Internal consistency reliability is a poor predictor of responsiveness

BACKGROUND: Whether responsiveness represents a measurement property of health-related quality of life (HRQL) instruments that is distinct from reliability and validity is an issue of debate. We addressed the claims of a recent study, which suggested that investigators could rely on internal consistency to reflect instrument responsiveness. METHODS: 516 patients with chronic obstructive pulmonary disease or knee injury participating in four longitudinal studies completed generic and disease-specific HRQL questionnaires before and after an intervention that impacted on HRQL. We used Pearson correlation coefficients and linear regression to assess the relationship between internal consistency reliability (expressed as Cronbach's alpha), instrument type (generic and disease-specific) and responsiveness (expressed as the standardised response mean, SRM). RESULTS: Mean Cronbach's alpha was 0.83 (SD 0.08) and mean SRM was 0.59 (SD 0.33). The correlation between Cronbach's alpha and SRMs was 0.10 (95% CI -0.12 to 0.32) across all studies. Cronbach's alpha alone did not explain variability in SRMs (p = 0.59, r(2 )= 0.01) whereas the type of instrument was a strong predictor of the SRM (p = 0.012, r(2 )= 0.37). In multivariable models applied to individual studies Cronbach's alpha consistently failed to predict SRMs (regression coefficients between -0.45 and 1.58, p-values between 0.15 and 0.98) whereas the type of instrument did predict SRMs (regression coefficients between -0.25 to -0.59, p-values between <0.01 and 0.05). CONCLUSION: Investigators must look to data other than internal consistency reliability to select a responsive instrument for use as an outcome in clinical trials

Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials

Objective To explore the extent to which components of composite end points in randomised controlled trials vary in importance to patients, the frequency of events in the more and less important components, and the extent of variability in the relative risk reductions across components. Design Systematic review of randomised controlled trials. Data sources Cardiovascular randomised controlled trials published in the Lancet, Annals of Internal Medicine, Circulation, European Heart Journal, JAMA, and New England Journal of Medicine, from 1 January 2002 to 30 June 2003. Component end points of composite end points were categorised according to importance to patients as fatal, critical, major, moderate, or minor. Results Of 114 identified randomised controlled trials that included a composite end point of importance to patients, 68% (n=77) reported complete component data for the primary composite end point; almost all (98%; n=112) primary composite end points included a fatal end point. Of 84 composite end points for which component data were available, 54% (n=45) showed large or moderate gradients in both importance to patients and magnitude of effect across components. When analysed by categories of importance to patients, the most important components were associated with lower event rates in the control group (medians of 3.3-3.7% for fatal, critical, and major outcomes; 12.3% for moderate outcomes; and 8.0% for minor outcomes). Components of greater importance to patients were associated with smaller treatment effects than less important ones (relative risk reduction of 8% for death and 33% for components of minor importance to patients). Conclusion The use of composite end points in cardiovascular trials is frequently complicated by large gradients in importance to patients and in magnitude of the effect of treatment across component end points. Higher event rates and larger treatment effects associated with less important components may result in misleading impressions of the impact of treatment

Association Between Myocardial Injury and Cardiovascular Outcomes of Orthopaedic Surgery

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is common and of prognostic importance. Little is known about MINS in orthopaedic surgery. The diagnostic criterion for MINS was a level of ≥0.03 ng/mL on a non-high-sensitivity troponin T (TnT) assay due to myocardial ischemia. METHODS: We undertook an international, prospective study of 15,103 patients ≥45 years of age who had inpatient noncardiac surgery; 3,092 underwent orthopaedic surgery. Non-high-sensitivity TnT assays were performed on postoperative days 0, 1, 2, and 3. Among orthopaedic patients, we determined (1) the prognostic relevance of the MINS diagnostic criteria, (2) the 30-day mortality rate for those with and without MINS, and (3) the probable proportion of MINS cases that would go undetected without troponin monitoring because of a lack of an ischemic symptom. RESULTS: Three hundred and sixty-seven orthopaedic patients (11.9%) had MINS. MINS was associated independently with 30-day mortality including among those who had had orthopaedic surgery. Orthopaedic patients without and with MINS had a 30-day mortality rate of 1.0% and 9.8%, respectively (odds ratio [OR], 11.28; 95% confidence interval [CI], 6.72 to 18.92). The 30-day mortality rate was increased for patients with MINS who had an ischemic feature (i.e., symptoms, or evidence of ischemia on electrocardiography or imaging) (OR, 18.25; 95% CI, 10.06 to 33.10) and for those who did not have an ischemic feature (OR, 7.35; 95% CI, 3.37 to 16.01). The proportion of orthopaedic patients with MINS who were asymptomatic and in whom the myocardial injury would have probably gone undetected without TnT monitoring was 81.3% (95% CI, 76.3% to 85.4%). CONCLUSIONS: One in 8 orthopaedic patients in our study had MINS, and MINS was associated with a higher mortality rate regardless of symptoms. Troponin levels should be measured after surgery in at-risk patients because most MINS cases (>80%) are asymptomatic and would go undetected without routine measurements. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence