The new decree on non-profit studies: Data and results may now be sold
The Italian version of this article has been published on March 17, 2022 on AboutPharma.com, within our bi-monthly column on the new Clinical Trials Regulation EU 536/2014.
On February 16, 2022, more than two years later than planned, the Ministerial Decree of November 30, 2021, containing measures to facilitate and support the development of nonprofit clinical trials of medicinal products and observational studies, as well as to regulate the transfer of data and results of nonprofit trials for registration purposes, was finally published in the Official Gazette. The decree entered into force on March 3, 2022.
This decree was eagerly awaited by stakeholders, who had to deal with a set of rules that were rather outdated and, above all, inadequate for regulating and exploiting the potential of Italian research carried out by means of public-private partnerships. It certainly represents a crucial step forward, even though there are still many questions and gaps in relation to the ambitious goals that the law set for this measure. Let’s take a step back to get some context.
Until the entry into force of this decree, nonprofit research in Italy was regulated by the Ministerial Decree of December 17, 2004, which prohibited the potential use of data and results from research conducted by a nonprofit organization for registration or commercial purposes. Such data also could not be shared with private parties, not even private parties that had financed the research in certain ways (e.g., by allocating funds or providing drugs).
In this framework, Legislative Decree No. 52 of 2019, implementing Law No. 3 of 2018 (known as the “Lorenzin Law”), introduced the possibility of transferring data and results of nonprofit clinical trials for registration purposes, provided that the transferee reimbursed the nonprofit entity that had carried out the study for (i) direct and indirect trial expenses; (ii) the fees that apply to for-profit studies (originally not applied as it was a nonprofit study); and (iii) “potential revenues from the exploitation of intellectual property.” Legislative Decree No. 52 of 2019 specified that the modalities for the transfer of these data and their use for registration purposes were to be established by a ministerial decree to be issued by October 31, 2019.
Although Legislative Decree No. 52 of 2019 clearly stated that “transfer of the relevant data as well as of the results of the experimentation (not for profit) for registration purposes is allowed,” failure to issue an implementing decree effectively paralyzed application of this rule, since it was not clear, from an operational point of view which procedure should be followed for the transfer of data/results or which criteria should be used to calculate “the direct and indirect expenses related to experimentation” and “the potential revenues from the exploitation of intellectual property.” As a result, from May 2019 to March 2022, the provision on the transfer of data for registration purposes remained unimplemented.
Moreover, pursuant to Legislative Decree No. 52 of 2019, the same implementing decree was to establish measures to (i) facilitate and support the conduct of nonprofit clinical trials and observational studies; (ii) establish how to coordinate public and private sponsors within the same clinical trial or observational study, potentially to obtain information after medicinal products were placed on the market; and (iii) introduce criteria to identify the types and requirements of nonprofit trials, as well as trials performed with cooperation between public and private sponsors.
The decree was to address many complex issues, and the expectations of stakeholders were high. The text finally approved by the government has inevitably been met with a degree of disappointment with regard to certain issues that are not touched upon or not adequately regulated (for example, regulation of observational studies and public-private co-sponsorship).
Below we will deal with several issues, beginning with data transfer for registration purposes, but there are many aspects of the new decree to be analyzed that will be discussed in future articles as well.
Modalities for transferring data/results of nonprofit research
First of all, the new decree expressly repeals and thus replaces the previous Ministerial Decree of December 17, 2004. There are no substantial changes to the definition of and requirements for nonprofit trials, so we will not dwell on this aspect.
It is worth noting that in the past the Ministerial Decree of December 17, 2004 was widely used to regulate pre-clinical (i.e., non-interventional) studies and clinical investigations with medical devices, in the absence of a specific regulation. Therefore, despite the scope of the new decree and, in particular, of the provision on data transfer covering interventional clinical trials with drugs (including low-intervention clinical trials), this measure is certain to serve as a new parameter for regulating different types of nonprofit studies by analogy.
The specific modalities for transferring data/results of nonprofit research provided by the new decree are the following:
- the transfer may take place either during the trial or after the trial has ended; in the first case, as far as can be understood, it is necessary to proceed with a substantial amendment to change the sponsor (from the nonprofit organization to the transferee);
- when data and/or results are transferred to be used in the registration of one or more medicinal products, either in Italy or in another country, the sponsor or transferee is obliged to bear and reimburse all direct and indirect costs connected with the trial and to pay the relevant fees required by the AIFA and the relevant Ethics Committees;
- when data and results are found to be usable for registration purposes, the nonprofit trial sponsor and the party interested in becoming the transferee of the data and results shall jointly identify a patent attorney registered in the Register of Qualified Industrial Property Consultants or in the Register of Attorneys-at-Law, who shall then provide an estimate of the value of the asset to be transferred with a view to its expected commercial exploitation; if the transferee decides to purchase the asset, the price may not deviate from the value established by the expert;
- the transfer of data must be regulated by a contract between the sponsor and the transferee. The sponsor should send the AIFA, the relevant Ethics Committee, and the trial centers involved an official communication informing them that the data and/or results have been transferred and enclosing (i) a copy of the transfer agreement; (ii) proof of payment of the abovementioned fees; (iii) an account of the costs related to the medicinal products, hospital care, diagnostic investigations, and personnel costs borne by the National Health Service and reimbursed by the transferee; and (iv) a copy of the insurance contract.
There are numerous issues and open questions about the procedure set forth in the decree. For example:
- the question arises as to which criteria should be used by the expert to calculate the amount to be paid for exploitation of intellectual property: at an early stage of the drug’s development, this seems very difficult to determine, not to mention the fact that neither patent attorneys nor other lawyers tend to have any experience in determining the potential commercial value of research results;
- procedures to estimate asset value are to take place “when the usability of data and results for registration purposes is established,” which sounds as if doing so is not always necessary, but instead is necessary only when the usability of the data for registration purposes is established in advance. In any case, it is not clear under what circumstances and how this evaluation should take place;
- it is not clear how the costs to be reimbursed to nonprofit organizations should be calculated, and especially how to quantify the value of certain activities carried out by researchers that are not included in the regional tariffs for health services;
- it is provided that a study may be converted from a nonprofit purpose to a for-profit purpose while retaining the same sponsor. Even in this case, all direct and indirect costs related to the trial should be reimbursed, and the relevant fees charged by the AIFA and the Ethics Committees should be paid. Financing received up to that time must also be reimbursed. This provision seems to regulate the scenario in which a study is converted for the purpose of using the data for profit, beyond simply transferring them for registration purposes, although its exact scope of application is not specified.
Data transfer and informed consent
One issue that is conspicuous in its absence in the new decree is that of informed consent and the processing of personal data of research participants in case of data transfer to third parties.
The only provision contained in the decree on this topic specifies that, following the transfer, for all intents and purposes the transferee takes over the processing of personal data relating to the trial. However, nothing is stated about the requirements and conditions of that transfer.
The first issue to be examined is the following: Is the informed consent originally collected from participants for a nonprofit trial suitable to make using those data for a commercial purpose lawful? In order to manage this potentially critical aspect in advance, we can imagine that nonprofit organizations will include in their informed consent forms a provision that the data may also be used for commercial purposes, including transfer to third parties interested in using the data for registration purposes. Moreover, this formula is already used in some models to justify the conversion of a nonprofit study into a for-profit one by the same sponsor—an operation that has not yet been expressly regulated, but that has already occurred, albeit sporadically.
Consent to further use of personal data?
From the point of view of personal data processing, the situation is even more complex since there are many factors to be taken into account in the case of data transfer to third parties. This problem would not arise in the case of the transfer of mere results, i.e., data that have already undergone reprocessing, which do not in any way include personal data (i.e., pseudo-anonymized data that still can ultimately be traced to identifiable subjects). However, this scenario seems unlikely to occur frequently due to the importance of personal data in these types of research, rendering the issue of data management more crucial than ever in this context.
We know that the major obstacle in our legal system is that the reuse of personal data, even for research purposes (apart from certain exceptional cases), always requires the consent of the data subjects. So, what would not be required under the GDPR is still mandatory in Italy under the Privacy Code, as amended in 2018. Exceptions to this obligation are only possible under certain conditions and with the authorization of the Privacy Guarantor (as provided in Art. 110-bis of the Privacy Code, which regulates data transfer to third parties for scientific research purposes and provides the adoption of measures to minimize processing, such as anonymization).
In addition, the consent must be specific, i.e., it cannot be given for future, unidentified studies that will be conducted by unspecified third parties in unspecified ways and by unspecified means. In other words, it cannot be a form of blank-check consent. Hence the need to find a compromise to allow nonprofit study sponsors to collect consent from participants that is valid for a likely future transfer of their data to third parties when the terms of that potential transfer are not yet known (or knowable). The alternative of having to recontact all participants to obtain new consent would paralyze operations under the rule.
On this point, it is hoped that concrete indications will be provided at the regulatory level or by the Privacy Guarantor with the aim of simplifying research and collaboration between the public and private sectors. Moreover, on a related issue, Legislative Decree No. 52 of 2019 also set the goal of promoting the use of biological and clinical material remaining from previous diagnostic and therapeutic activities or for any other reason held by research facilities for clinical research purposes. The Italian National Institute of Health was tasked with issuing guidelines identifying criteria for the use of biological samples, taking into account the methods for accessing and acquiring patients’ consent for subsequent use of samples (guidelines that have not yet been implemented).