The new regulations on observational studies of medicinal products for human use reduce procedures and introduce significant new legislation

Clinical research with medicines includes clinical trials, on the one hand, and observational studies, on the other. Whereas clinical trials are research processes conducted to determine or confirm the clinical effects and/or identify the adverse reactions associated with investigational medicinal products to determine their safety or effectiveness, in observational studies the medicines are prescribed in the customary manner, in accordance with the terms of their authorization. Their therapeutic strategies will be determined by the customary practice of medicine, as a necessary tool for obtaining essential data on their conditions of use, safety and effectiveness in a real healthcare context.

Royal Decree 957/2020, of November 3, 2020, on observational studies of medicinal products for human use (RD 957/2020) was published in the Official State Gazette on November 26, 2020 and will come into force on January 2, 2021.

In this alert published by Garrigues, we summarize the key changes introduced by RD 957/2020 into the regulations on observational studies of medicinal products for human use, together with the transitional rules with respect to the legislation in force.

In outline, RD 957/2020 seeks to simplify the regulatory framework in force on the subject by establishing a number of significant changes to the legal regime in force defined mainly in Order SAS/3470/2009, of December 16, 2009, publishing the guidelines on post-authorization observational studies of medicinal products for human use, which RD 957/2020 expressly repeals.

1. New single classification

As stated in its Preamble, RD 957/2020 is aimed at simplifying the procedures for observational studies by reducing the bureaucratic burden. For that reason, one of the biggest changes in RD 957/2020 is to remove the observational study types defined in Order SAS/3470/2009 and the related special procedures it defines in the process for each type of study.

Accordingly, although RD 957/2020 contains certain specific provisions on prospective observational studies, it instates a common single evaluation procedure for all observational studies of medicinal products for human use.

2. Amendment of the prior requirements

Regarding the prior requirements, RD 957/2020 removes the obligation to have the relevant prior authorization from the Spanish Medicinal Products and Medical Devices Agency (AEMPS), which ceases to be necessary for either the authorization of studies or amendments of study protocols. These will only require a favorable report by a Research Ethics Committee for Medicinal Products (CEIm), which must be a single binding report recognized throughout Spain.

As a result, the regime introduced by RD 957/2020 reduces the requirements for observational studies to obtaining a favorable report by a Research Ethics Committee for Medicinal Products and an agreement with the healthcare institution treating the participants in the observational study, and as a result the Post-Authorization Studies Coordination Committee will now disappear, due to an overlapping of its powers with those of the Research Ethics Committee for Medicinal Products.

3. New legislation on prospective observational studies of medicinal products

The protocol for prospective observational studies of medicinal products must explicitly mention and describe the procedures carried out to ensure that the study does not include any change to the prescribing or dispensing habits and guidelines for those medicinal products.

Additionally, the competent autonomous government authorities may, after the study obtains a favorable report from the Research Ethics Committee for Medicinal Products, lay down additional requirements that are justified by relevance and feasibility criteria, but do not relate to any matters that had already been studied by the Research Ethics Committee for Medicinal Products.

4. Informed consent and financial matters

RD 957/2020 largely maintains the obligation to obtain the informed consent of patients participating in observational studies that involve the performance of interviews. In order for the participant’s informed consent not to be necessary in those studies, the following three conditions must be met: (i) the Research Ethics Committee for Medicinal Products must find in its report that the study has important social value; (ii) the conduct of the study must not be feasible without that waiver; and (iii) the risks posed for the participants must be minimal.

On the subject of financial matters, the participants are allowed to receive compensation, although this cannot ever influence their decision to take part in the study. The remuneration received by healthcare professionals must only relate to compensation for time spent and costs incurred. These provisions, together with the study’s funding sources must be included in the documents filed for the evaluation by the Research Ethics Committee for Medicinal Products.

5. Patient support programs

The express regulations on patient support programs embody another change introduced by RD 957/2020, by specifying that any programs that expect to record information relating to the use of medicinal products through a planned system of contacts with patients can only be carried out within Spain in the context of a protocol that states as its objectives those defined in RD 957/2020 (to determine the beneficial effects of medicinal products, characterize or quantify the adverse reactions to medicinal products, obtain information on the patterns of medicinal product utilization patterns among the population, etc.).

6. Obligations regarding transparency and reporting, and regarding notification of suspected adverse reactions

RD 957/2020 requires sponsors of prospective observational studies on medicinal products to publish on the Spanish Clinical Studies Register (REec) the information specified in article 47 and article 48 of Royal Decree 1090/2015, of December 4, 2015. The publication of this information is voluntary for other studies.

Separately from the information required to be published on the Spanish Clinical Studies Register, it will be mandatory to publish - and state in those publications the study’s funding sources - the results of the observational studies before they are communicated to non-healthcare professional audiences regardless of whether or not their results are favorable. It specifies that it is preferable for these publications to be made in scientific journals.

Additionally, and separately from the transparency obligations mentioned above, it lays down an obligation to report to the Spanish Medicinal Products and Medical Devices Agency (AEMPS) any information that may affect the risk/benefit ratio of a medicinal product.

Lastly, the sponsor is required to notify the Spanish Pharmacovigilance System of any suspected adverse reactions to medicinal products, and the protocol must specify which types of adverse reactions must be registered systematically by healthcare professionals and conveyed to the sponsor.

7. Archiving of study documents

The Masterfile for every observational study must provide the basis for audits and inspections by the competent health authorities, and it falls within the powers of the Spanish Medicinal Products and Medical Devices Agency (AEMPS) to publish the relevant instructions specifying the documents that must form part of the Masterfile and the conditions for archiving it.

8. Entry into force and transitional regime

RD 957/2020 will come into force on January 2, 2021, although any observational studies on which a classification decision has been rendered by the Spanish Medicinal Products and Medical Devices Agency (AEMPS) before the entry into force of RD 957/2020 will be subject to the legislation in force when they obtained that classification decision.

Lastly, RD 957/2020 specifies a one year period from the date of its entry into force for adapting any autonomous community legislation that is incompatible with its provisions.