Common use of Study Rationale Clause in Contracts

Study Rationale. COPD is a disease with rising morbidity and mortality. The recent Global Burden of Disease Study [▇▇▇▇▇▇, 1997] ranks COPD as the 6th leading cause of mortality and the 12th leading cause of morbidity (defined as disability-adjusted life years [DALYs]) world-wide. These figures are expected to rise, with COPD becoming the 3rd leading cause of mortality and the 5th leading cause of morbidity by the year 2020. Furthermore, trends in the use of medical care resources indicate that the economic cost of COPD continues to rise in direct relation to the ageing population, the increase in prevalence of disease, and the cost of new and existing medical and public health interventions (▇▇▇▇▇ S; ERS 1999). The largest share of medical care costs for COPD is a consequence of an acute exacerbation resulting in hospitalisation. COPD exacerbations have also been associated with decrements in pulmonary function, and contribute substantially to the reduced quality of life in patients with the disease. In much of the world, the full effect of existing smoking patterns has not been seen so that COPD mortality is rising. Post-hoc analysis of data from ISOLDE [▇▇▇▇▇, 2000] suggests a reduced mortality rate in COPD subjects randomised to FP compared with placebo, during the 3 years post-randomisation. Although ▇▇▇▇▇▇ was not designed to investigate mortality, and therefore the study should be regarded as a pilot, the data provide a rationale on which to base a definitive mortality study. No prospective mortality data are available for subjects treated with salmeterol. However, it can be hypothesised that the properties of salmeterol, particularly its cytoprotective effects and hence its potential to reduce infective exacerbations, could have a significant impact on subject survival. If this is the case, there could be, at least, an additive effect of salmeterol and FP in reducing mortality in subjects with COPD. The purpose of the present study is to determine the effects on mortality and morbidity of the salmeterol/FP combination product (SERETIDE) at a dose of 50/500µg bd compared with each component alone and with placebo, when added to usual COPD therapy (defined as any treatment but excluding inhaled corticosteroids, inhaled long-acting † SERETIDE, ▇▇▇▇▇, ADVAIR, DISKUS and ACCUHALER are Trade Marks of GlaxoSmithKline group of companies. Registered in US Patent and Trademark Office. bronchodilators, and long term oral corticosteroids), in moderate to severe COPD subjects with poorly reversible airflow obstruction.

Study Rationale. COPD is a disease with rising morbidity and mortality. The recent Global Burden of Disease Study [▇▇▇▇▇▇, 1997] (31) ranks COPD as the 6th leading cause of mortality and the 12th leading cause of morbidity (defined as disability-adjusted life years [(DALYs])) world-wide. These figures are expected to rise, with COPD becoming the 3rd leading cause of mortality and the 5th leading cause of morbidity by the year 2020. Furthermore, trends in the use of medical care resources indicate that the economic cost of COPD continues to rise in direct relation to the ageing population, the increase in prevalence of disease, and the cost of new and existing medical and public health interventions (▇▇▇▇▇ S; ERS 1999). The largest share of medical care costs for COPD is a consequence of an acute exacerbation resulting in hospitalisation. COPD exacerbations have also been associated with decrements in pulmonary function, and contribute substantially to the reduced quality of life in patients with the disease. In much of the world, the full effect of existing smoking patterns has not been seen so that COPD mortality is rising. Post-hoc analysis of data from ISOLDE [▇▇▇▇▇, 2000] suggests suggest a reduced mortality rate in COPD subjects randomised to FP compared with placebo, during the 3 years post-randomisation. Although ▇▇▇▇▇▇ was not designed to investigate mortality, and therefore the study should be regarded as a pilot, the data provide a rationale on which to base a definitive mortality study. No prospective mortality data are available for subjects treated with salmeterol. However, it can be hypothesised that the properties of salmeterol, particularly its cytoprotective effects and hence its potential to reduce infective exacerbations, could have a significant impact on subject survival. If this is the case, there could be, at least, an additive effect of salmeterol and FP in reducing mortality in subjects with COPD. The purpose of the present study is to determine the effects on mortality and morbidity of the salmeterol/FP combination product (SERETIDESERETIDE†) at a dose of 50/500µg bd † DISKUS and SERETIDE are Trade Marks of GlaxoSmithKline group of companies. Registered in US Patent and Trademark Office. compared with each component alone and with placebo, when added to usual COPD therapy (defined as any treatment but excluding inhaled corticosteroids, inhaled long-long- acting † SERETIDE, ▇▇▇▇▇, ADVAIR, DISKUS and ACCUHALER are Trade Marks of GlaxoSmithKline group of companies. Registered in US Patent and Trademark Office. bronchodilators, and long term oral corticosteroids), in moderate to severe COPD subjects with poorly reversible airflow obstruction.