Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial

 

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dc.contributor.author Lesosky, Maia
dc.contributor.author Joska, John
dc.contributor.author Decloedt, Eric
dc.date.accessioned 2017-06-13T06:50:10Z
dc.date.available 2017-06-13T06:50:10Z
dc.date.issued 2017-06-07
dc.identifier.citation Lesosky, M., Joska, J., & Decloedt, E. (2017). Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial. Trials, 18(1), 261.
dc.identifier.uri http://dx.doi.org/10.1186/s13063-017-1992-6
dc.identifier.uri http://hdl.handle.net/11427/24567
dc.description.abstract Background: Therapeutic drug monitoring (TDM) is essential practice when dosing drugs with a narrow therapeutic index in order to achieve a plasma drug concentration within a narrow target range above the efficacy concentration but below the toxicity concentration. However, TDM with dose individualisation is challenging during a double-blind clinical trial with laboratory staff and investigators blinded to treatment arm allocation. Methods: Drug concentrations were simulated for participants in the placebo arm by an unblinded independent statistician, utilising the measured values from the treatment arm participants. Simulated and actual concentrations were re-blinded and passed on to a dose-adjusting investigator, who made dose adjustment recommendations but was not directly responsible for clinical care of participants. Results: A total of 257 sham lithium plasma concentrations were simulated utilising 242 true lithium plasma concentrations in real time as the trial progressed. The simulated values had a median (interquartile range) of 0.59 (0.46, 0.72) compared to 0.53 (0.39, 0.72) in the treatment arm. Blinding of the laboratory staff and dose-adjusting investigator was maintained successfully. Conclusions: We succeeded in simulating sham lithium plasma concentrations while maintaining blinding. Our simulated values have a smaller range than the observed data, which can be explained by the challenges with respect to drug adherence and dose timing that were experienced. Trial registration: Pan African Clinical Trials Registry, PACTR201310000635418. Registered on 30 August 2013.
dc.language.iso en
dc.publisher BioMed Central
dc.source Trials
dc.source.uri https://trialsjournal.biomedcentral.com/
dc.subject.other Dose adjustment
dc.subject.other Blinding
dc.subject.other Simulation
dc.title Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial
dc.type Journal Article
dc.date.updated 2017-06-11T03:15:01Z
dc.rights.holder The Author(s).
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Department of Public Health and Family Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Lesosky, M., Joska, J., & Decloedt, E. (2017). Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial. <i>Trials</i>, http://hdl.handle.net/11427/24567 en_ZA
dc.identifier.chicagocitation Lesosky, Maia, John Joska, and Eric Decloedt "Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial." <i>Trials</i> (2017) http://hdl.handle.net/11427/24567 en_ZA
dc.identifier.vancouvercitation Lesosky M, Joska J, Decloedt E. Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial. Trials. 2017; http://hdl.handle.net/11427/24567. en_ZA
dc.identifier.ris TY - Journal Article AU - Lesosky, Maia AU - Joska, John AU - Decloedt, Eric AB - Background: Therapeutic drug monitoring (TDM) is essential practice when dosing drugs with a narrow therapeutic index in order to achieve a plasma drug concentration within a narrow target range above the efficacy concentration but below the toxicity concentration. However, TDM with dose individualisation is challenging during a double-blind clinical trial with laboratory staff and investigators blinded to treatment arm allocation. Methods: Drug concentrations were simulated for participants in the placebo arm by an unblinded independent statistician, utilising the measured values from the treatment arm participants. Simulated and actual concentrations were re-blinded and passed on to a dose-adjusting investigator, who made dose adjustment recommendations but was not directly responsible for clinical care of participants. Results: A total of 257 sham lithium plasma concentrations were simulated utilising 242 true lithium plasma concentrations in real time as the trial progressed. The simulated values had a median (interquartile range) of 0.59 (0.46, 0.72) compared to 0.53 (0.39, 0.72) in the treatment arm. Blinding of the laboratory staff and dose-adjusting investigator was maintained successfully. Conclusions: We succeeded in simulating sham lithium plasma concentrations while maintaining blinding. Our simulated values have a smaller range than the observed data, which can be explained by the challenges with respect to drug adherence and dose timing that were experienced. Trial registration: Pan African Clinical Trials Registry, PACTR201310000635418. Registered on 30 August 2013. DA - 2017-06-07 DB - OpenUCT DO - 10.1186/s13063-017-1992-6 DP - University of Cape Town J1 - Trials LK - https://open.uct.ac.za PB - University of Cape Town PY - 2017 T1 - Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial TI - Simulating therapeutic drug monitoring results for dose individualisation to maintain investigator blinding in a randomised controlled trial UR - http://hdl.handle.net/11427/24567 ER - en_ZA


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