<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/NCT03253822</url>
  </required_header>
  <id_info>
    <org_study_id>2012-58-006--1-16-02-94-16</org_study_id>
    <nct_id>NCT03253822</nct_id>
  </id_info>
  <brief_title>The Effect of a Colorectal Cancer Screening Decision Aid Tailored to Lower Educational Attainment Citizens</brief_title>
  <acronym>LEAD</acronym>
  <official_title>The Effect of a Colorectal Cancer Screening Decision Aid Tailored for People With Lower Educational Attainment in the Central Denmark Region on Colorectal Cancer Knowledge and Colorectal Cancer Screening Attitude and Participation Rate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</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>
      The aim of the trial is to test the effect of a web-based decision aid (DA) on colorectal&#xD;
      cancer (CRC) knowledge, decisional conflict, participation rate, and informed choice&#xD;
      (evaluated based on knowledge, attitudes and actual participation).&#xD;
&#xD;
      The study includes three study arms. Citizens to be recruited are identified from the Danish&#xD;
      Civil Registration System based on residence (Central Denmark Region), age (50-74 years old),&#xD;
      and month of birth. A random sample of 15,000 citizens born in December (invited for CRC&#xD;
      screening through October/November/December 2017) (study arm 1+2) and 5,000 citizens born in&#xD;
      October (invited for CRC screening in January/February 2017) (study arm 3) is identified.&#xD;
&#xD;
      Citizens in study arm 1+2 will receive a baseline questionnaire assessing knowledge,&#xD;
      attitudes, worry, and health literacy. Non respondents will receive one reminder after two&#xD;
      weeks and after four weeks non-respondents will receive a phone call, offering them to fill&#xD;
      out the questionnaire via the phone. Baseline questionnaire respondents are included in the&#xD;
      study, and will be randomized into two study arms (intervention group and control group).&#xD;
&#xD;
      Citizens in the intervention group will be identified in the screening IT system. Date of&#xD;
      screening invitation and screening reminder (citizens who do not return a stool sample within&#xD;
      45 days of the screening invitation) is retrieved. Citizens receiving a screening reminder&#xD;
      will receive a link for the DA. Follow-up questionnaire will be sent to all included citizens&#xD;
      in study-arm 1+2 three months after the last screening invitation has been sent out. Citizens&#xD;
      have six weeks to respond to the questionnaire.&#xD;
&#xD;
      Study arm 3 is a historic cohort. The citizens receive only one questionnaire at the same&#xD;
      time as the baseline questionnaires are sent out to the intervention and control groups. The&#xD;
      citizens are included if they respond to the questionnaire within six weeks. Questionnaire&#xD;
      reminders are sent out at two and four weeks.&#xD;
&#xD;
      Data on screening invitation date, screening reminder date, returning a stool sample and&#xD;
      result will be retrieved from the screening IT system for all included citizens (Study arm&#xD;
      1-3). Lastly, data from Statistics Denmark (on socio-demographic and socio-economic factors)&#xD;
      will be included.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study setting The Danish national colorectal cancer (CRC) screening programme was implemented&#xD;
      in Denmark in March 2014. All citizens aged 50-74 years are invited to take up CRC screening&#xD;
      biennially, however, the first prevalence round is carried out during a four year period&#xD;
      (2014-2017). During the this period, citizens are invited according to month of birth, except&#xD;
      citizens aged 49 who are invited just before they turn 50 and citizens turning 75 who are&#xD;
      invited prior to their 75th birthday, if they were not invited earlier in the program.&#xD;
&#xD;
      Politically and organisationally the CRC screening programme is nationally directed, but the&#xD;
      administrative responsibility is placed within the five regions in Denmark. The Department of&#xD;
      Public Health Programmes is responsible for the administration of the CRC screening programme&#xD;
      in the Central Denmark Region (CDR).&#xD;
&#xD;
      The CDR has 1.3 million citizens (23% of the total population) of which roughly 390 000&#xD;
      citizens are 50-74 years of age. The citizens receive an invitation, containing a screening&#xD;
      kit. The screening test (collection of a stool sample) is performed in the citizen's own&#xD;
      home. The stool sample is sent to the clinical biochemical department at the hospital. If the&#xD;
      citizens do not return a stool sample within 45 days after receiving the invitation, a&#xD;
      screening reminder is received. Citizens, who still do not return a stool sample, are&#xD;
      automatically referred to the next screening round, and will receive another invitation two&#xD;
      years later. Citizens with a negative test are automatically referred to the next screening&#xD;
      round. Citizens with a positive test are invited to have a colonoscopy.&#xD;
&#xD;
      Since 2010, national digitisation has occurred in Denmark. Hence, communication to and from&#xD;
      Danish authorities occur via digital mail, in the public email platform E-Boks. Danish&#xD;
      residents are obliged to order a digital signature (NemID) which is used as a shared log-in&#xD;
      for E-boks, public and private online self-services, and online banking. Only disabled&#xD;
      citizens (e.g. physical or cognitive impairment) or citizens unable to satisfactorily&#xD;
      identify themselves (e.g. migrants with no permanent resident permit) can be exempted from&#xD;
      ordering a NemID. As of May 2016 more than 5 million Danish citizens (87.5% of the entire&#xD;
      population including children) have access to E-boks. Exemption from digital communication&#xD;
      has been granted to 9.8% of Danish Residents aged 45-74 years.&#xD;
&#xD;
      All letters in the CRC screening programme are sent by digital mail, except from invitation&#xD;
      letters, which contains a screening kit and are sent by conventional mail. Citizens exempt&#xD;
      from digital communication receive conventional letters via a remote printing system.&#xD;
&#xD;
      All invitations and reminders in the screening program are sent out based on lists generated&#xD;
      in the administrative CRC screening program IT system, which is linked to the daily updated&#xD;
      Danish Civil Registration System, in which all Danish citizens are registered with unique&#xD;
      civil registration numbers (CRN) assigned at birth or at immigration. The department of&#xD;
      public health programmes is administratively responsible for the screening program IT system.&#xD;
&#xD;
      Study flow The study population will be identified based on data extraction from the Danish&#xD;
      Civil Registration System. 10 000 citizens 50-74 years old, living in the Central Denmark&#xD;
      Region born in December (invited for CRC screening through October/November/December 2017)&#xD;
      and 5 000 citizens 50-74 years old, living in the Central Denmark Region born in October&#xD;
      (invited for CRC screening in January/February 2017) are identified.&#xD;
&#xD;
      The 10 000 citizens born in December comprise the population to be randomized (study arm 1&#xD;
      and 2). This group of citizens will receive a baseline questionnaire at the beginning of the&#xD;
      study period (before receiving screening invitations). Non-respondents receive a&#xD;
      questionnaire reminder after two weeks. After four weeks a telephone call is made offering&#xD;
      filling out the questionnaire via telephone. Respondents (at six weeks after receiving the&#xD;
      questionnaire) are included in the study and randomized into two groups (intervention and&#xD;
      control group). All included citizens are monitored in the screening program IT system, in&#xD;
      order to identify date of screening invitation and date of screening reminder. Citizens in&#xD;
      study arm one (intervention group) receive a decision aid (DA) on the same day as the&#xD;
      screening reminder or the next day. Both groups receive a follow-up questionnaire three&#xD;
      months after the date of invitation for the last citizen invited in the study population.&#xD;
      Questionnaire reminders are sent out at two and four weeks, and deadline for questionnaire&#xD;
      response will be after six weeks.&#xD;
&#xD;
      The 5 000 citizens born in October comprise a historic cohort of citizens invited to CRC&#xD;
      screening. This population receives only one questionnaire 3-4 months after they received&#xD;
      their screening invitations. In this survey reminders will be sent out at two and four weeks.&#xD;
      Respondents (at six weeks) will be included in the study.&#xD;
&#xD;
      All contact with the study participants in this study will occur via digital communication or&#xD;
      by postal mail via remote printing system. Hence all questionnaires, survey reminders, and&#xD;
      DAs will be sent out first via digital mail. However, it is crucial to reach a high&#xD;
      questionnaire participation rate in order to obtain generalizable results. The aim is to&#xD;
      reach a survey participation rate of no less than 50% for baseline and 80% for follow-up.&#xD;
&#xD;
      When questionnaire data has been collected, date of screening invitation and screening&#xD;
      reminder will be collected from the screening program IT system along with the date of test&#xD;
      registration laboratory and the test result.&#xD;
&#xD;
      Questionnaire data and IT system data are both uploaded to Statistics Denmark, where&#xD;
      socio-demographic data are appended for the data management and data analysis.&#xD;
&#xD;
      Materials Three different questionnaires will be administered in this trial: The baseline&#xD;
      questionnaire, the follow-up questionnaire, and the questionnaire for the historic cohort.&#xD;
      The questionnaires comprise five different scales. The worry scale, the knowledge scale, the&#xD;
      attitudes scale, the decisional conflict scale, and the health literacy scale, developed by&#xD;
      the European Union consortium (HLS-EU-Q16).&#xD;
&#xD;
      The DA is an online tool. The web-based design opens up possibilities to feature more&#xD;
      advanced functions, e.g. questions for the participant during the process, and a summary of&#xD;
      answers at the end. Further a web-based design has lower running costs, and can be provided&#xD;
      as a link via the E-boks platform. The development of the DA took place in five steps: (1)&#xD;
      scoping of the DA; (2) formation of the steering group (the research group); (3) Design&#xD;
      phase, in which the prototype was developed based on previous research by the research group;&#xD;
      (4) Alpha testing, including citizens and experts evaluating design and usability and a peer&#xD;
      review by experts and citizens, evaluating content and usability; (5) Beta testing, including&#xD;
      citizens, evaluating feasibility, comprehensibility and usability.&#xD;
&#xD;
      The development took place as an iterative process, in which the DA was revise between each&#xD;
      step based on the experiences gained from the previous step.&#xD;
&#xD;
      Background data on educational level, family income, occupation, marital status, and&#xD;
      ethnicity will be obtained from Statistics Denmark when questionnaire data have been&#xD;
      collected.&#xD;
&#xD;
      Statistical methods All statistical analyses are going to be carried out in Stata/SE 14&#xD;
      (STATACorp LP, College Station, Texas, USA), stratifying according to gender. All estimates&#xD;
      will be presented with 95% confidence intervals, and all analyses will be carried out on a 5%&#xD;
      significance level. Since citizens with lower educational attainment (LEA) are the target&#xD;
      group of this study, all citizens with medium or higher educational attainment will be&#xD;
      excluded from the statistical analyses.&#xD;
&#xD;
      Pearson's chi-square test will be used to test differences in demographic characteristic&#xD;
      distribution between respondents and non-respondents as well as between the study arms in&#xD;
      order to test whether the randomisation succeeds.&#xD;
&#xD;
      Differences in distributions of responses to the outcomes (informed choice, yes/no; Adequate&#xD;
      knowledge, yes/no; mean level of decisional conflict; mean level of decisional support; mean&#xD;
      level of effectiveness of decision made; mean level of worries; and participation, yes/no) in&#xD;
      the study arms are being analysed using the independent sample t test for continuous&#xD;
      variables and Pearson's chi-square test for categorical variables. Further, the relative risk&#xD;
      (RR) will be estimated for all dichotomous outcomes using a 2x2 table with study arm 2 and&#xD;
      historic study arm as the reference, respectively.&#xD;
&#xD;
      If randomisation does not succeed in producing groups with similar baseline characteristics,&#xD;
      a logistic regression will be completed for categorical outcomes and a linear regression for&#xD;
      continuous outcomes in order to estimate an adjusted odds ratio (OR) as a value to be&#xD;
      interpreted as a RR.&#xD;
&#xD;
      All analyses will be conducted as intention to treat (ITT) analyses, in which all LEA&#xD;
      citizens will remain in the study arms to which they were first assigned.&#xD;
&#xD;
      Power calculations Every month 9 900 citizens are invited to participate in CRC screening in&#xD;
      the CDR. On average, 47% of these (4 600) do not return a stool sample within 45 days, and&#xD;
      they receive a screening reminder. It is expected that at least 1 200 (26% of the population,&#xD;
      according to Statistics Denmark) have LEA. Power calculations (considering a 5% significance&#xD;
      level and an 80% statistical power) based on being able to detect expected differences of the&#xD;
      outcomes of 22% (proportion making an informed choice), 14% (proportion having a positive&#xD;
      attitude towards CRC screening), 16% (proportion participating in CRC screening) and 2.4&#xD;
      (difference in mean score of knowledge) between the groups (as observed in previous studies)&#xD;
      indicate that 200 citizens with LEA needs to be included in every group thereby a total of&#xD;
      770 citizens who receive a screening reminder. Analyses are stratified by gender; therefore&#xD;
      the study population is doubled to 1 540 participants in every group, so that adequate power&#xD;
      is retained to assess the effect of the DA in both genders.&#xD;
&#xD;
      With an expected participation rate of 58% for baseline questionnaire (study arm 1+2) and an&#xD;
      expected participation rate of 80% in the follow-up questionnaire in study arms 1 and 2, 10&#xD;
      000 citizens who will be invited for screening (5 000 in each study arm and hence an&#xD;
      allocation ratio of 1:1) are included. In the historic study arm a 50% participation rate is&#xD;
      expected (two written reminders, no telephone calls), hence we 5 000 citizens, who will be&#xD;
      invited for screening, are included.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 15, 2017</start_date>
  <completion_date type="Actual">April 23, 2018</completion_date>
  <primary_completion_date type="Actual">April 3, 2018</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>The LEAD trial is conducted as a two arm, randomised controlled trial nested into a population-based, organized CRC screening programme conducted in the Central Denmark Region. Citizens who are scheduled to be invited for CRC screening within the study period will be randomly allocated into one two study arms. Further, a historic study arm will be included, in order to be able to assess the effect of receiving the baseline questionnaire:&#xD;
To receive the DA along with the screening reminder and to receive both baseline and follow-up questionnaires (intervention group)&#xD;
To receive both baseline and follow-up questionnaires (control group)&#xD;
To receive a questionnaire comprisng scales from both baseline and follow-up questionnaires (historic cohort)&#xD;
Regardless of study arm, all citizens receive standard CRC screening information material according to the CRC screening program procedures.</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Since baseline questionnaire is filled out before randomizasion, and citizens will know if they receive the DA or not, participants will not be masked.&#xD;
No care providers are involved in the screening program in the phases we study (invitation, reminder, and stool sample), hence no masking in this groups.&#xD;
The outcomes are assessed via questionnaire data or from registries (Statistics Denmark and the screening IT system), and no masking is necessary in neither investigators nor outcomes assessors.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>CRC and CRC screening knowledge</measure>
    <time_frame>Assessed before screening invitation (study arm 1+2) and at least three months after screening invitation (study arm 1+2+3)</time_frame>
    <description>Assessed using questionnaire. Six items yielding a scale score between 0 and 100 %. Continous variable.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CRC screening attitude</measure>
    <time_frame>Assessed before screening invitation (study arm 1+2) and at least three months after screening invitation (study arm 1+2+3)</time_frame>
    <description>Assessed using questionnaire. Four items. Scores between 7 and 28. Continuous variable.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CRC screening participation</measure>
    <time_frame>Obtained at least three months after screening invitation.</time_frame>
    <description>Binary outcome (yes/no), retrieved from screening IT system.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CRC worry</measure>
    <time_frame>Assessed before screening invitation (study arm 1+2) and at least three months after screening invitation (study arm 1+2+3)</time_frame>
    <description>Assessed in questionnaire. Three items. Individually scored.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Decisional conflict</measure>
    <time_frame>Assessed at least three months after invitation (study arm 1+2+3)</time_frame>
    <description>Decisional conflict scale. Questionnaire. 16 items. score 0-100 points.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health literacy</measure>
    <time_frame>Assessed before screening invitation (study arm 1+2) or at least three months after screening invitation (study arm 3)</time_frame>
    <description>HLS-EU-Q16 scale. Questionnaire. 16 items. Score 0-16.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Educational level</measure>
    <time_frame>Up to 12 months before screening invitation</time_frame>
    <description>Socio-demographic outcome, Statistics Denmark. LEA (≤10 years of education) and medium or high educational attainment (&gt;10 years of education)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Family income</measure>
    <time_frame>Up to 12 months before screening invitation</time_frame>
    <description>Socio-demographic outcome, Statistics Denmark.The categories will be lower tertile, middle tertile, and upper tertile.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occupation</measure>
    <time_frame>Up to 12 months before screening invitation</time_frame>
    <description>Socio-demographic outcome, Statistics Denmark. Employed, Self-employed chief executive, Unemployed/receiving benefits, Retired, Social welfare recipients, and Others.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Marital status</measure>
    <time_frame>Up to 12 months before screening invitation</time_frame>
    <description>Socio-demographic outcome, Statistics Denmark. Married/cohabitant or single/widow</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ethnicity</measure>
    <time_frame>Up to 12 months before screening invitation</time_frame>
    <description>Socio-demographic outcome, Statistics Denmark. Danish, Immigrant (Western origin), and Immigrant (non-western origin)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">15030</enrollment>
  <condition>Decision Making</condition>
  <condition>Knowledge, Attitudes, Practice</condition>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group receives a baseline questionnaire before their screening invitation. Respondents are included, and those receiving a screening reminder receive the decision aid.&#xD;
At least three months after their screening invitation the included citizens (baseline questionnaire respondents) will receive a follow-up questionnaire.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>This group receives a baseline questionnaire before their screening invitation. Respondents are included. At least three months after their screening invitation, baseline questionnaire respondents will receive a follow-up questionnaire.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Historic cohort</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>A group of people already invited for colorectal cancer screening. This group receives a questionnaire at least three months after their screening invitation. Respondents are included in the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Decision aid</intervention_name>
    <description>The DA is an online tool. The web-based design opens up possibilities to feature more advanced functions, e.g. questions for the participant during the process, and a summary of answers at the end. The DA is tailored to lower educational attainment citizens, and is designed to embrace different information needs in the target population, ranging from a desire to receive a clear recommendation and a minimum of information to the desire to receive full information and make a personalized choice.</description>
    <arm_group_label>Intervention group</arm_group_label>
    <other_name>DA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Random sample of citizens 50-74 years of age.&#xD;
&#xD;
          -  Resident in the Central Denmark Region at time of data extraction (August 2017)&#xD;
&#xD;
          -  Month of birth: December or October&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-respondents to baseline questionnaire (study arm 1+2) or questionnaire (study arm&#xD;
             3)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pernille Gabel, MD PhD Fel.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Public Health Programmes, Randers Regional Hospital, Central Denmark Region, Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Public Health Programmes, Randers Regional Hospital</name>
      <address>
        <city>Randers</city>
        <zip>DK-8930</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>July 13, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>October 1, 2018</last_update_submitted>
  <last_update_submitted_qc>October 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 2, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Aarhus</investigator_affiliation>
    <investigator_full_name>Pernille Gabel</investigator_full_name>
    <investigator_title>M.D. PhD Fellow</investigator_title>
  </responsible_party>
  <keyword>Colorectal Neoplasms</keyword>
  <keyword>Decision Support Techniques</keyword>
  <keyword>Early Detection of Cancer</keyword>
  <keyword>Educational Status</keyword>
  <keyword>Decision Making</keyword>
  <keyword>Knowledge, Attitudes, Practice</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No individual patient data are to be shared with other researchers.</ipd_description>
  </patient_data>
  <!-- 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/NCT03253822
org study id: 2012-58-006--1-16-02-94-16
nct id: NCT03253822
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of the trial is to test the effect of a web-based decision aid (DA) on colorectal
      cancer (CRC) knowledge, decisional conflict, participation rate, and informed choice
      (evaluated based on knowledge, attitudes and actual participation).

      The study includes three study arms. Citizens to be recruited are identified from the Danish
      Civil Registration System based on residence (Central Denmark Region), age (50-74 years old),
      and month of birth. A random sample of 15,000 citizens born in December (invited for CRC
      screening through October/November/December 2017) (study arm 1+2) and 5,000 citizens born in
      October (invited for CRC screening in January/February 2017) (study arm 3) is identified.

      Citizens in study arm 1+2 will receive a baseline questionnaire assessing knowledge,
      attitudes, worry, and health literacy. Non respondents will receive one reminder after two
      weeks and after four weeks non-respondents will receive a phone call, offering them to fill
      out the questionnaire via the phone. Baseline questionnaire respondents are included in the
      study, and will be randomized into two study arms (intervention group and control group).

      Citizens in the intervention group will be identified in the screening IT system. Date of
      screening invitation and screening reminder (citizens who do not return a stool sample within
      45 days of the screening invitation) is retrieved. Citizens receiving a screening reminder
      will receive a link for the DA. Follow-up questionnaire will be sent to all included citizens
      in study-arm 1+2 three months after the last screening invitation has been sent out. Citizens
      have six weeks to respond to the questionnaire.

      Study arm 3 is a historic cohort. The citizens receive only one questionnaire at the same
      time as the baseline questionnaires are sent out to the intervention and control groups. The
      citizens are included if they respond to the questionnaire within six weeks. Questionnaire
      reminders are sent out at two and four weeks.

      Data on screening invitation date, screening reminder date, returning a stool sample and
      result will be retrieved from the screening IT system for all included citizens (Study arm
      1-3). Lastly, data from Statistics Denmark (on socio-demographic and socio-economic factors)
      will be included.
Study setting The Danish national colorectal cancer (CRC) screening programme was implemented
      in Denmark in March 2014. All citizens aged 50-74 years are invited to take up CRC screening
      biennially, however, the first prevalence round is carried out during a four year period
      (2014-2017). During the this period, citizens are invited according to month of birth, except
      citizens aged 49 who are invited just before they turn 50 and citizens turning 75 who are
      invited prior to their 75th birthday, if they were not invited earlier in the program.

      Politically and organisationally the CRC screening programme is nationally directed, but the
      administrative responsibility is placed within the five regions in Denmark. The Department of
      Public Health Programmes is responsible for the administration of the CRC screening programme
      in the Central Denmark Region (CDR).

      The CDR has 1.3 million citizens (23% of the total population) of which roughly 390 000
      citizens are 50-74 years of age. The citizens receive an invitation, containing a screening
      kit. The screening test (collection of a stool sample) is performed in the citizen's own
      home. The stool sample is sent to the clinical biochemical department at the hospital. If the
      citizens do not return a stool sample within 45 days after receiving the invitation, a
      screening reminder is received. Citizens, who still do not return a stool sample, are
      automatically referred to the next screening round, and will receive another invitation two
      years later. Citizens with a negative test are automatically referred to the next screening
      round. Citizens with a positive test are invited to have a colonoscopy.

      Since 2010, national digitisation has occurred in Denmark. Hence, communication to and from
      Danish authorities occur via digital mail, in the public email platform E-Boks. Danish
      residents are obliged to order a digital signature (NemID) which is used as a shared log-in
      for E-boks, public and private online self-services, and online banking. Only disabled
      citizens (e.g. physical or cognitive impairment) or citizens unable to satisfactorily
      identify themselves (e.g. migrants with no permanent resident permit) can be exempted from
      ordering a NemID. As of May 2016 more than 5 million Danish citizens (87.5% of the entire
      population including children) have access to E-boks. Exemption from digital communication
      has been granted to 9.8% of Danish Residents aged 45-74 years.

      All letters in the CRC screening programme are sent by digital mail, except from invitation
      letters, which contains a screening kit and are sent by conventional mail. Citizens exempt
      from digital communication receive conventional letters via a remote printing system.

      All invitations and reminders in the screening program are sent out based on lists generated
      in the administrative CRC screening program IT system, which is linked to the daily updated
      Danish Civil Registration System, in which all Danish citizens are registered with unique
      civil registration numbers (CRN) assigned at birth or at immigration. The department of
      public health programmes is administratively responsible for the screening program IT system.

      Study flow The study population will be identified based on data extraction from the Danish
      Civil Registration System. 10 000 citizens 50-74 years old, living in the Central Denmark
      Region born in December (invited for CRC screening through October/November/December 2017)
      and 5 000 citizens 50-74 years old, living in the Central Denmark Region born in October
      (invited for CRC screening in January/February 2017) are identified.

      The 10 000 citizens born in December comprise the population to be randomized (study arm 1
      and 2). This group of citizens will receive a baseline questionnaire at the beginning of the
      study period (before receiving screening invitations). Non-respondents receive a
      questionnaire reminder after two weeks. After four weeks a telephone call is made offering
      filling out the questionnaire via telephone. Respondents (at six weeks after receiving the
      questionnaire) are included in the study and randomized into two groups (intervention and
      control group). All included citizens are monitored in the screening program IT system, in
      order to identify date of screening invitation and date of screening reminder. Citizens in
      study arm one (intervention group) receive a decision aid (DA) on the same day as the
      screening reminder or the next day. Both groups receive a follow-up questionnaire three
      months after the date of invitation for the last citizen invited in the study population.
      Questionnaire reminders are sent out at two and four weeks, and deadline for questionnaire
      response will be after six weeks.

      The 5 000 citizens born in October comprise a historic cohort of citizens invited to CRC
      screening. This population receives only one questionnaire 3-4 months after they received
      their screening invitations. In this survey reminders will be sent out at two and four weeks.
      Respondents (at six weeks) will be included in the study.

      All contact with the study participants in this study will occur via digital communication or
      by postal mail via remote printing system. Hence all questionnaires, survey reminders, and
      DAs will be sent out first via digital mail. However, it is crucial to reach a high
      questionnaire participation rate in order to obtain generalizable results. The aim is to
      reach a survey participation rate of no less than 50% for baseline and 80% for follow-up.

      When questionnaire data has been collected, date of screening invitation and screening
      reminder will be collected from the screening program IT system along with the date of test
      registration laboratory and the test result.

      Questionnaire data and IT system data are both uploaded to Statistics Denmark, where
      socio-demographic data are appended for the data management and data analysis.

      Materials Three different questionnaires will be administered in this trial: The baseline
      questionnaire, the follow-up questionnaire, and the questionnaire for the historic cohort.
      The questionnaires comprise five different scales. The worry scale, the knowledge scale, the
      attitudes scale, the decisional conflict scale, and the health literacy scale, developed by
      the European Union consortium (HLS-EU-Q16).

      The DA is an online tool. The web-based design opens up possibilities to feature more
      advanced functions, e.g. questions for the participant during the process, and a summary of
      answers at the end. Further a web-based design has lower running costs, and can be provided
      as a link via the E-boks platform. The development of the DA took place in five steps: (1)
      scoping of the DA; (2) formation of the steering group (the research group); (3) Design
      phase, in which the prototype was developed based on previous research by the research group;
      (4) Alpha testing, including citizens and experts evaluating design and usability and a peer
      review by experts and citizens, evaluating content and usability; (5) Beta testing, including
      citizens, evaluating feasibility, comprehensibility and usability.

      The development took place as an iterative process, in which the DA was revise between each
      step based on the experiences gained from the previous step.

      Background data on educational level, family income, occupation, marital status, and
      ethnicity will be obtained from Statistics Denmark when questionnaire data have been
      collected.

      Statistical methods All statistical analyses are going to be carried out in Stata/SE 14
      (STATACorp LP, College Station, Texas, USA), stratifying according to gender. All estimates
      will be presented with 95% confidence intervals, and all analyses will be carried out on a 5%
      significance level. Since citizens with lower educational attainment (LEA) are the target
      group of this study, all citizens with medium or higher educational attainment will be
      excluded from the statistical analyses.

      Pearson's chi-square test will be used to test differences in demographic characteristic
      distribution between respondents and non-respondents as well as between the study arms in
      order to test whether the randomisation succeeds.

      Differences in distributions of responses to the outcomes (informed choice, yes/no; Adequate
      knowledge, yes/no; mean level of decisional conflict; mean level of decisional support; mean
      level of effectiveness of decision made; mean level of worries; and participation, yes/no) in
      the study arms are being analysed using the independent sample t test for continuous
      variables and Pearson's chi-square test for categorical variables. Further, the relative risk
      (RR) will be estimated for all dichotomous outcomes using a 2x2 table with study arm 2 and
      historic study arm as the reference, respectively.

      If randomisation does not succeed in producing groups with similar baseline characteristics,
      a logistic regression will be completed for categorical outcomes and a linear regression for
      continuous outcomes in order to estimate an adjusted odds ratio (OR) as a value to be
      interpreted as a RR.

      All analyses will be conducted as intention to treat (ITT) analyses, in which all LEA
      citizens will remain in the study arms to which they were first assigned.

      Power calculations Every month 9 900 citizens are invited to participate in CRC screening in
      the CDR. On average, 47% of these (4 600) do not return a stool sample within 45 days, and
      they receive a screening reminder. It is expected that at least 1 200 (26% of the population,
      according to Statistics Denmark) have LEA. Power calculations (considering a 5% significance
      level and an 80% statistical power) based on being able to detect expected differences of the
      outcomes of 22% (proportion making an informed choice), 14% (proportion having a positive
      attitude towards CRC screening), 16% (proportion participating in CRC screening) and 2.4
      (difference in mean score of knowledge) between the groups (as observed in previous studies)
      indicate that 200 citizens with LEA needs to be included in every group thereby a total of
      770 citizens who receive a screening reminder. Analyses are stratified by gender; therefore
      the study population is doubled to 1 540 participants in every group, so that adequate power
      is retained to assess the effect of the DA in both genders.

      With an expected participation rate of 58% for baseline questionnaire (study arm 1+2) and an
      expected participation rate of 80% in the follow-up questionnaire in study arms 1 and 2, 10
      000 citizens who will be invited for screening (5 000 in each study arm and hence an
      allocation ratio of 1:1) are included. In the historic study arm a 50% participation rate is
      expected (two written reminders, no telephone calls), hence we 5 000 citizens, who will be
      invited for screening, are included.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The LEAD trial is conducted as a two arm, randomised controlled trial nested into a population-based, organized CRC screening programme conducted in the Central Denmark Region. Citizens who are scheduled to be invited for CRC screening within the study period will be randomly allocated into one two study arms. Further, a historic study arm will be included, in order to be able to assess the effect of receiving the baseline questionnaire:
To receive the DA along with the screening reminder and to receive both baseline and follow-up questionnaires (intervention group)
To receive both baseline and follow-up questionnaires (control group)
To receive a questionnaire comprisng scales from both baseline and follow-up questionnaires (historic cohort)
Regardless of study arm, all citizens receive standard CRC screening information material according to the CRC screening program procedures.
primary purpose: Screening
masking: None (Open Label)
masking description: Since baseline questionnaire is filled out before randomizasion, and citizens will know if they receive the DA or not, participants will not be masked.
No care providers are involved in the screening program in the phases we study (invitation, reminder, and stool sample), hence no masking in this groups.
The outcomes are assessed via questionnaire data or from registries (Statistics Denmark and the screening IT system), and no masking is necessary in neither investigators nor outcomes assessors.
measure: CRC and CRC screening knowledge
time frame: Assessed before screening invitation (study arm 1+2) and at least three months after screening invitation (study arm 1+2+3)
description: Assessed using questionnaire. Six items yielding a scale score between 0 and 100 %. Continous variable.
measure: CRC screening attitude
time frame: Assessed before screening invitation (study arm 1+2) and at least three months after screening invitation (study arm 1+2+3)
description: Assessed using questionnaire. Four items. Scores between 7 and 28. Continuous variable.
measure: CRC screening participation
time frame: Obtained at least three months after screening invitation.
description: Binary outcome (yes/no), retrieved from screening IT system.
measure: CRC worry
time frame: Assessed before screening invitation (study arm 1+2) and at least three months after screening invitation (study arm 1+2+3)
description: Assessed in questionnaire. Three items. Individually scored.
measure: Decisional conflict
time frame: Assessed at least three months after invitation (study arm 1+2+3)
description: Decisional conflict scale. Questionnaire. 16 items. score 0-100 points.
measure: Health literacy
time frame: Assessed before screening invitation (study arm 1+2) or at least three months after screening invitation (study arm 3)
description: HLS-EU-Q16 scale. Questionnaire. 16 items. Score 0-16.
measure: Educational level
time frame: Up to 12 months before screening invitation
description: Socio-demographic outcome, Statistics Denmark. LEA (≤10 years of education) and medium or high educational attainment (>10 years of education)
measure: Family income
time frame: Up to 12 months before screening invitation
description: Socio-demographic outcome, Statistics Denmark.The categories will be lower tertile, middle tertile, and upper tertile.
measure: Occupation
time frame: Up to 12 months before screening invitation
description: Socio-demographic outcome, Statistics Denmark. Employed, Self-employed chief executive, Unemployed/receiving benefits, Retired, Social welfare recipients, and Others.
measure: Marital status
time frame: Up to 12 months before screening invitation
description: Socio-demographic outcome, Statistics Denmark. Married/cohabitant or single/widow
measure: Ethnicity
time frame: Up to 12 months before screening invitation
description: Socio-demographic outcome, Statistics Denmark. Danish, Immigrant (Western origin), and Immigrant (non-western origin)
arm group label: Intervention group
arm group type: Experimental
description: This group receives a baseline questionnaire before their screening invitation. Respondents are included, and those receiving a screening reminder receive the decision aid.
At least three months after their screening invitation the included citizens (baseline questionnaire respondents) will receive a follow-up questionnaire.
arm group label: Control group
arm group type: No Intervention
description: This group receives a baseline questionnaire before their screening invitation. Respondents are included. At least three months after their screening invitation, baseline questionnaire respondents will receive a follow-up questionnaire.
arm group label: Historic cohort
arm group type: No Intervention
description: A group of people already invited for colorectal cancer screening. This group receives a questionnaire at least three months after their screening invitation. Respondents are included in the study.
intervention type: Other
intervention name: Decision aid
description: The DA is an online tool. The web-based design opens up possibilities to feature more advanced functions, e.g. questions for the participant during the process, and a summary of answers at the end. The DA is tailored to lower educational attainment citizens, and is designed to embrace different information needs in the target population, ranging from a desire to receive a clear recommendation and a minimum of information to the desire to receive full information and make a personalized choice.
arm group label: Intervention group
other name: DA
criteria: 
gender: All
minimum age: 50 Years
maximum age: 74 Years
healthy volunteers: No
last name: Pernille Gabel, MD PhD Fel.
role: Principal Investigator
affiliation: Department of Public Health Programmes, Randers Regional Hospital, Central Denmark Region, Denmark
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: University of Aarhus
investigator full name: Pernille Gabel
investigator title: M.D. PhD Fellow
mesh term: Colorectal Neoplasms
sharing ipd: No
ipd description: No individual patient data are to be shared with other researchers.