Analyze the pre-clinical and clinical data to ensure requirements for safety, performance, risk-benefit profile, and undesirable side effects of a medical device. Appraised clinical data derived from the clinical evaluation and investigation, PMS, and literature are to be considered for analysis to demonstrate safety and performance.
Conformity assessment with the requirement for safety
Information from the label, IFU, and brochure shall be reviewed to ensure their consistency with the appraised clinical data. All hazards, Information regarding risk mitigation and clinically relevant information must be identified appropriately. In the analysis, a review is conducted to make sure the below is covered:
- The gaps identified in the risk management documents against the relevant standards are covered by the clinical data.
- All identified risks relating to patient treatment, method of operation of the device, and usability are minimized and if clinical risks are raised should be solved.
- The Harmonized standards should be applied to confer conformity.
- If technical developments provide a higher level of safety than the current Harmonized standard, then it must be prioritized to demonstrate compliance to meet the essential requirements and side effects must be acceptable.
Evaluation of the description of the intended purpose of the device
The information materials should be reviewed to evaluate whether the device description provided demonstrates conformity with the essential requirements through clinical evidence. There should be no ambiguity to the user on the intended use or the target population.
Clinical Evaluation of the device’s benefits to the patient
The nature, extent, probability and duration of benefits from the device should be considered and included in the MDR clinical evaluation report.
- Positive impact on clinical outcome
- Improvement of Patient’s quality of life
- Diagnosis-related outcomes
- Impact on public health
Quantification of benefit(s) to the patients
- Benefits should be evaluated along a scale or specific endpoints or pre-identified health threshold.
- The magnitude of benefit should be determined by the improvement or worsening of the endpoint.
- If Surrogate endpoints are met, benefits should be assumed to be validated.
- The endpoints should be clinically relevant, and surrogate endpoints should be valid. This shall be justified and documented.
Probability of benefits
- The probability of benefits for the population should be predicted.
- Benefits observed only in the subgroup should be indicated.
- Magnitude and probability of clinical benefits should be determined and put together when weighing benefits against risk.
Duration of effects
- Relevant clinical data and statistical approaches should characterize the duration.
- Data from PMCF should be analysed to determine the gaps in evidence.
- The extent of treatment and current knowledge and available alternatives also should be considered.
Clinical Evaluation of the clinical risks of devices
Risk management should address the significance of the residual risks remaining after mitigation. The regulatory status, reporting conducted, and estimates of the incidence of incidents reported in the PMS evaluation report should be considered. To demonstrate the extent of the risk, the following factors should be considered.
- Nature severity, number and rates of harmful events associated with the use of the device.
- Device-related serious adverse events and incidents
- Device-related non-serious and non-reportable harmful events
- Procedure-related incidents
- The probability of a harmful event
- Duration of harmful events
- Risk due to false-positive or false-negative results from diagnostic medical devices.
The harmful events should be assessed in totality considering the severity of the aggregate effect of multiple harmful effects at once. Any hazard identified during the analysis of clinical data not previously outlined in the risk management documentation should be provided with mitigation measures.
Evaluation of acceptability of the risk-benefit profile
Current knowledge and state of the art of the medical device should be identified and defined. The following should be documented:
- Clinical background
- Information on the clinical condition to be treated, managed, or diagnosed.
- Prevalence of the condition
- Natural Course of the condition
- Safety and performance of currently available medical alternatives
- Historical treatments
- Medical options available to the target population
- Existing devices, benchmark devices
Detail on the clinical background should consider all the data and not be selective. Deficiencies and alternative approaches available should be analysed. An analysis should be made if the device addresses a significant gap in healthcare, and when there is no such clinical need, the design should demonstrate improved or equivalent benefits to the existing products.
When treatment comparability versus accepted therapy is not available, it must be described in the IFU. When a device is not best in class, evidence can be provided for acceptable benefit for specific, groups or superior clinical performance under specific conditions.
Conformity assessment with the requirement on performance
The ability of the device to achieve its intended purpose, including direct or indirect effects, and clinical benefits, should be determined. The clinical data of the device achieves its intended performance during normal conditions of use and the intended performance should be analysed.
Conformity assessment with the requirement on the acceptability of undesirable side effects
A decision on whether an undesirable side effect is acceptable is made by weighing against the intended performance. The acceptability of the side effects of a device is evaluated based on the below information:
- Clinical data for evaluation of the nature, severity, and frequency of the side effects
- Adequate number of observations from the clinical data should be available to guarantee the scientific validity of conclusions.
- State of the art, properties of benchmark devices and medical alternatives and objective performance criteria from standards should be considered to evaluate the acceptability.
Conclusion
Medical device clinical evaluation Report documentation is of great importance in the CE Marking of medical devices as per new MDR 2017/745. Contact the I3CGLOBAL team of regulatory experts for proper guidance.
