General

Clinical Research in Portugal is regulated by the Law 21/2014 of 16 April which applies to all studies with human beings or data and/or samples of human origins in the health sector.

This law covers all clinical research with humans including not only clinical trials with medicinal products for human use but also studies with medical devices, cosmetics, food supplements and all kind of observational studies. This law also creates the National Ethics Committees Network (RNCES), coordinated by CEIC, a National Portal for register all clinical research (RNEC), and a clinical trials database.

With the entry into force of the European Clinical Trials Regulation [(CTR -Regulation No 536/2014] and European Regulation on medical devices and in vitro medical devices, respectively MDR (EU) 2017/745 and IVMDR (EU) 2017/746 (RDIV), Law 21/2014 of 16 no longer applies except on the issues not covered by the Regulations. Other laws related with clinical research in Portugal include:

All these documents can be found on the website of National Ethics Committee for Clinical Research, at http://www.ceic.pt, or at the website of the National Authority of Medicines and Health Products (INFARMED, I.P.) which is the Portuguese Competent Authority, at http://www.infarmed.pt .

Clinical trials with medicines´ assessment and authorization have changed with the application of the CTR; the same applies with the application of MDR.

The Regulation harmonises the submission, assessment and supervision processes for clinical trials in the EU through the Clinical Trials Information System (CTIS) which will be the single-entry point for submitting clinical trials. In Portugal the Authority INFARMED, I.P. support the activities related with part I CT dossier together with the national ethics committee for clinical research (CEIC). Part II, national information, is assessed exclusively by CEIC.

Regarding clinical studies with medical devices or medical devices for invitro diagnosis under European Regulations, INFARMED, I.P. is the Authority and CEIC the ethics committee for the ethical approval. According with the type of study, the authority and CEIC might undergo articulation in the review process or CEIC is the only responsible for the (ethical).

Despite any procedural interaction between the Competent Authority and the National Ethics Committee, clinical trials and studies with medical devices or in vitro medical devices, the final decision in Portugal for the approval or rejection of these studies must incorporate the independent decisions from INFARMED, I.P and CEIC. This means that for the study approval both regulatory entities must approve and issue favorable opinion respectively. This also applies to Part I clinical trials dossier for which both entities evaluate the proposal.

Until the medical devices portal EUDAMED is operational, submission of all requests for medical devices or in vitro medical devices studies have to be made directly and only to INFARMED, I.P. through the portal RNEC (rnec.pt).

Any other clinical study than clinical trials with medicines or studies with medical devices or medical devices for in vitro diagnosis under European Regulations, are assessed by institutional ethics committee, according with the requirements established in the Law 21/2014 of 16th April.

CEIC - National Ethics Committee for Clinical Research

National Ethics Committee for Clinical Research

National Ethics Committee for Clinical Research (CEIC) is the REC responsible for assessing Clinical trials with investigational medicinal products applications and also studies with f medical devices. Members of the National Ethics Committee are appointed by the Minister of Health and the law has established that CEIC is independent and multidisciplinary and that all the members must declare publicly their conflicts of interest (all this information is available in the CEIC webpage).

The National Ethics Committee for Clinical Research has 35 members: a president, a vice-president, seven executive committee members and 28 other members. Members have recognized qualifications on medical sciences (medical doctors, pharmacists, nurses, psychologists), ethics, theology, epidemiology and pharmacoepidemiology, sociology and philosophy. CEIC members include also lawyers, mathematicians, laymen and a patient’s representative. By law, and whenever necessary, CEIC may ask for independent external expertise.

There are no formal training requirements for REC members. Nevertheless, CEIC´s plenary meetings start with training sessions in different areas as considered adequate. New members are trained and helped with the old ones whenever they have to evaluate clinical research proposals. There are also standard operational procedures (SOP) and recommendations in writing for the experts’ assessing studies.

Meetings can only take place when the majority of its members are present. If the quorum is not reached at the first call, a new meeting must be convened and, in that case, the quorum is constituted as long as one third of the members with the right to vote are present. Decisions are taken by a qualified majority of two-thirds of the members attending the meeting.

The internal regulations of the ethics committee and the law ask for a permanent declaration for the conflict of interests. At the beginning of each meeting all members must declare any conflict of interests on any topic of the scheduled program. When this happens, that member cannot be present during the discussions related with that matter and cannot vote.

CEIC is supported from a secretariat, who makes all procedural managements research projects. There is also a system of quality assurance and internal standard operational procedures (SOPs). The secretariat is coordinated by the Executive Secretary.

CEIC issues guidelines on the ethical review of a clinical trial for an investigational medicinal product or medical devices, or other ethical topics, and for that CEIC might have subcommittees or working groups dedicated to special issues. These guidelines, have to be approved in the planarian meetings before made public.

The National Ethics Committee for Clinical Research and his secretariat are funded by the Competent Authority (INFARMED I.P.). No fee is directly charged by CEIC and INFARMED I.P. charge sponsors according to a scale of fees, legally established.

For clinical trials under the CT Regulations, the CTIS Portal can be accessed directly by the sponsor, and no information of timelines is disclosed in the CEIC website.

In urgent matters, the President of CEIC may take a decision. For example, in a safety urgent substantial amendment the president may authorize or decline it. His decision should then be ratified by the plenary of the committee. Both CEIC and INFARMED, I.P. have procedures for expedite assessment of clinical trials in some circumstances.

Language

Portuguese/ English for submission of documentation related to clinical trials according to guidelines; English for any contact.

CEIC website will be in English very soon.

National rules for submission of clinical trials under CTR are published at Eudralex 10.

Substantial amendments

Substantial modifications must be aligned with the rules established in the Legal framework, depending on the type of studies.

Investigators and Sites

The suitability of investigators is decided by the analysis of CVs. Investigational sites are considered suitable if the clinical director of the health institution declares so, explicitly reporting the human and material resources disposable in their site to do each specific study protocol.

Information regarding financial arrangements for CTs, studies with medical devices and in vitro medical devices under the European Regulations has to be submitted for assessment. No further approval of the financial arrangements is required after the approval of the studies. At CEIC´s site there is a list of the minimal information to be submitted.

The compensation arrangements for study subjects

The compensation arrangements for study subjects are required to be fully detailed in studies´ application and are evaluated in the review process. The reimbursement of the participants for all expenses with transportation, meals, and others such as salary lost is mandatory by law. Compensation to healthy participants is allowed in Portugal. A detailed guidance is published at CEIC´s website.

Commercial studies and non-commercial ones have exactly the same requirements concerning compensation arrangements for participants.

Insurance and indemnity arrangements

The ethics committee must verify if insurance and indemnity arrangements are in line with what is proposed to do in the study protocol and in the national law.

CEIC requests for an insurance for interventional studies covering the study procedures and sites involved in the study such as the study site and other sites that are required for the conduction of the study such as sites for exams or others (pharmaceutical services) different from the site of the clinical trial.

Commercial clinical trials and non-commercial clinical trials have exactly the same requirements concerning national indemnity scheme.

Approval Timelines

Timelines are defined by the European regulations. For the other studies not covered by the Regulations, national Law applies, having 30 day for the approval of initial submissions and 20 days for substantial amendments.

Institutional Ethics Committees

By law all health care institutions must have an institutional ethics committee that have also the responsibility for the evaluation of clinical research with human beings except in what concerns with clinical trials with human medicines and clinical investigations with medical devices or in vitro medical devices.

All other studies need ethical approval from institutional ethics committees. Law 80/2018 of 15th October established the need for institutional ethics committees not only in health care institutions but also at universities or other research sites where clinical research is performed.

There are more than one hundred ethics committees (public and private, health and academic ones). Institutional ethics committees have no funding and do not charge fees.

There is no recognition from one local ethics committee decision on a study protocol from another one. The newly created national network of ethics committees could override this problem. Local institutional ethics committee members are chosen by the clinical director of each healthcare institution or in the case of Academia by the director of the academic institution. Usually institutional or local health research ethics committees have seven members with no known specific training requirements; they must include external members and also one lay member. The National Research Ethics Committee (CEIC) is the coordinator of the national ethics committees’ network.

INFARMED, I.P.

http://www.infarmed.pt
http://www.infarmed.pt/portal/page/portal/INFARMED/ENGLISH

National Authority of Medicines and Health Products, IP is a government agency accountable to the Health Ministry. The objective is to monitor, assess and regulate all activities relating to human medicines and health products for the protection of Public Health. Portuguese Competent Authority is responsible for the Supervision of Investigational Medicinal Products.

INFARMED charge sponsors according to a scale of fees established by law.

CNPD – National Data Protection Authority

http://www.cnpd.pt/

CNPD (“Comissão Nacional de Proteção de Dados”) is the Portuguese Data Protection Authority.

CNPD is an independent body, with powers of authority throughout national territory. It is endowed with the power to supervise and monitor compliance with the laws and regulations in the area of personal data protection, with strict respect for human rights and the fundamental freedoms and guarantees enshrined in the Constitution and the law.

Clinical research studies must comply with The General Data Protection Regulation and those dealing with personal data must comply with the GDPR rules. CNPD is the entity to notify data breaches.

CONFLICT OF INTERESTS

Law 14/2014 of 22 January establishes the legal regime of incompatibilities of the members of committees or other groups participating, selecting, evaluating, issuing guidelines of clinical character, in the areas of drug and devices that belong to the National Service Health or agencies of the Ministry of Health.

All these persons have to declare the inexistence of conflict of interests and their declarations have to be made public.

Training of RECs members

Academic training on clinical ethics, bioethics, pharmacology and epidemiology is available at the Universities of Lisbon, Oporto and Coimbra. There are no formal programs for training REC members nor a mandatory training to become an ethic´s committee member.

VULNERABLE SUBJECTS

Informed consent is obtained from vulnerable subjects who are potentially to be involved in a clinical trial from his legal representative.

Incapacitated adults can only be recruited for interventional studies through his legal representative whenever the study cannot be performed with capacitated participants.

National regulations in Portugal do not allow research on healthy volunteer children.

The cut off age between paediatric and adult trial subjects is 18 years. Minors from 5 to 17 years old have to sign an assent form and their legal representatives (usually both parents) have to consent their participation in clinical research studies.