According to AIFA (for the complete information, see the 13th National Report- 2014 available on the Portal of the Italian Medicine Agency), in last three years the total number of clinical trials in Italy was lower than in the 2007 – 2009 timeframe and no profit researches registered a considerable decrease, reaching in 2013 a value less of 25 % (in previous years it exceeded 30%).

The causes for the decrease of clinical researches activity are several. Inter alia, the legal reforms of 2010.

In particular, in March 2010 the Decree of the Ministry of Labour, Health and Social Affaires dated 14 July 2009 (the ” Decree”) – implementing the Clinical Trials Directives 2001/20EC – had come into force. The Decree made it compulsory for promoters of all drugs’ clinical trials (and, according to the general application, also for Medical Device) to execute specific insurance contracts covering the damages caused to the participants to the trials conducted in Italy.

According to the provisions of the Decree, the existence of an insurance coverage meeting the minimum requirement provided for by the Decree is an essential element for the validity of all clinical trials, including no-profit.

The Decree’s provisions are too strict: the same requirements for insurance covering different clinical trials (including clinical trials of marked drugs/Phase IV studies) are required, for example: (i) a discovery period not shorter than 36 months from the date of completion of the clinical trial, (ii) a discovery period of at least 10 (ten) years for clinical trials conducted on minors of age; (iii) maximum sums insurable not smaller than those set out in the Decree, to be determined depending on the number of the individuals involved in the trial; (iv) no deductible to be opposed to third injured parties, if any, (v) a specific insurance certificate for each study.

Positive effects on patients’ safety but in certain cases (for all the academic/no-profit trials or industry trials regarding marketed drugs) not connected to the existing effective risks.

In a nutshell, high and unjustified costs for disproportionate requirements.

So a new risk for patients arises from these rules: the reduction of the number of trials.

The new regulation no. 536/2014 replaced the Clinical Trials Directives 2001/20EC making deep regulatory changes in order to simplify the law and regulations for clinical trials, also with regard to insurance matter.

According to the new regulation, “Member States shall ensure that system for compensation for any damages suffered by a subject resulting from participation in a clinical trial conducted on their territory are in place in the form of insurance, a guarantee, or a similar arrangement that is equivalent as regards its purpose and which is appropriate to the nature and the extend of the risk.” (Article no. 76, paragraph 1).

Therefore: not the same coverage for all trials. More flexibility since different trials have different levels of risk.

In particular: “Member States shall not require any additional use of the system referred to in paragraph 1 from the sponsor for low-intervention clinical trials” (Article no. 76, paragraph 3).

Low-intervention clinical trial means a clinical trials which fulfills all of the following conditions: “a) the investigational medicinal products, excluding placebos, are authorized; b) according to the protocol of the clinical trial, (i) the investigational medicinal products are used accordance with the terms of the marketing authorization; or (ii) the use of the investigational medicinal products in evidence-based and supported by published scientific evidence on the safety and efficacy of those investigational medicinal products in any of the Member States concerned; and c) the additional diagnostic or monitoring procedures do not pose more than minimal additional risk or burden to the safety of the subjects compared to normal clinical practice in any Member State concerned” (Article 2, paragraph 2).

In this case, damages shall be covered “by the applicable compensation system already in place” (Article no. 76, paragraph 3).

Consequently, for these kind of clinical trials (including no-profit/academic trials and all trials relating marketed drugs, it seems also in the contest of off label use) promoters and or center participating shall not have an obligation to enter into a specific insurance contract compliant with the requirement of the old Decree.

The same purpose could be achieved by an extension to the sponsor’s product liability insurance/hospital’s liability insurance or general clinical trial insurance already in place.

During these next months (the Reg. 536/2014 will become fully operational in June 2016), important changes are expected (and needed):

(i) the Italian legislation will have to be adapted in view of the entry into force of the European Regulation: the Decree can be amended and, in any case, no longer applied to no-profit trials;

(ii) Insurers will have to amend, inter alia, the existing product liability insurance policies for medical products manufacturers/companies and the existing general liability insurance for non- industry actors as hospitals and foundations in order to offer coverage also for low-intervention clinical trials;

(iii) Member States will have to collaborate to avoid diversity in interpretation and applying the new rules.

I think that it is time to grasp the nettle !

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