- Clinical trials refer to the series of scientific studies carried out in humans that validate the research and development stages in the medicine discovery process.
- They are a crucial step, and subject to rigorous regulatory controls, in obtaining a marketing authorization and determining the optimal use of a medicinal product to ensure therapeutic benefit for patients.
- Clinical trials can last several years and must follow precise organization that complies with stringent research protocols to ensure the safety of the participants.
Clinical research, or the requirement for scientific rigor
Clinical research designates all scientific studies carried out on volunteers in order to develop medicines and medical devices.1 Clinical trials are usually conducted in a hospital setting or a doctor’s office, under the supervision and responsibility of physicians.
Clinical trials are used to assess the safety, efficacy, and use of treatment in humans so that a new medicine can be made available on the market. They require the application of a rigorous scientific method in order to guarantee both the therapeutic benefit of the proven solution and the safety of the participants. In addition to its therapeutic interest, clinical research also contributes to the development of medical and biological knowledge.2
Four phases of clinical trials
Pre-clinical trial validation is a prerequisite for starting clinical trials. This involves testing the molecular entity on animals before administering the candidate drug to humans.
The development of a new medicinal product typically consists of four successive phases of clinical trials, which aim to observe the effects of the drug in the human body and measure its effectiveness.
- Phase I: Corresponds to the first study in humans and can take several months. The molecule is usually tested in a group of 20 to 100 people (healthy volunteers) to assess tolerance and pharmacokinetics (study of what happens to the drug in the body). This phase also determines the highest and safest dose to administer to patients.
- Phase II: Evaluates the effectiveness of the medicine in a group ranging from a few dozen patients to a few hundred. This phase checks whether the molecule is active in treating the target disease, determines the optimal dose, and measures adverse effects.
- Phase III: Often referred to as a “pivotal study”. The molecule is tested more widely on a larger group of patients, up to several thousand. In this phase, the benefit/risk ratio of the molecule can be calculated and precautions for use are specified. At the end of this phase, an application for a Marketing Authorization (MA) can be submitted to the health authorities.
- Phase IV: Takes place after MA approval. In this phase, the tolerance and efficacy of the medicine are measured over the long-term in real life. Post-marketing monitoring is essential because even after numerous tests, certain effects of the molecule may not be fully known.4
Currently, only one in ten medicines passes all the stages.3 However, for oncology or a rare disease, the clinical development process of a drug can be accelerated: there can be fewer patients and certain phases of development may be combined.
Pharmaceutical companies, researchers, doctors, and patients are all mobilized!
Clinical trials generally take several years, sometimes up to ten years, involving the daily commitment and efforts of numerous stakeholders in order to find new therapeutic solutions that are vital for treating patients.
Pharmaceutical companies most often initiate clinical trials, as well as their funding. All clinical trials are carried out by qualified health care professionals, called investigators. They are in charge of proper trial conduct, and are responsible for the inclusion of patients in the study and for their safety. As for the participants, they are always volunteers.
Ensuring transparency of results within a stringent legal framework
To start a clinical trial, various authorizations are required from the relevant authorities of each country. Approval times vary from country to country (from 30 days to more than 200 days).
Each participant must receive all information relating to the study in writing (including benefits and risks) and must give their consent by signing an informed consent form before they can be selected. The Nuremberg Code and the Declaration of Helsinki of 1964, as well as their successive updates, advocate the ethical aspects of medical research worldwide.
The publication of the results of a clinical trial is of major interest to medical and scientific research because it helps to ensure the transparency of results, whether positive or negative. The Declaration of Helsinki stipulates, “Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject.”
NEW CHALLENGES AHEAD
- Accelerating research and marketing authorization: Faced with the Covid-19 pandemic, many pharmaceutical companies have been running a veritable “vaccine race” and are looking to fast-track research so that they can urgently deliver an effective vaccine that is accessible to all.
- Increased need for transparency: In a context where the general public expresses a lack of confidence in the pharmaceutical industry, pharmaceutical stakeholders are mobilizing for more transparency. While only half of study results are published in Europe,5 several regulations have been put in place to promote the publication of clinical trial results.
- Digitization of clinical trials: Accelerating the digital shift is a challenge for all health care stakeholders. Digitizing clinical trials can be useful because it facilitates the participation of patients living far from the investigator centers, improving their compliance (eg, through notifications) and providing easier access to real-time data.
- Patients at the core of research: As the main players in clinical trials, patients are increasingly involved in the research and development process of pharmaceutical companies. They are in the best position to talk about their disease/condition, its course, and the effects of the treatments they experience. Involving patients, as early as possible, makes it possible to speed up research and deliver treatments that are best suited to their needs.
5 Goldacre Ben, DeVito Nicholas J, Heneghan Carl, Irving Francis, Bacon Seb, Fleminger Jessica et al. Compliance with requirement to report results on the EU Clinical Trials Register: cohort study and web resource BMJ 2018; 362 :k3218