X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive, and lifelong disease associated with significant morbidity [1, 2] and a negative impact on the quality of life of the affected individual[3]. As an inherited disease [2], XLH affects both children and adults, resulting in life-long consequences across the lifespan [4]. Age and female sex are some of the characteristics associated with significantly impaired quality of life in adult XLH patients [3], with many of these issues originating in childhood [5].
While there have been significant advances in the available treatment options and management of adults with XLH [6, 7], ongoing concerns regarding their quality of life and the accurate measurement of this construct remain [8]. Adopting any new treatment option relies not only on favourable supporting evidence being made available promptly but also that this evidence answers the specific research questions of any relevant 'gatekeepers' of its progression to the patient. Recent research advocated a multiple stakeholder approach to real-world evidence generation [9] and modelled the adoption of a new medicine as an open system comprising three subsystems in series: the regulator, the payor, and finally, the prescriber [9]. Each subsystem requires specific evidence to satisfy its internal logic for that medicine to progress in its adoption. Evidence of quality of life improvements in rare disease patients receiving a particular treatment is valuable in payor discussions [10] and therefore an essential input for the Payor subsystem [11].
Given the fundamental importance of quality of life evidence in new medicine adoption, various authors have highlighted accuracy in developing these measurement instruments as a necessity [12, 13]. Evidence from the review by Dowding et al. [14] suggests that generic quality of life measures may not effectively capture the impact of a specific disease, as they may be less sensitive to the condition. This argument raises how investigators select a reference against which they can assess the accuracy of their observations for a given construct. It is this question which forms the subject for Neutral theory [15]. The Neutral theory describes the construct of Neutrality (N0), or the accuracy, of observation of any given construct when measured against the reference of its true value, which an observer makes with complete accuracy or Neutrality. Making a Neutral or accurate observation relies on a Neutral list of indicators, for that construct, that the observer uses a) exclusively and b) without omission in their measurement of the construct. Should the observer deviate from either of these conditions, they reduce the Neutrality of their observation by reducing its sensitivity and sensitivity. Recent research applied Neutral theory and assessed the Neutrality of generic QoL instruments in diseases where disease-specific ones existed, using that latter as a surrogate for the Neutral list. The research concluded that 'Generic HRQoL tools appear poorly correlated with disease/condition-specific tools, which indicates that adoption of Neutral Theory in the development and assessment of HRQoL tools could improve their relevance, accuracy, and utility in economic evaluations of health interventions' [12, pg. 1].
The source of the indicators used to observe the construct of quality of life of an individual must be specific to that individual, as the construct is inherently personal. This suggestion builds on evidence for the subjective nature of quality of life measures because the patient usually reports them [16]. However, generic measures may overlook these individual dynamics in quality of life, which explains the continued advocacy in the published literature for idiographic assessment in measuring the quality of life in patients [17]. By their design, idiographic assessments consider the individual nature of patients completing quality of life measures and often have a qualitative interview component in the data collection methods [17]. Ibrahim [18] argues that, as a research methodology, qualitative interviewing is sensitive to eliciting the required responses when assessing patients' subjective nature of quality of life. Essentially, QoL is subjective and individual, and approaches to its measurement need to respect these aspects if they are accurate.
The Schedule for the Evaluation of Individual Quality of Life -Direct Weighting (SEIQoL-DW), as an idiographic assessment, is an established method of exploring quality of life [19, 20] and has been used extensively among patients with rare and non-rare diseases [21, 22]. Compared to other generic tools such as the EuroQoL-5D (EQ-5D) [23], the SEIQoL-DW is an exact and fitted tool. Furthermore, SEIQoL-DW uses semi-structured interviews and judgment analysis to elicit direct weighing from patients on areas of their lives that are important and have been affected by their disease condition [20, 22].
The use of judgment analysis [24], culminating in the generation of nominated life areas (cues) relating to five key domains that the individual considers important, ensures that the quality of life measured by the SEIQoL is individual-focused. Furthermore, these cues serve as the basis for the direct weighting of quality of life, which is used as the benchmark during the subsequent quality of life assessments [19]. Researchers may administer SEIQoL to an individual serially over a period of time to monitor the effect of time on the SEIQoL index and it's contributing domains, as well as their relative proportions
Although both the EQ-5D and the SEIQoL-DW are quality of life (QoL) tools completed by the individual [22], cost-effectiveness modellers often use the EQ-5D as part of health technology assessment (HTA) submissions [25]. It is unclear whether there are similarities in the quality of life scores generated by these two instruments and if both tools can detect a change in the quality of life over time.
The author proposes instruments such as SEIQoL-DW and EQ-5D exist on a continuum of Neutrality, with individual interviewing at one extreme and generic questionnaires at the other. Given the empirical importance of accuracy in measuring any construct and specific risks associated with inaccurate quality of life measurements in medicine adoption, an assessment of the instruments sitting towards each extreme has been selected as the subject of this work. Furthermore, SEIQoL-DW offers the opportunity to assess an intermediate option by removing the time-dependent subjectivity through applying the baseline cues at each subsequent visit, thus resulting in the SEIQoL mimicking a fixed quality of life instrument.
Study Aim and Objectives
This study aims to understand the comparative performance of the SEIQoL Index when applied using cues solicited at the Visit (SEIQoLvisit_cues Index) and when applied using cues solicited at baseline (SEIQoLbaseline_cues Index) and the EQ-5D instruments in measuring the quality of life in adult XLH patients over 12 months.
Objectives:
The objectives are to:
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Evaluate any change in QoL of adult XLH Patients over 12 months and at three-month intervals using EQ-5D, SEIQoLbaseline_cues, SEIQoLvisit_cues
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Explore the concordance between the quality of life measured by EQ-5D, SEIQoLvisit_cues, and SEIQoLbaseline_cues at baseline and each subsequent three-monthly visit.