<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/NCT03264170</url>
  </required_header>
  <id_info>
    <org_study_id>C&amp;W17/082017</org_study_id>
    <nct_id>NCT03264170</nct_id>
  </id_info>
  <brief_title>Psychological Impact of Predicting Early Pregnancy Outcomes in Women With Pregnancy of Uncertain Viability</brief_title>
  <acronym>IMPROVE</acronym>
  <official_title>Implementation of a Model for Predicting Early Pregnancy Outcome in Women With Pregnancy of Uncertain Viability: a Psychological Impact Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chelsea and Westminster NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chelsea and Westminster NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate if providing women diagnosed with an intrauterine pregnancy of&#xD;
      uncertain viability with a percentage likelihood of ongoing viability of their pregnancy at&#xD;
      the time of the follow-up ultrasound, will result in improved psychological well-being&#xD;
      (reduced anxiety and depression). Recruited women will be randomised to either receive the&#xD;
      prediction score (intervention arm) or not (control arm).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intrauterine pregnancy of uncertain viability (IPUVI) affects 10-28% of women seen in the&#xD;
      Early Pregnancy Assessment Unit (EPAU). Such women have a pregnancy correctly sited within&#xD;
      the uterus but the viability of the pregnancy cannot be determined at the initial scan. This&#xD;
      finding may represent a normally developing (but early) pregnancy. However, approximately 50%&#xD;
      of these pregnancies will eventually miscarry. The current recommendation from The National&#xD;
      Institute for Health and Care Excellence (NICE) is to offer a confirmatory scan after 14&#xD;
      days.&#xD;
&#xD;
      This 14-day interval is particularly distressing for women and diagnostic uncertainty in&#xD;
      early pregnancy is associated with heightened levels of anxiety and depression. NICE Evidence&#xD;
      Update 71 (2014) suggests that provision of more information about the likely outcome of the&#xD;
      pregnancy (prior to the repeat ultrasound) may benefit psychological health.&#xD;
&#xD;
      The investigators have previously developed, validated and published a mathematical tool to&#xD;
      predict pregnancy viability after diagnosis of IPUVI (549 participants). The tool (which&#xD;
      takes account of maternal age, vaginal bleeding score and ultrasound measurements) is&#xD;
      established as an accurate research tool having been externally validated in a different test&#xD;
      population. Having established its performance, the investigators would like to provide women&#xD;
      with this individualised prediction of their pregnancy outcome. If psychologically beneficial&#xD;
      (and not harmful) this tool may help up to a third of the EPAU population.&#xD;
&#xD;
      This will be a single centre, prospective non-blind randomised control study. All eligible&#xD;
      women with IPUVI ultrasound classification at Chelsea and Westminster Hospital will be&#xD;
      identified and invited to be recruited to the study.&#xD;
&#xD;
      Following recruitment, a woman will be randomised by random computer generator to either&#xD;
      Group I (intervention group - receive the prediction score) or Group II (control group - do&#xD;
      not receive the prediction score).&#xD;
&#xD;
      Potential participants will be identified on a daily basis by those that regularly perform&#xD;
      ultrasound scans within the department; sonographers, nurse specialists, research fellows and&#xD;
      consultants. Once identified, they shall be approached by the local researcher for a&#xD;
      face-to-face consultation who will confirm their eligibility criteria and explain the study.&#xD;
      In addition, the detailed patient information sheet (PIS) will be provided before taking&#xD;
      informed written consent. Clinicians who perform ultrasound scans out of hours, will be&#xD;
      notified of the study and asked to inform eligible women about the study and obtain consent&#xD;
      for the local researcher to contact them the next working day.&#xD;
&#xD;
      Written, informed consent will be taken prior to recruitment from all participants. It will&#xD;
      clearly state that the participant is free to withdraw from the study at any time for any&#xD;
      reason without prejudice to future care, and with no obligation to give the reason for&#xD;
      withdrawal.&#xD;
&#xD;
      It is estimated that a total of 250 women will be recruited (125 participants in each group).&#xD;
      Data will be collected from all women at three points during the course of the study. A&#xD;
      single, validated scale will be used for data collection regarding psychological well-being.&#xD;
      The questionnaire to be used is the Hospital Anxiety and Depression Scale (HADS) by Zigmond&#xD;
      and Snaith (1983).&#xD;
&#xD;
      Each questionnaire will take approximately 5-10 minutes to complete. The questionnaires will&#xD;
      be sent to participants via email (or post if participants do not have access to email). If a&#xD;
      participant does not initially respond the researcher may send one reminder email and contact&#xD;
      them by telephone on one occasion with prior consent from the participant. If the participant&#xD;
      does not respond following these reminders they will be withdrawn from the study. The local&#xD;
      researcher will monitor the progress of each participant's pregnancy prior to sending out the&#xD;
      questionnaires. Women who are known to have undergone termination of pregnancy prior to&#xD;
      completion of all three questionnaires will be withdrawn from the study and not contacted&#xD;
      with further questionnaires.&#xD;
&#xD;
      Participants in Group I will also be invited to complete a patient experience questionnaire&#xD;
      at the end of the study period to assess their perceived acceptability and usefulness of the&#xD;
      tool. This has been developed specifically for this study using modified versions of the&#xD;
      Technology Acceptance Model (Davis et al 1989).&#xD;
&#xD;
      The potential benefits of the study are outlined. This study will confirm whether this&#xD;
      prediction tool is of clinical and psychological benefit to the patient.&#xD;
&#xD;
      Women may find the questionnaires they are asked to complete prompt them to seek help earlier&#xD;
      for conditions which may otherwise have gone untreated such as anxiety and depression. In&#xD;
      addition, they may find it therapeutic to be able to express their opinions, emotions and&#xD;
      feelings during the period of uncertainty.&#xD;
&#xD;
      If the study shows that the prediction tool is acceptable to patients (as well as being&#xD;
      accurate in terms of the actual pregnancy outcome) this will allow units to more&#xD;
      appropriately triage follow-up plans were resources are limited.&#xD;
&#xD;
      Following the study, it is anticipated that the use of the tool could be extended to other&#xD;
      clinical sites to aid the management and expectations of women diagnosed with IPUVI. The NICE&#xD;
      Evidence Update specifically refers to this prediction tool and it is anticipated that this&#xD;
      will be a nationally recommended tool if validated in this study.&#xD;
&#xD;
      In terms of potential risks or burdens involved, there will be no physical risks incurred by&#xD;
      participation in the study. Recruited women will not be expected to have any additional&#xD;
      visits to the hospital during the study, over and above usual care. The investigators are&#xD;
      aware that when conducting a study of anxiety symptoms, it could potentially identify a woman&#xD;
      with an undiagnosed mental health condition, issues of self-harm or potential harm to others.&#xD;
      The principal investigator will check the survey responses regularly and will highlight any&#xD;
      responses which are of serious concern. The investigator will then contact the woman directly&#xD;
      to discuss her responses. The participant will be encouraged to see the General Practitioner&#xD;
      (GP) if deemed necessary. If the participant does not wish to see the GP or there is&#xD;
      persistent concern from the local researcher the confidentiality clause may need to be broken&#xD;
      in the interest of safety of the participant and others. The local researcher will then&#xD;
      contact the GP directly after informing the participant of their intended actions, to report&#xD;
      these concerns.It is possible that the participants will not perceive any individual benefit&#xD;
      from participating in this study. It is possible that the women will not perceive any&#xD;
      individual benefit from participating in this study.&#xD;
&#xD;
      A statistician will be consulted to assist in analysis of the data collected from the study.&#xD;
&#xD;
      To calculate the sample sizes, power calculations were performed on the HADS scale. Puhan et&#xD;
      al (2008) report the minimal important difference in HADS scores is 1.5 units for a&#xD;
      significance level of 0.05 and a statistical power of 80% when considering an intervention.&#xD;
      Based upon this assumption and a common standard deviation of 4 points, 125 women are needed&#xD;
      for each group (total 250 women). A drop-out rate of 10% is anticipated.&#xD;
&#xD;
      The following statistical analyses will be performed:&#xD;
&#xD;
      Descriptive statistics will be used to compare the two groups in terms of baseline&#xD;
      demographic characteristics. Continuous variables normally distributed will be described&#xD;
      reporting mean and standard deviation, otherwise median and interquartile range will be used.&#xD;
      Categorical variables will be reported with frequency tables. To compare HADS scores between&#xD;
      groups I and II, the t-test will be performed for continuous variables normally distributed,&#xD;
      otherwise the Mann-Whitney U test will be used. The Chi-squared test will be used for&#xD;
      categorical variables.&#xD;
&#xD;
      A statistically significant difference will be considered as a p-value &lt;0.05. The data will&#xD;
      be checked for abnormalities, spurious and missing data. These will be coded separately and&#xD;
      treated accordingly. Analyses will be carried out using Stata statistical software, Release&#xD;
      14 (StataCorp, College Station, TX).&#xD;
&#xD;
      Throughout the study (and afterwards), the research investigators will welcome inspections&#xD;
      and monitoring of the conduct of the research to ensure that the quality of the research is&#xD;
      upheld and that the agreed practice is being adhered to. This includes offering direct access&#xD;
      to any documents.&#xD;
&#xD;
      Data will be stored on secure computers at the specific hospital conducting the study using&#xD;
      password protected access to databases. Hard copy data (consent and registration forms) will&#xD;
      be stored within the unit site files which will be kept in secure areas.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">March 2018</start_date>
  <completion_date type="Anticipated">March 2020</completion_date>
  <primary_completion_date type="Anticipated">September 2019</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>Parallel Assignment</intervention_model>
    <intervention_model_description>All participating women will be randomised to one of two groups at the time of recruitment. The intervention group will receive the prediction score. The control group will not receive the prediction score.</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>A change in self-reported psychological well-being from diagnosis to follow-up between the two groups.</measure>
    <time_frame>14 days</time_frame>
    <description>To assess and compare if there is any significant difference in symptoms of anxiety and depression during the uncertain period, as measured by the Hospital and Anxiety Depression Score in the two groups of women all diagnosed with IPUVI. The two groups will be; 1) women randomised to receive the prediction tool and 2) women randomised to not receive the prediction tool.&#xD;
2. To assess and compare whether the symptoms of anxiety and depression in the two groups of women change over three defined time points: immediately after the initial ultrasound/ diagnosis, at 72 hours post ultrasound and immediately prior to the follow-up ultrasound at 14 days.&#xD;
The questionnaire has two components, one relating to anxiety symptoms (HADS-A) and one relating to depressive symptoms (HADS-D). Each component comprises seven statements. Each statement is scored 0-3 yielding a total of 0-21 points for each component.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient Experience of the prediction tool</measure>
    <time_frame>14 days</time_frame>
    <description>3. To assess the patient experience during the study period by applying a self-reported experience questionnaire on the acceptability and perceived usefulness of the prediction tool, in those women who receive it. The questionnaire has been developed by the study investigators using modified versions of the Technology Acceptance Model by Davis et al, 1989.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Uncertain Viability of Pregnancy</condition>
  <condition>Anxiety</condition>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>Prediction of pregnancy outcome</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Women will receive an individualised prediction score of the pregnancy being viable at the follow-up ultrasound generated from the prediction tool.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Women will not receive the prediction score</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Prediction of pregnancy outcome</intervention_name>
    <description>The intervention group will receive the individualised prediction of their pregnancy (as a percentage). The prediction is calculated by a validated, accurate mathematical model using specific background information and ultrasound data for each participant.</description>
    <arm_group_label>Prediction of pregnancy outcome</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years+&#xD;
&#xD;
          -  Diagnosis of IPUVI on initial ultrasound&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current mental health condition (anxiety, depression, eating disorder). The condition&#xD;
             will be considered current if it has required one or more consultations with a medical&#xD;
             professional (including a psychologist) over the past 6 months (women with past mental&#xD;
             health condition will not be excluded)&#xD;
&#xD;
          -  The patient is planning a termination&#xD;
&#xD;
          -  Multiple order pregnancies&#xD;
&#xD;
          -  Women who in the opinion of the researcher by virtue of language or learning&#xD;
             impairment would be unable to give fully informed consent to the study&#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>Cecilia Bottomley, MRCOG MD</last_name>
    <role>Study Chair</role>
    <affiliation>Chelsea and Westminster NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kim K Lawson, MBChB</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chelsea and Westminster NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kim K Lawson, MBChB</last_name>
    <phone>02033155070</phone>
    <email>kimlawson@nhs.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Cecilia Bottomley, MRCOG MD</last_name>
    <phone>02033155070</phone>
    <email>cecilia.bottomley@chelwest.nhs.uk</email>
  </overall_contact_backup>
  <reference>
    <citation>Bottomley C, Van Belle V, Mukri F, Kirk E, Van Huffel S, Timmerman D, Bourne T. The optimal timing of an ultrasound scan to assess the location and viability of an early pregnancy. Hum Reprod. 2009 Aug;24(8):1811-7. doi: 10.1093/humrep/dep084. Epub 2009 Apr 10.</citation>
    <PMID>19363041</PMID>
  </reference>
  <reference>
    <citation>Davison AZ, Appiah A, Sana Y, Johns J, Ross JA. The psychological effects and patient acceptability of a test to predict viability in early pregnancy: a prospective randomised study. Eur J Obstet Gynecol Reprod Biol. 2014 Jul;178:95-9. doi: 10.1016/j.ejogrb.2014.04.002. Epub 2014 Apr 18.</citation>
    <PMID>24837026</PMID>
  </reference>
  <reference>
    <citation>Richardson A, Raine-Fenning N, Deb S, Campbell B, Vedhara K. Anxiety associated with diagnostic uncertainty in early pregnancy. Ultrasound Obstet Gynecol. 2017 Aug;50(2):247-254. doi: 10.1002/uog.17214. Epub 2017 Jun 27.</citation>
    <PMID>27484256</PMID>
  </reference>
  <reference>
    <citation>Bottomley C, Van Belle V, Kirk E, Van Huffel S, Timmerman D, Bourne T. Accurate prediction of pregnancy viability by means of a simple scoring system. Hum Reprod. 2013 Jan;28(1):68-76. doi: 10.1093/humrep/des352. Epub 2012 Oct 30.</citation>
    <PMID>23111205</PMID>
  </reference>
  <reference>
    <citation>Bottomley C, Van Belle V, Pexsters A, Papageorghiou AT, Mukri F, Kirk E, Van Huffel S, Timmerman D, Bourne T. A model and scoring system to predict outcome of intrauterine pregnancies of uncertain viability. Ultrasound Obstet Gynecol. 2011 May;37(5):588-95. doi: 10.1002/uog.9007.</citation>
    <PMID>21520315</PMID>
  </reference>
  <reference>
    <citation>Lok IH, Neugebauer R. Psychological morbidity following miscarriage. Best Pract Res Clin Obstet Gynaecol. 2007 Apr;21(2):229-47. doi: 10.1016/j.bpobgyn.2006.11.007. Epub 2007 Feb 20.</citation>
    <PMID>17317322</PMID>
  </reference>
  <reference>
    <citation>Farren J, Jalmbrant M, Ameye L, Joash K, Mitchell-Jones N, Tapp S, Timmerman D, Bourne T. Post-traumatic stress, anxiety and depression following miscarriage or ectopic pregnancy: a prospective cohort study. BMJ Open. 2016 Nov 2;6(11):e011864. doi: 10.1136/bmjopen-2016-011864.</citation>
    <PMID>27807081</PMID>
  </reference>
  <reference>
    <citation>Guha S, Van Belle V, Bottomley C, Preisler J, Vathanan V, Sayasneh A, Stalder C, Timmerman D, Bourne T. External validation of models and simple scoring systems to predict miscarriage in intrauterine pregnancies of uncertain viability. Hum Reprod. 2013 Nov;28(11):2905-11. doi: 10.1093/humrep/det342. Epub 2013 Aug 26.</citation>
    <PMID>23980057</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>March 5, 2018</last_update_submitted>
  <last_update_submitted_qc>March 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2018</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>Depression</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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>March 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT03264170/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03264170
org study id: C&W17/082017
nct id: NCT03264170
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will evaluate if providing women diagnosed with an intrauterine pregnancy of
      uncertain viability with a percentage likelihood of ongoing viability of their pregnancy at
      the time of the follow-up ultrasound, will result in improved psychological well-being
      (reduced anxiety and depression). Recruited women will be randomised to either receive the
      prediction score (intervention arm) or not (control arm).
Intrauterine pregnancy of uncertain viability (IPUVI) affects 10-28% of women seen in the
      Early Pregnancy Assessment Unit (EPAU). Such women have a pregnancy correctly sited within
      the uterus but the viability of the pregnancy cannot be determined at the initial scan. This
      finding may represent a normally developing (but early) pregnancy. However, approximately 50%
      of these pregnancies will eventually miscarry. The current recommendation from The National
      Institute for Health and Care Excellence (NICE) is to offer a confirmatory scan after 14
      days.

      This 14-day interval is particularly distressing for women and diagnostic uncertainty in
      early pregnancy is associated with heightened levels of anxiety and depression. NICE Evidence
      Update 71 (2014) suggests that provision of more information about the likely outcome of the
      pregnancy (prior to the repeat ultrasound) may benefit psychological health.

      The investigators have previously developed, validated and published a mathematical tool to
      predict pregnancy viability after diagnosis of IPUVI (549 participants). The tool (which
      takes account of maternal age, vaginal bleeding score and ultrasound measurements) is
      established as an accurate research tool having been externally validated in a different test
      population. Having established its performance, the investigators would like to provide women
      with this individualised prediction of their pregnancy outcome. If psychologically beneficial
      (and not harmful) this tool may help up to a third of the EPAU population.

      This will be a single centre, prospective non-blind randomised control study. All eligible
      women with IPUVI ultrasound classification at Chelsea and Westminster Hospital will be
      identified and invited to be recruited to the study.

      Following recruitment, a woman will be randomised by random computer generator to either
      Group I (intervention group - receive the prediction score) or Group II (control group - do
      not receive the prediction score).

      Potential participants will be identified on a daily basis by those that regularly perform
      ultrasound scans within the department; sonographers, nurse specialists, research fellows and
      consultants. Once identified, they shall be approached by the local researcher for a
      face-to-face consultation who will confirm their eligibility criteria and explain the study.
      In addition, the detailed patient information sheet (PIS) will be provided before taking
      informed written consent. Clinicians who perform ultrasound scans out of hours, will be
      notified of the study and asked to inform eligible women about the study and obtain consent
      for the local researcher to contact them the next working day.

      Written, informed consent will be taken prior to recruitment from all participants. It will
      clearly state that the participant is free to withdraw from the study at any time for any
      reason without prejudice to future care, and with no obligation to give the reason for
      withdrawal.

      It is estimated that a total of 250 women will be recruited (125 participants in each group).
      Data will be collected from all women at three points during the course of the study. A
      single, validated scale will be used for data collection regarding psychological well-being.
      The questionnaire to be used is the Hospital Anxiety and Depression Scale (HADS) by Zigmond
      and Snaith (1983).

      Each questionnaire will take approximately 5-10 minutes to complete. The questionnaires will
      be sent to participants via email (or post if participants do not have access to email). If a
      participant does not initially respond the researcher may send one reminder email and contact
      them by telephone on one occasion with prior consent from the participant. If the participant
      does not respond following these reminders they will be withdrawn from the study. The local
      researcher will monitor the progress of each participant's pregnancy prior to sending out the
      questionnaires. Women who are known to have undergone termination of pregnancy prior to
      completion of all three questionnaires will be withdrawn from the study and not contacted
      with further questionnaires.

      Participants in Group I will also be invited to complete a patient experience questionnaire
      at the end of the study period to assess their perceived acceptability and usefulness of the
      tool. This has been developed specifically for this study using modified versions of the
      Technology Acceptance Model (Davis et al 1989).

      The potential benefits of the study are outlined. This study will confirm whether this
      prediction tool is of clinical and psychological benefit to the patient.

      Women may find the questionnaires they are asked to complete prompt them to seek help earlier
      for conditions which may otherwise have gone untreated such as anxiety and depression. In
      addition, they may find it therapeutic to be able to express their opinions, emotions and
      feelings during the period of uncertainty.

      If the study shows that the prediction tool is acceptable to patients (as well as being
      accurate in terms of the actual pregnancy outcome) this will allow units to more
      appropriately triage follow-up plans were resources are limited.

      Following the study, it is anticipated that the use of the tool could be extended to other
      clinical sites to aid the management and expectations of women diagnosed with IPUVI. The NICE
      Evidence Update specifically refers to this prediction tool and it is anticipated that this
      will be a nationally recommended tool if validated in this study.

      In terms of potential risks or burdens involved, there will be no physical risks incurred by
      participation in the study. Recruited women will not be expected to have any additional
      visits to the hospital during the study, over and above usual care. The investigators are
      aware that when conducting a study of anxiety symptoms, it could potentially identify a woman
      with an undiagnosed mental health condition, issues of self-harm or potential harm to others.
      The principal investigator will check the survey responses regularly and will highlight any
      responses which are of serious concern. The investigator will then contact the woman directly
      to discuss her responses. The participant will be encouraged to see the General Practitioner
      (GP) if deemed necessary. If the participant does not wish to see the GP or there is
      persistent concern from the local researcher the confidentiality clause may need to be broken
      in the interest of safety of the participant and others. The local researcher will then
      contact the GP directly after informing the participant of their intended actions, to report
      these concerns.It is possible that the participants will not perceive any individual benefit
      from participating in this study. It is possible that the women will not perceive any
      individual benefit from participating in this study.

      A statistician will be consulted to assist in analysis of the data collected from the study.

      To calculate the sample sizes, power calculations were performed on the HADS scale. Puhan et
      al (2008) report the minimal important difference in HADS scores is 1.5 units for a
      significance level of 0.05 and a statistical power of 80% when considering an intervention.
      Based upon this assumption and a common standard deviation of 4 points, 125 women are needed
      for each group (total 250 women). A drop-out rate of 10% is anticipated.

      The following statistical analyses will be performed:

      Descriptive statistics will be used to compare the two groups in terms of baseline
      demographic characteristics. Continuous variables normally distributed will be described
      reporting mean and standard deviation, otherwise median and interquartile range will be used.
      Categorical variables will be reported with frequency tables. To compare HADS scores between
      groups I and II, the t-test will be performed for continuous variables normally distributed,
      otherwise the Mann-Whitney U test will be used. The Chi-squared test will be used for
      categorical variables.

      A statistically significant difference will be considered as a p-value <0.05. The data will
      be checked for abnormalities, spurious and missing data. These will be coded separately and
      treated accordingly. Analyses will be carried out using Stata statistical software, Release
      14 (StataCorp, College Station, TX).

      Throughout the study (and afterwards), the research investigators will welcome inspections
      and monitoring of the conduct of the research to ensure that the quality of the research is
      upheld and that the agreed practice is being adhered to. This includes offering direct access
      to any documents.

      Data will be stored on secure computers at the specific hospital conducting the study using
      password protected access to databases. Hard copy data (consent and registration forms) will
      be stored within the unit site files which will be kept in secure areas.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: All participating women will be randomised to one of two groups at the time of recruitment. The intervention group will receive the prediction score. The control group will not receive the prediction score.
primary purpose: Screening
masking: None (Open Label)
measure: A change in self-reported psychological well-being from diagnosis to follow-up between the two groups.
time frame: 14 days
description: To assess and compare if there is any significant difference in symptoms of anxiety and depression during the uncertain period, as measured by the Hospital and Anxiety Depression Score in the two groups of women all diagnosed with IPUVI. The two groups will be; 1) women randomised to receive the prediction tool and 2) women randomised to not receive the prediction tool.
2. To assess and compare whether the symptoms of anxiety and depression in the two groups of women change over three defined time points: immediately after the initial ultrasound/ diagnosis, at 72 hours post ultrasound and immediately prior to the follow-up ultrasound at 14 days.
The questionnaire has two components, one relating to anxiety symptoms (HADS-A) and one relating to depressive symptoms (HADS-D). Each component comprises seven statements. Each statement is scored 0-3 yielding a total of 0-21 points for each component.
measure: Patient Experience of the prediction tool
time frame: 14 days
description: 3. To assess the patient experience during the study period by applying a self-reported experience questionnaire on the acceptability and perceived usefulness of the prediction tool, in those women who receive it. The questionnaire has been developed by the study investigators using modified versions of the Technology Acceptance Model by Davis et al, 1989.
arm group label: Prediction of pregnancy outcome
arm group type: Active Comparator
description: Women will receive an individualised prediction score of the pregnancy being viable at the follow-up ultrasound generated from the prediction tool.
arm group label: Control
arm group type: No Intervention
description: Women will not receive the prediction score
intervention type: Diagnostic Test
intervention name: Prediction of pregnancy outcome
description: The intervention group will receive the individualised prediction of their pregnancy (as a percentage). The prediction is calculated by a validated, accurate mathematical model using specific background information and ultrasound data for each participant.
arm group label: Prediction of pregnancy outcome
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Cecilia Bottomley, MRCOG MD
role: Study Chair
affiliation: Chelsea and Westminster NHS Foundation Trust
last name: Kim K Lawson, MBChB
role: Principal Investigator
affiliation: Chelsea and Westminster NHS Foundation Trust
last name: Kim K Lawson, MBChB
phone: 02033155070
email: kimlawson@nhs.net
last name: Cecilia Bottomley, MRCOG MD
phone: 02033155070
email: cecilia.bottomley@chelwest.nhs.uk
citation: Bottomley C, Van Belle V, Mukri F, Kirk E, Van Huffel S, Timmerman D, Bourne T. The optimal timing of an ultrasound scan to assess the location and viability of an early pregnancy. Hum Reprod. 2009 Aug;24(8):1811-7. doi: 10.1093/humrep/dep084. Epub 2009 Apr 10.
PMID: 19363041
citation: Davison AZ, Appiah A, Sana Y, Johns J, Ross JA. The psychological effects and patient acceptability of a test to predict viability in early pregnancy: a prospective randomised study. Eur J Obstet Gynecol Reprod Biol. 2014 Jul;178:95-9. doi: 10.1016/j.ejogrb.2014.04.002. Epub 2014 Apr 18.
PMID: 24837026
citation: Richardson A, Raine-Fenning N, Deb S, Campbell B, Vedhara K. Anxiety associated with diagnostic uncertainty in early pregnancy. Ultrasound Obstet Gynecol. 2017 Aug;50(2):247-254. doi: 10.1002/uog.17214. Epub 2017 Jun 27.
PMID: 27484256
citation: Bottomley C, Van Belle V, Kirk E, Van Huffel S, Timmerman D, Bourne T. Accurate prediction of pregnancy viability by means of a simple scoring system. Hum Reprod. 2013 Jan;28(1):68-76. doi: 10.1093/humrep/des352. Epub 2012 Oct 30.
PMID: 23111205
citation: Bottomley C, Van Belle V, Pexsters A, Papageorghiou AT, Mukri F, Kirk E, Van Huffel S, Timmerman D, Bourne T. A model and scoring system to predict outcome of intrauterine pregnancies of uncertain viability. Ultrasound Obstet Gynecol. 2011 May;37(5):588-95. doi: 10.1002/uog.9007.
PMID: 21520315
citation: Lok IH, Neugebauer R. Psychological morbidity following miscarriage. Best Pract Res Clin Obstet Gynaecol. 2007 Apr;21(2):229-47. doi: 10.1016/j.bpobgyn.2006.11.007. Epub 2007 Feb 20.
PMID: 17317322
citation: Farren J, Jalmbrant M, Ameye L, Joash K, Mitchell-Jones N, Tapp S, Timmerman D, Bourne T. Post-traumatic stress, anxiety and depression following miscarriage or ectopic pregnancy: a prospective cohort study. BMJ Open. 2016 Nov 2;6(11):e011864. doi: 10.1136/bmjopen-2016-011864.
PMID: 27807081
citation: Guha S, Van Belle V, Bottomley C, Preisler J, Vathanan V, Sayasneh A, Stalder C, Timmerman D, Bourne T. External validation of models and simple scoring systems to predict miscarriage in intrauterine pregnancies of uncertain viability. Hum Reprod. 2013 Nov;28(11):2905-11. doi: 10.1093/humrep/det342. Epub 2013 Aug 26.
PMID: 23980057
responsible party type: Sponsor
mesh term: Depression
sharing ipd: No
provided document: 