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The use of master protocols allows for innovative approaches to clinical trial designs, potentially enabling new approaches to operations and analytics and creating value for patients and drug developers. Pediatric research has been conducted for many decades, but the use of novel designs such as master protocols in pediatric research is not well understood. This study aims to provide a systematic review on the utilization of master protocols in pediatric drug development. A search was performed in September 2022 using two data sources (PubMed and ClinicalTrials.gov) and included studies conducted in the past10 years. General study information was extracted such as study type, study status, therapeutic area, and clinical trial phase. Study characteristics that are specific to pediatric studies (such as age of the participants and pediatric drug dosing) and important study design elements (such as number of test drug arms and whether randomization and/or concurrent control was used) were also collected. Our results suggest that master protocol studies are being used in pediatrics, with platform and basket trials more common than umbrella trials. Most of this experience is in oncology and early phase studies. There is a rise in the use starting in 2020, largely in oncology and COVID-19 trials. However, adoption of master protocols in pediatric clinical research is still on a small scale and could be substantially expanded. Work is required to further understand the barriers in implementing pediatric master protocols, from setting up infrastructure to interpreting study findings. [ABSTRACT FROM AUTHOR]

Objective: Examine the influence of household income on health‐related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). Design: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. Exposure: Household income was self‐reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. Outcome: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. Result: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2–20.2). Seven percent of enrolled patients presented with high acuity (ICU‐level care in the first 72 h), and 16% had high toxicity (any ICU‐level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. Conclusions: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research. [ABSTRACT FROM AUTHOR]

Background: Whether social determinants of health are associated with survival in the context of pediatric oncology-targeted immunotherapy trials is not known. We examined the association between poverty and event-free survival (EFS) and overall survival (OS) for children with high-risk neuroblastoma treated in targeted immunotherapy trials.Methods: We conducted a retrospective cohort study of 371 children with high-risk neuroblastoma treated with GD2-targeted immunotherapy in the Children's Oncology Group trial ANBL0032 or ANBL0931 at a Pediatric Health Information System center from 2005 to 2014. Neighborhood poverty exposure was characterized a priori as living in a zip code with a median household income within the lowest quartile for the cohort. Household poverty exposure was characterized a priori as sole coverage by public insurance. Post hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. All statistical tests were 2-sided.Results: In multivariable Cox regressions adjusted for disease and treatment factors, household poverty-exposed children experienced statistically significantly inferior EFS (hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.28 to 2.82, P = .001) and OS (HR = 2.79, 95% CI = 1.63 to 4.79, P < .001) compared with unexposed children. Neighborhood poverty was not independently associated with EFS or OS. In post hoc analyses exploring the joint effect of neighborhood and household poverty, children with dual-poverty exposure (neighborhood poverty and household poverty) experienced statistically significantly inferior EFS (HR = 2.21, 95% CI = 1.48 to 3.30, P < .001) and OS (HR = 3.70, 95% CI = 2.08 to 6.59, P < .001) compared with the unexposed group.Conclusions: Poverty is independently associated with increased risk of relapse and death among neuroblastoma patients treated with targeted immunotherapy. Incorporation of social and environmental factors in future trials as health-care delivery intervention targets may increase the benefit of targeted therapies. [ABSTRACT FROM AUTHOR]

This study is a pharmacoepidemiologic description of pediatric bortezomib use. Exposure was identified through billing codes in patients admitted to US children’s hospitals that participated with the Pediatric Health Information System between 2004 and 2013. Associated information on underlying diseases, demographics, institutional use, mortality, and physician type was collected. Exposure to bortezomib was identified in 314 patients. Hematologist/Oncologists prescribed half of the bortezomib used. Use increased during the study period. Inpatient volume was positively correlated with bortezomib utilization. Bortezomib use in pediatrics is increasing for a variety of diseases. Variation in use exists across institutions. Further studies are needed to characterize bortezomib’s efficacy in pediatric diseases. [ABSTRACT FROM AUTHOR]

SUMMARY Objective Fertility preservation (FP) is a widespread practice in paediatric oncology when gonadotoxic medications such as cyclophosphamide (CPO) are used. FP practice outside of oncology has not been studied, although nephrologists regularly use CPO. This is the first study to explore FP practice by paediatric nephrologists when CPO is used. Design Survey study. Descriptive statistics and chi-squared analyses were employed to analyse the data. Participants US paediatric nephrologists were sent a survey via email. The survey queried participants about FP practice behaviours, FP attitudes and barriers to practice. Main Outcome Measures Of 579 nephrologists invited, 32% responded to the survey. Results CPO was dosed in mg/kg by 23% of physicians, g/m2 by 40% and both by 37%. About 80% agreed that pubertal females should be offered a fertility referral, while 58% report that they actually refer. Factors negatively associated with referral include lack of training, lack of referral network and adherence to gonadotoxic dose limits. Results were similar for male patients. Conclusion The survey showed that FP practice in the United States is widespread among nephrologists. Lack of referral networks is a notable barrier for nephrologists. Perceived adherence to dose limits may be problematic given the variable dosing regimens utilised. This is due to the risk of unintended overdose in large adolescents dosed in mg/kg whose cumulative dose exceeds gonadotoxic limits in g/m2. This paper has implications for nephrology care providers and other specialists who utilise CPO, generalists who care for these patients and oncologists with extant FP referral networks. [ABSTRACT FROM AUTHOR]

Background: In the United States, cancer is common, with high morbidity and mortality; cancer incidence varies between states. Online searches reflect public awareness, which could be driven by the underlying regional cancer epidemiology.Objective: The objective of our study was to characterize the relationship between cancer incidence and online Google search volumes in the United States for 6 common cancers. A secondary objective was to evaluate the association of search activity with cancer-related public events and celebrity news coverage.Methods: We performed a population-based, retrospective study of state-level cancer incidence from 2004 through 2013 reported by the Centers for Disease Control and Prevention for breast, prostate, colon, lung, and uterine cancers and leukemia compared to Google Trends (GT) relative search volume (RSV), a metric designed by Google to allow interest in search topics to be compared between regions. Participants included persons in the United States who searched for cancer terms on Google. The primary measures were the correlation between annual state-level cancer incidence and RSV as determined by Spearman correlation and linear regression with RSV and year as independent variables and cancer incidence as the dependent variable. Temporal associations between search activity and events raising public awareness such as cancer awareness months and cancer-related celebrity news were described.Results: At the state level, RSV was significantly correlated to incidence for breast (r=.18, P=.001), prostate (r=-.27, P<.001), lung (r=.33, P<.001), and uterine cancers (r=.39, P<.001) and leukemia (r=.13, P=.003) but not colon cancer (r=-.02, P=.66). After adjusting for time, state-level RSV was positively correlated to cancer incidence for all cancers: breast (P<.001, 95% CI 0.06 to 0.19), prostate (P=.38, 95% CI -0.08 to 0.22), lung (P<.001, 95% CI 0.33 to 0.46), colon (P<.001, 95% CI 0.11 to 0.17), and uterine cancers (P<.001, 95% CI 0.07 to 0.12) and leukemia (P<.001, 95% CI 0.01 to 0.03). Temporal associations in GT were noted with breast cancer awareness month but not with other cancer awareness months and celebrity events.Conclusions: Cancer incidence is correlated with online search volume at the state level. Search patterns were temporally associated with cancer awareness months and celebrity announcements. Online searches reflect public awareness. Advancing understanding of online search patterns could augment traditional epidemiologic surveillance, provide opportunities for targeted patient engagement, and allow public information campaigns to be evaluated in ways previously unable to be measured. [ABSTRACT FROM AUTHOR]