Abstract
Accumulation of knowledge on Crohn’s disease, and development of biological products intended for the treatment of its underlying cause formed the basis for the development of objective methods for assessing the intensity of the pathological process, which in turn affected scientific approaches to the planning of clinical trials in this field. To date, many international recommendations related to planning, conduct of clinical trials, and analysis of their results, have been updated. Considerable experience has been gained with clinical trials of medicines intended for the treatment of Crohn’s disease. Therefore, the methodological approach to the planning of pivotal clinical studies needs to be reviewed. The aim of the study was to develop requirements for planning and expert evaluation of clinical trials conducted with the aim of obtaining marketing authorisation for medicinal products for the treatment of Crohn’s disease. The paper analyses regulations, recommendations, and scientific literature on the treatment of Crohn’s disease and describes the methodology for planning clinical trials. It describes the evolution of approaches to clinical research planning since biological medicines appeared. The authors substantiate the need for an integrated concept of clinical research, which covers goals, estimated therapeutic effect, design, and choice of the statistical analysis method. They also provide scientific arguments in favour of a combined primary endpoint including endoscopic remission and the assessment of treatment results by the patient. The paper lists patient eligibility criteria in terms of “inducing and/or maintaining remission of the disease”. The authors analyse the main intercurrent events, their influence on the therapeutic effect, and propose approaches to the planning of endpoints, including assessment of intercurrent events. The paper highlights the fact that the principles of planning and conducting Phase III clinical trials need to be consistent with the evidence-based strategies of reducing the risk of incorrect assessment of efficacy and safety of new medicines, and that the obtained results have to meet the requirements of the regulatory authorities at the stage of marketing authorisation.
Highlights
Accumulation of knowledge on Crohn’s disease, and development of biological products intended for the treatment of its underlying cause formed the basis for the development of objective methods for assessing the intensity of the pathological process, which in turn affected scientific approaches to the planning of clinical trials in this field
V. 10, No 2 and conducting Phase III clinical trials need to be consistent with the evidence-based strategies of reducing the risk of incorrect assessment of efficacy and safety of new medicines, and that the obtained results have to meet the requirements of the regulatory authorities at the stage of marketing authorisation
Article was received 21 October 2019 Revised 25 May 2020 Accepted for publication 28 May 2020
Summary
Целями лечения БК являются достижение и поддержание симптоматической и эндоскопической ремиссии [8]. В настоящее время накоплены данные о том, что у многих пациентов с БК продолжается активный процесс воспаления слизистой оболочки даже при отсутствии клинических проявлений и симптоматики [9]. Фазы лечения были разделены на индукцию и поддержание ремиссии. Однако накопленные на сегодняшний день научные данные не подтверждают возможности достижения ремиссии с помощью ГКС, так как свидетельствуют о том, что эти препараты неэффективны для применения в целях заживления слизистой оболочки ЖКТ [12, 13]. Традиционные иммунодепрессанты, которые также применяются в терапии БК, как правило, не подходят для индукции быстрого ответа на терапию, но способствуют поддержанию ремиссии, достигнутой с помощью других лекарственных препаратов. Тем не менее разделение на фазы лечения не потеряло свою актуальность и немаловажно, в частности, для разработки новых лекарственных средств, имеющих отложенное начало действия либо вызывающих нежелательные реакции при долговременном применении. Такие ЛП могут иметь показания к применению на одной из фаз лечения БК
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