Most IVD products undergo clinical performance studies using the observational design. This is because clinical performance studies are done parallel along with routine testing, and so do not determine patient management decisions. The specimens used in these studies are mostly:
- Previously-collected specimens, such as archived specimens or leftover specimens that would otherwise have been discarded (also called surplus specimens); and/or
- Additional specimens collected specifically for the study purposes (Ref. More details in GHTF SG5/N8)
For instance, a clinical performance study for an HIV or HBV kit can be planned using serum samples collected for routine testing and also certain certified panels. There are a lot considerations related to the use of archived samples.
An interventional design is to be used when an observational study cannot be planned. Consider a situation where there is no established test available. Here an interventional design may be required.
Secondly, another situation would be that the manufacturer intends to determine the impact on clinical outcomes by using the IVD product. Or thirdly, the IVD product is co-developed along with a therapeutic product and the information provided by the IVD will influence the patient treatment in a therapeutic clinical trial.
In both these cases an interventional design may be required for determining patient outcome by monitoring the analyte in question. This is determining what is referred to as treatment efficacy.
The CPSP must define the rationale, objectives, design and proposed analysis, methodology, monitoring, conduct, decision algorithms, and record-keeping of the clinical performance study. It should also include a description of the expected risks and benefits of the device and of the clinical performance study in the context of the state of the art in clinical practice. Parameters of clinical performance and the expected clinical outcomes should be clear and predetermined. The quality of data is crucial. The CPSP could be based on the ISO 20916:2019 which is a stand-alone standard specific for IVDs and therefore very appropriate. It provides guidance for conducting clinical studies for IVDs. By following the ISO standard, the study would be undertaken under GCP and a robust quality management system.
After creating a CPSP, the study can be initiated. For the study, products representative of the final manufactured IVD which is ready for commercialization should be used.
Annex XIII provides complete details regarding the contents of the CPSP. Also refer to the GHTF guidelines (Ref. GHTF SG5/N8).
A clinical performance study report should have complete details about the clinical performance study protocol plan, results, and conclusions of the clinical performance study, including negative findings. The results and conclusions should be transparent, free of bias, and clinically relevant. The report should also include any protocol amendments or deviations, and data exclusions with the appropriate rationale.
Clinical performance provides performance characteristics such as diagnostic sensitivity, diagnostic specificity, positive predictive value, negative predictive value, likelihood ratio, and expected values in normal and affected populations.
The Clinical performance report is to be included as a part of the Performance Evaluation report (PER) which provides the Clinical Evidence of the IVD. They are a part of the Technical Documentation of the device.
The level of detail of the CPSR depends on the class of the IVD:
||Clinical Study Report
||A clinical performance study is not expected
||The study report should have a summary of study protocol, results and conclusion.
||The complete study report should have the method of data analysis, the study conclusion and relevant details of the study protocol
||The complete study report should include the method of data analysis, the study conclusions, relevant details of the study protocol, and typically the individual data points (formatted raw data).
Table 1: Clinical Performance Study Report requirements by class of IVD device.