Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

Abstract

RationaleClinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities.MethodsThe Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF).ResultsA core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed.ConclusionIdentification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

Evaluating disease severity in idiopathic pulmonary fibrosis

“…The heterogeneity of phase 3 IPF trial characteristics illustrates the lack of a standardised approach to study design as well as disagreement about optimal primary and secondary end-points. A recent consensus effort including contributions from interstitial lung disease (ILD) experts and patients proposed the adoption of a core set of domains and outcome measures in future clinical trials of connective tissue disease-associated ILD (CTD-ILD) and IPF, but has yet to be put to the test [17,18].…”

“…Cough scales, questionnaires, challenge tests and monitors are among the methods used to assess cough severity in IPF and its impact on HRQoL [23]. The Leicester Cough Questionnaire (LCQ) has been shown to be sensitive to serial change and is therefore considered an appropriate outcome tool in IPF trials [17,24].…”

Serum KL-6 and surfactant protein-D as monitoring and predictive markers of interstitial lung disease in patients with systemic sclerosis and mixed connective tissue disease

“…Our subjects predominantly had NSIP, and this might have affected the positive correlation results. Because a recently published expert opinion report highlighted FVC as a core outcome of chronic ILD (29), originally, we expected to directly prove a significant correlation between serum KL-6 and FVC. However, our study could not show significant results at this point, possibly due to its small sample size.…”

Monitoring of Lung Involvement in Rheumatologic Disease

“…The severity of dyspnoea has been quantified in IPF using specific tools such as the Dyspnea-12 [5] and the Medical Research Council Dyspnoea scales [6,7]. However, these scales, validated at a single point in time and not as measures of serial change, have no current utility in the routine monitoring of CTD-ILD, although recommended as secondary end points in treatment trials [8]. …”