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Clinical Studies with Intervention or Clinical Trials

According to Law no.No. 21/of 16 April, which approves the clinical research law, a clinical study with intervention is any research that advocates an alteration, influence or programming of health care, behaviours or knowledge of the participants or caregivers, with the purpose of discovering or verifying health effects, including exposure to medication, the use of medical devices the performance of surgical techniques, exposure to radiotherapy, application of cosmetics and body hygiene products, physiotherapy intervention, psychotherapy intervention, use of transfusion, cell therapy, participation in individual or group education sessions, dietary intervention, intervention in access to or organisation of health care or intervention designated as non-conventional therapy;

According to the same Law, a clinical trial is any investigation conducted in human subjects with the aim of discovering or verifying the clinical, pharmacological or other pharmacodynamic effects of one or more investigational medicinal products, or identifying the undesirable effects of one or more investigational medicinal products, or analysing the absorption, distribution, metabolism and elimination of one or more investigational medicinal products, in order to ascertain their safety or efficacy.

We can consider that clinical trials are conducted in 4 phases:

1

First administration in humans

Phase 1 trials test a possible new medicine or treatment for the first time.

Phase 1 is usually carried out on individuals not affected by the disease, i.e. healthy individuals. Its main objective is to verify if the treatment produces effects in the organism. In addition, it aims to study clinical and biological tolerance, allowing the maximum dose tolerated by the body to be defined. Phase 1 studies also aim to evaluate the pharmacodynamics and pharmacokinetics of new drugs:

Pharmacodynamics: allows the effects on the organism to be defined and the minimum dose with therapeutic activity to be determined.

Pharmacokinetics: allows the fate of the molecule in the organism to be defined according to the mode of administration (oral, intravenous, etc.)

2

First administration in patients

Phase 2 corresponds to the first administration of the treatment in sick individuals. In this phase, only a limited number of individuals are involved and for a short period of treatment, with the objective of evaluating the therapeutic efficacy, while assessing its safety in the short term. For example, the appropriate dose to administer is one of the parameters assessed in this phase, as well as the physiological response obtained with that dose.

3

Therapeutic efficacy

Phase 3, also called ‘pivotal study’, is the final phase before the medicine is marketed, with pre-marketing authorisation (MA) therapeutic purposes. These studies make it possible to measure the therapeutic efficacy of the molecule and its safety in conditions closer to real life.

This step usually involves a large number of sick people over a long treatment period. The conditions of administration are close to the conditions of use of the future medicine. In order to draw reliable conclusions from the study, participants undergo a process of randomisation, where they are randomly selected to receive the innovator treatment, the placebo or the conventional treatment.

Phase 3 trials are the most frequent and many of them include hundreds or even thousands of patients from several research centres and often several countries.

Medicines with evidence of efficacy and safety at this stage may be submitted for approval by the regulatory authorities, followed by the marketing authorisation (MA) and commercialisation stage.

4

Safety monitoring and assessment

After the medicine is approved and marketed, in a post-approval phase, studies are carried out for long periods of time in order to guarantee its efficacy and safety. In this phase, its efficacy, benefits, and possible adverse events are studied in a broader context and are already accessible to the general population. It is also in this phase that the use of the medicine can be optimised, as well as evaluating drug interactions and additional adverse events (pharmacovigilance).