How to design a study to evaluate therapeutic drug monitoring in infectious diseases?

A. G. Märtson; M. G.G. Sturkenboom; J. Stojanova; D. Cattaneo; W. Hope; D. Marriott; A. E. Patanwala; C. A. Peloquin; S. G. Wicha; T. S. van der Werf; T. Tängdén; J. A. Roberts; M. N. Neely; J. W.C. Alffenaar

doi:10.1016/j.cmi.2020.03.008

How to design a study to evaluate therapeutic drug monitoring in infectious diseases?

A. G. Märtson, M. G.G. Sturkenboom, J. Stojanova, D. Cattaneo, W. Hope, D. Marriott, A. E. Patanwala, C. A. Peloquin, S. G. Wicha, T. S. van der Werf, T. Tängdén, J. A. Roberts, M. N. Neely, J. W.C. Alffenaar

Pharmacy Practice and Science

Research output: Contribution to journal › Review article › peer-review

29 Scopus citations

Abstract

Background: Therapeutic drug monitoring (TDM) is a tool to personalize and optimize dosing by measuring the drug concentration and subsequently adjusting the dose to reach a target concentration or exposure. The evidence to support TDM is however often ranked as expert opinion. Limitations in study design and sample size have hampered definitive conclusions of the potential added value of TDM. Objectives: We aim to give expert opinion and discuss the main points and limitations of available data from antibiotic TDM trials and emphasize key elements for consideration in design of future clinical studies to quantify the benefits of TDM. Sources: The sources were peer-reviewed publications, guidelines and expert opinions from the field of TDM. Content: This review focuses on key aspects of antimicrobial TDM study design: describing the rationale for a TDM study, assessing the exposure of a drug, assessing susceptibility of pathogens and selecting appropriate clinical endpoints. Moreover we provide guidance on appropriate study design. Implications: This is an overview of different aspects relevant for the conduct of a TDM study. We believe that this paper will help researchers and clinicians to design and conduct high-quality TDM studies.

Original language	English (US)
Pages (from-to)	1008-1016
Number of pages	9
Journal	Clinical Microbiology and Infection
Volume	26
Issue number	8
DOIs	https://doi.org/10.1016/j.cmi.2020.03.008
State	Published - Aug 2020

Keywords

Drug exposure
Personalized dosing study design
Pharmacodynamics
Pharmacokinetics
Randomized controlled trials
Therapeutic drug monitoring

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases

Access to Document

10.1016/j.cmi.2020.03.008

Cite this

Märtson, A. G., Sturkenboom, M. G. G., Stojanova, J., Cattaneo, D., Hope, W., Marriott, D., Patanwala, A. E., Peloquin, C. A., Wicha, S. G., van der Werf, T. S., Tängdén, T., Roberts, J. A., Neely, M. N., & Alffenaar, J. W. C. (2020). How to design a study to evaluate therapeutic drug monitoring in infectious diseases? Clinical Microbiology and Infection, 26(8), 1008-1016. https://doi.org/10.1016/j.cmi.2020.03.008

Märtson, AG, Sturkenboom, MGG, Stojanova, J, Cattaneo, D, Hope, W, Marriott, D, Patanwala, AE, Peloquin, CA, Wicha, SG, van der Werf, TS, Tängdén, T, Roberts, JA, Neely, MN & Alffenaar, JWC 2020, 'How to design a study to evaluate therapeutic drug monitoring in infectious diseases?', Clinical Microbiology and Infection, vol. 26, no. 8, pp. 1008-1016. https://doi.org/10.1016/j.cmi.2020.03.008

@article{f06483c8322045629311be6d63bf3b14,

title = "How to design a study to evaluate therapeutic drug monitoring in infectious diseases?",

abstract = "Background: Therapeutic drug monitoring (TDM) is a tool to personalize and optimize dosing by measuring the drug concentration and subsequently adjusting the dose to reach a target concentration or exposure. The evidence to support TDM is however often ranked as expert opinion. Limitations in study design and sample size have hampered definitive conclusions of the potential added value of TDM. Objectives: We aim to give expert opinion and discuss the main points and limitations of available data from antibiotic TDM trials and emphasize key elements for consideration in design of future clinical studies to quantify the benefits of TDM. Sources: The sources were peer-reviewed publications, guidelines and expert opinions from the field of TDM. Content: This review focuses on key aspects of antimicrobial TDM study design: describing the rationale for a TDM study, assessing the exposure of a drug, assessing susceptibility of pathogens and selecting appropriate clinical endpoints. Moreover we provide guidance on appropriate study design. Implications: This is an overview of different aspects relevant for the conduct of a TDM study. We believe that this paper will help researchers and clinicians to design and conduct high-quality TDM studies.",

keywords = "Drug exposure, Personalized dosing study design, Pharmacodynamics, Pharmacokinetics, Randomized controlled trials, Therapeutic drug monitoring",

author = "M{\"a}rtson, {A. G.} and Sturkenboom, {M. G.G.} and J. Stojanova and D. Cattaneo and W. Hope and D. Marriott and Patanwala, {A. E.} and Peloquin, {C. A.} and Wicha, {S. G.} and {van der Werf}, {T. S.} and T. T{\"a}ngd{\'e}n and Roberts, {J. A.} and Neely, {M. N.} and Alffenaar, {J. W.C.}",

note = "Funding Information: Jason Roberts reports personal fees from MSD, grants and personal fees from Pfizer, grants and personal fees from Biomerieux, personal fees from Accelerate Diagnostics, outside the submitted work. Michael Neely reports other fees from InsightRX, outside the submitted work. Sebastian Wicha reports grants from Boehringer Ingelheim Pharma, personal fees from UTILITY Therapeutics, personal fees from Medicines for Malaria Venture, personal fees from Bayer Healthcare, outside the submitted work.Anne-Grete M{\"a}rtson was funded by Marie Sk{\l}odowska-Curie Actions (grant agreement no. 713660 —PRONKJEWAIL—H2020-MSCA-COFUND-2015). Jason Roberts would like to acknowledge funding for a NHMRC Centre of Research Excellence ( APP1099352 ) and a Practitioner Fellowship ( APP1117065 ). Funding Information: Jason Roberts reports personal fees from MSD, grants and personal fees from Pfizer, grants and personal fees from Biomerieux, personal fees from Accelerate Diagnostics, outside the submitted work. Michael Neely reports other fees from InsightRX, outside the submitted work. Sebastian Wicha reports grants from Boehringer Ingelheim Pharma, personal fees from UTILITY Therapeutics, personal fees from Medicines for Malaria Venture, personal fees from Bayer Healthcare, outside the submitted work.Anne-Grete M?rtson was funded by Marie Sk?odowska-Curie Actions (grant agreement no. 713660?PRONKJEWAIL?H2020-MSCA-COFUND-2015). Jason Roberts would like to acknowledge funding for a NHMRC Centre of Research Excellence (APP1099352) and a Practitioner Fellowship (APP1117065). Publisher Copyright: {\textcopyright} 2020 European Society of Clinical Microbiology and Infectious Diseases",

year = "2020",

month = aug,

doi = "10.1016/j.cmi.2020.03.008",

language = "English (US)",

volume = "26",

pages = "1008--1016",

journal = "Clinical Microbiology and Infection",

issn = "1198-743X",