Intended for healthcare professionals

Rapid response to:


A risk adapted approach to the governance of clinical trials

BMJ 2011; 343 doi: (Published 25 October 2011) Cite this as: BMJ 2011;343:d6756

Rapid Response:

Re: A risk adapted approach to the governance of clinical trials

A risk adapted approach, like such initiative by the Medicine and Healthcare Products Regulatory Agency (MHRA), described by RL Smyth (BMJ 2011;343:d6756), seems reasonable and helpful to manage the issues of insurance and to reduce the costs in the regulation of clinical trials.

The Clinical Trial Directive 2001/20/EC (1) states that the liability of the investigator or sponsor for possible injury or death of the subjects has to be covered by insurance or indemnity.

From March 2010, Italian investigators and Research Ethics Committees(RECs) have been facing a new difficulty due to a recent Ministerial Decree (2) that obliges the investigator or the sponsor of a clinical trial to provide specific, very expensive, insurance coverage. Without this specific insurance coverage, the RECs cannot approve a trial.
This regulation is a challenge for “non–commercial” trials promoted by clinical investigators of the academic and/or National Healthcare System institutions. Particularly, this concern regards clinical trials that typically investigate (also through comparative studies) the therapeutic value and/or safety of products used according to their licensed indications in the EU. Really, many of these studies would always result in a “very minimal” risk or “no greater than” of those of current clinical settings, or, finally, risks are not greater than an off-label product utilized in clinical practice.

Perhaps, for this reason in Italy in 2010, after this Ministerial Decree, the non-commercial clinical trials and all the phase IV clinical trials are decreased, especially compared to two previous years 2008-2009: 229 non-profit studies in 2010 vs. 309 (2009) and 362 (2008); 77 phase IV clinical studies in 2010 vs. 124 (2009) and 104 (2008). (3)

Moreover, the Concept Paper put out for public consultation for the revision of the Directive 2001/20/EC (4) states that the clinical trials have very different risk-profiles.

In our opinion, it would be necessary to calibrate the requirements for the insurance coverage through the risk assessment of all aspects of clinical trial: risks associated with the investigational medicinal products; risks of clinical procedures; risks related to inclusion criteria. This could be helpful in identifying potential vulnerabilities of the clinical trial; setting up tailored monitoring plans to minimize risks, and a proportionate insurance coverage in case of harm due to the clinical trial.
The clinical research community needs to support this risk-adapted approach to reduce costs and bureaucracy of clinical research.

(1) Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Official Journal of the European Communities, 1.05.2001. Available at:

(2) Ministerial Decree 14th July 2009, Minimum requirements for insurance policies which safeguard participants to clinical trials of medicinal products, GURI n.213 (14.9.2009). Available at:

(3) AIFA (Italian Medicines Agency – Research and Clinical Trial Unit – National Monitoring Centre). Clinical trials of drugs in Italy – 10th National Report. 2011. Available at:

(4) European Commission – Health and Consumers Directorate-General. Revision of the ‘Clinical Trial Directive’ 2001/20/EC. Concept Paper submitted for public consultation. p.12. Available at:

Competing interests: No competing interests

28 February 2012
Roberta Minacori
Assistant Professor of Bioethics;
Dario Sacchini, Assistant Professor of Bioethics and Antonio Gioacchino Spagnolo, Professor of Bioethics.
Institute of Bioethics - "Agostino Gemelli" School of Medicine - Università Cattolica del Sacro Cuore
Largo Francesco Vito 1 - 00168 Rome (Italy)