Knowledge on clinical trials available to everyone

Nowadays there are several ways to search clinical trials, and we recommend consulting Clinical Studies section, which is sourced from ClinicalTrials.gov, an international database of clinical trials which is supported by public and private entities around the world and owned by the American National Institutes of Health. In this section, you will be able to find all clinical trials taking place in Portugal where you can apply several filters according to your interests. For additional information, you can also talk to your physician, contact patient organizations, or visit other dedicated websites.

Participation in a clinical trial always comes with potentially unknown risks. These risks may be more severe or marginal depending on the development phase of the clinical trial, the knowledge already available about the experimental drug, the knowledge already available about the experimental drug, the therapeutic being studied, or the procedures to be performed.

The potential participant will learn about the procedures involved, as well as the risks and potential consequences, through the informed consent form, which you must sign and agree with if you wish to participate in the study. [1] In addition to the informed consent form, the clinical trial investigator should clearly explain the planned interventions, associated risks, therapeutic alternatives, and among other aspects about the clinical trial to the participant or his/her legal representative.  Throughout the entire process, you may ask any questions to the research team involved. [2]

Some of the risks to consider in a clinical trial may include:

Experimental treatment efficacy

• Not having the expected effectiveness.
• Not having a positive benefit for the patient’s condition.

Integrate the control group

• The participant may be assigned to the control group, not receiving the new therapy, but receiving a comparator (existing therapy) or placebo. [3]

Risks or adverse events of the experimental treatment that may affect the participant’s health

• Associated risks with known adverse events.
• Associated risks to adverse events not yet known.

If you suffer any loss or damage as a result of the research or related procedures during the clinical trial, all liabilities will be covered by the liability insurance taken out by the promoter. 

[1] Law no. 21/2014, of April 16, Chap. I, Art. 2, al. l)

[2] Law no. 21/2014, of April 16, Chap. II, Art. 6, no. 1., al. a)

[3] A substance or procedure without any therapeutic property that serves as a control and comparison to the therapy being tested.

Yes, there are clinical trials that require the participation of healthy volunteers, mainly in the early stages of clinical research to determine the safety profile and dosage/frequency of a therapy.

The participation of healthy individuals is essential for the discovery of new therapies. To view the clinical trials in which healthy volunteers may participate, you can access the Clinical Studies section, using the adequate filter (select “Phase I” clinical trials). Before joining a clinical trial, you should consider that:

• Your participation will not be remunerated, since no incentives or financial benefits may be conceded in Portugal, with the exception of compensation for expenses and losses incurred as a result of participating in the clinical trial [1] or other situations duly justified and approved by CEIC [2].
• There may be adverse events from the therapy;
• You may have restrictions on what you can do and cannot do while participating in the trial;
• You may have to travel several times for your clinical monitoring.

[1] Law no. 21/2014, of April 16, Chap. I Art. 3, no. 2 e Chap. II Art. 6., no. 1, al. h

[2] CEIC guiding document: https://www.ceic.pt/documentos-orientadores

Clinical research centers are entities that conduct the clinical trial and are equipped with adequate human and material resources, regardless of whether they are part of a public or private health care establishment, laboratory, or other facilities, or whether they are located within the territory of member states of the European Union. [1] All clinical trial centers should have adequate facilities that comply with the requirements. [2]

For more information on clinical research centers developing clinical trials in Portugal, you can visit the Clinical Research Centers section. In this section, you can search for a clinical research center according to its characteristics, having access to its own and dynamic content, managed and updated by each institution, on the dedicated page of each clinical research center.

If you wish to obtain information about a specific clinical trial, we recommend you to visit the Clinical Studies section where you can find detailed information.

[1] Law no. 21/2014, of April 16, Chap. I, art.2, al. h).

[2] Regulation (EU) no. 536/2014 of the European Parliament and the Council of April 16, 2014, Chap. VIII Art. 50 and Annex I 67.

An experimental drug is a given pharmaceutical form, with one or more active substances or placebo, which is being tested or serves as a reference for a clinical trial. An experimental drug may thus include new active substances or others that already have the authorization for introduction in the market, as long as they are being used or prepared in pharmaceutical forms or packaging differently from those already approved. Can still include substances that are being studied for a new therapeutic indication not yet been approved or when further information is required. [1]

[1] Law no. 21/2014, of April 16, Chap. I, Art.2, al. bb).

After the clinical trial is completed, you may continue to participate in subsequent phases (follow-up), if these exist and you meet the eligibility criteria. Otherwise, you will be followed up by your regular physician, family practice physician, or specialist to continue to have access to the most adequate care and to your clinical monitoring.

When a clinical trial ends, all results are analyzed, and may be published in peer-reviewed scientific journals. For more information, you can also consult the principal investigator or other physician involved in the clinical trial.

When the clinical trial ends, the experimental treatment should be made available free of charge by the promoter until the authorization for introduction in the market is obtained, if the investigator considers it indispensable and that there are no therapeutic alternatives of equivalent safety and efficacy. In order to continue the experimental treatment after the end of the clinical trial, the investigator must obtain the informed consent of the participant (or legal representative), submit the clinical report that justifies the need for the continuation of the treatment, notify INFARMED, I.P. and CEIC, and maintain the safety communication obligations.

If the product does not yet have authorization for introduction in the market, participants, in some cases, can continue to have access to the product through the Early Access Programs for a limited time, until it obtains authorization for introduction in the market from medicine authorities (EMA and INFARMED, I.P.).

According to the current legislation, INFARMED, I.P. is the competent authority to permit clinical trials on medicinal products for human use.[1]

To conduct a clinical trial in Portugal, a favorable ethical opinion must be given by the Ethics Committee for Clinical Research (CEIC), and authorization must be given by INFARMED, I.P..

To conduct a clinical trial, the promoter uses clinical research centers [2], typically located in hospitals or other health institutions with material, technical, and human resources suitable for conducting a clinical trial, ensuring compliance with good clinical practices and respecting the applicable ethical principles.

[1] Law no. 21/2014, of April 16, Chap. I Art. 2º, c)

[2] Law no. 21/2014, of April 16, Chap. I Art. 2º, f)

By the current legislation, all clinical trials in Portugal are covered by Good Clinical Practices. These consist of a set of internationally recognized processes and guidelines that ensure ethical and scientific quality at all phases of clinical trials, aiming to protect the rights, safety, and well-being of participants, and the scientific credibility of these studies. [1]

Good Clinical Practice applies throughout the clinical trial, from the conception phase, execution, the reporting of results and clinical events, publications, and the review of studies. [2]

[1] Law no. 21/2014, of April 16, Chap. I, Art.2, al. f)

[2] Law no. 21/2014, of April 16, Section II, Art.26

Participants in a clinical trial are usually randomly assigned to different treatment groups (e.g., experimental treatment vs. control group - which may include comparison with an active treatment or placebo). These two groups are similar in composition and participant eligibility criteria, and the efficacy and safety in both groups are assessed comparatively.

As a control group, participants are assigned to receive either the treatment they would normally receive that is already licensed or a placebo that has no therapeutic efficacy, for example, if no treatment is available. This control group serves as a comparator to the experimental treatment, allowing to verify whether it has a greater or lesser efficacy and/or safety than already authorized treatments.

Most clinical trials are conducted blinded, so participants do not have information about whether they belong to the experimental treatment or the control group, in order to avoid influencing the interpretation of clinical effects and minimize bias in the results.

There are of types of concealment:

Simple concealment/single blind: patients have no knowledge about which treatment is assigned.

Double concealment/double blind: patients and researchers do not know which treatment has been assigned.

The remaining clinical trials are conducted in an open treatment regime, where both patients and the research team involved are aware of the assigned treatment.

Learn more about how clinical trials are designed here.

Clinical trials are regulated by Law No. 21/2014 of April 16 which establishes the legal framework for clinical research, its definition, information on the application of good clinical practices in the conduction of clinical trials on medicinal products for human use and other clinical studies. This law was amended by Law No. 73/2015 of July 27 and by Law No. 49/2018 of August 14.  The national legislation results from the transposition of the following directives at the European level [1]:

• Directive 2001/20/EC of the European Parliament and the Council of April 4, 2001, on clinical research on medicinal products for human use.
• Directive No. 2007/47/CE of the European Parliament and the Council of 5 September, on clinical investigation of medical devices.

For additional legislation, see the RNEC portal for clinical trials on medicinal products for human use and for clinical investigations of medical devices.

[1] Law no. 21/2014, of April 16, Art. 1.

As a participant or potential participant, it is natural to be interested in knowing more about your involvement and participation in the treatment research and development process. There are several official national and international sources where you can find out more information, one of the most comprehensive being the European platform on Patient Involvement through Education (EUPATI Toolbox). Here you can find several resources and support materials, in portuguese and english, built through public consultation and collaboration with several entities such as official entities, industry associations, patient organizations, and health professionals.