Assistance in conducting preclinical and clinical trials
The DOCLINX team provides services for preparing preclinical and clinical studies of medicinal products.
We will do for you:
- Assessment of the scope of necessary preclinical and/or clinical studies
- Selection and engagement of laboratories/specialists for conducting preclinical studies
- Selection and engagement of specialized clinical institutions
Why are preclinical studies of medicinal products needed?
The clinical stage of developing a new pharmacological substance begins only after carefully conducted preclinical studies on animals. Data from pharmacological and toxicological studies regarding the characteristics of action and effects of the drug when administered to animals help the researcher form a correct understanding of the nature, scope, and duration of planned clinical trials, and determine the prognosis of its safety for humans.
Necessary scope of preclinical studies
Original medicinal products:
- General toxic properties:
- acute and subacute (subchronic) toxicity
- chronic toxicity
- local irritant effect
- Specific types of toxicity:
- mutagenicity
- reproductive toxicity
- carcinogenic effect
- allergenic effect
- immunotoxic effect
- Pharmacological safety
- Specific pharmacological activity
- Pharmacokinetic studies
Generic medicinal products:
- General toxic properties:
- acute and subacute (subchronic) toxicity
- local irritant effect in comparison with the registered analog
Why are clinical trials of medicinal products needed?
Clinical trials are a necessary part of the development process for any new drug or expansion of indications for a drug already known to doctors. Clinical trials cannot be replaced by in vitro studies or studies on laboratory animals, including primates. The organism of laboratory animals differs from the human one in pharmacokinetic characteristics (absorption, distribution, metabolism, and excretion of the drug), as well as in the reaction of organs and systems to the drug.
Phases of clinical trials of medicinal products
| Phase I | Phase II | Phase III | Phase IV | |
| Objectives | Determining the safety and tolerability of the drug, creating an initial characterization of the pharmacodynamic and pharmacokinetic properties of the drug in healthy volunteers | Dose selection with efficacy assessment, short-term side effects, evaluation of overall risk for a specific population and specific disease | Obtaining additional information on clinical efficacy, assessment of overall benefit/risk ratio | Monitoring safety in a large population, identifying additional indications |
| Studied parameters | Vital signs, concentration levels, side effects | Dosing regimen and tolerability, side effects, efficacy | Laboratory data, side effects, efficacy | Efficacy, pharmacoeconomics, pharmacoepidemiology, side effects |
| Study population | Healthy volunteers or patients with a specific disease (cancer, HIV) | Patients with a specific disease | Patients with a specific disease | Patients with a specific disease, special populations |
| Number of patients | 20-80 | 200-300 | Hundreds-thousands | Thousands |
| Examples | Study of a single dose of drug X in healthy volunteers | Double-blind clinical trial of efficacy and safety of drug X compared to placebo in patients with arterial hypertension | Study of drug X compared to standard treatment for arterial hypertension | Pharmacoeconomic study of new drug X compared to standard treatment for arterial hypertension |
Phase I (most typical type of study: human pharmacology)
Phase I is the first experience of using a new active substance in humans with its preliminary evaluation. Usually, such studies are conducted on a small group (up to 100 healthy volunteers). The following are studied:
- safety and tolerability of a single dose;
- safety and tolerability of multiple doses;
- pharmacokinetic parameters;
- pharmacodynamic effects.
About one-third of drug candidate substances are eliminated in Phase I studies due to poor tolerability or poor absorption. Therefore, the main goal of the studies is to decide whether to continue work on the new drug, and, if possible, to establish doses that will be used in patients during Phase II clinical trials. During this phase, researchers obtain preliminary data on the safety of the new drug and describe its pharmacokinetics and pharmacodynamics in humans for the first time. The future fate of the drug and the effectiveness of clinical trials depend on the thoroughness of the studies in Phase I.
Phase II (most typical type of study: therapeutic evaluation (therapeutic study))
This is usually the first experience of use in patients with the disease for which the drug is intended to be used. The scope of these studies is significantly larger than in Phase I, 100-200 (up to 500) patients. The second phase is divided into IIa and IIb. Phase IIa consists of therapeutic pilot studies, as the results obtained in them provide optimal planning for subsequent studies. Phase IIb involves more extensive studies in patients with the disease that is the main indication for prescribing the new drug.
The main goal is to prove the efficacy and safety of the drug. The results of these studies (pivotal trial) serve as the basis for planning Phase III studies.
Phase II begins with the initiation of studies in which the primary goal is to study therapeutic efficacy in patients. A mandatory condition for conducting Phase II is a comparative design and the inclusion of a control group. Subsequent studies are usually randomized, placebocontrolled, and parallel-managed to evaluate the efficacy of the drug and safety for a specific therapeutic indication. Phase II studies are usually conducted in a group of patients selected according to relatively narrow criteria, i.e., a relatively homogeneous population is formed.
An important goal of Phase II is to determine the doses and dosing regimen for Phase III study. Early studies at this stage often use a dose titration design to form an early assessment of dose response, while later studies may confirm dose-response relationships for the trait under consideration using a recognized parallel (dose-response) approach. The "dose titration" clinical study design can also be applied in Phase III clinical trials (confirming dose-response reaction).
Additional goals of Phase II clinical trials may include evaluation of potential study endpoints: therapeutic regimens (including concomitant therapy); target populations (e.g., moderate versus severe condition) for further study in Phase II or Phase III. These goals can be achieved through evaluative analysis, data group analysis, by including multiple endpoints in the study.
Phase III (most typical type of study: therapeutic confirmation)
Multicenter studies involving large (and, if possible, diverse) groups of patients (on average, 1,000-3,000 people). The main goal is to obtain additional data on the safety and efficacy of various dosage forms of the drug, on the nature of the most common adverse reactions, etc. Most often, clinical trials of this phase are double-blind, controlled, randomized, and the study conditions are as close as possible to normal real-world routine medical practice. The data obtained in Phase III clinical trials form the basis for creating instructions for the medical use of the drug and for deciding on its registration.
Phase III begins with the initiation of studies in which the primary goal is to demonstrate or confirm therapeutic benefit.
Phase III studies are designed to confirm preliminary information accumulated in Phase II that the drug is safe and effective for use in specific indications and in appropriate populations. These studies are designed to provide an adequate basis for approval and marketing. Phase III studies may continue to study dose-effect relationships, use of the drug in broader populations, at different stages of the disease, or in combination with another drug. For drugs with a long half-life and used over a long period of time, studies are usually conducted in Phase III, although they may be started in Phase II. These studies are necessary to assess the overall clinical safety of long-term drugs, as well as their safety in the elderly. This information from Phase III is necessary to create adequate instructions for medical use.
The results of Phase III studies become decisive in making a decision on the registration of a new drug. A recommendation for medical use is considered justified if the new drug is more effective than already known drugs with similar action; has effects that are not characteristic of existing drugs; has better tolerability than known drugs (with the same efficacy); is effective in cases where treatment with known drugs is unsuccessful; is more advantageous in pharmacoeconomic terms or allows the use of simpler treatment methods or a more convenient dosage form; has advantages when used in combination with other drugs.
Phase IV (therapeutic use)
Phase IV clinical trials are conducted after registration and the drug's entry into the pharmaceutical market in order to obtain more detailed information about long-term use in various patient groups and with various risk factors, etc., and thus more fully evaluate the strategy of using the drug. A large number of patients participate in the study, which allows for the detection of previously unknown and rare adverse events.
If the drug is intended to be used for a new indication that has not yet been registered,
additional studies are conducted for this purpose, starting from Phase II.
Therapeutic use studies proceed outside the previous demonstration of drug safety, efficacy,
and dose determination. They can have any design but must have appropriate scientific
objectives. Usually, clinical trials conducted in Phase IV include additional study of drug-drug
interactions, safety, and studies designed to support the use of the drug for indications.
Personalized commercial offer
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Regulatory acts
- EEC Council Decision of 03.11.2016 No. 78 "On the Rules for Registration and Expertise of Medicinal Products for Medical Use"
- EEC Council Decision of 03.11.2016 No. 79 "On Approval of the Rules of Good Clinical Practice of the Eurasian Economic Union"
- EEC Council Decision of 03.11.2016 No. 81 "On Approval of the Rules of Good Laboratory Practice of the Eurasian Economic Union in the Field of Circulation of Medicinal Products"
- EEC Council Decision of 03.11.2016 No. 85 "On Approval of the Rules for Conducting Bioequivalence Studies of Medicinal Products within the Eurasian Economic Union"
- EEC Council Decision of 03.11.2016 No. 89 "On Approval of the Rules for Conducting Studies of Biological Medicinal Products of the Eurasian Economic Union"
- EEC Board Recommendation of 17.07.2018 No. 11 "On the Guidelines on General Issues of Clinical Trials"
- EEC Board Recommendation of 12.03.2019 No. 8 "On the Guidelines for Dose Selection of Medicinal Products"
- EEC Board Recommendation of 02.09.2019 No. 25 "On the Guidelines for Preclinical and Clinical Development of Combination Medicinal Products"
- EEC Board Recommendation of 21.05.2020 No. 10 "On the Guidelines for Conducting Preclinical Toxicity Studies with Repeated (Multiple) Administration of Active Substances of Medicinal Products for Medical Use"
- EEC Board Recommendation of 27.10.2020 No. 18 "On the Guidelines for the Study of Pharmacological Safety of Medicinal Products for Medical Use"
- EEC Board Decision of 26.11.2019 No. 202 "On Approval of the Guidelines for Preclinical Safety Studies for the Purpose of Conducting Clinical Trials and Registration of Medicinal Products"