Regulation (EU) 2017/746 of the European Parliament and of the CouncilDangos y teitl llawn

2. CLINICAL PERFORMANCE STUDIES

2.1. Purpose of clinical performance studies

The purpose of 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. When clinical performance studies are conducted, the data obtained shall be used in the performance evaluation process and be part of the clinical evidence for the device.

2.2. Ethical considerations for clinical performance studies

Each step in the clinical performance study, from the initial consideration of the need for and justification of the study to the publication of the results, shall be carried out in accordance with recognised ethical principles.

2.3. Methods for clinical performance studies

2.3.1. Clinical performance study design type

Clinical performance studies shall be designed in such a way as to maximize the relevance of the data while minimising potential bias.

2.3.2. Clinical performance study plan

Clinical performance studies shall be performed on the basis of a clinical performance study plan (CPSP).

The CPSP shall define the rationale, objectives, design and proposed analysis, methodology, monitoring, conduct and record-keeping of the clinical performance study. It shall contain in particular the following information:

(a)

the single identification number of the clinical performance study, as referred to in Article 66(1);

(b)

identification of the sponsor, including the name, address of the registered place of business and contact details of the sponsor and, if applicable, the name, address of the registered place of business and contact details of its contact person or legal representative pursuant to Article 58(4) established in the Union;

(c)

information on the investigator or investigators, namely principal, coordinating or other investigator; qualifications; contact details, and investigation site or sites, such as number, qualification, contact details and, in the case of devices for self-testing, the location and number of lay persons involved;

(d)

the starting date and scheduled duration for the clinical performance study;

(e)

identification and description of the device, its intended purpose, the analyte or analytes or marker or markers, the metrological traceability, and the manufacturer;

(f)

information about the type of specimens under investigation;

(g)

overall synopsis of the clinical performance study, its design type, such as observational, interventional, together with the objectives and hypotheses of the study, reference to the current state of the art in diagnosis and/or medicine;

(h)

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, and with the exception of studies using left-over samples, the medical procedures involved and patient management;

(i)

the instructions for use of the device or test protocol, the necessary training and experience of the user, the appropriate calibration procedures and means of control, the indication of any other devices, medical devices, medicinal product or other articles to be included or excluded and the specifications on any comparator or comparative method used as reference;

(j)

description of and justification for the design of the clinical performance study, its scientific robustness and validity, including the statistical design, and details of measures to be taken to minimise bias, such as randomisation, and management of potential confounding factors;

(k)

the analytical performance in accordance with point (a) of Section 9.1 of Chapter I of Annex I with justification for any omission;

(l)

parameters of clinical performance in accordance with point (b) of Section 9.1 of Annex I to be determined, with justification for any omission; and with the exception of studies using left-over samples the specified clinical outcomes/endpoints (primary/secondary) used with a justification and the potential implications for individual health and/or public health management decisions;

(m)

information on the performance study population: specifications of the subjects, selection criteria, size of performance study population, representativity of target population and, if applicable, information on vulnerable subjects involved, such as children, pregnant women, immuno-compromised or elderly subjects;

(n)

information on use of data out of left over specimens banks, genetic or tissue banks, patient or disease registries etc. with description of reliability and representativity and statistical analysis approach; assurance of relevant method for determining the true clinical status of patient specimens;

(o)

monitoring plan;

(p)

data management;

(q)

decision algorithms;

(r)

policy regarding any amendments, including those in accordance with Article 71, to or deviations from the CPSP, with a clear prohibition of use of waivers from the CPSP;

(s)

accountability regarding the device, in particular control of access to the device, follow-up in relation to the device used in the clinical performance study and the return of unused, expired or malfunctioning devices;

(t)

statement of compliance with the recognised ethical principles for medical research involving humans and the principles of good clinical practice in the field of clinical performance studies as well as with the applicable regulatory requirements;

(u)

description of the informed consent process, including a copy of the patient information sheet and consent forms;

(v)

procedures for safety recording and reporting, including definitions of recordable and reportable events, and procedures and timelines for reporting;

(w)

criteria and procedures for suspension or early termination of the clinical performance study;

(x)

criteria and procedures for follow up of subjects following completion of a performance study, procedures for follow up of subjects in the case of suspension or early termination, procedures for follow up of subjects who have withdrawn their consent and procedures for subjects lost to follow up;

(y)

procedures for communication of test results outside the study, including communication of test results to the performance study subjects;

(z)

policy as regards the establishment of the clinical performance study report and publication of results in accordance with the legal requirements and the ethical principles referred to in Section 2.2;

(aa)

list of the technical and functional features of the device indicating those that are covered by the performance study;

(ab)

bibliography.

If part of the information referred to in the second paragraph is submitted in a separate document, it shall be referenced in the CPSP. For studies using left-over samples, points (u), (x), (y) and (z) shall not apply.

Where any of the elements referred to in the second paragraph are not deemed appropriate for inclusion in the CPSP due to the specific study design chosen, such as use of left-over samples versus interventional clinical performance studies, a justification shall be provided.

2.3.3. Clinical performance study report

A clinical performance study report, signed by a medical practitioner or any other authorised person responsible, shall contain documented information on the clinical performance study protocol plan, results and conclusions of the clinical performance study, including negative findings. The results and conclusions shall be transparent, free of bias and clinically relevant. The report shall contain sufficient information to enable it to be understood by an independent party without reference to other documents. The report shall also include as appropriate any protocol amendments or deviations, and data exclusions with the appropriate rationale.