IVD Clinical Performance Studies
Before commencing a clinical performance study, the sponsor shall determine and consider the requirements for regulatory authority approval and ethics committee approval of the clinical performance study and the participating sites. It is the responsibility of the sponsor to ensure that specimens are collected following ethical requirements. The ethics committee can choose to exempt specific IVD medical device clinical performance studies from their approval and/or can waive informed consent.
Informed consent for leftover or archived specimens may exist in a general form to cover the specimens’ use in any clinical performance studies. Sponsors might not have direct access to this original informed consent but should obtain and verify the institution’s informed consent policy. Ethics committee approval should be sought when doubts are surrounding the validity and applicability of the original informed consent.
When written approval/favorable opinion from the ethics committee and/or the relevant regulatory authorities of the countries where the clinical performance study is taking place is required, the clinical performance study shall not commence until that approval/opinion has been received. The clinical performance study shall be conducted in accordance with the Clinical Performance Study Protocol (CPSP).
Performance Study Protocol (CPSP)
The CPSP is developed to ensure the clinical performance study is performed to yield high quality, accurate, and reliable data for the IVD medical device under investigation. The CPSP shall be developed by investigators or sponsors appropriately qualified by education, training, or experience. An appointed representative of the sponsor shall sign and date the protocol, indicating sponsor acceptance. The CPSP and all subsequent amendments to the CPSP shall be agreed upon between the sponsor and all principal investigators and shall be recorded with a justification for each amendment.
The CPSP shall include a summary or overview of the clinical performance study regarding the clinical performance study design, such as inclusion/exclusion criteria, number of specimens and, when applicable, subjects, duration of the clinical performance study, objective(s), endpoint(s). In particular, the CPSP shall describe the:
- Objectives, primary and secondary, if applicable.
- Relevant primary and secondary endpoints.
- Claims and intended performance of the IVD medical device under investigation.
- Risks and anticipated adverse device effects assessed.
When a comparator is used, they should be listed. When the comparator is a commercial assay, include name and manufacturer, and when applicable, the version or catalog number. When the comparator is a reference method or “gold standard”, it is essential to provide adequate published references supporting the methodology.
After the clinical performance study’s close-out, including premature termination, a report of the study shall be completed.
Purpose of Clinical Performance Studies
The purpose of the Clinical Performance Study is to establish 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 the relevant general safety and performance requirements concerning clinical performance. When clinical performance studies are conducted, the data obtained shall be used in the performance evaluation process and part of the device’s clinical evidence.
The manufacturer/sponsor of the IVD medical device is responsible for the design of the CPSP. The clinical performance study shall be carried out using a product representative of the final IVD medical device intended for commercialization, using controlled and accepted processes and procedures.
The choice of the design for the clinical performance study can depend on the following considerations:
a) study objectives;
b) the outcome of the risk evaluation;
c) intended use, specifically:
1) test purpose(s) (e.g. diagnosis, screening, monitoring);
2) target population(s) (e.g. age, race, gender, geography, clinical condition, treatment status);
3) specimen type(s) (e.g. serum, plasma, urine, whole blood);
4) intended user(s)/operator(s) (person performing the test e.g. lay person).
d) specimen/sample handling and storage conditions (e.g. sample cannot be frozen);
e) sample size estimate and description of planned statistical analysis;
f) quality, availability, and accessibility of specimens (e.g. limited number of leftover specimens available);
g) testing location (e.g. point-of-care setting, central laboratory);
h) intended use setting’s environmental conditions;
i) established analytical performance characteristics (e.g. precision, interference, measuring interval (range), cut-off, the limit of detection, the limit of quantification);
j) intended clinical performance characteristics (e.g., sensitivity, specificity, positive predictive value, negative predictive value, reference intervals, cut-off);
k) prevalence of the clinical condition/physiological or pathological state;
l) novelty of the technology and/or clinical use (e.g. relevant previous experience);
m) availability of the appropriate method(s) to establish the clinical status of the subject;
n) availability of quality control material;
o) mechanisms to avoid bias.
Setting up a CSP according to ISO standard 20916:2019
In particular, the manufacturer/sponsor shall be responsible for:
- Design of the Clinical Performance Study Plan (CPSP)
- Select clinical sites and Principal Investigator (PI)
- Obtain clinical investigation insurance
- Obtain the authorization from the Competent Authorities for the following studies:
- studies in which surgically invasive sample-taking is done only for the purpose of the performance study
- interventional clinical performance study
- where the conduct of the study involves additional invasive procedures or other risks for the subjects of the studies,
- studies involving companion diagnostic
- Obtain favorable approval from Ethics Committee
- Report serious adverse events (SAEs) occurring during the performance studies through the EUDAMED database.
- Prepare the Clinical Investigation Study Report (CSR), which should be incorporated in the technical documentation that has to be kept available by the manufacturer and the appointed European Authorized Representative (EAR) established within the Union (for non-EU manufacturers).
- The sponsor (or EAR) shall notify the competent authorities of the ending of the clinical investigation and submit the CSR to the relevant competent authorities.
- The sponsor shall provide the Notified Body the relevant data related to clinical investigation and evaluation to be reviewed during the technical documentation assessment as part of the conformity assessment procedure.
Manufacturer/sponsor may choose to appoint a medical device Clinical Research Organization (CRO) to seek regulatory approvals and to set up and manage the clinical performance study.
AKRN also has the experience and qualifications to prepare clinical study reports, performance evaluation reports, and all the necessary technical documentation for Notified Body conformity assessments.