The clinical development program includes completed and planned clinical trials. It should comply with Clause 18 of Federal Law N 61-FZ On Drug Circulation dated April 12, 2010 (Russian Federation Code, 2010, N 16, cl. 1815, N 31, cl. 4161) and Order N 750n of August 26, 2010 On Approval of Expertise of Medicinal Products for Human Use and Form of Conclusion by a Committee of Experts. A full list of completed and planned clinical trials, specifying trial aims and objectives of each study in the context of actual and expected clinical trial outcomes and the reference product (if applicable).

We write preclinical and clinical trial reviews and summaries - modules 2.4-2.7 in the CTD format (EEU), as well as modules 4 and 5 review, and SPC.

The Protocol contains instructions for clinical trial participants, including specific roles of each participant and instructions for performing tasks. The Protocol assures qualified conduct of studies, data collection and analysis followed by submission for expert evaluation by the Russian MoH. Serving to achieve several objectives, the Protocol must be thoroughly elaborated. Consultations with clinicians may be required. The Protocol contains trial planning, justification, objectives, statistical analysis, methods and conditions of conduct, tasks and sequence of activities by the study team and other persons involved in the study by specific tasks; standardized study procedures in case there is a need for a repeated study; information for regulatory and ethical compliance review.

A brief summary of the clinical trial not exceeding 3 pages. The Synopsis contains aims, objectives, subject enrollment criteria, visits, procedures and statistical aspects of the trial.

An Investigator Brochure (IB) is an analytical document based on preclinical and clinical data on the study product relevant for its human studies. Information on earlier clinical trials of the study product and draft instruction for medical use (Prescribing Information) are required for the IB preparation. The Investigator Brochure is intended to provide information facilitating understanding and compliance with major protocol provisions, such as dose, dosing frequency/periodicity, methods of administration, safety monitoring procedures, for investigators and other parties involved in the study. The IB also provides understanding of the study subjects’ clinical follow-up throughout the course of the clinical trial. The information is provided in a brief, objective, well-balanced non-commercial form, enabling the clinician and potential investigator to understand it and form their own objective opinion on the feasibility of the trial planned based on a risk-benefit ratio.

Case report forms (CRFs) are a medium for collection of the study data in paper form by the study site. Sometimes electronic CRFs are used for the purpose. We develop and deploy eCRFs using our own software. Case Report Forms are used for the following tasks: data collection per Protocol, compliance with regulatory data collection requirements; effective and complete data processing, data analysis and reporting of outcomes; sharing data on safety among investigators and sponsor’s project team. The data collected at the study site during the study must be complete and accurately describe what happened to each patient/volunteer. Only studies meeting these criteria can be considered to yield reliable product efficacy and safety results.

Patient Information Leaflet includes information about the study and informed consent form, both being integral parts of a single document. This document is considered a written agreement of the patient (or his/her legal representative, as provisioned by law) to the conditions of participating in the study. The Patient Information Leaflet includes the following: study title (full protocol title and number), information number and version, headers containing document ID, name of the trial Sponsor, name and contact details of the company conducting the trial in the Russian Federation, contact information of the Ethics Council, Local Ethics Committee, space for dating and signing of the document by the patient and investigator. If there is information and/or references to any supplementary materials for patients in the text of the Patient Information Leaflet, such materials must be appended to the PIL for review. The information must be complete, objective, reliable, it should be written in lay terms and contain clarifications as to the medical terms used. The document is prepared in the Russian language.

Diaries, questionnaires, patient cards etc

We prepare CT reports according to the EEU requirements.

Most phase 1 trials are conducted on healthy volunteers. However, for ethical and safety reasons only patients with the condition being investigated are allowed to participate. As a rule, single ascending doses are used in the first phase 1 trial to assess the tolerability, safety, pharmacokinetics and, if possible, pharmacodynamics of the study product. Study results are usually compared to the preclinical data. Single and multiple doses of the investigational drug may sometimes be used in the same trial. Food and age effects may also be studied, therefore, the first in man trials are the first step of a large study program.

These studies are performed to assess the product effectiveness and safety in patients with a specific condition. Sometimes phase 2 studies are divided into phase 2a and phase 2b. The phase 2 study objectives include acute safety assessment of the investigational product (2a) and evidence of clinical effectiveness of the product and finding the therapeutic dosing level in a group of patients (2b). Phase 2 studies are required to assess the effects of the investigational product. These studies may take from several months to 2 years. Such studies involve hundreds of patients. Most phase 2 clinical trials are randomized (assignment to groups is performed randomly), placebo-controlled (one group of patients receives the investigational product, while patients in the “reference” group receive standard treatment or placebo). Phase 2 trials are usually “blinded” (neither the patient nor the investigator know what product the patient receives). About 1/3 of investigational products pass the first two phases of clinical trials successfully.

Phase 3 trials are performed to assess the effectiveness and safety of the product over the study dose range compared to other drugs. Successful completion of phase 3 trials allows the drug manufacturer to submit it for marketing authorization for large-scale clinical use. As a rule, these are randomized, controlled trials involving 250-1000 and more patients, including patient categories at risk. Phase 3 trials help reveal relatively rare adverse events, product effects in patients with circulation, hepatic, renal failure, and assess interaction of the investigational product to other drugs.

Study phase 4 may be used to assess the following study parameters: various dosages of the product; dosing regimen; interaction with different types of food and/or other drugs; comparative analysis of standard treatment courses; analysis of treatment in different age groups, including different types of patients; pharmacoeconomic aspects of treatment and quality of life; late effects (quality of life, improvement of mortality rates in patients on long-term treatment).

The comparative study of equivalence of pharmacokinetic properties of generic and original products. These studies most commonly involve healthy volunteers.

We write FSA, statistical reports, randomization lists and other accompanying documents for the projects.

We conduct expert evaluation of statistical aspects of CT documentation.

We develop and deploy eCRFs using our own software.

Experience in organization and management of clinical trials