Introduction
SLE is a chronic autoimmune disease characterised by the presence of autoreactive B cells and autoantibodies that result in systemic inflammation and a relapsing, remitting autoimmune disease with multiorgan manifestations.1 The prevalence of SLE in the USA is estimated to be approximately 450 000 cases.2 The clinical presentation of SLE is heterogenous, and patients may experience multiorgan manifestations, which can range from mild to life-threatening. The most common symptoms of SLE are constitutional (eg, fatigue, fever and loss of appetite/weight loss), musculoskeletal (eg, joint/muscle pain, stiffness and swelling) and mucocutaneous (eg, skin rash, oral/nasal ulcers and hair loss).3
Lupus nephritis (LN) is a common and severe complication of SLE which occurs in as many as 50% of patients with SLE.4 LN is more common in men than in women,5 and often also in Hispanic, African–American and Asian individuals.6–8 In addition to SLE symptoms, patients with LN may also complain of symptoms including fatigue; foamy, dark and/or bloody urine; swelling in legs; weight gain; and increased nocturnal urination. LN is a significant risk factor for morbidity and mortality with end-stage renal disease occurring in 10.0%–30.0% of patients with LN. Therefore, SLE and LN have significant impacts on patients’ health-related quality of life (HRQoL) including physical functioning, ability to carry out activities of daily living, emotional well-being, work, and participation in family, social and leisure activities.9–18
Capturing information on the symptom presentation and HRQoL impact from the patient perspective provides a unique and clinically relevant view of a medical condition. Accordingly, patient-reported outcomes (PROs) are increasingly recognised as an integral component for the assessment of SLE in randomised controlled trials (RCTs), as they measure additional impacts of disease that cannot be assessed by physician-reported disease activity scores.19 20 The US Food and Drug Administration (FDA) Guidance for Industry on PROs and Patient-Focused Drug Development outline best practices for developing and evaluating PROs in a specific context of use to evaluate treatment benefit and ultimately support product label claims. As a first step, it is critical that qualitative evidence is generated in the target population to identify disease-defining concepts that are important and relevant to patients.21 22 To effectively evaluate treatment benefit, it is imperative that PROs are fit-for-population (patients with SLE and LN) and purpose, and have strong evidence of content validity (ie, that the content of the measure is appropriate and comprehensive relative to its intended measurement concept and context of use).21
The Outcome Measures in Rheumatology (OMERACT) international consensus effort (1998) recommended the assessment of HRQoL using both generic and disease-specific measures as one of five core domains to be assessed in all RCTs and longitudinal observational studies in SLE.23 Since the publication of OMERACT’s recommendations, the majority of RCTs have included one or several PROs. The Medical Outcomes 36-Item Short Form Health Survey (SF-36),24 Lupus Quality of Life (LupusQoL) questionnaire25 and Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) scale26 are generic-specific and disease-specific measures of HRQoL and fatigue (respectively) and commonly used as supportive endpoints in SLE trials.27 Documented evidence regarding the content validity and psychometric measurement properties of these measures supports their suitability for use in SLE as supportive trial endpoints.28–31
Although prior research in SLE and LN has demonstrated that these three PROs assess the majority of key disease impact domains,28 their assessment is either limited to select symptoms (eg, tiredness/fatigue), is non-specific (ie, generalised pain), or focuses on the HRQoL impacts of specific symptoms rather than symptom severity.21 32 A qualitative literature and online blog/forum review and qualitative concept elicitation (CE) interviews with patients with SLE and LN exploring the lived experience of each condition identified key symptoms (ie, skin rash, joint pain, joint stiffness and swelling of the legs/feet) and symptom properties (ie, severity) that were not specifically assessed by the SF-36, FACIT-F, and LupusQoL. Therefore, despite each PRO containing sufficient and relevant content for its intended purpose (eg, assessment of the impact of disease (SF-36), impact of SLE on HRQoL (LupusQoL) and the severity and impact of fatigue (FACIT-F)), novel PRO items (questions) assessing the severity of key symptoms have been developed to address measurement gaps in regard to the assessment of disease-specific symptomatology.33
The overall objective of this study was to conduct qualitative cognitive debriefing (CD) interviews to inform the selection of PROs for use in future SLE and LN RCTs and research studies. The aims of the interviews were first to extend content validity evidence that the symptom and impact concepts assessed by SF-36, FACIT-F, and LupusQoL PROs were consistently understood and relevant to patients with SLE and that no important concepts are missing. Determining whether the same concepts are relevant in a sample of patients with LN was a second aim. A third aim of the interviews was to evaluate the content validity of the four novel PRO symptom severity items developed based on previous qualitative research33 in a sample of patients with SLE and LN.