A Feasibility Study to Assess Novel Electronic Monitoring Devices (NEMD) for Monitoring Adherence in Children With Asthma
Phase: NA
Conditions: Asthma in Children
Sponsor: Imperial College London

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
 
 
 
 
 
 
 
A feasibility study to assess novel electronic monitoring devices 
for monitoring adherence in children with asthma 
 
 
Protocol 
Version 2 
 
 
 
MAIN SPONSOR: Imperial College London 
FUNDERS: Asthma UK 
STUDY COORDINATION CENTRE: Royal Brompton Hospital 
NRES reference: 18/LO/0923 
 
Investigators 
 
Dr Louise Fleming (PI) 
Clinical Senior Lecturer in Respiratory paediatrics, Imperial 
College, London 
Mrs Sukeshi Makhecha 
Senior Paediatric Pharmacist Royal Brompton Hospital and 
MSc student, University College, London 
 
 
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 
 
 
 
 
 
 
 
 
 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
 
 
 
 
 
 
 
 
 
 
Study Management Group 
 
Principle Investigator: Dr Louise Fleming 
 
Co-investigators:  
Mrs Sukeshi Makhecha 
 
 
 
Dr Amy Chan 
Ms Christina Pearce 
 
 
 
 
 
Statistician: Winston Banya 
 
Study Management:       
 
For general queries, supply of study documentation, and collection of data, please contact: 
 
Study Coordinator: Sukeshi Makhecha 
Address: Royal Brompton Hospital, Pharmacy. 
Registration:  
Tel: Bleep 7403  
 
 
 
 
E-mail:  s.makhecha@rbht.nhs.uk 
Fax:        
 
 
 
 
 
Web address:       
 
Clinical Queries 
Clinical queries should be directed to Sukeshi Makhecha who will direct the query to the 
appropriate person. 
 
Sponsor 
Imperial College London is the main research Sponsor for this study.  For further information 
regarding the sponsorship conditions, please contact the Head of Regulatory Compliance at: 
 
 
 
Joint Research Compliance Office 
Imperial College London & Imperial College Healthcare NHS Trust 
2nd Floor Medical School Building 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
St Mary’s Hospital 
Praed Street 
London 
W2 1NY 
Tel: 020759 41862 
 
 
Funder 
Asthma UK.  Funder Ref: AUK-SCF-2017-399 
Award No: WHRL_P68723 
 
This protocol describes the feasibility study to assess novel electronic monitoring devices (NEMD) for 
monitoring adherence in children with asthma and provides information about procedures for enrolling 
participants.  Every care was taken in its drafting, but corrections or amendments may be necessary. 
These will be circulated to investigators in the study.  Problems relating to this study should be referred, 
in the first instance, to the Principle Investigator, Dr Louise Fleming. 
 
This study will adhere to the principles outlined in the NHS Research Governance Framework for Health 
and Social Care (2nd edition). It will be conducted in compliance with the protocol, the Data Protection 
Act and other regulatory requirements as appropriate.  
 
 
 
 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
 
Table of Contents 
1. 
INTRODUCTION 
7 
1.1 
BACKGROUND 
7 
2.  STUDY OBJECTIVES 
9 
3.  STUDY DESIGN 
10 
4. 
PARTICIPANT ENTRY 
14 
4.1 
PRE-REGISTRATION EVALUATIONS 
14 
4.2 
INCLUSION CRITERIA 
14 
4.3 
EXCLUSION CRITERIA 
15 
4.4 
WITHDRAWAL CRITERIA 
15 
5. 
ASSESSMENT AND FOLLOW-UP 
15 
6. 
ADVERSE EVENTS 
16 
6.1 
DEFINITIONS 
16 
6.2 
REPORTING PROCEDURES 
17 
7. 
STATISTICS AND DATA ANALYSIS 
18 
8. 
REGULATORY ISSUES 
20 
8.1 
ETHICS APPROVAL 
20 
8.2 
CONSENT 
20 
8.3 
CONFIDENTIALITY 
21 
8.4 
INDEMNITY 
21 
8.5 
SPONSOR 
21 
8.6 
FUNDING 
21 
8.7 
AUDITS 
21 
9. 
STUDY MANAGEMENT 
21 
10. 
PUBLICATION POLICY 
21 
10. 
REFERENCES 
22 
APPENDIX 1. 
SUMMARY OF INVESTIGATIONS, TREATMENT AND ASSESSMENTS
 
24 
 
 
 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
GLOSSARY OF ABBREVIATIONS 
EMD 
Electronic monitoring device 
NEMD 
Novel electronic monitoring device 
ACT 
Asthma Control Test 
cACT 
Childhood asthma control test 
RBHT 
Royal Brompton and Harefield NHS Foundation Trust 
FeNO 
Fractional exhaled nitric oxide 
FEV1 
Forced expiratory volume in one second 
BDR 
Bronchodilator reversibility 
QoL 
Quality of Life 
PAQLQ 
Paediatric asthma quality of life questionnaire 
mPAQLQ 
Modified paediatric asthma  quality of life questionnaire 
rDOT 
Remote directly observed therapy 
NRAD 
National review of asthma deaths 
MARS-10 
Medication adherence report scale - 10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
KEYWORDS 
Electronic monitoring device (EMD) 
Novel electronic monitoring device (NEMD) 
Compliance 
Adherence 
Children 
Asthma 
 
STUDY SUMMARY 
TITLE 
A feasibility study to assess novel electronic monitoring devices for 
monitoring adherence in children with asthma 
DESIGN 
A mixed method (quantitative and qualitative) open label, block 
randomised feasibility study 
AIMS 
1. To assess the feasibility of 4 novel electronic monitoring 
devices in children aged 6-16 years with asthma, in terms of 
usability and acceptability by patients/ guardians and 
healthcare professionals (qualitative study) 
2. To evaluate the accuracy of these devices and assess 
whether they impact on asthma control (quantitative study) 
OUTCOME MEASURES Primary outcome: Acceptability and usability of devices to participants 
and healthcare professional at Royal Brompton and Harefield NHS 
foundation Trust (RBHT) 
Secondary outcomes: 1. Accuracy of the adherence data collected 
from the devices.  
2. Effect on asthma control as measured by asthma control test (ACT) 
or childhood asthma control test (cACT) score; exhaled nitric oxide 
(FENO), spirometry (FEV1) and bronchodilator reversibility (BDR). 
POPULATION 
Children aged 6-16 years with asthma on inhaled corticosteroid 
therapy. 
ELIGIBILITY 
Children aged 6-16 years with a diagnosis of asthma on inhaled 
corticosteroids who are being treated or followed up by the paediatric 
respiratory difficult asthma clinic at Royal Brompton hospital. 
DURATION 
Up to 16 weeks 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
 
1. 
INTRODUCTION  
 
1.1 
BACKGROUND 
Asthma affects 1.1 million children in the UK and is a significant economic burden to the NHS 
(NHS information centre). Despite advances in care, acute asthma attacks are one of the most 
common presentations to the Emergency Department. Persistent symptoms and frequent 
exacerbations can impact negatively on quality of life and sadly children still die from asthma. 
The National Review of Asthma Deaths (NRAD) included 28 deaths in young people under 
the age of 20 years.  The report highlighted that poor adherence to medical treatment, 
especially in children is one of the most important reasons for apparent treatment failure and 
recommends that adherence should be continually monitored.  
Suboptimal adherence has been linked to risk of exacerbations, hospital admissions, reduced 
quality of life and asthma related deaths (1)(2)(3). Once poor adherence has been identified, 
there is little evidence of benefit of adherence interventions(4). 
Adherence to inhaled corticosteroids (ICS) in asthma ranges from 30-70% (5). Patient or 
parent report is inaccurate, over-estimating the treatment taken. and physician assessment 
little better than chance (2) (6).Objective measures of medication use, such as prescription 
refill rate are a little more accurate; however even if inhalers are picked up they are not 
necessarily taken.  
 
Recently, there has been an increase in the use of electronic monitoring devices (EMD) which 
can be used to monitor adherence to inhaled treatments. The EMD’s are available with or 
without reminders and provide important data on activation, timing of the activation and the 
number of doses activated. They have the potential to transform care for people with asthma 
(7) (8). EMDs have two key roles to play; enabling healthcare professionals to interpret control 
in the context of know adherence and inform decision making and as a tool for the patient to 
aid self-management and improve adherence. We have demonstrated the role of currently 
available EMDs in supporting the decision making process and identifying children with severe 
asthma (9).  
The improvements across the range of asthma control measures suggested that adherence 
improved because the participants were aware they were being monitored. This supports the 
second role of EMDs as an intervention for adherence. 
Studies which have compared EMDs with standard care have demonstrated significant 
improvements in adherence in the EMD arm (30% versus 85% and 49% versus 70%), 
however, they have shown only modest improvements in asthma control (8) (10). This may in 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
part be due to the limitations of current EMDs. Although they measure activation they give no 
information on whether the inhaler was used correctly, or even if inhaled at all. This would 
provide plausible explanation for limited clinical benefit despite large differences in adherence. 
Furthermore, in these studies adherence remained suboptimal (<80%) in the majority despite 
monitoring. This is unsurprising as EMDs only address some of the reasons for poor 
adherence.  
 
Determinants of poor adherence 
The practicalities and perceptions (PAPA) model (5) divides the numerous reasons for poor 
adherence into two broad themes. Practical barriers include poor technique and forgetfulness. 
This leads to unintentional non adherence: the patient wants to take the treatment but is limited 
by their capabilities. Perceptual barriers lead to intentional non adherence: the patient is not 
motivated to take medication because of their concerns. Thus, ongoing poor control despite 
documented good adherence (with current EMDs) may be a result poor technique (practical 
barrier) or deliberate manipulation because of concerns about treatment efficacy or side 
effects (perceptual barrier).  
 
1.2 
RATIONALE FOR CURRENT STUDY 
A number of platforms are currently in development which will enable the clinician to monitor 
both activation and inhalation, thus ensuring more accurate estimates of adherence and better 
addressing practical barriers to adherence. Currently the utility and feasibility of these 
platforms and acceptability to children, their families and healthcare professionals is not 
known.    
 
Often devices are formulated for adults then extrapolated to children (11),(12) , highlighted the 
need and benefits of user involvement in the design of EMDs in children, particularly 
adolescents with asthma and the need to consider all aspects of medical design including 
data, usability and aesthetics in future studies to maximise the chance of success. 
The benefits of using user feedback in adherence monitoring have been highlighted in many 
studies some using focus groups other using one to one interviews(11), (13),(14). Other 
studies have recommended that robust technology support to troubleshoot technological 
issues arising during the intervention should also be taken into consideration into the feasibility 
of using EMD’s for monitoring adherence (14).  
 
We propose to conduct an open label, block randomised, mixed methods, feasibility study to 
assess the accuracy, usability and acceptance of four novel electronic monitoring devices 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
(NEMD) that monitor both activation and inhalation thereby providing information on dose 
taken and technique. 
 
We will conduct face to face focus group or one to one interviews using semi-structured 
questions to evaluate user feedback and assess the accuracy of the NEMD’s used. 
Additionally, asthma control will be assessed as part of routine clinical care using our difficult 
asthma protocol. 
 
2.  STUDY OBJECTIVES 
 
Research question: Which novel electronic monitoring device (NEMD) (measuring both 
inhalation & activation) is the most feasible to use as a tool for monitoring adherence in 
children aged 6-16 years with asthma in terms of accuracy, usability and acceptability? 
 
Aim: To conduct a feasibility study looking at four new electronic monitoring devices to monitor 
adherence in children with asthma aged 6-16 years prescribed inhaled corticosteroids. 
 
Our primary objective is to assess which novel electronic monitoring device is the most 
feasible to use as a tool for monitoring adherence in children with asthma, in terms of its 
perceived accuracy, usability and acceptability by patients/guardians and healthcare 
professionals by using a face to face focus group discussion meeting or one to one 
interviews.  
 
For the purposes of this study feasibility is the overarching term used to assess if the 
devices are capable of being used in clinical practice to monitor adherence.  
Accuracy of the device will be assessed by capturing usable data from the devices. 
Usability of the device will be assessed from the focus group or one to one interviews 
encompassing ease of use, time taken, problems encountered, easy to learn to use the 
device. 
Acceptability will also be assessed from the focus group discussions or one to one 
interviews in terms of aesthetically pleasing, liked the device, fits in with day to day living. 
 
Our secondary objective is to evaluate the effect on asthma control as measured by 
asthma control test (ACT) or childhood asthma control test (CACT) score; exhaled nitric 
oxide (FENO), spirometry (FEV1) and bronchodilator reversibility (BDR) 
 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
 
3.  STUDY DESIGN 
This is an open label, block randomised (10 in each block), mixed method (quantitative and 
qualitative) study to be conducted for a period of up to 16 weeks  
Children aged between 6-16 years with asthma attending the paediatric respiratory difficult 
asthma clinic will be recruited into the study and randomly allocated to one of three arms 
using block randomisation matched for age and size of group. Children will be assigned to 
trial one of the following four NEMD’s to be tested:  
 
1. Block 1 (10): Smartinhaler Plus™ (Adherium, New Zealand) 
• 
This measures inhalation usually flow sensors and is the next generation of a 
currently commercially available EMD 
 
2. Block 2a (5) : Flo-Tone (Clement Clarke, UK) plus Rafi-tone, acoustic enabled 
Smartphone App (clin-e-cal, UK) for children aged 6 – 11 years 
• 
The Flo-Tone attaches to an MDI and makes a sound when the inhaler is used 
correctly. Rafi-tone is a Smartphone App that detects the sound and activates a 
game The game is aimed at younger children and therefore children aged 6 – 11 
years will be randomised to this block.  
Block 2b (5) : Inhaler Compliance Assessment (INCA™) device (INCA, Ireland) 
• 
This is an audio recording device which attaches to a Diskus dry powder inhaler. 
Analysis of the digital audio recordings enables objective assessment of inhaler 
use and technique. As it can only be used with a Diskus only children ≥ 12 years 
will be randomised to this block 
 
3. Block 3: Video and Remote Directly Observed treatment (rDOT) 
• 
Children are filmed on a Smartphone using their inhaler. The clip is then 
automatically uploaded via a Smartphone App (Continga, UK) and reviewed by a 
Clinical Nurse Specialist to ensure inhaler technique is correct. 
 
 
Recruitment 
30 children will be recruited into the study; 10 per block (5 per block aged 6-11 years and 5 
aged 12-16 years)  
 
Visit 1:Novel electronic monitoring device (NEMD) issued 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
Routine clinical care assessments will be carried out at the end of the study period as below, 
including asthma control test (ACT) or the childhood asthma control test (cACT), exhaled 
nitric oxide (FeNO)  and spirometry (FEV1 and BDR) .  
 
Patient/parent/Carer will be invited to take part in the study. 
Information regarding the study and its objectives will be communicated to the 
Patient/parent/carer in both oral and written form using patient information leaflets. 
 
All children will be issued with a novel electronic monitoring device which will be 
attached to the child’s usual inhaler or require an app on their mobile phone as 
described above. Parents and children will be provided information and advice on the use of 
the novel electronic monitoring device and asked to conduct up to 16 weeks of home 
monitoring using their allocated NEMD on their first visit. 
 Information on how to contact the team in case of any problems will be related to the 
participant in both oral and written form. 
 
The data will be stored electronically and downloaded at the next clinic visit. 
Contact by telephone will be made at day 7-14 to ensure that the device is working and to 
answer any other queries then at week 6-7 to determine if the device is being used 
appropriately and to answer any related questions. 
 
Week 1 - for the rDOT arm, adherence data will be downloaded to check for consistencies in 
inhaler technique. If inhaler technique is inaccurate, the participants will be called by the 
respiratory nurse specialists to advise on correct technique. This will be documented as part 
of the data collection. 
 Week 4 – All devices, adherence data will be downloaded and checked to ensure that the 
devices are working correctly. 
 
Visit 2: up to 16 weeks of adherence data collection 
Routine clinical care assessments will be carried out at the end of the study period as below, 
including asthma control test (ACT) or the childhood asthma control test (cACT), exhaled 
nitric oxide and spirometry (FEV1 and BDR) .  
Adherence data will downloaded at the end of the study period and stored electronically. 
 
Visit 3: Focus group or one to one interviews 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
The participants and their carers will be invited to a face to face focus group interview, or a 
one to one interview, depending on their availability at the end of the study period. The focus 
group and one to one interviews will utilise a semi structured questionnaire, to provide 
qualitative feedback on the acceptability and usability of the devices.  
 
A separate focus group meeting will also be conducted with the peadiatric respiratory nurses 
who are part of the MDT to assess their views on the devices used as they routinely 
provided all asthma devices and are also involved in downloading data from other devices 
that we would use as part of routine care (smart-inhaler). They will also be consented to take 
part in the study 
Where possible a second researcher from University College London (UCL), Christina Pearce 
will sit in the focus groups discussion and interviews to ensure there is no bias.  
The conversations from the focus group and one to one interviews will be transcribed and 
coded into themes. We will utilise an external company for transcribing the conversations 
called 1st Class. https://www.1stclass.uk.com/ 
 
Analysis 
Qualitative: 
The focus group and one to one interviews will be audio recorded, transcribed and put into 
themes to conduct an inductive thematic analysis. 25% of the transcripts (8) will be double 
coded by an independent researcher from UCL, Dr Amy Chan, experienced in qualitative 
research to ensure that the correct themes have been used and to ensure that there is no 
bias. 
 
The focus group and one to one interviews will be used to assess the usability and 
acceptability of the devices 
 
Quantitative: 
The amount of usable data from each device will be quantified and compared.  
This will provide data on the perceived accuracy of the device. 
 
The quantitative and qualitative results will be amalgamated and an evidence report 
prepared to assess the feasibility of each device. 
An expert panel will be convened to select the most appropriate device to take forward to a 
larger randomised controlled trial to assess the impact of the device on adherence in 
children with asthma. 
 
 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
REFERENCE DIAGRAM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Home electronic monitoring for a period of up to 16 weeks 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Children attending the difficult asthma clinic 
at RBHT who fit the inclusion criteria.  
n=30 
Visit 1: Baseline assessment 
• Informed consent and information provided on devices 
• Demographics 
• Asthma control (ACT / cACT) 
• Spirometry (FEV1, BDR) 
• Inflammation (FENO) 
• Asthma related Qol (PAQLQ / PACQLQ) 
• MARS-10 questionaire 
• Drug history 
• 
Prescription uptake 
• Device issued 
Smartinhaler™ with flow 
sensors & reminders 
n=10 
 
(5=6-11yrs) 
(5= 12-16 years) 
Remote video monitoring 
Directly Observed 
Therapy (R-DOT) 
n=10 
 
(5=6-11yrs) 
(5= 12-16 years) 
 INCA/ Rafi-tone plus acoustic 
enabled Smartphone App 
(Clin-e cal) 
n=10 
(5=6-11yrs to use Rafi-tone) 
(5=12-16 years to use INCA) 
 
Visit 2 (up to 16 weeks): Reassessment 
• Asthma control test (ACT / cACT) 
• Spirometry (FEV1, BDR) 
• Inflammation (FENO) 
• Asthma related QoL (PAQLQ / PACQLQ) 
• Device data downloaded 
Visit 3 (Focus group or one to one interviews):  
• Opinions of participants collected on devices using semi-
structured interview 
• Opinions of respiratory nurse specialist collected using semi-
structured interview 
 Week 1-2: Telephone follow up to check device 
functioning & answer any questions & download rDOT data 
 
Week 4: telephone follow up & download further data. 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
4. 
PARTICIPANT ENTRY  
 
4.1 
PRE-REGISTRATION EVALUATIONS  
Children will be recruited from the outpatient clinics at the Royal Brompton Hospital 
 
Written information regarding the study (the patient information sheet) and contact details of 
the study team will be given to parents 
 
Written, informed consent from the parent / guardian and consent (if appropriate) or assent 
from the child will be obtained by a member of the study team prior to undertaking any study 
procedures. “Informed consent” requires individual discussion with the child and their parent / 
guardian about the study and the nature of the procedures to be conducted in a language that 
is easy to comprehend. The child and their parent /guardian will be given adequate time to 
decide whether or not they wish to participate. The child and their parent / guardian should 
understand that his / her refusal to participate in the study will not affect their subsequent 
medical care and if they do consent they may withdraw at any point without affecting their 
care. 
 
The participant consent form must be signed by a member of the study team to confirm that 
informed consent was obtained. The original of the signed declaration of consent will be stored 
in the case notes. A copy will be given to the parent / guardian 
 
Information sharing 
 
Consent will be sought to inform the child’s GP and usual hospital consultant of their enrolment 
in the study. If clinically important information is found as a result of the study this will be 
discussed with the participant and their parent / guardian and their consent sought to share 
this information with their GP and / or other relevant medical professionals.  
 
Follow up of participants after study completion 
 
At the end of the study (as a result of study completion or withdrawal) participants will continue 
to receive their usual clinical care.   
  
4.2 
INCLUSION CRITERIA 
 
A child will be included in the study if the following criteria applies: 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
• 
Informed consent obtained from parents/guardian/adolescents and/or assent from 
the child. 
• 
Children aged between 6-16 years with a diagnosis of asthma attending the Royal 
Brompton and Harefield Difficult asthma clinic. 
• 
Children on inhaled corticosteroids 
• 
Parents/ young person has a mobile phone which can download apps 
• 
Paediatric respiratory nurses working in the difficult asthma team at Royal Brompton 
Hospital. 
 
4.3 
EXCLUSION CRITERIA 
A child will not be eligible for the study if the following applies: 
• 
Unable to provide consent 
• 
As a result of medical interview, physical examination or screening investigation the 
physician responsible considers the child unfit for the study. 
• 
Those who, in the opinion of the investigator, have a risk of non-compliance with 
study procedures 
• 
Children under the age of 6 years. 
• 
Children not on inhaled corticosteroid 
• 
It is not anticipated that any children will be pregnant, however, if they are they will 
not be included in the study 
 
4.4 
WITHDRAWAL CRITERIA 
Children/parents/carers may withdraw any time without affecting their treatment or care. 
If adherence data has been collected for > 8 weeks of treatment then permission will be 
requested to use this data from parents/carers. If data has not been collected for > 8 weeks 
then this will not be used. 
 
5. 
ASSESSMENT AND FOLLOW-UP  
No study assessments will take place until written informed consent and age appropriate 
assent is obtained. 
 
Routine clinical care data will be collected at the baseline visit and at the end of the study as 
follows: 
 
 
 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
 
 
 
Routine clinical care monitoring tests 
Routine clinical care 
test to assess 
Test 
Visit 1: Study 
entry 
Visit 2: 
completion of 
study 
Asthma control 
ACT/cACT 
√ 
√ 
Spirometry 
FEV1/FVC/BDR 
√ 
√ 
Inflammation 
FeNO 
√ 
√ 
Asthma related 
quality of life 
questionnaire 
PAQLQ/PACQLQ 
√ 
√ 
Prescription uptake 
 
√ 
√ 
Drug history 
 
√ 
 
Data downloaded 
from device: Routine 
clinical care would be 
to download from 
smartinhaler 
Data downloaded 
from new device 
 
√ 
 
The main difference between data collection in this study and routine clinical care monitoring 
is that data will be downloaded from the new devices (NEMD) in comparison to the current 
smartinhaler device 
 
6. 
ADVERSE EVENTS 
 
6.1 
DEFINITIONS   
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study subject.   
 
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or effect 
that: 
• 
Results in death 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
• 
Is life-threatening – refers to an event in which the subject was at risk of death 
at the time of the event; it does not refer to an event which hypothetically might 
have caused death if it were more severe 
 
• 
Requires 
hospitalisation, 
or 
prolongation 
of 
existing 
inpatients’ 
hospitalisation 
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital anomaly or birth defect 
 
Medical judgement will be exercised in deciding whether an AE is serious in other situations.  
Important AEs that are not immediately life-threatening or do not result in death or 
hospitalisation but may jeopardise the subject or may require intervention to prevent one of 
the other outcomes listed in the definition above, should also be considered serious. 
 
6.2 
REPORTING PROCEDURES 
All adverse events will be reported.  Depending on the nature of the event the reporting 
procedures below will be followed.  Any questions concerning adverse event reporting should 
be directed to the Chief Investigator in the first instance.   
 
6.2.1 Non serious AEs 
All such events, whether expected or not, will be recorded.   
 
6.2.2 Serious AEs 
An SAE form will be completed and faxed to the Chief Investigator within 24 hours.  However, 
relapse and death due to asthma and hospitalisations for elective treatment of a pre-existing 
condition do not need reporting as SAEs. 
 
All SAEs should be reported to Sukeshi Makhecha where in the opinion of the Chief 
Investigator, the event was: 
• 
‘related’, ie resulted from the administration of any of the research procedures; 
and 
• 
‘unexpected’, ie an event that is not listed in the protocol as an expected 
occurrence 
 
Reports of related and unexpected SAEs will be submitted within 15 days of the Chief 
Investigator becoming aware of the event, using the NRES SAE form for non-IMP studies.  
The Chief Investigator will also notify the Sponsor of all SAEs. 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
 
Any SAEs will be reported as required by the Local Research Ethics Committee, Sponsor 
and/or Research & Development Office. 
 
There are no know SAEs from the use of these devices 
 It is not anticipated that there will be any SAE’s with the use of the devices, however, should 
anything occur as a result of the device then the child will be followed up daily in the first 
instance then weekly for the next four week. 
A period of four weeks of follow up care will occur after the last treatment for any adverse 
events to be recorded and reported. 
Contact details for reporting SAEs 
Fax: xxx, attention xxx 
Please send SAE forms to: Sukeshi Makhecha, Pharmacy Department, Royal 
Brompton Hospital. 
Tel: 0207-352-8121 Bleep 7403 (Mon to Fri 09.00 – 17.00) 
 
 
 
7. 
STATISTICS AND DATA ANALYSIS 
 
Sample Size 
This is largely a qualitative study, focusing on the views of the participants on the usability 
and acceptability aspect of the devices, though there is a component of quantitative 
analyses in the perceived accuracy of the device. 
Qualitative studies are different from quantitative studies in that they attempt to identify 
themes rather than quantify results. Therefore power analyses to calculate sample size are 
difficult to conduct and based largely on thematic saturation (where no further themes can be 
found). 
It has been argued that the main goal is to ensure that the sample size is small enough to 
manage the material and large enough to provide new and rich data (15). 
Braun and Clark, 2013 offer a guide on sample size based on the size of the project (small, 
medium, large). They suggest that for small projects, 6-10 participants for individual 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
interviews, 2-4 for focus groups, 10-50 participants for individual interviews in medium 
projects and  up to 100 or over for larger projects. 
Fugard and Potts, 2015 (16), offer a tool to quantify sample sizes for thematic analyses in 
qualitative studies to help support choices and decision making. They feel that the concept 
of theoretical saturation, whereby collecting more data does not add further themes is 
problematic for prospective study planning. They recommend that for adjusted prevalence of 
10%, 2 instances and 80%, 29 participants would be required. 
Though our sample size of 30 participants, randomised into blocks of 10 per each platform 
roughly fits into this model, it is nonetheless subjective, as this is largely an exploratory 
study. 
Data management 
The data entry will be collected by the study investigator (Sukeshi. Makhecha).The data 
analysis will be conducted by the study investigator (Sukeshi Makhecha) and the chief 
Investigator (Dr Louise Fleming).  
Additionally, an independent researcher will aid with the analysis of the themes for the 
qualitative aspect of the study to ensure there is no bias.  
All data will be entered on a paper clinical report form (CRF) and all data entered on a 
database (Excel or Access) held on the secure RBH server. 
 
Data analysis. 
➢ Qualitative data 
The focus group interviews will be audio recorded, transcribed and put into themes to 
conduct an inductive thematic analysis.  
25% of the transcripts will be double coded by an independent researcher from UCL, Dr 
Amy Chan, experienced in qualitative research. 
The focus group interviews will be used to assess the usability and acceptability of the 
devices 
 
➢ Quantitative data 
The amount of usable data from each device will be quantified and compared.  
This will provide data on the perceived accuracy of the device. 
Additionally, data on asthma control and quality of life will be assessed. 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
These will be analysed quantitatively statically using the Statistical Package for the 
Social Services (SPSS). Data will be tested for normality using visual inspection, 
histograms and Kolmogorov-Smirnov testing. Parametric tests will be used if the data is 
normally distributed. If the data is not normally distributed or there are only small 
numbers non parametric tests will be used or the data will be logarithmically transformed. 
The significance levels for all tests will be set at <0.5. 
Comparative analysis of variance between 2 groups for continuous data will be 
performed using the student’s t test for normally distributed data and the Mann Whitney 
U tests for non normally distributed data and for more than 2 groups the ANOVA or 
Kruskal Wallis respectively. A comparison of the proportions between groups will be 
performed using the Pearson Chi 2 tests. 
 
The quantitative and qualitative results will be amalgamated and an evidence report 
prepared to assess the feasibility of each device. 
An expert panel will be convened to select the most appropriate device to take forward to a 
larger randomised controlled trial to assess the impact of the device on adherence in 
children with asthma. 
 
Data and all appropriate documentation will be stored for a minimum of 10 years after the 
completion of the study, including the follow-up period.   
 
8. 
REGULATORY ISSUES 
 
8.1 
ETHICS APPROVAL 
The Study Coordination Centre has obtained approval from the xxx Research Ethics 
Committee (REC) and Health Regulator Authority (HRA).  The study must also receive 
confirmation of capacity and capability from each participating NHS Trust before accepting 
participants into the study or any research activity is carried out.   The study will be conducted 
in accordance with the recommendations for physicians involved in research on human 
subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions. 
 
8.2 
CONSENT  
 
Consent to enter the study will be sought from each participant only after a full explanation 
has been given, an information leaflet offered and time allowed for consideration.  Signed 
participant consent will be obtained.  The right of the participant to refuse to participate without 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
giving reasons must be respected.  After the participant has entered the study the clinician will 
remain free to give alternative treatment to that specified in the protocol at any stage if he/she 
feels it is in the participant’s best interest, but the reasons for doing so will be recorded.  In 
these cases the participants will remain within the study for the purposes of follow-up and data 
analysis.  All participants are free to withdraw at any time from the protocol treatment without 
giving reasons and without prejudicing further treatment. 
 
8.3 
CONFIDENTIALITY 
The Chief Investigator will preserve the confidentiality of participants taking part in the study 
and is registered under the Data Protection Act. 
 
8.4 
INDEMNITY 
Imperial College London holds negligent harm and non-negligent harm insurance policies 
which apply to this study.,  
 
8.5 
SPONSOR 
Imperial College London will act as the main Sponsor for this study.  Delegated responsibilities 
will be assigned to the NHS trusts taking part in this study.   
 
8.6 
FUNDING 
Asthma UK are funding this study. 
Participants will receive reimbursements costs for travel and for refreshments when 
attending the focus group meeting. 
   
8.7 
AUDITS  
The study may be subject to inspection and audit by Imperial College London under their remit 
as sponsor and other regulatory bodies to ensure adherence to GCP and the NHS Research 
Governance Framework for Health and Social Care (2nd edition).  
 
9. 
STUDY MANAGEMENT 
 
The day-to-day management of the study will be co-ordinated through Sukeshi Makhecha. 
 
10. 
PUBLICATION POLICY 
The study results will be submitted in abstract to National and international conferences and 
submitted for publication in appropriate peer reviewed journals.  

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
 
 
 
10. 
REFERENCES 
 
[List of useful and relevant references for the study] 
1.  
Klok T, Kaptein AA, Duiverman EJ, Brand PL. Long-term adherence to inhaled 
corticosteroids in children with asthma: Observational study. Respir Med. 
2015;109(9):1114–9.  
2.  
Burgess SW, Sly PD, Morawska A, Devadason SG. Assessing adherence and factors 
associated with adherence in young children with asthma. Respirology. 
2008;13(4):559–63.  
3.  
Chung KF, Royal College of Physicians (RCP), CDC, Siddiqui S, Gonem S, Wardlaw 
A. Why asthma still kills The National Review of Asthma Deaths (NRAD) Confidential 
Enquiry. Semin Respir Crit Care Med [Internet]. 2014;33(6):666–84. Available from: 
http://www.cdc.gov/vitalsigns/Asthma/?s_cid=vitalsigns_065%5Cnhttp://www.ncbi.nlm
.nih.gov/pubmed/26076339 
4.  
Nieuwlaat R, Wilczynski N, Navarro T, Hobson N, Jeffery R, Keepanasseril A, 
Agoritsas T, Mistry N, Iorio A, Jack S, Sivaramalingam B, Iserman E, Mustafa RA, 
Jedraszewski D, Cotoi C HR, Nieuwlaat R, Wilczynski N, Navarro T, Hobson N, 
Jeffery R, et al. Interventions for enhancing medication adherence. Cochrane 
database Syst Rev. 2014;11(11):CD000011.  
5.  
Horne R, Weinman J. Self-regulation and self-management in asthma: Exploring the 
role of illness perceptions and treatment beliefs in explaining non-adherence to 
preventer medication. Psychol Heal. 2002;17(1):17–32.  
6.  
Bender B, Wamboldt F, O’Connor SL, Rand C, Szefler S, Milgrom H, et al. 
Measurement of children’s asthma medication adherence by self report, mother 
report, canister weight, and Doser CT. Ann Allergy, Asthma Immunol. 
2000;85(5):416–21.  
7.  
NICE. Smartinhaler for asthma | Guidance and guidelines | NICE [Internet]. NICE. 
2017. Available from: https://www.nice.org.uk/advice/mib90 
8.  
Chan AHY, Stewart AW, Harrison J, Camargo CA, Black PN, Mitchell EA. The effect 
of an electronic monitoring device with audiovisual reminder function on adherence to 
inhaled corticosteroids and school attendance in children with asthma: A randomised 
controlled trial. Lancet Respir Med [Internet]. 2015;3(3):210–9. Available from: 
http://dx.doi.org/10.1016/S2213-2600(15)00008-9 
9.  
Jochmann A, Artusio L, Jamalzadeh A, Nagakumar P, Delgado-Eckert E, Saglani S, 
et al. Electronic monitoring of adherence to inhaled corticosteroids: an essential tool in 
identifying severe asthma in children. Eur Respir J [Internet]. 2017;50(6):1700910. 
Available from: http://erj.ersjournals.com/lookup/doi/10.1183/13993003.00910-2017 
10.  
Morton RW, Elphick HE, Rigby AS, Daw WJ, King DA, Smith LJ, et al. STAAR: A 
randomised controlled trial of electronic adherence monitoring with reminder alarms 
and feedback to improve clinical outcomes for children with asthma. Thorax. 
2017;72(4):347–54.  

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
11.  
Chan AHY, Stewart AW, Harrison J, Black PN, Mitchell EA, Foster JM. Electronic 
adherence monitoring device performance and patient acceptability: a randomized 
control trial. Expert Rev Med Devices [Internet]. 2017;14(5):401–11. Available from: 
https://doi.org/10.1080/17434440.2017.1322505 
12.  
Howard S, Lang A, Sharples S, Shaw D. See I told you I was taking it! – Attitudes of 
adolescents with asthma towards a device monitoring their inhaler use: Implications 
for future design. Appl Ergon [Internet]. 2017;58:224–37. Available from: 
http://dx.doi.org/10.1016/j.apergo.2016.06.018 
13.  
Vasbinder EC, Janssens HM, Rutten-Van Mölken MPMH, Van Dijk L, De Winter 
BCM, De Groot RCA, et al. E-Monitoring of Asthma Therapy to Improve Compliance 
in children using a real-time medication monitoring system (RTMM): The e-MATIC 
study protocol. BMC Med Inform Decis Mak. 2013;13(1):1–10.  
14.  
Kenyon CC, Chang J, Wynter S-A, Fowler JC, Long J, Bryant-Stephens TC. 
Electronic Adherence Monitoring in a High-Utilizing Pediatric Asthma Cohort: A 
Feasibility Study. JMIR Res Protoc [Internet]. 2016;5(2):e132. Available from: 
http://www.researchprotocols.org/2016/2/e132/ 
15.  
Sandelowski M. Sample size in qualitative research. Res Nurs Health [Internet]. 
1995;18(2):179–83. Available from: http://doi.wiley.com/10.1002/nur.4770180211 
16.  
Fugard AJB, Potts HWW. Supporting thinking on sample sizes for thematic analyses: 
a quantitative tool. Int J Soc Res Methodol [Internet]. 2015;18(6):669–84. Available 
from: http://dx.doi.org/10.1080/13645579.2015.1005453 
 
 
 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2 
Appendix 1. Summary of investigations, treatment and assessments 
 
 
 
 
 
 
Study Procedures 
Screening 
During treatment: 
Visits 
Follow 
up  
(7 
days) 
Follow 
up  
(4 
weeks) 
Follow 
up  
(up to 
16 
weeks) 
Follow 
up  
(up to 
6mnths) 
1 
2 
 
 
 
 
Informed consent 
√ 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
√ 
 
 
 
 
 
 
Medical history 
 
√ 
√ 
 
 
 
 
Demographies 
√ 
 
 
 
 
 
 
Rotuine clinical care 
monitoring: 
Spirometry 
FeNO 
Asthma control test 
 
 
√ 
√ 
 
 
 
 
Quality of Life 
Questionaires 
 
√ 
√ 
 
 
 
 
Prescription uptake 
 
√ 
√ 
 
 
 
 
Adherence monitoring 
 
 
 
√ 
√ 
√ 
 
End of visit 
 
 
 
 
 
 
√ 
 
 
 
 
 
 
 
 
Telephone call 
 
 
 
√ 
√ 
 
 
Provision of novel 
electronic monitoring 
device 
 
√ 
 
 
 
 
 
Data download 
 
 
 
√ 
√ 
√ 
 
Focus group or one to 
one interviews 
 
 
 
 
 
 
 
√ 

 
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Novel electronic monitoring devices (NEMD) to measure adherence in children 3/6/18 V2