SynthesisPloS one2015
Which and How Many Patients Should Be Included in Randomised Controlled Trials to Demonstrate the Efficacy of Biologics in Primary Sjögren's Syndrome?
Synthesis in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Development and Application of the Placebo Response Model in Clinical Trials for Primary Sjögren's Syndrome.Frontiers in immunology · 2021Pooled it
- Efficacy and safety of abatacept in active primary Sjögren's syndrome: results of a phase III, randomised, placebo-controlled trial.Annals of the rheumatic diseases · 2021Trial
- Comparative Analysis of Clinical Trials of Biologic Drugs for Patients with Primary Sjögren's Syndrome.Journal of clinical medicine · 2026Review
- Current and future therapies for primary Sjögren syndrome.Nature reviews. Rheumatology · 2021Review
- Go Ask Your Patients! PSS-QoL Reported Perception of Dryness Correlates With Lacrimal and Salivary Flow in Primary Sjögren's Syndrome.Frontiers in medicine · 2021Article
- Phosphatidylinositol 3-kinase delta pathway: a novel therapeutic target for Sjögren's syndrome.Annals of the rheumatic diseases · 2019Article
- Classification criteria in Sjögren's syndrome.Annals of translational medicine · 2017Article
- Incidence and Mortality of Physician-Diagnosed Primary Sjögren Syndrome: Time Trends Over a 40-Year Period in a Population-Based US Cohort.Mayo Clinic proceedings · 2017Article
- Treating the Underlying Pathophysiology of Primary Sjögren Syndrome: Recent Advances and Future Prospects.Drugs · 2016Review
- Treatment of primary Sjögren syndrome.Nature reviews. Rheumatology · 2016Review
- Recent advances in primary Sjogren's syndrome.F1000Research · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 19 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe goal of this study was to determine how the choice of the primary endpoint influenced sample size estimates in randomised controlled trials (RCTs) of treatments for primary Sjögren's syndrome (pSS).
methodsWe reviewed all studies evaluating biotechnological therapies in pSS to identify their inclusion criteria and primary endpoints. Then, in a large cohort (ASSESS), we determined the proportion of patients who would be included in RCTs using various inclusion criteria sets. Finally, we used the population of a large randomised therapeutic trial in pSS (TEARS) to assess the impact of various primary objectives and endpoints on estimated sample sizes. These analyses were performed only for the endpoints indicating greater efficacy of rituximab compared to the placebo.
resultsWe identified 18 studies. The most common inclusion criteria were short disease duration; systemic involvement; high mean visual analogue scale (VAS) scores for dryness, pain, and fatigue; and biological evidence of activity. In the ASSESS cohort, 35 percent of patients had recent-onset disease (lower than 4 years), 68 percent systemic manifestations, 68 percent high scores on two of three VASs, and 52 percent biological evidence of activity. The primary endpoints associated with the smallest sample sizes (nlower than 200) were a VAS dryness score improvement higher to 20 mm by week 24 or variable improvements (10, 20, or 30 mm) in fatigue VAS by week 6 or 16. For patients with systemic manifestations, the ESSDAI change may be the most logical endpoint, as it reflects all domains of disease activity. However, the ESSDAI did not improve significantly with rituximab therapy in the TEARS study. Ultrasound score improvement produced the smallest sample size estimate in the TEARS study.
conclusionThis study provides valuable information for designing future RCTs on the basis of previously published studies. Previous RCTs used inclusion criteria that selected a small part of the entire pSS population. The endpoint was usually based on VASs assessing patient complaints. In contrast to VAS dryness cut-offs, VAS fatigue cut-offs did not affect estimated sample sizes. SGUS improvement produced the smallest estimated sample size. Further studies are required to validate standardised SGUS modalities and assessment criteria. Thus, researchers should strive to develop a composite primary endpoint and to determine its best cut-off and assessment time point.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.