MKVT

Clinical trials, when the active substance is administered to humans, can only be performed after completing strict laboratory and animal testing. These are the so-called “preclinical” studies, which must demonstrate that the substance is relatively free from risk before the investigational product could proceed to the first phase of human testing. At this time, a detailed (human phase I) study plan (protocol) is prepared, which is evaluated by professional and ethics bodies both at national and international levels. These bodies decide whether the study plan should be approved or rejected based on the preclinical results, assessing the foreseeable benefits versus the potential risks. The well-being and safety of trial subjects, as well as a favorable risk-benefit ratio are regarded as the most important points of consideration when clinical trials are authorized and performed. Hungarian laws and regulations are harmonized with the international legislation, creating a scrutinous regulatory, authorization and supervisory system for the professional and ethical evaluation of studies, assuring that the rights, health and well-being of trial subjects are protected. (In Hungary, these bodies are the National Institute of Pharmacy and Nutrition and the Medical Research Council Ethics Committee for Clinical Pharmacology.)

Besides all of these, especially at the start of the process (e.g. phases I and II) when the trial is performed on a small number of subjects, participants might experience adverse effects which might result even in death or in a sustained impairment of health. Researchers apply a variety of risk-mitigation measures to prevent this, and early-phase studies are performed with specific scrutiny, after careful preparation, under increased supervision, slowly progressing over time.

The “safety” of the investigational product and the acceptability of the expected side effects depend on the disease to be treated: in serious conditions, where the currently available treatment options might also come with several adverse reactions (in case of, for example, malignant tumors or autoimmune diseases), the side effects emerging from the investigational treatment may also be more acceptable as long as they are proportionate with the expected benefit. Although still experimental, in later-stage, phase IIb to phase III studies the growing body of data and experience allows us to eliminate risk-increasing factors more efficiently. Before enrollment to the trial, the investigator informs the patient in detail, both verbally and in writing about the expected risks during the trial. Therefore, the patient can make an informed decision whether to take part or not. Should the patient wish to discontinue the trial for any reason, they can do so at any time, without suffering any adverse consequences.

Responsibility for patient safety is shared between the investigating physician, the entity initiating the study (e.g. a pharmaceutical company), as well as the regulatory and reviewing authorities. The clinical trial’s responsible stakeholders mentioned above are obliged by international regulations and process descriptions to detect, transmit and evaluate any serious adverse events which have occurred with the specific active substance at their respective study sites (investigators), or anywhere in the world during their research study (pharmaceutical companies), and to take appropriate measures for the protection of the affected patients and all patients participating in the trial (pharmaceutical companies, authorities). If necessary, the investigator might decide to withdraw the patient from the trial right away. In case of necessity, those who initiate the trial and the authorities might decide that the trial is modified or discontinued. Study data related to the investigational product are summarized and sent to the participants by the initiating body in a regular manner.

Furthermore, the patients themselves may help mitigating risks and promoting their own safety as well as that of other participant: upon enrollment and during the course of the study, they should duly inform the study staff about any previous diseases, medicines taken, symptoms experienced, hospitalizations or other events. These are evaluated by the investigators and if necessary, they provide appropriate care. Additionally, the investigators forward these issues in an anonymized format, so that data received from different study sites can be summarized, evaluated and considered for the trial continuation by the initiators and reviewers of the study.