Optimizing operational efficiencies in early phase trials: The Pediatric Trials Network experience

England, Amanda; Wade, Kelly C.; Smith, Patrick B.; Berezny, Katherine; Laughon, Matthew M.

doi:10.1016/j.cct.2016.03.002

Cited by 34 publications

(17 citation statements)

References 52 publications

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“…The distinction between AEs and serious adverse events (SAEs) for the laboratory events are defined in Table 1. 7 We reported the proportion of infants experiencing a clinical or laboratory AE while exposed to piperacillin-tazobactam. We assumed that infants did not have a clinical or laboratory AE or SAE if the event was not recorded in the medical chart.…”

Section: Methodsmentioning

confidence: 99%

Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin–Tazobactam Safety in Infants

Salerno

Cp²,

Cohen‐Wolkowiez³

et al. 2017

Pediatric Infectious Disease Journal

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Background Piperacillin, in combination with tazobactam, is frequently used in infants for treating nosocomial infections, although safety data in this population are limited. Electronic health record (EHR) data can be used to evaluate drug safety in infants, but measures of drug exposure are lacking. Methods To relate simulated piperacillin exposure with adverse events (AEs) in infants using EHR data, we identified infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012. Using a previously published population PK model in the target population, we simulated piperacillin steady-state area under the concentration vs. time curve from zero to tau (AUCss,0-τ) and maximal drug concentration (Cmaxss). Next we used multivariable logistic regression to evaluate the association between simulated AUCss,0-τ and Cmaxss with clinical AEs (seizure and rash) and laboratory AEs controlling for gestational age. The odds ratios (95% confidence intervals) comparing the third vs. the first tertiles for AUCss,0-τ and Cmaxss were reported. Results We identified 746 infants with a median (interquartile range) gestational age of 30 weeks (26, 33) and postnatal age of 11 days (6, 25). The median (interquartile range) piperacillin dose was 225 mg/kg/day (176, 300). No significant associations were found between simulated piperacillin exposure (AUCss,0-τ and Cmaxss) and clinical and laboratory AEs. Conclusions We found no associations between predicted piperacillin exposures and the occurrence of AEs. This study confirms the feasibility of using population pharmacokinetics and EHR to relate drug exposure with safety.

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Section: Methodsmentioning

confidence: 99%

Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin–Tazobactam Safety in Infants

Salerno

Cp²,

Cohen‐Wolkowiez³

et al. 2017

Pediatric Infectious Disease Journal

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“…Having an industry-academic group that is professional and neutral exerts a positive effect on trial quality through technical guidance, academic exchange and thirdparty audits. 40,41 The setting up of phase I clinical trial wards in medical institutions comes with the responsibility of allocating hardware and software facilities and implementing trial quality control. 15,18,42 Medical institutions that more carefully fulfil their obligations will generate better-quality trials.…”

Section: Discussionmentioning

confidence: 99%

Quality of phase I clinical drug trials: Influence of organizational management factors

2020

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What is known and Objective Focusing on the tolerance and pharmacokinetics of new drugs, phase I clinical drug trials are characterized by high risk, poor compliance and management difficulties. High‐quality clinical drug trials ensure subjects' safety while extending new drug research and development. Many studies have examined micro‐level concerns of trial design and implementation rather than macro‐level factors. Accordingly, we evaluated the quality of phase I clinical drug trials (trial quality) and analysed the influence of organizational management factors from a macro‐level perspective. Methods We surveyed staff at clinical trial institutions engaged in phase I clinical drug trials in China using convenience sampling. We employed a five‐point Likert‐scale questionnaire, comprising five items on phase I clinical drug trial quality and items on organizational management factors. Data from 604 questionnaires were analysed. We utilized a logistic regression model to estimate the influence of organizational management factors on trial quality, using individual demographic factors as controlling variables. Results and discussion The trial quality score was 3.81, which indicates that substantial improvement is required. Government regulation, industry management and medical institution management had a positive effect on trial quality: β = 0.842, 0.691 and 0.579, respectively; P < .01. Contract research organization management had a negative effect on trial quality: β = −0.476; P = .013. Research team management had no effect on trial quality: β = 0.325; P = .141. What is new and Conclusion This study is the first to model the influence of organizational management factors on the quality of phase I drug trials involving different organizations from a macro‐perspective. Efforts are needed to help research teams take responsibility for trial quality and to correct the negative impact of contract research organizations on trial quality.

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“…All AEs were defined a priori . 10 Clinical AEs included: hypotension; seizures; and renal failure requiring dialysis. Hypotension was defined as exposure to dopamine, dobutamine, epinephrine, norepinephrine or milrinone; actual blood pressures were not available.…”

Section: Methodsmentioning

confidence: 99%

Safety of High-dose Acyclovir in Infants With Suspected and Confirmed Neonatal Herpes Simplex Virus Infections

Ericson

Gostelow

Autmizguine

et al. 2017

Pediatric Infectious Disease Journal

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Background Acyclovir is used to treat herpes simplex virus (HSV) disease in infants. Treatment with high dose acyclovir, 60 mg/kg/day, is recommended; however, the safety of this dosage has not been assessed in the past 15 years, and this dosage is not currently approved for infants by the US Food and Drug Administration. Methods We included infants with neonatal HSV disease treated with ≥14 days of intravenous acyclovir starting in the first 120 days of life admitted to 1 of 42 neonatal intensive care units managed by the Pediatrix Medical Group from 2002–2012. We determined the frequency and proportion of infants with clinical and laboratory adverse events (AEs) as well as the number and proportion of infant days with laboratory AEs occurring during acyclovir exposure. Results We identified 89 infants during the study period with 1658 days of acyclovir exposure. Almost all received high-dose acyclovir therapy (79/89, 89%). The most common clinical AEs were hypotension and seizure, both occurring in 9% of infants. Thrombocytopenia was the most common laboratory AE occurring in 25% of infants and on 9% of infant-days. Elevated creatinine occurred in 2% of infants and 0.2% of infant-days and no infants developed renal failure requiring dialysis. Overall, 45% of infants had ≥1 AE. Conclusions In this cohort of infants treated during the high-dose acyclovir era, AEs were common, but usually not severe. Many of the AEs reported in this cohort may be related to the underlying infection rather than due to acyclovir exposure.

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Optimizing operational efficiencies in early phase trials: The Pediatric Trials Network experience

Cited by 34 publications

References 52 publications

Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin–Tazobactam Safety in Infants

Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin–Tazobactam Safety in Infants

Quality of phase I clinical drug trials: Influence of organizational management factors

Safety of High-dose Acyclovir in Infants With Suspected and Confirmed Neonatal Herpes Simplex Virus Infections

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