Discussion

Summary of the Evidence

This is the first review to summarise effective interventions to increase adherence in children with asthma, taking into account the reliability of the studies and the behaviour change framework and techniques used in a clinically meaningful way. Previous reviews of adherence interventions in adults and children have shown that only half of interventions are effective at increasing adherence10. Similarly, we found that only nearly half of the included studies (11/25) were effective at significantly increasing adherence 23-25; 32-34; 36-38; 41; 44. We then explored the crucial factors for an effective intervention to increase adherence.
Of the thirteen studies that were effective, nine were considered highly reliably 23; 24; 32-34; 36-38; 41. By comparing the effective and reliable studies (9/25) (accurate asthma diagnosis, objective adherence measure and low/moderate RoB) to the unreliable or ineffective studies this review should inform the development of future interventions. In terms of context high reliability interventions carried out in the UK (2/25) and New Zealand (2/25) were most likely to be effective. High reliability Interventions carried out in the USA were most often ineffective (6/25 versus 1/25 that was effective). However, regarding healthcare context there were no differences between different healthcare settings such as primary or secondary care. Three of the four high reliability but ineffective studies were not tailored to the patient group 21; 39; 47. This highlights the importance of tailoring as it has been well reported that tailoring is associated with more effective interventions 12.
The findings of this review support the use of technology as a channel to deliver the adherence intervention including electronic monitoring devices for measuring adherence and patient and health-care provider apps and telephone calls. Healthcare practitioner type is not as important as face-to-face contact while providing digital interventions. This finding supports a previous recent review based on digital interventions in long-term conditions 48. Those planning an adherence intervention should therefore consider the amount of contact alongside digital interventions as a key component to future effectiveness.
In terms of content, six out of the nine reliable effective interventions were coded as Level 3 PAPA 24; 32; 33; 36; 38; 41. Three high reliability and effective studies did not meet the criteria for Level 3 PAPA 23; 34; 37. Overall, only two of the highly reliable studies based on Level 3 PAPA did not result in effective interventions 26; 35. The two studies had moderate risk of bias and did not involved face-to-face contact with a healthcare professional.
PAPA is easy to apply when developing an intervention as it simply highlights the effective minimal ingredients for change in adherence49. This review found that currently developed interventions in this area largely neglect the role played by patient beliefs about asthma and ICS. Research shows that these are often important determinants of non-adherence in adults50; 51 and there is immerging evidence of relevance in children 52: in terms of parental 53; 54 and adolescent beliefs 14; 15. Patient’s perceptions that are of particular importance are beliefs about their personal need for treatment (even in the absence of symptoms) and concerns about steroid safety. These issues are important because necessity and concern beliefs may be the drivers of adherence as they influence motivation to adhere to treatment 55; 56.
The most common BCTs used in effective interventions were prompts/cues (e.g. reminders), feedback and monitoring; pharmacological support and instruction of how to perform a behaviour. Each BCT was found to be most effective as part of complex interventions when tailored to the patient. It is currently unknown how many and what combination of BCTs are likely to increase the effectiveness of an intervention. However, this review is the first to show that particular BCTs are important to consider when developing a tailored intervention for increasing adherence in children with asthma.

Strengths and Limitations

Due to the heterogeneity of the adherence outcomes, limited availability of raw data and a small number of eligible studies a meta-analysis was not possible within this review.
This systematic review focuses on adherence as an outcome as opposed to clinical health outcomes as unlike within the adult literature, few studies in paediatric asthma include both adherence and clinical outcomes. Focusing on adherence therefore allowed a greater number of studies to be synthesised. Ideally intervention studies should have an objective reliable clinical outcome as well as an adherence outcome to account for potential patient manipulation of the adherence measurement and for those patients that may have low adherence despite good control (likely over-medicated). However, unlike in some other conditions, adherence to ICS has been shown to be highly correlated with objective clinical outcomes 57 and therefore the use of adherence as a primary focus for this review is a reasonable proxy.
Most of the interventions had a moderate RoB which was increased by the high level of performance bias which is common in behavioural interventions. This is due to the lack of ability to blind patients and personnel to the purpose of the study, however, many of the studies tried to counteract that using deception (where ethically permitted). This included objective electronic monitoring devices also for control groups and additional measurements to distract from the adherence data collection. The studies often had low selection bias (for random sequence generation); detection bias and reporting bias; However, attrition bias and allocation concealment was frequently unclear with modern recommended reporting guidelines such as CONSORT58 not being followed. We recommend using objective methods of measuring adherence and also more than one method of measurement, and also for the diagnosis of asthma, alongside blinding to increase the reliability of future intervention findings.
One further limitation is not excluding interventions where the diagnosis of asthma reported was not rigorous, for example where primary care medical records were used to identify those with asthma despite no record of prescribing ICS or where a physician diagnosis was given without objective measurement of asthma59. Future intervention studies should ensure the children recruited have a reliable diagnosis of asthma and objective measurements of adherence so the true effectiveness of the interventions can be determined60. Therefore, this review considered the reliability of the evidence for both the diagnosis of asthma, the measurement of adherence and the risk of bias of the studies.

Conclusions

Adherence interventions in children with asthma have mixed effectiveness. Effective studies tended to be of higher quality, targeted both perceptual and practical adherence barriers in a tailored manner, and used a combination of BCTs. However, due to the small number of included studies and varying study design quality, conclusions drawn here are preliminary.
None of the studies have explicitly addressed ICS necessity and concern beliefs. This remains a potential area of investigation as a method for enhancing adherence. Future interventions could consider a closer use of the NICE guidelines including addressing patient’s beliefs and the channel by which the intervention is delivered; the increasing use of EMD with feedback delivered in a no-blame collaborative consultation. Future research is needed to test a PAPA-based intervention with a rigorous study design as outlined in this review.