An Advanced Decision Support Tool, Opt-IVF for Clinical Ivf Practice
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional

Summary: 
      Aim: A Clinical trial to determine the effectiveness of using the proposed decision support
      tool for each patient's customized optimal drug dosage profile. This will be a two-arm
      clinical trial involving 200 patients; one arm will undergo superovulation using dosages
      predicted by the decision support tool while the other arm will undergo current standard
      treatment. The investigators will compare the outcomes of the two groups of patients in terms
      of the numbers and percentage of mature follicles retrieved at the end of each cycle, total
      FSH and HMG dosages used, and the number of required testing days for that cycle. The
      patients considered will include all ages, with and without PCOS, and low, average, and high
      responders.
    

Detailed description: 
      Objectives/Aims

      Aim: A Clinical trial to determine the effectiveness of using the proposed decision support
      tool for each patient's customized optimal drug dosage profile.

      Subject Enrollment

      The recruitment plan designed is study-specific and site-specific. The investigators plan to
      recruit patients by reaching into the center's own database of patients. This 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 single-site cohort with two arms (one arm for the intervention and one arm for the
      traditional approach) clinical trial involving 200 patients.

      The main site for this task is the Akansha Hospital, 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. Patel will be an investigator from the Akansha
      Hospital. Apart from these two investigators, there will be a post-doctoral fellow from
      Stochastic Research Technologies LLC and medical personnel from the Akanksha Hospital other
      than Dr. Patel will be involved in this proposed clinical trial.

      In our 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.

      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. Dr. Diweakr's group have carried out retrospective studies with 150
      patients in the USA and India. The investigators also carried out a small prospective
      clinical trial 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

        1. 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.

        2. 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
           the University of Chicago IVF center. Nobody from stochastic research technologies will
           have access to personal identifiers.

        3. Backups The company provide automated computer backups.

        4. 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 SPSS 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 80 patients in each arm. Therefore, a sample size of 100 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. Patel is responsible for this. The signed consent forms hard
      copy data will be securely stored in a locking cabinet in the Akanksha hospital office.

      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.
    

Intervention name(s): traditional drug treatment; Opt-IVF predicted dosage
Intervention type(s): Other; Other
Intervention description(s): The patients in this arm will be given doctor specified dosage.; The patients in this arm will be given dosage predicted by Opt-IVF.
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: This will be randomized study of patients undergoing IVF treatment. The treatment given to one arm will be based on Opt-IVF decision support tool and standard doctor specified treatment with other arm.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: IVF; Opt-IVF