clinical studies

Giving an answer to the scientific questions and to the health needs of patients worldwide. This is the objective of clinical research.
The development path of a drug potentially able to make a difference follows certain very rigorous steps, which are required to evaluate the safety and efficacy of the study drug.

Clinical trials are an essential tool to answer specific questions on the effects and the mechanism of action of possible new treatments or of existing drugs. Without them, it would not be possible to develop new ones. A clinical trial is a research study that allows investigators to evaluate if potential treatments are safe and effective for preventive, diagnostic and therapeutic purposes, and is conducted only when experimental studies give favourable indications for the development of the new treatment. Clinical studies can be organised and supported directly by investigators, universities, institutions or pharmaceutical companies.

The involvement of patients

A clinical trial is an opportunity to provide increasingly effective treatment solutions able to improve the survival, quality of life and possibility of recovery of patients all over the world. The decision to participate in a clinical trial is a strictly personal choice, and requires a careful analysis and evaluation of one’s health conditions. This is why it is essential to act under the advice and control of a doctor.

Not all patients are equally eligible to participate in a clinical trial concerning their disease.

There are certain parameters, variable from trial to trial, which determine whether a patient is eligible to participate. These are called inclusion and exclusion criteria and are defined according to gender, age, type and level of the disease, other medical conditions, and the results of preliminary diagnostic tests. These criteria are crucial to obtain reliable results and to guarantee the appropriate level of safety for patients. Some studies may also enrol healthy subjects.

Phases of clinical research

Clinical research is subdivided into different steps, which may last several years and start when experimental studies justify further development of a candidate drug or treatment.

The objective is to answer the clinical questions identified in the study protocol, which is structured so as to meet scientific needs, without of course overlooking the related ethical aspects, first of all the protection and safeguard of patients’ health.

Phase I
The first phase of trial on humans aims to determine the study drug’s safety and mechanism of action. At this stage of development, the objective of the trial is to evaluate not only the drug’s tolerability and interaction with the human body (pharmacokinetics and pharmacodynamics), but also the safest dosage, in order to estimate the most appropriate dose for therapeutic use.

A limited number of healthy volunteers are generally enrolled; however, sometimes patients are involved, especially in the case of rare and orphan diseases. In these situations, even the first phase of trial can be useful to provide preliminary evidence on the efficacy of the treatment. The candidate drug must demonstrate acceptable toxicity in relation to the intended use, because the evaluation of the risk-benefit profile is obviously different depending on whether the treatment has no alternatives or other options are available.

Phase II
Once safety is confirmed, the drug is tried on a larger population of patients with a particular disease.

The investigators determine the minimum effective dose for humans and the best dosing regimen, or the method of use and treatment duration. In this phase, initial efficacy data are collected along with additional information on the agent’s safety and efficacy. Phase II trials are sometimes subdivided into two separate steps:

  • Phase IIa, aimed at identifying the required drug dose;
  • Phase IIb, specifically intended to evaluate efficacy.
Phase III
In this phase the key objective is to confirm the data of prior observations, involving a larger number of patients.

These trials are generally randomized (patients are assigned randomly to the new active principle, to the standard treatment or to placebo) and multicentre, i.e. carried out at multiple facilities. The information obtained in this phase concern the drug’s efficacy and tolerability.

Phase IV
Once Phase III is successfully completed, the drug can be introduced in the market after receiving the necessary authorisations from the regulatory agencies in charge of supervising and managing these aspects.

But the monitoring continues. These phases are conducted on limited numbers of patients: it is only once the sample is expanded and the limits of clinical trial inclusion/exclusion criteria are removed, that the agent’s safety can be realistically assessed. This is why patients treated with a new medicine should report any negative side effects to their doctor or pharmacist. A side effect is any harmful and unwanted effect caused not only by the authorised use of a drug at the prescribed dose, but also by therapeutic errors and uses not in line with the indications contained in the Marketing Authorisation, including improper use and abuse of the medicinal product. This phase includes all clinical studies conducted after drug registration, such as randomised and comparative studies, to collect additional efficacy and safety information.