PORTUGAL

Research Ethics Committees

General

The Law 46/2004 of 19 August 2004 which incorporates the principles of the Clinical Trials Directive 2001/20/EC and creates the “Comissão de Ética para a Investigação Clínica” (National Ethics Committee for Clinical Research – CEIC) was repealed by a new law (Law 21/2014 of April 16)

The Law 21/2014 of 16 April 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, coordinated by CEIC, a National Portal for register all clinical research, and a clinical trials database.

Other research related laws in Portugal include:

• The ratified convention on biomedicine.
• The national laws on medicinal products.
• The national law and privacy of personal data.
• The law on medical devices (some topics were repealed by the Law 21/2014 of 16 April).
• The law of genetic information and health information.

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

• For performing clinical trials in Portugal, sponsors have to get authorization from the Competent Authority and ethical approval from the Ethics Committee (CEIC) plus approval from the National Data Protection Authority (CNPD – “Comissão Nacional de Proteção de Dados”).
• The application to the REC, to the competent authority and to CNPD may be submitted in parallel, or in any order.
• There is no procedural interaction between the competent authority and the national or local research ethics committee during the approval process. Nevertheless, all of them can request for it.

For obtaining ethical review of a clinical trial protocol by a competent (research) ethics committee in Portugal, namely for clinical trials with medicines or studies with intervention of medical devices, regardless of whether this is for a single site or multiple sites, the sponsor have to request an opinion from the National Research Ethics Committee – CEIC - according to the guideline available on the website www.ceic.pt. For the other studies, the request has to be made to local health institution ethics committees.

The new law on the Clinical Research (Law 21/2014 of 16 April) creates a portal (RNEC) for the submission of all the requests for clinical studies. This portal is not yet operational.

Concerning the Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, which repeal Directive 2001/20/CE, it is not yet discussed or decided how will CEIC and the national competent authority work to achieve the single administrative decision for clinical trial authorisation.

CEIC - National Ethics Committee for Clinical Research

The National Ethics Committee for Clinical Research (CEIC) is the REC responsible for assessing Clinical trials with investigational medicinal products applications and also studies with intervention of medical devices. Nevertheless, CEIC may delegate this assessment to a local health research ethics committee The requirements for these ethics committees to be competent to do such evaluation have to be defined, by law, by the National Ethics Committee (CEIC).

Members of the National Ethics Committee are appointed by the Health Minister 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 RECs members Nevertheless there are in each plenary meeting a training session in different areas. New members are trained and helped with the old ones whenever they have to evaluate clinical trials proposals.

CEICs meetings may only occur when the majority of its members are present. If a quorum is not reached at the 1st call for the meeting, a new one must be called and then a quorum is constituted as long as one third of the voting members are present.

Deliberations are taken with the qualified majority of two thirds of the present members. The decisions are conveyed to the sponsor, to the competent authority and to the sites ethics committees involved in the clinical trial concerned.

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 every member must declare any conflict of interests on any topic of the scheduled programme. When this happens that member can not be present during the discussions related with that matter and can’t vote.

CEIC is supported from a secretariat of about 5 persons, two of them, pharmacists, who makes all procedural managements of clinical trials processes. There is also a system of quality assurance and internal standard operational procedures (SOPs).

CEIC issues guidelines on the ethical review of a clinical trial for an investigational medicinal product, or other ethical topics, and for that CEIC migh have subcommittees or working groups dedicated to special issues. These guidelines, have to be approved in the plenarium 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.

All Clinical trials assessments have a CEIC number. At CEIC website the sponsor can at any moment consult the evaluation process (by CEIC or Eudra-CT number) since its validation until a decision is taken. After each meeting CEIC´s website is updated with the status of the evaluation of each clinical trial or amendment.

In urgent matters, the president of the research ethics committee 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.

Languages used are Portuguese and English for submission of documentation related to clinical trials according to guidelines; English for any contact. CEIC website will be in English very soon.

Substantial amendments

Substantial amendments are defined according the Law 21/2014 of 16 April and the directive 2001/20/CE and also the Communication from the Commission of 30.03.2010 (2010/C 82/01).

Substantial amendments submitted during the review process are evaluated with all the other documentation, and the time frame is according with the new legislation 20 days. If additional questions (for the main trial) have already been raised, there is a new round of questions according with the amendment.

When an unfavourable opinion is given to the clinical trial protocol the amendment consequently obtains the same decision.

Investigators and Sites

For the time being the suitability of investigators is decided by the analysis of CVs. Investigational sites are considered suitable if the clinical director of the medical centre declares so, explicitly reporting the human and material resources disposable in their site to do each specific clinical trial protocol.

The national law requires that all financial arrangements (financial contracts between sponsors and health institutions) that are conducted with the board of each participating healthcare institution must be presented and approved by CEIC. The new law establishes that the site for the study has to approve the financial arrangements in 15 days from the request of the sponsor or researcher.

The compensation arrangements for study subjects

The compensation arrangements for study subjects are required to be fully detailed in the clinical trials 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.

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 clinical protocol and in the national law.

CEIC requests for an insurance covering the clinical trial and the name of it should be mentioned in the insurance document; this is a general document. In the other cases, CEIC requests for the insurance document specifying the name of the Principal Investigator, the site of the clinical trial and all sites involved in the clinical trial 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

CEIC timelines for approval are under legal obligation from 2001/20/EC directive and Law 21/2014 of 16 April. This means 30 days for new studies and 20 days for substantial amendments. Concerning 2013 average timelines: new trials: 42 days (min: 13; max 97); substantial amendments: 28 days (min: 5; max: 96).Concerning 2011 average timelines: new trials: 59,7 days (min: 18; max140); substantial amendments: 34,4 days (min: 3; max: 112).

Local EC

By law all health care institutions must have an institutional ethics committee that have also the responsibility for the evaluation of all clinical research with human beings except in what concerns with clinical trials with human medicines and intervention with medical devices. All other studies need ethical approval from local or institutional ethics committees.

There are almost one hundred ethics committees (public and private, health and academic ones). 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 have, so far, been 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.
The new legal framework attributes to the National Research Ethics Committee (CEIC) the accreditation of local committees based on a specific formation program to be implemented soon.
Local institutional ethics committees have no funding and do not charge fees.

INFARMED, I.P.

www.infarmed.pt
www.infarmed.pt/web/infarmed-en/

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.

Fees for clinical trials

New trials phase I, II e III: 1023 €; New Trial s Phase IV 460.35 €; substantial amendment: 102.30 €. These values are being revised.

CNPD – National Data Protection Authority

www.cnpd.pt
www.cnpd.pt/en

The CNPD – “Comissão Nacional de Protecção 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.

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 in the Universities of Lisbon, Oporto and Coimbra. There are no formal programmes for training REC members.

Vulnerable Subjects

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

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.