A clinical trial of a drug is a systemic study of a medicinal product through its use in humans to assess its safety and/or effectiveness, as well as to identify and/or confirm its clinical, pharmacological, pharmacodynamic properties, assess absorption, distribution, metabolism, excretion and/or interaction with other medicinal products.
Such studies are conducted by the fundamental ethical principles of the Declaration of Helsinki, GCP (Good Clinical Practice) Rules, and applicable regulatory requirements.
Assessment of risk-benefit ratio, as well as review and approval of the study protocol and other documentation related to clinical trials, is the responsibility of the Expert Council of the Organization / Independent Ethics Committee (ECA/IEC). Once approval has been received from the ESO/NEC, the clinical trial can be initiated.
There are several types of clinical trials:
- Pilot studies and feasibility studies.
- Prevention trials.
- Screening trials.
- Treatment trials.
- Multi-arm multi-stage (MAMS) trials.
- Cohort studies.
- Case-control studies.
- Cross-sectional studies
All clinical trials are classified according to certain characteristics: purpose, duration of time, presence of intervention in the usual tactics of patient management, etc.
Studies by a purpose:
– Preventive studies – finding the best ways to prevent disease in people who have never had it, or to prevent patients from relapsing;
– Screening studies – finding the best ways to detect certain diseases or conditions;
– Diagnostic studies – looking for ways to diagnose a certain disease or condition;
– Therapeutic studies are conducted to study the effectiveness and safety of experimental drugs, new drug combinations, or new methods in surgery or radiation therapy;
– Quality of life research is conducted to explore ways to improve the quality of life of patients with chronic conditions;
– extended access programs (under exceptional circumstances involve the use of an experimental drug in patients with serious or life-threatening conditions who cannot be included in a clinical trial because they do not meet the inclusion criteria.
Studies on the presence of interference in the usual tactics of patient management (in the standard procedures of examination and treatment of the patient):
– Observational (observational) study – a clinical study in which the investigator collects data by simply observing events in their natural course without actively intervening in them;
– non-interventional study (“non-intervention study”) – a study in which a drug is administered in the usual way by the conditions outlined in the marketing authorization.
– interventional study – a study of new, unregistered medicinal products, immunobiological agents, medical devices, or a study in which a medicinal product, immunobiological agent, or medical device is prescribed or administered in a manner different from the conditions outlined in the registered instructions (whether a new indication, a new dose of the product, new route of administration, new route of administration or a new patient category).
Studies by observation time interval:
– Retrospective (historical) study – A study that examines the outcomes of previous clinical trials or studies, that is, the outcomes that have already occurred before the study began. The researcher reviews medical records and selects patients according to certain criteria to study treatment outcomes.
– Prospective study – a study in which patients are recruited according to the criteria set out in the study protocol.
Patients receive the study drug and are followed for some time. The formation of groups receiving or not receiving the study drug takes place before the results are recorded. Most clinical trials are prospective.
Studies by duration:
– Single-study – looks at the effect of risk factors on a population and/or the prevalence of a disease (condition) in that population at a given point in time.
– long-term (longitudinal) – collecting data several times over a long period.
– longitudinal study – a long-term clinical study in which there is a long periodic follow-up of the same individuals.
– international study – a study that is conducted in multiple countries;
– multicenter study – a study conducted according to a single protocol in several research centers;
– meta-analysis – data from different studies on the same topic are summarized.
Studies by the degree of randomness of the experiment:
– randomized-when, after signing consent to an experiment, participants (scientists and study subjects) draw lots-who gets to do what type or part of the experiment.
– non-randomized. Not taken seriously in the scientific world at the moment. Participants may consciously or unconsciously collude and sabotage the results.
Research on participants’ awareness of the flow of the research process:
Blind or disguised research – there is no information about which group – the experimental or control group.
Disguised studies are used to eliminate systematic errors in clinical trials.
Studies on the effectiveness of the results obtained:
– Direct – accurately result in improvement in the patient’s life. Direct effectiveness criteria include recovery, reduced mortality, and complications, reduced hospitalization, improved quality of life;
– indirect (surrogate) – result in normalization of some medical parameters (for example – blood pressure), which theoretically should improve the patient’s life.
All studies are divided into three classes.
Class, I studies include the “Gold Standard” – randomized controlled (prospective) trials with double or triple-blind controls. The materials of these trials and the meta-analysis conducted on their basis should be used in medical practice as a source of the most reliable information.
Class II includes well-designed open experimental trials, observational prospective, and retrospective, which, with a certain degree of criticality, the results of these trials can be used in practice.
Class III studies with significant errors in their organization, case descriptions, and case series. They, like individual physician experience, the opinion of experts or “authorities” are considered to have an insufficient scientific basis.
Clinical trials are also divided by their design. They can be classified as follows:
* Depending on the method used to assign participants to treatment and control groups (non-randomized and randomized controlled trials).
* Depending on the awareness of participants or investigators (or both) as to which group participants are assigned to (simple or double-blind trials).
* Depending on the perceived degree of difference between the treatment and control groups (trials to confirm greater or not lesser efficacy).
In non-randomized controlled clinical trials, the investigator assigns participants to treatment and control groups. In these trials, the control groups may be parallel or historical. If a historical control is used, all patients in the trial receive the study drug; the results are compared to the patient’s previous condition (e.g., a patient with a chronic condition) or a control group from a previous study.
In randomized controlled trials, trial participants are randomly assigned to treatment or control groups. The process of randomly assigning trial participants to treatment or control groups is called “randomization. Different methods are used for randomization (closed envelopes, computer-generated sequencing, random numbers). Randomization requires two components: creating a random sequence and applying a random sequence, preferably in a way that participants do not know the sequence. Randomization avoids potential systematic errors.
Comparative clinical trial designs
There are several different types of comparative trials:
* Greater efficacy – to confirm that the study drug is better than the control.
* Equivalence – to confirm that the endpoint is no different (no better, no worse) than the control.
* No less effective – to confirm that the study drug is no worse than the control.
* Tests for dose-dependent effects to determine rates for different doses, including initial dose and maximum dose.