xml: <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/NCT05982600</url>
    </required_header>
    <id_info>
      <org_study_id>SAFEST Trial</org_study_id>
      <nct_id>NCT05982600</nct_id>
    </id_info>
    <brief_title>Safety and Avoidance of Futile Excisions Through Skin Tele-triage</brief_title>
    <acronym>SAFEST</acronym>
    <official_title>Effect of Teledermoscopic Triage on Clinical Management of Skin Lesions Suspected of Melanoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Herlev Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Herlev 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>
        The goal of this study is to estimate the triage values, efficiency and safety of&#xD;
        tele-dermoscopic triage of skin lesions suspected of melanoma. The main question[s] it aims&#xD;
        to answer are:&#xD;
  &#xD;
          -  What is the rate of correct patient management by a single, 2, 3 and 5 dermatologists.&#xD;
  &#xD;
          -  What is the consequence for the patients if teledermoscopic triage is implemented, in&#xD;
             termes of missed melanomas and reduced unnecessary excisions/biopsies.&#xD;
  &#xD;
        Retrospectively included patients will have their skin lesions re-examined by setups of 1, 2,&#xD;
        3 and 5 tele-dermoscopists who will assign a tentative diagnosis and a recommended clinical&#xD;
        action.&#xD;
  &#xD;
        The investigators will compare the rate of correct patient management between the different&#xD;
        setups.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background The incidence of melanoma has been increasing in Denmark for decades [1]. With an&#xD;
        age-standardized rate of 29.7 per 100.000 citizens, Denmark has the third highest melanoma&#xD;
        rate in the world, and the highest rate for women (33.6) [2].&#xD;
  &#xD;
        The excision rate in Danish departments of plastic surgery is close to 100%, although only&#xD;
        46% of referred patients have a malignant tumour [3].&#xD;
  &#xD;
        To combat this over-treatment, the patient should be triaged by an expert in evaluation of&#xD;
        skin tumours as early as possible, who, to a higher degree, could be able to distinguish&#xD;
        between benign and malignant skin lesions and dismiss patients with benign lesions without a&#xD;
        biopsy.&#xD;
  &#xD;
        This triage should therefore be made by subspecialized dermatologists with expertise&#xD;
        regarding diagnosing melanocytic skin lesions.&#xD;
  &#xD;
        Teledermoscopy has a high sensitivity equal to face-to-face examination [8], and images taken&#xD;
        in the primary care setting and at the hospital have been found to be of comparable quality&#xD;
        [9], enabling an accurate assessment of images acquired in the primary care setting.&#xD;
  &#xD;
        Our hypothesis is that a mandatory teledermoscopic triage by teledermoscopic experts for all&#xD;
        pigmented lesions referred for excision, may reduce the number of unnecessary benign&#xD;
        excisions. Yet even the experts may misdiagnose these tricky lesions, and so this study aims&#xD;
        to evaluate the management and diagnostic values of a teledermoscopic expert panel on a&#xD;
        high-incidence dataset and the safety of the triage method before potential clinical&#xD;
        implementation.&#xD;
  &#xD;
        Methods Based on a sample size calculation (see Statistics), 250 consecutive patients from&#xD;
        the dataset will be included. The patients, whose skin lesions are included in the study,&#xD;
        have been referred from PCPs or departments of dermatology at the local public hospitals, but&#xD;
        the majority were referred by privately practicing dermatologists.&#xD;
  &#xD;
        The teledermatological experts included in this study are dermatologists working mainly with&#xD;
        diagnosing melanoma, who have more than 10 years of clinical dermatology experience and have&#xD;
        clinical experience with teledermoscopy of melanocytic skin lesions.&#xD;
  &#xD;
        Patient and lesion data and images are obtained from the electronic medical record systems&#xD;
        Dermloop (Melatech ApS) and Sundhedsplatformen (Epic Systems), used at the Department of&#xD;
        Plastic Surgery, Herlev and Gentofte Hospital.&#xD;
  &#xD;
        The panel of tele-dermatologists will review all cases and determine a diagnosis and a&#xD;
        management. To be able to distinguish primary and secondary outcomes, both a diagnosis and&#xD;
        recommended clinical management are required from the experts.&#xD;
  &#xD;
        Outcomes The primary outcome of the study is the recommended clinical management, Triage&#xD;
        Values, of the TDT panels. The recommended clinical management for each lesion is assessed in&#xD;
        binary classification of correct vs incorrect by a list of pre-defined &quot;best practice&#xD;
        management&quot; rules based on its histopathological diagnosis outlined in Table 3.&#xD;
  &#xD;
        Both a Majority Consensus and a Worst-Case analysis (see Statistics for further explanation)&#xD;
        will be done.&#xD;
  &#xD;
        In addition, the investigators will report the number of each management option recommended&#xD;
        by the different modes of tele-dermatological assessment (single assessor, 2, 3 and 5&#xD;
        assessors).&#xD;
  &#xD;
        Secondary outcomes include assessing the diagnostic values (in terms of Sensitivity,&#xD;
        Specificity, False Negative and False Positive Rate using the dichotomized histopathological&#xD;
        diagnosis of benign vs malignant as Gold Standard) of the TDT expert panel.&#xD;
  &#xD;
        The diagnostic accuracy and range are reported separately. For the melanomas in the dataset,&#xD;
        a descriptive analysis will me made of how often the tele-dermatologists correctly identify&#xD;
        the Breslow thickness, in terms of true positives for each category.&#xD;
  &#xD;
        Statistical analysis and Sample Size Calculation In order to discern a disparity between the&#xD;
        conventional practice and the diagnostic efficacy of teledermatological assessment, a sample&#xD;
        size of 44 cases is sufficient to detect a statistically significant difference, with a level&#xD;
        of significance set at 0.05, accompanied by a statistical power of 80%. However, when&#xD;
        evaluating the safety of a pure teledermatological triage system, it is imperative to ensure&#xD;
        a sufficiently high sensitivity to avoid overlooking melanomas, while concurrently achieving&#xD;
        a narrow confidence interval to confidently articulate the findings.&#xD;
  &#xD;
        Based on a simulation model using R Studio [16] of five teledermoscopy experts diagnosing a&#xD;
        number of cases with a 40% prevalence of malignancy with a sensitivity and specificity&#xD;
        estimated from previous studies [8, 17] an estimated sensitivity of 99% can be found with a&#xD;
        narrow confidence interval from 99%-100% with five experts evaluating 250 patient cases.&#xD;
        Choosing an uneven number of experts for the panel enables a Majority Consensus analysis and&#xD;
        easier interpretation of the results in regard to clinical practice.&#xD;
  &#xD;
        Management is ranked hierarchically when defining &quot;worst case&quot; as follows, from least to&#xD;
        worst: Dismiss, Dermatological Treatment, Followup, Biopsy, Excision.&#xD;
  &#xD;
        Because incongruence between the experts is inevitable, separate analyses will be made using&#xD;
        1) majority consensus (ignoring answers given by less than half of the panel) and 2)&#xD;
        &quot;worst-case&quot; consensus (letting even a single expert's suspicion of malignancy or&#xD;
        recommendation for a management of a higher rank overrule the rest of the panel).&#xD;
  &#xD;
        Perspective This study will report the number of patients that could have avoided having&#xD;
        their skin lesions excised and to what degree malignant skin lesions would have been&#xD;
        incorrectly managed if the teledermoscopically recommended clinical management had been&#xD;
        followed.&#xD;
  &#xD;
        The knowledge gained from this study has the potential to significantly change how to&#xD;
        diagnose and triage patients suspected of having melanoma, which is the most common type of&#xD;
        cancer among young Danes aged 15-34 [18].&#xD;
  &#xD;
        The results of this and future studies will lead to the excision and treatment of fewer&#xD;
        benign skin lesions and pave the way for a smoother patient pathway with less physical&#xD;
        referrals, which will benefit not only patients but also lead to potential savings for the&#xD;
        healthcare system resources by reducing the number of unnecessary consultations and&#xD;
        procedures.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Enrolling by invitation</overall_status>
    <start_date type="Anticipated">August 1, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2023</completion_date>
    <primary_completion_date type="Anticipated">September 15, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Only</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Triage Values</measure>
      <time_frame>Immediately after all participants have completed the evaluations</time_frame>
      <description>Recommended clinical action, correct vs incorrect. Each teledermatologist will recommend a clinical action for each patient case. We evaluate the correctness of this recommended clinical action (in binary classification of correct vs incorrect) by a list of pre-defined &quot;best practice management rules&quot; for each diagnosis.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Diagnostic Values</measure>
      <time_frame>Immediately after all participants have completed the evaluations</time_frame>
      <description>Secondary outcomes include assessing the diagnostic values (in terms of Sensitivity, Specificity, False Negative and False Positive Rate using the dichotomized histopathological diagnosis of benign vs malignant as Gold Standard) of the TDT expert panel.</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">250</enrollment>
    <condition>Melanoma (Skin)</condition>
    <condition>Telemedicine</condition>
    <arm_group>
      <arm_group_label>Cancer Pathway referred patient</arm_group_label>
      <description>Patient referred for assessment and excision of their skin lesion, because of a suspicion of melanoma by the referring doctor.</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Single Assessor Teledermatological triage (TDT)</intervention_name>
      <description>The skin lesion is assessed, diagnosed and triaged by one dermatologist assessors.</description>
      <arm_group_label>Cancer Pathway referred patient</arm_group_label>
      <other_name>Single Assessor</other_name>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>2 people Teledermatological triage (TDT)</intervention_name>
      <description>The skin lesion is assessed, diagnosed and triaged by 2 dermatologist assessors. Worst case overrules.</description>
      <arm_group_label>Cancer Pathway referred patient</arm_group_label>
      <other_name>2 people assessment</other_name>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>3 people Teledermatological triage (TDT)</intervention_name>
      <description>The skin lesion is assessed, diagnosed and triaged by 3 dermatologist assessors. Worst case and majority consensus assessments are calculated separately.</description>
      <arm_group_label>Cancer Pathway referred patient</arm_group_label>
      <other_name>3 people assessment</other_name>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>5 people Teledermatological triage (TDT)</intervention_name>
      <description>The skin lesion is assessed, diagnosed and triaged by 5 dermatologist assessors. Worst case and majority consensus assessments are calculated separately.</description>
      <arm_group_label>Cancer Pathway referred patient</arm_group_label>
      <other_name>5 people assessment</other_name>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          250 retrospectively randomly selected patients referred to the Department of Plastic&#xD;
          Surgery at Herlev Hospital because of suspicion of melanoma in the period between May 1st&#xD;
          and December 31st 2022.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Referred to the Department of Plastic Surgery at Herlev Hospital because of suspicion&#xD;
               of melanoma&#xD;
  &#xD;
            -  Clinical and dermoscopic images registered in Dermloop&#xD;
  &#xD;
            -  Histopathological diagnosis available for the lesion&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  The patient's images cannot be anonymized adequately&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Gustav Gede Nervil</name>
        <address>
          <city>Brønshøj</city>
          <state>Copenhagen</state>
          <zip>2700</zip>
          <country>Denmark</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Denmark</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Herlev Hospital</investigator_affiliation>
      <investigator_full_name>Gustav Gede Nervil</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Teledermoscopy</keyword>
    <keyword>Melanoma</keyword>
    <keyword>Pigmented Skin Lesions</keyword>
    <keyword>Telemedicine</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Melanoma</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Sample-size simulation codes, data-analysis codes and deidentified data will be shared through data repository.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>Available after conclusion and for as long as appropriate.</ipd_time_frame>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05982600
  org study id: SAFEST Trial
  nct id: NCT05982600
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this study is to estimate the triage values, efficiency and safety of
        tele-dermoscopic triage of skin lesions suspected of melanoma. The main question[s] it aims
        to answer are:
  
          -  What is the rate of correct patient management by a single, 2, 3 and 5 dermatologists.
  
          -  What is the consequence for the patients if teledermoscopic triage is implemented, in
             termes of missed melanomas and reduced unnecessary excisions/biopsies.
  
        Retrospectively included patients will have their skin lesions re-examined by setups of 1, 2,
        3 and 5 tele-dermoscopists who will assign a tentative diagnosis and a recommended clinical
        action.
  
        The investigators will compare the rate of correct patient management between the different
        setups.
  Background The incidence of melanoma has been increasing in Denmark for decades [1]. With an
        age-standardized rate of 29.7 per 100.000 citizens, Denmark has the third highest melanoma
        rate in the world, and the highest rate for women (33.6) [2].
  
        The excision rate in Danish departments of plastic surgery is close to 100%, although only
        46% of referred patients have a malignant tumour [3].
  
        To combat this over-treatment, the patient should be triaged by an expert in evaluation of
        skin tumours as early as possible, who, to a higher degree, could be able to distinguish
        between benign and malignant skin lesions and dismiss patients with benign lesions without a
        biopsy.
  
        This triage should therefore be made by subspecialized dermatologists with expertise
        regarding diagnosing melanocytic skin lesions.
  
        Teledermoscopy has a high sensitivity equal to face-to-face examination [8], and images taken
        in the primary care setting and at the hospital have been found to be of comparable quality
        [9], enabling an accurate assessment of images acquired in the primary care setting.
  
        Our hypothesis is that a mandatory teledermoscopic triage by teledermoscopic experts for all
        pigmented lesions referred for excision, may reduce the number of unnecessary benign
        excisions. Yet even the experts may misdiagnose these tricky lesions, and so this study aims
        to evaluate the management and diagnostic values of a teledermoscopic expert panel on a
        high-incidence dataset and the safety of the triage method before potential clinical
        implementation.
  
        Methods Based on a sample size calculation (see Statistics), 250 consecutive patients from
        the dataset will be included. The patients, whose skin lesions are included in the study,
        have been referred from PCPs or departments of dermatology at the local public hospitals, but
        the majority were referred by privately practicing dermatologists.
  
        The teledermatological experts included in this study are dermatologists working mainly with
        diagnosing melanoma, who have more than 10 years of clinical dermatology experience and have
        clinical experience with teledermoscopy of melanocytic skin lesions.
  
        Patient and lesion data and images are obtained from the electronic medical record systems
        Dermloop (Melatech ApS) and Sundhedsplatformen (Epic Systems), used at the Department of
        Plastic Surgery, Herlev and Gentofte Hospital.
  
        The panel of tele-dermatologists will review all cases and determine a diagnosis and a
        management. To be able to distinguish primary and secondary outcomes, both a diagnosis and
        recommended clinical management are required from the experts.
  
        Outcomes The primary outcome of the study is the recommended clinical management, Triage
        Values, of the TDT panels. The recommended clinical management for each lesion is assessed in
        binary classification of correct vs incorrect by a list of pre-defined "best practice
        management" rules based on its histopathological diagnosis outlined in Table 3.
  
        Both a Majority Consensus and a Worst-Case analysis (see Statistics for further explanation)
        will be done.
  
        In addition, the investigators will report the number of each management option recommended
        by the different modes of tele-dermatological assessment (single assessor, 2, 3 and 5
        assessors).
  
        Secondary outcomes include assessing the diagnostic values (in terms of Sensitivity,
        Specificity, False Negative and False Positive Rate using the dichotomized histopathological
        diagnosis of benign vs malignant as Gold Standard) of the TDT expert panel.
  
        The diagnostic accuracy and range are reported separately. For the melanomas in the dataset,
        a descriptive analysis will me made of how often the tele-dermatologists correctly identify
        the Breslow thickness, in terms of true positives for each category.
  
        Statistical analysis and Sample Size Calculation In order to discern a disparity between the
        conventional practice and the diagnostic efficacy of teledermatological assessment, a sample
        size of 44 cases is sufficient to detect a statistically significant difference, with a level
        of significance set at 0.05, accompanied by a statistical power of 80%. However, when
        evaluating the safety of a pure teledermatological triage system, it is imperative to ensure
        a sufficiently high sensitivity to avoid overlooking melanomas, while concurrently achieving
        a narrow confidence interval to confidently articulate the findings.
  
        Based on a simulation model using R Studio [16] of five teledermoscopy experts diagnosing a
        number of cases with a 40% prevalence of malignancy with a sensitivity and specificity
        estimated from previous studies [8, 17] an estimated sensitivity of 99% can be found with a
        narrow confidence interval from 99%-100% with five experts evaluating 250 patient cases.
        Choosing an uneven number of experts for the panel enables a Majority Consensus analysis and
        easier interpretation of the results in regard to clinical practice.
  
        Management is ranked hierarchically when defining "worst case" as follows, from least to
        worst: Dismiss, Dermatological Treatment, Followup, Biopsy, Excision.
  
        Because incongruence between the experts is inevitable, separate analyses will be made using
        1) majority consensus (ignoring answers given by less than half of the panel) and 2)
        "worst-case" consensus (letting even a single expert's suspicion of malignancy or
        recommendation for a management of a higher rank overrule the rest of the panel).
  
        Perspective This study will report the number of patients that could have avoided having
        their skin lesions excised and to what degree malignant skin lesions would have been
        incorrectly managed if the teledermoscopically recommended clinical management had been
        followed.
  
        The knowledge gained from this study has the potential to significantly change how to
        diagnose and triage patients suspected of having melanoma, which is the most common type of
        cancer among young Danes aged 15-34 [18].
  
        The results of this and future studies will lead to the excision and treatment of fewer
        benign skin lesions and pave the way for a smoother patient pathway with less physical
        referrals, which will benefit not only patients but also lead to potential savings for the
        healthcare system resources by reducing the number of unnecessary consultations and
        procedures.
  observational model: Case-Only
  time perspective: Retrospective
  measure: Triage Values
  time frame: Immediately after all participants have completed the evaluations
  description: Recommended clinical action, correct vs incorrect. Each teledermatologist will recommend a clinical action for each patient case. We evaluate the correctness of this recommended clinical action (in binary classification of correct vs incorrect) by a list of pre-defined "best practice management rules" for each diagnosis.
  measure: Diagnostic Values
  time frame: Immediately after all participants have completed the evaluations
  description: Secondary outcomes include assessing the diagnostic values (in terms of Sensitivity, Specificity, False Negative and False Positive Rate using the dichotomized histopathological diagnosis of benign vs malignant as Gold Standard) of the TDT expert panel.
  arm group label: Cancer Pathway referred patient
  description: Patient referred for assessment and excision of their skin lesion, because of a suspicion of melanoma by the referring doctor.
  intervention type: Diagnostic Test
  intervention name: Single Assessor Teledermatological triage (TDT)
  description: The skin lesion is assessed, diagnosed and triaged by one dermatologist assessors.
  arm group label: Cancer Pathway referred patient
  other name: Single Assessor
  intervention type: Diagnostic Test
  intervention name: 2 people Teledermatological triage (TDT)
  description: The skin lesion is assessed, diagnosed and triaged by 2 dermatologist assessors. Worst case overrules.
  arm group label: Cancer Pathway referred patient
  other name: 2 people assessment
  intervention type: Diagnostic Test
  intervention name: 3 people Teledermatological triage (TDT)
  description: The skin lesion is assessed, diagnosed and triaged by 3 dermatologist assessors. Worst case and majority consensus assessments are calculated separately.
  arm group label: Cancer Pathway referred patient
  other name: 3 people assessment
  intervention type: Diagnostic Test
  intervention name: 5 people Teledermatological triage (TDT)
  description: The skin lesion is assessed, diagnosed and triaged by 5 dermatologist assessors. Worst case and majority consensus assessments are calculated separately.
  arm group label: Cancer Pathway referred patient
  other name: 5 people assessment
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: Accepts Healthy Volunteers
  facility: 
  country: Denmark
  responsible party type: Principal Investigator
  investigator affiliation: Herlev Hospital
  investigator full name: Gustav Gede Nervil
  investigator title: Principal Investigator
  mesh term: Melanoma
  sharing ipd: Yes
  ipd description: Sample-size simulation codes, data-analysis codes and deidentified data will be shared through data repository.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Analytic Code
  ipd time frame: Available after conclusion and for as long as appropriate.