xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05981898</url>
    </required_header>
    <id_info>
      <org_study_id>IIHPL-UDR/RCT/004-2022</org_study_id>
      <nct_id>NCT05981898</nct_id>
    </id_info>
    <brief_title>Opt-IVF Multi-center Trial 2 Including All Protocols</brief_title>
    <official_title>An Advanced Decision Tool Opt-IVf for Personalized Medicine for IVF Using Modeling and Optimization</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Stochastic Research Technologies LLC</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Indira IVF, India</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Stochastic Research Technologies LLC</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>
        A multi-center randomized clinical trial is proposed to study the effectiveness of the&#xD;
        advanced decision support tool Opt-IVF for ALL PROTOCOLS in reducing medication, testing, and&#xD;
        improving outcomes.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Aim: A Multi-center Randomized Clinical trial to determine the effectiveness of using the&#xD;
        proposed decision support tool for ALL PROTOCOLS for each patient's customized optimal drug&#xD;
        dosage profile.&#xD;
  &#xD;
        Subject Enrollment&#xD;
  &#xD;
        There are 13 centers involved in this trial. The recruitment plan designed is study-specific&#xD;
        and site-specific. The investigators plan to recruit patients by reaching into the each&#xD;
        center's own database of patients. Each center carries out on average 800 IVF cycles per&#xD;
        year. PIs anticipate easier recruitment since they are not excluding any IVF patients,&#xD;
        whether they are low, high, or average responders undergoing any protocol or patients with&#xD;
        PCOS or not. The in-reach activities to be used include:&#xD;
  &#xD;
        Chart review from site patient database Establishing an internal referral network with all&#xD;
        physicians within the site Educational meetings with providers and physicians Educational&#xD;
        sessions with patients and relatives Financial assistance to patients undergoing the&#xD;
        intervention Training staff to facilitate ICF process by o Effectively conveying risks and&#xD;
        benefits Creating an open environment Monthly calls to site physicians and staff to convey&#xD;
        success stories&#xD;
  &#xD;
        The retention activities include:&#xD;
  &#xD;
        Planning appointments with sites for initial/follow-up visits and providing&#xD;
        flexible/convenient appointment times Spending extra time with patients to understand their&#xD;
        concerns and address them effectively Providing a summary of laboratory results to patients&#xD;
        to demonstrate progress Appointment reminder services Travel assistance for patients/family&#xD;
        members/caregivers, and patient compensation services Identifying the warning signals for&#xD;
        potential drop-outs and working closely with these patients to support them to continue on&#xD;
        the study Study Design and Procedures&#xD;
  &#xD;
        This is a multi-site cohort with two arms (one arm for the intervention and one arm for the&#xD;
        traditional approach) clinical trial involving 60 patients per center i.e. 780 patients&#xD;
        total.&#xD;
  &#xD;
        This task includes thrteen Indira IVF centers all over India, and all the analysis will be&#xD;
        carried out at the Stochastic Research site. Dr. Urmila Diwekar will be an investigator from&#xD;
        the Stochastic Research Technologies LLC, and Dr. Bhoi will be an investigator from the&#xD;
        Indira IVF. Apart from these two investigators, there will be a post-doctoral fellow from&#xD;
        Stochastic Research Technologies LLC and medical personnel from the Indira IVF centers will&#xD;
        be involved in this proposed clinical trial.&#xD;
  &#xD;
        In this study, Opt-IVF will be using the patient's age and day three serum day AMH and AFc&#xD;
        levels to decide the starting dose for the patient's cycle. Opt-IVF will use the first day&#xD;
        and day 5 data collected (Follicular size distribution, estrogen levels) for that patient to&#xD;
        determine the optimal dosage profile for the entire cycle for that patient with the help of&#xD;
        the decision support tool OPTIVF for this intervention in the clinical trial.&#xD;
  &#xD;
        Primary and secondary outcomes: The study's primary outcome measures will be: the proportion&#xD;
        of women with an appropriate number of retrieved oocytes), total hormonal dosage employed&#xD;
        during the cycle, and serum oestradiol concentrations on rHCG day, no.of ultrasounds, no. of&#xD;
        M2s, no. of embryos obtained, no. of grade A embryos and pregnancy rate.&#xD;
  &#xD;
        The secondary outcome measures considered will be: the number of growing follicles (≥11 mm)&#xD;
        on rHCG day; the number of large ovarian follicles ≥17 mm on rHCG day embryos transferred,&#xD;
        fertilization rate, implantation rate, clinical pregnancy rate, OHSS rate, the number of&#xD;
        cryopreserved embryos and the proportion of patients with cryopreserved embryos.&#xD;
  &#xD;
        Data sources&#xD;
  &#xD;
        Data Sources will be View Point (GE) and Syngo Dynamics (Phillips) for the sonographic images&#xD;
        and Cerner for medical record information.&#xD;
  &#xD;
        Expected Risks/Benefits&#xD;
  &#xD;
        Current practice is to use every ultrasound and blood test every day to determine the dosage&#xD;
        for that day that patient by the attending physician. The proposed decision support tool will&#xD;
        be able to predict the patient's response to the hormonal dosage given each day of an IVF&#xD;
        cycle using data from the first two days of that particular cycle. It will also provide a&#xD;
        personalized optimal dosage profile for each patient, maximizing the outcomes and reducing&#xD;
        medications, testing, and side effects. Based on earlier preliminary results, the tool use is&#xD;
        expected to reduce the daily testing up to 75%, reduce the dosage up to 40%, thereby reducing&#xD;
        the side effects like overstimulation, and is expected to provide equal or better outcomes&#xD;
        for the patients. PI's group have carried out retrospective studies with 150 patients in the&#xD;
        USA and India. The investigators also carried out two prospective clinical trials in India.&#xD;
        Both studies support the above conclusion about the methodology. In this study, the&#xD;
        investigators will be conducting prospective clinical studies for this product in the United&#xD;
        States. This will establish the efficacy of this tool for use in clinical practice. There is&#xD;
        no additional risk with the use of this decision support tool other than the possibility of&#xD;
        an unsuccessful cycle, a risk that exists with current practice also. The same medications&#xD;
        are used at dosages 20-40% lower, thus reducing the side effects of the medications.&#xD;
  &#xD;
        Data Collection and Management Procedures&#xD;
  &#xD;
        Collecting the de-identified patient data without any PHI. All the information will be&#xD;
        digitized and managed securely (as needed), so it can be analyzed and researched. Proprietary&#xD;
        file formats may be used in this process.&#xD;
  &#xD;
        Data Protection Throughout the research work of this project, a large volume of data at&#xD;
        various levels of detail. All research members will adhere to the highest standards for&#xD;
        protecting subjects' privacy and the confidentiality of any information collected. Only&#xD;
        properly trained and authorized individuals may access data with personal identifiers at each&#xD;
        Indira IVF center. Nobody from stochastic research technologies will have access to personal&#xD;
        identifiers.&#xD;
  &#xD;
        Backups The company provide automated computer backups. Web Server It has been planned to&#xD;
        disseminate and maintain project information through Stochastic webservers. These are all&#xD;
        hosted on a Windows Server, a VMware virtual machine instance.&#xD;
  &#xD;
        Data Analysis Data analysis will be performed by the co-PI using Excel and Matlab software.&#xD;
  &#xD;
        Quality Control and Quality Assurance Data is recorded and coded in an electronic database.&#xD;
        Categorical data will be compared using Chi-square or Fischer exact test and ANOVA for&#xD;
        frequency table of baseline characteristics. Odds ratios and 95% confidence intervals will be&#xD;
        calculated, as well as 2-sided p values. A value less than 0.05 will be chosen for&#xD;
        significance without adjustment for multiple comparisons. A biostatistician will be consulted&#xD;
        for any statistical analysis beyond the scope of the PI or co-investigators.&#xD;
  &#xD;
        1 Data and Safety Monitoring De-identified data collected is in an excel spreadsheet in a&#xD;
        password-protected computer.&#xD;
  &#xD;
        Statistical Considerations Sample size: Earlier clinical trial shows that for obtaining&#xD;
        statistically significant outcomes for comparing dosage and grade A embryos a small sample 22&#xD;
        patients in each arm was sufficient. However, for other outcomes like number of M2s higher&#xD;
        samples size may be needed. Based on earlier results, the number of samples size is&#xD;
        calculated to be 60 patients in each arm. Therefore, a sample size of 390 in each arm will be&#xD;
        used in this trial.&#xD;
  &#xD;
        Analysis Methods: Between the groups, differences in continuous variables will be assessed&#xD;
        with parametric or non-parametric statistics, as appropriate. Z-tests will be conducted&#xD;
        comparing the proportion of individuals who reported an optimal outcome response.&#xD;
  &#xD;
        Regulatory Requirements Informed Consent The OPTIVF trial will be registered with Clinical&#xD;
        Trials.Gov as per ACTG guidelines. PIs have established IRB-approved consent forms. This&#xD;
        consent form is based on regular or long-form. The form presents detailed information about&#xD;
        the treatments, risks, and benefits, mitigation of risks, etc., in summary, complete details&#xD;
        on all elements of consent. Dr. Bhoi is responsible for this.&#xD;
  &#xD;
        Subject Confidentiality The confidentiality of participants will be safeguarded by the use of&#xD;
        a de-identified dataset. A master data spreadsheet including any necessary PHI will be kept&#xD;
        in a locked file on a secure drive. All data analysis will be performed on the de-identified&#xD;
        dataset. The key for the identification will be kept in a third locked file separate from the&#xD;
        data. Only the co-PI will have access to these files. Data will be entered into SPSS or other&#xD;
        statistical software programs for analysis without subject identifiers.&#xD;
  &#xD;
        Unanticipated Problems Any unanticipated problems will be reported to the IRB as soon as they&#xD;
        are discovered.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">September 15, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>This is a multi-centered randomized clinical trial study with two arms (one arm for OPTIVF and one arm for the conventional approach) In this study, the tool will be using the patient's age and day three serum AMH and FSH levels to decide the starting dose for the patient's cycle. Tool will use the first two days of data collected (Follicular size distribution, estrogen levels) for that patient to determine the optimal dosage profile for the entire cycle for that patient with the help of the decision support tool (OPTIVF )for this intervention in the clinical trial.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Outcomes Assessor)</masking>
      <masking_description>The investigator and outcomes assessor Dr. Urmila Diwekar will only know the de-identified patient details in each arm after the treatment.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Number of Follicles retrieved</measure>
      <time_frame>at the end of cycle (each cycle is 17 days)</time_frame>
      <description>Mature follicles retrieved</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Mii Follicles</measure>
      <time_frame>at the end of cycle (each cycle is 17 days)</time_frame>
      <description>Number of Mii Follicles</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Total number of Embryos</measure>
      <time_frame>at the end of cycle (each cycle is 17 days)</time_frame>
      <description>Total number of Embryos</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Grade A embryos</measure>
      <time_frame>at the end of cycle (each cycle is 17 days)</time_frame>
      <description>Number of Grade A embryos</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Total FSH+HMG Dosage in IUI for the complete cycle</measure>
      <time_frame>at the end of cycle (each cycle is 17 days)</time_frame>
      <description>Total FSH+HMG Dosage in IUI for the complete cycle</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Clinical Pregnancy Rate</measure>
      <time_frame>One month after implantation</time_frame>
      <description>Clinical Pregnancy Rate</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">780</enrollment>
    <condition>IVF</condition>
    <arm_group>
      <arm_group_label>OPTIVF predicted drug dosage</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>This arm will use dosage, trigger predicted by Opt-IVF</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Traditional drug treatment</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Traditional drug treatment</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>OPTIVF dosage</intervention_name>
      <description>Dosage predicted by Opt-IVf</description>
      <arm_group_label>OPTIVF predicted drug dosage</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>traditional Dosage</intervention_name>
      <description>Dosage used traditionally by doctors</description>
      <arm_group_label>Traditional drug treatment</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Inclusion Criteria:&#xD;
  &#xD;
            -  • All-female patients undergoing IVF with own oocyte&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  None&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <gender_based>Yes</gender_based>
      <gender_description>If is a fertility treatment for women</gender_description>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>50 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Urmila Diwekar</last_name>
      <role>Principal Investigator</role>
      <affiliation>Stochastic Research Technologies LLC/University of Illinois at Chicago</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Urmila Diwekar, Ph.D.</last_name>
      <phone>16308863047</phone>
      <email>urmila@vri-custom.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Sanjay Joag, MD, Ph.D.</last_name>
      <phone>16305014451</phone>
      <email>sjoag@yahoo.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Indira IVF</name>
        <address>
          <city>Udaipur</city>
          <state>Rajsthan</state>
          <country>India</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Nihar Bhoi, phD</last_name>
        <phone>07205783512</phone>
        <email>drnihar.bhoi@indiraivf.in</email>
      </contact>
      <contact_backup>
        <last_name>Abhishek Singh</last_name>
        <phone>+917049931933</phone>
        <email>abhishek.thakur@indiraivf.in</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>India</country>
    </location_countries>
    <link>
      <url>http://www.stochastic-research.com/DrDiwekar.htm</url>
      <description>Theoretical papers related to this work can be downloaded from the website</description>
    </link>
    <reference>
      <citation>Diwekar et al., 2022, A Non-Randomized Clinical Trial of a Decision Support Tool to Optimize Superovulation Cycles in Individual Patients, J Fertil In vitro IVF Worldw Reprod Med Genet Stem Cell Biol, Vol.10 Iss.3 No:1000268 Link to the paper: https://www.longdom.org/open-access/a-nonrandomized-clinical-trial-of-a-decision-support-tool-to-optimize-superovulation-cycles-in-individual-patients-93998.html</citation>
    </reference>
    <results_reference>
      <citation>Nisal A, Diwekar U, Bhalerao V. Personalized medicine for in vitro fertilization procedure using modeling and optimal control. J Theor Biol. 2020 Feb 21;487:110105. doi: 10.1016/j.jtbi.2019.110105. Epub 2019 Dec 3.</citation>
      <PMID>31809718</PMID>
    </results_reference>
    <results_reference>
      <citation>Yenkie KM, Diwekar UM, Bhalerao V. Modeling the superovulation stage in in vitro fertilization. IEEE Trans Biomed Eng. 2013 Nov;60(11):3003-8. doi: 10.1109/TBME.2012.2227742. Epub 2012 Nov 15.</citation>
      <PMID>23193444</PMID>
    </results_reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>September 15, 2023</last_update_submitted>
    <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>IVF</keyword>
    <keyword>Opt-IVF</keyword>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>We will provide deidentified data.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_time_frame>After publication of results</ipd_time_frame>
      <ipd_access_criteria>contact PI</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05981898
  org study id: IIHPL-UDR/RCT/004-2022
  nct id: NCT05981898
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  A multi-center randomized clinical trial is proposed to study the effectiveness of the
        advanced decision support tool Opt-IVF for ALL PROTOCOLS in reducing medication, testing, and
        improving outcomes.
  Aim: A Multi-center Randomized Clinical trial to determine the effectiveness of using the
        proposed decision support tool for ALL PROTOCOLS for each patient's customized optimal drug
        dosage profile.
  
        Subject Enrollment
  
        There are 13 centers involved in this trial. The recruitment plan designed is study-specific
        and site-specific. The investigators plan to recruit patients by reaching into the each
        center's own database of patients. Each center carries out on average 800 IVF cycles per
        year. PIs anticipate easier recruitment since they are not excluding any IVF patients,
        whether they are low, high, or average responders undergoing any protocol or patients with
        PCOS or not. The in-reach activities to be used include:
  
        Chart review from site patient database Establishing an internal referral network with all
        physicians within the site Educational meetings with providers and physicians Educational
        sessions with patients and relatives Financial assistance to patients undergoing the
        intervention Training staff to facilitate ICF process by o Effectively conveying risks and
        benefits Creating an open environment Monthly calls to site physicians and staff to convey
        success stories
  
        The retention activities include:
  
        Planning appointments with sites for initial/follow-up visits and providing
        flexible/convenient appointment times Spending extra time with patients to understand their
        concerns and address them effectively Providing a summary of laboratory results to patients
        to demonstrate progress Appointment reminder services Travel assistance for patients/family
        members/caregivers, and patient compensation services Identifying the warning signals for
        potential drop-outs and working closely with these patients to support them to continue on
        the study Study Design and Procedures
  
        This is a multi-site cohort with two arms (one arm for the intervention and one arm for the
        traditional approach) clinical trial involving 60 patients per center i.e. 780 patients
        total.
  
        This task includes thrteen Indira IVF centers all over India, and all the analysis will be
        carried out at the Stochastic Research site. Dr. Urmila Diwekar will be an investigator from
        the Stochastic Research Technologies LLC, and Dr. Bhoi will be an investigator from the
        Indira IVF. Apart from these two investigators, there will be a post-doctoral fellow from
        Stochastic Research Technologies LLC and medical personnel from the Indira IVF centers will
        be involved in this proposed clinical trial.
  
        In this study, Opt-IVF will be using the patient's age and day three serum day AMH and AFc
        levels to decide the starting dose for the patient's cycle. Opt-IVF will use the first day
        and day 5 data collected (Follicular size distribution, estrogen levels) for that patient to
        determine the optimal dosage profile for the entire cycle for that patient with the help of
        the decision support tool OPTIVF for this intervention in the clinical trial.
  
        Primary and secondary outcomes: The study's primary outcome measures will be: the proportion
        of women with an appropriate number of retrieved oocytes), total hormonal dosage employed
        during the cycle, and serum oestradiol concentrations on rHCG day, no.of ultrasounds, no. of
        M2s, no. of embryos obtained, no. of grade A embryos and pregnancy rate.
  
        The secondary outcome measures considered will be: the number of growing follicles (≥11 mm)
        on rHCG day; the number of large ovarian follicles ≥17 mm on rHCG day embryos transferred,
        fertilization rate, implantation rate, clinical pregnancy rate, OHSS rate, the number of
        cryopreserved embryos and the proportion of patients with cryopreserved embryos.
  
        Data sources
  
        Data Sources will be View Point (GE) and Syngo Dynamics (Phillips) for the sonographic images
        and Cerner for medical record information.
  
        Expected Risks/Benefits
  
        Current practice is to use every ultrasound and blood test every day to determine the dosage
        for that day that patient by the attending physician. The proposed decision support tool will
        be able to predict the patient's response to the hormonal dosage given each day of an IVF
        cycle using data from the first two days of that particular cycle. It will also provide a
        personalized optimal dosage profile for each patient, maximizing the outcomes and reducing
        medications, testing, and side effects. Based on earlier preliminary results, the tool use is
        expected to reduce the daily testing up to 75%, reduce the dosage up to 40%, thereby reducing
        the side effects like overstimulation, and is expected to provide equal or better outcomes
        for the patients. PI's group have carried out retrospective studies with 150 patients in the
        USA and India. The investigators also carried out two prospective clinical trials in India.
        Both studies support the above conclusion about the methodology. In this study, the
        investigators will be conducting prospective clinical studies for this product in the United
        States. This will establish the efficacy of this tool for use in clinical practice. There is
        no additional risk with the use of this decision support tool other than the possibility of
        an unsuccessful cycle, a risk that exists with current practice also. The same medications
        are used at dosages 20-40% lower, thus reducing the side effects of the medications.
  
        Data Collection and Management Procedures
  
        Collecting the de-identified patient data without any PHI. All the information will be
        digitized and managed securely (as needed), so it can be analyzed and researched. Proprietary
        file formats may be used in this process.
  
        Data Protection Throughout the research work of this project, a large volume of data at
        various levels of detail. All research members will adhere to the highest standards for
        protecting subjects' privacy and the confidentiality of any information collected. Only
        properly trained and authorized individuals may access data with personal identifiers at each
        Indira IVF center. Nobody from stochastic research technologies will have access to personal
        identifiers.
  
        Backups The company provide automated computer backups. Web Server It has been planned to
        disseminate and maintain project information through Stochastic webservers. These are all
        hosted on a Windows Server, a VMware virtual machine instance.
  
        Data Analysis Data analysis will be performed by the co-PI using Excel and Matlab software.
  
        Quality Control and Quality Assurance Data is recorded and coded in an electronic database.
        Categorical data will be compared using Chi-square or Fischer exact test and ANOVA for
        frequency table of baseline characteristics. Odds ratios and 95% confidence intervals will be
        calculated, as well as 2-sided p values. A value less than 0.05 will be chosen for
        significance without adjustment for multiple comparisons. A biostatistician will be consulted
        for any statistical analysis beyond the scope of the PI or co-investigators.
  
        1 Data and Safety Monitoring De-identified data collected is in an excel spreadsheet in a
        password-protected computer.
  
        Statistical Considerations Sample size: Earlier clinical trial shows that for obtaining
        statistically significant outcomes for comparing dosage and grade A embryos a small sample 22
        patients in each arm was sufficient. However, for other outcomes like number of M2s higher
        samples size may be needed. Based on earlier results, the number of samples size is
        calculated to be 60 patients in each arm. Therefore, a sample size of 390 in each arm will be
        used in this trial.
  
        Analysis Methods: Between the groups, differences in continuous variables will be assessed
        with parametric or non-parametric statistics, as appropriate. Z-tests will be conducted
        comparing the proportion of individuals who reported an optimal outcome response.
  
        Regulatory Requirements Informed Consent The OPTIVF trial will be registered with Clinical
        Trials.Gov as per ACTG guidelines. PIs have established IRB-approved consent forms. This
        consent form is based on regular or long-form. The form presents detailed information about
        the treatments, risks, and benefits, mitigation of risks, etc., in summary, complete details
        on all elements of consent. Dr. Bhoi is responsible for this.
  
        Subject Confidentiality The confidentiality of participants will be safeguarded by the use of
        a de-identified dataset. A master data spreadsheet including any necessary PHI will be kept
        in a locked file on a secure drive. All data analysis will be performed on the de-identified
        dataset. The key for the identification will be kept in a third locked file separate from the
        data. Only the co-PI will have access to these files. Data will be entered into SPSS or other
        statistical software programs for analysis without subject identifiers.
  
        Unanticipated Problems Any unanticipated problems will be reported to the IRB as soon as they
        are discovered.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: This is a multi-centered randomized clinical trial study with two arms (one arm for OPTIVF and one arm for the conventional approach) In this study, the tool will be using the patient's age and day three serum AMH and FSH levels to decide the starting dose for the patient's cycle. Tool will use the first two days of data collected (Follicular size distribution, estrogen levels) for that patient to determine the optimal dosage profile for the entire cycle for that patient with the help of the decision support tool (OPTIVF )for this intervention in the clinical trial.
  primary purpose: Treatment
  masking: Double (Participant, Outcomes Assessor)
  masking description: The investigator and outcomes assessor Dr. Urmila Diwekar will only know the de-identified patient details in each arm after the treatment.
  measure: Number of Follicles retrieved
  time frame: at the end of cycle (each cycle is 17 days)
  description: Mature follicles retrieved
  measure: Number of Mii Follicles
  time frame: at the end of cycle (each cycle is 17 days)
  description: Number of Mii Follicles
  measure: Total number of Embryos
  time frame: at the end of cycle (each cycle is 17 days)
  description: Total number of Embryos
  measure: Number of Grade A embryos
  time frame: at the end of cycle (each cycle is 17 days)
  description: Number of Grade A embryos
  measure: Total FSH+HMG Dosage in IUI for the complete cycle
  time frame: at the end of cycle (each cycle is 17 days)
  description: Total FSH+HMG Dosage in IUI for the complete cycle
  measure: Clinical Pregnancy Rate
  time frame: One month after implantation
  description: Clinical Pregnancy Rate
  arm group label: OPTIVF predicted drug dosage
  arm group type: Experimental
  description: This arm will use dosage, trigger predicted by Opt-IVF
  arm group label: Traditional drug treatment
  arm group type: Active Comparator
  description: Traditional drug treatment
  intervention type: Device
  intervention name: OPTIVF dosage
  description: Dosage predicted by Opt-IVf
  arm group label: OPTIVF predicted drug dosage
  intervention type: Device
  intervention name: traditional Dosage
  description: Dosage used traditionally by doctors
  arm group label: Traditional drug treatment
  criteria: 
  gender: Female
  gender based: Yes
  gender description: If is a fertility treatment for women
  minimum age: 18 Years
  maximum age: 50 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Urmila Diwekar
  role: Principal Investigator
  affiliation: Stochastic Research Technologies LLC/University of Illinois at Chicago
  last name: Urmila Diwekar, Ph.D.
  phone: 16308863047
  email: urmila@vri-custom.org
  last name: Sanjay Joag, MD, Ph.D.
  phone: 16305014451
  email: sjoag@yahoo.com
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: India
  url: http://www.stochastic-research.com/DrDiwekar.htm
  description: Theoretical papers related to this work can be downloaded from the website
  citation: Diwekar et al., 2022, A Non-Randomized Clinical Trial of a Decision Support Tool to Optimize Superovulation Cycles in Individual Patients, J Fertil In vitro IVF Worldw Reprod Med Genet Stem Cell Biol, Vol.10 Iss.3 No:1000268 Link to the paper: https://www.longdom.org/open-access/a-nonrandomized-clinical-trial-of-a-decision-support-tool-to-optimize-superovulation-cycles-in-individual-patients-93998.html
  citation: Nisal A, Diwekar U, Bhalerao V. Personalized medicine for in vitro fertilization procedure using modeling and optimal control. J Theor Biol. 2020 Feb 21;487:110105. doi: 10.1016/j.jtbi.2019.110105. Epub 2019 Dec 3.
  PMID: 31809718
  citation: Yenkie KM, Diwekar UM, Bhalerao V. Modeling the superovulation stage in in vitro fertilization. IEEE Trans Biomed Eng. 2013 Nov;60(11):3003-8. doi: 10.1109/TBME.2012.2227742. Epub 2012 Nov 15.
  PMID: 23193444
  responsible party type: Sponsor
  sharing ipd: Yes
  ipd description: We will provide deidentified data.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Clinical Study Report (CSR)
  ipd time frame: After publication of results
  ipd access criteria: contact PI