The article describes in detail the approach to be applied for clinical evidence for implantable pulse generator systems and also highlights the key points to be considered in this respect, including the matters related to the scope of evidence to be provided.
The Therapeutic Goods Administration (TGA), an Australian regulating authority in the sphere of healthcare products, has published a guidance document dedicated to clinical evidence for medical devices. The document is intended to provide additional clarifications regarding the applicable regulatory requirements for clinical evidence required depending on the type of medical device in question and specific risks associated thereto. The guidance also provides recommendations to be taken into consideration by medical device manufacturers and other parties involved to ensure compliance with the said requirements. Provisions of the guidance are non-binding, nor are intended to introduce new rules or impose new obligations, and could be subject to changes, should such changes be reasonably required to reflect corresponding changes to the existing legislation. The scope of the guidance covers, inter alia, the aspects related to the implantable pulse generator systems – active medical devices that produce electrical discharges, including cardiac active implantable devices and implantable electrical nerve stimulation devices.
Recommendations: Key Points
First of all, the document provides a summary of recommendations to be followed by medical device manufacturers and other parties interested in placing the devices covered by the scope of the guidance on the Australian market. In particular, the authority emphasizes the following:
- The medical devices in question are complex products that could be used in combination with other products, so the responsible parties are encouraged to provide exhaustive information about all possible components and combinations, together with the clinical evidence demonstrating compliance with the applicable requirements in terms of safety and effectiveness.
- In case a clinical investigation is to be conducted to collect additional clinical data, such an investigation (study) should be designed following the highest practical NHMRC Level of Evidence and duly address the main safety- and performance-related matters.
- When determining the clinical outcomes required to demonstrate compliance with the applicable requirements, the manufacturer should take into consideration the type of the device in question and the specific aspects associated thereto. For instance,
- The manufacturer is advised to benchmark the new device against devices of the same class as reported by an international registry, if available.
- Nominated values that indicate safety and performance should be appropriate to patient health status and indicated use and justified by a clinician who is an expert in the field.
- For patient performance, data manufacturers are advised to define the anticipated improvement in patient scores post-surgery or post-treatment. As further explained by the TGA, the appropriate measures should be conducted by the device of an internationally recognized assessment tool.
- In case the applicant refers to a literature review, it will be necessary to provide enough details to make it possible to reproduce the search.
- Applicants are also expected to provide information regarding the risk assessment and management system, including the details regarding the risks identified and corresponding reduction activities.
The authority also provides detailed recommendations regarding the approach to be applied when conducting a literature review or providing clinical evidence. For the latter, the authority mentions that all the clinical data collected should be subject to a rigorous review and assessment by an expert having the necessary qualifications in the relevant field. Such an expert has to determine the sufficiency of the data collected in the context of claims made by the manufacturer regarding the safety, quality, and effectiveness of the device. The authority also expects a CV of an expert involved to be provided.
The document further defines the products covered by its scope. In particular, recommendations provided in the guidance are applicable for medical devices intended to generate electrical discharges and used for numerous treatment solutions. According to the guidance, such products could be divided into the following categories:
- Active Implantable Cardiac Devices (AICD) include:
- Single and dual chamber pacemakers,
- Cardiac resynchronization therapy pacemakers, with or without defibrillation (i.e. CRT-D and CRT respectively),
- Implantable cardiac defibrillators (ICDs);
- Electrical nerve stimulation devices:
- Only implantable electrical nerve stimulation devices will be covered in this guidance; transcutaneous electrical nerve stimulation (TENS) devices are not included.
The authority also emphasizes the importance of considering the specific nature of the products covered by the scope of the guidance – they are intended for long in vivo use, hence, should remain safe and operate properly within the whole period of their intended life.
According to the guidance, clinical evidence admissible for implantable pulse generator systems includes the data derived from clinical studies and a comprehensive literature review. The applicants are also allowed to refer to the appropriate data related to comparable medical devices. It is explicitly stated by the TGA that all claims made by the manufacturer concerning the safety, quality, and performance of the device, as well as indications for use and contraindication should be duly supported by the respective data.
Under the general rule, direct clinical evidence (related to the device in the question itself, and not to a comparable product) is preferable. However, as it was mentioned before, indirect (related to a comparable device) data could still be used, provided substantial equivalence has been duly established by comparing the most important technical, clinical and biological characteristics of both products.
The authority also reminds that all changes made to the device after the clinical data has been collected should be duly documented, and the information should be provided to the authority upon request.
In summary, the guidance provides an overview of the regulatory requirements regarding the clinical evidence required for implantable pulse generator systems. The document outlines the key points to be considered when determining the scope of clinical data required and provides additional recommendations associated thereto.
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