Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Dear RAPS Forum members,

My question is about the requirement in the MDR Annex XV Clinical Investigations:
"The Sponsor shall appoint a monitor that is independent from the investigational site to ensure that the investigation is conducted in accordance with the CIP, the principles of good clinical practice and this Regulation."

We are budgeting for a multi-center clinical investigation in the EU that will include several large academic hospitals and are wondering whether it is sufficient to leverage the hospitals' own monitoring teams for clinical trials (via appropriate site agreements) or whether it is necessary to contract with a CRO to perform this function. It seems like maybe there is some flexibility under Article 72 (see below underlined wording), but your feedback would be welcome.

Article 72 Part 2 - In order to verify that the rights, safety and well-being of subjects are protected, that the reported data are reliable and robust, and that the conduct of the clinical investigation is in compliance with the requirements of this Regulation, the sponsor shall ensure adequate monitoring of the conduct of a clinical investigation. The extent and nature of the monitoring shall be determined by the sponsor on the basis of an assessment that takes into consideration all characteristics of the clinical investigation including the following: (a) the objective and methodology of the clinical investigation; and (b) the degree of deviation of the intervention from normal clinical practice.

Many thanks in advance!

Dear anonymous,

The requirement under the MDR in Annex XV regarding the need to appoint an independent monitor (Chapter III, Section 4) is separate and distinct from the requirement in Article 72(2). That is, Article 72(2) does not provide any flexibility regarding the requirement to appoint an independent monitor. 

Contracting with a CRO would be the normal pathway to ensuring independent monitoring, but you might also consider hiring freelance clinical research assistants (CRA). Should you do this, however, you will need to assume all the responsibilities in managing the CRAs, such as having documented procedures controlled within your QMS. This is often beyond the resource capabilities of sponsors.

Best regards,

Maria

------------------------------
Maria E Donawa, M.D.
President, Donawa Lifescience
Rome, Italy
medonawa@donawa.com
+39 06 578 2665
www.donawa.com
------------------------------

Original Message:
Sent: 30-Jul-2021 12:50
From: Anonymous Member
Subject: Monitoring requirement for Clinical Investigations

This message was posted by a user wishing to remain anonymous

Dear RAPS Forum members,

My question is about the requirement in the MDR Annex XV Clinical Investigations:
"The Sponsor shall appoint a monitor that is independent from the investigational site to ensure that the investigation is conducted in accordance with the CIP, the principles of good clinical practice and this Regulation."

We are budgeting for a multi-center clinical investigation in the EU that will include several large academic hospitals and are wondering whether it is sufficient to leverage the hospitals' own monitoring teams for clinical trials (via appropriate site agreements) or whether it is necessary to contract with a CRO to perform this function. It seems like maybe there is some flexibility under Article 72 (see below underlined wording), but your feedback would be welcome.

Article 72 Part 2 - In order to verify that the rights, safety and well-being of subjects are protected, that the reported data are reliable and robust, and that the conduct of the clinical investigation is in compliance with the requirements of this Regulation, the sponsor shall ensure adequate monitoring of the conduct of a clinical investigation. The extent and nature of the monitoring shall be determined by the sponsor on the basis of an assessment that takes into consideration all characteristics of the clinical investigation including the following: (a) the objective and methodology of the clinical investigation; and (b) the degree of deviation of the intervention from normal clinical practice.

Many thanks in advance!

This message was posted by a user wishing to remain anonymous

Thanks very much, Marie, for taking the time to reply.
It's greatly appreciated!
Original Message:
Sent: 02-Aug-2021 12:45
From: Maria Donawa
Subject: Monitoring requirement for Clinical Investigations

Dear anonymous,

The requirement under the MDR in Annex XV regarding the need to appoint an independent monitor (Chapter III, Section 4) is separate and distinct from the requirement in Article 72(2). That is, Article 72(2) does not provide any flexibility regarding the requirement to appoint an independent monitor.

Contracting with a CRO would be the normal pathway to ensuring independent monitoring, but you might also consider hiring freelance clinical research assistants (CRA). Should you do this, however, you will need to assume all the responsibilities in managing the CRAs, such as having documented procedures controlled within your QMS. This is often beyond the resource capabilities of sponsors.

Best regards,

Maria

------------------------------
Maria E Donawa, M.D.
President, Donawa Lifescience
Rome, Italy
medonawa@donawa.com
+39 06 578 2665
www.donawa.com

Original Message:
Sent: 30-Jul-2021 12:50
From: Anonymous Member
Subject: Monitoring requirement for Clinical Investigations

This message was posted by a user wishing to remain anonymous

Dear RAPS Forum members,

My question is about the requirement in the MDR Annex XV Clinical Investigations:
"The Sponsor shall appoint a monitor that is independent from the investigational site to ensure that the investigation is conducted in accordance with the CIP, the principles of good clinical practice and this Regulation."

We are budgeting for a multi-center clinical investigation in the EU that will include several large academic hospitals and are wondering whether it is sufficient to leverage the hospitals' own monitoring teams for clinical trials (via appropriate site agreements) or whether it is necessary to contract with a CRO to perform this function. It seems like maybe there is some flexibility under Article 72 (see below underlined wording), but your feedback would be welcome.

Article 72 Part 2 - In order to verify that the rights, safety and well-being of subjects are protected, that the reported data are reliable and robust, and that the conduct of the clinical investigation is in compliance with the requirements of this Regulation, the sponsor shall ensure adequate monitoring of the conduct of a clinical investigation. The extent and nature of the monitoring shall be determined by the sponsor on the basis of an assessment that takes into consideration all characteristics of the clinical investigation including the following: (a) the objective and methodology of the clinical investigation; and (b) the degree of deviation of the intervention from normal clinical practice.

Many thanks in advance!

Dear Member,
Utilizing hospitals own monitoring teams is not recommended. Apart from a CRO which will conduct monitoring either traditional or risk based, I would also recommend an independent auditor to monitor the sites on risk-based model? Based on the deviations, recruitment rate (too high compared to other sites), Data capturing error rate and other parameters, rate the sites and, a sample of sites can be selected for audit from the sponsor end.

------------------------------
Sreedhar Bunga
Head Clinical CoE
------------------------------

Original Message:
Sent: 30-Jul-2021 12:50
From: Anonymous Member
Subject: Monitoring requirement for Clinical Investigations

This message was posted by a user wishing to remain anonymous

Dear RAPS Forum members,

My question is about the requirement in the MDR Annex XV Clinical Investigations:
"The Sponsor shall appoint a monitor that is independent from the investigational site to ensure that the investigation is conducted in accordance with the CIP, the principles of good clinical practice and this Regulation."

We are budgeting for a multi-center clinical investigation in the EU that will include several large academic hospitals and are wondering whether it is sufficient to leverage the hospitals' own monitoring teams for clinical trials (via appropriate site agreements) or whether it is necessary to contract with a CRO to perform this function. It seems like maybe there is some flexibility under Article 72 (see below underlined wording), but your feedback would be welcome.

Article 72 Part 2 - In order to verify that the rights, safety and well-being of subjects are protected, that the reported data are reliable and robust, and that the conduct of the clinical investigation is in compliance with the requirements of this Regulation, the sponsor shall ensure adequate monitoring of the conduct of a clinical investigation. The extent and nature of the monitoring shall be determined by the sponsor on the basis of an assessment that takes into consideration all characteristics of the clinical investigation including the following: (a) the objective and methodology of the clinical investigation; and (b) the degree of deviation of the intervention from normal clinical practice.

Many thanks in advance!