Innovative study design for paediatric clinical trials

Baiardi, Paola; Giaquinto, Carlo; Girotto, Silvia; Manfredi, C.; Ceci, Adriana

doi:10.1007/s00228-011-0990-y

Cited by 36 publications

(32 citation statements)

References 15 publications

(13 reference statements)

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“…These novel methods include sequential design, adaptive design, Bayesian approach, randomized withdrawal design, randomized placebo phase design and three-stage clinical trial, which go some way to overcome the limitations of small sample numbers and of the ethical acceptability of the trial [78]. Consideration of appropriate methods for a paediatric pharmacokinetic clinical study should involve the formulation, dose, route of administration, sampling interval and population.…”

Section: Paediatric Clinical Study Designmentioning

confidence: 99%

Paediatric pharmacokinetics: key considerations

Batchelor

Marriott

2015

Brit J Clinical Pharma

236

177

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A number of anatomical and physiological factors determine the pharmacokinetic profile of a drug. Differences in physiology in paediatric populations compared with adults can influence the concentration of drug within the plasma or tissue. Healthcare professionals need to be aware of anatomical and physiological changes that affect pharmacokinetic profiles of drugs to understand consequences of dose adjustments in infants and children. Pharmacokinetic clinical trials in children are complicated owing to the limitations on blood sample volumes and perception of pain in children resulting from blood sampling. There are alternative sampling techniques that can minimize the invasive nature of such trials. Population based models can also limit the sampling required from each individual by increasing the overall sample size to generate robust pharmacokinetic data. This review details key considerations in the design and development of paediatric pharmacokinetic clinical trials.

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Section: Paediatric Clinical Study Designmentioning

confidence: 99%

Paediatric pharmacokinetics: key considerations

Batchelor

Marriott

2015

Brit J Clinical Pharma

236

177

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“…Given that recruitment of such a trial population would be extremely difficult, there is a need to use innovative trial designs24. Some efficiency could be gained by adopting alternative study designs (Table 2).…”

Section: Opportunities For Changementioning

confidence: 99%

Optimizing Research to Speed Up Availability of Pediatric Antiretroviral Drugs and Formulations

Penazzato

Gnanashanmugam

Rojo³

et al. 2017

Clinical Infectious Diseases

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Globally 1.8 million children are estimated to be living with HIV, yet only 51% of those eligible actually start treatment. The completion of research and development (R&D) for paediatric antiretrovirals (ARVs) is a lengthy process and licensing of new paediatric ARVs continues to lag considerably behind adults. Providing safe, effective, and well-tolerated drugs for children remains critical to ensuring scale-up of paediatric treatment globally. In this manuscript we review current approaches to R&D for paediatric ARVs and suggest innovations to enable simplified, faster, and more comprehensive strategies to develop optimal formulations. Several approaches could be adopted, including enrolment of multiple age-cohorts concurrently and the early introduction of dosing approaches for both single and fixed-dose combination (FDC) drug formulations (preferably scored and dispersible) that match WHO weight-bands. Efforts to speed up development of optimal drugs and formulations for children should focus on a limited number of prioritised formulations. This work should build upon existing partnerships and collaborations to ensure that paediatric investigation plans are developed early in the drug development process but can be modified in a streamlined manner as more information becomes available. In addition, simplified and more efficient mechanisms to undertake R&D need to be put in place, and financing mechanisms must be made more efficient and sustainable. Registration, implementation, and strategic use of drugs should not be seen as a sequential process, with research designed to address multiple questions simultaneously to respond to the needs of HIV-infected children where they live. It is imperative that lessons learned from HIV should be shared to support progress in developing paediatric formulations for other diseases with similar treatment challenges, including tuberculosis and viral hepatitis.

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“…Additional calculations showed a sample size of 16 total patients (eight per randomized group) would detect a difference of 50%, and a difference of 20% would require 80 total patients (40 per randomized group). An adaptive study design was planned a priori once preliminary data from the initial ten randomized patients demonstrated >50% difference in urine output, revealing adequate power would be achieved with only 20 randomized patients (10 per randomized group) (27, 28). Statistical analysis of data was performed with STATISTICA ™ software version 9 (StatSoft, Tulsa, OK, USA).…”

Section: Methodsmentioning

confidence: 99%

Peritoneal Dialysis does not Adversely Affect Kidney Function Recovery after Congenital Heart Surgery

et al. 2014

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Purpose Acute kidney injury (AKI) after cardiopulmonary bypass surgery to correct congenital heart disease is common. We prevent fluid overload and further cardiac compromise in oliguric infants with continuous peritoneal dialysis (CPD). The effect of CPD on kidney recovery is unknown, thus indications to discontinue CPD are unclear. We aimed to determine if CPD affects kidney recovery, measured by urine output and novel urinary AKI biomarker concentrations. Methods Twenty infants <90 days old with congenital heart disease who underwent bypass surgery and were post-operatively treated with CPD were randomized at the time of clinical readiness for CPD discontinuation to 1) discontinue CPD (control) or 2) continue 24 h more CPD (experimental). Urine output (ml/kg per h), total output (ml/kg per h) and urinary neutrophil gelatinase-associated lipocalin, interleukin-18, liver-type fatty acid binding protein, and kidney injury molecule-1 were assessed post-surgery until CPD catheter removal. Results 24 hours preceding randomization, there were no differences in mean urine output or total output; 24 hours post-randomization, the control group had higher mean urine output (4.2 ± 2.6 ml/kg per h vs. 2.8 ± 2.0 ml/kg per h, p = 0.02) but lower total output (6.3 ± 2.1 ml/kg per h vs. 4.7 ± 2.7 ml/kg per h, p = 0.01). Median biomarker concentrations did not differ significantly between groups at any time point. Conclusions Our results suggest renal replacement therapy does not change the time course of kidney function recovery.

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Innovative study design for paediatric clinical trials

Abstract: Thanks to their features, these methods represent a reliable way of ultimately improving paediatric care.

Cited by 36 publications

References 15 publications

Paediatric pharmacokinetics: key considerations

Paediatric pharmacokinetics: key considerations

Optimizing Research to Speed Up Availability of Pediatric Antiretroviral Drugs and Formulations

Peritoneal Dialysis does not Adversely Affect Kidney Function Recovery after Congenital Heart Surgery

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