The ISO 20916 is specific for in-vitro diagnostic (IVD) medical devices
The ISO 20916 was released in 2019 and uses definitions and concepts appropriate for IVDs. It is a stand-alone standard for clinical performance studies for IVD medical devices.
Purpose of ISO 20916
The initial efforts to develop ISO 20916 built on synergies with the GCP standard for clinical investigation of medical devices in human subjects, ISO 14155. Nonetheless, the intended purpose of IVDs is distinct from that of medical devices and many concepts are different between the two standards. IVDs utilize specimens taken from the human body for diagnosis or monitoring. The potential harm and risk to the patient associated with IVD devices are generally related to erroneous results obtained from the device or collection procedures, rather than to the device itself.
ISO 20916 is intended to provide requirements and guidance for the execution of IVD clinical performance studies (CPS). Clinical performance studies shall be conducted in a manner in which every precaution has been taken to protect the rights and the health and safety of the subject, user and other persons, considering all regulatory and ethical requirements, and using valid scientific principles.
- Ethical and regulatory considerations
- Study design and planning
- Informed consent process
- Site initiation, conduct, and close out
- Site monitoring and data quality
- Adverse event reporting
The standard is structured to accommodate clinical performance studies on all types of IVDs and takes into account that the design of the clinical performance studies will depend on:
- Test samples (e.g. fresh samples, leftover, or archived specimens)
- Study objectives (i.e. results will influence patient management decisions)
- Study design (i.e. procedure will present additional risk of direct harm for the subject)
Clinical performance of an IVD medical device
The clinical performance measures the ability of an IVD medical device to yield results that are correlated with a particular clinical condition or physiological/pathological process/state in accordance with the intended use (clinical test purpose, target population and intended user). In accordance with intended use, clinical performance can include expected values, diagnostic sensitivity and diagnostic specificity based on the known clinical condition or physiological/pathological process/state of the individual, and negative and positive predictive values based on the prevalence of the disease.
Clinical performance studies
How to collect clinical evidence compliant with IVDR
According to the IVDR, clinical evidence must support the device’s intended purpose as stated by the manufacturer and be based on a continuous process of performance evaluation, following a performance evaluation plan (PEP). The clinical evidence is presented in a performance evaluation report (PER) that should demonstrate the following elements.
- Scientific validity
- Analytical performance
- Clinical performance
If a clinical performance study is executed, it should be correctly presented in a clinical performance study report (CPSR), including the study plan and results, and conclusions. A summary of CPSR is presented in the performance evaluation report (PER) as support of the clinical performance requirement.
How to design clinical performance studies
Clinical performance studies are the studies undertaken to establish or confirm an IVD medical device’s clinical performance. The purpose of clinical performance studies is to verify or confirm aspects of device performance that 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 relevant general safety and performance requirements. The data obtained from clinical performance studies are used in the performance evaluation process as a part of the clinical evidence for the IVD.
Types of clinical performance study
An observational (non-interventional) 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.
- Observational study
- Interventional study
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. An interventional design would be appropriate if an observational clinical performance study cannot demonstrate performance claims for an IVD medical device.
Clinical validity is a test’s ability to accurately and reliably predict the clinically defined disorder of interest.
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 validity studies consist of the following test parameters:
- 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 studies should measure the following outcomes:
- Assess potential benefits and harms of testing from the patient perspective
- Consider that outcomes may occur at different time points and result from clinical management decisions guided by test results
- Include clinical assessments of disease remission and progression, response to therapy, functional status, and adverse events
Pre-market testing that has not been specifically designed to address the clinical performance of an IVD medical device (e.g. customer feedback studies, external analytical performance studies, research studies) shall not be considered a clinical performance study.
Clinical performance studies shall be carried out using product representative of the final manufactured IVD medical device intended for commercialization. It is mandatory to use controlled and accepted processes and procedures, even though scale up might not yet be completed.
Clinical performance studies shall be undertaken under an effective quality management system to ensure that the ISO 20916 principles are fulfilled. The study sponsor shall take responsibility for ensuring that these principles are met.
The team at AKRN Scientific Consulting can perform one or more of the sponsor’s clinical performance study-related duties and functions. Please contact us if you need support with the initiation, implementation and oversight of a clinical performance study.