Clinical Data Analysis

(1) Clinical data for evaluation of the nature, severity, and frequency of the side effects
(2) To ensure scientific validity of conclusions, an adequate number of observations from clinical data should be available.
(3) To assess acceptability, consider the state of the art, properties of benchmark devices and medical alternatives, and objective performance criteria from standards.

(1) The ability of the device to achieve its intended purpose, including direct or indirect effects, clinical benefits, should be determined.
(2) The clinical data of the device achieves its intended performance during normal conditions of use and the intended performance should be analyzed.

 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

o Detail on the clinical background should consider all the data and not be selective.
o Deficiencies and alternative approaches available should be analysed.
o An analysis should be made if the device addresses a significant gap in healthcare, and when there is no such clinical need, design should demonstrate improved or equivalent benefit to the existing products.
o When treatment comparability versus accepted therapy is not available, it must be described in the IFU.
o 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.

 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
 Probability of a harmful event
 Duration of harmful events
 Risk due to false-positive or false-negative results from diagnostic medical devices.

o The harmful events should be assessed in totality considering the severity of the aggregate effect of multiple harmful effects at once.
o Any hazard identified during analysis of clinical data not previously outlined in the risk management documentation, should be provided with mitigation measures.

o The nature, extent, probability and duration of benefits from the device should be considered and which include:
 Positive impact on clinical outcome
 Improvement of Patient’s quality of life
 Diagnosis related outcomes
 Impact on public health

a End points
o Benefits should be evaluated along a scale or specific endpoints or pre-identified health threshold.
o Magnitude of benefit should be determined by improvement or worsening of the endpoint.
o If Surrogate end points are met, benefits should be assumed to be validated
o The end points should be clinically relevant, and surrogate end points should be valid. This shall be justified and documented.

b Probability of benefits
o Probability of benefits on the population should be predicted.
o Benefits observed only in the subgroup should be indicated.
o Magnitude and probability of clinical benefits should be determined and put together when weighing benefits against risk.

c Duration of effects
o Relevant clinical data and statistical approaches should characterize the duration.
o Data from PMCF should be analyzed to determine the gaps in evidence.
o The extent of treatment and current knowledge and available alternatives also should be considered.