[site. View] Ji Wei: control key elements to avoid clinical design and implementation risks

There are five stages in the clinical research of new drugs, which are summarized as preclinical research (Basic Research), PK and safety research (clinical phase I), preliminary efficacy confirmation (clinical phase II), confirmatory research (clinical phase III), and post marketing research (clinical phase IV) It is a process of long period and high investment cost Therefore, the accuracy of efficacy is guaranteed at each stage It is very important to control the degree of risk "Clinical development is a very brain burning and money burning process How to reduce the development risk mainly lies in the control of two processes, clinical research design process and clinical research implementation process." Dr Ji Wei, vice president of medicine of Beijing Spring Pharmaceutical Technology Development Co., Ltd., shared his views on the 2019 China Pharmaceutical Health Industry Development Conference and the 4th China Pharmaceutical R & D Innovation Summit How to control the risk of brain burn? Classic cases inspire innovative ideas and avoid the risk of clinical design to refer to clinical research First of all, several basic problems in clinical research should be clarified, namely, research population, biomarkers, control group, treatment group and main research endpoints The end point as like as two peas of Talazoparib, Olaparib, Niraparib and three drugs, their research endpoints are the same From the treatment group, three drugs are all single drug treatment, and the standard treatment is decided by the control group From the statistical point of view, three drug statistics are different, Talazoparib research is more conservative, PFS has increased from 5.6 months to 8.6 Months, up 3 months; olaparib increased from 4.2 months to 7 months, up 2.8 months to reach the clinical end point With a successful example, is it more successful? What are the problems of developing drugs with the same mechanism? This is the second most important issue In fact, from the clinical research of gbrca + BC, the cost of monitoring is huge If we get 10000 cases by 3%, it will cost 30 million The clinical application ability is very high, and the total cycle is long In addition, there are few patients in the group, because this disease is not a conventional treatment disease in clinical treatment Therefore, most of the experts in the comprehensive evaluation and research, at the beginning of the new drug clinical design, have avoided the risks encountered by the first listed and selected the best design In addition to listing successful experiments, Dr Ji Wei also listed three failure cases, as well as completely independent innovation experiment cases For example, onartuzumab, both indications failed in phase III clinical; riloumab failed in phase III clinical treatment of lung cancer, ficlatuzumab stopped in phase II What is the cause of their failure? Is the access not work? As for met gene, there is overexpression of met, and IHC monitoring publication rate is relatively high, more than 50% or even 60% in lung cancer, and gene amplification is also much less; in fact, it is not that the pathway does not work, but that met selection is wrong, which leads to such failure Only by summing up the experience and lessons of previous failures can we avoid detours and reduce unnecessary risks 02 how to control the risk in the process of burning money? In addition to the process of brain burn, there is also a need to control the risk of the process of money burn The process of burning money is mainly the stage of clinical research implementation, which is manifested in two aspects: one is the standard of entry and discharge, the other is the evaluation of curative effect No matter how good the realization of PFS is, the evaluation of curative effect is very important In order to know whether the standards are the same, Dr Ji Wei's team investigated 70 research centers in large, middle and lower cities, including third tier cities It was found that no matter how small the trials are, there are teamworks, including research doctors (Research doctors come from clinicians, with clinical knowledge structure), data managers, statisticians, data management, CRA, CRC, PM, etc So how to look at clinical experiments from the perspective of research doctors is a concern of Dr Ji Wei's team It was found that the research doctors were concerned about two issues: the standard scheme and at least one measurable focus, complying with the measurement requirements of the target focus, and verifying medical data In addition, in controlling the risk of clinical research implementation stage, efficacy evaluation is indispensable The evaluation criteria are divided into complete remission, partial remission, disease stability, and disease progress, which are calculated according to the calculation principle and time tracing principle to ensure the scientificity and accuracy of efficacy analysis data The most important thing for the research center is to follow the program, follow the program, revise the details, not separate from the program and treat at will; record the data in time to ensure the accuracy of the data Only by controlling the content elements can we avoid risks In a word, in a word, only when you know yourself and your enemy can you win every battle Statement: this opinion only represents the author, not the position of yaozhi.com, welcome to exchange and supplement in the message area; if you need to reprint, please be sure to indicate the author and source of the article.