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?

Clin Microbiol Infect. 2020 Aug;26(8):1008-1016. doi: 10.1016/j.cmi.2020.03.008. Epub 2020 Mar 21.

Authors

A-G Märtson¹, M G G Sturkenboom¹, J Stojanova², D Cattaneo³, W Hope⁴, D Marriott⁵, A E Patanwala⁶, C A Peloquin⁷, S G Wicha⁸, T S van der Werf⁹, T Tängdén¹⁰, J A Roberts¹¹, M N Neely¹², J-W C Alffenaar¹³

Affiliations

¹ University of Groningen, University Medical Centre Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands.
² Interdisciplinary Centre for Health Studies (CIESAL), Universidad de Valparaíso, Valparaíso, Chile.
³ ASST Fatebenefratelli Sacco University Hospital, Unit of Clinical Pharmacology, Department of Laboratory Medicine, Milan, Italy.
⁴ University of Liverpool, Antimicrobial Pharmacodynamics and Therapeutics, Liverpool, UK; Royal Liverpool Broadgreen University Hospital Trust, Liverpool, United Kingdom.
⁵ St Vincent's Hospital, Sydney, Australia.
⁶ The University of Sydney, Sydney Pharmacy School, Sydney, New South Wales, Australia; Royal Prince Alfred Hospital, Sydney, Australia.
⁷ Infectious Disease Pharmacokinetics Laboratory, College of Pharmacy, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
⁸ University of Hamburg, Department of Clinical Pharmacy, Institute of Pharmacy, Hamburg, Germany.
⁹ University of Groningen, University Medical Centre Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, the Netherlands; University of Groningen, University Medical Centre Groningen, Department of Internal Medicine, Groningen, the Netherlands.
¹⁰ Uppsala University, Department of Medical Sciences, Uppsala, Sweden.
¹¹ University of Queensland Centre for Clinical Research, Faculty of Medicine & Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Australia; Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia; Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.
¹² Children's Hospital of Los Angeles, Laboratory of Applied Pharmacokinetics and Bioinformatics, Los Angeles, CA, USA.
¹³ University of Groningen, University Medical Centre Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands; The University of Sydney, Sydney Pharmacy School, Sydney, New South Wales, Australia; Westmead Hospital, Sydney, Australia; Marie Bashir Institute of Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia. Electronic address: johannes.alffenaar@sydney.edu.au.

PMID: 32205294
DOI: 10.1016/j.cmi.2020.03.008

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.

Publication types

Review

MeSH terms

Anti-Bacterial Agents / administration & dosage*
Anti-Bacterial Agents / pharmacokinetics
Communicable Diseases / drug therapy*
Drug Dosage Calculations
Drug Monitoring / methods*
Humans
Research Design
Sample Size

Substances

Anti-Bacterial Agents