Clinical trials are research studies involving patients and focusing on diseases or health conditions. They evaluate the efficacy and safety of treatments, survival rates, prevention strategies, and quality of life through the collection of epidemiological data. These data help assess incidence, prevalence, causes of disease, new diagnostic techniques, the effectiveness and safety of standard therapies, and patient status during follow-up.
Clinical trials may be designed and promoted by individual physicians or by groups of physicians.
A “clinical study” may also be referred to as a “clinical trial,” “clinical experimentation,” or “clinical protocol.” The term “protocol” specifically refers to the document that describes the study.
Clinical trials can be divided into the following main categories:
Non-interventional (observational) studies: in these studies, the researcher simply “observes”. They do not aim to evaluate the efficacy and/or safety of a new therapy and do not involve procedures beyond standard clinical practice. Their purpose is typically to identify risk factors, study disease causes, and explore possible intervention strategies. These studies provide data on the safety of therapies under routine conditions, the quality of clinical practice, appropriateness of care, and disease risk or protective factors.
Observational studies may be:
- Retrospective, when data are historical (e.g., extracted from medical records) and already available before the study begins
- Prospective, when patient data are collected over a defined period to observe specific outcomes (e.g., the effect of a particular therapy)
Interventional studies: these are primarily designed to evaluate the efficacy and safety of new treatments and to assess their risk–benefit balance.
Responsibility for patient safety in a clinical trial lies primarily with the sponsor, i.e., the institution proposing the study. In FIL trials, the sponsor is either FIL itself or a European/international research group partnering with FIL on a specific project. Responsibility for correctly conducting the study according to the protocol lies with the physicians at participating centers.
Ethics Committees are independent bodies responsible for evaluating the ethical aspects of a study and approving it. They require periodic reports to monitor progress. If the study involves a drug or medical device, authorization from AIFA or, in specific cases, the Istituto Superiore di Sanità is also required.
Clinical trials involving therapies are classified into four phases, following a preclinical phase in which drugs are tested in the laboratory.
Phase I trials: these are typically initiated and conducted by pharmaceutical companies, not for therapeutic purposes but to assess:
- Pharmacokinetics (how the drug is absorbed, distributed, metabolized, and eliminated)
- Pharmacodynamics (how the drug interacts with cellular targets)
- Preliminary safety and tolerability data
This phase also establishes appropriate dosage levels and evaluates initial side effects.
Phase II trials: these evaluate the drug’s activity, therapeutic effects, dose–response relationship, and risk–benefit profile. They involve a small number of patients (typically 10–60) with similar clinical characteristics defined in the protocol.
FIL sponsors numerous Phase II studies, which are particularly important because they allow access to innovative therapies and lay the groundwork for larger trials.
Phase III trials: these assess efficacy and adverse reactions on a large scale (hundreds of patients) and compare different treatments for the same condition. They provide definitive data on efficacy and tolerability.
Typically, an experimental therapy is compared with a standard treatment to demonstrate non-inferiority (or superiority) and an acceptable risk–benefit profile. Patient assignment to treatment arms (“randomization”) may follow predefined criteria or occur randomly (1:1). FIL conducts many Phase III trials.
Phase IV trials: these are post-marketing studies conducted after a drug has been approved for a specific indication. They continue to monitor adverse effects and properties not identified in earlier phases. These studies are linked to commercial authorization and renewal processes.
As a non-profit research organization, FIL promotes only studies aimed at improving care, clinical practice, and risk–benefit evaluation—not drug commercialization. FIL conducts Phase I/II, Phase II, and Phase III studies, but does not carry out Phase I-only or Phase IV trials.
Patients can ask their physician whether clinical trials are available for their condition. The “Centers List” section provides information on FIL centers in Italy.
Data on interventional clinical trials are also available on online platforms such as:
- clinicaltrials.gov (global registry)
- clinicaltrialsregister.eu (European registry)
As the study sponsor, FIL must obtain all required authorizations before a study can be activated at participating centers in Italy.
Interventional or observational studies involving one or more drugs must be evaluated by AIFA (or, in specific cases, the Istituto Superiore di Sanità) and by the relevant Ethics Committees for all participating centers.
The Ethics Committee is an independent body responsible for safeguarding the rights, safety, and well-being of participants by reviewing clinical, observational, and epidemiological study protocols.
Once approvals are obtained, FIL provides participating centers with all operational procedures for proper administrative and clinical management and activates the study.
At that point, the responsible physician may propose participation to eligible patients (based on lymphoma type, age, disease stage, etc.).
Patients who agree to participate must sign an informed consent form.
Clinical trials are not suitable for all patients, even those with the same disease.
Patients are not “guinea pigs.” Clinical research follows strict regulations.
The physician responsible for the study informs the patient about the trial, including potential risks and benefits. They must clearly explain the protocol and answer all patient questions. Patients must be given adequate time to consider participation.
Participation is entirely voluntary, and patients may withdraw at any time without penalty or loss of standard care rights. Withdrawal does not affect the quality of future medical care. The study physician will explain how to safely discontinue any ongoing treatment.
Participation in a clinical trial involves no cost and no financial compensation for the patient. Patients are closely monitored throughout the study according to protocol-defined procedures.
Despite significant advances in lymphoma research, many questions remain unanswered. Clinical trials are the primary method used in medicine to advance knowledge.
They are essential not only for developing new therapies, but also for improving standard treatments, refining diagnostic techniques, identifying new prognostic factors, and personalizing therapies—without increasing the burden on the National Health Service.
Clinical trials are conducted across all areas of medicine, but are especially important in oncology and hematology.
They play a crucial role in translating biomedical research into clinical practice.
In fact, the standard therapies currently used to treat lymphomas are the result of previous clinical trials.