Characteristics of the 23 studies using objective measures to assess adherence
| First author [ref.] | Design | Age years | Participants n | Adherence measure | Adherence cut-off | Exacerbation measure | Estimates | Quality score |
| Refill data (MPR and prescriptions) | ||||||||
| Children | ||||||||
| Rust [21] | Cohort | 5–12 | 43 166 | ICS PPDC 90 days; ratio controller to total drugs | PPDC: ⩾50% or <50%; ratio: ⩾0.5 or <0.5 | ED/hosp | Exacerbation nonadherent versus adherent ratio: ORadjED 1.21 (95% CI 1.14–1.27); ORadjhosp 1.70 (95% CI 1.45–1.98) | 8 |
| Camargo [22] | Cohort | 0–8 | 10 976 | MPR ICS | Dichotomised at median MPR: 0.08 | Combined: ED/hosp visit | Exacerbation adherent versus nonadherent; budesonide HRadj 0.32 (95% CI 0.19–0.68); non-nebulised ICS HRadj 0.25 (95% CI 0.13–0.47) | 8 |
| Bukstein [23] | Cohort | 0–4 | 11 407 | Number of ICS prescriptions | ⩾2 versus 1 prescription per 9 months before index date | Combined: ED/hosp | Exacerbations: adherent versus less adherent; all controller therapy: OR 0.80 (95% CI 0.59–1.10); ICS only: OR 0.60 (95% CI 0.37–0.99) | 8 |
| Bukstein [24] | Randomised cohort | 6–15 | 104 | Filled prescriptions | ED/hosp/office visit/OCS | Adherent (⩾6) versus nonadherent (⩽5 fills); OCS: 26% adherent versus 44% nonadherent; montelukast users more adherent than fluticasone users (p=0.0003); no significant difference in hosp/ED/office visits between montelukast/fluticasone groups | 7 | |
| Elkout [25] | Cohort | Children | 3172 | MPR ICS | Adequate MPR 80–120% | OCS | Adequate MPR (80–120%) was associated with higher risk of being prescribed OCS (ns); ICS only: ORadj 1.02 (95% CI 1.00–1.04); LABA/ICS: ORadj 1.12 (95% CI 0.58–2.11); LABA+ICS: ORadj 1.43 (95% CI 0.75–2.71) | 7 |
| Herndon [26] | Cohort | 2–18 | 10 878 | MPR ICS | 3 MPR categories: 0–19%, 20–49%, >50% | ED/hosp | Higher adherence, less ED (p=0.01), MPR ⩾0.50 versus ⩽0.19: ED: ORadj 0.56 (95% CI 0.43–0.72); hosp: ORadj 0.96 (95% CI 0.67–1.36) | 7 |
| Adults | ||||||||
| Price [27] | Retrospective matched cohort | 12–80 | 30 939 | Beclomethasone MPR; ratio controller to total | 4 MPR categories: <50%, 50–70%, 70–99%, >100%; ratio: <0.5 or ⩾0.5 | ED/hosp; OCS | Higher exacerbation rates by better adherence to ICS | 9 |
| Williams [28] | Prospective asthma cohort | 12–56 | 298 | Moving CMA ICS | Per 25% increase MPR | Combined and ED/hosp/OCS | 25% increased adherence: combined outcome: HRadj 0.89 (95% CI 0.81–0.97), p=0.009; OCS: HRadj 0.90 (95% CI 0.80–1.0), p=0.043; ED: HRadj 0.87 (95% CI 0.73–1.03), p=0.114; hosp: HRadj 0.99 (95% CI 0.65–1.51), p=0.971. High (76–100% MPR) versus low (0–25% MPR): OR 0.58 (0.39–0.87) | 8 |
| Williams [29] | Cohort | 18–50 | 405 | CMA; CMG; for ICS | Per 25% increase in CMA/CMG | Outpatient/ED/hosp/OCS | Per 25% increase gap: ED: RRadj 1.25 (95% CI 0.84–1.85); OCS: RRadj 1.26 (95% CI 0.95–1.67); hosp: RRadj 2.01 (95% CI 1.06–3.79). Per 25% increase CMA: OCS: RR 0.75 (95% CI 0.58–0.97). Correlation adherence CMA: ED: R −0.159, OCS: R -0.179, hosp: −0.130 (ns) | 8 |
| Balkrishnan [30] | Case–control | Older adults | 751 | Filled prescription ICS | 0, 1 or 2 refills in 2 months before event | Combined: ED/hosp | Exacerbation (referent=nonadherent=0 refills) ORadj good (2 refills ICS): 0.62 (95% CI 0.42–0.90); ORadj partial (1 refill ICS): 0.75 (95% CI 0.57–0.96) | 8 |
| Mattke [31] | Cohort | 0–65 | 12 476 | MPR ICS | MPR quarters: highest versus lowest | Combined: ED/hosp/office | Lowest versus highest adherence quarters; incidence of ED and hosp: not significantly different | 8 |
| Delea [32] | Cohort | ⩾12 | 12 907 | MPR FSC | MPR quartiles per 3 months of follow-up | ED/hosp or OCS | Per 25% increase mean adherence: ED/hosp: ORadj 0.90 (95% CI 0.89–0.92); OCS: ORadj 0.97(95% CI 0.94–0.996) | 8 |
| Stern [33] | Cohort | 6–99 | 97 743 | MPR all controllers | Combined ED/hosp | 75th percentile MPR cut-off versus less adherent; exacerbation ORadj 0.862 (95% CI 0.827–0.898) | 8 | |
| McMahon [34] | Cohort | 12–45 | 4535 | Days with ICS per 90 days | 0 days ICS; 1–89 days; 90 days | Combined: hosp+OCS and hosp only | Combined exacerbation: 0 days adherent: ORadj 0.77 (95% CI 0.44–1.35); 1–89 days adherent: ORadj 1.02 (95% CI 0.60–1.73). Hosp: 0 days adherent: ORadj 1.12 (95% CI 0.36–3.47); 1–89 days adherent: ORadj 0.91 (95% CI 0.31–2.72) | 7 |
| Smith [35] | Cohort | 5–62 | 3013 | MPR all controllers | MPR: 0–50%, 50–80% or >80% | ED/hosp | Risk of admission (ED/hosp) nonadherent versus: 50–80% adherent: OR 1.59 (95% CI 0.86–2.96); >80% highly adherent: OR 2.11 (95% CI 1.09–4.12) | 7 |
| Hyland [36] | Cohort | Adults | 166 | Prescription and records | >75% recommended prescriptions | Combined: GP visit/ED/hosp | Spearman correlation between asthma exacerbations and adherence 0.21 (p=0.007) | 6 |
| Osman [37] | Prospective cohort | Adults | 754 | Requested prescription | Among patients with <7 SABA: ⩽4 ICS versus 5-7 ICS versus ⩾8 ICS | Hosp/OCS | <7 SABA and ⩽4 ICS versus 5–7 ICS and ⩾8 ICS: used few OCS (p=0.06); more hospital admissions (p<0.05) | 5 |
| Electronic monitoring device (children only) | ||||||||
| Rohan [38] | Prospective cohort | 5–17 | 92 | Electronic monitoring device ICS | Daily ICS use averaged over 5-day intervals | Healthcare visits (ED/hosp/visit specialist) | Growth curve modelling: average healthcare-related visits per year low adherent (1 sd below mean): 0.76; moderate adherent: 0.70; good adherent (1 sd above mean): 0.65 | 6 |
| McNally [39] | Cohort | 5–17 | 63 ICS+LTRA users | Electronic monitoring device ICS adherence rate (mean % prescribed) | Highest quartile (mean 0.62) versus lowest quartile (mean 0.20) | Healthcare utilisation (hosp/ED/clinic visit) | Decline in fluticasone adherence was related to increased healthcare utilisation: p<0.05; rate of change in healthcare utilisation related to fluticasone low versus high adherence: R=-0.11, p=0.39 (ns) | 6 |
| Milgrom [9] | Cross-sectional (4 visits) | 8–12 | 24 | Electronic monitoring device ICS and β2-agonist | NA | OCS | Mean adherence 13.7% in cases versus 68.2% in patients without OCS (p=0.008) | 3 |
| Weighing/counting | ||||||||
| Children | ||||||||
| Krishnan [40] | Randomised controlled trial | 5–12 | 140 | Weighing/counting budesonide/placebo | NA | ED/OCS | Treatment group, adherence 4 years, interaction: ED visits (yes versus no), OR p=0.58; OCS (number of courses per 100 person-years) p=0.56 | 9 |
| Lasmar [41] | Prospective cohort | 3–12 | 122 | Weighing/counting beclomethasone | NA | Combined: asthma deterioration, OCS, ED, hosp | Adherence level 70.9% in group of patients without exacerbation versus 44% in group of patients with exacerbations (p=0.004) | 5 |
| Adults | ||||||||
| Santos [42] | Prospective cohort | >18 | 160 | Weighing/counting ICS | Cut-off point: 80% of prescribed dose administered | Exacerbation/ED | Adherent versus nonadherent: exacerbation: 45.5% versus 50% (ns); mean±sd ED visits: 0.9±1.9 versus 1.4±2.6 (p=0.2) | 3 |
MPR: medication possession rate; ICS: inhaled corticosteroids; PPDC: proportion of prescribed days covered; ED: emergency department; hosp: hospitalisation; ORadj: adjusted odds ratio; HRadj: adjusted hazard ratio; OCS: oral corticosteroids; ns: nonsignificant; LABA: long-acting β2-agonist; CMA: continuous measure of availability; CMG: continuous measure of gaps; RRadj: adjusted relative rate; FSC: fluticasone/salmeterol combination; GP: general practitioner; SABA: short-acting β2-agonist; LTRA: leukotriene receptor antagonist; NA: not applicable.