<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/NCT03789084</url>
  </required_header>
  <id_info>
    <org_study_id>D19044</org_study_id>
    <secondary_id>6K23MH116367-02</secondary_id>
    <nct_id>NCT03789084</nct_id>
  </id_info>
  <brief_title>Hybrid Trial of Brief Cognitive-Behavioral Therapy for Health Anxiety in Primary Care</brief_title>
  <official_title>A Hybrid Type 1 Trial Evaluating the Feasibility, Acceptability, Preliminary Effectiveness of Brief Cognitive-behavioral Therapy for Health Anxiety Delivered by Medical Assistants in Primary Care</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dartmouth-Hitchcock Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Dartmouth-Hitchcock Medical Center</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>
      This study is a randomized controlled pilot trial using a hybrid type 1&#xD;
      effectiveness-implementation design to evaluate the feasibility, acceptability, and&#xD;
      preliminary effectiveness of a brief cognitive-behavioral intervention delivered by medical&#xD;
      assistants in a primary care setting. The trial compares clinical outcomes of participants&#xD;
      assigned to the intervention condition to those of participants assigned to a usual care&#xD;
      condition. The clinical outcome is change on a self-report measure of health anxiety.&#xD;
      Assessments occur at baseline, four weeks, and 12 weeks post-treatment. The study will also&#xD;
      measure engagement with the intervention and assess feasibility and acceptability of the&#xD;
      intervention in terms of fidelity of trained study therapists and ratings of the intervention&#xD;
      by participants. The usual care condition consists of a referral to a mental health provider.&#xD;
      The intervention is comprised of four sessions of individually administered&#xD;
      cognitive-behavioral therapy addressing health anxiety. Treatment focuses on building&#xD;
      motivation for change, psychoeducation about health anxiety, cognitive restructuring, and&#xD;
      situational and interoceptive exposure. The study will recruit from three primary care&#xD;
      clinics within the Dartmouth-Hitchcock Health system. The study will also assess facilitators&#xD;
      and barriers to implementation using qualitative analyses of interview responses provided by&#xD;
      the medical assistants delivering the intervention, primary care providers, and clinic&#xD;
      administrators at the study sites.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Seventy-two health anxious patients with a diagnosis of Illness Anxiety Disorder or Somatic&#xD;
      Symptom Disorder will be randomly assigned to either receive brief cognitive-behavioral&#xD;
      therapy (CBT) administered by a medical assistant in the primary care practice where the&#xD;
      patient receives their primary care services (intervention condition) or receive a referral&#xD;
      to a mental health provider within the outpatient psychiatry clinic or another community&#xD;
      provider of their choice (usual care condition). Randomization will be determined by a random&#xD;
      number generation program at the point of enrollment. The randomization scheme will be&#xD;
      stratified by primary care site to reduce site effects. The primary care sites from which&#xD;
      patients will be recruited include the General Internal Medicine clinic at&#xD;
      Dartmouth-Hitchcock Medical Center, Dartmouth-Hitchcock Heater Road clinic, and&#xD;
      Dartmouth-Hitchcock Manchester. Recruitment will be evenly distributed across sites. The&#xD;
      investigators will over-sample racial and ethnic minority patients at Dartmouth-Hitchcock&#xD;
      Manchester due to the higher proportion of minority patients receiving services at that&#xD;
      location.&#xD;
&#xD;
      The brief CBT intervention is a 4-session psychotherapy comprised of techniques guided by&#xD;
      cognitive-behavioral theory and specifically derived from previously published materials.&#xD;
      Each technique has support from prior randomized controlled trials demonstrating their&#xD;
      efficacy for reducing symptoms of health anxiety and expert consensus. The techniques&#xD;
      employed include motivational interviewing, psychoeducation, cognitive restructuring, and&#xD;
      situational and interoceptive exposure. Each session of brief CBT is 45-minutes in duration&#xD;
      and is delivered by a medical assistant who is principally located at the patient's primary&#xD;
      care practice. All sessions are based on a manual developed by the Principal Investigator&#xD;
      that includes essential elements to deliver at each session, scripts to guide delivery of the&#xD;
      intervention, and homework assignments for the patient to complete between sessions and after&#xD;
      completion of the final session. The Principal Investigator provides clinical supervision of&#xD;
      the intervention over the course of the study.&#xD;
&#xD;
      The referral process employed in the usual care condition consists of an electronic referral&#xD;
      made by the patient's primary care provider to a mental health provider within the&#xD;
      Dartmouth-Hitchcock Health system, or a community provider outside of the system identified&#xD;
      by the patient in consultation with the primary care provider. The nature of the intervention&#xD;
      provided by the mental health provider is not prescribed or guided by the study protocol.&#xD;
&#xD;
      Examination of distributions of all variables using descriptive analyses will precede&#xD;
      inferential statistical analysis. Transformations or recoding will be applied to normalize&#xD;
      continuous data when necessary. The success of random assignment will be evaluated by&#xD;
      comparing the two study groups on baseline characteristics using chi-square tests for&#xD;
      categorical variables and t-tests for continuous covariates. If baseline variables are&#xD;
      significantly different between groups and are significantly associated with the outcomes&#xD;
      (e.g., medical comorbidity), the investigators will include them as covariates in the&#xD;
      analytic models.&#xD;
&#xD;
      The primary outcome of change in health anxiety will be tested using a model that&#xD;
      accommodates attrition and is appropriate for correlated data due to clustering (by 3 sites&#xD;
      and 6 medical assistants) and repeated measures (baseline, 4 and 12 weeks) on the outcomes.&#xD;
      Because there are only three assessment points, time will be treated as discrete and fitted&#xD;
      to a covariance pattern model to compare average change between groups over time. Group (CBT&#xD;
      vs usual care), time (baseline, 4 and 12 weeks), and the group by time interaction will be&#xD;
      specified for the model. The treatment effect of intervention relative to control will be&#xD;
      evaluated by testing significance of the group by time interaction term. An unstructured&#xD;
      variance-covariance structure will be specified to account for the correlated nature of the&#xD;
      data due to repeated measures.&#xD;
&#xD;
      The cluster size at site and provider levels are too small to be treated as random effects;&#xD;
      therefore, the analysis will take clustering effects due to site and provider into account&#xD;
      using small-sample robust estimate correction options implemented in the Statistical Analysis&#xD;
      Software (SAS) generalized linear mixed models procedure (PROC GLIMMIX) procedure. GLIMMIX&#xD;
      facilitates conducting mixed-effects and generalized estimating equation (GEE) modeling in&#xD;
      the same procedure simultaneously.&#xD;
&#xD;
      The sample size was determined by a combination of recruitment feasibility, study therapist&#xD;
      (medical assistant) availability, and power analysis. Given two groups, 3-assessment points,&#xD;
      and sample size of 72 (36 per arm) with 15% attrition at 12 months (N = 58), and assuming&#xD;
      cross-time correlation of 0.60, alpha of 0.05, and two-tailed tests, the study achieves 80%&#xD;
      power to detect a minimum effect size of 0.69, between medium (0.50) and large (0.80) in&#xD;
      Cohen's d-metric. If the analysis takes clustering effects due to site and providers into&#xD;
      account by adjusting the sample size with an intraclass correlation (ICC) of 0.01, the study&#xD;
      achieves 80% power to detect an effect size of 0.72. Statisticians recommend ICC between 0.01&#xD;
      and 0.02 in clinical studies with clustering; the investigators used ICC = 0.01 for this&#xD;
      power calculation. A larger sample size is needed to detect effect sizes smaller than 0.69&#xD;
      and 0.72; however, sample size for pilot study should be based on pragmatics of recruitment&#xD;
      and the necessities for examining feasibility, and not for purpose of inferential statistical&#xD;
      tests.&#xD;
&#xD;
      The investigators will assess acceptability of the intervention and strategy using scores on&#xD;
      a self-report measure of treatment acceptability using mean scores above a predetermined cut&#xD;
      score denoting moderate acceptability across all participants. The investigators assess study&#xD;
      therapist fidelity to the treatment by compiling standardized fidelity ratings for each&#xD;
      session, nested within each provider, and converted to a percentage fidelity score.&#xD;
&#xD;
      Finally, the investigators will assess acceptability qualitatively using qualitative&#xD;
      interviews with medical assistants, primary care providers, and clinic administrators.&#xD;
      Interview data will be transcribed and entered verbatim into a qualitative data management&#xD;
      software package for content analysis. Content analysis consists of reviewing the responses&#xD;
      of interviewees to identify responses that are coded to correspond to Consolidated Framework&#xD;
      for Implementation Research constructs. Coding will be conducted by two independent coders&#xD;
      (the Principal Investigator and a research assistant) and overseen by a medical&#xD;
      anthropologist.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">March 26, 2019</start_date>
  <completion_date type="Anticipated">October 24, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 24, 2023</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in health anxiety, measured by the Short Health Anxiety Inventory</measure>
    <time_frame>Baseline, Post-treatment (4 weeks followup), 12-weeks Post-Treatment (12 weeks followup)</time_frame>
    <description>The Short Health Anxiety Inventory is an 18-item measure of health anxiety in which respondents identify which statement applies best to them among four choices per item scored from 0 to 3 (e.g., &quot;I do not worry about my health&quot; = 0, &quot;I spend most of my time worrying about my health&quot; = 3). The scale range is 0 to 54. Higher scores correspond to increased health anxiety.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acceptability of the intervention, measured by the Treatment Evaluation Inventory-Short Form</measure>
    <time_frame>Post-treatment (4 weeks followup), 12-weeks Post-Treatment (12 weeks followup)</time_frame>
    <description>The Treatment Evaluation Inventory-Short Form is a 9-item measure of treatment acceptability (e.g., &quot;I like the procedures used in this treatment&quot;) rated on a five-point Likert scale from &quot;strongly disagree&quot; to &quot;strongly agree&quot; and modified to focus on interventions administered to adults. The scale range is 9 to 45. Higher scores correspond to greater acceptability of the intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in readiness for intervention, measured by the University of Rhode Island Change Assessment-Psychotherapy Version</measure>
    <time_frame>Baseline, Post-treatment (4 weeks followup), 12-weeks Post-Treatment (12 weeks followup)</time_frame>
    <description>The University of Rhode Island Change Assessment-Psychotherapy Version is a 32-item measure of readiness for change. Items are rated on a five-point Likert scale from &quot;strongly disagree&quot; to &quot;strongly agree&quot; for each item (e.g., &quot;I think I might be ready for some self-improvement.&quot;). The scale range is 32 to 160. Higher scores correspond to increased readiness for change.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Fidelity to the intervention following training, measured by the Cognitive Therapy Scale-Revised</measure>
    <time_frame>1 to 15 months before Baseline</time_frame>
    <description>The Revised-Cognitive Therapy Scale is a 12-item measure of therapist fidelity to cognitive-behavioral therapy (CBT). Items are rated on a seven-point scale of ability to apply CBT principles (0 = &quot;Incompetent&quot; to 6 = &quot;Expert&quot;), by an evaluator with expertise in CBT. A score of ≥36 is the recommended cut-off for CBT fidelity. The scale range is 0 to 72. Higher scores correspond to greater fidelity to the CBT model.</description>
  </other_outcome>
  <other_outcome>
    <measure>Psychiatric diagnostic comorbidity, assessed by the Mini-International Neuropsychiatric Interview</measure>
    <time_frame>Baseline</time_frame>
    <description>The Mini-International Neuropsychiatric Interview (MINI) is a widely used brief structured psychiatric diagnostic interview for 17 International Classification of Diseases-10 psychiatric disorders. Each item from the MINI is answered in a dichotomous, yes/no format with additional prompts used by the assessor to clarify ambiguous responses.</description>
  </other_outcome>
  <other_outcome>
    <measure>Medical diagnostic comorbidity, assessed by the Charlton Age-Comorbidity Index</measure>
    <time_frame>Baseline</time_frame>
    <description>The Charlson Age-Comorbidity Index is a combined age and comorbidity index in which each decade of life ≥50 years equals a 1-point increase in comorbidity alongside scores assigned to specific disease states. Scores range from 0 to 39, with comorbidities of greater severity assigned higher scores of 1, 2, 3, or 6. Higher scores are associated with greater likelihood of death from the identified comorbid conditions.</description>
  </other_outcome>
  <other_outcome>
    <measure>Determination of health anxiety diagnoses, assessed by the Health Anxiety Interview</measure>
    <time_frame>Baseline</time_frame>
    <description>The Health Anxiety Interview (HAI) is a brief clinician-administered semi-structured interview of health anxiety and related disorders. The HAI can be administered in approximately 30 minutes. Reliability data are not available for the HAI, but it has been used successfully in health anxiety outcome trials research. The HAI will be used to verify the presence of excessive health anxiety identified on the WI-7.</description>
  </other_outcome>
  <other_outcome>
    <measure>Measurement of health anxiety for screening purposes, assessed by the Whiteley Index-7</measure>
    <time_frame>1 week to 1 month before Baseline</time_frame>
    <description>The Whiteley Index-7 (WI-7) is comprised of seven items assessing health anxiety. Respondents indicate how much an item is representative of them (e.g., &quot;Do you often worry about the possibility that you have a serious illness'') using dichotomous scaling. The WI-7 has good sensitivity and specificity for identification of excessive health anxiety. A score of ≥2 is indicative of excessive health anxiety. The scale range is 0 to 7. Higher scores correspond to greater health anxiety.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Illness Anxiety Disorder</condition>
  <condition>Somatic Symptom Disorder</condition>
  <condition>Health Anxiety</condition>
  <arm_group>
    <arm_group_label>Cognitive-Behavioral Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Brief Cognitive-Behavioral Therapy for Health Anxiety</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Referral to mental health provider</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Provider makes referral to a mental health provider</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Brief Cognitive-Behavioral Therapy for Health Anxiety</intervention_name>
    <description>4-session in-person 45-minute psychotherapy sessions focused on building motivation for change, psychoeducation, cognitive restructuring, and situational and interoceptive exposure to health-related fear stimuli.</description>
    <arm_group_label>Cognitive-Behavioral Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Referral to mental health provider</intervention_name>
    <description>Provider makes a referral to a mental health provider in the outpatient psychiatry clinic or a community provider of the participant's choice.</description>
    <arm_group_label>Referral to mental health provider</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age of 18 years to 85&#xD;
&#xD;
          -  Have a primary care provider at Dartmouth-Hitchcock Medical Center-General Internal&#xD;
             Medicine, Dartmouth-Hitchcock Heater Road Clinic, or Dartmouth-Hitchcock Manchester&#xD;
&#xD;
          -  Primary care visit frequency of two standard deviations above the mean for patients in&#xD;
             the individual's age by gender cohort&#xD;
&#xD;
          -  Elevated self-reported health anxiety (≥2 on Whiteley Index-7)&#xD;
&#xD;
          -  Diagnosis of illness anxiety disorder or somatic symptom disorder determined by Health&#xD;
             Anxiety Interview&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-English speaking&#xD;
&#xD;
          -  Chronic medical illness necessitating an increased visit frequency confirmed through&#xD;
             consultation with the patient's primary care provider&#xD;
&#xD;
          -  Active suicidal ideation&#xD;
&#xD;
          -  Unmanaged psychosis or unmanaged bipolar disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert E Brady, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dartmouth-Hitchcock Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <last_update_submitted>August 15, 2023</last_update_submitted>
  <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dartmouth-Hitchcock Medical Center</investigator_affiliation>
    <investigator_full_name>Robert E. Brady</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Medically Unexplained Symptoms</mesh_term>
    <mesh_term>Anxiety Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Study results will be posted to ClinicalTrials.gov in a timely manner with the goal of posting the results as soon as possible following completion of primary analyses and not more than one year after completion of the final participant's participation in the trial. This corresponds to the third year of the career development award period for the hybrid trial covered in this study record. Deidentified individual participant data (IPD) will be available upon request from researchers with a sound research and analytic plan, including replication or inclusion in meta-analysis. IPD will be available immediately and indefinitely following primary outcome manuscript publication.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>IPD will be available immediately and indefinitely following primary outcome manuscript publication.</ipd_time_frame>
    <ipd_access_criteria>Replication trials, meta-analyses; requests should be made directly to Principal investigator at Robert.E.Brady@hitchcock.org.</ipd_access_criteria>
  </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/NCT03789084
org study id: D19044
secondary id: 6K23MH116367-02
nct id: NCT03789084
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is a randomized controlled pilot trial using a hybrid type 1
      effectiveness-implementation design to evaluate the feasibility, acceptability, and
      preliminary effectiveness of a brief cognitive-behavioral intervention delivered by medical
      assistants in a primary care setting. The trial compares clinical outcomes of participants
      assigned to the intervention condition to those of participants assigned to a usual care
      condition. The clinical outcome is change on a self-report measure of health anxiety.
      Assessments occur at baseline, four weeks, and 12 weeks post-treatment. The study will also
      measure engagement with the intervention and assess feasibility and acceptability of the
      intervention in terms of fidelity of trained study therapists and ratings of the intervention
      by participants. The usual care condition consists of a referral to a mental health provider.
      The intervention is comprised of four sessions of individually administered
      cognitive-behavioral therapy addressing health anxiety. Treatment focuses on building
      motivation for change, psychoeducation about health anxiety, cognitive restructuring, and
      situational and interoceptive exposure. The study will recruit from three primary care
      clinics within the Dartmouth-Hitchcock Health system. The study will also assess facilitators
      and barriers to implementation using qualitative analyses of interview responses provided by
      the medical assistants delivering the intervention, primary care providers, and clinic
      administrators at the study sites.
Seventy-two health anxious patients with a diagnosis of Illness Anxiety Disorder or Somatic
      Symptom Disorder will be randomly assigned to either receive brief cognitive-behavioral
      therapy (CBT) administered by a medical assistant in the primary care practice where the
      patient receives their primary care services (intervention condition) or receive a referral
      to a mental health provider within the outpatient psychiatry clinic or another community
      provider of their choice (usual care condition). Randomization will be determined by a random
      number generation program at the point of enrollment. The randomization scheme will be
      stratified by primary care site to reduce site effects. The primary care sites from which
      patients will be recruited include the General Internal Medicine clinic at
      Dartmouth-Hitchcock Medical Center, Dartmouth-Hitchcock Heater Road clinic, and
      Dartmouth-Hitchcock Manchester. Recruitment will be evenly distributed across sites. The
      investigators will over-sample racial and ethnic minority patients at Dartmouth-Hitchcock
      Manchester due to the higher proportion of minority patients receiving services at that
      location.

      The brief CBT intervention is a 4-session psychotherapy comprised of techniques guided by
      cognitive-behavioral theory and specifically derived from previously published materials.
      Each technique has support from prior randomized controlled trials demonstrating their
      efficacy for reducing symptoms of health anxiety and expert consensus. The techniques
      employed include motivational interviewing, psychoeducation, cognitive restructuring, and
      situational and interoceptive exposure. Each session of brief CBT is 45-minutes in duration
      and is delivered by a medical assistant who is principally located at the patient's primary
      care practice. All sessions are based on a manual developed by the Principal Investigator
      that includes essential elements to deliver at each session, scripts to guide delivery of the
      intervention, and homework assignments for the patient to complete between sessions and after
      completion of the final session. The Principal Investigator provides clinical supervision of
      the intervention over the course of the study.

      The referral process employed in the usual care condition consists of an electronic referral
      made by the patient's primary care provider to a mental health provider within the
      Dartmouth-Hitchcock Health system, or a community provider outside of the system identified
      by the patient in consultation with the primary care provider. The nature of the intervention
      provided by the mental health provider is not prescribed or guided by the study protocol.

      Examination of distributions of all variables using descriptive analyses will precede
      inferential statistical analysis. Transformations or recoding will be applied to normalize
      continuous data when necessary. The success of random assignment will be evaluated by
      comparing the two study groups on baseline characteristics using chi-square tests for
      categorical variables and t-tests for continuous covariates. If baseline variables are
      significantly different between groups and are significantly associated with the outcomes
      (e.g., medical comorbidity), the investigators will include them as covariates in the
      analytic models.

      The primary outcome of change in health anxiety will be tested using a model that
      accommodates attrition and is appropriate for correlated data due to clustering (by 3 sites
      and 6 medical assistants) and repeated measures (baseline, 4 and 12 weeks) on the outcomes.
      Because there are only three assessment points, time will be treated as discrete and fitted
      to a covariance pattern model to compare average change between groups over time. Group (CBT
      vs usual care), time (baseline, 4 and 12 weeks), and the group by time interaction will be
      specified for the model. The treatment effect of intervention relative to control will be
      evaluated by testing significance of the group by time interaction term. An unstructured
      variance-covariance structure will be specified to account for the correlated nature of the
      data due to repeated measures.

      The cluster size at site and provider levels are too small to be treated as random effects;
      therefore, the analysis will take clustering effects due to site and provider into account
      using small-sample robust estimate correction options implemented in the Statistical Analysis
      Software (SAS) generalized linear mixed models procedure (PROC GLIMMIX) procedure. GLIMMIX
      facilitates conducting mixed-effects and generalized estimating equation (GEE) modeling in
      the same procedure simultaneously.

      The sample size was determined by a combination of recruitment feasibility, study therapist
      (medical assistant) availability, and power analysis. Given two groups, 3-assessment points,
      and sample size of 72 (36 per arm) with 15% attrition at 12 months (N = 58), and assuming
      cross-time correlation of 0.60, alpha of 0.05, and two-tailed tests, the study achieves 80%
      power to detect a minimum effect size of 0.69, between medium (0.50) and large (0.80) in
      Cohen's d-metric. If the analysis takes clustering effects due to site and providers into
      account by adjusting the sample size with an intraclass correlation (ICC) of 0.01, the study
      achieves 80% power to detect an effect size of 0.72. Statisticians recommend ICC between 0.01
      and 0.02 in clinical studies with clustering; the investigators used ICC = 0.01 for this
      power calculation. A larger sample size is needed to detect effect sizes smaller than 0.69
      and 0.72; however, sample size for pilot study should be based on pragmatics of recruitment
      and the necessities for examining feasibility, and not for purpose of inferential statistical
      tests.

      The investigators will assess acceptability of the intervention and strategy using scores on
      a self-report measure of treatment acceptability using mean scores above a predetermined cut
      score denoting moderate acceptability across all participants. The investigators assess study
      therapist fidelity to the treatment by compiling standardized fidelity ratings for each
      session, nested within each provider, and converted to a percentage fidelity score.

      Finally, the investigators will assess acceptability qualitatively using qualitative
      interviews with medical assistants, primary care providers, and clinic administrators.
      Interview data will be transcribed and entered verbatim into a qualitative data management
      software package for content analysis. Content analysis consists of reviewing the responses
      of interviewees to identify responses that are coded to correspond to Consolidated Framework
      for Implementation Research constructs. Coding will be conducted by two independent coders
      (the Principal Investigator and a research assistant) and overseen by a medical
      anthropologist.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change from baseline in health anxiety, measured by the Short Health Anxiety Inventory
time frame: Baseline, Post-treatment (4 weeks followup), 12-weeks Post-Treatment (12 weeks followup)
description: The Short Health Anxiety Inventory is an 18-item measure of health anxiety in which respondents identify which statement applies best to them among four choices per item scored from 0 to 3 (e.g., "I do not worry about my health" = 0, "I spend most of my time worrying about my health" = 3). The scale range is 0 to 54. Higher scores correspond to increased health anxiety.
measure: Acceptability of the intervention, measured by the Treatment Evaluation Inventory-Short Form
time frame: Post-treatment (4 weeks followup), 12-weeks Post-Treatment (12 weeks followup)
description: The Treatment Evaluation Inventory-Short Form is a 9-item measure of treatment acceptability (e.g., "I like the procedures used in this treatment") rated on a five-point Likert scale from "strongly disagree" to "strongly agree" and modified to focus on interventions administered to adults. The scale range is 9 to 45. Higher scores correspond to greater acceptability of the intervention.
measure: Change in readiness for intervention, measured by the University of Rhode Island Change Assessment-Psychotherapy Version
time frame: Baseline, Post-treatment (4 weeks followup), 12-weeks Post-Treatment (12 weeks followup)
description: The University of Rhode Island Change Assessment-Psychotherapy Version is a 32-item measure of readiness for change. Items are rated on a five-point Likert scale from "strongly disagree" to "strongly agree" for each item (e.g., "I think I might be ready for some self-improvement."). The scale range is 32 to 160. Higher scores correspond to increased readiness for change.
measure: Fidelity to the intervention following training, measured by the Cognitive Therapy Scale-Revised
time frame: 1 to 15 months before Baseline
description: The Revised-Cognitive Therapy Scale is a 12-item measure of therapist fidelity to cognitive-behavioral therapy (CBT). Items are rated on a seven-point scale of ability to apply CBT principles (0 = "Incompetent" to 6 = "Expert"), by an evaluator with expertise in CBT. A score of ≥36 is the recommended cut-off for CBT fidelity. The scale range is 0 to 72. Higher scores correspond to greater fidelity to the CBT model.
measure: Psychiatric diagnostic comorbidity, assessed by the Mini-International Neuropsychiatric Interview
time frame: Baseline
description: The Mini-International Neuropsychiatric Interview (MINI) is a widely used brief structured psychiatric diagnostic interview for 17 International Classification of Diseases-10 psychiatric disorders. Each item from the MINI is answered in a dichotomous, yes/no format with additional prompts used by the assessor to clarify ambiguous responses.
measure: Medical diagnostic comorbidity, assessed by the Charlton Age-Comorbidity Index
time frame: Baseline
description: The Charlson Age-Comorbidity Index is a combined age and comorbidity index in which each decade of life ≥50 years equals a 1-point increase in comorbidity alongside scores assigned to specific disease states. Scores range from 0 to 39, with comorbidities of greater severity assigned higher scores of 1, 2, 3, or 6. Higher scores are associated with greater likelihood of death from the identified comorbid conditions.
measure: Determination of health anxiety diagnoses, assessed by the Health Anxiety Interview
time frame: Baseline
description: The Health Anxiety Interview (HAI) is a brief clinician-administered semi-structured interview of health anxiety and related disorders. The HAI can be administered in approximately 30 minutes. Reliability data are not available for the HAI, but it has been used successfully in health anxiety outcome trials research. The HAI will be used to verify the presence of excessive health anxiety identified on the WI-7.
measure: Measurement of health anxiety for screening purposes, assessed by the Whiteley Index-7
time frame: 1 week to 1 month before Baseline
description: The Whiteley Index-7 (WI-7) is comprised of seven items assessing health anxiety. Respondents indicate how much an item is representative of them (e.g., "Do you often worry about the possibility that you have a serious illness'') using dichotomous scaling. The WI-7 has good sensitivity and specificity for identification of excessive health anxiety. A score of ≥2 is indicative of excessive health anxiety. The scale range is 0 to 7. Higher scores correspond to greater health anxiety.
arm group label: Cognitive-Behavioral Therapy
arm group type: Experimental
description: Brief Cognitive-Behavioral Therapy for Health Anxiety
arm group label: Referral to mental health provider
arm group type: Other
description: Provider makes referral to a mental health provider
intervention type: Behavioral
intervention name: Brief Cognitive-Behavioral Therapy for Health Anxiety
description: 4-session in-person 45-minute psychotherapy sessions focused on building motivation for change, psychoeducation, cognitive restructuring, and situational and interoceptive exposure to health-related fear stimuli.
arm group label: Cognitive-Behavioral Therapy
intervention type: Behavioral
intervention name: Referral to mental health provider
description: Provider makes a referral to a mental health provider in the outpatient psychiatry clinic or a community provider of the participant's choice.
arm group label: Referral to mental health provider
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Robert E Brady, PhD
role: Principal Investigator
affiliation: Dartmouth-Hitchcock Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dartmouth-Hitchcock Medical Center
investigator full name: Robert E. Brady
investigator title: Assistant Professor
mesh term: Medically Unexplained Symptoms
mesh term: Anxiety Disorders
sharing ipd: Yes
ipd description: Study results will be posted to ClinicalTrials.gov in a timely manner with the goal of posting the results as soon as possible following completion of primary analyses and not more than one year after completion of the final participant's participation in the trial. This corresponds to the third year of the career development award period for the hybrid trial covered in this study record. Deidentified individual participant data (IPD) will be available upon request from researchers with a sound research and analytic plan, including replication or inclusion in meta-analysis. IPD will be available immediately and indefinitely following primary outcome manuscript publication.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: IPD will be available immediately and indefinitely following primary outcome manuscript publication.
ipd access criteria: Replication trials, meta-analyses; requests should be made directly to Principal investigator at Robert.E.Brady@hitchcock.org.