Results

Search Results

The literature search retrieved 255 articles. An additional nine were identified from other sources. Twenty-two duplicate articles were removed before abstract screening. Based on abstract screening, 202 papers were excluded and a further 13 papers were excluded based on the full text. Main reasons for exclusion were: study design not an RCT; no usual care control group; medication adherence not included as a usable outcome; trial compared medications or was conducted in adults. Twenty-five studies were included in the narrative synthesis21-45; see full PRISMA diagram (Figure 1).
Figure 1: PRISMA flow diagram showing study selection

Narrative Synthesis

Study characteristics

Effect on adherence
Less than half of the interventions (44%, 11/25) showed significant improvement in adherence in the intervention groups compared to the control groups 23-25; 32-34; 36-38; 41; 44 (Table 2).

Study Reliability

Although half of the studies were reported as effective at increasing adherence the study reliability varied widely (Table 3). A wide range of criteria were used for the diagnosis of asthma and therefore the patient sample included in each study was heterogeneous. Where reported, most diagnoses were based on guidelines such as GINA, National Heart, Lung, and Blood Institute (NHLBI) 24; 25; 35 or a physician diagnosis plus a prescription for ICS 23; 26; 28-30; 37 (50%, 9/18). Just under half (44%, 8/18) reported using an asthma diagnosis given by the emergency department physician21; 32; 38 , where patients asthma symptoms will have been directly observed by physicians, or by diagnosis from medical records 22; 27; 31; 34; 36. Asthma diagnosis criteria was generally poorly reported.
Based on the coding hierarchy which considers the reliability of the asthma diagnosis (E-table 2), seven studies used reliable means to diagnose asthma in their participants 21; 23; 24; 32; 36-38. Three studies used less reliable methods 25; 34; 35 and a further seven used unreliable diagnostic methods22; 26-31. In one study the method of diagnosis of asthma was unclear 33.
Adherence measurement varied with studies using objective and subjective measures. Based on our coding hierarchy of objectivity of adherence measurements (E-table 2), most studies used more objective measurements23; 24; 28; 31; 33; 34; 36; 37 or both objective and subjective measures 26; 27; 35. Six used subjective measurements of adherence only 21; 22; 25; 30; 32; 38and for one study, the method of adherence measurement was unclear29. Based on the RoB, reliability of asthma diagnosis and objectivity of the adherence measurement within each study the reliability of the evidence can be summarised (Table 3).

Risk of Bias

Risk of bias within studies
Nearly one third of the studies were considered low risk21; 23; 24; 34; 38; 39; 41; 43 , with most (n=10) being considered moderate risk 22; 26; 30; 32; 33; 35-37; 40; 44. Six studies were considered high risk25; 27-29; 31; 42 (Table 3 and Figure 2).
Figure 2: Risk of Bias within and across studies
Risk of bias across studies
The main bias identified was performance bias. Overall, RoB was low for most studies in terms of selection bias (random sequence generation); detection bias (blinding of outcome assessment) and reporting bias (selective reporting bias). Section bias (allocation concealment) was often low or unclear and was generally poorly reported. Attrition bias (incomplete outcome data) was frequently unclear or high risk (Figure 2).

Reliability of the evidence

The most reliable studies (i.e. moderate or high reliability based on asthma diagnosis and adherence measurement criteria) and low/ moderate RoB are discussed in more detail below. Nine of the thirteen studies in this category were effective at increasing adherence23; 24; 32-34; 36-38; 41 and four were ineffective21; 26; 35; 39. The following section compares the nine effective studies with the four ineffective studies within this high reliability group. Of those studies which reported effectiveness for increasing adherence, only one study was not considered to be in the high reliability group.
Components of effective interventions
This section will summarise the findings of this systematic review based on the 3CBC framework 11 in order to critically appraise the effectiveness of the components within the most reliable intervention study evidence.

Context

The eight effective studies were conducted in Brazil24; Greece 41;New Zealand23; 32; China44; the USA38; the UK 34; 36; and the Netherlands 37. The ineffective studies were conducted in the USA 21; 26; 28; 31; 39; 42, Taiwan35, Brazil45, the Netherlands40 and Sweden43; 46. Effective studies took place in an emergency care setting 23; 38; primary care 24; 34; hospital outpatients33; 36; 37; 41; 44; and in the community32; 44. The ineffective studies took place in: emergency care 21; 39, in the community26; 40, primary care42; 43 and in hospital outpatients 35; 43; 45.
There are no data regarding whether or not the interventions used a no-blame approach 11 but three of the high reliability effective studies were clearly tailored to the patient24; 32; 33; 41 compared with only one of the ineffective studies 35.

Channel of Delivery

Seven of the high reliability effective studies used technology to deliver the intervention including using electronic monitoring devices (EMDs 23; 33; 36; 37; 41), the telephone24, a patient and health-care provider app44 and a SMS-based system 37. Seven of the ineffective studies used technology to deliver the intervention via an educational video42, website and monthly telephone calls 26, SMS text reminder and tips (not personalised) 39, a smartphone app40; 43 and via the internet alone35. Different health care practitioners were involved in the interventions. Effective studies involved Pharmacists23; 37, nurses 23; 24; 32; 33; 36; 41; 44, specialist physicians 32; 33; 36-38; 44, community health workers 32 and researchers37. In one study (1/8), the only channel was a letter sent from the patients’ GP 34 to the parents of the child with asthma. The ineffective studies used limited contact with any health care practitioner 21, pharmacist40,nurse 26; 35; 42; 45 and physician 35; 42; 43.

Content

Summary of perceptions and practicalities targeted by adherence interventions
Of the nine effective and highly reliable studies, six met the criteria for Level 3 (67%; 24; 32; 33; 36; 38; 41 (Table 4). The three other effective and high reliability studies were categorised as Level 1 or Level 2 with one untailored intervention focusing practical and perceptual factors34, one focusing only on practical factors 23 and one targeting practicalities in a tailored way 37. Of the highly reliable studies only four were not effective- two were categorised as Level 3 26; 35, one was categorised as Level 239 and one was categorised as Level 121.
Only two effective studies were classified as low reliability and categorised as Level 3 25; 44. The ineffective and low reliability studies were either classed as Level 1 (no tailoring)27; 42; 43, Level 2 perceptual only29; 30, or both but not tailored 22or Level 3 28; 31; 40; 45. Therefore, only six studies using Level 3 PAPA were not effective (6/25, 24%), four of which were classed as low reliability studies. Overall, only 18% (2/11) of high reliability studies using Level 3 of the PAPA did not result in effective studies.
Summary of Behaviour Change Techniques used
The most commonly used Behaviour Change techniques within effective and highly reliable study interventions were: Non-specific rewards33; Prompts/cues 23; 24; 33; 34; 36; 37; 39; 41; 44; Feedback and Monitoring 23; 33; 36-38; Pharmacological support (this often involved providing free medications in countries where medications were not free and providing a longer-term supply when the medications were free) 23; 24; 33; 34; 38; Instruction on how to perform a behaviour32; 33; 36; 38; 41 and Information about antecedents32; 41. Relevant to the age of the participants, the BCTs most often targeted both parent and child with the aim (primary or secondary outcome) of improving the child’s adherence to ICS. Only in one instance did the BCT pharmacological support target only the parent in the form of a letter to encourage the parent to pick-up the child’s ICS prescription 34. Four further studies specified that the interventions targeted the child specifically23 and these were often with older children24; 28; 29. For extracted examples of common behaviour change technique and the studies they were used in see Table 5. For full details of the behaviour change technique extraction for each included study see Table 1.