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Methods
The methods used to develop hypotheses for the impact of infusion ICT on patients with iron
overload is detailed below. It involved a systematic literature review, patient and expert interviews.
Literature review
We conducted a literature review using
electronic databases (Medline and Embase) from 1966 to 2004. The review used a subject and text word search strategy with 'iron
chelation', 'thalassemia', 'sickle cell', and 'myelodysplastic syndrome' combined with the terms 'quality of life', 'burden of illness',
'compliance', 'cost', 'cost benefit', 'cost consequence', 'economic evaluation' and 'utility' as the main search terms. In addition,
Evidence Based Medicine (EMB) reviews were searched including Cochrane Database of Systematic Reviews (CDSR), American College of
Physicians Journal Club (ACP), Database of Abstracts of Reviews of Effects (Dare), and Cochrane Control Trial Register (CCTR).
Further, an additional search was done of the Health Economics Evaluation Database (HEED).
For HEED, the phrases 'iron chelation', 'thalassaemia', 'sickle cell', and 'myelodysplastic syndrome' were used.
The review was restricted to English language studies. To satisfy the inclusion criteria,
studies had to contain articles that were specific to:
• Iron overload and its treatment in thalassemia, SCD or MDS; or
• Iron overload and QoL research.
Any QoL measures that were found to have been used in the context of patients with iron
overload were further researched in the Patient Reported Outcomes Quality of Life International Database (PROQOLID), a database that
provides a brief overview of questionnaires used with patients.
Patient interviews
The interview transcripts of nine patients with iron overload were assessed (4 thalassemia, 1
SCD, and 4 MDS) to determine patients' experiences about the impact of iron overload and its treatment on their daily lives. In addition,
four patients (2 thalassemia, 1 SCD, and 1 MDS) participated in a market research study. As part of this study, the patients were asked to
provide an overview of the impact of iron overload on their lives. We reviewed the transcripts from these historical interviews in order
to gain further insight into how infusion ICT impacts patients' lives.
Expert interviews
Three iron overload experts representing the UK, US and Italy were interviewed about their
observations of the impact of iron overload and its treatment on patients.
Results
Literature review
At the onset of this review, 539 abstracts were screened, of which 409 were excluded because
of the absence of search terms from either the title or the abstract. In total, 130 articles were reviewed; of which only 15 empirical
studies had used validated QoL instruments. Of these, 7 were SCD studies [17-23], 4 were MDS studies [24-27], and 4 were thalassemia studies
[2,3,28,29]. All of the evaluated studies
focused on the impact of thalassemia, SCD or MDS on patient QoL rather than the impact of ICT on patient QoL. However, mention of the
impact on QoL of infusion ICT appears in a number of instances. In one such study, over 50% of patients reported that their activities
were often or very often prevented due to DFO treatment and 65% reported dislike of DFO. In addition, 56.2% reported that they would be
able to do more things if they did not have to take DFO [3]. In
another study, the degree of discomfort associated with DFO treatment was a strong predictor of negative perception of QoL, with the
majority on DFO reporting QoL to be fair or poor.
A recurring theme with these patients is the impact of infusion ICT. When these patients were
asked what might improve their QoL, the most frequent response concerned the improvement of ICT, particularly the development of an oral
drug [28].
Additionally, in another study results indicated that 33% of patients (17 out of 51) with
thalassemia or SCD recorded a score of zero in every category of the Sickness Impact Profile (SIP) indicating that some perceived a
reduced QoL during DFO therapy [30].
A significant number of anecdotal reports, as well as information derived from clinical
experience exist that corroborate our findings regarding the impact of iron overload or ICT on QoL. All the articles reviewed agreed that
the infusional (characteristic) of Desferal 5–12 h/d five days/week is a strong impediment of QoL [2,3]. As a
corollary, effective oral ICT should improve the QoL of those with iron overload [2,3,17-29]. Further, QoL domains reported as being affected included depression resulting in more
hospital visits [20], fatigue, dyspnoea, physical functioning,
psychological distress [25], and a general decrease in QoL
during hospitalisation [26].
QoL instruments identified from the search included uni-dimensional scales such as the
Geriatric Depression Scale (GDS), bi-dimensional scales such as the Hospital Anxiety and Depression Scale (HADS), and multidimensional
instruments such as the Medical Outcomes Study Short Form Health Survey 12 items or the 36 items. However, no iron overload-specific QoL
instruments were found.
Results from patient and expert interviews
Since results from the literature review revealed that there were no iron overload specific
QoL instruments, hypotheses were generated based on patient and expert interviews in order to develop a disease-specific instrument.
Results revealed that the impact of ICT or iron overload on QoL is high but will likely differ by the age of the patient (child,
adolescent, young adult, middle aged adult, elderly adult), the length of time on ICT, and by the condition (thalassemia, SCD, MDS).
Figure 1 provides an overview of the hypotheses for the impact of infusion ICT on the QoL
of patients with iron overload. In thalassemia, the impact of infusion ICT on QoL is most profound, since patients are required to begin
treatment at a very young age (often as young as two or three years old) and continue throughout their life. As a result, the impact on
the parent can also be quite high since they have to endure the daily task of inserting a needle into their child and constant battles
with their child in order to comply with the treatment regimen, which would then increase parental stress-levels. These battles can carry
on from the youngest age through adolescence and therefore may have a negative impact on the parents' relationship with their child and
may also cause the child to become over-dependent on their parent. In addition to this, the parent may feel tremendous guilt when they
'give in' to the child's wish not to comply, since they know that the ICT is required to help their child live longer. In addition, as the
child reaches adolescence or early adulthood and becomes more in control and responsible for their own treatment, parents may worry if
their child is not adequately adhering to the treatment regimen.
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