<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/NCT02218502</url>
  </required_header>
  <id_info>
    <org_study_id>NL44181.068.13</org_study_id>
    <nct_id>NCT02218502</nct_id>
  </id_info>
  <brief_title>Study Into a New Diagnostic Tool (Simple Ultrasound-based Rules) in Patients With Adnexal Masses</brief_title>
  <acronym>SUBSONiC</acronym>
  <official_title>Regional Study Into the Performance and Cost-effectiveness of Simple Ultrasound-based Rules Compared to the Currently Used Risk of Malignancy Index in the Diagnosis of Ovarian Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Laurentius Hospital Roermond</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>St.Jans Gasthuis Weert</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>VieCuri Medical Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Orbis Medical Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is performed to compare the diagnostic performance and cost-effectiveness of&#xD;
      different diagnostic methods for differentiating benign from malignant adnexal (ovary or&#xD;
      Fallopian tube) masses: the Risk of Malignancy Index (RMI) will be compared with a two-step&#xD;
      triage test called &quot;simple ultrasound-based rules&quot; supplemented -if necessary- with either&#xD;
      subjective assessment by an expert sonographer or Diffusion Weighted - Magnetic Resonance&#xD;
      Imaging (DW-MRI). The investigators will test the hypothesis that this two-step triage test&#xD;
      will have better diagnostic accuracy than the RMI and therefore will improve the management&#xD;
      of women with adnexal masses.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Estimating whether an adnexal mass is malignant or not is essential in the preoperative&#xD;
      management of adnexal masses. Recognizing cancer means treatment is not delayed and&#xD;
      appropriate staging or debulking surgery can be carried out after referral to specialized&#xD;
      surgical centers. Vice versa, benign lesions may be managed conservatively or with minimal&#xD;
      invasive surgery in non-centre hospitals. This will limit morbidity and will avoid&#xD;
      unnecessary costs: laparoscopic surgery offers lower estimated blood loss, shorter hospital&#xD;
      stay, and fewer postoperative complications with an improved quality of life and faster&#xD;
      return to normal functioning.&#xD;
&#xD;
      There are several methods to distinguish benign from malignant adnexal masses. The commonly&#xD;
      used method in clinical practice is the Risk of Malignancy Index (RMI). The RMI is an easy to&#xD;
      use scoring system recommended by many national guidelines concerning the management of&#xD;
      ovarian masses, including the national guideline in the Netherlands. The RMI combines&#xD;
      ultrasound variables, menopausal status and serum CA125 into a score used to predict the risk&#xD;
      of ovarian cancer before surgery. However, the reported sensitivity and specificity of RMI at&#xD;
      a cut-off value of 200 are relatively low; 75-80% and 85-90%, respectively.&#xD;
&#xD;
      Another method called 'simple ultrasound-based rules' (simple rules), uses different&#xD;
      morphological ultrasound features of adnexal masses (without including menopausal status or&#xD;
      serum CA125 measurement). It includes five simple ultrasound-based rules to predict&#xD;
      malignancy (M-rules) and five rules to predict a benign tumor (B-rules). If both or none of&#xD;
      the M- and B-rules are met (20% of the patients) the test is inconclusive. Recent reports&#xD;
      show that simple rules might be superior to the RMI. In adnexal masses for which the simple&#xD;
      ultrasound rules yield an inconclusive result, subjective assessment of Gray-scale and color&#xD;
      Doppler ultrasound images by an experienced ultrasound examiner can be used as a second stage&#xD;
      test to achieve an optimal diagnostic performance. Subjective assessment by an expert&#xD;
      sonographer is superior to any scoring system or mathematical model when classifying adnexal&#xD;
      masses as benign or malignant. However, it is not feasible and efficient that every patient&#xD;
      would undergo an expert ultrasonography. Therefore, this method is better used as a second&#xD;
      stage test.&#xD;
&#xD;
      Another option is to use Diffusion Weighted - Magnetic Resonance Imaging (DW-MRI) as a second&#xD;
      stage test, when the simple rules yield an inconclusive result. The use of MRI - when&#xD;
      interpret by specialized radiologists- also seems to be superior to RMI in the preoperative&#xD;
      identification of adnexal masses.&#xD;
&#xD;
      The Risk of Malignancy Index (RMI) is the current standard in differentiating benign from&#xD;
      malignant adnexal masses. The simple ultrasound-based rules as a first stage triage test&#xD;
      followed by either subjective assessment by an experienced ultrasound examiner or DW-MRI in&#xD;
      case the simple rules are inconclusive, is the test of comparison. Both the RMI and the&#xD;
      simple rules will be performed in the regional hospitals and MUMC+ by general gynaecologists&#xD;
      during the same ultrasound scan. Only when the simple rules are inconclusive the patient will&#xD;
      be referred to the MUMC+ for a second stage test. From previous publications it can be&#xD;
      deducted that this will be in approximately 20% of patients. Approximately 80% of patients&#xD;
      will not need any additional second stage test.&#xD;
&#xD;
      The histology of the surgically removed adnexal masses is the clinical reference standard.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    interim analysis showed incorrect use of simple rules&#xD;
  </why_stopped>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">October 1, 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sensitivity and specificity</measure>
    <time_frame>This analysis will take place after completing the inclusion of patients (approx. 2 years)</time_frame>
    <description>Sensitivity is defined as the percentage of women with ovarian cancer diagnosed with a malignancy by respectively the RMI and the two-step test. Specificity is defined as the percentage of correctly diagnosed benign masses.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Likelihood ratios</measure>
    <time_frame>This analysis will take place after completing the inclusion of patients (approx. 2 years)</time_frame>
    <description>The positive likelihood ratio is calculated by dividing the sensitivity by 100 minus the specificity. The negative likelihood ratio is calculated as the sensitivity minus 100 divided by the specificity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>positive and negative predictive values</measure>
    <time_frame>This analysis will take place after completing the inclusion of patients (approx. 2 years)</time_frame>
    <description>The positive predictive value is defined as the percentage of patients with a positive test result by respectively RMI and simple rules having malignant disease. The negative predictive value is defined as the percentage of patients with a negative test result having benign disease.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>cost-effectiveness</measure>
    <time_frame>This analysis will take place after completing the inclusion of patients (approx. 2 years)</time_frame>
    <description>The economic evaluation will explore the potential cost-effectiveness of RMI versus the triage test. Incremental cost-effectiveness will be expressed as the costs per correct diagnosis (i.e. either true positive or false negative for malignancy based on histology) including the costs of surgical management following diagnosis. The analysis will take a hospital perspective including all costs from inclusion up to hospital discharge following surgery. As not all data necessary for comparison between the diagnostic strategies will be collected empirically and surgical management will be based on RMI, a simple decision analytic model will be constructed. The comparative sensitivity, specificity and costs of the diagnostic strategies including surgical management for the diagnostic work up of patients with at least one pelvic mass that is suspected to be of ovarian origin, will explicitly be incorporated in the model.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Budget Impact Analysis (BIA)</measure>
    <time_frame>This analysis will take place after completing the inclusion of patients (approx. 2 years)</time_frame>
    <description>A budget impact analysis will be performed according to the ISPOR guidelines. The BIA addresses the financial stream of consequences related to the uptake and diffusion of the triage test to assess affordability. The budget impact will depend on both the costs of the diagnostic strategies, the effect in terms of correct diagnosis, as well as potential future levels of uptake of the triage test. All these elements which determine the potential budget impact will be addressed in this study.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Ovarian Carcinoma</condition>
  <condition>Ovarian Cancer</condition>
  <condition>Ovarian Mass</condition>
  <condition>Ovarian Cyst</condition>
  <arm_group>
    <arm_group_label>If simple rules are conclusive</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All patients included will undergo an ultrasound scan in which both the RMI and simple ultrasound-based rules are applied. This scan will take place in the hospital of inclusion. For 80% of all patients, this will be the only intervention.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>If simple rules are inconclusive</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>If the simple ultrasound-based rules, used in the first ultrasound scan, yield an inconclusive result (approx. 20% of all patients), patients are refered to the center hospital to undergo a second ultrasound (by an expert) and a DW-MRI scan. Furthermore, these group of patients will be asked to give an extra blood sample in order to perform translational research and validate new biomarkers in the diagnosis of ovarian cancer.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ultrasound by general gynaecologist</intervention_name>
    <description>All patients will undergo an ultrasound by a general gynaecologist at the moment of inclusion. Based on this ultrasound, the gynaecologist will use both the RMI and the simple rules to predict the chance of malignancy.</description>
    <arm_group_label>If simple rules are conclusive</arm_group_label>
    <arm_group_label>If simple rules are inconclusive</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ultrasound by an expert ultrasonographist</intervention_name>
    <description>Patients in which the simple rules yield an inconclusive result (about 20% of all patients) will undergo a second ultrasound scan. This scan is performed by an expert in gynaecological ultrasound.</description>
    <arm_group_label>If simple rules are inconclusive</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>DW-MRI</intervention_name>
    <description>Patients in which the simple rules yield an inconclusive result (about 20% of all patients) will undergo a diffusion weighted MRI.</description>
    <arm_group_label>If simple rules are inconclusive</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Give blood sample</intervention_name>
    <description>Patients in which the simple rules yield an inconclusive result (about 20% of the patients) will be asked for an extra blood sample. We will use these materials to perform translational research and validate new biomarkers in the diagnosis of ovarian cancer.</description>
    <arm_group_label>If simple rules are inconclusive</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female patient;&#xD;
&#xD;
          -  Diagnosed in one of the participating centers with at least one pelvic mass that is&#xD;
             suspected to be of ovarian origin;&#xD;
&#xD;
          -  Are to undergo surgery in order to obtain a final histological diagnosis;&#xD;
&#xD;
          -  18 years of age or older.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant patients;&#xD;
&#xD;
          -  Patients aged under 18 years;&#xD;
&#xD;
          -  Patients in whom the surgery does not take place, or takes place more than 120 days&#xD;
             after RMI and simple ultrasound-based rules are performed;&#xD;
&#xD;
          -  Patients with a prior bilateral oophorectomy;&#xD;
&#xD;
          -  Patients with insufficient or missing data;&#xD;
&#xD;
          -  Patients who do not give or are incapable of giving an informed consent;&#xD;
&#xD;
          -  Patients who are not able or willing to travel to the center hospital for additional&#xD;
             diagnostic procedures.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Evelyne MJ Meys, LLM, BsC</last_name>
    <role>Study Director</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Toon van Gorp, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastricht University Medical Centre (MUMC+)</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laurentius Ziekenhuis Roermond</name>
      <address>
        <city>Roermond</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orbis Medical Sittard</name>
      <address>
        <city>Sittard</city>
        <zip>6162 BG</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VieCuri Venlo</name>
      <address>
        <city>Venlo</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St.Jans Gasthuis Weert</name>
      <address>
        <city>Weert</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>Weber S, McCann CK, Boruta DM, Schorge JO, Growdon WB. Laparoscopic surgical staging of early ovarian cancer. Rev Obstet Gynecol. 2011;4(3-4):117-22.</citation>
    <PMID>22229064</PMID>
  </reference>
  <reference>
    <citation>Timmerman D, Ameye L, Fischerova D, Epstein E, Melis GB, Guerriero S, Van Holsbeke C, Savelli L, Fruscio R, Lissoni AA, Testa AC, Veldman J, Vergote I, Van Huffel S, Bourne T, Valentin L. Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group. BMJ. 2010 Dec 14;341:c6839. doi: 10.1136/bmj.c6839.</citation>
    <PMID>21156740</PMID>
  </reference>
  <reference>
    <citation>Timmerman D, Testa AC, Bourne T, Ameye L, Jurkovic D, Van Holsbeke C, Paladini D, Van Calster B, Vergote I, Van Huffel S, Valentin L. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol. 2008 Jun;31(6):681-90. doi: 10.1002/uog.5365.</citation>
    <PMID>18504770</PMID>
  </reference>
  <reference>
    <citation>Van Gorp T, Veldman J, Van Calster B, Cadron I, Leunen K, Amant F, Timmerman D, Vergote I. Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses. Eur J Cancer. 2012 Jul;48(11):1649-56. doi: 10.1016/j.ejca.2011.12.003. Epub 2012 Jan 5.</citation>
    <PMID>22226481</PMID>
  </reference>
  <reference>
    <citation>Valentin L, Jurkovic D, Van Calster B, Testa A, Van Holsbeke C, Bourne T, Vergote I, Van Huffel S, Timmerman D. Adding a single CA 125 measurement to ultrasound imaging performed by an experienced examiner does not improve preoperative discrimination between benign and malignant adnexal masses. Ultrasound Obstet Gynecol. 2009 Sep;34(3):345-54. doi: 10.1002/uog.6415.</citation>
    <PMID>19585547</PMID>
  </reference>
  <reference>
    <citation>Dodge JE, Covens AL, Lacchetti C, Elit LM, Le T, Devries-Aboud M, Fung-Kee-Fung M; Gynecology Cancer Disease Site Group. Preoperative identification of a suspicious adnexal mass: a systematic review and meta-analysis. Gynecol Oncol. 2012 Jul;126(1):157-66. doi: 10.1016/j.ygyno.2012.03.048. Epub 2012 Apr 6.</citation>
    <PMID>22484399</PMID>
  </reference>
  <reference>
    <citation>Tingulstad S, Hagen B, Skjeldestad FE, Halvorsen T, Nustad K, Onsrud M. The risk-of-malignancy index to evaluate potential ovarian cancers in local hospitals. Obstet Gynecol. 1999 Mar;93(3):448-52.</citation>
    <PMID>10074998</PMID>
  </reference>
  <reference>
    <citation>Tingulstad S, Hagen B, Skjeldestad FE, Onsrud M, Kiserud T, Halvorsen T, Nustad K. Evaluation of a risk of malignancy index based on serum CA125, ultrasound findings and menopausal status in the pre-operative diagnosis of pelvic masses. Br J Obstet Gynaecol. 1996 Aug;103(8):826-31. doi: 10.1111/j.1471-0528.1996.tb09882.x.</citation>
    <PMID>8760716</PMID>
  </reference>
  <reference>
    <citation>Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol. 1990 Oct;97(10):922-9. doi: 10.1111/j.1471-0528.1990.tb02448.x.</citation>
    <PMID>2223684</PMID>
  </reference>
  <reference>
    <citation>Mauskopf JA, Sullivan SD, Annemans L, Caro J, Mullins CD, Nuijten M, Orlewska E, Watkins J, Trueman P. Principles of good practice for budget impact analysis: report of the ISPOR Task Force on good research practices--budget impact analysis. Value Health. 2007 Sep-Oct;10(5):336-47. doi: 10.1111/j.1524-4733.2007.00187.x.</citation>
    <PMID>17888098</PMID>
  </reference>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <last_update_submitted>March 24, 2017</last_update_submitted>
  <last_update_submitted_qc>March 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ovarian cancer</keyword>
  <keyword>Diagnosis</keyword>
  <keyword>Risk of Malignancy Index</keyword>
  <keyword>RMI</keyword>
  <keyword>Ultrasound</keyword>
  <keyword>Simple ultrasound-based rules</keyword>
  <keyword>DW-MRI</keyword>
  <keyword>Subjective assessment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Ovarian Cysts</mesh_term>
  </condition_browse>
  <!-- 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/NCT02218502
org study id: NL44181.068.13
nct id: NCT02218502
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
This study is performed to compare the diagnostic performance and cost-effectiveness of
      different diagnostic methods for differentiating benign from malignant adnexal (ovary or
      Fallopian tube) masses: the Risk of Malignancy Index (RMI) will be compared with a two-step
      triage test called "simple ultrasound-based rules" supplemented -if necessary- with either
      subjective assessment by an expert sonographer or Diffusion Weighted - Magnetic Resonance
      Imaging (DW-MRI). The investigators will test the hypothesis that this two-step triage test
      will have better diagnostic accuracy than the RMI and therefore will improve the management
      of women with adnexal masses.
Estimating whether an adnexal mass is malignant or not is essential in the preoperative
      management of adnexal masses. Recognizing cancer means treatment is not delayed and
      appropriate staging or debulking surgery can be carried out after referral to specialized
      surgical centers. Vice versa, benign lesions may be managed conservatively or with minimal
      invasive surgery in non-centre hospitals. This will limit morbidity and will avoid
      unnecessary costs: laparoscopic surgery offers lower estimated blood loss, shorter hospital
      stay, and fewer postoperative complications with an improved quality of life and faster
      return to normal functioning.

      There are several methods to distinguish benign from malignant adnexal masses. The commonly
      used method in clinical practice is the Risk of Malignancy Index (RMI). The RMI is an easy to
      use scoring system recommended by many national guidelines concerning the management of
      ovarian masses, including the national guideline in the Netherlands. The RMI combines
      ultrasound variables, menopausal status and serum CA125 into a score used to predict the risk
      of ovarian cancer before surgery. However, the reported sensitivity and specificity of RMI at
      a cut-off value of 200 are relatively low; 75-80% and 85-90%, respectively.

      Another method called 'simple ultrasound-based rules' (simple rules), uses different
      morphological ultrasound features of adnexal masses (without including menopausal status or
      serum CA125 measurement). It includes five simple ultrasound-based rules to predict
      malignancy (M-rules) and five rules to predict a benign tumor (B-rules). If both or none of
      the M- and B-rules are met (20% of the patients) the test is inconclusive. Recent reports
      show that simple rules might be superior to the RMI. In adnexal masses for which the simple
      ultrasound rules yield an inconclusive result, subjective assessment of Gray-scale and color
      Doppler ultrasound images by an experienced ultrasound examiner can be used as a second stage
      test to achieve an optimal diagnostic performance. Subjective assessment by an expert
      sonographer is superior to any scoring system or mathematical model when classifying adnexal
      masses as benign or malignant. However, it is not feasible and efficient that every patient
      would undergo an expert ultrasonography. Therefore, this method is better used as a second
      stage test.

      Another option is to use Diffusion Weighted - Magnetic Resonance Imaging (DW-MRI) as a second
      stage test, when the simple rules yield an inconclusive result. The use of MRI - when
      interpret by specialized radiologists- also seems to be superior to RMI in the preoperative
      identification of adnexal masses.

      The Risk of Malignancy Index (RMI) is the current standard in differentiating benign from
      malignant adnexal masses. The simple ultrasound-based rules as a first stage triage test
      followed by either subjective assessment by an experienced ultrasound examiner or DW-MRI in
      case the simple rules are inconclusive, is the test of comparison. Both the RMI and the
      simple rules will be performed in the regional hospitals and MUMC+ by general gynaecologists
      during the same ultrasound scan. Only when the simple rules are inconclusive the patient will
      be referred to the MUMC+ for a second stage test. From previous publications it can be
      deducted that this will be in approximately 20% of patients. Approximately 80% of patients
      will not need any additional second stage test.

      The histology of the surgically removed adnexal masses is the clinical reference standard.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: Single (Care Provider)
measure: Sensitivity and specificity
time frame: This analysis will take place after completing the inclusion of patients (approx. 2 years)
description: Sensitivity is defined as the percentage of women with ovarian cancer diagnosed with a malignancy by respectively the RMI and the two-step test. Specificity is defined as the percentage of correctly diagnosed benign masses.
measure: Likelihood ratios
time frame: This analysis will take place after completing the inclusion of patients (approx. 2 years)
description: The positive likelihood ratio is calculated by dividing the sensitivity by 100 minus the specificity. The negative likelihood ratio is calculated as the sensitivity minus 100 divided by the specificity.
measure: positive and negative predictive values
time frame: This analysis will take place after completing the inclusion of patients (approx. 2 years)
description: The positive predictive value is defined as the percentage of patients with a positive test result by respectively RMI and simple rules having malignant disease. The negative predictive value is defined as the percentage of patients with a negative test result having benign disease.
measure: cost-effectiveness
time frame: This analysis will take place after completing the inclusion of patients (approx. 2 years)
description: The economic evaluation will explore the potential cost-effectiveness of RMI versus the triage test. Incremental cost-effectiveness will be expressed as the costs per correct diagnosis (i.e. either true positive or false negative for malignancy based on histology) including the costs of surgical management following diagnosis. The analysis will take a hospital perspective including all costs from inclusion up to hospital discharge following surgery. As not all data necessary for comparison between the diagnostic strategies will be collected empirically and surgical management will be based on RMI, a simple decision analytic model will be constructed. The comparative sensitivity, specificity and costs of the diagnostic strategies including surgical management for the diagnostic work up of patients with at least one pelvic mass that is suspected to be of ovarian origin, will explicitly be incorporated in the model.
measure: Budget Impact Analysis (BIA)
time frame: This analysis will take place after completing the inclusion of patients (approx. 2 years)
description: A budget impact analysis will be performed according to the ISPOR guidelines. The BIA addresses the financial stream of consequences related to the uptake and diffusion of the triage test to assess affordability. The budget impact will depend on both the costs of the diagnostic strategies, the effect in terms of correct diagnosis, as well as potential future levels of uptake of the triage test. All these elements which determine the potential budget impact will be addressed in this study.
arm group label: If simple rules are conclusive
arm group type: Other
description: All patients included will undergo an ultrasound scan in which both the RMI and simple ultrasound-based rules are applied. This scan will take place in the hospital of inclusion. For 80% of all patients, this will be the only intervention.
arm group label: If simple rules are inconclusive
arm group type: Other
description: If the simple ultrasound-based rules, used in the first ultrasound scan, yield an inconclusive result (approx. 20% of all patients), patients are refered to the center hospital to undergo a second ultrasound (by an expert) and a DW-MRI scan. Furthermore, these group of patients will be asked to give an extra blood sample in order to perform translational research and validate new biomarkers in the diagnosis of ovarian cancer.
intervention type: Other
intervention name: Ultrasound by general gynaecologist
description: All patients will undergo an ultrasound by a general gynaecologist at the moment of inclusion. Based on this ultrasound, the gynaecologist will use both the RMI and the simple rules to predict the chance of malignancy.
arm group label: If simple rules are conclusive
arm group label: If simple rules are inconclusive
intervention type: Other
intervention name: Ultrasound by an expert ultrasonographist
description: Patients in which the simple rules yield an inconclusive result (about 20% of all patients) will undergo a second ultrasound scan. This scan is performed by an expert in gynaecological ultrasound.
arm group label: If simple rules are inconclusive
intervention type: Other
intervention name: DW-MRI
description: Patients in which the simple rules yield an inconclusive result (about 20% of all patients) will undergo a diffusion weighted MRI.
arm group label: If simple rules are inconclusive
intervention type: Other
intervention name: Give blood sample
description: Patients in which the simple rules yield an inconclusive result (about 20% of the patients) will be asked for an extra blood sample. We will use these materials to perform translational research and validate new biomarkers in the diagnosis of ovarian cancer.
arm group label: If simple rules are inconclusive
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Evelyne MJ Meys, LLM, BsC
role: Study Director
affiliation: Maastricht University Medical Center
last name: Toon van Gorp, MD, PhD
role: Principal Investigator
affiliation: Maastricht University Medical Center
facility: 
facility: 
facility: 
facility: 
facility: 
country: Netherlands
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PMID: 22229064
citation: Timmerman D, Ameye L, Fischerova D, Epstein E, Melis GB, Guerriero S, Van Holsbeke C, Savelli L, Fruscio R, Lissoni AA, Testa AC, Veldman J, Vergote I, Van Huffel S, Bourne T, Valentin L. Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group. BMJ. 2010 Dec 14;341:c6839. doi: 10.1136/bmj.c6839.
PMID: 21156740
citation: Timmerman D, Testa AC, Bourne T, Ameye L, Jurkovic D, Van Holsbeke C, Paladini D, Van Calster B, Vergote I, Van Huffel S, Valentin L. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol. 2008 Jun;31(6):681-90. doi: 10.1002/uog.5365.
PMID: 18504770
citation: Van Gorp T, Veldman J, Van Calster B, Cadron I, Leunen K, Amant F, Timmerman D, Vergote I. Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses. Eur J Cancer. 2012 Jul;48(11):1649-56. doi: 10.1016/j.ejca.2011.12.003. Epub 2012 Jan 5.
PMID: 22226481
citation: Valentin L, Jurkovic D, Van Calster B, Testa A, Van Holsbeke C, Bourne T, Vergote I, Van Huffel S, Timmerman D. Adding a single CA 125 measurement to ultrasound imaging performed by an experienced examiner does not improve preoperative discrimination between benign and malignant adnexal masses. Ultrasound Obstet Gynecol. 2009 Sep;34(3):345-54. doi: 10.1002/uog.6415.
PMID: 19585547
citation: Dodge JE, Covens AL, Lacchetti C, Elit LM, Le T, Devries-Aboud M, Fung-Kee-Fung M; Gynecology Cancer Disease Site Group. Preoperative identification of a suspicious adnexal mass: a systematic review and meta-analysis. Gynecol Oncol. 2012 Jul;126(1):157-66. doi: 10.1016/j.ygyno.2012.03.048. Epub 2012 Apr 6.
PMID: 22484399
citation: Tingulstad S, Hagen B, Skjeldestad FE, Halvorsen T, Nustad K, Onsrud M. The risk-of-malignancy index to evaluate potential ovarian cancers in local hospitals. Obstet Gynecol. 1999 Mar;93(3):448-52.
PMID: 10074998
citation: Tingulstad S, Hagen B, Skjeldestad FE, Onsrud M, Kiserud T, Halvorsen T, Nustad K. Evaluation of a risk of malignancy index based on serum CA125, ultrasound findings and menopausal status in the pre-operative diagnosis of pelvic masses. Br J Obstet Gynaecol. 1996 Aug;103(8):826-31. doi: 10.1111/j.1471-0528.1996.tb09882.x.
PMID: 8760716
citation: Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol. 1990 Oct;97(10):922-9. doi: 10.1111/j.1471-0528.1990.tb02448.x.
PMID: 2223684
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PMID: 17888098
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Ovarian Cysts