Reporting of data monitoring committees and adverse events in paediatric trials: a descriptive analysis (original) (raw)
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Data monitoring committees, interim analysis and early termination in paediatric trials
Acta Paediatrica, 2011
To evaluate whether paediatric randomized clinical trials (RCTs) adopt recent guidance on Data Monitoring Committees (DMCs), interim analysis and early termination. Methods: We reviewed paediatric RCTs that reported on DMCs, interim analysis or early termination, published in eight general medical and paediatric journals (2005-2007). We searched full-text databases for eligible trials and recorded predefined parameters on each item. Reported activities were compared with current scientific guidance. Results: A total of 110 of 648 paediatric trials (17%) reported on DMC, interim analysis or early stopping. Various approaches for convening a DMC were identified; information on DMC composition and independence was limited. Strict predefined statistical stopping 'rules' were reported in 10 of 23 trials, and interim analyses were more frequently performed on efficacy than on safety outcomes (39 ⁄ 45 vs 27 ⁄ 45). No adjustment for repeated testing was reported in 11 of 33 trials reporting monitoring methods and in 7 of 17 early terminated trials. Validity of results from early stopped trials was threatened by small sample sizes. Incomplete reporting hampered a full analysis. Conclusion: Few paediatric trials report on DMCs' roles, interim analysis or early stopping. Heterogeneous practices and apparent shortcomings jeopardize the validity of trial results. Easily accessible guidelines for the design, conduct and reporting of paediatric DMCs are needed.
BMC Pediatrics, 2009
Background: Decisions about interim analysis and early stopping of clinical trials, as based on recommendations of Data Monitoring Committees (DMCs), have far reaching consequences for the scientific validity and clinical impact of a trial. Our aim was to evaluate the frequency and quality of the reporting on DMC composition and roles, interim analysis and early termination in pediatric trials. Methods: We conducted a systematic review of randomized controlled clinical trials published from 2005 to 2007 in a sample of four general and four pediatric journals. We used full-text databases to identify trials which reported on DMCs, interim analysis or early termination, and included children or adolescents. Information was extracted on general trial characteristics, risk of bias, and a set of parameters regarding DMC composition and roles, interim analysis and early termination. Results: 110 of the 648 pediatric trials in this sample (17%) reported on DMC or interim analysis or early stopping, and were included; 68 from general and 42 from pediatric journals. The presence of DMCs was reported in 89 of the 110 included trials (81%); 62 papers, including 46 of the 89 that reported on DMCs (52%), also presented information about interim analysis. No paper adequately reported all DMC parameters, and nine (15%) reported all interim analysis details. Of 32 trials which terminated early, 22 (69%) did not report predefined stopping guidelines and 15 (47%) did not provide information on statistical monitoring methods. Conclusions: Reporting on DMC composition and roles, on interim analysis results and on early termination of pediatric trials is incomplete and heterogeneous. We propose a minimal set of reporting parameters that will allow the reader to assess the validity of trial results.
Systematic review of safety in paediatric drug trials published in 2007
European Journal of Clinical Pharmacology, 2012
Background There is now greater involvement of children in drug trials to ensure that paediatric medicines are supported by sound scientific evidence. The safety of the participating children is of paramount importance. Previous research shows that these children can suffer moderate and severe adverse drug reactions (ADRs) in clinical trials, yet very few of the trials designated a data safety monitoring board (DSMB) to oversee the trial. Methods Safety data from a systematic review of paediatric drug randomised controlled trials (RCTs) published in 2007 were analysed. All reported adverse events (AEs) were classified and assessed to determine whether an ADR had been experienced. ADRs were then categorised according to severity. Each trial report was examined as to whether an independent DSMB was in place. Results Of the 582 paediatric drug RCTs analysed, 210 (36%) reported that a serious AE had occurred, and in 15% mortality was reported. ADRs were detected in more than half of the RCTs (305); 66 (11%) were severe, and 79 (14%) were moderate. Severe ADRs involved a wide range of organ systems and were frequently associated with cytotoxic drugs, antiparasitics, anticonvulsants and psychotropic drugs. Two RCTs reported significantly higher mortality rates in the treatment group. Only 69 (12%) of the RCTs stated there was a DSMB. DSMBs terminated five RCTs and changed the protocol in one. Conclusions Children participating in drug RCTs experience a significant amount and a wide range of ADRs.
The DEC-net European register of paediatric drug therapy trials: contents and context
European Journal of Clinical Pharmacology, 2008
Objective To describe the results and conclusions of DEC-net, an international, publicly available register of paediatric drug therapy clinical trials, and to assess which paediatric health areas are covered by research and by which trial types. Methods The contents of the register, which was set up by four groups (Italy, UK, France, Spain) who searched for paediatric trials and collected data between 2004–2006, were analysed. The disease areas reflected were compared with those covered by published trials and Burden of Disease (BD) data. Results In all, 257 trial records were analysed, 86 of which were entered by the Italian partner, 84 by the UK partner, 56 by the French partner and 31 by the Spanish partner. Spain entered the majority of multinational trials, while the UK had the majority of single-centre national trials. Most trials were experimental (79%), and the most commonly represented diseases were neoplasms (14% trials). In all, 28% were double-blind randomised controlled trials (RCTs). The most common disease areas addressed in the 257 trials were similar to the published trials’ areas. In contrast, the primary research area was low on the BD list. Conclusions DEC-net has demonstrated that international research efforts exist, even for paediatrics, although there may be an imbalance between national and multinational studies and a limited approach to double-blind RCTs. Recent initiatives will increase the number of children participating in research, and European legislation will require prospective registration. Paediatric research priorities must be better defined, however, and this can be done by registering research and making the information available to all relevant actors.
Standard 5: Selection, Measurement, and Reporting of Outcomes in Clinical Trials in Children
PEDIATRICS, 2012
People making choices in health care should use the findings of clinical trials (ideally, incorporated in systematic reviews) to inform their decisions. If these findings are to be useful and reliable, researchers must select appropriate outcomes, measure them in a scientifically robust manner, and report results thoroughly. There are difficulties, however, relating to the selection and measurement of outcomes in clinical trials, and special considerations are needed when these studies are conducted in children. This article provides guidance for researchers working on clinical trials in children. Although this article is focused on trials of effectiveness, which are similar to therapeutic confirmatory trials, certain sections may also relate to efficacy trials, pharmacokinetic trials, therapeutic exploratory trials, and trials conducted earlier in drug development. SELECTION OF APPROPRIATE OUTCOMES To be useful, clinical trials that evaluate potential benefits and harms of health care interventions must measure outcomes of relevance to practitioners and patients who make shared decisions about treatment options; regulatory authorities who consider applications for marketing authorizations for medicines; organizations who decide whether to provide funding for an intervention (eg, health care commissioners, insurance companies); and policy makers interested in the impact of an intervention.
BMC Pediatrics, 2010
Background: Randomized controlled trials (RCTs) are the gold standard for trials assessing the effects of therapeutic interventions; therefore it is important to understand how they are conducted. Our objectives were to provide an overview of a representative sample of pediatric RCTs published in 2007 and assess the validity of their results. Methods: We searched Cochrane Central Register of Controlled Trials using a pediatric filter and randomly selected 300 RCTs published in 2007. We extracted data on trial characteristics; outcomes; methodological quality; reporting; and registration and protocol characteristics. Trial registration and protocol availability were determined for each study based on the publication, an Internet search and an author survey.
Perspectives in pediatric clinical trials: a review
International Journal of Clinical Trials, 2016
Children are different from adults in many aspects of pharmacotherapy, including capacity to absorb, distribute, metabolize and excrete drugs and have their own taste preferences. International Conference on Harmonisation (ICH) guidelines classify pediatric age groups into five groups namely preterm, term new born infants, infants and toddlers, children and adolescents. United States conducts maximum number of pediatric drug trials as compared to developing countries. Most of the prescribed drugs are either unlicensed or have an off label use. That is these have not been evaluated for their safety and efficacy in children. As children are separate population entity and not mini-adults, these clinical trials with adults cannot be simply generalized or extrapolated to pediatric population. Thus it is mandatory to conduct clinical trials involving pediatric population in order to get full benefits to the children. To study this gap between adults and children for their wellbeing, disease prevention, diagnosis and treatment, high quality clinical trials are required.
Archives of Disease in Childhood, 2021
Conduct of clinical trials in babies, children and young people is often hindered by issues that could have been foreseen before the trial opened; that is, some clinical trials are often underprepared. In order to identify a good approach to trial preparedness, the European Network of Paediatric Research at the European Medicines Agency formed a working group. The Working Group included representation from regulators, industry, academics, paediatric clinical research networks and parents. The Working Group consulted widely about how to prepare for paediatric clinical trials. The Group’s detailed recommendations have been published (https://www.ema.europa.eu/en/documents/other/preparedness-medicines-clinical-trials-paediatrics-recommendations-enpr-ema-working-group-trial\_en.pdf). This paper is a summary of the key recommendations including the following: start early, preferably in parallel to designing the medicine’s development plan and individual protocols; identify the rationale a...