Minimal Clinically Important Differences in COPD Lung Function

To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease. Double blind, placebo controlled study. Eighteen UK hospitals. 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV(1)) 50% of predicted normal. Inhaled fluticasone propionate 500 microgram twice daily from a metered dose inhaler or identical placebo. Efficacy measures: rate of decline in FEV(1) after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events. There was no significant difference in the annual rate of decline in FEV(1 )(P=0.16). Mean FEV(1) after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P<0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P=0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P=0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v 19%, P=0.034). Fluticasone propionate 500 microgram twice daily did not affect the rate of decline in FEV(1) but did produce a small increase in FEV(1). Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.

This study used the standard error of measurement (SEM) to evaluate intra-individual change on both the Chronic Respiratory Disease Questionnaire (CRQ) and the SF-36. After analyzing the reliability and validity of both instruments at baseline among 471 COPD outpatients, the SEM was compared to established minimal clinically important difference (MCID) standards for three CRQ dimensions. A value of one SEM closely approximated the MCID standards for all CRQ dimensions. This SEM-based criterion was then validated by cross-classifying the change status (improved, stable, or declined) of 393 follow-up outpatients using the one-SEM criterion and the MCID standard. Excellent agreement was achieved for all three CRQ dimensions. Although MCID standards have not been established for the SF-36, the one-SEM criterion was explored in these change scores. Among SF-36 scales demonstrating acceptable reliability and reasonable variance, the percent of individuals within each change category was consistent with those seen in the CRQ dimensions. These results replicate previous findings where a value of one SEM also closely approximated MCIDs for all dimensions of the Chronic Heart Disease Questionnaire among cardiovascular outpatients. The one-SEM criterion should be explored in other health-related quality of life instruments with established MCIDs.