Study design.

A randomised intervention trial design was used in which participants were randomised to receive either an immediate (IM) or a delayed (DE) MDOT intervention. Randomisation was restricted [20] based on two factors i.e. age (categorised as ‘young children’ aged 2 to 5 years; ‘children’ aged 5 to 12 years; ‘young people’ aged 12 to 16 years) and patient gender.

Participants allocated to the IM group participated in the MDOT intervention for the first 6 weeks of the study. Those participants allocated to the DE group commenced the MDOT intervention after a 6 week “intervention-free” period, with usual Asthma Clinic care up to that point. The original plan was to recruit 72 children (36 per group). Although the MDOT approach was well accepted by clinicians (including asthma nurses), parents and patients, due to research staffing pressures a lower sample size was achieved (n = 24). The main focus was therefore on combined data at study baseline and endpoint, i.e. baseline and 12 weeks post initiation of the MDOT intervention.

Recruitment of participants.

The parents/guardians of children and young people with asthma (aged from 2 to16 years) who had continuing symptoms of partially controlled or uncontrolled asthma, despite receiving specialist asthma clinic care, were invited to participate in the research i.e. children who had asthma symptoms despite being prescribed ICS (> 400 mcg/day budesonide equivalent for children < 5 years, or 800 mcg/day budesonide equivalent for children > 5 years) and a second line therapy such as a long acting beta agonist (LABA), leukotriene receptor antagonist (LTRA) or theophylline [21]. Access to a suitable mobile device and internet connection at home, as for the feasibility study, was also required. Subjects were only included in the study after obtaining written informed consent from their parents/guardians and assent from children older than 6 years. Recruitment of participants began in August 2015 and follow-up completed by the end of September 2016.

All subjects (parents and children as appropriate) were trained, on proper inhaler technique (by a respiratory nurse) using the Teach-to-Goal (TTG) approach [22] and received standard-of-practice asthma education and management in the Asthma Clinic prior to study enrolment i.e. educated about the role of medications in asthma management, the importance of regular preventer therapy and were able to demonstrate good inhaler technique.

Intervention and data collection.

Before the study intervention period was initiated in a given subject, the participant and/or parents/guardians were trained in use of the MDOT platform. Children aged ≥ 8 years were asked to use the MDOT approach independently while parent/guardian assistance was recommended for younger children. Usual asthma treatment for each participant was used throughout the study. Regarding inhaler use, in general children aged 5 years or older administered the medication themselves while a parent/guardian was responsible for inhaler administration in patients 2 to 5 years of age, however, parent/guardian administration was acceptable if that was usual asthma care in any age of child.

Participants (or parents/guardians of participants) were asked to capture a MDOT video twice daily as in the feasibility study. A member of the research team evaluated the MDOT uploads daily through password protected access to the University based digital repository and followed up with parents/guardians and/or participants by telephone if two consecutive days of video uploads were missed. The asthma clinical team (consultant/nurse) was notified about children identified with poor inhaler technique; they viewed the videos and contacted the participants by telephone to provide advice on improving inhaler technique.

Outcome measurements.

The range of measures at baseline were as follows:

1. Participant demographics and relevant clinical data including laboratory data and comorbid conditions.
2. Clinician assessment of asthma severity and degree of disease control i.e. controlled, partially controlled, or uncontrolled [23].
3. Asthma medication profile and any changes made at the clinic visit.
4. Number of asthma attacks, oral corticosteroids courses, and emergency attendances over the previous year.
5. Spirometry measurements (FEV₁, FVC, FEV₁/ FVC)
6. Fraction of exhaled nitric oxide (FeNO)
7. Self-reported Medication Adherence Report Scale (MARS)–appropriate scales for parent/guardian and child if 9 years of age or greater [24–26].
8. Interview-administered Pediatric Asthma Quality of Life Questionnaire (PAQLQ) if child >9 years of age, and the Pediatric Asthma Caregiver Quality of Life Questionnaire (PACQLQ) [27].
9. Interview-administered Asthma Control Test (ACT) or Childhood Asthma Control Test (C-ACT) [28, 29] for children aged to 12 to 16 and 4 to 11 years respectively.

At six weeks and 12 weeks post commencement of the MDOT intervention, outcome measures ii to ix were repeated during return visits to the clinic.

Assessment of adherence.

In addition to the MARS questionnaire approach to assess adherence to ICS (see above), GP prescribing records for the 12 months prior to study commencement were collected and analysed using the medication refill adherence (MRA) approach described by Hess et al. [30] to ascertain baseline adherence. Adherence to MDOT video uploads was also assessed during the 6 week MDOT intervention in all participants. A patient was classified as adherent if the MRA value was ≥80% to <120% and non-adherent if MRA< 80%. If the MRA was found to be >120% this was considered as oversupply. This classification method was utilised by previous researchers [31–34]. Patients were classified as adherent if the MARS (parent; child) score was ≥ 80% of the maximum score achievable in the respective versions (parent and child) of the MARS questionnaire.

Assessment of asthma severity and inhaler technique.

Clinician assessment of participant asthma severity was defined according to accepted guidelines and asthma control was categorised as uncontrolled, partially controlled, or controlled [23]. Patient inhaler technique was evaluated by reviewing each video uploaded in the first 2 days of the intervention period and then via a weekly review of videos uploaded to the repository. Inhaler technique was categorised on a three-point scale as effective, partially effective or poor [35]. Inhaler technique evaluation was based on the individual steps relevant to the type of inhaler being used by individual children (manufacturer administration directions). Effective technique was recorded when the participant met all relevant criteria for their inhaler type. Partially effective technique was recorded when errors in technique were observed but it was thought that the participant would receive some medication. Poor inhaler technique was recorded when critical errors in technique occurred and it was considered unlikely that any medication would be inhaled [35,36]. Sample videos was reviewed and scored by two members of the research team (FA; JM).

Feedback questionnaire.

Parents/guardians were asked to complete an ‘open question’ feedback questionnaire to provide their views and experience with the use of the technology at the end of intervention period. Feedback questionnaires were sent to each participant by post and each participant was contacted by telephone as a reminder if the questionnaire was not returned within a two week period. Two feedback questionnaires were used: one for participants who completed the 6 week period of using MDOT and the second for participants who consented to take part but did not upload videos or who uploaded videos for a shorter period that the 6 weeks requested.

Data management and analysis.

All data were coded as appropriate and entered into a study database (SPSS^® version, 21, USA). All categorical data collected during the pilot study were analysed using percentages and proportions. Continuous variables were described using mean and standard deviation (SD) or if skewed median and interquartile range (IQR). Standard statistical methodology (t-test and Mann-Whitney U test) were used to compare outcome data.

Patient demographics.

The gender distribution of children was 17 male and 5 female. The age range of children entering the study was 2–16 (mean 9.4 + 3.7 years). The mean (+ SD) ACT scores in the participating patients were 13.1+ 5.7 at baseline while the mean (+ SD) FeNO levels at baseline were 38.7 + 28.8 PPM. Over 50% of the cohort (12/22) had been prescribed oral steroids in the year prior to study entry and approximately 40% (9/22) had used ‘out of hours’ GP services in the previous year. The majority (13/22) had a comorbid illness, primarily hay fever and eczema.

Inhaler technique.

Despite all children being able to demonstrate good inhaler technique during study enrolment at the clinic, a total of 77% (17/22) of the participants had partially effective or poor inhaler technique in the first week of MDOT assessment. This is an important finding indicating that satisfactory technique at the clinic is not carried forward to home use. By week 4 of MDOT engagement, approximately 90% (17/19) of the children had inhaler technique which was judged as effective (Table 5). At this stage, 3 patients had stopped recording their inhaler use and were not responding to phone calls or text messages. By week 5 all children still enrolled in the study (n = 18) were judged to have effective inhaler technique, i.e. inhaler technique improved after tailored inhalation instructions over the telephone by a member of clinical team. From inhaler observation, slow inspiration was found to be the most common mistake related to the use of dry power inhalers while forgetting to shake the inhaler before use and poor sealing of lips around the mouthpiece were common with pressured aerosol inhalers.

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Table 5. Classification of inhaler technique in children during the 6 week use of the MDOT approach in the pilot study in children with asthma.

https://doi.org/10.1371/journal.pone.0190031.t005

Influence of MDOT on outcomes.

A summary of the data on impact of the MDOT intervention on asthma outcomes, 12 weeks post the initiation of the intervention is presented in Table 6. The two main markers of asthma control (ACT and FeNO) were improved significantly (P<0.05) at the 12 week assessment; the minimum clinical difference required (i.e. 3 points in the ACT) to mark improved asthma control was achieved [55]. The MDOT approach also led to a reduction in the mean FeNO value (PPM) to normal levels, i.e. 38.7+28.8 (n = 22) to 19.3 + 14.4 (n = 16) (Table 6). Within this small pilot sample spirometry values did not vary to a statistically significant degree between baseline and 12 weeks (P>0.05).

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Table 6. Summary data on impact of MDOT intervention on asthma outcomes (at 12 weeks post initiation of MDOT) in the pilot study in children with asthma.

https://doi.org/10.1371/journal.pone.0190031.t006

All parents/guardians (n = 22) completed the QOL questionnaires (PACQLQ) at baseline while 19 parents completed the questionnaire at 12 weeks post initiation of DOT. The results demonstrated improved QOL at 12 weeks compared with baseline (P< 0.001). A mean score of > 4 (moderate to excellent QOL) was achieved by participants at week 12. A total of 12 children > 9 years old completed the QOL questionnaire (PAQLQ) at baseline and at 12 weeks post initiation of MDOT. An improvement in the mean score of greater than one unit was achieved, however, this did not reach statistical significance (p = 0.079; Table 6). A statistically significant correlation were found between ACT scores and parent QOL scores at baseline (r = 0.55; p<0.001) and at 12 weeks post MDOT initiation (r = 0.74; p<0.001). Similarly, statistically significant correlations were found between ACT scores and child QOL scores at baseline (r = 0.75; p<0.001), and at 12 weeks post MDOT initiation (r = 0.65; p<0.001). Clinician assessment of asthma control indicated that at 12 weeks post initiation of the intervention, patients were moving towards the partially controlled or controlled categories, with a marked reduction in the patients deemed uncontrolled i.e. 14 at baseline vs 4 at 12 weeks (Table 6).

Adherence to video upload.

A total of 1083 video clips were recorded and uploaded during the six week MDOT period by participants. Using the video upload approach, 72.7% of the children (16/22) achieved moderate adherence to video uploads (≥ 50%) for the intervention period. The frequency / reasons for not uploading videos were as follows: busy schedule (e.g. school exam)– 6; child visits father’s home at weekend and father not trained in MDOT process– 3; forget to take video– 3; large video file size -3 (corrected by decreasing video resolution on mobile phone); lost phone– 2; no space on mobile phone storage– 2; child was unwell (e.g. gastroenteritis)– 2; mother was admitted to hospital– 2; travelling outside the country– 1. A total of four participants had a video upload adherence rate of less than 30%. There is clear scope for significant improvement in this aspect of MDOT including automated reminders, video compression (to reduce memory requirements on the mobile device), familiarisation of more than one family member with MDOT and perhaps a reduced frequency of monitoring (e.g. one upload each evening, with a tick box to confirm whether the inhaler has been used in the morning).

Adherence to inhaler use (GP records and MARS).

All of the GP prescribing data requested were received. Using the cut point of 80%, 10 children (45.4%) were deemed adherent and 12 children (54.6%) were classified as non-adherent in the 12 months prior to enrolment in the present study.

All 22 parents/guardians of the children who participated in the study completed the MARS questionnaires at baseline. Using a cut point of ≥ 80% of the maximum score achievable to represent adherence, the level of non-adherence reported for the participants was 18.2% at baseline. Nineteen parents completed the questionnaire at 12 weeks with 0% non-adherence reported. Regarding the child MARS, 12 children (≥ 9 years) completed the questionnaire at baseline with a reported non-adherence rate of 61.5%. By 12 weeks post MDOT initiation, again 100% adherence was reported by those children. Although the numbers within the pilot are small, the strong trend towards improvement in self-reported adherence is clear.

Parent feedback on use of MDOT.

Feedback from parents was very positive. They found the MDOT approach: ‘Very easy to access with patient ID, take a video and simply upload’. There was general support for loading videos twice per day e.g. ‘I think loading videos twice daily was worthwhile as it drew emphasis to the need to take medication’. Another parent commented ‘It seems normal to do it twice because it only lasts for a few minutes and does not take up any time’. Parents were asked whether 6 weeks was an appropriate duration for use of the MDOT intervention. The responses here were generally supportive of a 6 week intervention, however, some parents thought the intervention could be longer or indeed shorter. A period of 4–6 weeks seems ideal. Variable answers were provided to the question regarding what age a child could use the MDOT independently. The most pertinent answer was that: ‘If a child is able to use a smartphone, they would not find any problems’ and indeed one parent reported: ‘My child of 5 years old was able to use it’. Other parents suggested ages of 8–13 years old as being appropriate for self-use of MDOT.

The main barrier reported by parents was slow uploading of videos when internet / mobile network speeds were slow and on a few occasions videos did not upload. Parents were asked to suggest improvements to the MDOT platform. One suggested: ‘Maybe a little alarm would be useful’ while another suggested that there ‘could be a place to upload comments along with the video of inhaler use to help the doctor know how the child is getting on’. Both those suggestions are being incorporated into a redeveloped MDOT platform (www.continga.co.uk).

Advantages of using the MDOT proffered by parents were focused on (i) observing inhaler technique, (ii) monitoring / improving treatment and (iii) working as a reminder. Typical comments within these three areas respectively were: (i) ‘I think it is a great idea because the doctor is able to see how the child is using the inhaler’; ‘It has been a great help in finding out faults’, (ii) ‘I think it is great as [it] showed children are getting [the] correct treatment’; ‘I think 6 weeks was ideal because it got my son into a routine and he still is on it’; ‘It is good to learn how to control your child’s asthma’; ‘It gives parent peace of mind to know that the child with asthma is controlled right’, (iii) ‘It helped my son remember to take his inhalers twice daily’. Our findings support the views of other users (with other chronic illness) that the MDOT approach is convenient, not time consuming and with minimal disruption can be integrated into routine daily activities (Table 1).

As detailed earlier a small number of parents agreed to use the MDOT but either did not get started with the MDOT monitoring or discontinued early. Reasons for this were generally related to practical matters e.g. parking difficulties at hospital (parent did not have mobile phone at clinic visit and did not return to get the MDOT software uploaded; not being at home when child was using inhaler due to shift work; difficulty getting up in the mornings to help child. Approaches to overcome some of these logistical challenges are currently being developed by the research team.

The overall assessment of the pilot study by the researchers is that all aspects of study ran very much as planned. Although this is a small pilot study, the clinical outcome improvements at 12 weeks post MDOT initiation were encouraging as was the acceptability of the MDOT approach to parents and children. The focus of the pilot study was on improvements from baseline when the MDOT intervention was in place. It was noted, however, that there were improvements in the DE group outcome measures (particularly FeNO) at the end of the 6 week period at the start of the study i.e. before the MDOT intervention was initiated in that group. This was likely due to their enrolment in a clinical trial and becoming better engaged in their therapy because of this (Hawthorne effect). These aspects will be explored further in a larger study that is being planned by members of the research team. The MDOT approach has been used successfully for prolonged periods in TB management. However, since medication adherence is known to drop off over time in children [56] future research is required to ascertain if adherence to MDOT deteriorates over longer term use in inhaler management. Further work is also required to ascertain exactly how long MDOT is needed for to give rise to sustained improvement in inhaler technique and if further specific interventions are required to give rise to sustained adherence to the MDOT intervention.