<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03248895</url>
  </required_header>
  <id_info>
    <org_study_id>QUB B14/39</org_study_id>
    <nct_id>NCT03248895</nct_id>
  </id_info>
  <brief_title>Evaluation of a Mobile Direct Observation Therapy (DOT) Approach in Children and Young People With Asthma</brief_title>
  <official_title>Evaluation of a Mobile Direct Observation Therapy (DOT) Approach in Children and Young People With Asthma. Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Queen's University, Belfast</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Queen's University, Belfast</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Mobilte Direct Observation Therapy (MDOT) is a technology has the potential to be a cost&#xD;
      effective approach to direct observation of therapy administration, the latter being one of&#xD;
      the most accurate methods of evaluating adherence. Use to date, as confirmed by the rapid&#xD;
      systematic review, has been limited mainly to TB and sickle cell disease and there have been&#xD;
      no published reports on the use of MDOT to monitor inhaled therapy. Due to the increasing&#xD;
      incidence of childhood asthma worldwide, there is a need for new innovative approaches to&#xD;
      support children and their parents with asthma management, especially since national and&#xD;
      international guidelines have advised healthcare providers to periodically assess inhaler use&#xD;
      as part of asthma management.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Asthma is the most common chronic disease in childhood. It is defined as a chronic&#xD;
      inflammatory disorder of the airways in which many cells and cellular elements promote airway&#xD;
      obstruction and hyper-responsiveness (GINA, 2012). According to the World Health Organization&#xD;
      (WHO, 2014), asthma is estimated to affect approximately 253 million people worldwide.&#xD;
      Despite advances in biological and pathological research, the prevalence of asthma in&#xD;
      children has significantly increased over the past decade (Massingham et al., 2014).&#xD;
&#xD;
      Moreover, the economic burden of asthma is increasing. In the US, it is estimated that the&#xD;
      yearly cost of asthma in children and adults is around $1.48 billion (Price et al., 2013). A&#xD;
      decade ago, the total annual asthma expenditure in the UK was determined to be £752.6 million&#xD;
      with 8% of costs associated with hospital admission, 13% attributable to general practitioner&#xD;
      consultations and 79% due to prescription costs (Gupta et al., 2004).&#xD;
&#xD;
      The British Thoracic Society (BTS/SIGN, 2012) and Global Initiative for Asthma (GINA, 2012)&#xD;
      guidelines provide the background definitions for three broad categories of asthma control.&#xD;
      They include controlled (no nocturnal wakening, infrequent short acting beta 2 agonist (SABA)&#xD;
      use e.g. &lt; 2 puffs/week, occasional mild symptoms e.g. with exercise and no exacerbations in&#xD;
      last 3 months), partially controlled (nocturnal wakening &lt; 3 nights/week, SABA use e.g. &lt; 4&#xD;
      puffs/day, mild limitation in exercise tolerance due to asthma, and 2 or fewer mild&#xD;
      exacerbations in the previous 3 months) or uncontrolled (nocturnal wakening 4-7 nights/week,&#xD;
      SABA use e.g. &gt; 5 puffs/day, limitation in exercise tolerance due to asthma and or&#xD;
      significant asthma exacerbations requiring oral steroid, Emergency Department attendance or&#xD;
      hospital admission in the previous 3 months). Children who present with partially controlled&#xD;
      or uncontrolled asthma can be divided into difficult to treat asthma (DTA) and true severe&#xD;
      therapy resistant asthma (STRA) after careful investigation (Hedlin et al., 2012). DTA occurs&#xD;
      when asthma is uncontrolled but the impact of concomitant disorders and the basics of asthma&#xD;
      care (inhaler technique and adherence) have not been adequately resolved.&#xD;
&#xD;
      Many children with asthma can achieve symptom and disease control by using inhaled&#xD;
      corticosteroid (ICS) therapy combined with a long acting B2 agonist (LABA) and/or a&#xD;
      leukotriene receptor antagonist (LTRA) (International ERS/ATS guideline, 2014). However, a&#xD;
      number of children with asthma experience frequent symptoms despite being prescribed high&#xD;
      dose ICS (Nagakumar and Thomas, 2013; Hedlin et al., 2014).&#xD;
&#xD;
      Drug delivery by inhalation of various medications is the most common treatment approach for&#xD;
      asthma in all patient populations. Inhalation therapy offers rapid onset and improved&#xD;
      efficacy compared to systemic drug delivery (Bisgaard, 1997). While ICS therapy is well&#xD;
      accepted as the foundation of optimal therapy for most asthma patients, efficacy of the&#xD;
      therapy depends on drug being delivered correctly into the lungs and taken on a regular basis&#xD;
      as a preventer therapy (Machira et al., 2011).&#xD;
&#xD;
      It has been suggested that good inhaler technique is an essential aspect of optimal asthma&#xD;
      management. Education on inhaler technique has been shown to improve self- management and&#xD;
      adherence to asthma therapy. Evidence is available demonstrating that asthma outcomes&#xD;
      correlate with proper inhaler technique and that periodically assessing this treatment aspect&#xD;
      has a positive impact on asthma control (Bryant et al., 2013; AL-Jahdali et al., 2013).&#xD;
      Moreover, early and repeated tailored education and follow-up assessment can result in&#xD;
      sustained good inhaler technique (Klot et al., 2011). However, many asthma clinics treating&#xD;
      children are unable to effectively evaluate these important patient treatment variables.&#xD;
&#xD;
      Adherence to pharmacotherapy is also considered an important basic tenet of asthma&#xD;
      management. Adherence can simply be defined as the extent to which a patient follows the&#xD;
      instructions of the prescriber (Osterberg and Blaschke, 2005). While inhaled therapy&#xD;
      technique is an essential feature of asthma pharmacotherapy, some patients with good&#xD;
      technique may have poor inhaler adherence. Available data suggest the average medication&#xD;
      adherence to ICS in children is only approximately 50% (Fish et al., 2001; Osterberg and&#xD;
      Blaschke, 2005).&#xD;
&#xD;
      It is known that adherence to ICS in children is a complicated matter influenced by diverse&#xD;
      issues including socioeconomic factors, parents' beliefs about asthma and asthma medications,&#xD;
      and poor patient-doctor communication (Osterberg and Blaschke, 2005; Armstrong et al., 2014).&#xD;
      In addition, parent/guardian health issues such as depression or substance abuse may&#xD;
      negatively affect adherence in young children as a result of the parent/guardian's failure to&#xD;
      remind, or assist the child in the use of their medication (Brackis-Cott et al., 2003).&#xD;
      Non-adherence to medication can have various negative patient consequences such as more&#xD;
      frequent clinic visits, disease exacerbations, hospital admissions, and increased cost of&#xD;
      care (AL-Jahdali et al., 2013). Indeed, a recent review of childhood asthma deaths in SE&#xD;
      England showed that medication non-adherence was a contributing factor in more than 50% of&#xD;
      cases, including patients with milder disease (Anagnostou et al.,2012) Despite being an area&#xD;
      of active research, many interventions such as isolated educational efforts are ineffective&#xD;
      in improving adherence (Drotar and Bonner, 2009). In a qualitative study in the primary care&#xD;
      setting, asthmatic children of parents who expressed medication beliefs of a high concern-low&#xD;
      need pattern had poor outcomes. Researchers subsequently showed that these beliefs could be&#xD;
      modified by repeated tailored education and close follow-up, to result in high medication&#xD;
      adherence. They concluded that &quot;it is not the education per se, but rather the intensity,&#xD;
      quality and frequency of education about self-management and follow-up that help to improve&#xD;
      adherence&quot; (Klot et al., 2011). A multicentre clinical trial in the USA was designed to&#xD;
      determine what medication was best to add in children with severe asthma already taking ICS&#xD;
      and LABA. However,the trial was cut short due to an inability to recruit an adequate number&#xD;
      of children. Patient improvement while under close supervision during the run in period was&#xD;
      the main reason for the lack of patient recruitment. (Strunk et al., 2008) Different methods&#xD;
      used to assess patient adherence to prescribed therapy have resulted in variable outcomes.&#xD;
      Adherence can be measured by collecting data from patients or their parent/guardians,&#xD;
      pharmacy dispensing records, electronic monitoring devices, or patient observation (Osterberg&#xD;
      and Blaschke, 2005). Since the approaches have produced variable results, it can be concluded&#xD;
      that presently there is no preferred method to effectively measure or improve medication&#xD;
      adherence in asthma (Sumino and Cabana, 2013).&#xD;
&#xD;
      Direct observation therapy (DOT) is recommended by the WHO to promote adherence in the&#xD;
      management of tuberculosis (TB) and this approach was adopted in 187 countries by 2005 (WHO,&#xD;
      2010). DOT allows assessment of correctly taking and completing therapy, but also can be&#xD;
      valuable to promote adherence to medication use. DOT involves a healthcare professional&#xD;
      observing patients taking their medication at home or in the clinic (Dosumu, 2001; Otu,&#xD;
      2013). The DOT approach to TB management has been utilised successfully in different&#xD;
      countries as this approach has been shown to enhance medication adherence, improve outcomes&#xD;
      including microbiologic success, and decrease acquired drug resistance to therapy (Favorov et&#xD;
      al., 2012; Walley et al., 2001; Pasipanodya and Gumbo, 2013).&#xD;
&#xD;
      While data exist to show that observation of inhaler technique can positively affect asthma&#xD;
      management, there are no published studies using a DOT approach as a means to improve&#xD;
      medication adherence. However, it has been suggested that using DOT with nurses directly&#xD;
      observing asthmatic children's inhaler technique and adherence, for example at school or&#xD;
      home, would be very resource intensive and likely not feasible for continued use (Otu, 2013).&#xD;
&#xD;
      In recent years, there has been widespread use of mobile smartphone and computer devices&#xD;
      within the healthcare environment. A recent survey of teenagers and caregivers in urban&#xD;
      paediatric practices showed that 84% of respondents were smartphone owners, a finding that&#xD;
      was independent of age group, gender, ethnicity, and socioeconomic status (Singh et al.,&#xD;
      2014). DeMaio et al. (2001) conducted a pilot study that compared videophone telemedicine&#xD;
      (V-DOT) to standard DOT (S-DOT) in the treatment of TB. In the videophone group, patients&#xD;
      took videos of medication administration that were provided to clinicians involved in their&#xD;
      management. The adherence rate was 95% for V-DOT compared to 97.5 % for S-DOT, but personnel&#xD;
      time was decreased by 288 hours with V-DOT in only 6 patients. Similarly, a telehealth&#xD;
      videophone home monitoring approach to TB was shown to enhance treatment compliance and use&#xD;
      less clinic resources in a larger study by Wade et al. (2012).&#xD;
&#xD;
      More recently, Creary et al. (2014) developed a novel mobile DOT approach utilising&#xD;
      smartphone and computer devices that resulted in a median monthly observed adherence of 93.3%&#xD;
      over the 6 month trial in children with sickle cell disease. Finally, specific to asthma&#xD;
      patients, Vasbinder et al., (2013) has developed a study to access the effectiveness of using&#xD;
      mobile phone text-messages to remind and encourage non-adherent patients to take their&#xD;
      medication and thereby improve control of their disease; results of the study are not yet&#xD;
      available. Limited available evidence, therefore, suggests that communication technology&#xD;
      could be utilised to achieve therapeutic goals of correct administration technique and&#xD;
      improved adherence to therapy in asthma patients while limiting resource utilisation.&#xD;
&#xD;
      The principal aim of this study is to evaluate the feasibility and clinical impact of a&#xD;
      mobile DOT approach (via video capture in the patient's home) on the administration technique&#xD;
      for, and adherence to, ICS in children with partially controlled or uncontrolled asthma. A&#xD;
      secondary aim is to determine factors that influence adherence to ICS in children with&#xD;
      asthma.&#xD;
&#xD;
      The specific objectives are to:&#xD;
&#xD;
        1. Investigate the feasibility, practicality, and persistence of a mobile DOT technology&#xD;
           approach in the home setting to assist with disease management of children and young&#xD;
           people with partially controlled or uncontrolled asthma.&#xD;
&#xD;
        2. Assess inhaler technique and adherence to ICS therapy by use of DOT videos,&#xD;
           parent/guardian and child self-report questionnaires (Medication Adherence Report Scale&#xD;
           (MARS)), pharmacy records and patient's general practitioner (GP) records.&#xD;
&#xD;
        3. Evaluate the impact of the DOT intervention on asthma clinical outcomes including&#xD;
           physician assessment of disease control, medication changes, asthma control tests,&#xD;
           health-related quality of life and pulmonary function studies in participating children.&#xD;
&#xD;
        4. Identify parental/guardian and patient factors that influence adherence to ICS in&#xD;
           participating children and young people with asthma&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2015</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>A randomised intervention trial will be used. Participants will be randomised to either an immediate (I-med) or a delayed (D-med) intervention. Randomisation will be restricted based on two factors including age and patient gender.&#xD;
Both subject groups will receive standard-of-practice asthma education and management in the Asthma Clinic prior to study enrolment. Participants allocated to the I-med group will take part in the mobile technology DOT intervention for the first 6 weeks. Outcomes will be evaluated at the start (week 0) and end of the 6 week intervention period and during clinic visits at weeks 12 and 18 for follow-up. Those participants allocated to the D-med group will have the DOT intervention started after a 6 week &quot;intervention-free&quot; interval with usual Asthma Clinic care.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinician assessment of asthma control</measure>
    <time_frame>Recruitment - 18 weeks post intervention</time_frame>
    <description>Clinician assessment of degree of disease control recorded at baseline and during follow-up period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinician assessment of asthma severity</measure>
    <time_frame>Recruitment - 18 weeks post intervention</time_frame>
    <description>Clinician assessment of asthma severity recorded at baseline and during follow-up period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Asthma medication profile</measure>
    <time_frame>Recruitment - 18 weeks post intervention</time_frame>
    <description>Current medication profile and any changes made</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of asthma attacks</measure>
    <time_frame>Recruitment - 18 weeks post intervention</time_frame>
    <description>Number of attacks taken during follow-up period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Oral corticosteroids courses</measure>
    <time_frame>Recruitment - 18 weeks post intervention</time_frame>
    <description>Numbers of courses of oral corticosteroids taken during follow-up period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Attendances at Emergency Department (ED)</measure>
    <time_frame>Recruitment - 18 weeks post intervention</time_frame>
    <description>Numbers of attendances to ED during follow-up period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Spirometry measurement; Fraction of exhaled nitric oxide (FeNO)</measure>
    <time_frame>Recruitment - 18 weeks post intervention</time_frame>
    <description>Measurements taken at each intervention</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Self reported Medication Adherence Report Scale (MARS)</measure>
    <time_frame>Recruitment - 18 weeks post intervention</time_frame>
    <description>Parent/guardian completes MARS if child younger than 9yrs old</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Interview-administered Paediatric Asthma Quality of Life Questionnaire (PAQOLQ) or Paediatric Asthma Caregiver Quality of Life Questionnaire (PACQOLQ)</measure>
    <time_frame>Recruitment - 18 weeks post intervention</time_frame>
    <description>PAQOLQ if 9 years or older; PACQOLQ if under 9</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Interview-administered Asthma Control Test (ACT) or Childhood Asthma Control (C-ACT)</measure>
    <time_frame>Recruitment - 18 weeks post intervention</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>ICS inhaler technique</measure>
    <time_frame>Recruitment - 18 weeks post intervention</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Asthma in Children</condition>
  <arm_group>
    <arm_group_label>Immediate (I-med)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants allocated to the I-med group will take part in the mobile DOT intervention for the first 6 weeks. Outcomes will be evaluated at the start (week 0) and end of the 6 week intervention period and during clinic visits at weeks 12 and 18 for follow-up</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Delayed (D-med)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Those participants allocated to the D-med group will have the DOT intervention started after a 6 week &quot;intervention-free&quot; interval with usual Asthma Clinic care. Outcomes in the D-med group will be assessed at baseline (week 0), week 6 (intervention start), week 12 (end of intervention), and at weeks 18 and 24 for follow-up.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Mobile Direct Observation of Therapy (MDOT)</intervention_name>
    <description>Patients who are enrolled in the study will be randomised into two groups (I-med or D-med) to receive Mobile Direct Observation of Therapy (MDOT). Participants or parents/guardians of participants will be asked to capture a DOT video twice daily (morning and evening) on their mobile devices of ICS use by the patient. In the I-med group, participants will be asked to upload daily video recordings via the internet to a repository for a 6 week period at the start of the study. Participants in the D-med group will be free from DOT for the first 6 weeks of the study and will be asked to carry out their usual therapy management. After that, DOT as described above will be applied for the next 6 weeks.</description>
    <arm_group_label>Delayed (D-med)</arm_group_label>
    <arm_group_label>Immediate (I-med)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Children and young people aged from 2-16 years with apparent partially controlled or&#xD;
             uncontrolled DTA. The children will have asthma symptoms despite being prescribed ICS&#xD;
             (&gt; 400 mcg/day for children &lt; 5 years, 800 mcg/day for children &gt; 5 years) and a&#xD;
             second line therapy such as a LABA, LTRA, or theophylline (Nagakumar and Thomas,&#xD;
             2013).&#xD;
&#xD;
          2. One member of the household has access to a smartphone, tablet or other mobile device&#xD;
             that is capable submitting a video image to an internet accessible repository. This&#xD;
             person must have access to the device for the entire period of the intervention phase&#xD;
             (6 weeks) of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Children whose asthma symptoms are controlled.&#xD;
&#xD;
          2. Children and/or parents without access or unwilling to allow use of a suitable mobile&#xD;
             device for the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mike Shields, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Queen's University, Belfast</affiliation>
  </overall_official>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>August 14, 2017</last_update_submitted>
  <last_update_submitted_qc>August 14, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Queen's University, Belfast</investigator_affiliation>
    <investigator_full_name>James McElnay</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Inhaler assessment</keyword>
  <keyword>Direct observation of therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03248895
org study id: QUB B14/39
nct id: NCT03248895
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Mobilte Direct Observation Therapy (MDOT) is a technology has the potential to be a cost
      effective approach to direct observation of therapy administration, the latter being one of
      the most accurate methods of evaluating adherence. Use to date, as confirmed by the rapid
      systematic review, has been limited mainly to TB and sickle cell disease and there have been
      no published reports on the use of MDOT to monitor inhaled therapy. Due to the increasing
      incidence of childhood asthma worldwide, there is a need for new innovative approaches to
      support children and their parents with asthma management, especially since national and
      international guidelines have advised healthcare providers to periodically assess inhaler use
      as part of asthma management.
Asthma is the most common chronic disease in childhood. It is defined as a chronic
      inflammatory disorder of the airways in which many cells and cellular elements promote airway
      obstruction and hyper-responsiveness (GINA, 2012). According to the World Health Organization
      (WHO, 2014), asthma is estimated to affect approximately 253 million people worldwide.
      Despite advances in biological and pathological research, the prevalence of asthma in
      children has significantly increased over the past decade (Massingham et al., 2014).

      Moreover, the economic burden of asthma is increasing. In the US, it is estimated that the
      yearly cost of asthma in children and adults is around $1.48 billion (Price et al., 2013). A
      decade ago, the total annual asthma expenditure in the UK was determined to be £752.6 million
      with 8% of costs associated with hospital admission, 13% attributable to general practitioner
      consultations and 79% due to prescription costs (Gupta et al., 2004).

      The British Thoracic Society (BTS/SIGN, 2012) and Global Initiative for Asthma (GINA, 2012)
      guidelines provide the background definitions for three broad categories of asthma control.
      They include controlled (no nocturnal wakening, infrequent short acting beta 2 agonist (SABA)
      use e.g. < 2 puffs/week, occasional mild symptoms e.g. with exercise and no exacerbations in
      last 3 months), partially controlled (nocturnal wakening < 3 nights/week, SABA use e.g. < 4
      puffs/day, mild limitation in exercise tolerance due to asthma, and 2 or fewer mild
      exacerbations in the previous 3 months) or uncontrolled (nocturnal wakening 4-7 nights/week,
      SABA use e.g. > 5 puffs/day, limitation in exercise tolerance due to asthma and or
      significant asthma exacerbations requiring oral steroid, Emergency Department attendance or
      hospital admission in the previous 3 months). Children who present with partially controlled
      or uncontrolled asthma can be divided into difficult to treat asthma (DTA) and true severe
      therapy resistant asthma (STRA) after careful investigation (Hedlin et al., 2012). DTA occurs
      when asthma is uncontrolled but the impact of concomitant disorders and the basics of asthma
      care (inhaler technique and adherence) have not been adequately resolved.

      Many children with asthma can achieve symptom and disease control by using inhaled
      corticosteroid (ICS) therapy combined with a long acting B2 agonist (LABA) and/or a
      leukotriene receptor antagonist (LTRA) (International ERS/ATS guideline, 2014). However, a
      number of children with asthma experience frequent symptoms despite being prescribed high
      dose ICS (Nagakumar and Thomas, 2013; Hedlin et al., 2014).

      Drug delivery by inhalation of various medications is the most common treatment approach for
      asthma in all patient populations. Inhalation therapy offers rapid onset and improved
      efficacy compared to systemic drug delivery (Bisgaard, 1997). While ICS therapy is well
      accepted as the foundation of optimal therapy for most asthma patients, efficacy of the
      therapy depends on drug being delivered correctly into the lungs and taken on a regular basis
      as a preventer therapy (Machira et al., 2011).

      It has been suggested that good inhaler technique is an essential aspect of optimal asthma
      management. Education on inhaler technique has been shown to improve self- management and
      adherence to asthma therapy. Evidence is available demonstrating that asthma outcomes
      correlate with proper inhaler technique and that periodically assessing this treatment aspect
      has a positive impact on asthma control (Bryant et al., 2013; AL-Jahdali et al., 2013).
      Moreover, early and repeated tailored education and follow-up assessment can result in
      sustained good inhaler technique (Klot et al., 2011). However, many asthma clinics treating
      children are unable to effectively evaluate these important patient treatment variables.

      Adherence to pharmacotherapy is also considered an important basic tenet of asthma
      management. Adherence can simply be defined as the extent to which a patient follows the
      instructions of the prescriber (Osterberg and Blaschke, 2005). While inhaled therapy
      technique is an essential feature of asthma pharmacotherapy, some patients with good
      technique may have poor inhaler adherence. Available data suggest the average medication
      adherence to ICS in children is only approximately 50% (Fish et al., 2001; Osterberg and
      Blaschke, 2005).

      It is known that adherence to ICS in children is a complicated matter influenced by diverse
      issues including socioeconomic factors, parents' beliefs about asthma and asthma medications,
      and poor patient-doctor communication (Osterberg and Blaschke, 2005; Armstrong et al., 2014).
      In addition, parent/guardian health issues such as depression or substance abuse may
      negatively affect adherence in young children as a result of the parent/guardian's failure to
      remind, or assist the child in the use of their medication (Brackis-Cott et al., 2003).
      Non-adherence to medication can have various negative patient consequences such as more
      frequent clinic visits, disease exacerbations, hospital admissions, and increased cost of
      care (AL-Jahdali et al., 2013). Indeed, a recent review of childhood asthma deaths in SE
      England showed that medication non-adherence was a contributing factor in more than 50% of
      cases, including patients with milder disease (Anagnostou et al.,2012) Despite being an area
      of active research, many interventions such as isolated educational efforts are ineffective
      in improving adherence (Drotar and Bonner, 2009). In a qualitative study in the primary care
      setting, asthmatic children of parents who expressed medication beliefs of a high concern-low
      need pattern had poor outcomes. Researchers subsequently showed that these beliefs could be
      modified by repeated tailored education and close follow-up, to result in high medication
      adherence. They concluded that "it is not the education per se, but rather the intensity,
      quality and frequency of education about self-management and follow-up that help to improve
      adherence" (Klot et al., 2011). A multicentre clinical trial in the USA was designed to
      determine what medication was best to add in children with severe asthma already taking ICS
      and LABA. However,the trial was cut short due to an inability to recruit an adequate number
      of children. Patient improvement while under close supervision during the run in period was
      the main reason for the lack of patient recruitment. (Strunk et al., 2008) Different methods
      used to assess patient adherence to prescribed therapy have resulted in variable outcomes.
      Adherence can be measured by collecting data from patients or their parent/guardians,
      pharmacy dispensing records, electronic monitoring devices, or patient observation (Osterberg
      and Blaschke, 2005). Since the approaches have produced variable results, it can be concluded
      that presently there is no preferred method to effectively measure or improve medication
      adherence in asthma (Sumino and Cabana, 2013).

      Direct observation therapy (DOT) is recommended by the WHO to promote adherence in the
      management of tuberculosis (TB) and this approach was adopted in 187 countries by 2005 (WHO,
      2010). DOT allows assessment of correctly taking and completing therapy, but also can be
      valuable to promote adherence to medication use. DOT involves a healthcare professional
      observing patients taking their medication at home or in the clinic (Dosumu, 2001; Otu,
      2013). The DOT approach to TB management has been utilised successfully in different
      countries as this approach has been shown to enhance medication adherence, improve outcomes
      including microbiologic success, and decrease acquired drug resistance to therapy (Favorov et
      al., 2012; Walley et al., 2001; Pasipanodya and Gumbo, 2013).

      While data exist to show that observation of inhaler technique can positively affect asthma
      management, there are no published studies using a DOT approach as a means to improve
      medication adherence. However, it has been suggested that using DOT with nurses directly
      observing asthmatic children's inhaler technique and adherence, for example at school or
      home, would be very resource intensive and likely not feasible for continued use (Otu, 2013).

      In recent years, there has been widespread use of mobile smartphone and computer devices
      within the healthcare environment. A recent survey of teenagers and caregivers in urban
      paediatric practices showed that 84% of respondents were smartphone owners, a finding that
      was independent of age group, gender, ethnicity, and socioeconomic status (Singh et al.,
      2014). DeMaio et al. (2001) conducted a pilot study that compared videophone telemedicine
      (V-DOT) to standard DOT (S-DOT) in the treatment of TB. In the videophone group, patients
      took videos of medication administration that were provided to clinicians involved in their
      management. The adherence rate was 95% for V-DOT compared to 97.5 % for S-DOT, but personnel
      time was decreased by 288 hours with V-DOT in only 6 patients. Similarly, a telehealth
      videophone home monitoring approach to TB was shown to enhance treatment compliance and use
      less clinic resources in a larger study by Wade et al. (2012).

      More recently, Creary et al. (2014) developed a novel mobile DOT approach utilising
      smartphone and computer devices that resulted in a median monthly observed adherence of 93.3%
      over the 6 month trial in children with sickle cell disease. Finally, specific to asthma
      patients, Vasbinder et al., (2013) has developed a study to access the effectiveness of using
      mobile phone text-messages to remind and encourage non-adherent patients to take their
      medication and thereby improve control of their disease; results of the study are not yet
      available. Limited available evidence, therefore, suggests that communication technology
      could be utilised to achieve therapeutic goals of correct administration technique and
      improved adherence to therapy in asthma patients while limiting resource utilisation.

      The principal aim of this study is to evaluate the feasibility and clinical impact of a
      mobile DOT approach (via video capture in the patient's home) on the administration technique
      for, and adherence to, ICS in children with partially controlled or uncontrolled asthma. A
      secondary aim is to determine factors that influence adherence to ICS in children with
      asthma.

      The specific objectives are to:

        1. Investigate the feasibility, practicality, and persistence of a mobile DOT technology
           approach in the home setting to assist with disease management of children and young
           people with partially controlled or uncontrolled asthma.

        2. Assess inhaler technique and adherence to ICS therapy by use of DOT videos,
           parent/guardian and child self-report questionnaires (Medication Adherence Report Scale
           (MARS)), pharmacy records and patient's general practitioner (GP) records.

        3. Evaluate the impact of the DOT intervention on asthma clinical outcomes including
           physician assessment of disease control, medication changes, asthma control tests,
           health-related quality of life and pulmonary function studies in participating children.

        4. Identify parental/guardian and patient factors that influence adherence to ICS in
           participating children and young people with asthma
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A randomised intervention trial will be used. Participants will be randomised to either an immediate (I-med) or a delayed (D-med) intervention. Randomisation will be restricted based on two factors including age and patient gender.
Both subject groups will receive standard-of-practice asthma education and management in the Asthma Clinic prior to study enrolment. Participants allocated to the I-med group will take part in the mobile technology DOT intervention for the first 6 weeks. Outcomes will be evaluated at the start (week 0) and end of the 6 week intervention period and during clinic visits at weeks 12 and 18 for follow-up. Those participants allocated to the D-med group will have the DOT intervention started after a 6 week "intervention-free" interval with usual Asthma Clinic care.
primary purpose: Health Services Research
masking: None (Open Label)
measure: Clinician assessment of asthma control
time frame: Recruitment - 18 weeks post intervention
description: Clinician assessment of degree of disease control recorded at baseline and during follow-up period
measure: Clinician assessment of asthma severity
time frame: Recruitment - 18 weeks post intervention
description: Clinician assessment of asthma severity recorded at baseline and during follow-up period
measure: Asthma medication profile
time frame: Recruitment - 18 weeks post intervention
description: Current medication profile and any changes made
measure: Number of asthma attacks
time frame: Recruitment - 18 weeks post intervention
description: Number of attacks taken during follow-up period
measure: Oral corticosteroids courses
time frame: Recruitment - 18 weeks post intervention
description: Numbers of courses of oral corticosteroids taken during follow-up period
measure: Attendances at Emergency Department (ED)
time frame: Recruitment - 18 weeks post intervention
description: Numbers of attendances to ED during follow-up period
measure: Spirometry measurement; Fraction of exhaled nitric oxide (FeNO)
time frame: Recruitment - 18 weeks post intervention
description: Measurements taken at each intervention
measure: Self reported Medication Adherence Report Scale (MARS)
time frame: Recruitment - 18 weeks post intervention
description: Parent/guardian completes MARS if child younger than 9yrs old
measure: Interview-administered Paediatric Asthma Quality of Life Questionnaire (PAQOLQ) or Paediatric Asthma Caregiver Quality of Life Questionnaire (PACQOLQ)
time frame: Recruitment - 18 weeks post intervention
description: PAQOLQ if 9 years or older; PACQOLQ if under 9
measure: Interview-administered Asthma Control Test (ACT) or Childhood Asthma Control (C-ACT)
time frame: Recruitment - 18 weeks post intervention
measure: ICS inhaler technique
time frame: Recruitment - 18 weeks post intervention
arm group label: Immediate (I-med)
arm group type: Active Comparator
description: Participants allocated to the I-med group will take part in the mobile DOT intervention for the first 6 weeks. Outcomes will be evaluated at the start (week 0) and end of the 6 week intervention period and during clinic visits at weeks 12 and 18 for follow-up
arm group label: Delayed (D-med)
arm group type: Active Comparator
description: Those participants allocated to the D-med group will have the DOT intervention started after a 6 week "intervention-free" interval with usual Asthma Clinic care. Outcomes in the D-med group will be assessed at baseline (week 0), week 6 (intervention start), week 12 (end of intervention), and at weeks 18 and 24 for follow-up.
intervention type: Device
intervention name: Mobile Direct Observation of Therapy (MDOT)
description: Patients who are enrolled in the study will be randomised into two groups (I-med or D-med) to receive Mobile Direct Observation of Therapy (MDOT). Participants or parents/guardians of participants will be asked to capture a DOT video twice daily (morning and evening) on their mobile devices of ICS use by the patient. In the I-med group, participants will be asked to upload daily video recordings via the internet to a repository for a 6 week period at the start of the study. Participants in the D-med group will be free from DOT for the first 6 weeks of the study and will be asked to carry out their usual therapy management. After that, DOT as described above will be applied for the next 6 weeks.
arm group label: Delayed (D-med)
arm group label: Immediate (I-med)
criteria: 
gender: All
minimum age: 2 Years
maximum age: 16 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mike Shields, PhD
role: Principal Investigator
affiliation: Queen's University, Belfast
responsible party type: Principal Investigator
investigator affiliation: Queen's University, Belfast
investigator full name: James McElnay
investigator title: Professor
mesh term: Asthma