Our company provides a services related to CR. In particular:
Conducting clinical trials of early phases (Phase I) and bioequivalence studies, conducting post-marketing safety studies;
Conducting pharmacovigilance in CR.
Therefore, we decided to explain in a popular way what is meant by CR and into which phases it is divided.
Clinical research of medicinal products – the study of the diagnostic, therapeutic, prophylactic, pharmacological properties of the drug in the process of its use in humans, animals, including the processes of absorption, distribution, change and excretion, by using scientific assessment methods in order to obtain evidence of safety, quality and effectiveness medicinal product, data on adverse reactions of the human body, animal to the use of the medicinal product and the effect of its interaction with other medicinal products and (or) food products, feed (Article 4, paragraph 41 of the Federal Law of April 12, 2010 No. 61-FZ “On the Circulation of Medicines”).
There are two types of clinical trials: for medical use and for bioequivalence studies. The first is actually the study of new substances, the second is comparison, the degree of similarity between the reproduced (generics) and original drugs. In any case, the process takes place in several stages.
Preclinical
The first, preclinical research begin shortly after the synthesis of a new, potentially effective molecule. Their essence is to test the hypothesis about the alleged pharmacological action of a new compound. In parallel, the toxicity of the compound, its oncogenic and teratogenic effects are being studied. All these studies are performed on laboratory animals, and their total duration is 5-6 years. As a result of this work, out of 5-10 thousand new compounds, about 250 are selected.
The next step is human testing. This process is clearly regulated by law, in which all the nuances are detailed. In addition, tests, wherever they take place, must comply with international GCP (Good Clinical Practice) guidelines. Clinical trials are considered one of the most legally protected areas of life
Clinical researches
Phase 1
At this stage, a new drug is offered to humans for the first time. Basically, a small number of healthy volunteers participate, 50-100 people. Exceptions include some groups of drugs: for example, cytotoxic drugs for the treatment of malignant neoplasms should be used only in cancer patients. During the first phase, the main purpose of testing is to identify the toxicity of the drug to the human body. Also, if possible, the maximum allowable dose, pharmacokinetics, pharmacodynamics of the drug are determined. The process itself goes through several stages. First, the volunteer receives a single low dose of the drug, is closely monitored and examined. Then there is a gradual increase in the dose and duration of the drug intake. The patient is under constant medical supervision. A strict record is kept of any manifestations of undesirable effects.
Phase 2
At this moment, the medicine first encounters the patient, and the vaccines are further tested on volunteers. The number of people participating in the experiment is already 300-600 people. The phase is conventionally divided into 2a and 2b.
Phase 2a
First, the safety of the drug is assessed in a larger sample. Secondly, phase 2a is a pilot study, that is, at this stage, the researchers “ask the estimate” – on a relatively small group of people they are trying to determine the effective dose, the maximum allowable dose, dose-dependent effect and frequency of administration. Third, pharmacokinetics and pharmacodynamics continue to be monitored.
Phase 2b
After calculating the most optimal dosing regimen in the previous step, the researchers check how effective the drug is. If the desired result is not achieved in a small sample, the question arises about the expediency of further testing.
Phase 3
If at the previous stages small groups of people participated in the study, then during the third phase the number of patients increases to several thousand people (as a rule, 3-6 thousand). The third phase is also conditionally subdivided into 3a – until the approval of the relevant authorities (FDA, Ministry of Health, etc.) and 3b – after approval, but before the drug is released on the market.
Phase 3a
At this stage, the main assessment of the effectiveness of treatment takes place, and groups of patients are identified that respond well to therapy. In addition, the new treatment is compared with the existing one. Throughout the research, unwanted adverse reactions are identified, and all data is collected for the safest and most effective use.
Phase 3b
Having received permission to put the drug on the market, the researchers re-check all the information received, make any additions, identify strengths and weaknesses, and develop topics for post-marketing research.
The results of Phase III become decisive when deciding on the registration of a new drug. This decision can be made if the drug:
– more effective than already known drugs of similar action;
– has effects that are not characteristic of existing drugs;
– has a more advantageous dosage form;
– it is more beneficial in pharmacoeconomic terms or allows the use of simpler methods of treatment;
– has advantages when combined with other drugs;
– has an easier way of application.
We can say that Phase 3 is the main and most costly and time-consuming stage.
Phase 4
Competition with new drugs makes it necessary to continue research after the registration of a new drug (post-marketing studies) to confirm the effectiveness of the drug and its place in pharmacotherapy. In addition, phase IV studies allow us to answer some questions that arise during the use of drugs (the optimal duration of treatment, the advantages and disadvantages of a new drug in comparison with others, including newer drugs, the specifics of prescribing in the elderly, children, long-term effects of treatment, new readings, etc.).
Bioequivalence research
Most drugs on the pharmaceutical market are generic drugs. The pharmacological action and clinical efficacy of the drugs that make up these drugs are generally well understood. However, the effectiveness of generics can vary significantly.
Registration of generic drugs can be simplified (in terms of time and volume of research). Bioequivalence studies allow to make a strictly informed conclusion about the quality of these funds. In these studies, the generic drug is compared with the original drug in terms of bioavailability (comparing the fractions of the drug reaching the systemic circulation and the rate at which this process occurs). If two drugs have the same bioavailability, they are bioequivalent. In this case, it is assumed that bioequivalent drugs have the same efficacy and safety.
Bioequivalence is studied on a small number of healthy volunteers (20-30), using standard procedures for the study of pharmacokinetics (construction of a pharmacokinetic curve, studies of the value of AUC, Tmax, Smax).
Sources:
1.Sedgwick P. Phases of clinical trials // BMJ: British Medical Journal (Online). – 2011 .– T. 343.
- Wright B. Clinical Trial Phases // A Comprehensive and Practical Guide to Clinical Trials. – 2017 .– S. 11-15
- Rosenberger W. F., Lachin J. M. Randomization in clinical trials: theory and practice. – John Wiley & Sons, 2015.
- Lin AA, Sokolov BI, Orlov AS Pharmaceutical market: a segment of clinical trials of drugs // Problems of modern economy. – 2015. – No. 1 (53).
- Clinical pharmacology and pharmacotherapy. – 3rd ed., Rev. and add. / ed. V. G. Kukes, A. K. Starodubtseva. – 2012 .– 840 p.