<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/NCT04474652</url>
  </required_header>
  <id_info>
    <org_study_id>RD19/125787</org_study_id>
    <nct_id>NCT04474652</nct_id>
  </id_info>
  <brief_title>Guide for Prioritisation of Patients for Referral to Breast Clinics</brief_title>
  <official_title>Development of a Decision Support Tool for Ruling Out Cancer in Patients Referred From Primary Care for Possible Breast Cancer Diagnosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Leeds Teaching Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Innovate UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>PinPoint Data Science Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Leeds Teaching Hospitals NHS Trust</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      GPs in primary care in England currently refer over 2.17 million patients per year with vague&#xD;
      symptoms to the urgent cancer referral pathway. While this catches over 150,000 cancer cases&#xD;
      each year, 93% of the referred patients do not have cancer. For breast cancer, GPs refer&#xD;
      343,000 cases per year. Each of these patients are referred to a one stop clinic for&#xD;
      diagnosis. The Leeds teaching Hospitals' Trusts' Breast Unit, receives 10,000 per year, with&#xD;
      only 5% of patients actually being diagnosed with cancer.&#xD;
&#xD;
      The breast cancer pathway involves a triple assessment process, which includes a clinical&#xD;
      examination, imaging (mammogram or ultrasound) and possibly a biopsy test. It is a&#xD;
      particularly expensive process as it is an imagingintense pathway; this places considerable&#xD;
      strain on NHS diagnostic facilities. Small changes will not be enough to solve this problem -&#xD;
      a new approach is needed. The purpose of this study is to see if we can develop a blood test&#xD;
      that can support doctors in identifying patients for whom the likelihood of having breast&#xD;
      cancer is extremely low. This would avoid unnecessary referral for those patients to the one&#xD;
      stop clinic. Patients with higher chances of suspected breast cancer would be referred to the&#xD;
      one stop clinic in the usual way.&#xD;
&#xD;
      Key to the idea of safely &quot;ruling-out&quot; patients is that the test must not miss patients who&#xD;
      do have cancer. By measuring a broad range of indicators (markers) in blood, the test will&#xD;
      provide a more accurate picture of the underlying biology. The test is also being developed&#xD;
      within the NHS, so that it can be adopted quickly into NHS computer systems and laboratories&#xD;
      to maximise patient benefit, whilst being held to the NHS's high standards for clinical&#xD;
      evidence and value.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Following on from the service evaluation of retrospective TWW cases within The Leeds Teaching&#xD;
      Hospitals Trust (between 2011-2018), the aim is to undertake a prospective analysis of a&#xD;
      cohort of patients (4000) that have been referred from primary care (via their GP) for&#xD;
      possible breast cancer diagnosis in the Leeds area. The analysis will include de-identified&#xD;
      routine clinical data and blood tests from patients on the primary care referral cancer&#xD;
      diagnosis pathway for cancer risk assessment.&#xD;
&#xD;
      This is intended as a non-interventional study, where results from this study will not&#xD;
      influence patient care.&#xD;
&#xD;
      The study includes 3 phases/workstreams:&#xD;
&#xD;
        1. Validate previously developed prototype algorithm (computer instructions)&#xD;
&#xD;
        2. Update algorithm incorporating additional blood biomarkers and other relevant clinical&#xD;
           data&#xD;
&#xD;
        3. Validate diagnostic accuracy of updated algorithm The study will include 4000 patients&#xD;
           on TWW pathways. Note: The TWW pathway constitutes part of the urgent cancer referral&#xD;
           pathway. This study aims to address a major unmet clinical need for breast cancer&#xD;
           services within the NHS by safely combining the wealth of routinely collected clinical&#xD;
           data and testing of blood samples within the NHS, with secure IT infrastructure in the&#xD;
           NHS and the University of Leeds, to efficiently develop a risk assessment tool (guide)&#xD;
           to rule-out cancer within a routine NHS environment.&#xD;
&#xD;
      Inclusion criteria are:&#xD;
&#xD;
        -  Age ≥ 18 years old&#xD;
&#xD;
        -  Male and female patient must have been referred from primary care for possible breast&#xD;
           cancer diagnosis&#xD;
&#xD;
        -  Patient consented to have blood tests The data sets will be divided into a development&#xD;
           and validation data set (50:50 split). A range of statistical approaches will be&#xD;
           performed on the training data set. The algorithm parameters will then be 'locked down'&#xD;
           and validated on the remaining test data set. Performance will be assessed via ROC&#xD;
           (Receiver Operator Characteristic) curves, sensitivity and specificity,&#xD;
           Area-Under-Curve, negative/positive predictive values and diagnostic odds ratios. The&#xD;
           algorithm generation and data analysis will be conducted at the University of Leeds,&#xD;
           specifically within a secure VRE within the Leeds Institute for Data analytics (LIDA).&#xD;
           Particular scrutiny will be given to the test set patients most likely to be false&#xD;
           negatives in this analysis (i.e. those patients with cancer whose predicted probability&#xD;
           is very low). Key to further improvements in this approach will be to characterise this&#xD;
           sub-group and identify possible ways in which they might be identified by an improved&#xD;
           analysis in a future study. Eligible participants will be observed electronically for 2&#xD;
           years post blood testing to ensure any patients with undetected cancer, who develop&#xD;
           cancer within a year, are not missed. The study will end once the consented sample and&#xD;
           data retention periods have completed therefore the expected duration of project is 5&#xD;
           years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    COVID-19&#xD;
  </why_stopped>
  <start_date type="Actual">February 12, 2020</start_date>
  <completion_date type="Anticipated">February 11, 2023</completion_date>
  <primary_completion_date type="Anticipated">February 11, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Outcome</measure>
    <time_frame>3 years</time_frame>
    <description>Positive diagnosis of cancer (as diagnosed by the TWW referral)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Outcome</measure>
    <time_frame>3 years</time_frame>
    <description>Positive outcome of non-cancer disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Outcome</measure>
    <time_frame>3 years</time_frame>
    <description>Positive diagnosis with an interval cancer, despite being given the all-clear by their TWW referral</description>
  </secondary_outcome>
  <enrollment type="Anticipated">4000</enrollment>
  <condition>Breast Cancer</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Single Blood Draw from each participant</intervention_name>
    <description>Health Professionals will seek informed consent and take a single blood collection from the participant. This will take place during the patient's visit to the breast one stop clinic as part of their routine urgent breast referral pathway.</description>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      We will be collecting a single blood collection from patients who have been referred in to&#xD;
      the breast LTHT clinic via the 'urgent cancer referral pathway' to have tests performed&#xD;
      through NHS blood sciences laboratories. These samples will be processed into serum and&#xD;
      plasma (i.e. not covered by the Human Tissues Act).&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        A cohort of patients (4000) that have been referred from primary care (via their GP) for&#xD;
        possible breast cancer diagnosis in the Leeds area. These patients will be on a Two Week&#xD;
        Wait (TWW) pathway.&#xD;
&#xD;
        Note: The TWW pathway constitutes part of the urgent cancer referral pathway.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; or = 18 years old.&#xD;
&#xD;
          -  Males and females referred from primary care for possible breast cancer diagnosis.&#xD;
&#xD;
          -  Informed consent to provide a single blood collection for analysis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18 years old.&#xD;
&#xD;
          -  Informed consent to provide a single blood collection for analysis not given&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Leeds Teaching Hospital NHS Trust</name>
      <address>
        <city>Leeds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>April 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>July 13, 2020</last_update_submitted>
  <last_update_submitted_qc>July 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT04474652
org study id: RD19/125787
nct id: NCT04474652
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
GPs in primary care in England currently refer over 2.17 million patients per year with vague
      symptoms to the urgent cancer referral pathway. While this catches over 150,000 cancer cases
      each year, 93% of the referred patients do not have cancer. For breast cancer, GPs refer
      343,000 cases per year. Each of these patients are referred to a one stop clinic for
      diagnosis. The Leeds teaching Hospitals' Trusts' Breast Unit, receives 10,000 per year, with
      only 5% of patients actually being diagnosed with cancer.

      The breast cancer pathway involves a triple assessment process, which includes a clinical
      examination, imaging (mammogram or ultrasound) and possibly a biopsy test. It is a
      particularly expensive process as it is an imagingintense pathway; this places considerable
      strain on NHS diagnostic facilities. Small changes will not be enough to solve this problem -
      a new approach is needed. The purpose of this study is to see if we can develop a blood test
      that can support doctors in identifying patients for whom the likelihood of having breast
      cancer is extremely low. This would avoid unnecessary referral for those patients to the one
      stop clinic. Patients with higher chances of suspected breast cancer would be referred to the
      one stop clinic in the usual way.

      Key to the idea of safely "ruling-out" patients is that the test must not miss patients who
      do have cancer. By measuring a broad range of indicators (markers) in blood, the test will
      provide a more accurate picture of the underlying biology. The test is also being developed
      within the NHS, so that it can be adopted quickly into NHS computer systems and laboratories
      to maximise patient benefit, whilst being held to the NHS's high standards for clinical
      evidence and value.
Following on from the service evaluation of retrospective TWW cases within The Leeds Teaching
      Hospitals Trust (between 2011-2018), the aim is to undertake a prospective analysis of a
      cohort of patients (4000) that have been referred from primary care (via their GP) for
      possible breast cancer diagnosis in the Leeds area. The analysis will include de-identified
      routine clinical data and blood tests from patients on the primary care referral cancer
      diagnosis pathway for cancer risk assessment.

      This is intended as a non-interventional study, where results from this study will not
      influence patient care.

      The study includes 3 phases/workstreams:

        1. Validate previously developed prototype algorithm (computer instructions)

        2. Update algorithm incorporating additional blood biomarkers and other relevant clinical
           data

        3. Validate diagnostic accuracy of updated algorithm The study will include 4000 patients
           on TWW pathways. Note: The TWW pathway constitutes part of the urgent cancer referral
           pathway. This study aims to address a major unmet clinical need for breast cancer
           services within the NHS by safely combining the wealth of routinely collected clinical
           data and testing of blood samples within the NHS, with secure IT infrastructure in the
           NHS and the University of Leeds, to efficiently develop a risk assessment tool (guide)
           to rule-out cancer within a routine NHS environment.

      Inclusion criteria are:

        -  Age ≥ 18 years old

        -  Male and female patient must have been referred from primary care for possible breast
           cancer diagnosis

        -  Patient consented to have blood tests The data sets will be divided into a development
           and validation data set (50:50 split). A range of statistical approaches will be
           performed on the training data set. The algorithm parameters will then be 'locked down'
           and validated on the remaining test data set. Performance will be assessed via ROC
           (Receiver Operator Characteristic) curves, sensitivity and specificity,
           Area-Under-Curve, negative/positive predictive values and diagnostic odds ratios. The
           algorithm generation and data analysis will be conducted at the University of Leeds,
           specifically within a secure VRE within the Leeds Institute for Data analytics (LIDA).
           Particular scrutiny will be given to the test set patients most likely to be false
           negatives in this analysis (i.e. those patients with cancer whose predicted probability
           is very low). Key to further improvements in this approach will be to characterise this
           sub-group and identify possible ways in which they might be identified by an improved
           analysis in a future study. Eligible participants will be observed electronically for 2
           years post blood testing to ensure any patients with undetected cancer, who develop
           cancer within a year, are not missed. The study will end once the consented sample and
           data retention periods have completed therefore the expected duration of project is 5
           years.
observational model: Cohort
time perspective: Prospective
measure: Primary Outcome
time frame: 3 years
description: Positive diagnosis of cancer (as diagnosed by the TWW referral)
measure: Secondary Outcome
time frame: 3 years
description: Positive outcome of non-cancer disease
measure: Secondary Outcome
time frame: 3 years
description: Positive diagnosis with an interval cancer, despite being given the all-clear by their TWW referral
intervention type: Other
intervention name: Single Blood Draw from each participant
description: Health Professionals will seek informed consent and take a single blood collection from the participant. This will take place during the patient's visit to the breast one stop clinic as part of their routine urgent breast referral pathway.
We will be collecting a single blood collection from patients who have been referred in to
      the breast LTHT clinic via the 'urgent cancer referral pathway' to have tests performed
      through NHS blood sciences laboratories. These samples will be processed into serum and
      plasma (i.e. not covered by the Human Tissues Act).
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Breast Neoplasms
sharing ipd: Undecided