The new article highlights the aspects related to the investigation plan and the way it should be developed.
Table of Contents
The Food and Drug Administration (FDA or the Agency), the US regulatory authority in the sphere of healthcare products, has published a guidance document dedicated to the Investigational Device Exemptions (IDEs) for Devices Indicated for Nocturnal Home Hemodialysis (NHHDs). The guidance provides additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be considered by medical device manufacturers and other parties involved to ensure compliance thereto. At the same time, provisions of the guidance are non-binding and are not intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with existing legislation and has been agreed with the authority in advance.
The authority pays additional attention to the aspects related to home use, as this is always associated with specific risks and considerations due to the nature of this use environment. The scope of the guidance covers, inter alia, the matters related to investigational plans to be developed by the parties responsible for NHHDs.
Investigational Plan: Key Points
According to the guidance, a party responsible for a medical device should submit a complete description of the investigational plan. It is further explained that the IDE study should be designed in a way ensuring the clinical data obtained will demonstrate the safety of the product in question when used for its intended purpose in the respective use environment. The plan should cover the aspects related to the ability of the product to deliver the treatments prescribed, and also adverse events that may occur during the use of the device. To ensure the reliability of the results, the authority recommends medical device manufacturers conduct an investigation partially in the controlled clinical setting, and partially – in a home use environment, as this will allow assessing the way the device operates when it is subject to factors that are common for this use environment. The authority additionally emphasizes that the study does not have to evaluate the long-term effectiveness of nocturnal hemodialysis treatment as an endpoint. The document further highlights the key points to be considered for an investigation plan.
Study Design
As it was mentioned before, a study should be designed in a way covering both in-clinic and home-use periods to ensure the accuracy and reliability of the results. At the same time, the actual length of the study and the number of devices needed to complete it (samples) would depend on such factors as the study endpoints, the indications for use, and any performance characteristics and claims [the manufacturer] proposes to include in labeling.
Subject Selection and Endpoints
The authority further recommends selecting study participants (subject) from established hemodialysis patients, and also including the ones with established vascular access. Apart from this, it is also important to take into consideration the physical ability of the study subject or another person who will assist in using the device (care partner) to perform the treatment.
Since the study will include an in-home period, the investigation plan should describe the approach to be applied when assessing the actual home environment in which the device will be used to ensure all the facilities needed (e.g., electric and water supply) are in place, and that all the environments that are not suitable will be excluded.
The plan should also provide a future comparison between the results achieved during in-clinic and home-use periods, including:
- Adverse events;
- Ability to deliver the prescribed treatment; and
- The reliability of the device to provide each treatment as scheduled.
Statistical Plan
Apart from the above mentioned aspects, the applicant should provide a detailed enough description of the statistical plan. Such a plan should cover the following aspects: sample size, proposed randomization scheme (if applicable), proposed interim analysis and early stopping procedures (if applicable), probability of the data, and proposed analytical methods. In this respect, the authority also refers to the Statistical Guidance for Clinical Trials of Non-Diagnostic Medical Devices.
Monitoring
As explained by the FDA, the scope of the investigation plan should also cover the aspects related to subject monitoring, monitoring by the care partner, and also monitoring of dialysate chemistries and water quality. All these types of monitoring are important to ensure the device operates as intended within the whole period of a study. According to the document, the applicant should describe the monitoring-related features of the product in question. Furthermore, the authority encourages the involvement of the care providers even in case the NHHD system has a real-time remote monitoring feature. The care providers should be present within the whole period of treatment. Hence, remote monitoring should not be the only monitoring method used to monitor the matters related to the study participant.
In the case the NHHD system subject to review does not use a premixed dialysate solution, the scope of monitoring activities should also cover the aspects related to the quality of water used by the system. In particular, the authority encourages medical device manufacturers to provide a sampling procedure to be conducted regularly, followed by the respective testing intended to ensure that the water used by the device (after purification) meets the acceptance criteria outlined in the study protocol. The investigational plan should also describe an approach to be applied when monitoring the dialysate the device prepares in the course of its operations. In this respect, the investigation plan should specify the criteria to be used when assessing the dialysate, as well as the particular time intervals for sampling.
In summary, the present FDA guidance highlights the key points to be considered when developing an investigation plan related to NHHD systems. The authority pays special attention to the aspects related to the intended use environment and its specifics and also describes the measures to be taken during the trial (e.g., subject monitoring).
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