The new article describes in detail the aspects related to clinical trials, including the determination of study endpoints and duration, as well as follow-up schedule, statistical considerations, and adverse events monitoring.
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Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a draft guidance document dedicated to Photobiomodulation (PBM) devices in the context of premarket notification submissions under the 510(k) framework. Once finalized, the document will provide additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be followed by medical device manufacturers and other parties involved in order to ensure compliance thereto. At the same time, provisions of the guidance are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations, but rather to provide an overview and highlight specific aspects to be taken into consideration when applying for marketing approval. The authority also mentions that an alternative approach could be applied, provided such an approach is in line with the existing regulations and has been agreed with the authority in advance. 

The scope of the guidance covers, inter alia, the aspects related to clinical performance testing the devices should undergo to demonstrate they operate as intended and meet the applicable safety requirements. 

infusion pumps

Study Endpoints 

According to the guidance, a party responsible for clinical trials should identify the endpoints before initiating the investigation. The document further outlines specific aspects to be taken into consideration when selecting the endpoints for a clinical study, namely:

  • The characteristics subject to review should be the ones that could be assessed. 
  • The metrics used should employ objective quantitative data, when possible. The authority also mentions that validated scales and patient-reported outcomes can be used in conjunction with objective measures and as endpoints, while for endpoints that involve observable changes, endpoints should quantify the change. It is also stated that the primary data should be included in the submission for the authority to be able to review it. 
  • Criteria for success should be determined per subject and per study. 
  • Determination should also cover the time at which endpoints will be assessed. 
  • Special attention should be paid to safety and effectiveness. The endpoints related to safety will depend on the principal mode of action of the product in question. 
  • The assessment should also cover the device parameter ranges. 
  • Should the endpoints determined include subjective outcomes, the authority encourages to engage external observers who should be blinded to the history of the treatment. According to the document, this will contribute to increasing the data validity and reliability. The guidance suggests engaging three observers. It is also stated that in case the design of a study developed by a sponsor depends on the respective recommendations provided by the FDA, a sponsor shall get in touch with the authority to discuss the related matters. 


Study Duration and Follow-Up Schedule 

The scope of the guidance also covers the aspects related to the determination of the proper study duration and follow-up schedule to be used. As explained by the FDA, the duration of follow-up will depend on the indications for use, while it is recommended that the study duration and follow-up schedule be based on the anticipated interval needed to assess the durability of the response, as well as the duration and consequent effects of any adverse events, and the incidence of delayed adverse events. According to the recommendations provided by the authority, the follow-up schedule should be designed in a way ensuring proper detection of both early and delated adverse events study participants may face. In terms of the effectiveness of a medical device subject to investigation, tissue effects should be taken into consideration when determining the duration and frequency of follow-up assessments to be conducted. The authority also mentions that in case the device in question is initially intended for ongoing use, the approach to the follow-up schedule would be slightly different. 

According to the guidance, clinical studies for PBM devices should be well designed with valid statistical analysis plans…developed in conjunction with the study design to ensure the data set will be robust. The guidance also refers to a separate document issued by the authority and dedicated to the design considerations for pivotal clinical investigations for medical devices. 


Adverse Event Monitoring 

The authority explicitly states that any and all adverse events occurring during the clinical investigation should be duly documented and reported. As explained by the FDA, such information will be vitally important for proper understating of risks and benefits associated with the medical device in question. 

In summary, the present FDA guidance provides an overview of the applicable regulatory requirements for clinical investigations related to PBM devices, highlights the aspects resulting from the specific nature of such products, and provides recommendations to be followed by medical device manufacturers and study sponsors in order to ensure the accuracy and reliability of study results. The document describes in detail each of such aspects and outlines the key points to be taken into consideration when determining the study endpoints, timelines and follow-up schedule. 




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