کیفیت زندگی مرتبط به دهان و دندان در مقابل کلیشن آهن زیر جلدی : مطالعه زمان تجارت کردن

Objective To investigate the utility associated with subcutaneous infusion (deferoxamine) compared with once-daily oral administration (deferasirox) of iron chelation therapy. Methods Interviews using the time trade-off technique were used to estimate preferences (utility) for health states by finding the point at which respondents were indifferent between a longer but lower quality of life (QoL) and a shorter time in full health. Participants (n = 110) were community-based, 51% women, median age 35 years, from four regions in Sydney, Australia. Respondents rated three health states involving equal outcomes for people with thalassemia but with different treatment modalities for iron chelation; an “anchor state” describing a patient receiving iron chelation without administration mode specified, anchor state plus iron chelation via subcutaneous infusion, and anchor state plus iron chelation through once-daily oral medication. Results On an interval scale between 0 (death) and 1 (full health), median (interquartile range) utility of 0.80 (0.65–0.95) for the anchor state, 0.66 (0.45–0.87) for subcutaneous infusion, and 0.93 (0.80–0.97) for once-daily oral administration was obtained. The mean (median) difference of 0.23 (0.27) between the two treatments was statistically significant (Wilcoxon-signed rank test, P < 0.001). Subcutaneous infusion was associated with a mean (median) utility 0.13 (0.14) lower than the anchor state (P < 0.001), and once-daily oral treatment had a utility 0.10 (0.13) higher (P < 0.001). Conclusion Community respondents associate oral administration of an iron chelator such as deferasirox with enhanced QoL compared with subcutaneous treatment. Assuming equal safety and efficacy, QoL gains from once-daily oral treatment compared with subcutaneous infusion are significant.

The health-related quality of life (HRQoL) of patients has become increasingly important when considering options for individual patient care and in allocating health-care resources between competing treatments. Chronic iron overload is a major complication of potentially lifesaving blood transfusions used in the ongoing treatment of hematological conditions such as the thalassemias, myelodysplastic syndrome, and sickle cell disease. Excess iron is deposited in various tissues of the body, particularly the liver, heart, and endocrine organs [1]. Once the body’s storage capacity is exceeded, free iron catalyzes the formation of highly reactive hydroxyl radicals which lead to membrane damage and denaturation of proteins. This process leads to tissue damage and ultimately to significant morbidity and mortality. The current standard of care for chronic iron overload is the subcutaneous administration of deferoxamine, for 8 to 12 hours per day, 5 to 7 days a week. This treatment regimen in some cases leads not only to poor compliance, and hence a reduction in the extent of effective iron chelation, but also to a reduction in HRQoL. Deferasirox, a recently developed treatment for transfusional iron overload, is a once-daily oral therapy [2,3]. Evidence to date indicates that this treatment has equivalent efficacy to subcutaneous deferoxamine [2]; however, little is known about the comparative HRQoL impacts of these alternative treatments. There has been a dearth of research exploring the HRQoL impacts of iron overload treatments including the route of administration, although a preliminary study using the Sickness Impact Profile indicated that route of administration affected patientperceived HRQoL [4]. The current study aimed to elicit the strength of community preferences (utility) between the different modes of administration where the current standard treatment, deferoxamine (subcutaneous administration), was compared with the new once-daily oral treatment, deferasirox.

The study sought to estimate the strength of preference society places on receiving treatment for iron overload through a subcutaneous versus an oral administration route. People from the general population were selected to obtain a societal perspective rather than a patientspecific perspective. These community-based preferences reflect “utility” values as applied in economic evaluations and are more informative than patientbased preferences when making judgments about the allocation of societal resources within health care [5,6]. Although the applicability of community-based preferences to decisions regarding patient treatment at the individual patient level is limited, a recent review highlighted that the mode of administration of iron chelation therapy is perceived by patients with thalassemia as an important determinant of HRQoL [8]. Our results clearly show that community respondents prefer the health state in which patients receive the daily oral treatment compared with that where patients receive subcutaneous treatment. The mean difference was large: 0.23 (median 0.27) units. In QoL research, a change of 10% of a scale is regarded as at least a minimal important difference [7]. The mean utility value associated with the health state in which the oral treatment (deferasirox) is used was relatively high (mean 0.85), suggesting respondents appear willing to only give up a median of 11 months of life out of 10 years. This implies that most respondents regard having iron overload that is treated by an oral daily treatment as still offering good HRQoL. In contrast, having iron overload that is treated with subcutaneous infusion on about 5 days of the week is regarded as a suboptimal health state; people are willing to give up about 3.5 years of life out of 10 years to live in normal health. Previous work undertaken to investigate a similar question in the area of intravenous versus oral ganciclovir for maintenance treatment of AIDS-related cytomegalovirus retinitis showed a significant impact of the route of drug administration on the utility value that patients associate with treatment. In this study, utility differences of greater than 0.3 units were reported, slightly larger than what we observed in the present study [9]. That a preference exists for oral therapy compared with subcutaneous infusion is not surprising. This study provides further confirmation of the strength of that preference. When compared with HRQoL studies in other clinical contexts, the reduction in HRQoL in our study of 0.23 from oral administration to subcutaneous infusion is similar to that reported from normal health to angina and congestive heart failure [10], less than 4 months post lung transplant [11], or for an acute depressive episode [12]. In this study, we aimed to ensure the utilities extracted by the TTO exercise resulted in consistent and reliable data. In previous studies, acceptable reliability data have been reported for the TTO technique where intraclass correlation coefficient estimates ranged from 0.61 to 0.88 [13–15]. In the present study, the widest range of preference scores was observed for subcutaneous administration (Fig. 1), but a clear pattern of higher utility was observed for the oral route. As we presented only three TTO exercises to each participant (anchor, intravenous, and oral), we included a randomization procedure for the latter two vignettes with the aim of reducing ordering effects and potential for consequent systematic bias. The clear differentiation between the latter two vignettes implies that this was achieved and the large variation of Subcutaneous Oral medication infusion Anchor 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Utility value (95% CI) Figure 2 Mean and 95% confidence intervals (CI) for utility values for each health state (0.0 = death equivalent health-related quality of life, 1.0 = full health).responses to the subcutaneous infusion presumably reflects wide community preferences for the QoL this administration procedure confers. A potential weakness of the study is the lack of population-based sampling. The sample did include a substantial number of respondents from higher socioeconomic backgrounds and it is unknown how other population subgroups may have responded to the vignettes. The study could have been improved through the inclusion of cognitive debriefing interviews to ratify respondent’s answers and inclusion of formal test–retest studies to assess statistical reliability of the TTO interviews. Although this study incorporated a purposeful sampling, rather than a more rigorous population-based sampling approach, the consistency of the results across the respondents suggests that they may be generalizable across members of the community. These results indicate that society associates oral administration of an iron chelator with an advancement in the HRQoL of patients who require such treatment. Source of financial support: Financial support for this study was provided by a contract with Novartis Pharmaceuticals Australia Pty Ltd. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing and publishing the report. RHO, RDAL, and AD contributed to the conception and design, analysis and interpretation of data; drafting the article, revising it critically for intellectual content, and final approval of the version to be published. RDAL was an employee of Novartis Pharmaceuticals Australia Pty Ltd, North Ryde, NSW, Australia when this study was conducted.