The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published guidance dedicated to feasibility and early feasibility clinical studies for certain medical devices intended to therapeutically improve glycemic control in patients with Type 2 Diabetes Mellitus (T2DM).
The document constitutes a draft guidance the authority has published in order to collect feedback from industry representatives and other parties involved regarding the regulatory approach suggested. Thus, the provisions described in the present draft guidance could be subject to changes due to new information becoming available to the authority.
The Agency will accept comments within two months from the date the document has been initially published. Once finalized, the document will provide additional recommendations and clarifications on the matter.
Due to their legal nature, guidance documents do not introduce any requirements themselves. The approach described therein should be taken into consideration by the medical device manufacturers or other parties engaged in operations with medical devices in the context of achieving and sustaining compliance with the applicable regulatory requirements set forth by the current legislation. Additionally, the Agency states that an alternative approach could be applied, provided such an approach has been approved by the authority in advance.
Thus, the present FDA guidance provides suggested recommendations for the design of feasibility and early feasibility clinical studies for certain medical devices. These recommendations are mostly based on existing clinical practice guidelines.
Regulatory Background
The intended purpose of medical devices covered by the scope of the present guidance is to therapeutically reduce glycated hemoglobin (HbA1c) in T2DM patients independent of medication (e.g., insulin) delivery. The aforementioned disorder is associated with the relative lack of insulin. Since the disorder is widespread in the US, numerous medical device manufacturers are engaged in the development of medical devices intended to measure or monitor glucose or dose and deliver insulin. However, the authority states that there are not medical devices that are able to therapeutically improve glycemic control on the US market nowadays. Due to the increasing demand for such devices, the medical device manufacturers engaged in their development have contacted the authority requesting additional clarifications on the regulatory matters associated thereto, especially in terms of feasibility and early feasibility clinical studies.
According to the document, medical device manufacturers are encouraged to submit a Pre-Submission before initiating a clinical study in order to obtain feedback from the authority. In such cases, the Q-Submission framework could be applied.
The present draft guidance addresses the regulatory matters related to the design of feasibility and early feasibility clinical studies for the medical devices described herein. In particular, the scope of the document covers neurostimulators, and those that mimic or result in anatomical changes similar to those made by bariatric surgical procedures, alter the anatomy and/or physiology of the small intestines or manipulate the sympathetic nervous system. At the same time, studies related to medical devices intended to measure or monitor blood sugar or deliver insulin, as well as the Software as a Medical Device (SaMD), fall outside of its scope.
Clinical Study Recommendations
According to the document, a clinical study should be carried out in order to assess and evaluate the safety and effectiveness of a medical device intended to be used for the purpose described herein. Such a study should be carried out under the Investigational Device Exemptions (IDE) framework. The Agency states that medical devices intended to therapeutically reduce glycemic levels for T2DM patients are associated with significant risks. Thus, the appropriate provisions on significant risk medical device studies should be applied. Should such an investigation take place in the US, it should also meet the requirements set forth under the current legislation in terms of institutional review boards and informed consent. However, clinical data deriving from clinical studies carried out abroad could be acceptable, provided it complies with the applicable regulatory requirements.
The present draft guidance highlights the most important aspects related to early feasibility studies, including the following:
1. Study objectives. As stated by the FDA, an early feasibility study is intended to evaluate the device design concept with respect to initial clinical safety and device functionality in a small number of subjects (generally fewer than ten initial subjects) when this information cannot be provided practically through additional nonclinical assessments or if appropriate nonclinical tests are unavailable. For instance, such an approach could be applied in the case of medical devices based on novel technologies. A party responsible for a clinical study (a sponsor) should take into consideration the provisions of this guidance when developing a study design. In general, a feasibility study is intended to collect initial safety and effectiveness data which would later be used as a basis for a clinical investigation. The Agency encourages sponsors to pay special attention to safety-related matters by gathering and analyzing information on adverse events associated with the medical device in question. From the effectiveness and performance standpoint, special attention should be paid to measuring glycated hemoglobin (HbA1c), while additional measures could be applied as well.
2. Study design. When determining the sample size, a sponsor shall take into consideration such factors as the current stage of medical device development, availability of data, and also the risks associated thereto. Under the general rule, the size of an early feasibility study should not exceed ten subjects. Consequently, the information to be collected by virtue of such a study would not be sufficient to completely assess the performance of the medical device subject to review. Nevertheless, performance-related aspects should also be taken into consideration. The Agency states that inaccurate or inefficient glycemic control will expose patients to additional risks. Thus, even if the data collected in the course of an early feasibility study is not sufficient for the assessment of all the aspects, it still provides a solid base for future clinical trials.
3. Study duration and follow-up. The studies described herein should include the appropriate follow-up period, which should be proportionate to the risks associated with the medical device subject to review. For instance, in the case of high-risk studies, such a period should exceed twelve months in order to assess the durability of effects. The protocol of the clinical study shall prescribe the way the information about adverse events should be collected and processed. Additionally, it should prescribe that the subjects be monitored until any and all adverse events are stabilized.
Additional Recommendations
Besides those described above, the FDA guidance on feasibility clinical trials for T2DM-related devices provides some additional recommendations to be considered by sponsors of such trials. These recommendations include the following:
- The patient population engaged in a study should be determined on the basis of benefit-risk analysis.
- The subjects enrolled in a study should be individuals who will potentially benefit from such an escalation of care.
- Apart from the disorder addressed herein, the patients involved in a feasibility study should be healthy.
In summary, the FDA guidance on medical devices intended to therapeutically improve glycemic control in patients with Type 2 Diabetes Mellitus outlines the key aspects to be considered when developing and initiating a feasibility study. The document describes in detail the way such studies should be carried out and how the information should be collected.
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