On 26 November 2020, the Spanish Official State Bulletin published the Royal Decree 957/2020, of 3 November, regulating observational studies with medicinal products for human use, which will come into effect on 2 January 2021. This royal decree intends to ease the administrative procedures applicable to observational studies in light of recently adopted instruments at EU level (with the European Medicines Agency-approved guidance on post-authorization efficacy studies) and Spanish level (with the enactment of Royal Decree 1090/2015 on clinical trials with medicinal products, which introduced the legal concept of observational study). Observational studies are an essential tool to gather personal health data on conditions for use, safety and effectiveness of medicinal products, and to ultimately enhance clinical practice in the interest of patients.
The royal decree sets out conditions for the assessment, realization and monitoring of observational studies in Spain. Some major changes introduced by Royal Decree 957/2020 include the elimination of former requirements such as the classification of study protocols and the prior authorization — where it was mandatory — by the Spanish Agency of Medicinal Products and Medical Devices, and the elimination of the Coordination Committee of Post-Authorization Studies. Arts. 9 and 10 of the royal decree regulate the obligations of the sponsor and the main researcher as responsible for the study. Furthermore, the royal decree:
- requires observance of guidelines and instructions by the European Commission and the Spanish Agency of Medicinal Products and Medical Devices (art. 3), and a favorable opinion by a certified ethical committee on the ethics of the research with medicinal products (CEIm) before the start of the study and before any substantial modification thereof (arts. 4 and 14). Regarding observational studies of prospective monitoring, the protocol of the study must indicate how to ensure the study does not alter prescribing or dispensing habits (art. 3), and regional health authorities may impose additional requirements (art. 4). In addition, where the information is obtained from the participant or their treating healthcare professional at a healthcare center, that center must also approve the study’s protocol and other documents (art. 3).
The sponsor must submit an application along with the documents specified in Annex II. Once the application is validated and assessed, the CEIm will issue an opinion within 30 days; if no opinion is notified, the application will be deemed dismissed (arts. 12 and 13). Criteria that the CEIm will assess include characteristics of the study and whether they are adequate to attain its objective; reliability and strength of the data that can be obtained; rights and guarantees of participants; or necessity, modality and content of the informed consent (art. 11). Documents supporting compliance by the sponsor and the researchers will be compiled in a master file and available for audits and inspections by health authorities (art. 17).
- requires informed consent where the observational study involves interviewing the participant in the study. This requirement can be waived if the CEIm finds that the observational investigation is of great social value, or that the study cannot reasonably be carried out unless the informed consent is waived — and this entails minimal risk for participants (art. 5).
- requires sponsors of observational studies of prospective monitoring to publish some minimum information in the Spanish Registry of Clinical Studies (REec) at the beginning, during the course of the study and once the positive or negative results are known. For other observational studies, publication in the REec will be voluntary. However, sponsors of all kinds of observational studies are required to disclose results, preferably in scientific journals, before release to the general public (art. 6).
- prevents sponsors from planning, carrying out or funding observational studies aimed at promoting the prescription of medicinal products. With regard to patient support programs (PSPs), where they imply registering information on use of medicinal products based on contact with patients, they will only be permitted as long as there is a protocol pursuing any of the legitimate objectives in art. 2.1.a). It is worth noting that PSPs are defined and addressed in this royal decree for the first time in the Spanish legal system.
The royal decree also prohibits payments to healthcare professionals beyond a strict compensation for the time devoted to the study and the expenses incurred, and forbids unduly influencing participation in the study by means of offering high payments. Financing sources and compensations will be disclosed in the documents provided to the CEIm for assessment (arts. 3 and 7).
- requires healthcare professionals to notify any suspected adverse reactions to the Spanish Pharmacovigilance System and to health authorities. The royal decree also requires sponsors to inform the Spanish Agency of Medicinal Products and Medical Devices about any data resulting from the observational study that may alter the benefit-risk relationship concerning an authorized medicinal product (arts. 15 and 16).