About Clinical Research and Trials
We develop innovative solutions through clinical research in collaboration with partners and health care professionals, always placing the patient at the heart care. This page tells you more about clinical trials and how can an idea can move to a new drug approved for public use.
About Clinical Research and Trials
Clinical research is medical research that involves people and contributes to improve knowledge of diseases and find new and better ways to detect, diagnose, treat and prevent them. There are different types of clinical research:
- Clinical trials are interventional studies performed in human volunteers to test new or existing health technologies including drugs and other therapies. Carefully conducted clinical trials are mandatory steps for a new molecule to become an approved drug. They are designed to answer essential questions such as whether a new drug is safe and beneficial to people. The goal of clinical trials is to improve and even cure a certain disease by finding new or more effective therapies and treatments than what is currently being used: the standard of care.
- Non interventional studies, also referred to as observational studies, are conducted to observe effectiveness, safety and tolerability of a medicine under real life conditions as the drugs is prescribed during routine medical practice, in accordance with the term of the marketing authorization label.
The 4 phases of Clinical Research
Researchers test first the potential drugs in laboratories. Preclinical research can take many years. After screening hundreds of potiential condidates, most promising drugs are move into clinical trials. The potential new drug must go through different clinical research phases of testing on human before becoming available to patients who need it. This is a long and rigorous process that can last from 5 to 15 years.
Developing a new drug and bringing it all the way through the clinical trial process is a long and difficult task. It is designed to guarantee that potential drugs and treatments are both safe for use and effective at treating the disease or condition they were designed for. The different phases each play a vital role in ensuring that only safe and efficacious drugs and treatments are made available on the market. In each phase, several trials may be performed.
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o All participants in a clinical trial are volunteers who are free to discontinue the use of the tested drug and the trial at any time and whatever the reason.
o The safety of participant is the priority: the trial protocol takes the safety of the participants into account and is reviewed by competent and independent authorities before start.
o In practice there might be variations in the number of phases to complete drug development notably for promising interventions: Phases can be combined or overlapping, to fasten market approval.
Phase I
Is the drug Safe?
To determine a safe dose
To identify side effects
To describe pharmacokinetics
May last several weeks to several months
From few participants to several dozen
Phase II
Does the drug work?
To assess how well the drug works
To collect information on safety
May last up to one or two years
A few dozen to more than a hundred patients with the targeted disease or condition
Phase III
Is the drug better?
To confirm benefits & safety by comparison with placebo / standard of care
May last several years
Up to hundreds or thousands of patients with the targeted disease or condition
Phase IV
What else should we learn after approval?
To assess side effects continuously
to seek information about benefits an optimal use
Phase I trials, a first step to control that tested drug is safe for human
Phase I trials have several objectives as the determination of a safe dose, identification of side effects the drug may have and the description of its pharmacokinetic. The pharmacokinetic is how the body absorbs, transforms, and eliminates the drug.
Assessing the safety of the drug looks at identifying the most appropriate dose with regards to the expected activity for which the risk remains acceptable. In some Phase I studies the first signs of efficacy of the new intervention(s) could be sought.
Phase I trials often take place in a hospital or dedicated structure, with staff experienced in running such trials and closely observing the participants. The trials usually last a few weeks to a few months and are performed on small number of participants (up to a few dozen).
o The drug may enter Phase II only if a tolerated dose has been identified and pharmacokinetic is well described.
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o Phase I studies involved frequently healthy volunteers. It means that participants are not affected by the disease or condition the tested drug intends to treat. Healthy volunteers contribute to the development of safe drugs and accept potential risks without anticipated health benefits from participation.
In certain circumstances, as for cancer clinical research, Phase I studies directly involve patients for whom standard treatment is ineffective, inappropriate, or unavailable.
o Some trials (not only in Phase I) set up Independent Data and Safety Monitoring Board (IDSMB) composed of external and independent experts. This board provides recommendations on trial conduct, notably based on regular monitoring of safety concerns that may occur.
Phase II trials, a second step to know if the tested drug may work
For these trials, participants are patients with the disease or condition the drug intends to treat. These trials are designed to get information on drug activity and safety.
Phase II trials often take place in hospitals or clinics where patients with the disease are usually treated. They can generally last 1 or 2 years and are performed on a larger number of participants than Phase I (up to more than 100).
o The drug may enter Phase III only if it shows a promising activity and a confirmed acceptable safety at the chosen dose.
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o Nature, frequency, and severity of the side effects are the primary way to describe safety of the drug. The larger the trial population the better the drug safety is assessed.
o To be enrolled, participants must fulfill eligibility criteria defined in the protocol, related notably, but not only, to their health conditions and their medical history. Some of these conditions are important for the individual safety during the trial, others are required to eliminate potential biases in research e.g. ensure that studied population is representative of patients for whom the drug is developed.
o Phase II trials are usually not randomized but some may be to explore/compare several options.
Phase III trials, a final step to confirm that tested drug would be safe and effective for the patients with the disease or condition
Usually, the objective of Phase III trials is to compare the drug with the existing options (standard of care or surveillance) if any or a placebo.
The design of Phase III trials depends on the research question to test. To do so, participants are split in groups. In classic randomized clinical trials (RCTs) one group receives the tested drug, others the standard of care and/or the placebo to be compared with.
Phase III trials are performed on many participants (sometimes up to several thousands) to provide clear evidence on differences observed between groups.
o The drug may overcome Phase III if it demonstrates a favourable benefits/risks balance in comparison to the available options.
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Trial comparing different groups of participants requires rigorous methods:
o Randomization is a process for assigning participants to a group by an element of chance and is performed using a computer program. Hence, assignment is not the decision of anyone (participant, investigator, or sponsor) the population in each group should remain comparable.
o A blinded trial is a trial where the participant or/and the investigator and data evaluators do not know which drug has been assigned. Hence, investigator' s assessments and participant's perception should not be influenced by this information. If it is not the case, this is an open-label trial.
Some Phase III trials could use an adaptive multi-arms and multi-stage design to screen more treatments and compare them with a control group. Through the use of interim analyses different arms can be modified or even closed to further recruitment to focus on the drugs which are showing best efficacy.
After the drug has successfully overcome the development phases, sponsor seeks for drug approval by competent authorities.
Sponsor build a dossier gathering notably all pre-clinical data, clinical trial analyses and conclusions on safety and efficacy. The Dossier is evaluated by Drug Regulatory Authorities Health Authorities (as EMA for Europe Union, and FDA for USA) who grant or not a marketing authorization for a specific indication and a dedicated population of patients.
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o Evaluation of a new drug combines evaluation of benefits (the effectiveness of the drug against the disease) and risks (mainly side effects a participant may experience by taking the drug). A new drug must demonstrate a favourable balance in comparison to available options.
Phase IV trials, following marketing authorization, clinical research goes on to extend drug knowledge
Phase IV studies may explore ways to increase benefits of the marketed drug and improve the knowledge of the side effects and how to better manage them.
Some of these studies are observational, collecting information on patients following their therapy as routine care, and providing information on real-life usage. These are called Real World Evidence studies.
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New side effects may be identified after the drug has been marketed. They are continuously collected and analysed. The activity of detection and understanding of side effects is called pharmacovigilance. This is a primary responsibility of the pharmaceutical company and required by Health and Drug Regulatory Authorities.