Targeted Literature Review

Thirty-nine symptoms were identified from the literature, organized into eight symptom domains: physical, dermatological, pain, ocular, oral, gynecological, gastrointestinal, and neurological. Additionally, 32 HRQoL impacts were identified across seven HRQoL functioning domains: physical functioning, ADL, cognition, emotional well-being, sleep, social and family functioning, and work. The results informed a preliminary conceptual model which supported the development of the first draft of the SRQoL.

Qualitative Interviews: Sample Characteristics

Twenty participants were interviewed. Demographic and clinical sampling quotas were met or exceeded except for age, educational level, and physician-reported disease activity (based on physician-completed Physical Global Assessment of disease activity) was narrowly missed. The target sampling quotas for race, specifically the “American Indian or Alaska Native”, “Asian”, and “Native Hawaiian or Other Pacific Islander” categories, were an exception, as no participants were successfully recruited. The mean age of participants was 54 years (range 22–82 years) and the sample predominantly included female patients (n = 14/20; 70.0%). Just over half of participants were white (n = 13/20; 65.0%), with representation of other races across the overall sample. There was good representation of different educational levels across both interview rounds.

The mean number of years since Sjögren’s diagnosis was 7 years (range 1–15 years) and overall disease activity (based on Physician Global Assessment score) was moderate for most US participants (42.9%) (not collected for UK participants). At screening, all participants reported experiencing ocular/eye dryness (100%), and all but one participant also reported experiencing oral/mouth dryness (95.0%). Mean ESSPRI total score across all participants was 5.3 (minimum 2; maximum 8). Dryness was rated as the most severe symptom as assessed by the ESSPRI, followed by fatigue and then pain. See Supplementary Tables S4, S5, and S6 for a summary of demographic, clinical characteristics, and achievement of target sampling quotas, respectively.

Concept Elicitation Findings

All participants discussed the impact of Sjögren’s on their HRQoL, with a total of 64 unique impact concepts reported during CE. The most commonly reported impacts included daytime sleepiness (n = 20), waking during the night (n = 19), worry (n = 19), stress (n = 19), driving difficulties (n = 19), difficulty looking at screens (n = 19), reading difficulties (n = 18), requiring naps (n = 17), and concentration difficulties (n = 17). Impacts were categorized into eight HRQoL domains, including emotional well-being, sleep, ADL, cognition, physical functioning, social and family functioning, work, and sexual functioning (Table 1 provides example quotes for each domain). Of the 16 participants who described the most bothersome HRQoL impact, six reported impacts to social and family functioning to be the most bothersome, followed by physical functioning, ADL, cognition, and work.

Table 1 Overview of health-related quality of life (HRQoL) impact domains reported by participants (N = 20)

CE results informed the final Sjögren’s conceptual model (Fig. 2), developed independently to the preliminary conceptual model (derived from the literature review findings with the exclusive aim of informing the first draft of the SRQoL).

Fig. 2

Conceptual model of Sjögren’s disease: signs/symptoms and health-related quality of life (HRQoL) impacts derived from concept elicitation (CE) interviews (N = 20)

All impact domains were spontaneously reported for the first time within the first 10 interviews; thus, saturation analyses indicate that saturation of important and proximal HRQoL impacts of Sjögren’s was achieved.

Cognitive Debriefing of the SRQoLInstruction Understanding

Most participants demonstrated understanding of the overall SRQoL and domain specific instructions (> 80.0%, Fig. S4).

Item Understanding and Relevance

Table 2 provides examples of supportive quotes to illustrate when items were considered relevant to participants. All SRQoL items were understood by at least 80.0% of participants and most items (32/37) were considered relevant to at least 50.0% of participants (Table 3). However, items assessing “walking short distances”, “moving”, “climbing down stairs”, “self-care”, and “feeling distant” were reported as relevant by less than 50.0% of participants asked.

Table 2 Item relevance exemplary quotesTable 3 Overview of the number of participants who reported Sjögren’s Related Quality of Life (SRQoL) items as understood and relevantUnderstanding of RESPONSE Scales and Recall Period

Overall, frequency and severity response scales were well understood across participants in both rounds. Only three participants (30.0%) demonstrated unclear or misunderstanding of response options across multiple items (five instances) during round 1, and only two participants (20.0%) in round 2 demonstrated minor misunderstanding across more items (nine instances). No amendments were made as the response scales were well understood by the majority.

Overall, most participants (75.0%) demonstrated understanding of the 7-day recall period. Six items elicited unclear or misunderstanding of the recall period from two or more participants, specifically items assessing “speaking”, “going up stairs”, “focusing”, “driving”, “daytime sleepiness”, and “moving”. Reasons for misunderstanding included participants only considering the present day, a specific time of day the difficulty occurred, and considering the concept more generally outside of the specified recall period. No amendments were made as the recall period was well understood by the majority. Additionally, five participants described that a longer recall period would make it difficult to recall their experiences.

Willingness to Complete the SRQoL Within Clinical Trials/Clinical Practice

Twelve participants were asked about willingness to complete the SRQoL within a clinical practice setting, of which all 12 reported that they would be willing to complete the SRQoL in this setting. Of these 12, nine participants were asked about their willingness to complete the SRQoL in a clinical trial; all nine of the participants asked reported that they would be willing to complete the SRQoL within a clinical trial.

Overview of SRQoL Modifications

Several modifications were made to the SRQoL following both interview rounds to ensure that development of the instrument was thorough and iterative. Modifications included: updates to the SRQoL formatting to better delineate content and improve clarity, changes to the listed examples within items to support relevancy and understandability across the USA and UK, inclusion of items which otherwise were not conceptually captured (following round 1 and tested in round 2), and removal of items deemed not relevant to participants (following round 2 only).

Participants did not report any missing concepts within the SRQoL.

Final SRQoL and Conceptual Framework

The final version of the SRQoL consists of 28 items assessing the impact of Sjögren’s across three domains of functioning (physical functioning, ADL, and overall HRQoL). Seven items assess impacts to physical functioning, five items assess impacts to ADL, and 16 items assess overall HRQoL. The overall HRQoL domain is separated further to assess cognition (three items), sleep (three items), emotional well-being (five items), social and family functioning (four items), and work (one item). A conceptual framework (Fig. 3) was developed to illustrate how concepts elicited during qualitative interviews are assessed by items within the instrument [36].

Fig. 3

Conceptual framework for the final Sjögren’s Related Quality of Life (SRQoL) patient-reported outcome (PRO) instrument. COA clinical outcome assessment

Cognitive Debriefing of the PGI-S and PGI-C Items

Overall, the PGI-S and PGI-C instructions and items were understood by most participants. Most participants reported that the PGI-S and PGI-C items were relevant and that the response options and recall periods were easy to understand. Of the seven participants who provided general feedback on these items, all reported they would be willing to complete the items within a clinical trial.

PGI-S and PGI-C Modifications

Modifications were made to the PGI items following round 1 and round 2 interviews to ensure that development of the instrument was thorough and iterative. Modifications included updates to the item wording to better delineate content and improve clarity, and updates to examples within items to support relevancy.