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Research and Innovation: Office of Research Regulatory Affairs

IND – IDE Monitoring Plan

IND or IDE Monitoring Plan

“Protocol Title”

Sponsor:                                University of Arkansas for Medical Sciences (UAMS)

Principal Investigator:     

IRB Number:                       

IND or IDE Number:         

1. Purpose of Monitoring Plan

The purpose of this monitoring plan is to present the approach of the Office of Research Regulatory Affairs for monitoring the specified research study. The plan facilitates compliance with applicable regulations (21 CFR 312 or 812), which require monitors to verify that:

  • The rights and well-being of human subjects are protected.
  • Reported study data are accurate, complete, and verifiable from source documentation.
  • The conduct of the trial is in compliance with the currently approved protocol and all applicable regulatory requirements.

This document identifies key monitoring activities and specifies the data to be reviewed over the course of the study. The assigned monitor(s) will conduct monitoring visits in accordance with this plan.

2. Office of Research Regulatory Affairs – Monitoring Unit

Study monitoring is a resource offered by the Office of Research Regulatory Affairs Monitoring Unit (ORRA-MU). The primary intent of the ORRA-MU is to support study compliance with applicable federal regulations at the University of Arkansas for Medical Sciences and its affiliate sites. The focus of the ORRA-MU is on supporting UAMS-sponsored investigator-initiated research studies. ORRA-MU services are not directed toward studies monitored by industry sponsors or CROs.

3. Monitoring Approach

  • Methods

       This study will be conducted on the UAMS campus (and/or NAME SITE) and will utilize paper Case Report Forms (CRFs), source documents, and regulatory files. Monitoring will occur on-site.

       OR

       This study will be conducted on the UAMS campus (and/or NAME SITE) and will utilize electronic Case Report Forms (CRFs), source documents, and regulatory files. Monitoring will occur remotely from the Office of Research Regulatory Affairs.

OR

      This study will be conducted on the UAMS campus (and/or NAME SITE) and will utilize a combination of paper and electronic Case Report Forms (CRFs), source documents, and regulatory files. Monitoring will occur on-site and remotely from the Office of Research Regulatory Affairs when possible.

OR

       Other – Describe the data collection method(s) to be used and the monitoring arrangement.

  • Assessment

       The following criteria were used in determining the timing, frequency, and intensity of planned monitoring activities:

  1. Category: This study is being conducted under a UAMS-sponsored IND/Significant Risk IDE/Non-Significant Risk IDE/Single Patient IND/Other.
  2. Complexity of study design
  3. Study phase
  4. Investigator/staff experience
  5. Complexity of study population
  6. Data Quantity
  • Changes to Monitoring Plan

       This monitoring plan may be amended to accommodate the following:

  1. Lack of enrollment
  2. Increased enrollment rate
  3. High volume of protocol deviations
  4. Lack of appropriate action regarding potential issues identified during monitoring visits
  5. Stage of study progress
  6. FDA and/or institutional audit preparation or response
  7. Major changes to protocol or investigational plan
  8. Addition or removal of study sites
  9. Additional reasons as determined by the Office of Research Regulatory Affairs

4. Scope

  • Investigator Qualifications

Monitors will verify the Investigator(s) has adequate qualifications to conduct the trial by:

  1. Ensuring there is a CV, medical license (if applicable), HSPT training certificate, GCP training certificate and/or other documentation of qualification on file for each investigator involved in the trial.
  2. Verifying that all of the above documentation of qualification was current at the time of study initiation.
  • Facilities

Monitors will ensure that facilities remain adequate throughout the study by:

  1. Verifying that current certifications and normal ranges for the laboratory(ies) performing protocol-required procedures or tests are on file.
  2. Verifying documentation (SOPs, procedure manuals, temp. logs) of the adequacy of laboratories and equipment not covered under CLIA or CAP certifications.
  • Investigational Product

For investigational drugs, monitors will verify that:

  1. Study documents provide information on how subjects will be provided with necessary instruction on how to use, handle, store, and return investigational product.
  2. Labels on the drug(s) comply with the requirements for investigational drug labeling.
  3. Pharmacy records match product disposition records.
  4. The investigational product is stored under conditions specified in product labeling or packaging.
  5. The time the product has been stored does not exceed the shelf life specified in the labeling or packaging.
  6. Documentation for receipt and return of product is on file.
  7. Manufacturer guidelines or other instructions for handling the product are present.
  8. Records are maintained to indicate product has been supplied only to eligible subjects at/within protocol specified doses.

OR

For investigational devices, monitors will:

  1. Verify labels on the device(s) comply with the requirements for investigational device labeling.
  2. Verify documentation of receipt of the device(s) by the investigator/institution.
  3. Assess the condition of the device.
  4. Ensure tracking records are on file for use and/or dispensation/return of the device(s).
  5. Verify management and servicing of the device(s).
  6. Verify disposition of damaged or unused devices(s).
  7. Verify that records are maintained to indicate product has been administered only to eligible subjects at/within protocol specified limits.
  • Protocol

Monitors will ensure that the site is following the approved protocol by:

  1. Verifying the current approved protocol is present in the regulatory files.
  2. Verifying that the protocol identifies any source data that will be recorded directly on CRFs (if applicable).
  3. Reviewing and approving Case Report Forms (CRFs) prior to study initiation by comparing data to be collected on CRFs with the current approved protocol.
  4. Verifying the number and type of subjects entered in the study is consistent with criteria defined in the approved protocol.
  5. Verifying that no changes to the approved protocol were implemented without prior review and documented approval from the Sponsor and IRB (except where necessary to eliminate an immediate hazard to trial subjects or when the change involves only logistical or administrative aspects of the trial).
  • Informed Consent

Monitors will verify that written consent was obtained before subjects’ participation by verifying:

  1. Subjects/LARs signed and dated the correct IRB-approved consent form.
  2. Subjects/LARs signed and dated the correct IRB-approved HIPAA authorization document.
  3. Date and time the consent form was signed.
  4. Presence of source documentation detailing the consent process.
  5. Any opt-in/opt-out decisions (if applicable) (i.e. future use of samples, future contact, etc.).
  6. Subjects/LARs are appropriately re-consented to new versions of the consent and/or HIPAA forms (if applicable).
  • Essential Documents

Monitors will verify that all essential documents are maintained by:

  1. Verifying that all applicable documents exist and are currently on file as of the date of monitoring.
  2. Comparing site files to the Sponsor files.
  • Study Staff

Monitors will ensure that study staff is informed about the investigation and authorized to perform assigned tasks by:

  1. Noting the identity of all persons involved in data collection and study activities by viewing the delegation of authority log kept by the site.
  2. Verifying that staff listings and duties on the delegation of authority log match those in CLARA.
  3. Checking the delegation of authority log to verify all authorized personnel are included and have signed the log.
  4. Comparing study documents, IRB submissions, and delegation of authority log to determine if responsibilities have been delegated to unauthorized individuals.
  5. Verifying that license (if applicable), HSPT training certificate and/or other documentation of qualification (as required) is on file for each staff member involved in the trial.
  6. Checking documentation for information about distribution of the currently approved protocol and investigational product information to the study team, both at SIV and with any study modifications.
  7. Checking documentation (SIV sign-in sheet, training attestation form(s), other training documentation) of any protocol- specific training of authorized individuals.
  • Subject Eligibility

Monitors will verify that only eligible subjects are enrolled by:

  1. Verifying whether the existence of the condition for which the investigational product being studied is documented by a compatible history.
  2. Comparing the protocol inclusion/exclusion criteria against the source documentation to determine whether the enrolled subject is eligible for inclusion in the study.
  • Enrollment Rate

Monitors will report current enrollment information by:

  1. Counting the number of subjects enrolled (defined by this plan as having signed an informed consent form) and comparing this number to the enrollment goal approved by the IRB.
  2. Checking the enrollment log or other documentation provided by the site concerning enrollment statistics (if applicable).
  3. Confirming correct placement of subjects in cohorts as defined by the study protocol (if applicable).
  • Study Records

Monitors will ensure trial records are accurate, complete, and current by:

  1. Verifying that all current CRFs have been completed and signed/dated appropriately.
    • Verifying that all study visits and procedures have been performed according to protocol.
    • Verifying that source documentation was used to complete CRFs.
    • Verifying that the data collection points required by the protocol are reported accurately on the CRFs and are consistent with source documentation.
    • Verifying that the Investigator has made required reports and/or submissions to the regulatory authorities.
    • Comparing the information in the reports to information in the study site regulatory file and/or source documents.
    • Informing the Investigator and/or study staff of any errors on CRFs, trial records or logs and ensuring appropriate corrections are made.
  • Adverse Events

Monitors will ensure that all adverse events are appropriately recorded/reported by verifying:

  1. AEs, SAEs and/or UADEs have been reported to the proper regulatory authorities (Sponsor, IRB, FDA) by reviewing correspondence files and comparing against subject medical records.
  2. SAEs and/or UADEs have been reported to the regulatory authorities within the specified time frames as appropriate.
  3. Any non-serious AEs not meeting the criteria for expedited reporting requirements are reported to the IRB at the time of continuing review.
  4. AEs related to the investigational device are documented in the Annual Progress Report (APR) and that the APR is provided to the IRB who will act as FDA’s proxy for the NSR IDE.

OR

Any non-serious adverse events not meeting the criteria for expedited reporting requirements are reported to the IRB at the time of continuing review and reported to the FDA at the time of the Annual Progress Report (APR).

  • Deviations
  1. Monitors will ensure that all deviations from the protocol or regulatory requirements are recorded/reported by verifying:
  2. Subject visits have taken place as stated in the protocol.
  3. All tests and procedures have been completed as stated in the protocol.
  4. All deviations are documented in the record and/or CRF/source.
  5. Deviations have been reported to the Sponsor, if applicable.
  6. Deviations have been reported by the Investigator to the IRB at the time of continuing review, unless affecting subject safety, which should be reported immediately.
  7. Deviations are documented in the Annual Progress Report (APR) and that the APR is provided to the IRB (for IDE studies only).

5. Extent and Nature of Monitoring

  • Timing

A site initiation visit (SIV) is required before enrollment begins.

OR omit statement – no SIV required/requested.

  1. The first monitoring visit for verification of regulatory documents will be conducted within 30 days of the SIV.
  2. The first monitoring visit will be scheduled after the first subject is enrolled.

OR

The first monitoring visit will be scheduled after the third subject is enrolled.

OR

The first monitoring visit will be scheduled within 3 months of enrolling the first subject.

OR

The first monitoring visit will be scheduled within 6 months of enrolling the first subject.

Real-time monitoring visits will be scheduled (for the first subject or periodically throughout the study) at the monitoring unit’s discretion.

OR omit statement – no real-time monitoring required/requested.

A closeout visit (COV) is required at the end of the study prior to IRB closure. The IND / SR IDE will not be withdrawn until closeout activities are complete, as determined by the Sponsor. IRB closure prior to the COV is discouraged.

OR

A closeout visit (COV) is required at the end of the subject’s participation for a SPIND and will consist of verification that all outstanding queries from previous monitoring visits are resolved.

OR omit statement – no COV required/requested.

Re-SIV will be scheduled when studies meet one or more of the following criteria:

  • No enrollment for ≥2 years or more
  • Major revisions (i.e. new study design)
  • Change of PI
  • Major changes in staff
  • Mitigation of non-compliance
  • Need for re-training due to multiple deviations/violations
  • Other situations, as determined by ORRA MU or RU

Frequency

Monitoring visits will take place approximately every 6-8 weeks or at least yearly depending on enrollment.

OR

Monitoring visits will take place approximately quarterly or at least yearly depending on enrollment.

OR

Monitoring visits will take place approximately every 3-6 months or at least yearly depending on enrollment.

OR

Monitoring visits will take place yearly or other.

  • Intensity

Monitoring will include:

Up to 100% subject data verification.

OR

Subject data verification of a random sample of a minimum of 75% of enrolled subjects.

OR

Subject data verification of a minimum of 50% of study visits.

OR

Subject data verification of a random sample of up to 50% of enrolled subjects.

  • 100% of subject eligibility
  • 100% verification of informed consent forms.
  • 100% verification of AEs/SAEs/UADEs.
  • 100% verification of drug/device accountability records.
  • 100% verification of regulatory files.

6. Data and Safety Monitoring Board (DSMB)/Data Monitoring Committee (DMC)

This study will not utilize a DSMB/DMC.

OR

This study will utilize an external DSMB/DMC: (specify).

OR

This study will utilize a UAMS DSMB/DMC: (specify).

  • Communication
  • Prior to departing each visit, the monitor(s) will attempt to conduct a brief exit meeting with the Principal Investigator and/or designated study staff to discuss the outcomes of the visit.
  • A formal report (Attachment I) reflecting monitoring activities will be completed by the monitor(s) after each visit. This report will be maintained as part of the Sponsor’s files.
  • A follow-up letter summarizing monitoring activities will be sent to the Principal Investigator and relevant study staff following the completion of each visit. The letter will include the following at minimum:
  • The date of the activity and individuals present.
  • A summary of the data or activities reviewed.
  • A description of any noncompliance, potential noncompliance, data irregularities, or other deficiencies identified.
  • A description of any actions taken, to be taken, and/or recommended.

7. Management of Noncompliance

Monitors will verify that all action items identified at past monitoring visits have been resolved at subsequent monitoring visits, or sooner if appropriate.

Monitors will escalate any issues that continually remain unresolved to the Director of the Office of Research Regulatory Affairs and/or the Vice-Chancellor of Research. Additional oversight bodies may be notified if necessary.

I have reviewed this monitoring plan and understand that I am required to allow study monitoring in compliance with applicable regulations (21 CFR 312 or 812) by the ORRA Monitoring Unit as outlined above.

Principal Investigator Signature / Date

Monitoring Unit Manager Signature / Date