Outcome measurement instrument recommendations
| Death from any cause | Death from any cause during study period. Record date of death. |
| Death from COPD exacerbation | Consider the immediate cause of death as documented in the death summary. In cases of death due to an immediate complication of an exacerbation, such as a ventricular arrhythmia, massive pulmonary embolism or myocardial infarction, the exacerbation should be considered the cause of death. Ideally, cause of death will need to be confirmed by a blinded adjudication committee. However, this may not always be feasible. |
| Treatment success | Treatment success defined as sufficient improvement of the signs and symptoms of the exacerbation that no additional systemic treatments (antibiotics or systemic corticosteroids) are required. |
| Need for hospital admission for the presenting exacerbation | A clinical need to admit a patient to the hospital, or equivalent intensification of the monitoring or care that may be provided in other settings (including patient's home). Admissions for social reasons should be reported separately. For evaluation of this outcome, investigators should record whether a patient required admission at any time point and whether they still required hospital admission at a specific follow-up time point. |
| Need for admission to the ICU for the presenting exacerbation | Need for ICU admission should be evaluated on the basis of the need for invasive mechanical ventilation, defined as: 1) persistent or deteriorating respiratory acidosis despite optimised medical treatment and delivery of NIV; 2) persistent or deteriorating respiratory acidosis despite optimised medical treatment and a contraindication for the use of NIV, for example due to severe facial deformity where fitting a mask is impossible, upper airway obstruction, or facial burns; 3) respiratory arrest or peri-arrest situations unless there is a rapid recovery from manual ventilation or provision of NIV. For evaluation of this outcome, investigators should record whether a patient required admission at any time point and whether they still require ICU admission at a specific follow-up time point. |
| Levels of oxygen and carbon dioxide in the blood (arterial blood gases) | A setting- and intervention-specific outcome. A baseline and at least one follow-up measurement are required with a clear indication of whether or not the patient was receiving oxygen at the time of the measurement, and if yes, how much. It may not be feasible for studies evaluating outpatients. |
| Breathlessness | Breathlessness should be evaluated using the modified Borg scale. It should be measured at approximately the same time every day. It can be self-completed. |
| Health-related quality of life | The COPD Assessment Test should be used for assessing health-related quality of life. |
| Activities of daily living | The Capacity of Daily Living During the Morning Questionnaire should be used for evaluating basic activities of daily living during the exacerbation. The Manchester Respiratory Activities of Daily Living Questionnaire should be used for evaluating basic and instrumental activities of daily living, during recovery (long-term impact of the exacerbation). |
| Worsening of symptoms after the initial treatment | The modified Borg scale and the COPD Assessment Test should be used to detect symptom worsening after the initial treatment. |
| Disease progression | Permanent deterioration in lung function should be used to evaluate the impact of exacerbations on disease progression. Two pulmonary function tests during stable clinical condition are needed: one within 6 months prior to the index exacerbation, and one within 2–6 months afterwards. Change from baseline in FEV1, FVC and FEV1/FVC ratio should be noted. The number of exacerbations experienced between the two measurements should be noted. Ideally, only the index exacerbation should be included between the two measurements. Disease progression as a core outcome is only relevant for longer-term studies that recruit participants during stable disease state, in anticipation of an exacerbation. |
| Future exacerbations | Future exacerbations, noting whether they are moderate or severe, after treatment success is confirmed. |
| Future hospital admissions | Future hospital admissions for any medical reason, or equivalent intensification of the monitoring or care that may be provided in other settings, after treatment success is confirmed. |
| Serious adverse events from treatments | Following the definition of the International Council for Harmonisation. A serious adverse event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment, that fulfils any of the following: 1) results in death; 2) is life threatening; 3) requires inpatient hospitalisation or prolongation of existing hospitalisation; 4) results in persistent or significant disability/incapacity; 5) is a congenital anomaly or birth defect. Suspected unexpected serious adverse reactions should also be reported. |
| Development of resistant bacteria | Trials evaluating antimicrobials, antimicrobial stewardship strategies, novel immune modifiers or other interventions that may affect bacterial resistance should evaluate bacterial resistance to the administered antibiotics in spontaneous sputum. As a minimum, resistance should be evaluated at baseline and within a week after treatment completion. Sputum induction may provide additional information. However, in each study, researchers should consider the balance between the added value compared to the risk, participants' discomfort and required resources. |
| Development of pneumonia | Pneumonia confirmed by the presence of new consolidation upon chest radiography or other imaging modalities of the chest, in the presence of consistent clinical signs and symptoms. When possible, chest imaging should be acquired at baseline, to assess for the presence of pneumonia. This may not be possible for trials recruiting patients outside the hospital setting. Follow-up chest imaging should be driven by clinical need. |
| Treatment adherence | An intervention-specific outcome. Methods for assessing treatment adherence should be reported clearly. |
| ▪ Strong recommendation | ▪ Interim recommendation, with research agenda |
ICU: intensive care unit; NIV: noninvasive ventilation; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity.