More requirements for conducting prospective observational studies with medicinal products at regional level

On 2 January 2021, Royal Decree 957/2020 regulating observational studies with medicinal products for human use (EOMs) came into force. This regulation meant the simplification of the requirements, as well as a reduction of bureaucratic burdens, for conducting EOMs in Spain.

EOMs provide essential data on the conditions of use, safety and effectiveness of medicinal products in routine clinical practice. The regime applicable to each observational study differs depending on its design. Royal Decree 957/2020 distinguishes between prospective observational studies and those that are non-prospective (i.e. retrospective and/or cross-sectional). In prospective studies, the study period of the participating subjects is always subsequent the start of the research, while in the latter the study period is present or prior to the start of the research.

By their nature, prospective studies may have a greater impact on the prescribing and dispensing decisions of healthcare professionals. For this reason, Royal Decree 957/2020 already established several mechanisms to ensure that these studies do not modify prescribing or dispensing habits and, in short, that are of genuine scientific interest and not purely promotional in nature. Likewise, this regulation also empowered the health authorities of the Autonomous Communities to lay down additional requirements for commercial prospective studies, or those in which the sponsor is not a Public Administration, and which may only be justified on the basis of feasibility or relevance criteria.

Three years after the entry into force of Royal Decree 957/2020, five regions –Navarre, Valencia, Catalonia, Galicia and Aragon– have developed their own regulations, thus introducing additional requirements for conducting prospective EOMs in the centres within their territorial scope.

Below, we highlight the most relevant aspects established in each of these regional regulations.

Region of Navarre

Navarre was the first region to introduce additional requirements for conducting prospective studies through Foral Order 157E/2022, of 9 May, of the Health Department’s Head. In Navarre, these studies require express authorisation from the Directorate-Management of the centres where the study will be conducted. To this end, prior to its administrative authorisation, the so-called Committee of Experts for the Evaluation of Prospective Observational Studies with Medicinal Products in Navarre will evaluate the study and prepare a report-proposal on compliance with the feasibility and relevance criteria.

Regarding the criteria for assessing feasibility, the Committee may only approve those studies with medicinal products for hospital use if such medicinal products have been selected for use in each centre by its pharmacy committee, or in accordance with the instructions of the respective Directorate-Management. The inclusion criteria must be aligned with those established by the Central Pharmacy Commission or the pharmacy commissions of the centres. Likewise, studies that generate a greater workload than usual for laboratories and radiology services may not be authorised, unless required by the health authorities or included in the EMA’s Risk Management Plan.

Regarding the criteria for assessing relevance, the Committee may only approve those studies relevant to clinical practice in Navarre. Specific criteria to be considered includes that the study allows obtaining information on efficacy, safety, convenience or comparative efficiency when there are several medicinal products that are therapeutic alternatives for the same indication. If the study consists of a patient registry, it will only be considered relevant when it is considered useful to obtain information for the clinical management of people who are under clinical care or with the pathology in question in Navarre and do not interfere with the clinical information registration systems established in the regional public health centres.

Region of Valencia

In the region of Valencia, the additional requirements for conducting this type of studies were approved by Decree 203/2022, of 2 December, of the Generalitat Valenciana. These studies are subject to authorisation from the Directorate-General of Pharmacy.

Previously, the Autonomous Committee for Prospective Observational Studies of Medicinal Products of the Region of Valencia (CAEPO) must evaluate the study and issue a report-proposal for resolution. The CAEPO will evaluate the feasibility and relevance of the study based on the following criteria: (i) possible induction to prescription or dispensing; (ii) verifiable scientific interest and its applicability in clinical practice; (iii) possible interference with the healthcare tasks and the routine clinical practice of the sites; and (iv) compliance with conditions established for the use of medicinal products in the NHS.

Catalonia

In accordance with Decree 17/2023, of 31 January, of the Generalitat of Catalonia, prospective observational studies conducted in Catalonia are subject to prior administrative authorisation from the Directorate-General for Health Planning and Regulation.

The Commission for Prospective Observational Studies with Medicinal Products (CEOM) will evaluate the study protocol to verify compliance with the feasibility and relevance criteria, and it will issue the corresponding report. The CEOM will consider that the study complies with the feasibility criterion when: (i) the medicinal product under study is already authorised and marketed; (ii) the protocol is aligned with the existing clinical practice guidelines or, failing that, with the routine clinical practice of the centre; (iii) the study is carried out in accordance with the centre’s healthcare circuits, (iv) the medicinal product has already been used in the centre prior to the Ethics Committee’s (CEIm) opinion; (v) there are no interventions that induce a change in treatment; and (vi) it does not induce the prescription or dispensing of the medicinal product under study.

In addition, the study will be considered to meet the relevance criterion when: (i) the objective of the study is aligned with the purposes of an EOM and generates additional information to that obtained during the clinical trials; (ii) it clearly identifies the medicinal products under study; (iii) it follows the authorised indications, or there is sufficient scientific evidence derived from routine clinical practice that supports its use under the research conditions described in the protocol; (iv) the medicinal product is used in accordance with the Therapeutic Positioning Report (TPR), or with the harmonisation criteria established by the Catalan Health Service, or with the site’s pharmacotherapeutic guide, and; (v) the inclusion criteria meet the treatment criteria established by the health authorities.

Galicia

Galicia has approved the additional requirements for conducting prospective observational studies by Decree 131/2023, of 14 September, of the Xunta de Galicia. These studies are also subject to prior authorisation from the Galician Department of Health, with the Sub-Directorate General of Pharmacy being the body in charge of evaluating that the study meets the feasibility and relevance requirements

This regulation includes assessment criteria for evaluating the feasibility and relevance requirements similar to those required by other regions. For instance, these are that the medicinal product in the study is used under the financing conditions established in the NHS, according to its SmPC or the conditions of routine clinical practice when it is sufficiently supported by the available scientific evidence; the non-induction to prescribe or dispense the medicinal product; the adequacy to the protocols or clinical guidelines; the non-interference with the healthcare tasks, and the non-inclusion of diagnostic or follow-up procedures not used in routine clinical practice.

Furthermore, Galicia has established as assessment criteria the compliance with the recommendations, strategies and lines of work set out by Galician Healthcare Service (SERGAS) in the field of pharmaceutical provision; and the adequacy with the content and conditions of execution of the contracts in force regarding medicinal products. Likewise, prospective studies must have a verifiable scientific justification, in order to avoid indiscriminate indications and unnecessary safety risks, as well as to respect equity and homogeneity in access to pharmaceutical services for SERGAS’ service users.

Aragon

Aragon has been the last region to introduce additional requirements for the conduct of prospective observational studies in its territory; specifically, through Order SAN/1951/2023, of 22 December.

The body in charge of authorising these studies is the Aragonese Institute of Health Sciences (IACS). The Commission for the Evaluation of Prospective Observational Studies with Medicinal Products of Aragon (CEOPA) will prepare a report evaluating the feasibility and relevance requirements of each study. To this end, the CEOPA will consider the recommendations for use elaborated by the Commissions established in Order SAN/1112/2017, (i.e., mainly the Commission for the Monitoring of the Rational Use of Medicinal Products and the Committee for the Evaluation of New Medicinal Products in Primary Care), and the corresponding TPR. In addition, it will ensure that the conduct of the study does not alter prescription or dispensing habits, issuing well-founded recommendations on its performance in the centres of Aragon.

Although there is no obligation to establish any type of additional requirement for conducting prospective studies to those already included in Royal Decree 957/2020, it is possible that some other Autonomous Communities will issue regulations with similar criteria to those established by those that have already opted to regulate them. In the cases in which previous regional regulations exist; they will be applicable in everything that does not contradict or oppose the provisions of Royal Decree 957/2020.