How to submit a combined study with a medicinal product and a companion diagnostic IVD (CDx) or other IVD studies the Ethics Committee

Definitions:

In vitro diagnostic medical device (IVD) is defined in Art 3 of the Swiss Ordinance on In Vitro Medical Devices (IvDO) and in Art. 2 (2) of the EU-IVDR, as any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following:
(a) concerning a physiological or pathological process or state;
(b) concerning congenital physical or mental impairments;
(c) concerning the predisposition to a medical condition or a disease;
(d) to determine the safety and compatibility with potential recipients;
(e) to predict treatment response or reactions;
(f) to define or monitoring therapeutic measures.
Specimen receptacles shall also be deemed to be in vitro diagnostic medical devices; 

Companion Diagnostic (CDx) is defined in Art. 2 (7) of the EU-IVDR, as a device which is essential for the safe and effective use of a corresponding medicinal product to: identify, before and/or during treatment, patients who are most likely to benefit from the corresponding medicinal product; or  identify, before and/or during treatment, patients likely to be at increased risk for serious adverse reactions as a result of treatment with the corresponding medicinal product.
IVD that are used with a view to monitoring treatment with a medicinal product in order to ensure that the concentration of relevant substances in the human body is within the therapeutic window are not considered to be companion diagnostics.
More information on companion diagnostic can be found on the EMA webpage here.

A combined study is a clinical trial of a medicinal product in parallel with a clinical investigation of a medical device, respectively with an interventional performance study of an IVD.

Performance study means a study undertaken to establish or confirm the analytical or clinical performance of a device in accordance with the Ordinance on In Vitro Diagnostic Medical Devices (IvDO) (art. 2 letter a^ter ClinO-MD).

An interventional performance study is a study in which the test results may influence patient management decisions or treatment (art. 2 letter a^ter ClinO-MD)^.

A non-interventional performance study is a study in which the test results cannot influence patient management decisions or treatment (art. 2 a^ter ClinO-MD).

Sponsor means any person or institution that takes responsibility for organising a clinical trial – specifically its initiation, management and financing – in Switzerland (art. 2 letter d ClinO-MD)

For sake of simplicity only the generic term study is used in this FAQ, which includes the legal terms “clinical trial”, “performance study” and “research project”.

Applicable Ordinances:

The Ordinance on Clinical Trials with Medical Devices (ClinO-MD) applies to the performance study when conducted to establish or confirm the analytical or clinical performance of the IVD.
If the medicinal product is also under investigation, the requirements of both the Clinical Trials Ordinance (ClinO) and ClinO-MD apply at the same time.

In case of uncertainties the applicant should seek advice from Swissmedic or the Ethics Committee to confirm that the study is indeed a CDx performance study.

How to submit via BASEC to the Ethics Committee:

We distinguish between the two following cases:

A. There is at least one centre in Switzerland that enrols study participants.
B. There are no centres in Switzerland that enrol study participants. Only the IVD testing is done in Switzerland.

A. There is at least one centre in Switzerland that enrols study participants.

Before starting the application process, it is advisable to clarify which Ordinance is applicable to the project and so use the appropriate submission form.

Preliminary note:

A) The conduct of non-interventional performance studies is governed by Chapter 2 of the Human Research Ordinance (HRO) when:

a.) biological material is collected from the participants without a surgically invasive procedure; or
b.) the participants do not undergo additional invasive or burdensome procedures compared to the procedures performed under the normal conditions of use of the device to be investigated.

Submit the study to the ethics committee with the submission form «Research project application form».

On screen 1 of the submission form select «Research involving persons, but not a clinical trial».

The approval timelines are those of HRO.

Indicate in the cover letter, that this is an exception from the scope according to article 2a ClinO-MD. 

B) In case A) does not apply here, the submission of the CDx or IVD performance study is done using the submission form «Research Project Application Form for Medical Devices / In Vitro Diagnostic Medical devices». The study is governed by ClinO-MD.

On screen 1, select the Lead-ethics committee.

In a multicentric study in Switzerland, the coordinating centre/coordinating investigator must be chosen among the centres that enrol patients. The ethics committee responsible for this centre becomes the Lead-ethics committeee.
If there is an enrolling centre in a Canton, that also does the IVD testing (address of the IVD testing center), the ethics committee responsible for this center will become the Lead-ethics committee by default.

The following table summarise the 3 possible cases in multicentric studies:

In BASEC on screen 2, select «in vitro diagnostic medical devices (CDx) / drugs» or «in vitro diagnostic medical devices», as appropriate.

Fill in the form as indicated in the instructions in BASEC.

Notes:

If the study is conducted jointly by two independent sponsors (e.g. a Med. Tech. company and a pharmaceutical company) and there are two distinct protocols (a clinical performance study plan (CPSP) for the IVD device and a study protocol for the clinical trial with an investigational medicinal product (IMP)), the two protocols can be submitted separately*.

If submitted separately, the CPSP is submitted via the «Research Project Application Form for Medical Devices / In Vitro Diagnostic Medical devices» while the clinical study protocol is submitted via the «Research Project Application Form» for the IMP.
In such case, the fields on the IMP on screen 6 of the submission form «Research Project Application Form for Medical Devices / In Vitro Diagnostic Medical devices», will be left empty, since all information on the IMP are submitted via the «Research Project Application Form». Indicate this case in the cover letter.

*Submission via the two forms in BASEC is accepted for practical reasons, even if the two components (i.e. the two protocols) of the study are legally regarded as one single study. The review/approval timelines are governed by the Ordinance on Clinical Trials with Medical Devices (ClinO-MD). Note: Swissmedic accepts only one single submission.

There must be an agreement/contract between the two sponsors that regulates their roles and responsibilities (e.g. regarding safety notification, etc.). The two protocols must both clearly indicate the overall scope of the study, the IVD, the IMP, …

Both ClinO and ClinO-MD apply.

Even if there are no enrolling centers left open in Switzerland, the study in Switzerland remains open until the study is completed globally.

B. There are no centres in Switzerland that enrol study participants. Only the IVD testing is done in Switzerland.

Before starting the application process, it is advisable to clarify which Ordinance is applicable to the study and so use the appropriate submission form !!

Preliminary notes:

The conduct of interventional or non-interventional performance studies in which only already sampled biological material or already collected health-related personal data is used is governed by Chapter 3 ("further use") of the HRO.
Submit the study to the ethics committee with the submission form «Research project application form».

On screen 1 of the submission form select «Further use of health-related personal data and/or biological material».

On screen 1, select the Lead-ethics committee competent for the Canton where the IVD tests are conducted.

On screen 2, select «in vitro diagnostic medical devices» or «in vitro diagnostic medical devices (CDx) / drugs», as appropriate.

Fill in the form as indicated in the instructions in BASEC.

The approval timelines are those of HRO.

Notes:

In case of an international study, the IVD-testing centre in Switzerland must make sure that the study is duly approved in the foreign countries involved. The Lead-ethics committee can ask the applicant to provide the corresponding documentation, if deemed necessary.

The Lead-ethics committee can ask the applicant to submit the study protocol for the investigational medicinal product (IMP) used abroad, and other study documentation, if deemed necessary.

In case of an international study, when only samples from abroad are analysed by the IVD testing centre in Switzerland, the study in Switzerland remains open until the study is completed globally.