Precision dosing in clinical medicine: present and future

Polasek, Thomas M.; Shakib, Sepehr; Rostami‐Hodjegan, Amin

doi:10.1080/17512433.2018.1501271

Cited by 69 publications

(62 citation statements)

References 29 publications

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“…For these reasons, tumor heterogeneity, molecular mechanisms of resistance in pretreated patients conferring a complex pattern of mutations, could cause resistance to single targeted agents and could become the final cause of the imprecision of precision medicine. Moreover, Several limitations could also derive from pharmacodynamic or kinetic aspects that could cause inter-and intraindividual variability, limiting the use of targeted agents such as gender, weight, ethnicity, and renal and hepatic functions [69]. A precision approach could be difficultly adopted when a patient presents more than one factor which could interfere with drug exposure or response.…”

Section: Limitations Of Molecular Driven Treatments In the Clinicmentioning

confidence: 99%

Personalized Medicine: Recent Progress in Cancer Therapy

Gambardella

Tarazona

Cejalvo

et al. 2020

Cancers

191

100

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Translational research has revolutionized how we develop new treatments for cancer patients. The change from an organ-centric concept guiding treatment choice towards deep molecular analysis, driving a personalized approach, is one of the most important advances of modern oncology. Several tools such as next generation sequencing and RNA sequencing have greatly improved the capacity to detect predictive and prognostic molecular alterations. Detection of gene mutations, amplifications, and fusions has therefore altered the history of several diseases in both a localized and metastatic setting. This shift in perspective, in which attention is focused on the specific molecular alterations of the tumor, has opened the door to personalized treatment. This situation is reflected in the increasing number of basket trials selecting specific molecular targets. Nonetheless, some weaknesses need to be addressed. The complexity of cancer cells enriched with concomitant molecular alterations complicates identification of the driver. Moreover, tumor heterogeneity could be responsible for the lack of benefit when targeted agents are used. In light of this, there is growing interest in the role of multidisciplinary committees or molecular tumor boards to try to enhance selection. The aim of this review is to critically analyze the evolution of cancer treatment towards a precision approach, underlining some recent successes and unexpected failures.

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Section: Limitations Of Molecular Driven Treatments In the Clinicmentioning

confidence: 99%

Personalized Medicine: Recent Progress in Cancer Therapy

Gambardella

Tarazona

Cejalvo

et al. 2020

Cancers

191

100

View full text Add to dashboard Cite

show abstract

“…Bayesian guided dosing has shown excellent predictive performance in various clinical studies though estimation methods heavily rely on the availability and accuracy of population PK models (de Jonge et al, 2004;Mar Fernández de Gatta et al, 2009). For patients lacking sufficient data to inform population PK models, PBPK/PD models may be useful as dose predictions are mechanistic-based and derived from known impacts of organ/tissue function on PK/PD, though significant understanding of the metabolism and in vitro preclinical data is required for accuracy (Polasek et al, 2018). PBPK/PD modeling offers the advantage of drawing from human physiology, drug physicochemical properties, and enzyme/ protein variability in patients to individualize dosing and has been successfully used in estimating drug exposure (Gonzalez et al, 2017;Polasek et al, 2019).…”

Section: Pk/pd Variabilitymentioning

confidence: 99%

Precision Dosing Priority Criteria: Drug, Disease, and Patient Population Variables

et al. 2020

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The administered dose of a drug modulates whether patients will experience optimal effectiveness, toxicity including death, or no effect at all. Dosing is particularly important for diseases and/or drugs where the drug can decrease severe morbidity or prolong life. Likewise, dosing is important where the drug can cause death or severe morbidity. Since we believe there are many examples where more precise dosing could benefit patients, it is worthwhile to consider how to prioritize drug-disease targets. One key consideration is the quality of information available from which more precise dosing recommendations can be constructed. When a new more precise dosing scheme is created and differs significantly from the approved label, it is important to consider the level of proof necessary to either change the label and/or change clinical practice. The cost and effort needed to provide this proof should also be considered in prioritizing drug-disease precision dosing targets. Although precision dosing is being promoted and has great promise, it is underutilized in many drugs and disease states. Therefore, we believe it is important to consider how more precise dosing is going to be delivered to high priority patients in a timely manner. If better dosing schemes do not change clinical practice resulting in better patient outcomes, then what is the use? This review paper discusses variables to consider when prioritizing precision dosing candidates while highlighting key examples of precision dosing that have been successfully used to improve patient care.

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“…Clinical pharmacology can also be applied in direct patient care by personalizing medicine for patients. Tools such as therapeutic drug monitoring (TDM), PGx and Model Informed Precision Dosing can be used to optimize dosing for patients at an individual level ( Roberts et al, 2014 , Polasek et al, 2019 , Polasek et al, 2018 , Gonzalez et al, 2017 , Perera et al, 2014 , Standing, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Clinical pharmacology applications in clinical drug development and clinical care: A focus on Saudi Arabia

Alsultan

Alghamdi

et al. 2020

Saudi Pharmaceutical Journal

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Drug development, from preclinical to clinical studies, is a lengthy and complex process. There is an increased interest in the Kingdom of Saudi Arabia (KSA) to promote innovation, research and local content including clinical trials (Phase I-IV). Currently, there are over 650 registered clinical trials in Saudi Arabia, and this number is expected to increase. An important part of drug development and clinical trials is to assure the safe and effective use of drugs. Clinical pharmacology plays a vital role in informed decision making during the drug development stage as it focuses on the effects of drugs in humans. Disciplines such as pharmacokinetics, pharmacodynamics and pharmacogenomics are components of clinical pharmacology. It is a growing discipline with a range of applications in all phases of drug development, including selecting optimal doses for Phase I, II and III studies, evaluating bioequivalence and biosimilar studies and designing clinical studies. Incorporating clinical pharmacology in research as well as in the requirements of regulatory agencies will improve the drug development process and accelerate the pipeline. Clinical pharmacology is also applied in direct patient care with the goal of personalizing treatment. Tools such as therapeutic drug monitoring, pharmacogenomics and model informed precision dosing are used to optimize dosing for patients at an individual level. In KSA, the science of clinical pharmacology is underutilized and we believe it is important to raise awareness and educate the scientific community and healthcare professionals in terms of its applications and potential. In this review paper, we provide an overview on the use and applications of clinical pharmacology in both drug development and clinical care.

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Precision dosing in clinical medicine: present and future

Cited by 69 publications

References 29 publications

Personalized Medicine: Recent Progress in Cancer Therapy

Personalized Medicine: Recent Progress in Cancer Therapy

Precision Dosing Priority Criteria: Drug, Disease, and Patient Population Variables

Clinical pharmacology applications in clinical drug development and clinical care: A focus on Saudi Arabia

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