When Not to Use a Generic: Measuring HRQoL in Chronic Digestive Disease Necessitates the Use of Disease-Specific Questionnaires

Abstract

Health-Related Quality of Life (HRQoL) is a complex, subjective construct that encompasses patient perceptions of the social, emotional, occupational, functional, and financial effects of a chronic medical condition [1]. Guidance from the US Food and Drug Administration (FDA) strongly encourages measuring HRQoL as a secondary outcome in pharmaceutical clinical trials, further emphasizing the importance of questionnaire selection. In this issue of Digestive Diseases and Sciences, Chang and colleagues [2] report on how the MOS Short-Form 36 (SF-36), a widely used cross-condition measure of HRQoL, relates to symptom severity in a cohort of patients with eosinophilic esophagitis (EoE). The authors conclude the SF-36 may have limitations as a tool to evaluate HRQoL in these patients. There is much debate regarding the merits of “generic” (i.e., can be applied to any condition) versus “disease-specific” (i.e., applied to only one type of condition) measures of HRQoL in terms of their application to research, especially for clinical trials [3]. In reality, since there are costs and benefits to each approach, in some instances both generic and disease-specific approaches may be appropriate. Nevertheless, in patients with EoE, a disease-specific measure may be the preferred option. A 2017 systematic review of previous measures of HRQoL in adult patients with EoE found the most widely used generic questionnaire is the SF-36, or its abbreviated version (SF-12), across six studies [4]. Strengths of the SF-36 and the SF-12 are their composite scores for physical functioning (e.g., bodily pain, mobility) and mental functioning (e.g., anxiety, social function), as well as the existence of comparator populationbased norms for healthy controls and diverse chronic illness groups. In EoE cohorts where HRQoL is assessed via the SF-36 or SF-12, the results are mixed [5]. Some studies find no differences between patients with EoE and population norms, and others identify degradations in HRQoL across physical and mental health domains [4]. An additional strength of the SF-36 is that it does not include questions about distinct disease symptoms. Though physical function is an aspect of HRQoL, the inclusion of disease symptoms within the HRQoL measurement can lower scores and distort the clinical picture of a unique and separate construct. In the present study, the authors report that both the physical and mental functioning composite scores of the SF-36 had small but significant correlations with dysphagia severity. This finding aligns with multiple studies across digestive diseases, including EoE, which consistently find relatively small–moderate relationships between SF-36 scales and symptom severity. Thus, it is safe to say that the SF-36 likely discerns between dysphagia symptoms and HRQoL in EoE. Yet, for a measure of HRQoL to be clinically useful, it also must demonstrate responsiveness and sensitivity to changes in overall health status. This is where the utility of the SF-36 in understanding EoE patient outcomes deteriorates. One issue, replicated in the present study, is that patients with EoE inconsistently differ from population-based norms of the SF-36. In some studies, patients with EoE report significantly poorer mental function than healthy controls, whereas physical function domains are the same. Conversely, patients with EoE may report similar physical functioning to healthy controls or superior physical functioning than other disease groups (e.g., allergies, stomach diseases), yet equivalent mental health to patients with gastroesophageal reflux disease [4]. In this study’s cohort, patients with EoE did not significantly differ from population-based norms. While variances are to be expected across studies, the inconsistent ability of the SF-36 to detect differences between patients with EoE and other populations is problematic. As HRQoL is included in clinical trials of EoE, whether dietary or pharmacological, using a measure that is consistently sensitive to changes in disease status is essential. * Tiffany H. Taft [email protected]