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Non-Significant Risk Medical Devices
Non-Significant Risk Medical Devices
- Guidance Contact:
IU Human Research Protection Program (HRPP)
There are three types of medical device studies described in 21 CFR Part 812: significant risk (SR) device studies, non-significant risk (NSR) device studies, and studies using devices that are exempt from the IDE requirements. The investigator and/or sponsor is responsible for initially determining the device risk. As part of its review, the IRB must agree with the assessment based on the proposed use of the device in the research and not on the device alone; however, the FDA has the ultimate decision in determining if a device is IDE exempt, NSR, or SR.
To qualify as an NSR device, the device must not pose a serious risk to human subjects. Medical devices that do not meet IDE exempt criteria qualify as NSR devices provided they do not meet the SR device criteria. Medical devices are SR if they are:
- A banned device,
- Intended as an implant and present a potential for serious risk to the health, safety, or welfare of a subject,
- Purported or represented to be for use in supporting or sustaining human life and present a potential for serious risk to the health, safety, or welfare of a subject,
- For a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and present a potential for serious risk to the health, safety, or welfare of a subject, or
- Otherwise present a potential for serious risk to the health, safety, or welfare of a subject.
NSR devices must follow a portion of the regulations outlined in 21 CFR 812, or “abbreviated requirements.” These abbreviated requirements (§ 812.2(b)) include
- Labeling of the device (§ 812.5)
- IRB approval and maintaining approval
- Informed consent from the subject (21 CFR 50)
- Monitoring of the trial (§ 812.46)
- Record keeping (§ 812.140) and reporting (§ 812.150)
- Prohibition from promotion, commercialization, and misrepresentation of the device (§ 812.7)
The goal of trial monitoring is to ensure adequate protection of the rights, welfare, and safety of human subjects and the quality of data collected. With respect to monitoring an NSR medical device study’s progress, the regulations focus on two concepts: identifying and investigating any unanticipated adverse device effects and ensuring compliance with the investigational plan, applicable regulations, and any conditions of IRB approval. The procedures taken to comply with NSR monitoring requirements, however, may vary from study to study.
Independent of the device-specific risks, the FDA encourages broader, risk-based monitoring of clinical trials based on other study characteristics. The FDA permits variation in the types and intensity of monitoring activities best suited to address a particular study’s characteristics. While the regulations and guidance materials refer to monitoring as a “sponsor” responsibility, it is important to remember that in the absence of a formal external sponsor, the PI assumes the role of the sponsor and must fulfill these requirements.
The FDA provides helpful Guidance in assisting sponsors and investigators in developing risk-based monitoring strategies and plans for investigational studies. When developing a monitoring plan, numerous considerations should be made related to timing, types, frequency, and extent of monitoring which should vary based on the complexity of the study design, inclusion of clinically complex or vulnerable study populations, relative safety of the investigational product, experience and qualifications of the PI and study team, and quantity of data and data collection methods.
Who should perform monitoring?
Study monitoring does not necessarily require independent review by an individual external to the study team. Depending on the study characteristics, the required study monitoring might be accomplished through the routine and ongoing oversight by the PI and study team. Increased complexity of the trial or increased risk of participation, however, might justify a more formal approach, including selecting someone external to the study team to serve as the study monitor. In this situation, the Indiana CTSI may be able to provide monitoring services for more complex NSR device studies or those with more relative risk.
What should be monitored?
The FDA Guidance provides examples of data and processes that should ordinarily be identified as critical for monitoring including, but not limited to:
- Verification that informed consent was obtained appropriately,
- Adherence to protocol eligibility,
- Appropriate accountability and administration of the investigational device, and
- Conduct and documentation of procedures and assessments related to study endpoints, safety assessments, and evaluating, documenting, and reporting SAEs and unanticipated adverse device effects
The extent of data review will vary from study to study. While the FDA’s Guidance highlights the importance of monitoring critical data and processes, it does not require that they be monitored across all subjects. While data could be randomly selected for review, you may instead wish to consider the pace of enrollment, the amount of data to be collected, and the number of personnel involved in study conduct when determining what data to review and how often. Monitoring critical data and processes soon after the first, or first few, subjects are enrolled may help to catch and fix potential problems early in the study’s conduct. Additionally, monitoring may need to be increased – either in frequency or scope – in response to study events such as staff turnover, protocol amendments, and/or to satisfy corrective and preventive action plans.
Self-audit templates and tools are available on the IU HRPP Website. These templates may be helpful to assist study teams when conducting their own monitoring in identifying potential noncompliance, protocol deviations, and data management issues. While the monitoring process may be accomplished in a number of ways, regardless of the approach, all monitoring activities should be documented in the research record. Additionally, observations from monitoring activities should be discussed with the PI and study team to determine appropriate corrective and preventive actions and whether events must be reported to the FDA or IRB.
How should monitoring be documented?
While the FDA regulations do not require the monitoring plan to be a formal written document, in the event of an inspection, it will be critical for the PI and study team to be able to describe how they monitor the study’s progress, how the PI is engaged in these activities, and to provide evidence that monitoring has occurred. For informal monitoring, this may include an explanation of team/department practices or SOPs, and/or documentation related to study team meetings and study team correspondence. For more formal monitoring, this might include documentation of self-reviews and/or external monitor reviews, including dates of occurrence, the individual performing the review, the outcomes of the self-reviews, and communication of observations to the PI.
Assessing study characteristics
The plan for study monitoring should be based on the characteristics of the trial and the overall risks to subject health, safety, and welfare and to the quality and integrity of the study data.
|Study Risk||Study Characteristics||Level of Monitoring|
|Low Risk||This may include open label or single arm trials; minimal device risks related to safety, no plans to enroll vulnerable or medically complex study population; and conducted by an experienced PI and study team.||Study monitoring might be done informally through compliance with regular researcher roles and responsibilities and study team communications.|
|Moderate Risk||This may include randomized, blinded, or cross-over designs; more moderate device risks related to safety; inclusion of some vulnerable or medically complex subjects; conduct of study procedures at multiple locations and/or by numerous staff with varied experience.||Study monitoring might be done more formally through periodic and ongoing self-review or self-auditing of a portion of the data.|
|High Risk||This may include complex study designs, such as adaptive trial designs or those in which exposure to the device is altered based on subject response; higher risks related to safety and/or the inclusion of safety related stopping rules; inclusion of vulnerable populations or those that may be seriously ill or medically complex and require more intensive safety monitoring during the study conduct; complex protocol driven procedures; inexperienced PI or study team; extensive data transcription or data conversions prior to analysis.||A formal study monitoring plan might be established and monitoring might be performed by someone external to the study team.|