Frequently Asked Questions

Clinical research is scientific research designed to:

• find better treatments for diseases and disorders;
• improve existing treatments;
• find out more about a disease or condition or to better detect it.

Clinical trials are used to develop drugs, non-drug treatments and medical devices. Clinical research proceeds in several successive phases. If non-clinical studies in the laboratory and in animals are successful, clinical studies in humans will follow: healthy volunteers and/or patients. Clinical studies help researchers answer the following questions:

• Purpose and safety: Is the treatment being studied effective and safe and does it achieve the original purpose?
• Effectiveness: How effective is the study treatment? And is that better than the treatments already available?
• Benefits and risks: What are the consequences or outcomes of the investigated treatment? What are the benefits? What are the side effects and risks?

For patients, the main benefits of participating in clinical trials are:

• Participants gain access to an innovative treatment that is not yet commercially available.
• The new treatment may be more effective than the standard treatment currently used (standard of care).
• Participants are closely monitored by a qualified medical team and according to a rigorous protocol.
• The results of the clinical trial will help researchers better understand the disease.
• A clinical trial is a valuable experience regardless of the results. If the study is successful, it will allow other patients to benefit from an innovative and effective treatment. If it is not, it will prevent further research into an ineffective or harmful treatment.

The main risks to patients are:

• A clinical study is designed to evaluate whether a new treatment can have added value, that it can add value over existing treatments. It is possible that this is not the case.
• The new treatment may cause side effects that may be minor and temporary or potentially serious. Some side effects may not occur until later, causing damage to vital organs, such as the heart or kidneys, or leading to the development of another condition or disease.

A clinical trial is a step-by-step process in which a treatment is tested to find the right dosage and possible side effects. After going through three phases, if the treatment appears to be effective and safe, it is made available to the public for use by the FDA (in the U.S.) or the EMA (in Europe). Even after approval, the relevant authorities continue to monitor for side effects.

No, there is no cost to participate in a clinical trial. Some institutions pay volunteers to participate.

In the preclinical phase, preclinical or non-clinical studies take place. They study the chemical and pharmaceutical properties of promising molecules (drug candidates) and their possible toxic and carcinogenic properties. This is done at first in vitro, in test tubes or petri dishes in the laboratory, on human cell cultures. Afterwards, the efficacy and safety of the drug candidates are also studied in laboratory animals. Only when preclinical studies show that a drug candidate is effective and sufficiently safe can human clinical studies begin. The preclinical phase usually lasts several years.

Before Phase I studies can begin, the drug candidate has been thoroughly and extensively tested in the laboratory and in animals in so-called non-clinical studies. Phase I studies test the drug on humans for the first time; therefore, this phase is also called "first-in-human".

Participants in these studies are usually healthy volunteers (i.e., people who do not suffer from the disease for which the drug candidate is being developed), but in some cases patients are recruited, for example for cancer treatments. The number of participants in Phase I studies is limited: 20 to 100. These studies are open-label.

The objective of Phase I studies is to determine whether the drug candidate is safe, what the maximum dose the human body can tolerate is, and what its side effects (tolerance) are. Thus, a low dose will be started and gradually increased if no or only mild side effects are observed.

In addition, Phase I studies will analyze:

• what happens to the drug in the body (pharmacokinetics) – how it is absorbed and distributed and how it is transformed and eliminated?
• the effect of the drug on the body (pharmacodynamics)
• interactions (e.g., between drugs, with food and drink)

In addition to information on the mechanism of action of the drug candidate, side effects associated with increased dosing and information on efficacy, Phase I studies also provide information on the optimal way to administer the drug, such as orally or intravenously.

Phase I usually lasts up to one year. If the studies show that the drug candidate meets predetermined criteria, it can proceed to Phase II.

Phase II studies can only begin once all Phase I studies have been completed. Phase II studies are so-called exploratory therapeutic studies that test the drug candidate in patients, i.e. participants suffering from the disease for which the drug is being developed.

The number of participants in this phase varies from 100 to 500 and they are usually selected according to strict inclusion criteria, which makes the study population fairly homogeneous. This makes it easier to interpret the study results.

The objective of Phase II studies is to determine whether the drug candidate has beneficial therapeutic effects for patients with the disease in question and whether it is safe.

Research into therapeutic efficacy is carried out in so-called proof-of-concept studies, in which the drug candidate is compared to a placebo or, if one exists, to an existing treatment (usually the standard of care). These studies are usually randomized and (double)blind, but open label studies are not excluded.

To test efficacy and maximize effect, proof-of-concept studies generally use the maximum tolerated dose determined in phase I. But Phase II also investigates the optimal dose and frequency of administration of the drug candidate and collects additional information on side effects. This is done in dose-response studies. Dose-response studies are usually randomized, placebo-controlled studies with parallel study groups studying different dose levels. The zero-dose level is then placebo. Crossover studies are also possible.

In total, Phase II can last several years. The drug candidate can proceed to Phase III if, based on the results of these Phase II studies, it meets predefined criteria. These results form the basis for the design of phase III clinical trials.

Phase III studies are large-scale studies that further test the effectiveness and monitor adverse reactions of the new treatment. These studies typically involve hundreds to thousands of participants across multiple locations. Phase III studies compare the new treatment to the current standard treatment to determine if it is more effective, equally effective, or has fewer side effects.