Clinical performance studies for In-Vitro Diagnostic devices are needed when analytical performance studies or other methods like literature research are not sufficient to evaluate the performance of the IVD device. There has been for many years a gap for lack of clear guideline on the design and management of performance studies for IVD devices. However, ISO 20916: 2019 – In vitro diagnostic medical devices — Clinical performance studies using specimens from human subjects — Good study practice – has been published in 2019 to cover this specific gap.

The IVDR 2017/746 established specific requirements for the clinical performance studies of IVD, mainly in articles 57 to 77 and in Annex XIII, section 2. The ISO 20916 provides a further guidance in how it is possible to cover the specific requirements of the IVDR.

In the medical device world there are three standards which can be taken in considerations for clinical evaluation:

  • EN 13612:2002 – Performance evaluation of in vitro diagnostic medical devices. This standard is IVD-specific and deals with the requirements for performance evaluation of IVD device.
  • ISO 20916:2019: this is also an IVD-specific standard, it contains 9 clauses, which basically means it has the common structure.
  • ISO 14155:2020 – this standards deals with clinical evaluation for medical device but it excludes IVD from its scope.

Types of Clinical Performance Studies

There are different types of Clinical Performance Studies for IVD devices, based whether there is the necessity of patient management based on the results of the test. In case there is the need of patient management, the study is interventional and, in this scenario, the following Annex of the standards are applicable:

  • Body of the standard by Annex G + all the annexes from A to F

In case the study is non interventional, usually only Annex G, along with the whole body of the standard, is applicable.

Structure of the Standard ISO 20916:2019

The ISO 20916 is characterised by the following clauses:

  • Clauses 4 : Ethical Considerations
  • Clauses 5: Study Planning
  • Clauses 6: Site Initiation
  • Clauses 7: Study Conduct
  • Clauses 8: Clouse-Out

We will not go through all the clauses, but we can take in consideration clauses 4 and clauses 5.

Clause 4 – Ethical Considerations within ISO 20916

Ethical considerations are always at the bases of clinical studies. Ethical considerations are in general based on the Declaration of Helsinki, which plays a fundamental role in defining guideline for safety, dignity and well-being of the subjects. This part of the standard defines as well the responsibilities of all the parties involved and the involvement of ethics committees for the type of studies.

Clauses 5 – Study Planning

Clauses 5 of the ISO 20491 is surely the longest section of the whole standard. This part defines the requirements for the planning of the clinical performance studies. The clauses 5 contains 12 sections which are listed below:

  • 5.1 General
  • 5.2 Risk Evaluation
  • 5.3 Design
  • 5.4 Investigation Brochure
  • 5.5 Clinical Performance Study Protocol
  • 5.6 Case Report Forms
  • 5.7 Recording of specimen information
  • 5.8 Specimen accountability and integrity
  • 5.9 Study site selection
  • 5.10 Monitoring Plan
  • 5.11 Agreements
  • 5.12 Labelling

It is not possible to go through all the sections for all the clauses, however we are going to highlight specific requirements which are necessary to be highlighted.

Clinical performance studies shall be undertaken under an effective quality management system, with the requirements defined in the ISO 13485. Since clinical performance studies is a validation activity, they must be performed on product representative of the final IVD, like any type of validation.

Furthermore it is very important that all the external entities involved in the studies (CRO, labs, investigator) are well identified and written agreements are in place to properly define the responsibilities.

Clause 6 – Study Site Initiation Requirements for ISO 20916

In conclusion; few words about the clause 6 related to Study Site Initiation. It is important that, for this phase, there is a visit to the site and all the pre-requisites for performing the clinical study are met.

Furthermore, it is essential that the site is trained, and that training is properly documented. Training shall also be performed in case of any specific changes which can affect the study.

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