Non-Significant Risk (NSR) Medical Devices: Monitoring Requirements

When conducting human subject research with a medical device that is determined (by FDA or IRBMED) to be a non-significant risk (NSR) device, there are additional FDA investigational device exemption (IDE) requirements that must be followed. These requirements are also known as abbreviated IDE requirements and are outlined in 21 CFR 812.2(b). One of the abbreviated IDE requirements of NSR studies is to comply with the monitoring requirements outlined in 21 CFR 812.46.

In the IRB application (eResearch Regulatory Management), Section 32 (“DSMP - Data Safety and Monitoring Plan”) is designed to capture the required information about the study’s data and safety monitoring plans. Completing Section 32 is required for FDA-regulated studies. IRBMED will consider what constitutes an appropriate data safety and monitoring plan for each study at the time of IRB review and approval per applicable regulations (21 CFR 56.111) and institutional policies.

NOTE: Classifying an investigational device ‘significant risk’ or ‘non significant risk’ according to FDA regulations at 21 CFR 812.2(m) is a separate determination from whether the overall study poses minimal or greater than minimal risk to participants per 45 CFR 46.102(j) and 21 CFR 56.102(i). These two kinds of risk determination may not always coincide in the context of a given research study.

This section details how study teams should complete Sections 32-1 (“Data Safety and Monitoring Plan - AE Reporting”) and 32-2 (“Data Safety and Monitoring Plan - Monitoring the Study”) for a minimal-risk study involving an NSR device.

At a minimum, the following should be considered by the study team and the IRBMED (selected questions within Sections 32-1 and 32-2): Screenshots from eResearch Section 32 are included in the references below.

1. Section 32-1 (AE reporting) should indicate an AE reporting plan (IRBMED standard or study-specific) to report AEs to IRBMED. Note that identifying and reporting AEs is also part of the monitoring requirements.
2. Section 32-2 (“Monitoring the Study”) should include details about any additional monitoring activities. In the current eResearch application, completing Section 32-2 is required when Section 32-1 is triggered.
   1. In Question 32-2.1, the study team should indicate that the study team will conduct periodic assessments. They should select a timeframe that is appropriate and realistic from the available options. Generally, quarterly or semi annual, or annual assessments is appropriate for low-risk NSR studies; the weekly or monthly assessments should be carefully considered.
   2. In Question 32-2.2, the study team may select the "No Additional Monitoring Required” option. Do not select any other options in 32-2.2 unless there are specific plans to do additional monitoring; any selection of additional monitoring within 32-2.2 may be required as the study progresses.
      NOTE: The FDA recommends a risk-based monitoring approach and practices to ensure appropriate oversight of clinical investigations. This means that minimal-risk clinical investigations involving a device determined to be NSR generally do not require a formal data safety monitoring board (DSMB) or an independent monitor. However, each IRBMED board should determine what constitutes an appropriate plan based on the risk proposed by the study (this is in accordance with the FDA guidance on monitoring).
   3. When selecting the "No Additional Monitoring…" option in 32-2.2, do not complete the sub-questions (32-2.2.1, 32-2.2.2, 32-2.2.3, and 32-2.2.4).
   4. In 32-2.3 (“Submitting Monitoring Reports”), select "IRB," as this is a required question. In most cases, if Section 32-2 is completed as instructed above, there will not be any monitoring reports to submit to IRBMED. See Section III below for information on what the study teams are required to report to IRBMED.

Reminder for study teams and IRBMED: Ensure that there is no conflicting information in Section 32-2 regarding monitoring. For example, do not indicate one timeline in 32-2.1 and another in other places.

U-M's Office of Research Compliance Review (ORCR) provides self-assessment tools to assist UM investigators in complying with the additional requirements for NSR studies. Particularly, they include the following:

• NSR Device Self-Audit: The purpose of this self-assessment is to help researchers determine whether they’re meeting their regulatory obligations and institutional guidance for NSR devices.
• NSR Self-Monitoring Report: This form is designed to assist researchers in submitting the required documentation of monitoring.

U-M study teams should utilize ORCR’s NSR Self-Monitoring Report to document the monitoring activities as indicated in the approved IRB application (Section 32-2). Please also refer to Section V of FDA guidance on monitoring for information on documentation requirements. If the only monitoring proposed by the study team and approved by the IRBMED are periodic assessments conducted by the study team, the IRBMED strongly suggests that these assessments be documented using the ORCR’s NSR Self-Monitoring Report (or other equivalent). Usually, there is no requirement to submit these reports to IRBMED.

FDA Guidance Responsibilities of Sponsors of Non-significant Risk Device Studies

IRBMED’s U-MIC presentations on Post-Approval Study Monitoring

MICHR-MIAP’s comprehensive list of the abbreviated requirements for NSR studies

Screenshots from eResearch HUM application: 32, 32-1, 32-2