What Should Be Submitted under Clinical Evidence - Requirements Related to Medical Device Rules & Regulation (CDSCO, EU, US FDA)

The convergence of requirements for clinical evidence is expected to yield several significant benefits for all stakeholders involved in the medical device ecosystem. By harmonizing data submissions across regions and regulatory bodies, a clearer understanding of medical device safety, clinical performance, and effectiveness can be achieved. This alignment fosters greater transparency and confidence in the global regulatory model, benefiting patients, healthcare providers, regulators, and industry alike.

Standardized data requirements streamline the clinical evaluation process, optimizing the allocation of resources within the clinical community, regulatory agencies, and industry. This efficiency ensures that valuable time and resources are utilized effectively, ultimately improving patient care and outcomes.

The diversity of medical devices and the technologies on which they are based pose special challenges for manufacturers, conformity assessment bodies and regulators alike when trying to identify what should constitute evidence sufficient to demonstrate compliance with the Essential Principles. Some technologies have been available for many years and are well characterised from a safety, clinical performance and/or effectiveness viewpoint. On the other hand, many medical devices utilise new, state-of-the-art technology that has had little prior application in the treatment of humans.

Furthermore, their intended purpose and clinical application can vary widely with end results influenced by a wide range of different and differently experienced end-users. Given the complexity of the medical devices milieu, the assessment of what is acceptable clinical evidence for the purpose of demonstrating compliance with the Essential Principles must be undertaken on a case-by-case basis. To this end, it is important to have an understanding of how medical devices are brought to market and of the role that clinical data and its evaluation plays in this process.

Clinical investigation

Any systematic investigation or study in or on one or more human subjects, undertaken to assess the safety, clinical performance and/or effectiveness of a medical device, refers to the process of conducting research or clinical studies involving human participants to evaluate various aspects of a medical device.

This term is synonymous with ‘clinical trial’ and ‘clinical study’. Effectiveness is the ability of a medical device to achieve clinically meaningful outcome(s) in its intended use as claimed by the manufacturer. Clinical investigations include feasibility studies and those conducted for the purpose of gaining market approval, as well as investigations conducted following marketing approval.

Clinical data

Safety, clinical performance and/or effectiveness information that is generated from the clinical use of a medical device.

Sources of clinical data may include:

• results of pre- and post-market clinical investigation(s) of the device concerned
• results of pre- and post-market clinical investigation(s) or other studies reported in the scientific literature of a comparable device
• published and/or unpublished reports on clinical experience of either the device in question or a comparable device
• other sources of clinical experience such as registries, adverse event databases and medical records.

Clinical evaluation

A set of ongoing activities that use scientifically sound methods for the assessment and analysis of clinical data to verify the safety, clinical performance and/or effectiveness of the medical device when used as intended by the manufacturer.

• This is a process undertaken by manufacturers of medical devices to help establish compliance with the relevant Essential Principles for safety and performance. The result of this process is a report, which can be reviewed by conformity assessment bodies and regulators. The report details the extent of available data and its quality, demonstrating how the clinical data satisfies compliance with the Essential Principles. Clinical evaluation is an ongoing process - information about safety, clinical performance and/or effectiveness (e.g. adverse event reports, results from any further clinical investigations, published literature etc.) should be monitored routinely by the manufacturer once the device is available on the market and the benefits and risks reassessed in light of this additional information.
• The inputs for clinical evaluation are primarily clinical data in the form of clinical investigation reports, literature reports/reviews and clinical experience. The data required to establish the evidence of compliance with the Essential Principles may vary according to the characteristics of the medical device, its intended use, the claims made by the manufacturer, the existence and adequacy of warnings and other restrictions, and the extent of experience with its use. A key goal of the clinical evaluation is to establish that any risks associated with the use of the medical device are acceptable when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety. The clinical evaluation will, therefore, also need to cross-reference risk management documents.

Clinical evidence

The Clinical Evaulation Report along with all relavent clinical data pertaining to medical device is togther considered as Clinical Evidence. 

• Clinical evidence is an important component of the technical documentation of a medical device, which along with other design verification and validation documentation, device description, labelling, risk analysis and manufacturing information, is needed to allow a manufacturer to demonstrate conformity with the Essential Principles. It should be cross-referenced to other relevant parts of the technical documentation that impact on its interpretation.
• In accordance with applicable local regulations, clinical evidence, in part or in total, may be submitted to and reviewed by conformity assessment bodies and regulatory authorities. The clinical evidence is used to support the marketing of the medical device, including any claims made about the safety, clinical performance and/or effectiveness of the device, and the labelling of the device. Figure 1 shows how the need for clinical evidence drives the processes of data generation and clinical evaluation, which produce clinical data and clinical evidence, respectively.
• Clinical evidence should be reviewed and updated throughout the product life cycle by the manufacturer as new information relating to safety, clinical performance and/or effectiveness is obtained from clinical experience during marketing of the device in question and/or comparable devices.