To ensure effective planning and execution of a clinical performance study, it is recommended to generate a clinical performance study protocol (CPSP), also referred to as a clinical performance study plan in the In Vitro Diagnostic Regulation 2017/746. The topics that are typically included in a CPSP are described in detail in a stand-alone standard ISO 20916 which is specific for in vitro diagnostic medical devices (IVDs). CPSP is defined in section 5.5.3 and normative Annex B. Bellow we are highlighting specific requirements which are necessary to be emphasized.
In clinical performance studies, the study sponsor plays a critical role in ensuring the study is conducted appropriately and meets regulatory and ethical standards. The study sponsor can be an individual or organization that takes responsibility for the initiation, management, financing, and oversight of the study. One of the primary responsibilities of the study sponsor is to ensure that a comprehensive and scientifically-sound study protocol is developed. This involves collaborating with experts, such as principal investigators, statisticians, and other subject matter experts (regulatory affairs specialist, data manager, …).
Identification and description of the IVD and intended use
The protocol shall include summary description of the IVD medical device under investigation and its intended use.
Specimens and when applicable, subjects providing specimens
The protocol shall also clearly define validated specimen type, inclusion criteria, exclusion criteria, information necessary to characterise the subject/specimen, number of specimens/subjects, specimen storage, handling, transport and disposal. If subjects are providing specimens, it shall include the information regarding criteria and procedures for subject withdrawal and discontinuation, expected number of each subject’s participation, number of subjects providing specimens required to be included, and estimated time needed to select this number (enrolment period).
Objectives and endpoints (primary and secondary)
The proposed clinical performance study should have a clear and well-defined rationale that explains its purpose and objectives. The study’s primary and secondary objectives and endpoints should be clearly defined and aligned with the study’s hypothesis. The objectives should be measurable and achievable, allowing for the collection of meaningful data and the evaluation of the device’s safety and performance in real-world conditions.
Procedure represents methodology and all study-related procedures that the specimens will undergo during the study.
Informed consent process
Informed consent process describes the general process for obtaining inform consent, including the process for providing subjects with new information. Also, it describes the process in circumstances when the subject is unable to give a consent.
Statistical consideration describes and justifies statistical design, method and analytical procedures, sample size, level of significance and power of clinical performance study, pass/fail criteria to be applied to results etc.
Monitoring and data management
A detailed strategy for monitoring the clinical performance study should be developed, which includes defining how the source data will be accessed and the extent of source data verification necessary. It is important to note that monitoring can occur during and/or after the clinical performance study. The comprehensive monitoring plan is typically separate from the CPSP.
Adverse event, adverse device effects and device deficiency documentation and reporting
The protocol should describe also how to categorise, evaluate and report adverse events and device deficiencies which could result in serious adverse event. Depending on individual study requirements, rare or very rare events may be included or excluded.
Furthermore, it is very important that all the external entities participating in the studies (CRO, labs, investigator) are well identified and written agreements are complete to properly define the responsibilities.
The CPSP should clearly define the objectives, design, methodology, risk and benefit assessment, expected outcomes, and quality management system for the study. Parameters for clinical performance and expected outcomes should be predetermined. Data quality is critical. The ISO 20916:2019 standard, which provides guidance for conducting clinical studies for IVDs, is highly recommended. Following the ISO standard ensures that the study is conducted under Good Clinical Practice guidelines and a robust quality management system. Once the CPSP is finalized, the study can commence.