Increasing the number of minor salivary glands from patients with Sjögren's disease improves the diagnostic and measurement precision of the histological focus score.

Abstract

Objectives: Minor salivary gland (MSG) biopsy has an important role in Sjögren's disease diagnosis and research. MSGs show within-patient variation in number of lymphocytic foci per unit area, but the optimal number of MSGs required to balance reproducibility and clinical acceptability has not been determined.

Methods: Monte Carlo simulations were performed to investigate impact of MSG number on (i) diagnosis based on focus score (FS) ≥1; (ii) reproducibility, defined as the extent to which 2 FS measurements obtained from 2 within-patient biopsies are the same, assuming no systematic differences have occurred in between biopsies; and (iii) smallest sample size required to detect a clinically meaningful difference in FS. Data simulation was repeated for different MSG numbers (range, 2-7).

Results: Higher reproducibility was noted for every unit increase in MSG number, with the median absolute difference between 2 within-patient FS measurements decreasing from 1.05 (SD = 0.25) with 2 glands to 0.52 (SD = 0.12) with 7 glands. MSG number influenced the probability of a simulated patient receiving a FS ≥1, increasing from a median of 0.67 with 2 glands to 0.77 with ≥5 glands. MSG number influenced clinical trial sample sizes. For example, 80% statistical power to detect a 40% FS reduction required a sample size per group of 62 with 2 glands and 25 with 7 glands.

Conclusions: For a diagnostic threshold of FS ≥1, a minimum of 5 glands should ideally be targeted. For continuous FS values, a larger number of MSGs (eg, 6) will increase reproducibility further and reduce clinical trial sample size requirements.