Table 1.
List of outcome measures. For each outcome measure, the importance is indicated, and for critical and important outcome measure the minimal clinically important difference is reported.
| Outcome measures | Importance | Measure unit | Minimal clinically important difference |
|---|---|---|---|
| Mortality | Critical* | ||
| Exacerbation rate | Critical | Average reduction in the annual number of exacerbations | 25% (a minimum reduction of 0,5 exacerbations per year) |
| Number of patients who experience 0 exacerbations annually | 10 percentage points | ||
| Oral corticosteroid-maintenance treatment | Critical | Average %-reduction in daily dose (maintenance-treatment) | 20% (at least 2.5-mg prednisolone equivalent dose) |
| Percentage of patients who are discontinued oral corticosteroid-maintenance treatment | 5 percentage points | ||
| Percentage of patients who experience ≥50% reduction of oral corticosteroid treatment | 10 percentage points# | ||
| Lung function FEV1 | Important | Average change in lung function | 200 ml |
| Percentage of patients who experience an improvement of 200 ml or more | 15 percentage points | ||
| Asthma control | Important | Average change in asthma control. A prioritised list of scores: · ACQ 5 (Asthma Control Questionnaire) · ACT (Asthma Control Test) · Other similar questionnaires |
ACQ: 0.5 ACT: 3 |
| Quality of life (QoL) | Important | Average change in QoL. A prioritised list of scores: · Astma Quality of Life Questionnaire (AQLQ) · Other questionnaires |
AQLQ: 0.5 points |
| Serious adverse events (SAEs) | Important | The added number of SAEs | 5 percentage points for the added number of SAEs |
| Specific subgroups of SAEs, including anaphylaxis is assessed if they are distributed uniformly between the groups | No minimal clinically important difference is reported | ||
| Dropout rate | Important | The percentage of patients who dropped out when the study was completed (difference between intention-to-treat population and patients who completed the study) | 10 percentage points |
| Sick leave | Important | Average number of sick leave days per year | 5 days per year |
| Eosinophil count | Less | Eosinophils per microL | |
| Adverse events (AEs) | Less | The added number of AEs |
* Mortality is always considered to be a critical effect goal, albeit not an effective efficacy measure in the assessment of biological drugs in severe asthma. Asthma-related death occurs rarely, and it is therefore not estimated that outcome measure will provide any relevant information. In relation to safety, it is included in outcome measure: serious adverse events (SAEs). Mortality will therefore not act as a separate outcome measure in the assessment of the therapy.
# The Expert Committee defined this outcome measure after the protocol was approved as data could not be extracted for the average OCS reduction. FEV1 = forced expiratory volume