Childhood Asthma Management in Primary Care: Implementation Of Exhaled Nitric Oxide and Spirometry Testing
Conditions: Asthma
Sponsor: University of Leicester

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STUDY PROTOCOL 
 
Full Study Title:  Childhood Asthma Management in Primary Care: Implementation Of Exhaled 
Nitric Oxide and Spirometry Testing (CHAMPIONS study) 
Sponsor Reference No: UNOLE 0566 
Ethics Ref:  
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Chief Investigator: 
Dr. Erol Gaillard 
Investigators: 
Prof. Andrew Wilson 
Dr. David Lo  
 
Sponsor: 
University of Leicester  
Funders: 
1. Midlands Asthma and Allergy Association 
2. Aerocrine 
3. Health Care East Midlands 
 
Signatures: 
 
 
 
 
  
Confidentiality Statement 
All information contained within this protocol is regarded as, and must be kept confidential.  No part 
of it may be disclosed by any Receiving Party to any Third Party, at any time, or in any form 
without the express written permission from the Chief Author/Investigator and / or Sponsor. 
 
 

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Authors 
 
List here all authors / collaborators that have assisted with the writing of the protocol 
Dr. Erol Gaillard  
Professor Andrew Wilson 
Dr. David Lo 
Dr. Caroline Beardsmore 
Dr. Damian Roland 
Dr. Yaling Yang 
Dr. Matthew Richardson 
Ms Karen Moore 
Mr. Robert Kirk 
Dr. Brigitte Gaillard 
 

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Signature Page 
 
Chief Investigator Name: 
Dr. Erol Gaillard _______________ 
Chief Investigator signature: 
_________________________________ 
Date: _________________________________________________ 
  
 
Sponsor Representative Name: 
__Wendy Gamble_________ 
Sponsor Representative signature: _____________________________ 
Date: 
________________________________________________ 
  
(In cases of Multi-centre studies, this must be replicated for each site) 
 
 
 

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TABLE OF CONTENTS 
Press the ‘F9’ button.  Choose ‘update entire table’.   
1. 
AMENDMENT HISTORY ......................................................................................................... 6 
2. 
SYNOPSIS .............................................................................................................................. 7 
3. 
ABBREVIATIONS .................................................................................................................... 8 
4. 
BACKGROUND AND RATIONALE .......................................................................................... 9 
5. 
OBJECTIVES ......................................................................................................................... 13 
5.1 
Primary Objectives .......................................................................................................... 13 
5.2 
Secondary Objectives ..................................................................................................... 13 
6. 
STUDY DESIGN SUMMARY ................................................................................................. 14 
6.1 
Summary of Trial Design ................................................................................................ 14 
6.2 
Primary and Secondary Endpoints .................................................................................. 16 
7. 
Study PARTICIPANTS ........................................................................................................... 17 
7.1 
Overall Description of Study Participants ........................................................................ 17 
7.2 
Inclusion Criteria ............................................................................................................. 17 
7.3 
Exclusion Criteria ............................................................................................................ 17 
8. 
STUDY PROCEDURES ......................................................................................................... 18 
8.1 
Informed Consent ........................................................................................................... 18 
8.2 
Screening and Eligibility Assessment .............................................................................. 18 
8.3 
Baseline Assessments .................................................................................................... 19 
8.4 
Randomisation and Codebreaking .................................................................................. 20 
8.5 
Subsequent Assessments .............................................................................................. 20 
8.6  
Definition of End of Trial .................................................................................................. 20 
8.7 
Discontinuation/Withdrawal of Participants from Study Treatment .................................. 20 
8.8 
Source Data .................................................................................................................... 20 
9. 
TREATMENT OF TRIAL PARTICIPANTS ............................................................................. 22 
9.1 
Description of Study Treatment ....................................................................................... 22 
9.2 
Storage of Study Equipment or Related apparatus ......................................................... 23 
9.3 
Compliance with Study Treatment .................................................................................. 23 

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10. SAFETY REPORTING ........................................................................................................... 24 
10.1 Definitions ....................................................................................................................... 24 
10.2 Reporting Procedures for All Adverse Events ................................................................. 25 
10.3 Reporting Procedures for Serious Adverse Events ......................................................... 25 
11. STATISTICS .......................................................................................................................... 26 
11.1 Description of Statistical Methods ................................................................................... 26 
11.2 The Number of Participants ............................................................................................ 26 
11.3 The Level of Statistical Significance ................................................................................ 26 
11.4 Criteria for the Termination of the Trial. ........................................................................... 26 
11.5 Procedure for Accounting for Missing, Unused, and Spurious Data. ............................... 26 
11.6 Procedures for Reporting any Deviation(s) from the Original Statistical Plan .................. 26 
11.7 Inclusion in Analysis........................................................................................................ 27 
12. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .......................................................... 28 
13. QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES .................................... 29 
14. CODES OF PRACTICE AND REGULATIONS ....................................................................... 30 
14.1 Ethics .............................................................................................................................. 30 
14.2 Sponsor Standard Operating Procedures ....................................................................... 30 
14.3 Declaration of Helsinki .................................................................................................... 30 
14.4 ICH Guidelines for Good Clinical Practice ....................................................................... 30 
14.5 Approvals ........................................................................................................................ 30 
14.6 Participant Confidentiality ............................................................................................... 30 
15. DATA HANDLING AND RECORD KEEPING ......................................................................... 31 
16. STUDY GOVERNANCE......................................................................................................... 32 
16.1 Trial Steering Committee (TSC) ...................................................................................... 32 
17. FINANCING AND INSURANCE ............................................................................................. 33 
18. PUBLICATION POLICY ......................................................................................................... 35 
19. REFERENCES ...................................................................................................................... 36 
20. APPENDIX A: STUDY GANTT CHART ................................................................................. 37 
 

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1. 
AMENDMENT HISTORY 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes 
made 
1 
3.0 
25/5/2016 
David Lo 
 

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2. 
SYNOPSIS 
 
Study Title 
Childhood Asthma Management in Primary Care: Implementation Of Exhaled 
Nitric Oxide and Spirometry Testing (CHAMPIONS study) 
Trial Design 
Implementation study 
Trial Participants 
Children aged 5-16 years 
Planned Sample Size 
1000  
Follow-up duration 
Postal questionnaire at 3-6 months 
Planned Trial Period 
2 years 
Primary Objective 
The main objective for this study will be to evaluate the training and capacity 
requirements of primary care sites in order for them to be able to deliver routine 
spirometry and FeNO testing for children aged 5-16 years as recommended by 
draft NICE guidelines. 
Secondary 
Objectives 
The secondary outcomes measured relate to the impact of implementing the 
new NICE guidelines on the processes and outcomes of childhood asthma 
care and will include: 
1.The number of children in which a diagnosis of asthma can be confirmed 
using spirometry and FeNO testing 
2.The number of misdiagnoses identified using lung function tests 
3.The impact of implementation to health economics 

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3. 
ABBREVIATIONS 
ACT                       Asthma Control Test 
AE 
Adverse event 
AR  
Adverse reaction 
CCG                      Clinical Commissioning Group 
CI 
Chief Investigator 
CRA 
Clinical Research Associate (Monitor) 
CRF 
 
Case Report Form 
CRN                      Clinical Research Network 
CRO  
Contract Research Organisation 
CT 
 
Clinical Trials 
EC 
 
Ethics Committee (see REC) 
FeNO 
Fractional Exhaled Nitric Oxide 
GCP 
Good Clinical Practice 
GLI                        Global Lung Function Initiative 
GP 
General Practitioner 
GTAC 
Gene Therapy Advisory Committee 
HCA                      Health Care Assistant 
ICF 
Informed Consent Form 
NHS 
National Health Service 
NICE                     National Institute of Health and Care Excellence 
NRES 
National Research Ethics Service  
PI 
Principal Investigator 
PIL/S 
Participant/ Patient Information Leaflet/Sheet 
PN                         Practice Nurse 
R&D 
NHS Trust R&D Department 
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event 
SAR 
Serious Adverse Reaction 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TMF 
Trial Master File 
 
 

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4. 
BACKGROUND AND RATIONALE 
In the UK the latest figures indicate that a total of 4.1 million people receive treatment for asthma 
(1).  Of these approximately 1.1 million are children over the age of 5 years, which is the equivalent 
of one in ten children in the UK (2).   
Despite the common nature of asthma there is no gold standard test available to diagnose the 
condition.  The diagnosis is generally based on a thorough clinical history taken by an experienced 
clinician.  Studies in adult populations however suggest that many are misdiagnosed including over 
and under-diagnosis of asthma (3-6).  Over-diagnosis may affect up to 30% of adults diagnosed 
with asthma (3) and can result in inappropriate and unnecessary use of asthma medications and 
increased healthcare costs.  Under-diagnosis often results in poor control and reduced quality of 
life. 
Under-diagnosis and under-treatment of childhood asthma in primary care have been reported 
from several European countries (7-8) including the UK (9).  The International Study of Asthma and 
Allergies in Childhood (ISAAC) for example reported that one-third of children aged 12 to 14 years 
in Great Britain with frequent night time wheezing had no diagnosis of asthma (9).  Getting the 
diagnosis right in children is important because children have the highest asthma hospital 
admission rates for any age-group with asthma and under-diagnosis is associated with poor 
asthma control.  Moreover, inappropriate treatment of children who do not have asthma with 
asthma medications can lead to unnecessary side-effects including a decreased growth velocity 
resulting from long-term inhaled corticosteroid use.   
A recent draft NICE guideline (10) for asthma diagnosis and monitoring, originally due for 
publication in July 2015, recommends the use of objective tests including spirometry and FeNO 
testing to diagnose asthma in all patients 5 years and older under investigation for asthma.  Recent 
BTS/SIGN asthma guidelines published in October 2014 also state that spirometry is superior to 
peak flow measurements, currently the most widely used lung function test in primary care in the 
management of asthma (11).   
Proposed NICE asthma diagnostic algorithm:  For children aged 5 to 16 years and adults with 
symptoms of asthma the draft guideline recommends spirometry testing for diagnosis and where 
obstructive spirometry is present bronchodilator reversibility should be considered.  FeNO, an 
inflammatory marker in exhaled breath linked with asthma, should be considered where spirometry 
is normal and where obstructive spirometry does not reverse with bronchodilators.  The proposed 
NICE guidance for diagnosis of asthma is summarised below. 
 
Diagnostic criteria for asthma in children aged 5-16 years: 
• 
Clinical symptoms compatible with the diagnosis 

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• 
Objective tests including 
o Obstructive spirometry 
o Reversibility following short acting beta-2-agonists (≥12% increase in FEV1) 
o Raised FeNO (≥35ppb) 
o Peak flow variability (>20%) 
No single positive test is diagnostic for asthma 
 
Draft NICE diagnostic algorithm for children aged 5-16 years with suspected asthma 
 
 
Asthma monitoring:  Spirometry should be done in adults with asthma and considered in children at 
every asthma review.   
Spirometry:  Spirometry is available in primary care and performed in adults with COPD where it is 
already part of the Quality Outcome Framework (QOF).  NICE and BTS/SIGN state that spirometry 
is preferable to measurement of peak expiratory flow because it allows clearer identification of 
airflow obstruction, and the results are less dependent on effort.   
Spirometry is however only rarely performed in children in primary care.  Children benefit from 
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practices.  Interpretation of spirometry in children also requires a slightly different approach.  
Consequently, practice nurses/health care assistants (PN/HCA) usually have no experience in 
performing and interpreting spirometry in children, but could be trained to do so.  The amount of 
training required and how best to deliver it are currently not known and addressing these 
knowledge gaps is one of the main implementation research questions.   
FeNO testing:  The draft NICE asthma guideline recommends that FeNO testing should be 
considered in children with symptoms and under investigation for asthma who have normal 
spirometry and those with obstructive spirometry but no bronchodilator reversibility.  FeNO testing 
in the diagnosis of asthma has been the topic of a separate NICE review published in April 2014, 
recommending FeNO testing as an option to diagnose asthma in children and adults with an 
intermediate probability of asthma in combination with other diagnostic options (12) There will be 
limited training requirements to perform the test and NICE have provided clear-cut guidelines for 
interpretation of the results. 
Preliminary data/focus group meeting results: 
Primary care practice focus group meeting:  In preliminary work leading up to this protocol we 
conducted a focus group meeting with GPs, PN/HCAs and managers to explore attitudes, 
feasibility and potential barriers to implementation which have informed our implementation study 
proposal.  Generally practice health care workers attitude towards spirometry and FeNO testing 
was favourable but training and capacity issues were raised as a major barrier to implementation.   
One major finding from the focus group meetings was that the number of children aged 5-16 years 
on the asthma register appeared to be much lower than what would be predicted from 
epidemiological data.  This data was gathered to understand how many children would need 
spirometry as part of their asthma review.  Further inquiry of the practice database revealed that 
the number of children prescribed regular inhaled corticosteroids was more than double the 
number on the practice asthma register and when children were added who had been prescribed 
at least two short acting beta-2 agonist inhalers in the previous 12 months the total number of 
children rose to approximately 4-times the number on the asthma register and very close to the 
10% of children predicted by epidemiological data.   
These findings resulted from a small sample of children and may not be generalizable.  
Nonetheless, practice GPs felt that the ‘cleaning up’ of the asthma register by establishing the 
diagnosis or misdiagnosis of asthma would be a positive effect resulting from the objective tests 
recommended by NICE.   
CCGs and commissioning:  In two meetings with Samantha Little, the principal commissioner of 
children’s services and CCG GP leads there was clear support for the proposed study to inform 
implementation of the NICE guideline into Leicestershire GP practices.  This was identified as a 
priority funding area for discussion in the next financial year. 

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Leicestershire Partnership Trust Respiratory Specialist Nurse Lead:  The implementation study 
was discussed with Ms Karen Moore, lead respiratory nurse in the Leicestershire Partnership Trust 
(LPT).  The LPT respiratory nurse team helped implement and continues to support the 
implementation of spirometry testing for patients with COPD in Leicestershire primary care 
practices.  Ms Moore’s experience with implementation informed the study protocol and advised on 
how best to start addressing the training needs and barriers to implementation and joined the study 
team.  
The current training package is usually delivered to individual PN/HCAs during a 2-hour training 
session preceding a joint COPD clinic and consists of a PowerPoint presentation on performance 
and interpretation of spirometry followed by hands on training.  Depending on the level of 
experience of the PN/HCA the spirometry testing of patients in the clinic will be either supervised or 
supported where necessary or, where the PN/HCA is naïve to spirometry, she/he will observe at 
least 10 patients before performing supervised spirometry.  Nurses are referred to ‘A Guide to 
Performing Quality Assured Diagnostic Spirometry’ (13) for further information on spirometry 
testing.  The guide is supported by the NHS, Asthma UK, Primary Care Respiratory Society UK, 
BTS, the Association for Respiratory Technology & Physiology and others but its emphasis is on 
the testing in adults with COPD.  Additionally, in order to obtain LPT accreditation the PN/HCA has 
to send in 10 spirometry tracings of which 8 have to comply with Association for Respiratory 
Technology & Physiology standards and be correctly interpreted.  Group sessions for several 
practices located in close proximity are offered up to four times per year and one to one sessions 
are offered as appropriate with GPs who interpret the spirometry.  
Rationale 
The use of the lung function tests in children is already routinely done in hospitals, has been shown 
to be safe in children and is now being recommended (at least in draft guidance) by NICE. As 
such, our research question is not whether we should use spirometry and FeNO testing in primary 
care, indeed they are not viewed as research interventions in this study; the question is – how can 
this be achieved? 
Therefore the primary rationale for this study is to identify the training needs and capacity 
requirements of primary care practices in order for objective lung function testing to be made 
available for all children with suspected or confirmed asthma cared for in the non-hospital setting.  
 

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5. 
OBJECTIVES 
 
5.1 
Primary Objectives 
The main objective for this study will be to evaluate the training and capacity requirements 
of primary care sites in order for them to be able to deliver routine spirometry and FeNO 
testing for children with suspected or presumed asthma. 
 
5.2 
Secondary Objectives 
The secondary objectives relate to investigating the impact of implementing the new NICE 
guidelines on the processes and outcomes of childhood asthma care and will include: 
1. The number of children in which a diagnosis of asthma can be confirmed using 
spirometry and FeNO testing 
2. The number of misdiagnoses identified using lung function tests 
3. The impact of implementation to health economics 
 
 

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6. 
STUDY DESIGN SUMMARY 
6.1 
Summary of Trial Design 
This study will employ both qualitative and quantitative measures in order to evaluate the 
resources required to implement routine lung function testing for children in primary care; and to 
investigate the impact this would have on diagnosis in children with suspected or presumed 
asthma.  In total we hope to recruit between 3-6 GP sites across Leicestershire and 
Northamptonshire for the study, which would represent a patient population of ~120,000-150,000 
people, representing 1500-2000 children potentially eligible to take part in the study based on our 
preliminary data. Primary care sites will be approached by the study team with assistance from the 
CCG R+D manager for Leicester (Debbie Wall) and the CRN locality manager for East Midlands 
(Debbie Jeffrey). We aim to recruit sites of differing sizes and with different patient demographics.  
 
Site survey questionnaires will be completed for each site by the study team to gather information 
about the individual practice’s patient population and current asthma review set up. Readiness for 
change questionnaires will be used to investigate staff opinions, concerns and perceived barriers to 
implementation. These will be sent out to GPs, practice nurses, HCAs and practice managers at 
each participating site. The study team will develop and refine a package of training and support 
which will be based on an existing training programme for primary care practitioners to perform 
spirometry on adult patients with COPD in Leicestershire primary care practices.  We will evaluate 
the success of the training by supporting and monitoring the primary care practitioners utilising 
these tests in primary care asthma review clinics. The length of training required in order for 
different staff groups to be able to perform spirometry and FeNO testing independently will be 
documented.  
 
To investigate the impact of implementing lung function testing for children into primary care, we 
will consent children onto the study for the purposes of accessing their electronic records (see 
below for details) and a follow up postal questionnaire only. All children between the ages of 5-16 
years inclusive who meet the inclusion criteria (see below) and who are registered patients at the 
study sites are eligible for recruitment onto the study; we aim to recruit 1000 children based on a 
50-70% response rate. We anticipate that the study will last 2 years from beginning to end, which 
will include time for data analysis and publication of results. This is an outline of the proposed study 
plan -  
 

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Please see Appendix for Gantt chart detailing anticipated duration of study periods.  
 
The study interventions are described in detail below:  
 
Firstly, the study team will meet with interested GP practices to present an overview of the study. 
The participating practice teams are then expected to complete readiness for change 
questionnaires and assist the study team in completing the site survey questionnaires in order for 
the study team to identify training and capacity needs and potential barriers to implementation. 
Secondly, designated staff (PNs/HCAs) at each practice are expected to complete a package of 
training aimed at helping them achieve competencies to be able to deliver lung function testing to 
children independently. 
 
The GPs will then be asked to perform searches of their electronic records to identify children who 
require or who would benefit from an asthma review based on the inclusion criteria detailed below. 
The GP practices will then send out clinic appointment letters to these children inviting them to 
book into an asthma review clinic. The letters from the GPs will make the families aware that they 
will also be invited to take part in the CHAMPIONS study in addition to their routine review and lung 
function tests. A patient information sheet will be included with the letters which the GPs send out.   
 
On the day of the clinic, a member of the study team will introduce themselves to the parent and 
child prior to the appointment in order to give further information about the study, answer questions 
and to take written consent from those families who wish to participate. It will be made clear that 
they are welcome to the asthma review and lung function tests whether they choose to consent to 
the study or not.  
 
For consented patients, the onlyadditional study interventions are 1) the initial health economics 
questionnaires (CHU9D and PAQLQ), 2) the follow up postal health economics and asthma quality 
control questionnaires, and 3) allowing us access to their medical records to collect data as 
detailed below.  
 
Data analysis will be performed using statistical methods described below.  
 

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We intend for the results derived from this study to be presented at scientific meetings and 
published in medical journals and asthma websites. A plain language summary will also be 
published online which families will be able to access. No identifiable data of any child will be 
included in any report or publication. 
 
6.2 
Primary and Secondary Endpoints 
 
The primary end point to this study will be when designated healthcare staff at each participating 
GP practice are able to independently and competently perform and interpret objective lung 
function tests; and have done so on all the children with suspected/presumed asthma on their 
patient register who have agreed to attend an asthma review clinic.  
 
The secondary endpoint is when we have developed and refined a training and support package 
for primary care staff in the use of spirometry and FeNO testing in children; that is both acceptable 
to end-users and sustainable by the team delivering the training.  
  
 

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7. 
STUDY PARTICIPANTS 
7.1 
Overall Description of Study Participants 
 
       
Children with asthma or who have suspected asthma managed in primary care.                           
 
 
7.2 Inclusion Criteria 
 
Male or Female, aged 5-16 years who are: 
 
1. On the practice asthma register or 
2. Are prescribed regular (on repeat prescription) inhaled corticosteroids including 
beclometasone, fluticasone and budesonide and also search specifically for ‘brands’ 
that are commonly prescribed to include ‘clenil’, ‘seretide’, ‘symbicort’, and ‘qvar’ or 
3. Have been prescribed ≥ 2 Salbutamol MDI’s in the last 12 months or 
4. Had a documented exacerbation of asthma in the last 12 months 
5. Able and willing, in the opinion of the Investigator, to give informed consent 
 
7.3 
Exclusion Criteria 
 
1. Children who are unable to perform lung function tests for any reason 
2. Children and young people <5 years and >16 years 
3. Unable or unwilling, in the opinion of the Investigator, to give informed consent 
 
 
 
 
 

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8. 
STUDY PROCEDURES 
 
8.1 
Informed Consent 
 
Children aged 5 to 16 years who fulfil the inclusion criteria will be identified from 
electronic searches performed by the practice staff for the purposes of inviting them 
for an asthma review. We will provide the practices with patient information sheets 
(PIS) to post out with the invitation letters sent out by the GPs themselves. The PIS 
will detail no less than: the exact nature of the study and that the parent is free to 
withdraw the participant from the study at any time for any reason without prejudice to 
future care, and that there is no obligation to give consent for access to their child’s 
records in the first place. Even if the parent does not consent to the study, their child 
is still welcome to the full asthma review including lung function tests as these are 
part of recommended standard care.  
 
On the day of the clinic, a member of the research team will talk to the family prior to 
their appointment and explain the study and to answer any questions. The participant 
will be allowed as much time as wished to consider the information, and the 
opportunity to question the study team to decide whether they will participate in the 
study.  
 
It will be made clear that none of the tests performed in the asthma clinic, except the 
short health economic questionnaires, are part of the research and should be viewed 
as best practice. We are only seeking consent to: 1) access their child’s electronic 
records in order to obtain information including recent exacerbations and medications 
prescribed, 2) record answers to a health economic questionnaires onto the CRF, 3) 
time how long it takes to perform each lung function test and 4) ask their GPs to 
contact them in 3-6 months’ time by post to complete a follow up health economic 
questionnaire and ACT. Written consent will then be taken from the parents should 
they agree to participate. 
 
The person who obtains the consent will be suitably qualified and experienced, and 
have been authorised to do so by the Chief Investigator as detailed on the Delegation 
of Authority and Signature log for the study. The original signed form will be retained 
at the study site within Investigator Site File (ISF). A copy of the signed Informed 
Consent will be given to participants and a copy retained in the participant medical 
notes. Anyone not medically qualified will undergo UHL consent training.  
 
8.2 
Screening and Eligibility Assessment 
Children who clinically warrant an asthma review, which are also our potential 
participants, will be identified by the direct care team from participating GP sites. The 
direct care team will search their practice electronic database for children who meet 
the inclusion criteria using age limits “5 to 16 years,” and to include children who are 
either on the asthma register or based on asthma medications prescribed as detailed 
in the inclusion criteria above.  
 
Once identified, the direct care team will send by post the standardised PIS along 
with the asthma review invitation letters to families. The invitation letter will invite 
families to phone the GP practice to book onto an asthma review clinic. We anticipate 
that there will be a minimum of 1 week between the time families receive PIS and the 
next available asthma review clinic.  
 
 
Demographics 
The date of birth, gender, race, primary language and country of birth will be recorded 
by the research team in the CRF following written consent at the asthma review.  

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Medical History 
Details of length of asthma diagnosis or duration of “asthma” symptoms will be 
recorded at time of asthma review by study team following written consent along with 
concomitant medication and any physical examination (detailed below).  
 
 
Concomitant Medication  
All prescription “asthma” medications (bronchodilators, inhaled steroids, leukotriene 
receptor antagonists etc.) will be recorded on CRFs and assigned to a corresponding 
asthma treatment step as detailed in BTS/SIGN asthma guidelines. We will also 
record number of days of oral steroids prescribed in the preceding 6 months.  
 
 
Physical Examination 
 
Height and weight of participating children will be recorded. 
 
 
8.3 
Baseline Assessments 
 
Health Care Workers’ Training Needs 
 
The study team will gather information using site survey and readiness for change 
questionnaires at each participating practice.  It is expected that practice GPs, 
nurses, HCAs and managers will complete these questionnaires.   
The study team will seek the views particularly, but not exclusively, of the healthcare 
workers performing the objective tests (spirometry and FeNO) on the delivery and 
content of the training package and the training time available to those performing 
the tests. 
 
Assessments Performed as Part of Recommended Standard Asthma Review 
 
Asthma control test:  We will use validated asthma control tests for children 4 to 11 
years (7 questions) (17) and children 12 years and older (5 questions).   
 
Check inhaler technique:  Inhaler technique will be checked by the PN/HCA 
following training if required.  An instruction sheet with written information and 
pictures will be given to the family.   
 
Check prescription record:  We will check and document the electronic prescribing 
record and dispensing record where available for asthma medication in the previous 
6 months including the number of reliever and preventer inhalers.  As part of the 
asthma review the practice PN/HCA will also check the prescription records and 
inform the GP if they have concerns regarding: suboptimal asthma control; where 
reliever and preventer medication use are unbalanced for example in cases where 
preventer prescribing is low and reliever prescriptions are high; and where there are 
concerns regarding adherence (i.e. fewer than expected number of inhalers 
dispensed). 
 
Any child presenting to the review visit unwell or with poor lung function (FEV1 
<75% predicted) will be referred to the practice GP for assessment.   
 
Written personalised asthma action plan:  All children will be given a written 
personalised asthma action plan.  Where children already have an action plan this 
will be reviewed.   
 
Spirometry and FeNO testing: Children will be asked to perform spirometry and a 
FeNO measurement where indicated.   

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Incentive spirometry:  Forced expiratory manoeuvres will be performed according to 
American Thoracic Society/European Respiratory Society standards (15,16).  
Children will be invited to perform a forced expiratory manoeuvre at least three 
times with a maximum of eight attempts.  Where readings are within 5% of each 
other the recorded value is the best of these three readings.  Achieving such 
reproducibility can be difficult in younger children and we will then use the best effort 
as the recorded values. Incentive spirometry will be used in all children, whereby 
visual aids are provided on the spirometer screen like for example a series of 
candles have to be blown out encouraging the child to breathe out hard for longer.  
This technique is very successful, even in young children.  The PN/HCA will assess 
the forced expiratory volume in 1 second (FEV1) and the FEV1/FVC ratio.  Where 
the FEV1/FVC ratio is lower than the GLI threshold or where FEV1 is <80% 
predicted they will perform reversibility testing using Salbutamol 400 micrograms (4 
puffs) given via spacer and repeat the forced expiratory manoeuvre after 15 
minutes.  Any change in FEV1 of ≥12% will be taken as demonstrating reversible 
airway narrowing and this in conjunction with the clinical history will be taken as 
diagnostic for the presence of asthma.  The data and the lung function trace will be 
recorded on the practice electronic patient records and the GP informed.  
 
FeNO measurements: Will be taken in all children five years and older using a NIOX 
MINO (Aerocrine, Sweden), which is a hand-held device with a mouthpiece.  The 
result of the FeNO concentration in exhaled breath is available immediately in parts 
per billion (ppb) and we will use the cut-off value of 35ppb and above as diagnostic 
for asthma as per NICE guideline.   
 
 
8.4 
Randomisation and Codebreaking  
 
 
There is no randomisation of participants in this study.  
 
8.5 
Subsequent Assessments 
We will have only one face to face contact with each study participant throughout the 
study. Having taken appropriate consent, we will review each participants electronic 
record 3-6 months following the initial asthma review to record any changes in 
prescription patterns, additional primary care review for exacerbations or hospital 
attendances. In patients who have agreed, we will also send out a follow up postal 
health economic questionnaire and asthma control test 3-6 months following the 
review. 
 
8.6  Definition of End of Trial 
The end of trial is when the last participant has attended his/her asthma review 
clinic and we have reviewed his/her records 3-6 months following this date. 
 
8.7 
Discontinuation/Withdrawal of Participants from Study Treatment 
Each participant has the right to withdraw from the study at any time and may 
withdraw consent for their patient records to be accessed by informing the study 
team directly or via their GP.  
 
8.8 
Source Data 
Source documents are original documents, data, and records from which participants’ 
CRF data are obtained.  These include, but are not limited to, GP electronic records 
(from which medical history and previous and concurrent medication may be 
summarised into the CRF) and hospital correspondence. 
 
CRF entries will be considered source data if the CRF is the site of the original 

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recording (e.g., there is no other written or electronic record of data). In this study the 
CRF will be used as the source document for time taken to perform spirometry and 
FeNO and health economic questionnaire answers only.  
 
All documents will be stored safely in confidential conditions.  On all study-specific 
documents, other than the signed consent, the participant will be referred to by the 
study participant number/code, not by name. 
 
 

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9. 
TREATMENT OF TRIAL PARTICIPANTS 
9.1 
Description of Study Treatment  
 
Educational sessions for Primary Care Staff 
 
We will provide 2 levels of education: 
 
Level 1: This will be conducted by the implementation team as part of the initial 
meeting with the GPs, PN/HCAs and managers/administrators. These will be update 
sessions on the latest draft asthma guidelines issued by NICE and BTS/SIGN with an 
emphasis on proposed changes to current practice.  We will discuss in more detail 
the diagnostic algorithm for children under investigation for asthma and the objective 
tests underpinning a diagnosis of asthma in children.  An understanding of objective 
tests includes (i) an appreciation that tests need to be technically acceptable to be 
useful, and (ii) reference values appropriate for the individual are essential for correct 
interpretation.  Equipment needs (incentive spirometry) and NIOX MINO or VERO for 
FeNO testing will be discussed, as will the training package to be offered by the 
implementation team. 
 
Level 2:  The implementation team will provide formal face-to-face teaching and 
additional online training material to practice health care workers on performing 
spirometry and FeNO. In order to maximise the impact of the asthma reviews the 
initial training intervention will need to be focused, but flexible to the differing learning 
requirements of the health care professionals involved. 
 
The training session will address practical aspects and clinical interpretation of 
spirometry in children. We plan to work in small teaching groups (possibly as few as 
1-2 people) which will itself lead to mixed teaching methods, including a short 
PowerPoint presentation (delivered on a laptop), videoclips, demonstrations, 
opportunities for practical experience with others acting as the subject, and 
interpretation of results from an available bank of anonymised data/traces.  
 
The training session will cover: a) essential physiological principles underlying 
spirometry b) Setting up and calibrating spirometers (directed towards the type of 
spirometer to be used in that particular practice setting) c) how to encourage children 
of different ages to perform spirometry, including the use of incentive spirometry d) 
how to recognise when sufficient technically acceptable data have been collected for 
reporting (or when the child is not capable of performing spirometry)and e) 
interpretation of data. 
 
Participants will be shown how to interpret the data first by examining the graphical 
recordings, (‘pattern recognition’), and then by comparing measured outputs (FEV1, 
FVC, and FEV1/FVC) with predicted values appropriate for the sex, age and height of 
the child.  This approach aims to identify any individual who may have a condition 
other than asthma (e.g. fixed obstruction), and then quantify the extent of any deficit 
in lung function.  Where measurements are available before and after a 
bronchodilator the extent of any change in lung function is a measure of bronchial 
responsiveness. 
 
In addition to training in spirometry, participants will be trained in the performance 
and interpretation of exhaled nitric oxide testing in children.  While this requires 
careful instructions to be provided to the child so that s/he exhales steadily into the 
machine, there is minimal requirement for training in interpretation, since this is a 
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We will also discuss asthma control tests, asthma action plans and inhaler technique 
but we are aware that many PN/HCAs will be familiar with asthma action plans and 
the checking of inhaler technique already.  PN/HCAs will be able to retain copies of 
the teaching materials for private learning or revision, and are encouraged to contact 
the implementation team at any time if they have questions or want further training. 
 
We will supervise the PN/HCAs performing at least 10 paediatric lung function tests 
or until they are assessed as competent by both the study team and themselves.  
This will be continually assessed and feed-back given to the PN/HCA.  This approach 
has been employed successfully by the Respiratory Specialist Nurse Team for the 
Leicestershire Partnership NHS Trust.  We will also point nurses towards accredited 
courses for further training.   
 
A virtually-delivered quality improvement programme designed to improve primary 
care management for children with asthma has shown increased spirometry quality 
and improved assessment of asthma severity levels (14).  
 
Success of the intervention will be defined as every participating surgery having a 
team which can regularly and competently provide objective lung function tests to 
children 5-16 years old.  
 
Capacity Requirements 
 
We will assess additional capacity needs by timing how long each lung function test 
takes to perform in addition to the routine asthma review at each surgery. We will 
also be able to evaluate the number of patients who can be reliably reviewed and 
tested per session, thus elucidating how many sessions a typical GP practice would 
have to support in order to provide regular lung function testing to children. This 
information would further inform the costs required to sustain new NICE 
recommended practice.  
 
Health Economic Analysis 
 
This will take the form of a questionnaire delivered to parents at the time of the 
asthma review and a further postal questionnaire 3-6 months following the review. 
Analysis of this data will be supported by a health economist.  
 
Assessment of Impact of Implementation to Processes of Care 
 
Following the initial review appointment, we will access the electronic records of 
consented participants. We will seek information on changes to prescribed asthma 
medications (bronchodilators, oral steroids and inhaled steroids), exacerbations since 
review, hospital admissions/attendances since review and whether their originally 
diagnoses had changed as a result of the availability of objective tests.  
 
With parental consent, we will also send out a repeat ACT by post 3-6 months 
following the initial review.  
 
9.2 
Storage of Study Equipment or Related apparatus 
There is no specific equipment used for this study. The spirometer and FeNO 
analysers are not study equipment (they are part of recommended routine care) and 
will be stored in locked University of Leicester or participating GP premises when 
not in use.  
 
9.3 
Compliance with Study Treatment 
There are no compliance issues with this study plan 

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10. 
SAFETY REPORTING 
10.1 Definitions 
 
10.1.1 Adverse Event (AE) 
An AE or adverse experience is: 
Any untoward medical occurrence in a patient or clinical investigation participants, 
which does not necessarily have to have a causal relationship with this treatment. 
An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom or disease temporally associated with the 
the study, whether or not considered related to the study. 
 
10.1.2 Adverse Reaction (AR) 
All untoward and unintended responses related to the study. 
All cases judged by either the reporting medically qualified professional or the 
sponsor as having a reasonable suspected causal relationship to the study qualify 
as adverse reactions.   
 
10.1.3 Severe Adverse Events 
To ensure no confusion or misunderstanding of the difference between the terms 
"serious" and "severe", which are not synonymous, the following note of clarification 
is provided: 
The term "severe" is often used to describe the intensity (severity) of a specific 
event (as in mild, moderate, or severe myocardial infarction); the event itself, 
however, may be of relatively minor medical significance (such as severe 
headache).  This is not the same as "serious," which is based on patient/event 
outcome or action criteria usually associated with events that pose a threat to a 
participant's life or functioning.  Seriousness (not severity) serves as a guide for 
defining regulatory reporting obligations. 
 
10.1.4 Serious Adverse Event or Serious Adverse Reaction 
A serious adverse event or reaction is any untoward medical occurrence that at any 
dose: 
• 
Results in death, 
• 
Is life-threatening, 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in 
which the participant 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 inpatient hospitalisation or prolongation of existing hospitalisation, 
• 
Results in persistent or significant disability/incapacity, or 
• 
Is a congenital anomaly/birth defect. 
• 
Other important medical events* 
*Other events that may not result in death, are not life threatening, or do not require 
hospitalisation, may be considered a serious adverse event when, based upon 
appropriate medical judgement, the event may jeopardise the patient and may require 
medical or surgical intervention to prevent one of the outcomes listed above. 
 
10.1.5 Expected Serious Adverse Events/Reactions 
There are no active interventions involved with this study. As such we do not expect 
any adverse events directly related to the study.  
 
10.1.6 Suspected Unexpected Serious Adverse Reactions 
A serious adverse reaction, the nature or severity of which is not consistent with the 
applicable product information. 
 

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10.2 Reporting Procedures for All Adverse Events 
All AEs occurring during the study observed by the investigator or reported by the 
participant, whether or not attributed to study, will be recorded on the CRF.   
The following information will be recorded: description, date of onset and end date, 
severity, assessment of relatedness to study, other suspect device and action 
taken.  Follow-up information should be provided as necessary.  
AEs considered related to the study as judged by a medically qualified investigator 
or the sponsor will be followed until resolution or the event is considered stable.  All 
related AEs that result in a participant’s withdrawal from the study or are present at 
the end of the study, should be followed up until a satisfactory resolution occurs. 
It will be left to the investigator’s clinical judgment whether or not an AE is of 
sufficient severity to require the participant’s removal from treatment (see section 
7.7).  A participant may also voluntarily withdraw from treatment due to what he or 
she perceives as an intolerable AE.  If either of these occurs, the participant must 
undergo an end of study assessment and be given appropriate care under medical 
supervision until symptoms cease or the condition becomes stable. 
The severity of events will be assessed on the following scale:  1 = mild, 2 = 
moderate, 3 = severe.   
The relationship of AEs to the study will be assessed by a medically qualified 
investigator.  
 
Note: Due to the nature of the study it is not the intention to be recording or 
reporting AEs or SAEs 
 
10.3 Reporting Procedures for Serious Adverse Events 
All SAEs, except those expected ones defined in section 10.1.5 that do not require 
immediate reporting (see 10.1.5), must be reported to the Sponsor within one 
working day of discovery or notification of the event.  The Sponsor will perform an 
initial check of the information and ensure that it is reviewed at the next R&D 
Management meeting.  All SAE information must be recorded on an SAE form and 
sent to the Sponsor using the appropriate reporting form and the contact details on 
there. Additional information received for a case (follow-up or corrections to the 
original case) needs to be detailed on a new SAE form which must be sent to the 
Sponsor using the appropriate reporting form and the contact details on there.  
The Sponsor will report all SUSARs to the Research Ethics Committee concerned. 
Fatal or life-threatening SUSARs must be reported within 7 days and all other 
SUSARs within 15 days. The CI will inform all investigators concerned of relevant 
information about SUSARs that could adversely affect the safety of participants. 
In addition to the expedited reporting above, the CI shall submit once a year 
throughout the study or on request an Annual Report to the Ethics Committee which 
lists all SAEs / SUSARs that have occurred during the preceeding 12 months. 
 
Note: Due to the nature of the study it is not the intention to be recording or 
reporting AEs or SAEs 
 
 

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11. 
STATISTICS 
 
11.1 Description of Statistical Methods 
The qualitative data regarding opnions and barriers to implementation derived from change 
questionnaires conducted with the participating GP practices will be presented in report 
form. Appropriate non-parametric tests such as Kruskal-Wallis, Wilcoxon paired signed and 
Friedmans 2-Way ANOVA will be used to assess data; including the changes in number of 
children diagnosed with asthma, the number of misdiagnoses and alterations in prescribing 
(number of salbutamol inhalers/steroid courses) as a result of implementation of objective 
lung function tests. Paired t-tests or paired Wilcoxon signed rank tests will be used to 
assess the change in asthma control test scores, number of school days missed and 
number of carer work days missed. 
 
A generalized linear mixed model with logit link function will also be used to compare the 
proportion of children with a personalised asthma plan and other secondary outcomes. The 
models will include important covariates such as age, gender and ethnicity, and the 
clustering effect of GP clinic will be accounted for. The effect of GP clinic will also be 
assessed by fitting a mixed effects model, GP clinic will be fitted as a random effect, 
covariates such as age, gender and ethnicity will be fitted as fixed effects.  
 
All statistical analysis will be performed using R 3.2.0 (http://www.r-project.org/) and SPSS 
v22. 
 
11.2 The Number of Participants 
 
We plan to recruit 1000 children into the study. This number has been derived from the 
expected number of children in the participating practices who would meet the inclusion 
criteria based on epidemiological data and preliminary searches. It also takes into 
consideration the capacity of the study team, the study length and anticipated recruitment 
rates of 50-70%.  
 
11.3 The Level of Statistical Significance 
 
All statistical tests will be performed at the alpha=5% level. 
 
11.4 Criteria for the Termination of the Trial. 
 
Once we have accessed the records of the final child to be recruited and they have 
returned the follow up questionnaire.  
 
11.5 Procedure for Accounting for Missing, Unused, and Spurious Data. 
 
A table listing all key variables with percentage of missing data will be reported and where 
possible the reason for missing data will be reported. Within the multivariate regression 
framework missing data will be imputed using multiple imputation. To avoid bias, where it 
can be reasonably established that data is not missing at random, covariates will not be 
imputed, a complete case analysis will be used. Outcome variables missing not at random 
will not be imputed, sensitivity analysis will be performed and an assessment of the models 
made based on the missing at random assumption. Spurious data will be reported and 
where possible correct values will be inserted, if it is not possible to supply correct values, 
value will be deleted. 
 
11.6 Procedures for Reporting any Deviation(s) from the Original Statistical Plan 
 

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Any deviations from the original statistical analysis plan will be detailed in the final report. 
 
11.7 Inclusion in Analysis 
 
We plan to include data from all participants in the analysis. 
 
 

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12. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
Direct access will be granted to authorised representatives from the sponsor, host 
institution and the regulatory authorities to permit trial-related monitoring, audits and 
inspections. 
 
 

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13. 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES 
The study will be conducted in accordance with the current approved protocol, ICH GCP, relevant 
regulations and standard operating procedures.  
 
Regular monitoring will be performed according to ICH GCP. Data will be evaluated for compliance 
with the protocol and accuracy in relation to source documents. Following written standard 
operating procedures, the monitors will verify that the clinical trial is conducted and data are 
generated, documented and reported in compliance with the protocol, GCP and the applicable 
regulatory requirements.  
 
 

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14. 
CODES OF PRACTICE AND REGULATIONS 
14.1 Ethics 
Annual review follow-up of children aged 5 to 16 years on the practice asthma 
register are expected as part of QOF.  All aspects of the proposed review are 
recommended by national guidelines.  The reviews are expected to be performed by 
the PN/HCA and will not involve written informed consent.  All the data recorded by 
the research team will be fully anonymised and no patient identifiable data will leave 
the practice at any stage. 
 
14.2 Sponsor Standard Operating Procedures 
All relevant Sponsor SOPs will be followed to ensure that this study complies with 
all relevant legislation and guidelines  
 
14.3 Declaration of Helsinki 
The Investigator will ensure that this study is conducted in full conformity with the 
current revision of the Declaration of Helsinki (last amended October 2000, with 
additional footnotes added 2002 and 2004). 
 
14.4 ICH Guidelines for Good Clinical Practice 
The Investigator will ensure that this study is conducted in full conformity with 
relevant regulations and with the ICH Guidelines for Good Clinical Practice 
(CPMP/ICH/135/95) July 1996. 
 
14.5 Approvals  
Once Sponsor authorisation has been confirmed, the protocol, informed consent 
form, participant information sheet and any proposed advertising material will be 
submitted to an appropriate Research Ethics Committee (REC), regulatory authorities 
(MHRA in the UK), and host institution(s) for written approval.   
 
Once Sponsor authorisation has been confirmed, the Investigator will submit and, 
where necessary, obtain approval from the above parties for all substantial 
amendments to the original approved documents.    
 
14.6 Participant Confidentiality 
The trial staff will ensure that the participants’ anonymity is maintained.  The 
participants will be identified only by initials and a participants ID number on the CRF 
and any electronic database.  All documents will be stored securely and only 
accessible by trial staff and authorised personnel. The study will comply with the Data 
Protection Act which requires data to be anonymised as soon as it is practical to do 
so.   
 

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15. 
DATA HANDLING AND RECORD KEEPING 
All the data will be entered on the practice computer and the spirometry tracing scanned in. Patient 
data will be recorded on a Redcap database in fully anonymised fashion in accordance with 
information governance guidelines developed in consultation with the National Research Ethics 
Service, the Ethics and Confidentiality Committee.  
 
The participants will be identified by a study specific participants number and/or code in 
any database.  The name and any other identifying detail will NOT be included in any study 
data electronic file.  
 
 

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16. 
STUDY GOVERNANCE 
16.1 Trial Steering Committee (TSC) 
A study steering committee will be appointed and meet twice yearly.  It is anticipated 
that Mr Kirk the patient representative will sit on the steering committee. The role of 
the Trial Steering Committee (TSC) will be to provide the overall supervision of the 
trial. The TSC will include members who are independent of the investigators, their 
employing organisations, funders and sponsors. The TSC will monitor trial progress 
and conduct and advise on scientific credibility. 
 
 

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17. 
FINANCING AND INSURANCE 
 
Insurance 
 
University of Leicester insurance will be in place to cover for insurance and/or indemnity to meet 
the potential legal liability of the sponsor(s) for harm to participants arising from the management of 
the research and also to meet the potential legal liability of the sponsor(s) or employer(s) for harm 
to participants arising from the design of the research. 
 
NHS indemnity scheme will act as insurance and/ or indemnity to meet the potential legal liability of 
investigators/collaborators arising from harm to participants in the conduct of the research. 
 
Costings 
We have funding of £136,465.73p to cover the costs of the study programme (£29,368 from 
Midlands Asthma and Allergy Research Association and £107,097.73p from Aerocrine). We also 
have additional funding from Health Education East Midlands for the salary of the fellow which is 
paid directly to the fellow (David Lo) amounting to £113,483.69 over 2 years. Total funding – 
£249,949.42p. 
 
This will include salaries for one full-time research nurse for 18 months (£63,018.77). We have 
allocated £15,000 to Dr Yang to perform the health economic analysis.   
 
Further funds are requested for: travel of the implementation team between base and practices 
(£5,000), the cost of 2 spirometers (£4,000), consumables inc. postage costs (£4000), conference 
attendance costs (£3,000), MD course fees for project fellow (£4,200), computer equipment 
(£2900) and estates inc. investigator costs (£15,346.96). 
 
We have also allocated £100 for each asthma review session performed by the PN/HCA, allowing 
for 200 sessions (3-4 sessions per week for 60 weeks) equates to a total of £20,000.  Without this 
funding the study would not be possible due to lack of capacity.   
 
Justification of costs:   
Project fellow:  The fellow will coordinate the study working closely with the study PI.  David will 
help liaise with participating practices to organise the teaching and training events and participate 
in the asthma review clinics and support the research nurse.  The project fellow will be responsible 
for the data collection and management and perform the data analysis with the help and support of 
the statistician. He will take a strong role in the data dissemination and presentation.  David will 
gain significant skills in the diagnosis and management of childhood asthma generally and in 
primary care particularly and will build capacity. During the course of this project he will also 
undertake a MD degree to support his research training.  
 
Research nurse:  The research nurse will take a strong role in the coordination of training of 
PN/HCAs in the performance and interpretation of spirometry to and be involved in the practice 
teaching.  The nurse will take a lead in organising the joint follow-up asthma clinics in participating 
practices and she/he will be involved in data acquisition and entry into the database. 
 
Spirometers:  Purchase of two spirometers from Carefusion with incentive software suitable for 
children, appropriate size mouthpieces and disposable bacterial filters, maintenance and 
consumables.  Costs include the mandatory yearly maintenance costs. 
Additional consumables include petrol money calculated using a standard University template of 45 
pence per mile for the project fellow and nurse, costs for stationary and postage.  
 
We will buy PN/HCA time and pay £100 to the practice for each session to cover salary and on-
costs as there is no capacity in primary care currently to support implementation of the NICE 

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guideline.  We will also reimburse practices for administrator time to perform the relevant database 
searches. 
 

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18. 
PUBLICATION POLICY 
 
Authorship 
 
The list of authors should accurately reflect who carried out the research and who wrote 
the article. All multi-authored papers should include an ‘Authors’ Contributions’ section at 
the end of the paper. 
 
The list of authors should correspond to the following criteria (based on ICMJE 
guidelines). Authors must meet all 4 of these conditions: 
 
1. Substantial contributions to conception and design, or acquisition of data, or analysis 
and interpretation of data; 
2. Drafting the article or revising it critically for important intellectual content;  
3. Final approval of the version to be published; and  
4. Agreement to be accountable for all aspects of the work in ensuring that questions 
related to the accuracy or integrity of any part of the work are appropriately 
investigated and resolved. 
 
All authors must meet these criteria for authorship and, conversely, no-one should be 
omitted from the list if he/she meets these criteria (18).  
 
Affiliation 
 
All University authors must cite University of Leicester as their institutional research base 
when recording their affiliation in research articles, conference papers and other 
publications, irrespective of where the affiliation actually appears in the publication. 
 
Review 
 
Manuscripts will be submitted to peer-review journals and data will be presented in 
anonymised fashion at relevant national and international conferences.  
 
 

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19. 
REFERENCES 
1. Health and Social Care Information Centre. The Quality and Outcomes Framework (QOF) 2013/14 
results. 2015. Available from: http://qof.hscic.gov.uk/ [Last accessed: 16 April 2015 
2. Lai CK, Beasley R, Crane J, Foliaki S, Shah J, Weiland S, et al. Global variation in the prevalence and 
severity of asthma symptoms: phase three of the International Study of Asthma and Allergies in 
Childhood (ISAAC). Thorax 2009;64:476-483 
3. LindenSmith J, Morrison D, Deveau C, Hernandez P. Overdiagnosis of asthma in the community. Can 
Respir J 2004;11:111-116 
4. Marklund B, Tunsater A, Bengtsson C. How often is the diagnosis bronchial asthma correct? Fam Pract 
1999;16:112-116 
5. van Schayck CP, van Der Heijden FM, van Den Boom G, Tirimanna PR, van Herwaarden CL. 
Underdiagnosis of asthma: is the doctor or the patient to blame? The DIMCA project. Thorax 
2000;55:562-565 
6. Montnemery P, Hansson L, Lanke J, Lindholm LH, Nyberg P, Lofdahl CG, et al. Accuracy of a first 
diagnosis of asthma in primary health care. Fam Pract 2002;19:365-368 
7. Kuprys-Lipinska I, Elgalal A, Kuna P. The underdiagnosis and undertreatment of asthma in general 
population of the Lodz Province (Poland). Pneumonol Alergol Pol 2010;78:21-27 
8. van Schayck OC. Global strategies for reducing the burden from asthma. Prim Care Respir J 
2013;22:239-243 
9. Kaur B, Anderson HR, Austin J, Burr M, Harkins LS, Strachan DP, et al. Prevalence of asthma 
symptoms, diagnosis, and treatment in 12-14 year old children across Great Britain (international study 
of asthma and allergies in childhood, ISAAC UK). BMJ 1998;316:118-124 
10. http://www.nice.org.uk/guidance/gid-cgwave0640/resources/asthma-diagnosis-and-monitoring-draft-
guideline2 
11. https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-
2014/ 
12. https://www.nice.org.uk/guidance/dg12 
13. https://www.pcc-cic.org.uk/sites/default/files/articles/attachments/spirometry_e-guide_1-5-13_0.pdf 
14. Stout JW, Smith K, Zhou C, Solomon C, Dozor AJ, Garrison MM, et al. Learning from a distance: 
effectiveness of online spirometry training in improving asthma care. Acad Pediatr 2012;12:88-95 
15. Loeb JS, Blower WC, Feldstein JF, Koch BA, Munlin AL, Hardie WD. Acceptability and repeatability of 
spirometry in children using updated ATS/ERS criteria. Pediatr Pulmonol 2008;43:1020-1024 
16. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for 
lung function tests. Eur Respir J 2005;26:948-968 
17. Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT, Marcus P, et al. Development of the asthma 
control test: a survey for assessing asthma control. J Allergy Clin Immunol 2004 ;113:59-65 
18. https://royalsociety.org/journals/ethics-policies/openness/ 
 
 

Date and Version No:  
        25th May 2016                                         Version 3.0  
 
 
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Page 37 of 37 
CHAMPIONS Study 
 
20. 
APPENDIX A: STUDY GANTT CHART 
Study Task 
Time in Months 
-3 
-6 
-9 
-12 
-15 
-18 
-21 
-24 
Identify Participating Practices 
 
 
 
 
 
 
 
 
 
Site Survey and Change Readiness Questionnaires 
 
 
 
 
 
 
 
 
 
Develop training package 
 
 
 
 
 
 
 
 
 
Delivery of training package to healthcare workers 
performing the test 
 
 
 
 
 
 
 
 
Identification of patients under investigation/review 
for asthma 
 
 
 
 
 
 
 
 
Perform asthma reviews 
 
 
 
 
 
 
 
 
 
Review and refine training package 
 
 
 
 
 
 
 
 
 
Collection of health outcome data 
 
 
 
 
 
 
 
 
 
Quantitative and qualitative data analysis 
 
 
 
 
 
 
 
 
 
Dissemination and publication of study results