Pharmacogenomics – how close/far are we to practising individualized medicine for children?

Sing, Chor‐Wing; Cheung, Ching‐Lung; Wong, Ian C. K.

doi:10.1111/bcp.12338

Cited by 14 publications

(27 citation statements)

References 59 publications

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“…In other words, physicians would receive support from education, guidelines and computational tools, all integrated in 1 programme. An example is the translational pharmacogenomic programme led by St Jude Children's Research Hospital (St Jude, Memphis, TN, USA), where PG4KDS is a project aimed at evaluating PGx test results in children and selectively choosing the tests that have strong evidence and closely linking them to drug response, in order to incorporate them into patient medical records . Although other such initiatives are already in place, albeit only in countries with very high HDI, further collaborations and communications between PGx experts and healthcare professionals are needed.…”

Section: Discussionmentioning

confidence: 99%

Implementation and obstacles of pharmacogenetics in clinical practice: An international survey

Diwan

Zeitoun

Haidar

et al. 2019

Brit J Clinical Pharma

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Aims Eight years ago, a paper‐based survey was administered during the World Pharma 2010 meeting, asking about the challenges of implementing pharmacogenetics (PGx) in clinical practice. The data collected at the time gave an idea about the progress of this implementation and what still needs to be done. Since then, although there have been major initiatives to push PGx forward, PGx clinical implementation may still be facing different challenges in different parts of the world. Our aim was therefore to distribute a follow‐up international survey in electronic format to elucidate an overview on the current stage of implementation, acceptance and challenges of PGx in academic institutions around the world. Methods This is an online anonymous LimeSurvey‐based study launched on 11 November 2018. Survey questions were adapted from the initially published manuscript in 2010. An extensive web search for worldwide scientists potentially involved in PGx research resulted in a total of 1973 names. Countries were grouped based on the Human Development Index. Results There were 204 respondents from 43 countries. Despite the wide availability of PGx tests, the consistently positive attitude towards their applications and advances in the field, progress of the clinical implementation of PGx still faces many challenges all around the globe. Conclusions Clinical implementation of PGx started over a decade ago but there is a gap in progress around the globe and discrepancies between the challenges reported by different countries, despite some challenges being universal. Further studies on ways to overcome these challenges are warranted.

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Section: Discussionmentioning

confidence: 99%

Implementation and obstacles of pharmacogenetics in clinical practice: An international survey

Diwan

Zeitoun

Haidar

et al. 2019

Brit J Clinical Pharma

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“…30,37,38 Implementing pharmacogenetic testing for certain gene-drug pairs has been challenging, especially in a pediatric setting. 39 The objective of the present study was to conduct a pilot study of genotype-guided dosing of PPIs based on CYP2C19 metabolizer phenotype in pediatric patients to evaluate the feasibility for a larger multisite clinical trial. To determine implementation fidelity, we investigated the prescribed PPI dose as a measure of acceptance of the genotype-guided recommendation.…”

Section: What Does This Study Add To Our Knowledge?mentioning

confidence: 99%

“…Indeed, several authors have recommended genotype‐guided PPI dosing to avoid treatment failures and adverse events . Implementing pharmacogenetic testing for certain gene‐drug pairs has been challenging, especially in a pediatric setting . The objective of the present study was to conduct a pilot study of genotype‐guided dosing of PPIs based on CYP2C19 metabolizer phenotype in pediatric patients to evaluate the feasibility for a larger multisite clinical trial.…”

mentioning

confidence: 99%

Novel Implementation of Genotype‐Guided Proton Pump Inhibitor Medication Therapy in Children: A Pilot, Randomized, Multisite Pragmatic Trial

Cicali

Blake

Gong

et al. 2018

Clinical Translational Sci

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The efficacy of proton pump inhibitor (PPI) medications is highly dependent on plasma concentrations, which varies considerably due to cytochrome P450 ( CYP2C19 ) genetic variation. We conducted a pragmatic, pilot study of CYP2C19 genotype‐guided pediatric dosing of PPI medications. Children aged 5–17 years old with gastric‐acid‐related conditions were randomized to receive either conventional dosing of a PPI or genotype‐guided dosing for a total of 12 weeks. Sixty children (30 in each arm) were enrolled and had comparable baseline characteristics. The mean daily omeprazole equivalent dose prescribed to participants across metabolizer phenotype groups was significantly different in the genotype‐guided dosing arm ( P < 0.001), but not in the conventional dosing arm. Prescribers waited for the genotype result before prescribing the PPI medication for 90% of the participants in the genotype‐guided dosing arm. The number of participants who reported an infection was marginally lower in genotype‐guided dosing vs. conventional dosing (20% vs. 44%; P = 0.07). Sinonasal symptoms were higher in the conventional dosing arm as compared with genotype‐guided dosing arm: (2.6 (2.0, 3.4) vs. 1.8 (1.0, 2.3), P = 0.031). CYP2C19 genotype‐guided PPI therapy is feasible in a clinical pediatric setting, well accepted by providers, resulted in differential PPI dosing, and may reduce PPI‐associated infections. A future large scale randomized clinical trial of CYP2C19 genotype‐guided pediatric dosing of PPI medications in children is warranted.

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“…When deciding on suitable dosing, other aspects which may have an impact on the PKPD of a drug product in an individual child must be considered as well, e.g. genetic variability (24,25), maturity of enzymatic systems involved in metabolism (26), concomitant drug use and coexisting diseases (27,28), hypothermic treatment procedures (29,30), obesity (31).…”

Section: Paediatric Drug Development: Dosing Aspectsmentioning

confidence: 99%

Paediatric Drug Development and Formulation Design—a European Perspective

Riet‐Nales

Kozarewicz²,

Aylward

et al. 2016

AAPS PharmSciTech

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Abstract.The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed drug use are associated with a greater risk for harm than on-label drug use, a range of global initiatives have been developed to realize Bbetter^medicines for children. This review describes the challenges and achievements of the European Union to realize this goal, with a focus on paediatric drug development and formulation design. In 2007, a European Paediatric Regulation was installed enforcing companies to consider children in the early development of drugs with a new drug substance, for a new indication or with a new route of administration. The Regulation, e.g. requires companies to develop a paediatric investigation plan discussing the proposed clinical trials in children of different ages and the formulations for future marketing. Since 2013, the pharmaceutical design of any newly marketed paediatric drug should comply with the BGuideline on the Pharmaceutical Development of Medicines for Paediatric Use.^Companies should, e.g. justify the route of administration, dosage form, formulation characteristics, safety of excipients, dosing frequency, container closure system, administration device, patient acceptability and user information. In this review, the guideline's key aspects are discussed with a focus on novel formulations such as mini-tablets and orodispersible films, excipients with a potential risk for harm such as azo dyes and adequate user instructions.

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Pharmacogenomics – how close/far are we to practising individualized medicine for children?

Cited by 14 publications

References 59 publications

Implementation and obstacles of pharmacogenetics in clinical practice: An international survey

Implementation and obstacles of pharmacogenetics in clinical practice: An international survey

Novel Implementation of Genotype‐Guided Proton Pump Inhibitor Medication Therapy in Children: A Pilot, Randomized, Multisite Pragmatic Trial

Paediatric Drug Development and Formulation Design—a European Perspective

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