Dataset Information

Development and testing of an alternative responder definition for EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI).

ABSTRACT:

Objectives

Dryness, fatigue and joint/muscle pain are typically assessed in Sjögren's trials using European Alliance of Associations for Rheumatology Sjögren's Syndrome Patient Reported Index (ESSPRI). A Patient Acceptable Symptom State of <5 and a Minimal Clinically Important Improvement (MCII)/responder definition (RD) of ≥1 point or 15% on ESSPRI have previously been defined. This study explored alternative RDs to better discriminate between active treatment and placebo in trials.

Methods

Anchor-based and distribution-based methods were used to derive RD thresholds in blinded phase IIb trial data (N=190) and confirm these in blinded data pooled from three early phase II trials (N=126). The populations consisted of individuals with moderate-to-severe systemic primary Sjögren's. Anchors were prioritised by ESSPRI correlations and used in similar conditions. Triangulated estimates were discussed with experts (N=3). The revised RD was compared with the original using unblinded data to assess placebo and treatment responder rates.

Results

Patients were predominantly female (>90%), white (90%), with mean age of 50 years. Receiver operating characteristic estimates supported an MCII threshold of 1.5-1.6 in the phase II data, whereas correlation-weighted mean change estimates supported a low/minimal symptom severity threshold of ≥2. A low/minimal symptom severity of ≤3 showed the greatest sensitivity/specificity balance. Analyses in the pooled data supported these thresholds (MCII: 1.5-2.1; low/minimal symptom severity: 2.7-3.7). Unblinded analyses confirmed the revised RD reduced placebo rates.

Conclusions

Completing a trial with an improvement of ≥1.5 points compared with baseline and an ESSPRI score of ≤3 points is a relevant RD for moderate-to-severe systemic Sjögren's and reduces placebo rates.

SUBMITTER: Wratten S

PROVIDER: S-EPMC10030922 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Development and testing of an alternative responder definition for EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI).

Wratten Samantha S Abetz-Webb Linda L Arenson Ethan E Griffiths Pip P Bowman Simon S Hueber Wolfgang W Ndife Briana B Kuessner Daniel D Goswami Pushpendra P

RMD open 20230301 1

<h4>Objectives</h4>Dryness, fatigue and joint/muscle pain are typically assessed in Sjögren's trials using European Alliance of Associations for Rheumatology Sjögren's Syndrome Patient Reported Index (ESSPRI). A Patient Acceptable Symptom State of <5 and a Minimal Clinically Important Improvement (MCII)/responder definition (RD) of ≥1 point or 15% on ESSPRI have previously been defined. This study explored alternative RDs to better discriminate between active treatment and placebo in trials.<h4> ...[more]

PMID: 36931685

Similar Datasets

Project description:BackgroundOne of the main clinical features of Sjögren's Syndrome is oral dryness, which is associated with an increased risk of oral diseases and a lower oral life quality. Dentists have a key role to play in the Sjögren's Syndrome diagnosis and specific management. In parallel, many patients rely on patient associations, which offer opportunities for members to seek information about their disease and share their experiences. We aimed to evaluate patients experience with dry mouth and the importance of dentists in Sjögren's Syndrome diagnosis and its management.MethodsWe carried out a cross-sectional survey in 2020 based on a questionnaire drafted in collaboration with clinicians specializing in Sjögren's Syndrome and patient members of a patient association. The survey consisted of 27 questions divided into the six sections: the patient's profile, their experience with dry mouth and treatments used to manage, characteristics of experienced oral-health problems, effects of dry mouth and its consequences on the quality of life, evaluation of the dentist role in the screening of Sjögren's Syndrome, and its management by the dentist. Recruitment was carried out via the patient association's newsletter, website, and social networks. Sjögren's diagnosis was self-reported.ResultsOne thousand four hundred fifty-eight patients fully responded to the survey. Most respondents were women over 50 and were mainly concerned with primary Sjögren's Syndrome. Overall, 86.97% of respondents reported experiencing frequent or constant dry mouth and 69.01% declared having had oral problems (candidiasis, oral pain, loss or alteration of taste, bad breath, gastro-esophageal reflux). We found a positive correlation between the frequency of dry mouth and each of these disorders and between the frequency of dry mouth and alterations in life quality dimensions. Finally, 74.9% of patients did not report having dry mouth to their dentist prior to being diagnosed with Sjögren's Syndrome and 58% had not been informed about the oral risks associated with it by their dentist and sought information themselves or from their physician.ConclusionsWe confirm the significant consequences of dry mouth on oral quality of life, as well as its association with oral health problems. Sjögren's Syndrome screening by dentists should be increased, as well as prevention of the associated oral health risks.

Project description:BackgroundXerostomia is a chief complaint of patients with Sjögren's syndrome (SS). However, newer proposals for SS classification remove xerostomia and hyposalivation from the criteria list. Given these developments and the importance of patient-centered research outcomes, we sought to evaluate the utility of patient-reported xerostomia with implications for classification criteria, and clinical trials targeting SS treatment modalities.MethodsA nested case-control study was designed within The National Institute of Dental and Craniofacial Research/National Institutes of Health (NIDCR/NIH) SS Cohort - one of the largest SS cohorts in the US. Clinical characteristics of those with and without xerostomia in SS and other salivary gland dysfunctions were compared. Several analytical methods were employed, including multivariable logistic regression modeling.FindingsThe NIDCR/NIH Sjögren's Syndrome Clinic has an open cohort with ongoing enrollment since 1984. This open cohort comprised of 2046 participants by August 27, 2015. Baseline data of 701 SS, 355 Sicca, and 247 ISS participants within the source cohort were analyzed. Xerostomia was highest among SS participants (87.4%, 95% CI: 84.8%-89.8%) compared to Sicca (72.4%, 95% CI: 67.4%-77.0%, p<0.001) and ISS groups (38.1%, 95% CI: 32.0%-44.4%, p<0.001). Those with xerostomia were more likely to have SS than Sicca/ISS (OR=4.98, 95% CI: 3.78-6.56). The ability of xerostomia to screen for SS among those with salivary gland dysfunction was higher than screening for Sicca/ISS. Screening diagnostics of xerostomia were of greater utility compared to hyposalivation. After adjusting for confounding in multivariable modeling, SS participants with xerostomia were more likely to be White (Black/African Americans (OR: 0.40, 95% CI: 0.23-0.68, p-value=0.001) and Asians (OR: 0.49, 95% CI: 0.25-0.96, p-value=0.038) were less likely to have xerostomia compared to Whites), have dry eye symptoms for >3months (OR: 5.80, 95% CI: 3.62-9.28, p-value <0.001), a lower Van Bijsterveld score (OR: 0.55, 95%CI: 0.34-0.90, p-value=0.017), a lower stimulated salivary flow rate (OR: 1.67, 95% CI: 1.06-2.65, p-value=0.028), a focus score of >2 (OR: 1.92, 95% CI: 1.20-3.09, p-value=0.007), and salivary gland swelling (OR: 49.39, 95% CI: 2.02-1206.30, p-value=0.017). Age, gender, fatigue, pain, anxiety, and autoantibodies were not significantly associated with xerostomia.InterpretationFindings from this study indicate that patient-reported xerostomia is highly prevalent among SS patients and is associated with several clinical phenotypes of this complex syndrome, thereby making it an important indicator of SS. The evidence also suggests that xerostomia is not limited to low salivary flow but might be reflective of compositional changes of saliva. Consequently, these findings suggest the need to consider xerostomia in the development of SS classification criteria and in patient-centered outcomes research in SS intervention trials. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR) Grant # DE000704-15. Dr. Baer is supported by RO1-DE-12354-15A1.

Project description:BACKGROUND:Nonmuscle invasive bladder cancer (NMIBC) is a chronic condition requiring intensive follow-up, repeated endoscopic examinations, tumor resections, and intravesical treatments that can occur every 3 months for life. In this clinical context, patient-reported outcomes (PROs) are a critical concern for patients and their managing clinicians. PROs have enormous potential to be integral to treatment assessment and recommendations for NMIBC; however, current PRO measures are inadequate for NMIBC because they lack key NMIBC-specific symptoms and side effects associated with contemporary treatments. OBJECTIVE:The overarching aim of this study was to develop and evaluate a patient-reported symptom index (SI) for individuals with NMIBC (the NMIBC-SI) that is acceptable to patients; reliable, valid, and responsive to differences between contemporary treatments for NMIBC; and fit for purpose as an endpoint in clinical trials. METHODS:The NMIBC-SI will be evaluated in 2 field tests across a total of 3 years. Field test 1 is a cross-sectional study design involving 225 adult NMIBC patients recruited while undergoing active treatment or those who completed final treatment within the past week. Data collected include patient demographics, clinical features of the tumor, risk category, treatment type, comorbidity, and PROs. Field test 2 is a prospective longitudinal study involving 225 newly diagnosed NMIBC-SI patients. Clinical data and patient-completed questionnaires will be collected at 4 time points during treatment: before tumor resection, 1 week after resection, end-of-induction intravesical therapy, and 1-year follow-up. Standard psychometric tests will be performed to assess the reliability, validity, responsiveness, and clinical utility of the NMIBC-SI. RESULTS:Participant recruitment to field test 1 commenced in February 2017. Recruitment for field test 2 is planned to commence in January 2018. Final results are expected to be published in 2019. The NMIBC-SI will be freely available for use via registration. CONCLUSIONS:This study protocol contains detailed methods that will be used across multiple international sites. Phase 2 in the development of the NMIBC-SI will enable a comprehensive evaluation of its reliability, validity, and responsiveness to ensure that the NMIBC-SI is fit for purpose in clinical research and provides an evidence base for the ongoing improvement of future therapies for NMIBC. TRIAL REGISTRATION:ClinicalTrials.gov NCT03091764; http://clinicaltrials.gov/ct2/showNCT03091764 (Archived by WebCite at http://www.webcitation.org/6umBhQeNX).