How are clinical trials conducted?
Clinical trials are normally conducted by professionals in healthcare institutions, universities or institutions specialized for conducting such trials according to predefined protocols. In addition to physicians (investigators) who are directly involved, a number of other professionals may be involved in clinical trials such as: scientists, nurses and other healthcare professionals, experts in safety monitoring, experts in assessing and monitoring ethics, statisticians, sponsors etc.
Persons who can participate in clinical trials are subjects who voluntarily agree to take part and who sign a document called informed consent. The term “informed consent” denotes the procedure in which trained medical staff, generally the investigator, explains to potential subjects all elements of the clinical trial, its purpose, the properties of the investigational medicinal product, other treatment options, risks, benefits and the subjects’ rights. This information is also provided in writing, in the form of the informed consent document, which the subject and the investigator personally sign and date if the subject chooses to participate in the trial. The subject keeps one copy of the signed document. Informed consent is signed by a parent, legal representative or guardian for subjects belonging to vulnerable groups (children, psychiatric patients without legal capacity, unconscious patients, etc.). If a subject cannot or is unable to read, informed consent is signed by an impartial witness in order to confirm that it was read to the subject.
It is of utmost importance that future subjects are fully aware of all aspects of treatment and that they receive answers to all their questions before they sign the informed consent document. They must have enough time to examine all information and, if they wish, they may consult their family, friends or their family doctor. Informed consent plays a central role in the protection of patients’ rights.
The procedure of providing detailed information to subjects continues throughout the trial. The trial doctor must keep a subject informed of any new knowledge that may affect his/her participation in the trial.
To participate in a trial, subjects must meet certain predefined participation criteria (the inclusion and exclusion criteria). These criteria may contain diagnosis of a certain disease, age, gender, medical condition, certain disease indicators, etc. The presence of such criteria is genrally established through doctor’s interviews with subjects, review of medical documentation and examinations and different tests performed during the screening procedure.
After establishing that a patient meets all criteria and that the baseline assessments of his/her medical condition are satisfactory, the subject is given the investigational medicinal product, comparator or placebo and further evaluations of the effects of treatment are made.
To ensure the investigators and subjects’ impartiality with respect to the treatment results and outcome of the trial, subjects are often randomized into different treatment groups (randomization). An additional method of ensuring impartiality is called blinding, which means that the subjects and/or the investigators are not aware of the medicinal product (or dose) a subject receives. In case of an emergency, this information can be made immediately available to the investigator.
Subjects can withdraw from a clinical trial at any time without giving a reason and without this affecting their patient rights or usual care. Such subjects should inform the trial doctor of this for their own safety. In addition, the trial doctor may decide to discontinue the treatment for a subject if he/she believes this is in the subject’s best interest. The sponsor may also decide to discontinue a trial, especially if it is established through an interim analysis that the medicinal product does not have the expected efficacy or that it carries unacceptable risks.
The duration of a subject’s participation in a clinical trial may last from one day to several years. Subjects should be informed of the duration of the trial, the frequency of visits to the institution where the trial is conducted and their other obligations prior to beginning the trial.
Most clinical trials generate no expense to a subject. The cost of the medicinal product and protocol procedures are paid by the sponsor and any other procedures that patients may undergo irrespective of their participation in the clinical trial are covered by their health insurance. In some trials, subjects may be reimbursed for their travel expenses.
Pregnant and nursing women are not allowed to participate in clinical trials, and women of childbearing age have to undertake an appropriate and safe birth control method to avoid any potential adverse effects a medicinal product may have on the foetus, most of which are usually unknown. In some trials, men may also be required to use an appropriate birth control method for the same reason.
During a trial, information required under the protocol is gathered by different methods such as interviews, examinations, laboratory and other tests. The most important data being gathered focus on the efficacy and safety of the medicinal product, but frequently other data are also gathered, such as information on the quality of life, treatment costs and the like. Special attention is paid to constant and prompt gathering of information on adverse events in order to, at all times, promptly protect subjects against any adverse consequences of the treatment. Data are processed in specialized centres. After the data are analysed, the clinical trial results are published. The decision is then made on the efficacy and safety of the investigational medicinal product and either further trial procedures are undertaken or the medicinal product is registered.