Characteristics of pediatric pulmonary hypertension trials registered on ClinicalTrials.gov

Awerbach, Jordan D.; Krasuski, Richard A.; Hill, Kevin D.

doi:10.1177/2045893217695567

Cited by 8 publications

(6 citation statements)

References 25 publications

(34 reference statements)

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“…However, we found similar rates of noncompletion and nonpublication among pediatric and adult studies. The pediatric trial discontinuation rate of 30% in our study is comparable with prior studies demonstrating noncompletion among 18% to 40% of trials in pediatric populations [10,20,25,26]. The nonpublication rate of 24% for rare disease trials was slightly lower than previously reported rates of 30% to 37% among various cohorts of pediatric trials and may reflect improvements in this practice over time [10,20,25,26].…”

Section: Discussionsupporting

confidence: 83%

Noncompletion and nonpublication of trials studying rare diseases: A cross-sectional analysis

et al. 2019

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BackgroundRare diseases affect as many as 60 million people in the United States and Europe. However, most rare diseases lack effective therapies and are in critical need of clinical research. Our objective was to determine the frequency of noncompletion and nonpublication of trials studying rare diseases.Methods and findingsWe conducted a cross-sectional analysis of randomized clinical trials studying rare diseases as defined by the Genetic and Rare Disease Information Center database that were registered in ClinicalTrials.gov between January 1, 2010, and December 31, 2012, and completed or discontinued by December 31, 2014. Our main outcome measures were the frequency of trial noncompletion and, among completed studies, frequency of trial nonpublication at 2 and 4 years following trial completion. Reasons for discontinuation were extracted from the registry, and trial sponsors were contacted for additional information, as needed. Two independent investigators performed publication searches for each trial in PubMed, EMBASE, and GoogleScholar, allowing for a minimum of 45 months between trial completion and publication. When a publication could not be identified, trial sponsors were contacted to confirm publication status. The impact of funding source on trial noncompletion was assessed with multivariable logistic regression, and the effect on time to publication was examined with Cox proportional hazards regression. Control variables included intervention type, trial phase, masking, enrollment, and study population. We analyzed 659 rare disease trials accounting for 70,305 enrolled patients. Industry was the primary funder for 327 trials (49.6%) and academic institutions for 184 trials (27.9%). There were 79 trials (12.0%) focused on pediatric populations. A total of 199 trials (30.2%) were discontinued. Lack of patient accrual (n = 64, 32.1%) and informative termination (n = 41, 20.6%) were the most common reasons for trial noncompletion. Among completed trials, 306 (66.5%) remained unpublished at 2 years and 142 (31.5%) at 4 years. In multivariable analyses, industry-funded trials were less likely to be discontinued than trials funded by healthcare centers (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.34–4.39, P = 0.003). We found no significant association between funding source and time to publication. A total of 18,148 patients were enrolled in trials that were discontinued or unpublished 4 years after completion. A potential limitation of our study is that certain interventional trials for rare diseases may not have been registered in ClinicalTrials.gov, in particular Phase 0 and Phase I trials, which are not required to be registered.ConclusionsIn this study, over half of clinical trials initiated for rare diseases were either discontinued or not published 4 years after completion, resulting in large numbers of patients with rare diseases exposed to interventions that did not lead to informative findings. Concerted efforts are needed to ensure that participation of patients in rare disease trials a...

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Section: Discussionsupporting

confidence: 83%

Noncompletion and nonpublication of trials studying rare diseases: A cross-sectional analysis

et al. 2019

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“…In 2012, a study by Pasquali et al found that an assessment of the clinical trial site data set could describe the overall mix of clinical trials related to children in the United States, which was previously impossible [12]. Afterwards, descriptive analyses of clinical registration trial characteristics for different pediatric diseases began to emerge [13][14][15]. The development of pediatric clinical studies and regulations on registration of ClinicalTrials.gov had offered the opportunity to characterize the landscape of pediatric studies.…”

Section: Introductionmentioning

confidence: 99%

Updated analysis of pediatric clinical studies registered in ClinicalTrials.gov, 2008–2019

et al. 2021

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Background Since the national clinical trials registry (ClinicalTrials.gov) launched in February 2000, more than 360,000 research studies in the United States and over 200 countries have registered. As the characteristics of pediatric clinical studies keep changing over time and the results-reporting mechanism is under evolving, to know about the relevant updates of data elements and the effect of policies on the quality of reporting results is significant. Methods In this research, 53,060 clinical studies related to children registered from January 2008 to December 2019 were downloaded from ClinicalTrials.gov on August 1st, 2020. Different types of studies and critical categorical variables were identified, based on which, Cochran-Armitage test was performed to explore temporal trend of study characteristics and common pediatric clinical conditions in four time subsets. Further, to examine heterogeneity among subgroups (funding sources, funding sites, pediatric clinical conditions,etc), chi-squared test was applied. Results A total of 36,136 clinical trials and 16,692 observational studies were identified during the study period. The pediatric clinical trials increased from 7,029 (January 2008–December 2010) to 11,738 (January 2017–December 2019). The number of missing data has declined, with the maximum extent decline from 3.7 to 0.0% (Z = − 15.90, p < 0.001). Drug trials decreased from 48.8 to 28.9% (Z = − 24.68, p < 0.001). Behavioral trials, on the other hand, increased from 12.6 to 20.4% (Z = 12.28, p < 0.001). Most pediatric clinical trials were small-scale (58.9% enrolling 1–100 participants), single-site (61.4%) and funded neither by industry nor by the NIH (59.2%). The proportion of reporting study results varied by study type (χ2 = 1,256.8, p < 0.001), lead sponsor (χ2 = 4,545.6, p < 0.001), enrollment (χ2 = 29.4, p < 0.001) and trial phase (χ2 = 218.8, p < 0.001). Conclusion Pediatric clinical studies registered in ClinicalTrials.gov were dominated by small-scale interventional trials, containing significant heterogeneity in funding sources, funding sites, pediatric clinical conditions and study characteristics. Although the results database has evolved in the past decade, efforts to strengthen the practice of systematic reporting must be continued.

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“…Therefore, there remains the need for creative trial designs to overcome the difficulties of studying rare and heterogeneous patient population and for long‐term continuation of blinded dose‐ranging for adverse event surveillance 47 . More robust pediatric pharmacokinetic and safety data are also required.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil for pulmonary hypertension in neonates: An updated systematic review and meta‐analysis

Zhu

Zhou

et al. 2021

Pediatric Pulmonology

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Objectives: To provide an updated review and meta-analysis on the efficacy and safety of sildenafil for treating persistent pulmonary hypertension in neonates (PPHN).Methods: PubMed/Medline, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science were searched from the inception of publication to January 2021. The principal outcomes include oxygenation parameters, hemodynamic metrics and echocardiographic measurements, as well as adverse outcomes.Results: A total of eight studies were included with 216 term and premature neonates with PPHN. Compelling evidence showed the use of sildenafil could improve the prognosis of PPHN neonates, compared with baseline or placebo in neonates with PPHN, and a time-dependent pattern of the improvements can be observed.After 24 h of treatment, the Oxygenation index suggested a steady decrease (SD: −1.80, 95% confidence interval [CI]: −2.92, −0.67) and sildenafil exerted peak effects after 72 h of treatment (SD: −4.02, 95% CI: −5.45, −2.59). No clinically significant side effects were identified. Egger's test and funnel plots of the major outcomes were performed, and the publication bias was not significant. Conclusion:Improvements were shown in oxygenation index, pulmonary arterial pressure, and adverse outcomes after using sildenafil for PPHN in neonates.However, future research with robust longitudinal or randomized controlled design is still needed.

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Characteristics of pediatric pulmonary hypertension trials registered on ClinicalTrials.gov

Cited by 8 publications

References 25 publications

Noncompletion and nonpublication of trials studying rare diseases: A cross-sectional analysis

Noncompletion and nonpublication of trials studying rare diseases: A cross-sectional analysis

Updated analysis of pediatric clinical studies registered in ClinicalTrials.gov, 2008–2019

Sildenafil for pulmonary hypertension in neonates: An updated systematic review and meta‐analysis

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