in duration (median 29&min, and mean 32&min).
Characteristics of children with SCD and their interviewed caregivers
During the iterative review of the transcripts, we identified common themes. Caregivers
shared similar comments and views about how SCD’s impacts their daily life and fears
that they had about initiating HU therapy. There were other themes where the two caregiver
groups had more contrasting comments and views (i.e. caregivers’ SCD knowledge, caregivers’
perception of their child’s disease severity, caregivers’ interactions with their
medical team, and experiences with HU).
SCD’s impacts daily life
Most caregivers expressed difficulty living and coping with having a child with SCD.
Many commented that SCD can be unpredictable and sometimes unrelenting. “Well there
is never any rhyme or reason with sickle cell. We learned that over the years.” Others
shared that having a child with SCD significantly affected the entire family because
it frequently interrupted their familys’ plans, careers, and even their ability to
make a living. One stated, “Oh, (the pain episodes) were overwhelming with dealing
with his pain, and I have two other kids. So, it was really overwhelming, plus work.
Like trying to get the strength down and you don’t know where you are going to get
the strength from. But it works. I’ve prayed about it and prayed about it and I’ve
prayed about it and that helps me get through it more than anything.” Caregivers admitted
that their children had become emotionally upset because of their SCD, especially
when the disease limited their activities or resulted in an emergency room visit or
hospitalization.
Fears about initiating HU therapy
Commonly, caregivers stated they were fearful about starting HU therapy, even if they
ultimately decided to choose HU. They expressed anxiety and difficulty understanding
why a child with SCD would be offered HU, especially when they learned it was a chemotherapy
medication. “She (the nurse practitioner) was saying that they use it (HU) on chemo
patients. My thing was like, ‘Well it’s not going to cause him to get cancer or anything
like that?’ And she was like, ‘No, it is not that type of medication,’ and I was like,
‘Oh, okay.’ Because when you hear… when she was explaining to me the medication, when
she was saying that this is what the chemo patients use, and I was like well, my first
instinct was like, do we have cancer and you’re not telling me? That was my first
instinct.”
Caregivers’ SCD knowledge
When caregivers were asked what they felt was important for a physician to know when
caring for patients with SCD, all caregivers commented that providers should give
as much information to parents as possible to better prepare them to deal with their
children’s health. Both groups indicated that they felt they would benefit from having
more information about SCD and some suggested an education program for parents and
patients could be beneficial.
Both caregiver groups had caregivers who achieved a variety of different education
levels (Table&). Responses from caregivers who chose HU suggested that they had a better understanding
of SCD and that they specifically sought more detailed and in-depth information about
SCD and HU. “I’m a parent. They (the providers) just gave me a pamphlet. The pamphlet
doesn’t tell you everything… there’s more research behind the pamphlet… I think that’s
very important to a parent to give their child medication.” In contrast, many caregivers
who did not choose HU admitted during the interview that they had a poor understanding
of SCD and what to expect in the future. “I don’t even know what’s going to happen
when she turns 18 or becomes an adult. Like I don’t know how this runs from now to
Caregiver’s perception of SCD severity
All of the caregivers in the study had a child who had experienced a severe SCD-related
complication, such as ACS or VOC (Table&). Caregivers who did not choose HU, however, indicated that they would only consider
HU if their child had more severe complications in the future. “I see her to be severe,
(to have severe SCD), but I don’t see her to be as severe as some of the cases that
I’ve seen.” A few caregivers in this group also tended to focus on their child’s short-term
health. “More than likely, we’re just concerned about keeping him healthy and stuff
for now.” In comparison, caregivers who chose HU identified medications, such as HU,
as a way to prevent complications and to extend their child’s life. “They say that
your life expectancy (with SCD) is up, like, when you are 42&years old. I know people
who live way past 42&years old. So, there are other ways around it. You have to take
care of yourself. You have to take your medication (HU).”
Caregivers’ interaction with the medical team
All caregivers in this study identified themselves as a decision maker for their child
and stated that they were responsible for their child’s health and medications. When
asked if they trusted their child’s hematologist, most spoke positively about their
relationship with their child’s physician and consistently stated they would recommend
their child’s SCD team to other caregivers.
Although caregivers sought guidance from their families and their child’s health providers,
caregivers who chose HU felt the need to be proactive and ask their child’s providers
questions. “They (the doctors) are easy to talk to, which is good, but also as a parent,
you have to ask questions. You know, if you don’t understand anything. You know, a
closed mouth doesn’t get fed. So if you don’t ask, they’re not going to answer it
for you.” In contrast, caregivers who did not choose HU depended on their child’s
physician to direct the medical decision-making process for their child. “I don’t
second guess anything because I know it’s best for his care. If they (the doctors)
say to do something, then we do it.” Furthermore, some of these caregivers reported
that when their physician offered HU to them as a potential therapy, they did not
engage their child’s physician in a discussion about HU, even when they were fearful
about what they had read or heard from other sources. “I was curious (about HU) and
I came home and I got on the computer and there were so many things about it that
kind of frightened me… There was just a lot and I’m thinking, ‘Wow, what type of medication
is this?’” But when asked in follow up questioning if this caregiver had asked her
provider about what she had read, she paused and said, “No, I didn’t.”
Experiences with HU
Two caregivers who did not chose HU revealed during their interviews that their children
had previously tried HU but discontinued it. They both admitted that their children
took HU for less than 6&months and missed doses. Ultimately, they stated that they
decided to discontinue HU because their children continued to have VOC, experienced
side effects, and did not seem to benefit from HU. “If her (the patient’s) stomach
was hurting too much, we would stop (HU) for a couple of days and then we’d say, ‘Ok
let’s try it again’ and that type of deal. But it really was bad. It (HU) really made
her stomach hurt a lot. She really did not enjoy taking it whatsoever.” One of these
caregivers went on to state that her child’s experience with HU was so terrible that
she would not consider HU therapy in the future, even if their child’s SCD-related
symptoms were to worsen.
In contrast, we asked caregivers who chose HU to share what they would tell another
caregiver of a child with SCD about HU. They consistently stated that they would recommend
HU because their own children had fewer SCD-related complications and more energy
with HU. “I’d strongly recommend that they give it (HU) a chance and see what it can
do because I’m sure it doesn’t work the same in everybody, but you never know until
you try.” A few of these caregivers also expressed that they would be reluctant to
stop HU therapy under any circumstances because their child was doing so well.
Discussion
HU is an efficacious medication for pediatric patients with SCD, yet many caregivers
do not choose HU for their child when it is offered []. The most recent version of the National Heart, Lung and Blood Institute Guidelines
recommends that providers “offer HU” to all children with severe SCD to encourage
shared decision making about HU []. The caregiver perspective, however, is largely unknown, and pediatric hematologists
and nurses may find this information useful to better counsel caregivers about HU
and to improve HU utilization.
It is important to note that all caregivers reported that SCD negatively affects their
daily lives. These comments are striking and highlight the need for more widespread
use of efficacious therapies, such as HU, to mitigate SCD complications. We also found
that even caregivers who choose HU for their children reported being fearful about
initiating HU. To overcome this fear, we suggest that providers initiate early and
ongoing discussions about HU with families. This gives families time to gather information
about HU and allows providers the opportunity to address parental fears before severe
SCD complications begin to manifest and persist in patients’ daily lives.
Also, our interviews suggest that knowledge among caregivers of children with SCD
is quite variable. It is clear, however, that caregivers want more information about
SCD, its complications, and HU therapy so that they can make informed decisions. We
suggest that the first step is to formally assess caregivers’ health literacy since
this is associated with health outcomes [], [] and then to assess caregivers’ SCD knowledge, potentially using the validated Sickle
Cell Knowledge Questionnaire []. Once health literacy and SCD knowledge gaps are identified, targeted interventions
such as group education sessions, which have been shown to successfully improve knowledge
for patients with chronic diseases, could be used to inform caregivers [].
All of the caregivers in this study had children who had experienced a severe SCD
complication, but similar to Oyeku et al. [], many caregivers who did not choose HU did not perceive that their child had severe
enough SCD to warrant HU therapy. Some possible explanations for this are that caregivers
may not understand that frequent VOC and ACS are severe complications, have other
children with SCD to use as a comparison, or want to acknowledge that their child
has severe SCD.
It is important to note that a few caregivers on this study who did not choose HU
had children with Hemoglobin SC disease. Although patients with Hemoglobin SC SCD
typically have a milder clinical phenotype compared to patients with Hemoglobin SS
SCD, patients with Hemolglobin SC can still have severe disease manifestations and
for these patients, many providers will offer HU since small studies show it can be
beneficial []. Thus, we suggest that providers routinely update families each time their child
has a severe SCD-related complication so they can accurately assess their child’s
risk and disease severity, since as many as half of parents will rate that their child
has mild SCD [].
In contrast to prior studies [], [], caregivers in our study did not consistently state that HU side effects were an
important factor in their decision to choose or not choose HU. The caregivers of the
patients that discontinued HU therapy did comment that side effects were a problem.
Our results and other surveys suggest that caregivers may still have concerns and
misconceptions about HU therapy and its potential to cause malignancy []. To overcome these potential barriers, we suggest that clinicians anticipate these
questions and specifically address these concerns in their early discussions about
HU with families. For instance, physicians could provide all families with the same
information on HU, such as the indication for wanting to start this therapy, the length
of time to expect before HU may begin to reduce symptoms, the importance of regular
HU adherence, the theoretical malignancy risk, and the common side effects they may
encounter so that caregivers have fewer unanswered questions and unrealistic expectations
Our study has a few limitations. First, inherent in the qualitative study design,
the data is limited to the information that subjects chose to share during the interview.
To facilitate participant sharing, we did reassure caregivers of their privacy and
anonymity prior to their interview. We acknowledge though that the first author [SC]
created the interview guide, completed the interviews, and was a hematology fellow
who intermittently cared for some of the patients around the time that the interviews
were completed and this may have limited the information that some caregivers chose
to disclose. Second, three of the interviewed caregivers were from the same family.
Although it is reasonable to expect that caregivers from the same family would report
similar answers in the interview, each caregiver’s interview was conducted independently
and privately so that caregivers could openly share their opinions even if they were
different from other caregivers within the same family. To prevent over-representation
of one family’s opinion in our results, we continued to interview caregivers of independent
patients sequentially until thematic saturation was achieved. Lastly, although CHP
is a tertiary children’s hospital with similar resources and a similar patient population
to other pediatric SCD Comprehensive Programs in the United States, all of the caregivers
we interviewed had children who were followed at a single institution and may limit
the generalizability of our results.
Conclusions
This study is unique as it provides an in-depth perspective about caregivers’ decision
to have their children take or not take HU. Our results suggest areas where interventions
could be developed (e.g. caregivers’ SCD knowledge or caregivers’ interactions with
the medical team) and tested to determine if they result in increased HU use and improved
outcomes in pediatric patients with SCD. These results could also be used when developing
decision aid tools so that all the factors identified by caregivers as potential barriers
are addressed and caregivers feel empowered and informed to make a decision about
HU and other disease modifying therapies []. Finally, although most pediatric hematologists and published guidelines support
that HU therapy be offered to all pediatric patients with Hemoglobin-SS and Sβ
SCD, a consensus that HU is a standard-of-care treatment for children with SCD may
provide the necessary reassurance to caregivers that HU is effective and safe and
may result in more caregivers choosing HU for their children.
Abbreviations
HU: hydroxyurea
SCD: sickle cell disease
VOC: vaso-occlusive pain
ACS: acute chest syndrome
CHP: Children’s Hospital of Pittsburgh
Authors’ contributions
SC, SZ, DB were responsible for the study design and development. SC enrolled the
participants, performed the qualitative interviews, and collected the data, and SC
and DR performed the qualitative data analysis. SC prepared the first draft of the
manuscript, although all of the authors (SZ, DR, LK, and DB) helped to prepare the
final draft of this manuscript. All authors read and approved the final manuscript.
Authors' information
Susan Creary is an Assistant Professor of Pediatrics at The Ohio State University,
Nationwide Children’s Hospital in Columbus, Ohio. She completed her fellowship in
Pediatric Hematology/Oncology at the University of Pittsburgh and her goal is to improve
utilization of therapies, such as hydroxyurea, for children with sickle cell disease.
Susan Zickmund is an expert in mixed qualitative-quantitative methods focusing on
barriers to adherence as well as other complex topics, such as Military Sexual Trauma,
and patient satisfaction. She is an Associate Professor in Medicine and the Clinical
and Translational Science at the University of Pittsburgh and is the Co-Chair of the
Veterans Administration (VA) Center for Health Equity Research and Promotion’s (CHERP)
Qualitative Core located in Pittsburgh, Pennsylvania. She has a PhD in Communication
Studies from the University of Wisconsin-Madison which she gained in 1993.
Diana Ross has 12 years of research experience with a focus in qualitative and mixed
methods. She is currently a research coordinator at Emory University in the Hematology
Department and is pursuing a PhD in nursing research.
Lakshmanan Krishnamurti is a Professor of Pediatrics and the Director of Bone Marrow
Transplant within the Emory University School of Medicine. He is board certified in
Pediatrics and Pediatric Hematology/Oncology. He has over 20 years of research experience.
Debra L. Bogen is a board certified pediatrician. She directs the HRSA NRSA T32 in
Primary Care Research at the University of P Dr. Creary was a fellow in
this program. Dr. Bogen also conducts maternal-child health research and provides clinical care to children in the Children’s Hospital
of Pittsburgh Primary Care Center and Magee-Women’s Hospital of UPMC.
Acknowledgements
The authors would like to thank Lionola Juste, MS for assistance in data collection
and table preparation and Melissa Byrne, MPH, RN for protocol development and data
monitoring.
Sources of support
T32HP22240 HRSA NRSA for Primary Medical Care Research. National Institutes of Health
UL1 RR024153 and UL1TR000005 Grant.
Compliance with ethical guidelines
Competing interests The authors declare that they have no competing interests.
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