采访嘉宾：

        Professor Joel Tarning, PhD, leads a large and diverse team of 30 people studying clinical pharmacology at the Mahidol-Oxford Tropical Medicine Research Unit (MORU) in Bangkok, Thailand. The main scientific directions within the department are pharmacometric data analysis, bioanalytical method development, drug quantification of clinical study samples, omics-based research and medicine quality. His main research is focused on antimalarial dose-optimisation in vulnerable populations at risk of treatment failure and resistance development, such as children and pregnant women. He was conferred the title Professor of Clinical Pharmacology at the University of Oxford, UK in 2016. Professor Tarning has published >175 peer-reviewed articles, resulting in a total of >10,000 citations. His work on clinical pharmacology of antimalarial drugs have already made an impact on public health and he was awarded the biennial Giorgio Segre Prize from the European Federation for Pharmaceutical Sciences in 2014, the annual Bailey K. Ashford Medal from the American Society for Tropical Medicine and Hygiene in 2019, and the biennial Grahame-Smith Prize from the British Pharmacological Society in 2020 for his research.

采访者：

        Junjie Ding, head of Clinical Pharmacology, AstraZeneca R&D China. In his role, Junjie provided clinical pharmacology (CP) and modelling & simulation (M&S) supports for clinical development of a list of compounds. He has more than 15 years experience in pharmacological M&S. He did 3 years of postdoctoral training on pharmacokinetic-pharmacodynamic (PK-PD) M&S at University of Oxford and led PK-PD analyses in infectious diseases (malaria, tuberculosis and dengue) to investigate exposure-response relationships for a list of compounds. He has published >40 papers in peer-reviewed journals in clinical pharmacology area, including the top journals, such as ‘Clinical Pharmacology & Therapeutics’ and ‘Clinical Pharmacokinetics’.  Currently, Junjie is a vice-chairman of Quantitative Pharmacology Professional Committee, China Pharmacology Society. Before joining AstraZeneca team, Junjie has worked in academia for many years. In 2019 he joined Novartis China and was most recently a scientific and team leader in the CP Department.

Junjie:

Hi, Professor Tarning, thank you so much for acceptance of the invitation of 2021 ISQP. You did a number of clinical pharmacology research on anti-malaria therapies. Although China has eliminated malaria in Middle of 2021, malaria still bring significant disease burden in some regions, like Africa. My first question is regarding the artemisinin resistance. You know the artemisinin resistant malaria is spreading very rapidly through South-east Asian countries and become a big challenge in current malaria treatments. According to your view, how can the pharmacometrics inform the optimal treatment for artemisinin resistant malaria

Joel:

I believe that well-designed and appropriately conducted clinical trials, analysed with an in-depth pharmacometrics approach, is crucial to understand how to treat artemisinin-resistant malaria successfully Only trough characterising the dynamic relationship between drug exposure and parasite killing, in sensitive and drug-resistant infections, can we understand how to treat these infections. Pharmacometric modelling and simulation can provide an evidence based approach to optimal dosing.

Junjie:

I know you have conducted several pooled population PK/PD analyses in anti-malaria treatment, especially in vulnerable population, based on the data in WWARN platform . In your opinion, what is advantage of pooled population PK/PD analysis in anti-malaria therapy. Again, sharing some successful experience about the PK data contribution in WWARN would be great.

Joel:

The WWARN collaboration provides a unique opportunity to pool individual patient level data from multiple clinical trials. In reality, many clinical trials in malaria are underpowered to provide the evidence needed to optimise the dosing in vulnerable groups of patients, such as pregnant women and young children. These groups of patients are not studied extensively and often excluded from clinical trials. Pooling data from several studies allows us to use to gain the power to confidently conclude if dose adjustments are needed or not. Developed pharmacometrics models can then be used to optimise dosing, to improve the treatment of malaria in these groups of patients.

Junjie:

As far as I know, there is no well-defined mechanistic parasite growth model. What is the limitations of current model? What is of most importance for a well-defined model for the anti-malaria drug development?

Joel:

Most of the published parasitic growth models, built on clinical data, are simplified descriptions of the relatively complicated malaria life cycle. One limitation when developing mechanistic parasite growth models are the difficulty in measuring total parasite density. Only infected red blood cell

cells in the circulation can be measured in a blood sample, and we know that as much as 99% of the infected blood cells can adhere to blood vessels during the latter part of the life cycle (i. e sequestration). Another limiting factor is the poor sensitivity associated with microscopy (LOD of 10⁸ parasites) and qPCR(LOD of 10⁶ parasites). Patients with uncomplicated malaria, recruited in standard clinical trials, often have approximately 10¹¹parasites at enrollment. Thus, it is a very small part of the dynamic parasite-time curve that we can observe with the current technology. Furthermore it is very time consuming to generate parasite stage specific observations with microscopy, and not at all possible with qPCR. To have accurate and sensitive, stage-specific, densely collected parasite measurements would certainly help when developing more mechanistic models

Junjie:

You have achieved a lot of great achievements in clinical pharmacology/ pharmacometrics in the field of infectious disease therapeutic area. Would you please share some success cases for your research journey?

Joel:

One of the most rewarding experience has been our work on dose optimisation of antimalarial drugs in young children we used pharmacometric approaches to demonstrate that young children were under-dosed both in the treatment of uncomplicated and severe malaria We used modelling and simulation to optimise dosing in these patients, and managed to propose practical dosing schedules achieving equivalent exposures in young children compared to older children and adults. This work resulted in revised dosing recommendations, with an increased dosing in young children in the 3^rd edition of the WHO Guidelines for the Treatment of Malaria(2015).

Junjie:

Thank you so much for your time for the interview. Very useful information for the audience. We are looking forward to your presentation in the upcoming 2021 ISQP event.

大会报告信息：

大会报告：Pharmacometric considerations in antimalarial drug research

分会主题：分会主题5（传染性疾病新药与疫苗临床开发：临床药理学与定量药理学的应用与挑战）

报告地点：分会场2（定量药理学研究与学科交叉分会场）

黄  钦  博士

        先声药业高级副总裁，原国家药审中心（CDE）生物统计审评部负责人。自1995年起在卫生部临床药理基地、国家疾控中心和国家药审中心从事药物临床研发和审评监管工作25年。曾负责预防性疫苗、肿瘤、消化、精 神、神经和抗生素等领域的化学/生物制品药的临床审评，具有极其丰富的审评经验，是资深高级审评员和主审报告人。2011-2016年负责组建CDE生物统计学审评部并主持工作，建立了统计学审评技术框架和专业要点。主持制定了国家药监局发布的临床审评和统计审评等多个重要法规文件。也是国家药审中心《药物临床试验登记与信息公示平台》的创建者和主要设计人。黄博士是中国临床试验数据管理学组（CDMC）的创始人和首任组长、曾任国际药物协会（DIA）的中国顾问委员会（ACC）成员以及DIA 中国定量科学（QSF）论坛的发起人和首届轮值主席。也曾任北京大学、复旦大学兼职教授。

宋海峰  博士

        军事医学研究院生命组学研究所研究员，博士研究生导师。蛋白质药物国家工程研究中心主任，兼任国家新药审评中心药品注册审评专家咨询委员会委员、中国药学会抗肿瘤药物专业委员会副主任委员、中国生物技术创新服务联盟（ABO）候任执委会主席、抗COVID-19新药特别审评委员会委员等。长期致力于生物技术药物研究与开发，参与制订多项国家新药研究技术指导原则和行业规范。

ISQP重要时间：
        2021年9月30日                优惠注册截止日期
        2021年12月5日-6日         大会正式议程（含现场注册）
        2021年12月7日                东亚论坛（线上会议）
        2021年12月25日-12月4日   会前和会后培训班
大会网站： https://isqp2021.sciconf.cn