TABLE 2.
Definitions of non-response and response to biological therapy for severe asthma and their quality of evidence
| Study, year [ref.] | Scale | Patient input in scale development | Time-point from baseline | Method of development of definition of response | Definition of response | Range of scores | GRADE |
| Composite outcome measures | |||||||
| Fitzpatrick, 2020 [53] | ASSESS | No | 12 months | Distribution-based method | MID 2 points | 0–20 points (higher=worse) | ⊕⊕⊕○A |
| Krouse, 2017 [52]# | CASI | No | 60 weeks | Anchor-based method | MCID 1 point | 0–18 points (higher=worse) | ⊕⊕⊕⊕ |
| Perez de Llano, 2021 [54] | FEOS | No | NR | Delphi exercise, conjoint analysis | Response defined according to different thresholds for each outcome measure with respect to baseline; response ranges from 0 (worsening) to 100 (best) | 0–100 points (higher=better) | ⊕⊕⊕⊕ |
| Asthma symptom outcome measures | |||||||
| Shen, 2021 [50] | ASUI | Yes | 12 weeks | Anchor-based method | MCID 0.07 to 0.11 | 0–1 points (higher=better) | ⊕⊕⊕⊕ |
| Shen, 2021 [50] | ASI | Yes | 12 weeks | Anchor-based method | MCID −0.42 to −0.26 | 0–3 points (higher=worse) | ⊕⊕⊕⊕ |
| Globe, 2019 [51] | ASD¶ | Yes | 12, 24 weeks | MID (change −0.5 to −1.0 ACQ); responder (change ≤ −1.0 ACQ) | Reported for 12 and 24 weeks: Mean 7-day score: MID −0.35 and −0.35; responder −0.54 and −0.68 7-day symptomatic days: MID −1.75 and −1.98; responder −2.34 and −3.22 Minimal symptomatic days-1: MID 1.97 and 2.16; responder 2.43 and 3.23 Minimal symptomatic days-2: MID 1.02 and 1.36; responder 2.31 and 2.56 |
0–4 points (higher=worse) | ⊕⊕⊕⊕ |
| Asthma control outcome measure | |||||||
| Lloyd, 2007 [56] | GETE | No | 28 weeks | Physician consensus | Responder (complete control; marked improvement of asthma); non-responder (discernible, but limited improvement in asthma, no appreciable change in asthma; worsening of asthma) | 0–5 points (higher=better) | ⊕⊕⊕⊕ |
| Asthma quality of life outcome measure | |||||||
| Masoli, 2021 [49] | SAQ | Yes | 4, 8, 12 weeks | Anchor-based method | MCID (SAQ) 0.5 points; MCID (SAQ-global) 11 points | SAQ: 1–7 points; SAQ-global: 0–100 points (higher=better) | ⊕⊕⊕⊕ |
ACQ: Asthma Control Questionnaire; ASSESS: Asthma Severity Scoring System; ASUI: Asthma Symptom Utility Index; ASI: Asthma Symptom Index; ASD: Asthma Symptom Diary; CASI: Composite Asthma Severity Index; FEOS: forced expiratory volume in 1 s, exacerbations, oral corticosteroids, symptoms score; GETE: Global Evaluation of Treatment Effectiveness; GRADE: Grading of Recommendations, Assessment, Development and Evaluation; MCID: Minimal Clinically Important Difference; MID: Minimal Important Difference; NR: not reported; SAQ: Severe Asthma Questionnaire. #: definition was developed in mild to severe using anchor-based method and then evaluated in biologicals (MID was changed to MCID by the review team); ¶: symptomatic days (defined as mean of the 10 ASD daily symptom items ≥1, otherwise non-symptomatic day), minimal symptom days-1 (defined as mean of the 10 ASD daily symptom items ≤1 and no single symptom item score>1, otherwise non-minimal symptom day-1) and minimal symptom days-2 (defined as no single ASD daily symptom item). Certainty of evidence was assessed using the GRADE approach [39, 41, 43]. The reason for downgrading was: A: indirectness.