June 2, 2020 Medical Device - Clinical

At present, the regulatory discussion pretty much focuses on MDR Regulation (EU) 2017/745 on medical devices. However, it seems the impact of Regulation (EU) 2017/746 on in vitro medical devices (IVDR) on the industry is expected to be much more intense. With the updated in vitro diagnostic medical devices (IVD) classification, at least 80% of IVDs will be moving under Notified Body scrutiny, compared to 20% previously. Therefore, most manufacturers should now be gearing up to shift from self-certification to notified body oversight as IVDR will be fully enforceable on May 2022.

According to the IVDR, clinical evidence must support the intended purpose of the device as stated by the manufacturer and be based on a continuous process of performance evaluation, following a performance evaluation plan. The performance evaluation reports should demonstrate the following elements-

  • Scientific validity
  • Analytical performance
  • Clinical performance

As far as clinical performance is concerned, Clinical Performance Studies are the studies undertaken to establish or confirm the clinical performance of an IVD medical device.The purpose of a clinical performance studies is to establish or confirm aspects of device performance which cannot be determined by analytical performance studies, literature and/or previous experience gained by routine diagnostic testing. This information is used to demonstrate compliance with the relevant general safety and performance requirements with respect to clinical performance. The data obtained from clinical performance studies is used in the performance evaluation process as a part of the clinical evidence for the IVD.

The two important aspects of clinical performance studies are clinical validity and clinical utility studies.

Clinical Validity Studies is the ability of a test to accurately and reliably predict the clinically defined disorder orphenotype of interest. The clinical validity studies consist of the following test parameters-

Test Parameters Definitions
Clinical Sensitivity The percentage of individuals with the target condition (disease) that will have positive test results
Clinical Specificity The percentage of individuals that do not have the target condition who will have negative test results
Positive Predictive Value The proportion of individuals in the intended use populations who have the target condition
Negative Predictive Value The proportion of individuals in the intended use populations who do not have the target condition

Clinical Utility is the ability of a test to implicitly improve patient health outcomes, when used to inform and support clinical decisions that increase the chances of improved patient outcomes.

Clinical Utility Studies include-

  • Outcome measures that assess both potential benefits and harms of testing from the patient perspective
  • Recognizing that these outcomes may occur at different time points and are the result of clinical management decisions guided by test results
  • These outcome measures include such as clinical assessments of disease remission and progression, response to therapy, functional status as well as adverse events.

Clinical utility will vary with each new IVD based on its intended use, existing tests. Although it is common to separate the terms clinical validity and clinical utility, a clear-cut separation is not always possible since the clinical validity of the tests depends on the intended use or the claims made on the use of the test.

The designs of IVD clinical performance studies could be two types – Observational and Interventional study

  • An observational study refers to a study in which test results obtained during the study are not used for patient management and do not impact treatment decisions.
  • An interventional study refers to a study in which test results obtained during the study may influence patient management decisions and may be used to guide treatments.

If performance claims for an IVD medical device cannot be demonstrated by an observational clinical performance study, an interventional design would be appropriate

The clinical performance studies require a clinical performance study report, which will include the study plan, procedure, results, and conclusions. These reports will have to contain enough information to be understood by an independent party without reference to other documents. As planning, execution and collection of the data on clinical performance studies take considerable amount of time; the IVD manufacturers should seriously look into the need of clinical performance studies of their IVD products based on the clinical data available with them.