The new article highlights aspects related to clinical outcomes to be used in the context of studies involving devices intended to treat opioid use disorder. In particular, the article describes in detail the change in drug use as one of the possible clinical outcomes to be used by study sponsors.

The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a draft guidance document dedicated to clinical considerations for studies of devices intended to treat opioid use disorder (OUD). Once finalized, the guidance will provide an overview of the applicable regulatory requirements as well as additional clarifications and recommendations to be taken into consideration by medical device manufacturers and other parties involved in order to ensure compliance therewith.

At the same time, provisions of the guidance are non-binding in their legal nature, and they 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 the existing legislation and has been agreed upon with the authority in advance. 

The document describes in detail certain specific aspects to be considered by medical device manufacturers and parties responsible for clinical investigations (study sponsors), including, inter alia, those related to clinical outcomes.

Clinical Outcomes: Key Points

First of all, the authority emphasizes the importance of clinical outcomes since they provide the scientific evidence  necessary to demonstrate the benefits associated with the use of the device for its intended purpose. According to the guidance, the FDA considers a clinically significant benefit to be an improvement in how a study participant feels, functions, or survives, such as a reduction in hospitalizations or improvements in daily life including the ability to resume work, school, and other activities. 

As further explained by the authority, when choosing primary outcomes for pivotal OUD device studies, sponsors should identify the clinical objectives of the device for the target patient population and align the objectives with the desired indications for use, a relevant definition of a clinically significant benefit, and the choice of effectiveness outcomes. 

Moreover, the authority also encourages study sponsors to use secondary outcomes in order to improve the robustness and reliability of the clinical evidence generated by the primary outcome. All this evidence will be vitally important for supporting claims made by the medical device manufacturer when applying for marketing approval for the product in question. 

As further explained by the authority, the main purpose of secondary outcomes is to support the primary ones, so under the general rule, they cannot be used as standalone ones. It is mentioned that, to the extent possible, secondary outcomes should be limited in number and should be minimally burdensome to participants and investigators to enhance retention and prevent missing data. 

With respect to missing data and specific approaches to be followed in this regard, the authority refers to the appropriate section of the present guidance. According to the guidance, secondary outcomes could be used to provide evidence confirming the effect initially demonstrated through the primary outcomes. 

The authority encourages the parties responsible for clinical investigations to choose specific study outcomes to be used based on the intended use population, indications for use, and clinical situation. In order to assist study sponsors and other parties involved, the authority further provides examples of primary and secondary outcomes and explains the way they should be selected based on the specific factors to be taken into account when making such a selection. 

It is important to mention that study sponsors should not choose all the outcomes provided as examples for any study. Furthermore, the list provided in the guidance is not exhaustive, so additional outcomes could be reasonably necessary based on the specifics of the study in question and the product subject to review.

Device Description

First of all, the document describes the scope of information the authority expects to be included in the submission with respect to the medical device in question. According to the guidance, the submission should include the following elements:

  • A comprehensive description of the device, including technology, functionalities, features, and connectivity capabilities (e.g., wireless-enabled, Bluetooth-enabled, internet-connected, and network-connected devices), if applicable. The information should be accompanied by pictures and drawings for illustrative purposes. 
  • An indication of a risk class and applicable classification rule for the medical device according to the regulations
  • Product specifications include the version number of the software, if applicable. 
  • List of medical device accessories intended to be used in combination with the devices. According to the guidance, the submission should also provide information about accessories that are intended to be used with the device but are supplied separately. 
  • Should the safety and effectiveness data related to similar medical devices already on the market be used to support claims made by the manufacturer, the applicant is also expected to provide:
  • A list of such devices and specific information on the registration status of these devices with HSA (for instance, the appropriate registration numbers);
  • A comparison, preferably in a table, of the design, specifications, and intended use/indication for use between the subject device in the current submission and the comparator devices (similar and/or previous generation). As in case of the general description of the device, the authority encourages medical device manufacturers to provide images and other visual elements illustrating the information. 

A list of all materials in direct or indirect contact with the patient or use. The authority additionally emphasizes that in the event of specific concerns with respect to the safety of the materials used, the HSA may request additional information be provided by the manufacturer to address such concerns.

Change in Drug Use Pattern

According to the guidance, the FDA generally accepts a positive change in drug use patterns as a surrogate for the benefits of abstaining from drug use or for the presumed benefits of reducing drug use. As further explained, a reduction in drug-taking behavior has been used as a surrogate outcome for the benefit of abstinence or the presumed benefit of reducing drug-taking in many investigations, including those used to elevate drug products for the treatment of OUD. 

In accordance with the recommendations provided in the present guidance, when “change in drug use pattern” is used as a clinical outcome, the parties responsible for clinical investigations should compare the percentages not for groups in general, but for specific responders – study participants. The specific thresholds to be used should be determined on a case-by-case basis, taking into consideration numerous factors related to the study design, the medical device in question, and other aspects. 

The authority also explains that usually these thresholds are study-specific and, consequently, are not transferrable due to their significant dependence on population, treatment, risks, and benefits, as well as methods used in the course of respective analysis. 

The authority expects study sponsors to provide proper justification for the thresholds used and the way they are supposed to improve the patients’ state and lives in general. For example, studies of devices for use with prescribed medication-assisted treatments for OUD should demonstrate clinically significant improvement compared to a group not receiving active device treatment and receiving the same protocol-defined medication-assisted treatment. 

In summary, the present FDA draft guidance provides an overview of the regulatory matters associated with the primary and secondary clinical outcomes to be taken into consideration when developing a design of a clinical investigation involving an OUD device. The document pays special attention to the “change in drug use pattern” as one of the outcomes and describes in detail the approach to be applied in this respect.

How Can RegDesk Help?

RegDesk is a holistic Regulatory Information Management System that provides medical device and pharma companies with regulatory intelligence for over 120 markets worldwide. It can help you prepare and publish global applications, manage standards, run change assessments, and obtain real-time alerts on regulatory changes through a centralized platform. Our clients also have access to our network of over 4000 compliance experts worldwide to obtain verification on critical questions. Global expansion has never been this simple.