Methodological and ethical aspects of randomized controlled clinical trials in minors with malignant diseases

Rothenberger, Lillian Geza; Henschel, Andreas Dirk; Schrey, Dominik; Becker, Andreas; Boos, Joachim

doi:10.1002/pbc.23171

Cited by 7 publications

(5 citation statements)

References 19 publications

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“…The over-arching theme was the consideration of pediatric age during the design, conduct and reporting of pediatric relevant trials. The age(s) of the participating children affects all aspects of a trial, including choice of intervention and comparator, selection and measurement of relevant and valid outcomes, expected treatment effect, differences in risk/benefit profile, effects on growth and development and disease processes [ 21 , 34 , 48 , 50 – 65 ]. Therefore, the detailed reporting of the age distribution of children in a trial is essential for the assessment of the appropriateness of age groups selected, the interventions, and outcomes, and the potential effects on growth and development.…”

Section: Resultsmentioning

confidence: 99%

“…If this justification is not satisfying, studies may be performed in adults but not in children. Ninety-one of 175 publications (52 %) gave a scientific justification for including minors, 84 publications (48 %) did not” [ 48 ]. This example of evidence was coded as “Scientific justification.” After coding the evidence, reviewers compared their codes, resolved any differences, and collaboratively created one final version of coding.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Recommendations and evidence for reporting items in pediatric clinical trial protocols and reports: two systematic reviews

Clyburne-Sherin

Thurairajah

Kapadia

et al. 2015

Trials

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Background: Complete and transparent reporting of clinical trial protocols and reports ensures that these documents are useful to all stakeholders, that bias is minimized, and that the research is not wasted. However, current studies repeatedly conclude that pediatric trial protocols and reports are not appropriately reported. Guidelines like SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) may improve reporting, but do not offer guidance on issues unique to pediatric trials. This paper reports two systematic reviews conducted to build the evidence base for the development of pediatric reporting guideline extensions: 1) SPIRIT-Children (SPIRIT-C) for pediatric trial protocols, and 2) CONSORT-Children (CONSORT-C) for pediatric trial reports. Method: MEDLINE, the Cochrane Methodology Register, and reference lists of included studies were searched. Publications of any type were eligible if they included explicit recommendations or empirical evidence for the reporting of potential items in a pediatric protocol (SPIRIT-C systematic review) or trial report (CONSORT-C systematic review). Study characteristics, recommendations and evidence for pediatric extension items were extracted. Recurrent themes in the recommendations and evidence were identified and synthesized. All steps were conducted by two reviewers. Results: For the SPIRIT-C and CONSORT-C systematic reviews 366 and 429 publications were included, respectively. Recommendations were identified for 48 of 50 original reporting items and sub-items from SPIRIT, 15 of 20 potential SPIRIT-C reporting items, all 37 original CONSORT items and sub-items, and 16 of 22 potential CONSORT-C reporting items. The following overarching themes of evidence to support or refute the utility of reporting items were identified:

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Recommendations and evidence for reporting items in pediatric clinical trial protocols and reports: two systematic reviews

Clyburne-Sherin

Thurairajah

Kapadia

et al. 2015

Trials

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“…Off-label use is of utmost importance in pediatrics beacause many drugs are not evaluated in randomized trials in children, meaning that they are not specifically approved for use in children [64]. This is especially relevant in oncology patients [65]. Approved drugs are thus often prescribed outside the terms of the product approval in relation to age.…”

Section: Resultsmentioning

confidence: 99%

Contrast Enhanced Ultrasound in Pediatric Patients: A Real Challenge

et al. 2014

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Ultrasound (US) imaging in the paediatric population has been a routine technique for decades, in part because of the advantages it offers over other imaging modalities. Off-label use (and its funding) is of the utmost importance in paediatrics because many drugs have not been evaluated in randomised trials in children. As a consequence such drugs are not specifically approved for use in children. This is also true for the contrast agents used in CEUS. The off-label use of CEUS in paediatric patients illustrates the need to deal with unresolved legal issues while at the same time balancing this with the need for high diagnostic performance in daily clinical routine. In addition to approved indications with a focus on the liver and Doppler enhancement, CEUS is safe and effective for the examination of many organs, as recently highlighted by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). This article provides a summary of the available literature describing the utility of CEUS in paediatric patients. Furthermore, we suggest the establishment of a registry to collect data on safety and applications of ultrasound contrast agents in children. A paediatric registry has recently been introduced by EFSUMB (www.efsumb.org).

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“…70 Other issues are rather phase-specific, although baseline cases suggest that these can also arise in different settings. Main issues in Phase 1 trials are: scientific justification, 3,22,45 "net risk research", 23,48 lack of benefit due to underdosing, 58 and "therapeutic misconception"; 28 in Rob's case, father's attitude may be interpreted as an instance of therapeutic misconception outside phase 1 since he conflates a research objective (to compare four strategies) with a therapeutic decision ("whatever you need to do, do it!"). In phase 2 trials, belief in the supposed efficacy of a new agent is problematic if it leads to use drugs off-trial or to overestimate the prospect of benefit; 23 in Alberto's case, parents' motives ("they … nurtured the hope that if he lived a few more years a cure might be found") suggest a correct estimate of their child's prospect of benefit, making consent valid despite their difficulties to cope with distressing information.…”

Section: Research Ethicsmentioning

confidence: 99%

“…However, as shown by a recent review, compliance with biomedical ethics principles is often insufficiently documented in scientific publications. 3 Lack of proper documentation does not necessarily mean that ethical standards are not met, nor underestimated by investigators; lack of clarity and certainty about those demands is another, arguably more plausible, explanation.…”

Section: Introductionmentioning

confidence: 99%

Ethical issues of clinical trials in paediatric oncology from 2003 to 2013: a systematic review

Dupont

Pritchard‐Jones

Doz

2016

The Lancet Oncology

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A state-of-the art approach to the debates on ethical issues is key in order to gain guidance on research practices involving sick children and adolescents, as well as to identify research avenues in which it might be worth cooperating, to generate better or supplementary evidence. Based on a systematic literature search using MEDLINE, we report the main ethical developments in paediatric oncology clinical trials from 2003-13. The present knowledge about normative and empirical ethical demands in this setting is quantified and summarised in a list of 46 issues. This list primarily aims to provide readers with a comprehensive account of the main decision nodes and professional attitudes that enable families to make a safe, competent, and satisfactory decision about their child's enrolment, or non-participation, in cancer clinical trials. Our systematic Review shows how important it is for professionals to engage in a constant reflection on optimum trial designs, on the effect of offering trial participation on key family dynamics, and on the ways to understand families' needs and values accurately. In view of present scientific developments, we further emphasise the need to enhance societal awareness about research in children and adolescents, to prevent so-called research fatigue in small populations due to multiple solicitations or inadequate legal demands, and to reassess longstanding ethical certainties in the strictest view of promoting sick children's interests. This systematic Review allows a series of questions to be drawn to guide and encourage collective and individual endeavours that should lead to constant improvements in our research practices in paediatric clinical oncology research.

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Methodological and ethical aspects of randomized controlled clinical trials in minors with malignant diseases

Abstract: In the publications analyzed, we found only limited information concerning methods and reflections on ethical principles of the trials. Improvements are thus necessary and possible. We suggest how such trials and their respective publications can be optimized for these aspects.

Cited by 7 publications

References 19 publications

Recommendations and evidence for reporting items in pediatric clinical trial protocols and reports: two systematic reviews

Recommendations and evidence for reporting items in pediatric clinical trial protocols and reports: two systematic reviews

Contrast Enhanced Ultrasound in Pediatric Patients: A Real Challenge

Ethical issues of clinical trials in paediatric oncology from 2003 to 2013: a systematic review

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