The added value for assessing the health-related quality of life (HRQOL) in chronic conditions is now well documented for evaluation of treatment eflectiveness in clinical trials and as a criterion for licensing new medications and in policy decisions. However; European standards still need to be developed for the measurement and reporting of HRQOL in clinical trials. This is one of the objectives of the European Regulatory Issues on Quality of Life Assessment (ERIQA) Working Group. This document reviews the major issues arising from the selection of an HRQOL instrument; the integration of HRQOL assessment into the research protocol (methodological design, practicalities of HRQOL administration and collection, prevention and handling of missing data); the statistical analysis plan: and the presentation and interpretation of the results. Finally, to gain wider acceptance, whether HRQOL is considered as a primary or secondary endpoint, the scientific principles of clinical trial design should apply to HRQOL.

Background: The MOSAIC study compared moxifloxacin with three standard antibiotic regimens in patients with Anthonisen type 1 acute exacerbations of chronic bronchitis (AECB). Further exploratory analyses were performed to identify prognostic factors of short and long term clinical outcomes and their value for clinical research. Methods: Outpatients aged >45 years were screened between AECB episodes, randomised to treatment upon presenting with an AECB, assessed 7-10 days after study treatment, and followed monthly until a new AECB or for up to 9 months. Logistic regression assessed the predictive factors for clinical cure (return to pre-AECB status) and clinical success (cure or improvement), and a stepwise Cox regression model time to a composite event (failure of study treatment, new AECB, or further antibiotic treatment for AECB). Results: In multivariate analyses, clinical cure was positively influenced by treatment with moxifloxacin (odds ratio (OR) 1.49; 95% CI 1.08 to 2.04) while cardiopulmonary disease (OR 0.59; 95% CI 0.38 to 0.90), forced expiratory volume in 1 second (FEV 1 ) ,50% predicted (OR 0.48; 95% CI 0.35 to 0.67), and >4 AECBs in the previous year (OR 0.68; 95% CI 0.48 to 0.97) predicted a poorer outcome. For clinical success, treatment with moxifloxacin had a positive influence (OR 1.57; 95% CI 1.03 to 2.41) while cardiopulmonary disease (OR 0.41; 95% CI 0.25 to 0.68) and use of acute bronchodilators (OR 0.50; 95% CI 0.30 to 0.84) predicted a poorer outcome. The occurrence of the composite event was influenced by antibiotic treatment (hazard ratio (HR) 0.82; 95% CI 0.68 to 0.98), age >65 years (HR 1.22; 95% CI 1.01 to 1.47), FEV 1 ,50% predicted (HR 1.27; 95% CI 1.05 to 1.53), >4 AECBs in previous year (HR 1.63; 95% CI 1.34 to 1.99), and acute bronchodilator use (HR 1.48; 95% CI 1.17 to 1.87). For the composite event the beneficial effect of moxifloxacin was primarily seen in patients aged >65 years. Conclusion: Despite selection of a homogeneous population of patients with chronic bronchitis, between group differences relating to antibiotic treatment could still be confounded by factors related to medical history, severity of disease, and use of concomitant medications. The design of future clinical trials should take these factors into account.

The results of this study demonstrate that acute hospitalization is frequent in AD patients resulting in considerable cost implications. Interventions that support patients and their cares to manage their loss of ADL may be a practical approach to reducing the need for acute hospital admissions.