Radiography as primary outcome in rheumatoid arthritis: acceptable sample sizes for trials with 3 months' follow up

Abstract

Objectives: To investigate whether plain radiographs can show changes in joint damage due to rheumatoid arthritis (RA) within 3 months. Methods: 188 film pairs taken with a 3 month interval were evaluated. They were scored with (chronological) and without (paired) knowledge of the sequence of the films according to the Sharp/van der Heijde method. Changes in joint damage were analysed on a group and an individual level for different subsets of patients. Sample sizes required to detect statistically and clinically significant differences were estimated based on the percentages of patients with progression larger than the smallest detectable change (SDC). Results: Changes in joint damage were seen by both the chronological and the paired scoring method. The percentage of patients with progression of joint damage larger than the corresponding SDCs (1.7 and 2.4) varied in the subsets from 18% to 64% if based on the chronological change-scores and from 9% to 36% using paired change-scores. Acceptable sample size estimates were seen in several subsets, depending on (a) how the investigated drug would reduce the individual risk of progression of joint damage (by an absolute or a relative risk reduction model); (b) how damage was scored (chronological or paired); (c) the baseline risk; and (d) whether a two sided or one sided test would be used. Conclusions: Changes in joint damage due to RA can be detected reliably already within 3 months. This finding can be used to plan short term, randomised controlled trials with radiographic progression as primary outcome.

EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT)

“…146 No evidence from an appropriately designed clinical trial exists to support monitoring of radiographic progression. The expert committee considered monitoring of radiographic progression useful in view of the objective of the management of early arthritis (to prevent joint destruction), the observation that radiographic progression is greatest during the first two years after disease onset, and the appreciation that radiographic progression is clinically meaningful in case of a change of 4 Sharp units (during six months follow up) and can be reliably established at the group level after a three to six months interval 147 (category III). In order to facilitate radiographic monitoring, it could be desirable to use the simple erosion and narrowing score (SENS), a scoring method based on the van der Heijde modified Sharp score and validated for use in clinical practice.…”

The ‘therapeutic window’ and treating to target in rheumatoid arthritis

“…In early RA with high disease activity it is possible to detect changes in joint damage within 3 months using plain radiographs. 7 Therefore, early diagnosis and immediate intervention with diseasemodifying therapy is vital to prevent disability. The heterogeneity in presentation of RA can lead to delays in diagnosis, and previous criteria for RA have demonstrated low sensitivity and specificity for early disease.…”

Updating the OMERACT Filter: Implications for Imaging and Soluble Biomarkers

“…With respect to RA, participants agreed that structural damage depicted by radiography fulfilled most aspects of the former OMERACT Filter of truth, discrimination, and feasibility 8,9 , and it was recognized that semiquantitative assessment of erosions and joint space narrowing (JSN) were currently accepted as structural outcomes for RCT 10,11 .…”