Mentoring in Clinical Pharmacology and Early Phase Trials

临床药理学和早期试验的指导

• 批准号: 10620632
• 负责人: Michael Cohen-Wolkowiez
• 金额: $ 17.77万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-10 至 2024-11-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10620632
• 关键词: Adult; Age; Anti-Infective Agents; Award; Biometry; Career Mobility; Child; Childhood; Clinical Pharmacology; Clinical Research; Clinical Trials; Clinical Trials Network; Clinical Trials Unit; Cohort Studies; Committee Members; Contracts; Data; Data Analyses; Data Set; Development; Doctor of Philosophy; Dose; Drug usage; Educational Status; Elderly; Ensure; Extramural Activities; Faculty; Fellowship; Funding; Funding Mechanisms; Future; Goals; Health Sciences; Individual; Infrastructure; Institution; Investigation; Knowledge; Label; Lead; Licensing; Longevity; Medical; Medicine; Mentors; Mentorship; Methods; Modeling; National Institute of Allergy and Infectious Disease; National Institute of Child Health and Human Development; North Carolina; Pathway interactions; Pediatrics; Peer Review; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Pharmacy Schools; Phase; Phase I Clinical Trials; Physicians; Physiology; Population; Positioning Attribute; Pregnant Women; Public Health; Publications; Research; Research Infrastructure; Research Institute; Research Personnel; Research Project Grants; Research Support; Resources; Role; Safety; Science; Scientist; Secure; Services; Therapeutic Agents; Time; Training; Training Programs; Training and Infrastructure; United States National Institutes of Health; Universities; Vulnerable Populations; Work; antimicrobial; base; career; career development; data management; drug development; drug efficacy; early phase trial; educational atmosphere; expectation; experience; improved; interest; investigator training; mid-career faculty; next generation; patient oriented research; pediatric department; pediatrician; pharmacokinetics and pharmacodynamics; professor; programs; recruit; skill acquisition; skills; success; trial design

Historically, >50% of drugs have insufficient labeling to inform physicians on dosing, safety, or efficacy in vulnerable populations including children, pregnant women, and the elderly. Mechanisms requiring the study of new products in vulnerable populations are relatively new and highlight a training gap in junior scientists related to the investigation of therapeutic agents. There is an urgent need for well-trained adult and pediatric investigators with quantitative research skills in clinical pharmacology and clinical trials. In this award, the investigator, Michael Cohen-Wolkowiez, MD, PhD, will prepare adult and pediatric junior scientists for a career in patient-oriented research to bridge this gap in accordance with his own long-term research goals: to improve drug development by establishing proper dosing, safety, and efficacy of drugs used in vulnerable populations. To date, Dr. Cohen-Wolkowiez has achieved early success in training beginning scientists by leveraging every research mechanism for training in clinical pharmacology and clinical trials. Most of these research projects and trainees have been focused on anti-infectives. In this award, he will further expand his training program to include more adult trainees and use several research infrastructures for training. These include funding mechanisms such as the NIAID Phase 1 Clinical Trial Unit (P1CTU) of Anti-Infectives contract, the Pediatric Trials Network (PTN), and the FDA Global Pediatric Clinical Trials Network (GPCTN). The NIAID-sponsored P1CTU is a 10-year contract to conduct early phase studies of anti-infectives at the Duke Phase 1 Clinical Research Unit, which he directs. The NICHD-sponsored PTN, for which the applicant is an Executive Committee Member and PI of several clinical trials within the network, has ~30 ongoing clinical trials that the applicant has used for training of junior investigators. Through this mechanism, the candidate has successfully developed four young investigators who have secured their own NIH funding. The FDA-sponsored GPCTN is a recent mechanism that aims to provide pediatric clinical trial infrastructure to conduct studies for labeling. Additional strengths of Dr. Cohen-Wolkowiez program include the unparalled research infrastructure of the Duke Clinical Research Institute, and a longstanding academic partnership with the renowned University of North Carolina School of Pharmacy. Through this integral partnership, Dr. Cohen-Wolkowiez serves as the Duke Fellowship director of an NIH-sponsored T-32 clinical pharmacology fellowship training program and a pathway for junior investigators to secure PhD or Masters level training in clinical pharmacology.Trainees in clinical pharmacology and clinical trials will be recruited at Duke University to lead research projects. Specifically, the proposed studies, will offer mentees the opportunity to capitalize on the diverse research program that Dr. Cohen-Wolkowiez has developed. Feasibility of the proposed award is shown by Dr. Cohen- Wolkowiez' early success in funding and career development of current trainees at Duke and UNC and by trainees' publication track record; >80 peer-reviewed articles with trainees as first author.

从历史上看，>50%的药物没有足够的标签来告知医生剂量，安全性或有效性， 包括儿童、孕妇和老年人在内的弱势群体。需要研究的机制 针对弱势群体的新产品相对较新，突出了初级科学家的培训缺口 与治疗剂的研究有关。迫切需要训练有素的成人和儿童 具有临床药理学和临床试验定量研究技能的研究者。在这个奖项中， 调查员，迈克尔科恩-沃尔克维兹，医学博士，博士，将准备成人和儿科初级科学家的职业生涯 在以病人为导向的研究，以弥合这一差距，按照他自己的长期研究目标：提高 通过确定用于弱势群体的药物的适当剂量、安全性和有效性来开发药物。 到目前为止，科恩-沃尔克维兹博士已经取得了早期的成功，培训开始科学家利用每一个 临床药理学和临床试验培训的研究机制。大多数研究项目 而受训人员则专注于抗感染药物。在这个奖项中，他将进一步扩大他的培训计划， 包括更多成年受训人员，并利用若干研究基础设施进行培训。其中包括资金 机制，如NIAID第1阶段临床试验单位（P1 CTU）的抗过敏药合同，儿科 试验网络（PTN）和FDA全球儿科临床试验网络（GPCTN）。NIAID赞助的 P1 CTU是一份为期10年的合同，在杜克1期临床试验中进行抗感染药物的早期研究。 他领导的研究小组。NICHD赞助的PTN，申请人是其执行人员 委员会成员和网络内多项临床试验的PI，有约30项正在进行的临床试验， 申请人用于初级研究者的培训。通过这一机制，候选人成功地 培养了四名年轻的研究人员，他们已经获得了自己的NIH资金。FDA赞助的GPCTN是一个 最近的机制，旨在提供儿科临床试验基础设施，以进行标签研究。 Cohen-Wolkowiez博士计划的其他优势包括美国大学无与伦比的研究基础设施。 杜克临床研究所，并与著名的牛津大学建立了长期的学术合作伙伴关系。 北卡罗来纳州药学院。通过这种不可分割的伙伴关系，科恩-沃尔克维兹博士担任 杜克奖学金主任NIH赞助的T-32临床药理学奖学金培训计划和 初级研究者获得临床药理学博士或硕士水平培训的途径。 临床药理学和临床试验将在杜克大学招聘领导研究项目。 具体而言，拟议的研究将为学员提供利用各种研究的机会。 科恩-沃尔科维兹博士开发的一个项目科恩博士证明了拟议裁决的可行性- 沃尔克维兹在杜克和杜克大学为目前的学员提供资金和职业发展方面取得的早期成功， 受训人员的出版记录;以受训人员为第一作者的同行评审文章超过80篇。

项目成果

Physiologically Based Pharmacokinetic Modeling for Trimethoprim and Sulfamethoxazole in Children.

基于生理学的儿童甲氧苄啶和磺胺甲恶唑药代动力学模型。

• DOI: 10.1007/s40262-018-00733-1
• 发表时间: 2019
• 期刊: Clinical pharmacokinetics
• 影响因子: 4.5
• 作者: Thompson,ElizabethJ;Wu,Huali;Maharaj,Anil;Edginton,AndreaN;Balevic,StephenJ;Cobbaert,Marjan;Cunningham,AnthonyP;Hornik,ChristophP;Cohen-Wolkowiez,Michael
• 通讯作者: Cohen-Wolkowiez,Michael

External Evaluation of Two Pediatric Population Pharmacokinetics Models of Oral Trimethoprim and Sulfamethoxazole.

口服甲氧苄啶和磺胺甲恶唑的两种儿童群体药代动力学模型的外部评价。

• DOI: 10.1128/aac.02149-20
• 发表时间: 2021
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Wu,YiShuanS;Cohen-Wolkowiez,Michael;Hornik,ChristophP;Gerhart,JacquelineG;Autmizguine,Julie;Cobbaert,Marjan;Gonzalez,Daniel;BestPharmaceuticalsforChildrenAct—PediatricTrialsNetworkSteeringCommittee
• 通讯作者: BestPharmaceuticalsforChildrenAct—PediatricTrialsNetworkSteeringCommittee

RADx-UP Testing Core: Access to COVID-19 Diagnostics in Community-Engaged Research with Underserved Populations.

• DOI: 10.1128/jcm.00367-23
• 发表时间: 2023-08-23
• 期刊: JOURNAL OF CLINICAL MICROBIOLOGY
• 影响因子: 9.4
• 作者: Narayanasamy, Shanti;Veldman, Timothy H.;Lee, Mark J.;Glover II, William A.;Tillekeratne, L. Gayani;Neighbors, Coralei E.;Harper, Barrie;Raghavan, Vidya;Kennedy, Scott W.;Carper, Miranda;Denny, Thomas;Tsalik, Ephraim L.;Reller, Megan E.;Kibbe, Warren A.;Corbie, Giselle;Cohen-Wolkowiez, Michael;Woods, Christopher W.;Petti, Cathy A.
• 通讯作者: Petti, Cathy A.

A Dried Blood Spot Analysis for Solithromycin in Adolescents, Children, and Infants: A Short Communication.

青少年、儿童和婴儿中索利霉素的干血斑分析：简短的交流。

• DOI: 10.1097/ftd.0000000000000670
• 发表时间: 2019
• 期刊: Therapeutic drug monitoring
• 影响因子: 2.5
• 作者: Beechinor,RyanJ;Cohen-Wolkowiez,Michael;Jasion,Theresa;Hornik,ChristophP;Lang,JasonE;Hernandez,Robert;Gonzalez,Daniel
• 通讯作者: Gonzalez,Daniel

A Pharmacoepidemiologic Study of the Safety and Effectiveness of Clindamycin in Infants.

克林霉素在婴儿中的安全性和有效性的药物流行病学研究。

• DOI: 10.1097/inf.0000000000002524
• 发表时间: 2020
• 期刊: The Pediatric infectious disease journal
• 作者: Greenberg,RachelG;Wu,Huali;Maharaj,Anil;Cohen-Wolkowiez,Michael;Tomashek,KayM;Osborn,BlaireL;Clark,ReeseH;Walter,EmmanuelB
• 通讯作者: Walter,EmmanuelB