Document paper New medtech regulations

Clinical evidence update – Proposal for an IVD regulation

The ongoing negotiations with regards the to the new IVD regulation have brought to the fore a number of critical concepts which need to be addressed or revisited as follows:

Studies using leftover specimens:

The majority of studies carried out in the field of IVDs take place using leftover specimens. There are three features that distinguish these studies from interventional studies:

  • Patients are not directly involved; therefore there is no need for requirements related to patient management when working with leftover specimens.
  • Ethics committees ensure that the policies on the use of leftover specimens are in line with the ethical principles of the Helsinki declaration on Bioethics.
  • Consent is given by patients at the moment of specimen collection in line with national guidelines and policies established by the ethics committees.

This needs to be taken into account when considering requirements for informed consent (already given) and approval of ethics committee. If the study is conducted in line with what had already been approved at the time of specimen collection, a second approval is not needed.

Given that the majority of IVD studies are carried out using leftover specimens, clinical performance study plans should take this into account and not impose and undue administrative burden by requiring a systematic justification for exclusion of certain requirements.

Proposal: The clinical performance study plan under annex XII section 2.3.2 to clarify up front which sections are not relevant for studies using leftover specimens.


Studies using invasive sampling procedures which constitute a negligible risk to patients: (See annex for procedures which constitute a negligible risk)

Even when patients are recruited into studies for IVDs, in the majority of cases a routine sampling procedure which causes a negligible risk to the patient is the only interaction that the patient will have with the study. In such studies the risks to patients which need to be managed are different considerably lower than when an interventional study takes place. As such, the requirements developed for interventional studies are an unnecessary burden.

As patients are actively recruited to provide a specimen for the study however, informed consent and approval from ethics committees should be obtained for the study.

Proposal: Annex XIII intended for interventional studies, should not be applicable to studies conducted using invasive sampling procedures which constitute a negligible risk to patients.

Clinical benefit for IVDs

The concept of clinical benefit for IVDs is substantially different than that of clinical benefit for therapeutic products, as the information provided by the IVD is critical for establishing a proper diagnosis, rather than directly improving the condition of a patient. Further IVDs are rarely the sole component of a diagnosis which is part of a broader multidisciplinary approach.

Proposal: Ensure that this specificity of IVDs is clearly explained in the new regulation via a clear recital so that there is no confusion between the nature of clinical benefit for IVDs and clinical benefit for other devices or pharmaceuticals.

Continuous assessment of clinical evidence as part of post-market follow-up:

In order to ensure that IVDs are safe and fulfil their intended purpose throughout their lifecycle, it is essential that manufacturers systematically monitor scientific developments, epidemiology and changes in clinical practices which are relevant to their IVDs. When manufacturers become aware of such a change this may then trigger a new assessment of the clinical evidence.

Proposal: Clarify the meaning and impact of what continuous assessment of clinical evidence means for IVDs via a recital.

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Posted on 20.04.2016

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