<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/NCT04458766</url>
  </required_header>
  <id_info>
    <org_study_id>1K23HL145109-01A1</org_study_id>
    <nct_id>NCT04458766</nct_id>
  </id_info>
  <brief_title>The Use of Mobile Health Technology and Behavioral Economics to Encourage Adherence in Adolescents</brief_title>
  <official_title>The Use of Mobile Health Technology and Behavioral Economics to Encourage Adherence to Statins in Adolescents With Familial Hypercholesterolemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Wellth Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>MMAS-8 with permission from Dr Donald Morisky. as written below</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Boston Children's Hospital</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>
      Familial hypercholesterolemia (FH) affects over one million Americans and increases the risk&#xD;
      of cardiovascular disease (CVD) by as much as 20-fold. Although the use of statins can&#xD;
      substantially reduce this risk, adherence to statins in adults and adolescence is poor. In&#xD;
      adults, lower rates of adherence are associated with an increased rate of CVD events and&#xD;
      all-cause mortality, as well as an additional $44 billion annually in health care costs.&#xD;
      Novel interventions are needed to improve medication adherence in patients with FH, starting&#xD;
      in adolescents. An underused strategy to improve medication adherence incorporates the&#xD;
      principles of behavioral economics. Traditional economic theory suggests that providing an&#xD;
      incentive to perform a behavior will increase the frequency of that behavior. However, two&#xD;
      prominent theories in behavioral economics, Present Bias and Loss Aversion, suggest that not&#xD;
      all types of incentives are effective and that poorly structured incentives can actually be&#xD;
      negative enforcers. With novel mobile health technologies (mHealth), interventions based on&#xD;
      behavioral economics can now be studied on a larger scale. In this proposal, the&#xD;
      investigators will test the use of monetary incentives ($30 per 30 days) to improve&#xD;
      medication adherence in eligible subjects. The investigators will test the subject's&#xD;
      adherence prior to the use of incentives (using the Morisky Medication Adherence Scale and&#xD;
      the Wellth Mobile Application) and during the period of time the incentives are provided.&#xD;
      Lastly, the investigators will test the subject's adherence (using the Morisky Medication&#xD;
      Adherence Scale and Wellth App) during the 60 days following discontinuation of the&#xD;
      incentives to determine if any effect of the incentive persists after the incentive is&#xD;
      discontinued.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preventing cardiovascular disease (CVD) in children and adolescents depend partly on the&#xD;
      efficacy of the patients' self-management of their disease between clinic visits. One example&#xD;
      of a health behavior that is particularly important for patients with CVD is medication&#xD;
      adherence. Although the development of statins provides an opportunity to substantially&#xD;
      reduce this risk of CVD, adherence to statins in both adults and adolescents is frequently&#xD;
      inadequate. In recent study of youth prescribed a statin using claims data, nearly 75% of&#xD;
      adolescents have at least one 90-day period of nonadherence. In adults, statin nonadherence&#xD;
      is often as low as 50% and is associated with an increased risk for of CVD events and&#xD;
      all-cause mortality, as well as almost $44 billion annually in additional health care costs.&#xD;
      Unfortunately, successful interventions to improve statin adherence in adults are rare and&#xD;
      there are no formally tested interventions to improve statin adherence in adolescents.&#xD;
&#xD;
      It is critical novel interventions are developed that address medication adherence in&#xD;
      adolescents with chronic diseases that increase the risk of CVD. Studies in adolescents with&#xD;
      other diseases demonstrate that they appear to be particularly vulnerable to nonadherence&#xD;
      across a wide-variety of conditions, including in adolescents with solid organ transplants&#xD;
      and diabetes mellitus. Unfortunately, previous studies using text messaging reminders to take&#xD;
      a medication or computerized action plans have not consistently shown positive results.&#xD;
      Therefore, the significance of this proposal is that I will pilot a novel mobile health&#xD;
      (mHealth) intervention that incorporates two theories in behavioral economics, Present Bias&#xD;
      and Loss Aversion, to develop a better understanding of barriers to medication adherence in&#xD;
      adolescents with cardiovascular risk factors.&#xD;
&#xD;
      Traditional economic theory suggests that providing individuals with incentives to complete&#xD;
      an action will lead to increased frequency of the occurrence of the desired action. However,&#xD;
      behavioral economics studies in adult populations suggest that not all incentive structures&#xD;
      are effective and that some incentives may act like negative enforcers. Studies suggest that&#xD;
      patients are biased towards the present and often discount future risks, which is termed&#xD;
      Present Bias. For instance, studies of Present Bias suggest that even small rewards, if&#xD;
      provided frequently and immediately after a participant completes a desired task can improve&#xD;
      adherence in adults. This strategy can be improved by using the principles of Loss Aversion,&#xD;
      which suggest that individuals place more value on money or objects that they have than on&#xD;
      new objects of the same value. Therefore, incentives framed as a loss can be more powerful&#xD;
      than if it is framed as a gain. Unfortunately, only a few studies in adolescents have&#xD;
      incorporated behavioral economics into interventions aimed at behavior change. One promising&#xD;
      study in youth with type 1 diabetes mellitus found behavioral economics approaches could&#xD;
      influence adherence to insulin regimens and glucose monitoring. Whereas diabetes mellitus is&#xD;
      symptomatic if not properly managed, statins typically are used as primary prevention in&#xD;
      asymptomatic patients with familial hypercholesterolemia (FH), which may require unique&#xD;
      incentive structures. Although monetary incentives have been used with varying degrees of&#xD;
      success in adults, it is unclear if these findings translate to adolescents. Adolescents may&#xD;
      discount future events more, have different attitudes towards health, and have less mature&#xD;
      cognitive function and capacities than adults. In addition, interventions that improve&#xD;
      medication adherence are often resource intensive, which decreases the likelihood of larger&#xD;
      scale implementation. Using an mHealth application may reduce costs by automating processes&#xD;
      previously requiring human time and resources. Further, an mHealth intervention may be more&#xD;
      successful as it uses a medium that is ubiquitous in adolescence. For instance, mobile&#xD;
      applications that use gamification have demonstrated that adolescents find these health&#xD;
      applications engaging and that they are interested in using mHealth in the management of&#xD;
      their disease across a diverse set of socioeconomic and cultural backgrounds. As many health&#xD;
      behaviors track into adulthood, establishing healthy behaviors early is crucial, which&#xD;
      requires using developmentally appropriate interventions to promote adherence and ultimately&#xD;
      minimize the risk of CVD.&#xD;
&#xD;
      APPROACH Determine the efficacy of a monetary incentive to improve medication adherence. Aim&#xD;
      1.1 The investigators will determine the baseline adherence level in adolescents with FH&#xD;
      prescribed a statin using the Morisky Medication Adherence Scale (MMAS).&#xD;
&#xD;
      Aim 1.2 The investigators will determine the efficacy of a monetary incentive on medication&#xD;
      adherence. Patients who are found to have low adherence according to the MMAS in Aim 1.1 will&#xD;
      be enrolled into an intervention using the Wellth® mobile health application (Wellth App).&#xD;
&#xD;
      Aim 1.3 Next, the investigators will determine adherence 60 days after the incentives have&#xD;
      been discontinued using the tracking features in the Wellth App and the MMAS.&#xD;
&#xD;
      Description of Wellth Application (Wellth App) The Wellth App has the following three&#xD;
      features/functions: 1) it reminds users to take the prescribed medication through&#xD;
      alerts/notifications on the smart phone; 2) it records medication adherence by determining&#xD;
      whether the user takes the prescribed medication in the allotted time frame through&#xD;
      photographic evidence termed a &quot;check in&quot;; and 3) it determines whether the predetermined&#xD;
      reward is delivered to the patient instantly. The first function reminds the patient with an&#xD;
      audible or haptic alert (i.e., vibration) using the phone's alert notification function.&#xD;
      These alerts are not delivered through an email or text messaging service, but rather are&#xD;
      similar to news alerts, alarms, or low battery notifications. The second function of the&#xD;
      Wellth app is to document whether a patient takes the prescribed medication within the&#xD;
      correct period of time. The Wellth App determines adherence by having the patient to take a&#xD;
      photograph of the correct dose of medication out of the bottle/container and in the patient's&#xD;
      hand using the Wellth app and smart phone's built-in camera. This will provide a time-stamped&#xD;
      and individually-linked document of adherence. For example, a valid photograph in the current&#xD;
      study would be a photograph of a statin tablet in the patient's hand during a calendar day&#xD;
      that starts at 00:00 and ends at 23:59. If no photograph is captured within this time period,&#xD;
      the subject is considered non-adherent. Taking more than one dose of the medication another&#xD;
      day does not &quot;make up&quot; for previous missed days, even if it is recommended by a health care&#xD;
      provider.&#xD;
&#xD;
      Participants will be able to download the app to their smartphone without any additional&#xD;
      software or encryption needed. In order to prevent patients from being excluded based on the&#xD;
      costs of the necessary hardware, the investigators will provide a smartphone and data plan&#xD;
      free of charge to patients based on an existing partnership if needed. Patients use the App&#xD;
      to receive reminders, make check-ins, check their reward balance, and view their adherence&#xD;
      history.&#xD;
&#xD;
      Description of the reward system:&#xD;
&#xD;
      In this proposal, subjects will receive money to incentivize adherence. Subjects will receive&#xD;
      a $30 credit at 30-day intervals, which can only be spent at the end of the 30-day period.&#xD;
      For each payout, the full $30 will be earned only if the individual submits all the required&#xD;
      photos of his/her medications each day through the Wellth app. For each missed check-in, the&#xD;
      subject loses $2 from the amount to be paid out at the end of the 30-day period. In this&#xD;
      study, there will be two consecutive 30-day periods in which the subject can earn rewards.&#xD;
      After this 60-day period, the subject will continue to use the Wellth App to document&#xD;
      adherence for 60 days, but will not receive any rewards during this time period. The final&#xD;
      60-day period is used to determine if the reward period has influence on medication adherence&#xD;
      after the incentive is stopped.&#xD;
&#xD;
      Adherence will be measured by two methods. The first will be through the Morisky Medication&#xD;
      Adherence Scale (MMAS) and the second will be using the proportion of prescribed pills taken.&#xD;
      The choice to measure adherence with two methods is because the investigators only want to&#xD;
      include patients who have poor adherence in the study. As self-reported adherence may be&#xD;
      inaccurate, the investigators will use the validated Morisky Medication Adherence Scale&#xD;
      (MMAS) to assess baseline adherence. However, during the study period, adherence will be&#xD;
      measured much more accurately through the use of the Wellth App. As the score of the MMAS&#xD;
      cannot be converted to the proportion of prescribed pills taken, the investors will simply&#xD;
      measure changes in MMAS score throughout the study as well as measure changes in the&#xD;
      proportion of prescribed days taken. The investigators provide power calculations for both&#xD;
      scenarios below. Participants will complete the MMAS at the screening visit, after the 60-day&#xD;
      intervention, and 60 days after the intervention ends. The investigators will measure&#xD;
      adherence using the Wellth app continuously once the subject has access to the Wellth app.&#xD;
      The adherence values used for analysis will be the proportion of pills prescribed in which&#xD;
      the subjects completes a &quot;checked in&quot; during the three following periods: a)&#xD;
      &quot;pre-intervention period&quot; of 14 days prior to the start of incentive period, b) the entirety&#xD;
      of the Incentive Period, and c) the final 30 days after the Post-Incentive period.&#xD;
      Sensitivity analysis will also compare adherence in the last 14 days of each period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2021</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a pre-post study design. The intervention group will have medication adherence measured prior to receiving incentives, medication adherence while receiving incentives, and medication adherence after discontinuation of the incentives.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>1.1: Baseline adherence level</measure>
    <time_frame>Day 0</time_frame>
    <description>Baseline adherence level to determine eligibility of subjects</description>
  </primary_outcome>
  <primary_outcome>
    <measure>1.2: Change in adherence with monetary incentives</measure>
    <time_frame>Days 14-74</time_frame>
    <description>Change in statin adherence in enrolled subjects following an intervention that includes access to the Wellth mobile phone application with reminders to take their medication, and will receive monetary incentives for taking medication as prescribed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>1.3: Change in adherence withOUT monetary incentives</measure>
    <time_frame>Days 75-134</time_frame>
    <description>Change in statin adherence in enrolled subjects following an intervention that includes access to the Wellth application with reminders to take their medication, but with no monetary incentives.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Familial Hypercholesterolemia</condition>
  <condition>Adherence, Medication</condition>
  <arm_group>
    <arm_group_label>Interventions</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects in this trial will receive the following interventions:&#xD;
Pre-Intervention (Days 0-14): Subjects given access to Wellth application reminders, no incentives provided. A virtual &quot;check in&quot; with the study team will occur at the end of the pre-intervention period (14 days).&#xD;
Intervention (Days 15-74): Subjects will use Wellth app for 60 days, with incentives provided at the 30- and 60-day mark. At the end of the intervention period (Day 60), the subject will attend a clinic visit with the medical provider and a fasting lipid panel and MMAS will also be collected at this time.&#xD;
Post-intervention (Days 74-134): Subjects will continue to use the Wellth app and receive reminders, but with no incentives provided, for 60 days. A clinic visit, fasting lipid profile, and MMAS will also be collected following the post-intervention period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Monetary incentives</intervention_name>
    <description>This intervention will assess the efficacy of subjects using the Wellth mobile phone application to provide reminders to take their statin medication, and receiving monetary incentives for taking their medication as prescribed.</description>
    <arm_group_label>Interventions</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of FH based on National Lipid Association (NLA) criteria and/or genetic&#xD;
             testing&#xD;
&#xD;
          2. Prescribed a statin&#xD;
&#xD;
          3. Be able to provide written, informed consent or have a parent/guardian provide&#xD;
             written, informed consent&#xD;
&#xD;
          4. Be able to use a mobile phone and application&#xD;
&#xD;
          5. Morisky Medication Adherence Scale score of ≤ 6&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of Homozygous FH&#xD;
&#xD;
          2. Residence in a long-term care facility where medications are administered&#xD;
&#xD;
          3. May become pregnant&#xD;
&#xD;
          4. History of adverse effect or allergy to a statin, or any ingredient in a statin&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jacob C Hartz, MD,MPH</last_name>
    <phone>617-355-0955</phone>
    <email>jacob.hartz@cardio.chboston.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sarah D de Ferranti, MD,MPH</last_name>
    <phone>617-355-0955</phone>
    <email>sarah.deferranti@cardio.chboston.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hannah Palfrey</last_name>
      <phone>617-355-0955</phone>
      <email>Hannah.palfrey@childrens.Harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Jacob Hartz, MD, MPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.sefap.it/servizi_lineeguida_200711/NICE_TA094guidance.pdf</url>
    <description>Ref 1: Statins for the prevention of cardiovascular events</description>
  </link>
  <link>
    <url>https://pdfs.semanticscholar.org/09f2/815f972db3a181802632df6c59651591c0e0.pdf</url>
    <description>Ref 30: Doing it now or later.</description>
  </link>
  <link>
    <url>https://www.ssoar.info/ssoar/bitstream/handle/document/28311/ssoar-jebo-2009-3-gachter_et_al-are_experimental_economists_prone_to.pdf?sequence=1</url>
    <description>Ref 31: Are experimental economists prone to framing effects? A natural field experiment.</description>
  </link>
  <link>
    <url>http://www.pewinternet.org/data-trend/mobile/cell-phone-and-smartphone-ownership-demographics.</url>
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  </link>
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    <url>https://jhu.pure.elsevier.com/en/publications/promoting-adherence-and-increasing-life-span-5</url>
    <description>Red 47: Promoting adherence and increasing life span</description>
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  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>January 10, 2023</last_update_submitted>
  <last_update_submitted_qc>January 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Boston Children's Hospital</investigator_affiliation>
    <investigator_full_name>Jacob Hartz</investigator_full_name>
    <investigator_title>Staff Cardiologist and Instructor of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>Adolescents</keyword>
  <keyword>Medication adherence</keyword>
  <keyword>Familial hypercholesterolemia</keyword>
  <keyword>Behavioral economics</keyword>
  <keyword>Mobile health technology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperlipoproteinemia Type II</mesh_term>
    <mesh_term>Hypercholesterolemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>MMAS-8 with permission from Dr Donald Morisky. as written below:</doc_type>
      <doc_url>http://www.moriskyscale.com</doc_url>
      <doc_comment>The MMAS-8 Scale, content, name, and trademarks are protected by US copyright and trademark laws. Permission for use of the scale and its coding is required. A license agreement is available from MMAR, LLC.</doc_comment>
    </study_doc>
  </study_docs>
  <!-- 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/NCT04458766
org study id: 1K23HL145109-01A1
nct id: NCT04458766
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Familial hypercholesterolemia (FH) affects over one million Americans and increases the risk
      of cardiovascular disease (CVD) by as much as 20-fold. Although the use of statins can
      substantially reduce this risk, adherence to statins in adults and adolescence is poor. In
      adults, lower rates of adherence are associated with an increased rate of CVD events and
      all-cause mortality, as well as an additional $44 billion annually in health care costs.
      Novel interventions are needed to improve medication adherence in patients with FH, starting
      in adolescents. An underused strategy to improve medication adherence incorporates the
      principles of behavioral economics. Traditional economic theory suggests that providing an
      incentive to perform a behavior will increase the frequency of that behavior. However, two
      prominent theories in behavioral economics, Present Bias and Loss Aversion, suggest that not
      all types of incentives are effective and that poorly structured incentives can actually be
      negative enforcers. With novel mobile health technologies (mHealth), interventions based on
      behavioral economics can now be studied on a larger scale. In this proposal, the
      investigators will test the use of monetary incentives ($30 per 30 days) to improve
      medication adherence in eligible subjects. The investigators will test the subject's
      adherence prior to the use of incentives (using the Morisky Medication Adherence Scale and
      the Wellth Mobile Application) and during the period of time the incentives are provided.
      Lastly, the investigators will test the subject's adherence (using the Morisky Medication
      Adherence Scale and Wellth App) during the 60 days following discontinuation of the
      incentives to determine if any effect of the incentive persists after the incentive is
      discontinued.
Preventing cardiovascular disease (CVD) in children and adolescents depend partly on the
      efficacy of the patients' self-management of their disease between clinic visits. One example
      of a health behavior that is particularly important for patients with CVD is medication
      adherence. Although the development of statins provides an opportunity to substantially
      reduce this risk of CVD, adherence to statins in both adults and adolescents is frequently
      inadequate. In recent study of youth prescribed a statin using claims data, nearly 75% of
      adolescents have at least one 90-day period of nonadherence. In adults, statin nonadherence
      is often as low as 50% and is associated with an increased risk for of CVD events and
      all-cause mortality, as well as almost $44 billion annually in additional health care costs.
      Unfortunately, successful interventions to improve statin adherence in adults are rare and
      there are no formally tested interventions to improve statin adherence in adolescents.

      It is critical novel interventions are developed that address medication adherence in
      adolescents with chronic diseases that increase the risk of CVD. Studies in adolescents with
      other diseases demonstrate that they appear to be particularly vulnerable to nonadherence
      across a wide-variety of conditions, including in adolescents with solid organ transplants
      and diabetes mellitus. Unfortunately, previous studies using text messaging reminders to take
      a medication or computerized action plans have not consistently shown positive results.
      Therefore, the significance of this proposal is that I will pilot a novel mobile health
      (mHealth) intervention that incorporates two theories in behavioral economics, Present Bias
      and Loss Aversion, to develop a better understanding of barriers to medication adherence in
      adolescents with cardiovascular risk factors.

      Traditional economic theory suggests that providing individuals with incentives to complete
      an action will lead to increased frequency of the occurrence of the desired action. However,
      behavioral economics studies in adult populations suggest that not all incentive structures
      are effective and that some incentives may act like negative enforcers. Studies suggest that
      patients are biased towards the present and often discount future risks, which is termed
      Present Bias. For instance, studies of Present Bias suggest that even small rewards, if
      provided frequently and immediately after a participant completes a desired task can improve
      adherence in adults. This strategy can be improved by using the principles of Loss Aversion,
      which suggest that individuals place more value on money or objects that they have than on
      new objects of the same value. Therefore, incentives framed as a loss can be more powerful
      than if it is framed as a gain. Unfortunately, only a few studies in adolescents have
      incorporated behavioral economics into interventions aimed at behavior change. One promising
      study in youth with type 1 diabetes mellitus found behavioral economics approaches could
      influence adherence to insulin regimens and glucose monitoring. Whereas diabetes mellitus is
      symptomatic if not properly managed, statins typically are used as primary prevention in
      asymptomatic patients with familial hypercholesterolemia (FH), which may require unique
      incentive structures. Although monetary incentives have been used with varying degrees of
      success in adults, it is unclear if these findings translate to adolescents. Adolescents may
      discount future events more, have different attitudes towards health, and have less mature
      cognitive function and capacities than adults. In addition, interventions that improve
      medication adherence are often resource intensive, which decreases the likelihood of larger
      scale implementation. Using an mHealth application may reduce costs by automating processes
      previously requiring human time and resources. Further, an mHealth intervention may be more
      successful as it uses a medium that is ubiquitous in adolescence. For instance, mobile
      applications that use gamification have demonstrated that adolescents find these health
      applications engaging and that they are interested in using mHealth in the management of
      their disease across a diverse set of socioeconomic and cultural backgrounds. As many health
      behaviors track into adulthood, establishing healthy behaviors early is crucial, which
      requires using developmentally appropriate interventions to promote adherence and ultimately
      minimize the risk of CVD.

      APPROACH Determine the efficacy of a monetary incentive to improve medication adherence. Aim
      1.1 The investigators will determine the baseline adherence level in adolescents with FH
      prescribed a statin using the Morisky Medication Adherence Scale (MMAS).

      Aim 1.2 The investigators will determine the efficacy of a monetary incentive on medication
      adherence. Patients who are found to have low adherence according to the MMAS in Aim 1.1 will
      be enrolled into an intervention using the Wellth® mobile health application (Wellth App).

      Aim 1.3 Next, the investigators will determine adherence 60 days after the incentives have
      been discontinued using the tracking features in the Wellth App and the MMAS.

      Description of Wellth Application (Wellth App) The Wellth App has the following three
      features/functions: 1) it reminds users to take the prescribed medication through
      alerts/notifications on the smart phone; 2) it records medication adherence by determining
      whether the user takes the prescribed medication in the allotted time frame through
      photographic evidence termed a "check in"; and 3) it determines whether the predetermined
      reward is delivered to the patient instantly. The first function reminds the patient with an
      audible or haptic alert (i.e., vibration) using the phone's alert notification function.
      These alerts are not delivered through an email or text messaging service, but rather are
      similar to news alerts, alarms, or low battery notifications. The second function of the
      Wellth app is to document whether a patient takes the prescribed medication within the
      correct period of time. The Wellth App determines adherence by having the patient to take a
      photograph of the correct dose of medication out of the bottle/container and in the patient's
      hand using the Wellth app and smart phone's built-in camera. This will provide a time-stamped
      and individually-linked document of adherence. For example, a valid photograph in the current
      study would be a photograph of a statin tablet in the patient's hand during a calendar day
      that starts at 00:00 and ends at 23:59. If no photograph is captured within this time period,
      the subject is considered non-adherent. Taking more than one dose of the medication another
      day does not "make up" for previous missed days, even if it is recommended by a health care
      provider.

      Participants will be able to download the app to their smartphone without any additional
      software or encryption needed. In order to prevent patients from being excluded based on the
      costs of the necessary hardware, the investigators will provide a smartphone and data plan
      free of charge to patients based on an existing partnership if needed. Patients use the App
      to receive reminders, make check-ins, check their reward balance, and view their adherence
      history.

      Description of the reward system:

      In this proposal, subjects will receive money to incentivize adherence. Subjects will receive
      a $30 credit at 30-day intervals, which can only be spent at the end of the 30-day period.
      For each payout, the full $30 will be earned only if the individual submits all the required
      photos of his/her medications each day through the Wellth app. For each missed check-in, the
      subject loses $2 from the amount to be paid out at the end of the 30-day period. In this
      study, there will be two consecutive 30-day periods in which the subject can earn rewards.
      After this 60-day period, the subject will continue to use the Wellth App to document
      adherence for 60 days, but will not receive any rewards during this time period. The final
      60-day period is used to determine if the reward period has influence on medication adherence
      after the incentive is stopped.

      Adherence will be measured by two methods. The first will be through the Morisky Medication
      Adherence Scale (MMAS) and the second will be using the proportion of prescribed pills taken.
      The choice to measure adherence with two methods is because the investigators only want to
      include patients who have poor adherence in the study. As self-reported adherence may be
      inaccurate, the investigators will use the validated Morisky Medication Adherence Scale
      (MMAS) to assess baseline adherence. However, during the study period, adherence will be
      measured much more accurately through the use of the Wellth App. As the score of the MMAS
      cannot be converted to the proportion of prescribed pills taken, the investors will simply
      measure changes in MMAS score throughout the study as well as measure changes in the
      proportion of prescribed days taken. The investigators provide power calculations for both
      scenarios below. Participants will complete the MMAS at the screening visit, after the 60-day
      intervention, and 60 days after the intervention ends. The investigators will measure
      adherence using the Wellth app continuously once the subject has access to the Wellth app.
      The adherence values used for analysis will be the proportion of pills prescribed in which
      the subjects completes a "checked in" during the three following periods: a)
      "pre-intervention period" of 14 days prior to the start of incentive period, b) the entirety
      of the Incentive Period, and c) the final 30 days after the Post-Incentive period.
      Sensitivity analysis will also compare adherence in the last 14 days of each period.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a pre-post study design. The intervention group will have medication adherence measured prior to receiving incentives, medication adherence while receiving incentives, and medication adherence after discontinuation of the incentives.
primary purpose: Treatment
masking: None (Open Label)
measure: 1.1: Baseline adherence level
time frame: Day 0
description: Baseline adherence level to determine eligibility of subjects
measure: 1.2: Change in adherence with monetary incentives
time frame: Days 14-74
description: Change in statin adherence in enrolled subjects following an intervention that includes access to the Wellth mobile phone application with reminders to take their medication, and will receive monetary incentives for taking medication as prescribed.
measure: 1.3: Change in adherence withOUT monetary incentives
time frame: Days 75-134
description: Change in statin adherence in enrolled subjects following an intervention that includes access to the Wellth application with reminders to take their medication, but with no monetary incentives.
arm group label: Interventions
arm group type: Experimental
description: All subjects in this trial will receive the following interventions:
Pre-Intervention (Days 0-14): Subjects given access to Wellth application reminders, no incentives provided. A virtual "check in" with the study team will occur at the end of the pre-intervention period (14 days).
Intervention (Days 15-74): Subjects will use Wellth app for 60 days, with incentives provided at the 30- and 60-day mark. At the end of the intervention period (Day 60), the subject will attend a clinic visit with the medical provider and a fasting lipid panel and MMAS will also be collected at this time.
Post-intervention (Days 74-134): Subjects will continue to use the Wellth app and receive reminders, but with no incentives provided, for 60 days. A clinic visit, fasting lipid profile, and MMAS will also be collected following the post-intervention period.
intervention type: Behavioral
intervention name: Monetary incentives
description: This intervention will assess the efficacy of subjects using the Wellth mobile phone application to provide reminders to take their statin medication, and receiving monetary incentives for taking their medication as prescribed.
arm group label: Interventions
criteria: 
gender: All
minimum age: 12 Years
maximum age: 21 Years
healthy volunteers: No
last name: Jacob C Hartz, MD,MPH
phone: 617-355-0955
email: jacob.hartz@cardio.chboston.org
last name: Sarah D de Ferranti, MD,MPH
phone: 617-355-0955
email: sarah.deferranti@cardio.chboston.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.sefap.it/servizi_lineeguida_200711/NICE_TA094guidance.pdf
description: Ref 1: Statins for the prevention of cardiovascular events
url: https://pdfs.semanticscholar.org/09f2/815f972db3a181802632df6c59651591c0e0.pdf
description: Ref 30: Doing it now or later.
url: https://www.ssoar.info/ssoar/bitstream/handle/document/28311/ssoar-jebo-2009-3-gachter_et_al-are_experimental_economists_prone_to.pdf?sequence=1
description: Ref 31: Are experimental economists prone to framing effects? A natural field experiment.
url: http://www.pewinternet.org/data-trend/mobile/cell-phone-and-smartphone-ownership-demographics.
description: Ref 41: Cell phone and smartphone ownership demographics.
url: https://jhu.pure.elsevier.com/en/publications/promoting-adherence-and-increasing-life-span-5
description: Red 47: Promoting adherence and increasing life span
citation: 1. National Institute for Health and Clinical Excellence. Statins for the prevention of cardiovascular events. Technology Appraisal. London: National Institute for Health and Clinical Excellence, 2006.
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responsible party type: Principal Investigator
investigator affiliation: Boston Children's Hospital
investigator full name: Jacob Hartz
investigator title: Staff Cardiologist and Instructor of Pediatrics
mesh term: Hyperlipoproteinemia Type II
mesh term: Hypercholesterolemia
sharing ipd: No
study doc: 