WE.SPEED.
The medicines available today in pharmacies are the outcome of medical research. Medical research has tremendously evolved over the last 50 years, contributing through new therapies and innovative medicines to cure many diseases and therefore prolonging lifespans.
Researchers predict that every second child born today is likely to live beyond the age of 100 years, due to the progress of medical research!
Each medicinal product, before being sold in a pharmacy and being used for the treatment of countless diseases, goes through a long process of research, testing, efficacy confirmation, identification of possible side effects, and eventually being approved for marketing.
Clinical research adheres to very strict national and international regulations, which are carried out based on the ICH-GCP (International Conference of Harmonization - Good Clinical Practice) Guidelines and the Helsinki Declaration, adopted by the General Assembly of the World Medical Association.
All the European states, USA, Canada, Japan and most countries throughout the world adhere to these international regulations in order to facilitate the progress of medical science for the good of mankind.
Clinical trials are conducted in many different locations such as hospitals, universities, medical practices, or medical clinics, all certified for research activities by the competent health authorities.
A clinical study may be single centre (taking place at one single centre/clinic, i.e., in one single country) or multicentre (taking place at multiple centres in several countries). Most clinical trials involving human volunteers are multicentre and are conducted simultaneously in European Union countries, the United States, Canada, Japan, the Russian Federation, Australia, New Zeeland, etc., whose volunteers contribute together to international clinical research.
Countries with a long-standing tradition in pharmaceutical clinical research are also the undisputed leaders regarding the number of clinical trials conducted per capita. The USA holds the first place in this respect, followed by European Union countries.
Good Clinical Practice (GCP) Guidelines are internationally accepted, ethical and scientific quality standards for designing, conducting, recording and reporting trials that involve volunteer participation of human subjects to ensure:
For additional information on clinical trials, please visit the websites of:
Medical research sets out to understand the disease mechanism. Therefore, researchers usually identify a way to influence this mechanism: block harmful molecules, kill germs, stimulate a favourable process. At this stage researchers create new compounds (molecules) that, theoretically, could act in a beneficial manner to disrupt the disease mechanism.
Subsequently, the compound goes through multiple stages to confirm its safety and efficacy. Firstly, computer models select potential molecular candidates (in silico), then appropriate lab testing is performed (in vitro). Tests are then conducted on laboratory animals selected as they show a reaction pattern similar to that of humans (in vivo or pre-clinical trials). In the late phases of the drug development process, clinical trials are finally implemented, and the medicinal product is administered to humans.
Only a small proportion of the compounds created by researchers reach this phase of clinical trials, most of them getting lost on this lengthy pathway as they do not prove to be as effective as expected.
Clinical research is divided into two main categories:
Clinical trials go through the following phases, in chronological order:
It is a relatively recent form of optional exploratory trials. Phase 0 trials are called micro-dosing studies in humans as well and are intended to accelerate the development of promising medicines or imaging agents, establishing much faster whether the drug or agent works in humans as expected based on pre-clinical studies. Distinctive features of phase 0 studies include the administration of single sub-therapeutic doses of the investigational medicines to a small number of subjects (10-15) to collect preliminary data on the pharmacokinetics of the agent.
A phase 0 trial does not provide data on safety or efficacy, the dose being by definition too low to determine any therapeutic effect. Based on the data obtained during these trials, a decision is made whether to proceed or not with the drug development, based on relevant human models, instead of exclusively relying on sometimes inconsistent animal data.
Usually, the number of participants in such a trial varies from 20 to 100 healthy volunteers or volunteers with a certain illness/condition. The study lasts for several months. Investigational medicine is given to a small number of healthy volunteers to see which dose is safe, starting with a single dose administration. Different participants receive different doses to determine which dose is safer, then either multiple doses are administered to healthy volunteers and/or single/multiple dose(s) in volunteer patients with a condition (disease) possibly targeted by the investigational medicinal product. The information is useful for the design of phase II studies.
Phase I studies can be further divided as follows:
In Phase II trials, the investigational medicinal product is administered to a group of patients having the condition (disease) for which it has been developed. Typically involving several hundreds of patients, these studies are not large enough to show whether the investigational medicine is going to be beneficial. Instead, Phase II studies provide investigators with additional safety information. This data is used to design new Phase III research protocols.
Phase II studies can be further divided as follows:
Some studies combine Phase I and Phase II and test both efficacy and safety and tolerability.
The investigational medicinal product is administered to a much larger number of people (thousands of patients) over several years, in order to determine whether it continues to be effective or causes side effects, which only occur after a longer period of time and/or compare this investigational medicinal product to others already in use. If an investigational medicinal product is successful at this time, it could be approved for large scale use.
A treatment is often studied even after it has been authorized; these are called “post marketing studies”. These studies monitor the side effects or problems that could occur only after several years of use or test the treatment in different prevention or therapy settings.
The document that governs the conduct of a clinical trial and establishes all the activities carried out within is known as the Study Protocol. The Protocol provides information on the research purpose, criteria for including volunteers in the study, the schedule of activities, methods and treatments, dosages, the study period and the reporting methods. Another important document is the Investigator's Brochure (Ib), made available to researchers/investigators by the Sponsor, which includes pharmacology data and pre-clinical and clinical experience (beneficial effects and adverse events) accumulated in previous studies with that test product.
Before a patient is included in a clinical trial, he/she signs a document called Informed Consent Form (ICF). Prior to the decision to participate in a clinical trial, patients spend more time with one of the investigators who explains what the study is about (what tests will be done, how often the patients will have to come to the clinic, what the patient will have to do at home, what discomforts or risks may occur). Patients will be informed about the medication they will receive. The patient is then encouraged to ask questions to make sure he or she understands all the implications of study participation. The patient also receives this information in a written document, through the informed consent form.
During informed consent process, investigators will need to:
The purpose of the informed consent process is to protect the participants. It begins when a potential participant first requests information about a study and continues throughout until the end of the study. The investigator and potential participant have conversations that include answering the participant's questions regarding the research. All important information about the study should also be provided to the potential participant in a clear and easy-to-understand written document. The informed consent form is reviewed and approved by regulatory authorities, respectively independent ethics committee, before the document is given to potential participants. A person has to sign an informed consent form to be enrolled in a clinical trial.
The confidentiality of study participants’ personal data will be strictly protected, and only the investigation team will have access to such data.
All data referring to the study will use only the initials of the participants.
The investigator (researcher) is a highly experienced and qualified medical doctor. He/she requires scientific knowledge and clinical experience in patient care. Investigators are usually specialists trained in clinical trial practice. The investigator is responsible for conducting the clinical study at an investigation site, and in case the study is performed by a team at that site, the team leader is appointed Principal Investigator (PI).
The legislation governing the conduct of clinical trials is based on a set of recommendations called "Good Clinical Practice - GCP - Guidelines".
The Good Clinical Practice Guidelines are a standard for the clinical trial design, management, development, monitoring, auditing, recording, analysis, and reporting, which guarantees both the reliability and accuracy of the reported data and results, and protection of patients’ rights and integrity as well as the confidentiality of their personal data.
The investigational medicinal product (IMP) is the pharmaceutical form of a drug substance or placebo that is tested or used as a reference in a clinical study.
Clinical trial Sponsors are usually pharmaceutical companies or governmental agencies that perform research and manufacture medicines. These Sponsors design the strategy and ensure financial support to conduct the clinical trials. If the Sponsors do not have adequate internal resources to organize clinical trials, they outsource (contract) the implementation of clinical trials to specialized companies called Contract Research Organizations (CROs).
Clinical trials are conducted in many different locations, such as hospitals, physician practices, medical clinic or teaching hospitals, all certified for research activities by the competent health authorities.
In order to conduct a clinical trial in any country, the approval of two regulatory authorities is needed: the Health Authority (HA) and the Ethics Committee (EC) in the given country. The clinical trial can only start after obtaining the approvals of these authorities based on the legislation in force.