Table 1

Data for the benefit–harm assessment of roflumilast for patients with COPD

Numbers of patients with ≥1 event, person-years and relative risks of roflumilast for patients with COPD11*
Type of outcomeNumber of patients with ≥1 eventPerson-yearRelative risk (95% CI)
Roflumilast 500 µgPlaceboRoflumilast 500 µgPlacebo
Moderate or severe exacerbation717821118612400.91 (0.82 to 1.01)
Severe exacerbation (for sensitivity analysis)157198118612400.83 (0.67 to 1.03)
Acute pancreatitis51326134055.22 (0.58 to 246.93)
Insomnia17861326134053.05 (2.27 to 4.15)
Anxiety8244326134051.95 (1.33 to 2.87)
Depression8049326134051.70 (1.18 to 2.48)
Suicide (completed)†20326134056.00
Diarrhoea585143326134054.27 (3.55 to 5.17)
Nausea29779326134053.93 (3.05 to 5.10)
Weight loss394101326134054.07 (3.27 to 5.12)
Headache266110326134052.52 (2.01 to 3.18)
Dizziness13965326134052.23 (1.65 to 3.05)
Incidence rates and mortality rates (per 1000 person-years) without roflumilast for patients with COPD
Type of outcomeIncidence rateType of outcomeIncidence rate
Acute pancreatitis160.077Weight loss1513.4
Insomnia1117.9Headache1132.3
Anxiety1112.9Dizziness1119.1
Depression1416.2Mortality18
Suicide (completed)170.124 Men
Diarrhoea1142.0  Age <6587.8
Nausea1123.2  Age ≥65106.4
   Women
    Age <6572.1
    Age ≥6585.2
Weights (relative importance): numerically (eg, 0.5 as used in analysis) and visualised from lowest (◖) to highest importance (••••••••••)
Analysis IAnalysis IIAnalysis III (main analysis)Sensitivity analysis
Type of outcomeEqual weightsWeights based on importance of outcomesWeights based on importance and co-occurrence of harm outcomesAnalysis focusing on severe exacerbations
Exacerbation1.0
••••••••••
0.5
•••••
0.5
•••••
1.0
••••••••••
Acute pancreatitis1.0
••••••••••
0.5
•••••
0.5
•••••
0.5
•••••
Insomnia1.0
••••••••••
0.5
•••••
0.25
••◖
0.25
••◖
Anxiety1.0
••••••••••
0.5
•••••
0.25
••◖
0.25
••◖
Depression1.0
••••••••••
0.5
•••••
0.25
••◖
0.25
••◖
Suicide (completed)1.0
••••••••••
1.0
••••••••••
1.0
••••••••••
1.0
••••••••••
Diarrhoea1.0
••••••••••
0.1
0.05
0.05
Nausea1.0
••••••••••
0.1
0.05
0.05
Weight loss1.0
••••••••••
0.1
0.05
0.05
Headache1.0
••••••••••
0.1
0.05
0.05
Dizziness1.0
••••••••••
0.1
0.05
0.05
  • *We estimated the treatment effects for exacerbations based on the ‘pivotal studies pool’ (including trials M2-124 and M2-125). We estimated the treatment effects for other harm outcomes based on the ‘COPD safety pool’ (including trials FK1-101, FK1-103, M2-107, M2-110, M2-111, M2-112, M2-118, M2-119, M2-121, M2-124, M2-125, M2-127, M2-128, and IN-108).

  • †The relative risk for suicide (completed) was not estimable. We assumed the relative risk was 6.00.