WHAT ARE CLINICAL STUDIES?
Clinical studies are researches that concern the study of a disease. They assess the efficacy and safety of the studied treatment, the survival rate, the prevention, the quality of life through the collection of epidemiological data to evaluate the incidence, the prevalence, the causes of the disease, the new diagnostic techniques, the efficacy and safety of standard therapies and the status of the patient during the follow-up.
Clinical studies can be designed and promoted by individual doctors or medical groups.
The “clinical study” can also be called “clinical trial” or clinical protocol. When we talk about “Protocol” we mean the document that describes the study.
Clinical studies can be divided into the following macro categories:
- non-interventional or observational studies: the researcher limits himself to “observing”, therefore the name of observational. These studies do not evaluate the efficacy and / or the safety of a new therapy and they do not supervise the different procedures from those provided by the normal clinical practice. The aims of these studies are to identify the risk factors of the disease, to study their causes and possible intervention strategies. Therefore, it is possible obtain the safety data of the therapies and the goodness of the clinical practice. Observational studies can be retrospectives when the collected data are “historical” data (e.g. they are extrapolated from medical records) and the studies conducted based on documentation collected in the past, therefore, they were already available before the start of a new study. Observational studies are prospective when the data of patients with certain characteristics are collected in a well-defined period of time with the aim of observing a particular event (e.g. effect of a particular therapy).
- Interventional studies: these are the studies used to evaluate the efficacy and safety of new therapies in order to assess the risks and/or the benefits of its.
The responsibility of the patients’ safety who participate in a clinical trial is a responsibility of the promoter, the institution that proposes the study. In the FIL studios the promoter is directly the FIL or a European / international research group partner of the FIL for the single project. The responsible physicians have the responsibility for the correct application of what is defined in the clinical study, respecting what is defined by the Protocol. The ethics committees of the centres are independent bodies which have the task of evaluating the ethics of the study and they decide to approve it or not. They request periodic reports from the responsible physicians for the study in order to supervise it. If the study involves the use of a drug or medical device, it should have the authorization from the AIFA (Agenzia Italiana del Farmaco / Italian Medicine Institution) or, in clearly defined cases, from the Istituto Superiore di Sanità.
HOW ARE INTERVENTIONAL CLINICAL STUDIES CLASSIFIED?
The clinical studies that have as their object a therapy, are classified into four phases. These phases follow the pre-clinical phase in which the drugs are tested in laboratories.
The studies on new drugs begin with Phase I. These studies are generally started and conducted by Pharmaceutical Companies to verify:
- the pharmacokinetics, which studies how the drug is absorbed, distributed, metabolized and eliminated by our body;
- the pharmacodynamics, which studies the cellular targets of the therapy in progress;
- some preliminary data on safety and tolerability of the drug.
In this phase the dosages of the drug are established to see the first effect on the body and the possible side effects.
The Phase II of clinical trials studies the drug activity in the organism, the possible therapeutic effects, the dose and the risk / benefit profile. They allow to study the efficacy of a therapy and the toxicity of the drug on a small number of patients (generally from 10 to 60) with the same disease and similar clinical features well described by the Protocol. FIL is the promoter of several Phase II studies. For patients these studies are important because they could have the possibility of accessing innovative therapies.
The Phase III of a clinical trial evaluates the efficacy and the reactions of large-scale therapy (hundreds of patients) and the aim is to compare different therapies for the same type of patients. These studies carry out the definitive evaluation of tolerance and efficacy of the therapy. In general, an innovative experimental therapy is compared with a standard therapy already used for that particular type of disease to prove to patients an efficacy not inferior to the standard therapy and acceptable risks / benefits. The assignment of the patient to a therapy branch (“randomization”) can be defined according to criteria established by the study (specific molecular characteristics, lymphoma stage, etc.) or randomly 1: 1 (1 patient in each branch). The FIL conducts several Phase III studies.
The Phase IV of the clinical trial includes the post-marketing studies, after the drug has been put on the market and it obtained an authorization for a specific therapeutic indication. At this stage the side effects or pharmaceutical properties not highlighted during the first three phases continue to be evaluated. These are studies related to the marketing authorization of medicines and their renewal. They are related to commercial reality.
The FIL, as a non-profit research organization, promotes only studies with the aim to improve healthcare and clinical practice and to assess the risk / benefit ratio and not the commercial development of drugs. It leads the Phase I / II, Phase II and Phase III. It does not conduct Phase I and Phase IV trials.
WHERE CAN I FIND A FIL CLINICAL STUDY?
A patient will ask to his doctor if there are clinical studies available for his illness or medical condition. In the Research Area of the FIL site it is possible to find the list of FIL studies for pathology, while in the List of Centres section it is possible to find FIL centres in Italy.
The data on interventional clinical trials are also available on online platforms such as https://clinicaltrials.gov/ in which all clinical studies in the world are recorded or https://www.clinicaltrialsregister.eu in which all European clinical studies are recorded.
HOW IS A CLINICAL STUDY APPROVED?
FIL, as promoter of the clinical study, must request the necessary authorizations and assessments to make available a study. Interventional or observational studies with one or more drugs must be evaluated by AIFA (or, in specific cases, by the Istituto Superiore di Sanità) and by the relevant Ethics Committees. The Ethics Committee is an independent body and it has the responsibility to guarantee the protection of the rights, the safety and the wellness of the trial subjects through the evaluation of clinical trial protocols, observational and epidemiological studies. Once the legal approvals have been obtained, the FIL sends the operating procedures, for the correct administrative and operational management of the study, to the doctors in charge of the centres and it provides for the opening of the centre. From that moment the doctor in charge at the centre can propose the participation in the study to the patients with the characteristics foreseen by the study (type of lymphoma, age, disease stage, etc.). The patient who agrees to participate in a study signs the consent.
HOW CAN YOU PARTICIPATE IN A FIL CLINICAL STUDY?
The doctor, the responsible for the study at the haematology centre, informs the patient about the study, the side effects and the benefits that the patient can derive from the research. The doctor has the task to explain the protocol and to satisfy all the requests and doubts of the patient. The participation in a study is a free choice of the patient who can withdraw even during the study, without any penalty and loss of any benefit. The decision to leave the study does not compromise the quality of medical care that the patient will receive after the withdrawal of his consent. The doctor of the study will have the task of illustrating the modalities of interruption of the therapy to avoid risks to the health of the patient. Participation in a clinical trial does not involve any compensation or any cost for the patient. The patient will be followed carefully at every stage of the research, according to precise indications defined by the Protocol.
WHY ARE CLINICAL STUDIES IMPORTANT?
Clinical studies are fundamental not only to find new therapies, but also to improve standard therapies and diagnostic techniques, to find new prognostic criteria and techniques to personalize therapies and to improve clinical practice without increasing the National Health Service.