<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/NCT04431908</url>
  </required_header>
  <id_info>
    <org_study_id>2000028259</org_study_id>
    <nct_id>NCT04431908</nct_id>
  </id_info>
  <brief_title>Validation of a Rapid Quantitative Test for Loss of Smell in COVID-19 Subjects</brief_title>
  <official_title>Validation of a Rapid Quantitative Test for Loss of Smell in COVID-19 Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the performance of a non-invasive olfactory device&#xD;
      as a rapid indicator of COVID-19 in positive subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The major hypothesis is that a quantitative and unbiased smell test will be a useful tool to&#xD;
      identify COVID-19 positive individuals.&#xD;
&#xD;
      The study will address what fraction of outpatients truly have a loss-of-smell (including a&#xD;
      partial loss) and is expected to outperform the current question that is used to identify&#xD;
      COVID-19 related anosmia &quot;Do you have a new loss of smell or taste?&quot; (yes/no) in terms of&#xD;
      sensitivity and specificity.&#xD;
&#xD;
      The study will address if high-risk asymptomatic people whom are SARS-CoV-2 positive have a&#xD;
      partial (or perhaps transitory) loss of smell.&#xD;
&#xD;
      The primary objective of this study is to validate the utility (sensitivity, specificity and&#xD;
      accuracy) of a quantitative non-biased olfactory device for the rapid identification of&#xD;
      SARS-CoV-2 infected subjects (as identified by PCR). The performance of the device will also&#xD;
      be compared to the standard CDC patient query for 'new loss of smell or taste'.&#xD;
&#xD;
      The secondary objective is to test if SARS-CoV-2 positive 'asymptomatic' COVID-19 subjects&#xD;
      may actually present with a mild or transitory defect in smell (hyposmia), which is revealed&#xD;
      through our quantitative olfactory smell test.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Actual">November 18, 2020</completion_date>
  <primary_completion_date type="Actual">October 15, 2020</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>Sensitivity, Specificity and Accuracy</measure>
    <time_frame>24 hours</time_frame>
    <description>The subject's score on using the olfactory device will be compared to the PCR results (SARS-CoV-2 negative or positive) on COVID19 outpatients. As the smell test has a variable scale (0-5) the ideal cutoff will be determined to maximize these factors:&#xD;
Sensitivity (Represents True Positives Divided by True Positives plus False Negatives)&#xD;
Specificity (Represents True Negatives Divided by True Negatives plus False Positives)&#xD;
Accuracy (Represents Sensitivity x Prevalence + Specificity x (1-Prevalence) True Positives are patients who got 3 or less correct answers on the smell test and had a positive PCR COVID test.&#xD;
True Negatives are patients who got 4 or 5 correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Positives are patients who got 3 or less correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Negatives are patients who got 4 or 5 correct responses on the smell test and had a positive PCR COVID test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Repeatability</measure>
    <time_frame>48 hours</time_frame>
    <description>Repeatability will also be examined in a test-retest score conducted within 24 hours with a second device in which the sequence of the odorants is altered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Asymptomatic Sensitivity, Specificity and Accuracy</measure>
    <time_frame>24 hours</time_frame>
    <description>We will determine if 'asymptomatic' SARS-CoV-2 positive subjects experience a partial loss of smell (hyposmia) and if so determine the fraction of subjects in which this occurs. We will evaluate sensitivity, specificity and accuracy.&#xD;
Sensitivity (Represents True Positives Divided by True Positives plus False Negatives)&#xD;
Specificity (Represents True Negatives Divided by True Negatives plus False Positives)&#xD;
Accuracy (Represents Sensitivity x Prevalence + Specificity x (1-Prevalence) True Positives are patients who got 3 or less correct answers on the smell test and had a positive PCR COVID test.&#xD;
True Negatives are patients who got 4 or 5 correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Positives are patients who got 3 or less correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Negatives are patients who got 4 or 5 correct responses on the smell test and had a positive PCR COVID test.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">1320</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Outpatients (Drive Thru)</arm_group_label>
    <description>Patients receiving testing through a drive thru location.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Risk Asymptomatics</arm_group_label>
    <description>Asymptomatic patients (residents) in a high risk location.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>olfactory device</intervention_name>
    <description>A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).</description>
    <arm_group_label>High Risk Asymptomatics</arm_group_label>
    <arm_group_label>Outpatients (Drive Thru)</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The population will be either individuals receiving drive-thru COVID-19 testing or&#xD;
        residents of a nursing facility receiving tests.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of signed and dated informed consent form&#xD;
&#xD;
          -  Stated willingness to comply with all study procedures and availability for the&#xD;
             duration of the study&#xD;
&#xD;
          -  Have a corresponding PCR test for SARS-CoV-2 on the same day.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Adults unable to consent&#xD;
&#xD;
          -  Individuals who are not yet adults (infants, children, teenagers)&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Individuals with allergic to fragrances&#xD;
&#xD;
          -  History of surgery on the nose or paranasal sinuses&#xD;
&#xD;
          -  Asthmatics&#xD;
&#xD;
          -  Patients with known neurocognitive disorders: dementia, Alzheimer's disease,&#xD;
             Parkinson's disease&#xD;
&#xD;
          -  Adults with Acute or Chronic rhinosinusitis (They will be asked if they have a 'stuffy&#xD;
             or runny nose'; they may be included in some tests, but their analysis would be&#xD;
             segregated as they may be false positives due to allergies or a common cold or flu)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>R Peter Manes, MD, FACS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Professor of Surgery (Otolaryngology)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale New Haven Hospital</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06519</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <results_first_submitted>March 3, 2021</results_first_submitted>
  <results_first_submitted_qc>May 28, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 2, 2021</results_first_posted>
  <last_update_submitted>May 28, 2021</last_update_submitted>
  <last_update_submitted_qc>May 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>olfactory device</keyword>
  <keyword>COVID-19</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Anosmia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 1, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT04431908/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>We did end up testing more individuals than expected due to increased ability</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Outpatients (Drive Thru)</title>
          <description>Patients receiving testing through a drive thru location.&#xD;
olfactory device: A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).</description>
        </group>
        <group group_id="P2">
          <title>High Risk Asymptomatics</title>
          <description>Asymptomatic patients (health care workers) in a high risk location.&#xD;
olfactory device: A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1042"/>
                <participants group_id="P2" count="278"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1042"/>
                <participants group_id="P2" count="278"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Outpatients (Drive Thru)</title>
          <description>Patients receiving testing through a drive thru location.&#xD;
olfactory device: A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).</description>
        </group>
        <group group_id="B2">
          <title>High Risk Asymptomatics</title>
          <description>Asymptomatic patients (residents) in a high risk location.&#xD;
olfactory device: A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1042"/>
            <count group_id="B2" value="278"/>
            <count group_id="B3" value="1320"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1042"/>
                    <count group_id="B2" value="278"/>
                    <count group_id="B3" value="1320"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="878"/>
                    <measurement group_id="B2" value="251"/>
                    <measurement group_id="B3" value="1129"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="164"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="191"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1042"/>
                    <count group_id="B2" value="278"/>
                    <count group_id="B3" value="1320"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="615"/>
                    <measurement group_id="B2" value="200"/>
                    <measurement group_id="B3" value="815"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="427"/>
                    <measurement group_id="B2" value="78"/>
                    <measurement group_id="B3" value="505"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <population>Race and Ethnicity data were not collected for the purposes of this study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>Race and Ethnicity data were not collected for the purposes of this study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="1042"/>
                    <count group_id="B2" value="278"/>
                    <count group_id="B3" value="1320"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1042"/>
                    <measurement group_id="B2" value="278"/>
                    <measurement group_id="B3" value="1320"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Sensitivity, Specificity and Accuracy</title>
        <description>The subject's score on using the olfactory device will be compared to the PCR results (SARS-CoV-2 negative or positive) on COVID19 outpatients. As the smell test has a variable scale (0-5) the ideal cutoff will be determined to maximize these factors:&#xD;
Sensitivity (Represents True Positives Divided by True Positives plus False Negatives)&#xD;
Specificity (Represents True Negatives Divided by True Negatives plus False Positives)&#xD;
Accuracy (Represents Sensitivity x Prevalence + Specificity x (1-Prevalence) True Positives are patients who got 3 or less correct answers on the smell test and had a positive PCR COVID test.&#xD;
True Negatives are patients who got 4 or 5 correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Positives are patients who got 3 or less correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Negatives are patients who got 4 or 5 correct responses on the smell test and had a positive PCR COVID test.</description>
        <time_frame>24 hours</time_frame>
        <population>Only participants in the drive thru were analyzed for this outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Outpatients (Drive Thru)</title>
            <description>Patients receiving testing through a drive thru location.&#xD;
olfactory device: A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).</description>
          </group>
        </group_list>
        <measure>
          <title>Sensitivity, Specificity and Accuracy</title>
          <description>The subject's score on using the olfactory device will be compared to the PCR results (SARS-CoV-2 negative or positive) on COVID19 outpatients. As the smell test has a variable scale (0-5) the ideal cutoff will be determined to maximize these factors:&#xD;
Sensitivity (Represents True Positives Divided by True Positives plus False Negatives)&#xD;
Specificity (Represents True Negatives Divided by True Negatives plus False Positives)&#xD;
Accuracy (Represents Sensitivity x Prevalence + Specificity x (1-Prevalence) True Positives are patients who got 3 or less correct answers on the smell test and had a positive PCR COVID test.&#xD;
True Negatives are patients who got 4 or 5 correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Positives are patients who got 3 or less correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Negatives are patients who got 4 or 5 correct responses on the smell test and had a positive PCR COVID test.</description>
          <population>Only participants in the drive thru were analyzed for this outcome.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1042"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>True Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="889"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>False Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="106"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>False Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>True Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Sensitivity, specificity and accuracy was measured utilizing the true and false positives, as well as the true and false negatives. For a subject to have a true positive, the subject must have had a positive PCR test for COVID-19 as well as scored 0, 1 or 2 correct answers on the smell test. For a subject to have a true negative, the subject must have had a negative PCR test for COVID-19 as well as scored 3, 4 or 5 correct answers on the smell test.</non_inferiority_desc>
            <param_type>Specificity</param_type>
            <param_value>89.35</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Sensitivity, specificity and accuracy was measured utilizing the true and false positives, as well as the true and false negatives. For a subject to have a true positive, the subject must have had a positive PCR test for COVID-19 as well as scored 0, 1 or 2 correct answers on the smell test. For a subject to have a true negative, the subject must have had a negative PCR test for COVID-19 as well as scored 3, 4 or 5 correct answers on the smell test.</non_inferiority_desc>
            <param_type>Sensitivity</param_type>
            <param_value>42.55</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Sensitivity, specificity and accuracy was measured utilizing the true and false positives, as well as the true and false negatives. For a subject to have a true positive, the subject must have had a positive PCR test for COVID-19 as well as scored 0, 1 or 2 correct answers on the smell test. For a subject to have a true negative, the subject must have had a negative PCR test for COVID-19 as well as scored 3, 4 or 5 correct answers on the smell test.</non_inferiority_desc>
            <param_type>Accuracy</param_type>
            <param_value>87.24</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Repeatability</title>
        <description>Repeatability will also be examined in a test-retest score conducted within 24 hours with a second device in which the sequence of the odorants is altered.</description>
        <time_frame>48 hours</time_frame>
        <population>It was not feasible to get return visits as intended in the proposed protocol and therefore these data were not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Outpatients (Drive Thru)</title>
            <description>Patients receiving testing through a drive thru location.&#xD;
olfactory device: A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).</description>
          </group>
          <group group_id="O2">
            <title>High Risk Asymptomatics</title>
            <description>Asymptomatic patients (residents) in a high risk location.&#xD;
olfactory device: A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).</description>
          </group>
        </group_list>
        <measure>
          <title>Repeatability</title>
          <description>Repeatability will also be examined in a test-retest score conducted within 24 hours with a second device in which the sequence of the odorants is altered.</description>
          <population>It was not feasible to get return visits as intended in the proposed protocol and therefore these data were not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Asymptomatic Sensitivity, Specificity and Accuracy</title>
        <description>We will determine if 'asymptomatic' SARS-CoV-2 positive subjects experience a partial loss of smell (hyposmia) and if so determine the fraction of subjects in which this occurs. We will evaluate sensitivity, specificity and accuracy.&#xD;
Sensitivity (Represents True Positives Divided by True Positives plus False Negatives)&#xD;
Specificity (Represents True Negatives Divided by True Negatives plus False Positives)&#xD;
Accuracy (Represents Sensitivity x Prevalence + Specificity x (1-Prevalence) True Positives are patients who got 3 or less correct answers on the smell test and had a positive PCR COVID test.&#xD;
True Negatives are patients who got 4 or 5 correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Positives are patients who got 3 or less correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Negatives are patients who got 4 or 5 correct responses on the smell test and had a positive PCR COVID test.</description>
        <time_frame>24 hours</time_frame>
        <population>Only asymptomatic patients were analyzed for this outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>High Risk Asymptomatics</title>
            <description>Asymptomatic patients (residents) in a high risk location.&#xD;
olfactory device: A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).</description>
          </group>
        </group_list>
        <measure>
          <title>Asymptomatic Sensitivity, Specificity and Accuracy</title>
          <description>We will determine if 'asymptomatic' SARS-CoV-2 positive subjects experience a partial loss of smell (hyposmia) and if so determine the fraction of subjects in which this occurs. We will evaluate sensitivity, specificity and accuracy.&#xD;
Sensitivity (Represents True Positives Divided by True Positives plus False Negatives)&#xD;
Specificity (Represents True Negatives Divided by True Negatives plus False Positives)&#xD;
Accuracy (Represents Sensitivity x Prevalence + Specificity x (1-Prevalence) True Positives are patients who got 3 or less correct answers on the smell test and had a positive PCR COVID test.&#xD;
True Negatives are patients who got 4 or 5 correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Positives are patients who got 3 or less correct responses on the smell test and had a negative PCR COVID test.&#xD;
False Negatives are patients who got 4 or 5 correct responses on the smell test and had a positive PCR COVID test.</description>
          <population>Only asymptomatic patients were analyzed for this outcome.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="278"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>True Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="244"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>False Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>False Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>True Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Sensitivity, specificity and accuracy was measured utilizing the true and false positives, as well as the true and false negatives. For a subject to have a true positive, the subject must have had a positive PCR test for COVID-19 as well as scored 0, 1 or 2 correct answers on the smell test. For a subject to have a true negative, the subject must have had a negative PCR test for COVID-19 as well as scored 3, 4 or 5 correct answers on the smell test.</non_inferiority_desc>
            <param_type>Specificity</param_type>
            <param_value>88.73</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Sensitivity, specificity and accuracy was measured utilizing the true and false positives, as well as the true and false negatives. For a subject to have a true positive, the subject must have had a positive PCR test for COVID-19 as well as scored 0, 1 or 2 correct answers on the smell test. For a subject to have a true negative, the subject must have had a negative PCR test for COVID-19 as well as scored 3, 4 or 5 correct answers on the smell test.</non_inferiority_desc>
            <param_type>Sensitivity</param_type>
            <param_value>33.33</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Sensitivity, specificity and accuracy was measured utilizing the true and false positives, as well as the true and false negatives. For a subject to have a true positive, the subject must have had a positive PCR test for COVID-19 as well as scored 0, 1 or 2 correct answers on the smell test. For a subject to have a true negative, the subject must have had a negative PCR test for COVID-19 as well as scored 3, 4 or 5 correct answers on the smell test.</non_inferiority_desc>
            <param_type>Accuracy</param_type>
            <param_value>88.13</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>An average of 30 minutes after administration of the smell test</time_frame>
      <desc>Serious and Other Adverse Event definitions do not differ from those of ClinicalTrials.gov</desc>
      <group_list>
        <group group_id="E1">
          <title>Outpatients (Drive Thru)</title>
          <description>Patients receiving testing through a drive thru location.&#xD;
olfactory device: A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).</description>
        </group>
        <group group_id="E2">
          <title>High Risk Asymptomatics</title>
          <description>Asymptomatic patients (health care workers) in a high risk location.&#xD;
olfactory device: A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1042"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="278"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1042"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="278"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1042"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="278"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>It is possible that the PCR COVID test results were incorrect, as these tests are not 100% accurate.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. R. Peter Manes</name_or_title>
      <organization>Yale School of Medicine</organization>
      <phone>(203) 785-5430</phone>
      <email>rpeter.manes@yale.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04431908
org study id: 2000028259
nct id: NCT04431908
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to evaluate the performance of a non-invasive olfactory device
      as a rapid indicator of COVID-19 in positive subjects.
The major hypothesis is that a quantitative and unbiased smell test will be a useful tool to
      identify COVID-19 positive individuals.

      The study will address what fraction of outpatients truly have a loss-of-smell (including a
      partial loss) and is expected to outperform the current question that is used to identify
      COVID-19 related anosmia "Do you have a new loss of smell or taste?" (yes/no) in terms of
      sensitivity and specificity.

      The study will address if high-risk asymptomatic people whom are SARS-CoV-2 positive have a
      partial (or perhaps transitory) loss of smell.

      The primary objective of this study is to validate the utility (sensitivity, specificity and
      accuracy) of a quantitative non-biased olfactory device for the rapid identification of
      SARS-CoV-2 infected subjects (as identified by PCR). The performance of the device will also
      be compared to the standard CDC patient query for 'new loss of smell or taste'.

      The secondary objective is to test if SARS-CoV-2 positive 'asymptomatic' COVID-19 subjects
      may actually present with a mild or transitory defect in smell (hyposmia), which is revealed
      through our quantitative olfactory smell test.
observational model: Cohort
time perspective: Prospective
measure: Sensitivity, Specificity and Accuracy
time frame: 24 hours
description: The subject's score on using the olfactory device will be compared to the PCR results (SARS-CoV-2 negative or positive) on COVID19 outpatients. As the smell test has a variable scale (0-5) the ideal cutoff will be determined to maximize these factors:
Sensitivity (Represents True Positives Divided by True Positives plus False Negatives)
Specificity (Represents True Negatives Divided by True Negatives plus False Positives)
Accuracy (Represents Sensitivity x Prevalence + Specificity x (1-Prevalence) True Positives are patients who got 3 or less correct answers on the smell test and had a positive PCR COVID test.
True Negatives are patients who got 4 or 5 correct responses on the smell test and had a negative PCR COVID test.
False Positives are patients who got 3 or less correct responses on the smell test and had a negative PCR COVID test.
False Negatives are patients who got 4 or 5 correct responses on the smell test and had a positive PCR COVID test.
measure: Repeatability
time frame: 48 hours
description: Repeatability will also be examined in a test-retest score conducted within 24 hours with a second device in which the sequence of the odorants is altered.
measure: Asymptomatic Sensitivity, Specificity and Accuracy
time frame: 24 hours
description: We will determine if 'asymptomatic' SARS-CoV-2 positive subjects experience a partial loss of smell (hyposmia) and if so determine the fraction of subjects in which this occurs. We will evaluate sensitivity, specificity and accuracy.
Sensitivity (Represents True Positives Divided by True Positives plus False Negatives)
Specificity (Represents True Negatives Divided by True Negatives plus False Positives)
Accuracy (Represents Sensitivity x Prevalence + Specificity x (1-Prevalence) True Positives are patients who got 3 or less correct answers on the smell test and had a positive PCR COVID test.
True Negatives are patients who got 4 or 5 correct responses on the smell test and had a negative PCR COVID test.
False Positives are patients who got 3 or less correct responses on the smell test and had a negative PCR COVID test.
False Negatives are patients who got 4 or 5 correct responses on the smell test and had a positive PCR COVID test.
arm group label: Outpatients (Drive Thru)
description: Patients receiving testing through a drive thru location.
arm group label: High Risk Asymptomatics
description: Asymptomatic patients (residents) in a high risk location.
intervention type: Device
intervention name: olfactory device
description: A quantitative non-biased olfactory device intended for the rapid identification of SARS-CoV-2 infected subjects (as identified by PCR).
arm group label: High Risk Asymptomatics
arm group label: Outpatients (Drive Thru)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
last name: R Peter Manes, MD, FACS
role: Principal Investigator
affiliation: Associate Professor of Surgery (Otolaryngology)
facility: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Anosmia
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: It is possible that the PCR COVID test results were incorrect, as these tests are not 100% accurate.
point of contact: 