During the course of the study, recruitment activities generate calls, emails, and text messages handled directly by our call center. Call center personnel screen subjects for potential eligibility with standardized screening logs and then schedule subjects using the clinical trial management software. When subjects arrive at the research facility, they undergo an extensive informed consent process to ensure that they fully understand the potential risks and benefits of participating in the study. Once the subject and the investigator have completed the informed consent process and all necessary signatures are in place, only then can the formal screening process begin. Subjects undergo a full medical history and physical examination and are asked detailed questions about their current and past medication use, allergies, family history, and social history. Additionally, psychological screening questionnaires for the assessment of compliance and alcohol usage are employed to further ensure reliability. Any required specimen collection procedures are performed (blood, urine, stool, saliva) and subjects are educated once again on the requirements of the study, how and when to take the study product, how to record necessary information in their diaries, and how to contact the study personnel with questions or medical issues.

The subject eligibility is confirmed through a separate step requiring the investigator to review all of the individual components of eligibility including medical history, physical exam, lab results, questionnaire results, and any other study specific requirements. Only after the investigator has verified their eligibility is the subject assigned a randomization ID number and the dispensing of study product can occur.

Subjects return for visits and assessments according to the protocol. A compliance call is scheduled for the midpoint between each visit and a reminder call is scheduled for 2 days before each appointment.

The monitoring team receives copies of the standardized source documents / CRFs each week by fax or by scanning into a secure system. 100% of every page of every source / CRF document is reviewed for 24 different types of possible errors/omissions. If errors are found, queries are sent to the site personnel who have 1 week to resolve the query and resend the pages for validation of resolution of the query. The monitoring team also visits the site on a scheduled basis in order to further validate the source/CRF documents, reconcile the study product, review the regulatory binders, and ensure the appropriate storage of the study product.

Enrollment and progress are tracked on a weekly basis and these reports are sent to the sponsor at the end of every week. Any clinical issues are evaluated and any serious adverse events are reported to the sponsor and the IRB (and the FDA depending on the regulatory requirement) within 24 hours of learning of the event.