Helen Mahony

Evolution of treatment regimens in multiple myeloma: a social network analysis.

Background Randomized controlled trials (RCTs) are considered the gold standard for assessing the efficacy of new treatments compared to standard treatments. However, the reasoning behind treatment selection in RCTs is often unclear. Here, we focus on a cohort of RCTs in multiple myeloma (MM) to understand the patterns of competing treatment selections. Methods We used social network analysis (SNA) to study relationships between treatment regimens in MM RCTs and to examine the topology of RCT treatment networks. All trials considering induction or autologous stem cell transplant among patients with MM were eligible for our analysis. Medline and abstracts from the annual proceedings of the American Society of Hematology and American Society for Clinical Oncology, as well as all references from relevant publications were searched. We extracted data on treatment regimens, year of publication, funding type, and number of patients enrolled. The SNA metrics used are related to node and network level centrality and to node positioning characterization. Results 135 RCTs enrolling a total of 36,869 patients were included. The density of the RCT network was low indicating little cohesion among treatments. Network Betweenness was also low signifying that the network does not facilitate exchange of information. The maximum geodesic distance was equal to 4, indicating that all connected treatments could reach each other in four “steps” within the same pathway of development. The distance between many important treatment regimens was greater than 1, indicating that no RCTs have compared these regimens. Conclusion Our findings show that research programs in myeloma, which is a relatively small field, are surprisingly decentralized with a lack of connectivity among various research pathways. As a result there is much crucial research left unexplored. Using SNA to visually and analytically examine treatment networks prior to designing a clinical trial can lead to better designed studies.

Rural and Urban Differences in Sexual Behaviors Among Adolescents in Florida

The national teen birth rate is higher in rural compared to urban areas. While national data suggest rural areas may present higher risk for adverse sexual health outcomes among adolescents, it is unknown whether there are differences within the state of Florida. Overall, Florida has poorer sexual health indicators for adolescents compared to national rates. The purpose of this study was to assess differences in sexual behaviors among Florida adolescents by rural–urban community location. This study includes baseline data from a randomized controlled trial conducted in Florida high schools. Of the 6316 participants, 74% were urban and 26% were rural. Participants responded to questions on sexual behaviors, sexual behavior intentions, and demographics. We estimated the effect of rural–urban status on risk outcomes after controlling for demographic variables using generalized linear mixed models. More teens from rural areas reported ever having sex (24.0%) compared to urban teens (19.7%). No significant differences were observed for most of sexual behaviors assessed. Nonetheless, urban participants were less likely to intend to have sex without a condom in the next year compared to rural participants (aOR = 0.76, 95% CI 0.63–0.92). Overall, there were no major differences in sexual behaviors between rural and urban adolescents in Florida. However, sexual intentions differed between rural and urban adolescents; specifically, rural adolescents were more likely to intend to have sex without a condom in the next year compared to urban adolescents. Understanding the specific disparities can inform contraception and sexual health interventions among rural youth.

How Florida youths measure up to US youths in sexual and reproductive health: implications for youths across the United States

The United States surpasses other developed nations in teen birthrates and sexually transmitted infections, and Florida youths are disproportionately affected. Projections have placed Florida to have the second largest population of youths in the nation by 2025. The racial and ethnic diversity as well as a growing number of youths in Florida make sexual and reproductive health (SRH) outcomes in this state reflective of the increasing diversity of youths throughout the United States. The purpose of this research was to compare a representative sample of Florida youths and US high school youths sexual behaviors, overall and by gender and race/ethnicity, to identify disparities. Employing 2011 Centers for Disease Control and Prevention Youth Risk Behavior Survey data, outcomes of interest were ever having had sexual intercourse; intercourse before age 13 years (early sex); condom use; oral contraceptive pill (OCP) use; and use of Depo-Provera®, Nuva Ring®, Implanon®, or any intrauterine device (IUD) at last sex. The analysis calculated relative risk and corresponding 95% confidence interval between Florida (N = 6,212) and US youths (N = 15,425) using SAS version 9.3 (SAS Institute, Inc., Cary, NC, USA). There were statistically significant differences in four of five behaviors, all of which were worse for Florida youths compared with US youths (except for condom use). Florida youths were more likely to report early sex and less likely to have used OCPs. Florida youths were less likely to have used Depo-Provera®, Nuva Ring®, Implanon, or any IUD, including differences by grade level and among male, female, Hispanic, and white youths. This study can inform policy and the need to develop strategies for intervention or service provision among Florida youths so resources can be allotted to priority populations. In addition this study, highlights areas of SRH that may be faced by a growing and diverse population of youths in the United States.

Trial sequential analysis may be insufficient to draw firm conclusions regarding statistically significant treatment differences using observed intervention effects: A case study of meta-analyses of multiple myeloma trials

Trial sequential analysis (TSA) has been proposed as a method to assess the risk of random error in cumulative meta-analysis (MA), which increases due to repeated significance testing. The aim of TSA is to assist researchers from wrongly concluding treatment differences in the absence of a benefit (i.e. true versus false positive). Similar to monitoring boundaries applied in individual randomized controlled trials, recent literature has advocated the use of TSA for assessing the conclusiveness of results from MAs to determine the requirement for future studies in case of true positive results. While this may be desirable, we present empirical evidence from a recent systematic review to demonstrate that the use of TSA may lead to a premature declaration of statistically significant treatment difference, when further accumulated evidence suggested otherwise. Using all apparently conclusive MAs in multiple-myeloma, we empirically studied under what thresholds for the risk ratio reduction and power a true positive result becomes false positive. We recommend that the conclusion of significant treatment differences in cumulative MA should be weighed against acceptable thresholds regarding the type I error, power and apriori specified clinically meaningful treatment difference.

Evaluating the Effects of the Teen Outreach Program on Positive Youth Development Constructs

Introduction: The Teen Outreach Program (TOP) is a positive youth development (PYD) program that seeks to reduce the risk of adolescent pregnancy, school dropout, and course failure. As TOP has not been evaluated for its impact on PYD constructs, our purpose was to assess this potential. Methods: A pair-matched, cluster randomized controlled trial to evaluate TOP among youth in 26 high schools was conducted in 2013-2014. Youth (N=3740) were surveyed at baseline and immediately following program completion. A linear mixed effects model compared scores of the Lerner’s Five Cs measure of PYD between treatment and control youth and by race/ethnicity and gender subgroups. Results: After a multiple comparison adjustment, no statistically significant results were observed. Conclusions: Despite the lack of statistically significant findings, the current study can provide insight for future evaluations of TOP regarding adaptation and evaluation of core components, implementation, PYD impacts, and sexual and reproductive health outcomes.

Preventing Risky Sexual Behavior in Adolescents

Preventing risky sexual health behavior in adolescents has become a critical focus among public health professionals, educators, and policy makers in the USA, and for good reason. Risky sexual behavior contributes to unintended pregnancy and sexually transmitted infections (STIs), including HIV/AIDS. Such outcomes are highly related to the overall physical, social/emotional, academic, and economic well-being of adolescents, children born to teens, and society as a whole. This chapter addresses the prevention of risky sexual health behavior in adolescents in four sections. In the first section, we summarize the epidemiology of risky sexual behavior among adolescents, focusing on statistics of adolescent pregnancy, STIs, and HIV/AIDS in the USA, and the economic and social costs of risky adolescent sexual behavior. In the second section, we discuss the relationship between risky sexual behavior and behavioral theory and why maintaining a focus on behavioral theory in prevention programming is critical. In the third section, we identify venues where interventions designed to prevent risky sexual behavior among adolescents can be implemented, including schools, community settings, and clinical settings, and provide examples of evidence-based programs designed to be implemented in each of these settings. In the fourth and final section, we present recommendations for future prevention programming, provide guidance on developing effective programs, and list helpful resources for planning prevention programs, including planning frameworks such as intervention mapping, RE-AIM, and PRECEDE-PROCEED.

Concordance between decision analysis and matching systematic review of randomized controlled trials in assessment of treatment comparisons: a systematic review

BackgroundSystematic review (SR) of randomized controlled trials (RCT) is the gold standard for informing treatment choice. Decision analyses (DA) also play an important role in informing health care decisions. It is unknown how often the results of DA and matching SR of RCTs are in concordance. We assessed whether the results of DA are in concordance with SR of RCTs matched on patient population, intervention, control, and outcomes.MethodsWe searched PubMed up to 2008 for DAs comparing at least two interventions followed by matching SRs of RCTs. Data were extracted on patient population, intervention, control, and outcomes from DAs and matching SRs of RCTs. Data extraction from DAs was done by one reviewer and from SR of RCTs by two independent reviewers.ResultsWe identified 28 DAs representing 37 comparisons for which we found matching SR of RCTs. Results of the DAs and SRs of RCTs were in concordance in 73% (27/37) of cases. The sensitivity analyses conducted in either DA or SR of RCTs did not impact the concordance. Use of single (4/37) versus multiple data source (33/37) in design of DA model was statistically significantly associated with concordance between DA and SR of RCTs.ConclusionsOur findings illustrate the high concordance of current DA models compared with SR of RCTs. It is shown previously that there is 50% concordance between DA and matching single RCT. Our study showing the concordance of 73% between DA and matching SR of RCTs underlines the importance of totality of evidence (i.e. SR of RCTs) in the design of DA models and in general medical decision-making.