Effect of Pediatric Influenza on Caregivers’ Burden—A Literature Review

Influenza, or the flu, is a common and potentially serious infection that disproportionally affects children with more than 20,000 yearly hospitalizations in children under the age of 5. A literature review of the caregiver burden associated with pediatric influenza was conducted. Two main types of burdens were identified: economic and noneconomic. Flu treatment costs $3,990 for pediatric inpatients services and $730 for emergency department (ED) pediatric patients. Caregivers may also face out-of-pocket costs ($178 for inpatients, $125 for ED patients, and $52 for outpatients) or those not covered by health insurance. Caregivers can also face indirect costs while caring for their children with the flu. Indirect costs were common, and 75% of pediatric caregivers reported these costs when caring for a sick child. Missed work is the most common indirect cost and is estimated as high as 73 work hours ($1,456) missed while caring for a sick child. Other costs associated with pediatric influenza included noneconomic burden: sudden changes in daily life, loss of leisure time, social disruption, and psychological impact or stress. Noneconomic burdens were also found to be significant and lowered the quality of life of caregivers even after the child’s illness. Socioeconomic status is an important predictor of influenza rates. Residents in high-poverty areas are three times more likely to have hospitalizations due to pediatric influenza than those in low-poverty areas. From the literature it is evident that pediatric influenza has demonstrated a considerable impact on caregivers’ lives both financially and in other aspects.     

An adaptive seamless phase II/III design for oncology trials with subpopulation selection using correlated survival endpoints

Although the statistical methods enabling efficient adaptive seamless designs are increasingly well established, it is important to continue to use the endpoints and specifications that best suit the therapy area and stage of development concerned when conducting such a trial. Approaches exist that allow adaptive designs to continue seamlessly either in a subpopulation of patients or in the whole population on the basis of data obtained from the first stage of a phase II/III design: our proposed design adds extra flexibility by also allowing the trial to continue in all patients but with both the subgroup and the full population as co-primary populations. Further, methodology is presented which controls the Type-I error rate at less than 2.5% when the phase II and III endpoints are different but correlated time-to-event endpoints. The operating characteristics of the design are described along with a discussion of the practical aspects in an oncology setting.     

A Bayesian dose‐finding design for drug combination clinical trials based on the logistic model

In early phase dose‐finding cancer studies, the objective is to determine the maximum tolerated dose, defined as the highest dose with an acceptable dose‐limiting toxicity rate. Finding this dose for drug‐combination trials is complicated because of drug–drug interactions, and many trial designs have been proposed to address this issue. These designs rely on complicated statistical models that typically are not familiar to clinicians, and are rarely used in practice. The aim of this paper is to propose a Bayesian dose‐finding design for drug combination trials based on standard logistic regression. Under the proposed design, we continuously update the posterior estimates of the model parameters to make the decisions of dose assignment and early stopping. Simulation studies show that the proposed design is competitive and outperforms some existing designs. We also extend our design to handle delayed toxicities. Copyright © 2014 John Wiley & Sons, Ltd.     

浅谈心理学与人文关怀在临床肿瘤学教学中的意义

随着肿瘤发病率的逐渐升高和诊治水平的提高,临床肿瘤学的教育显得越发重要,本人就肿瘤学的教学现状,结合目前肿瘤疾病诊治过程中的特点,浅谈心理学与人文学在临床肿瘤教学过程中的重要性.     

Oncology phase II proof‐of‐concept studies with multiple targets: Randomized controlled trial or single arm?

For oncology drug development, phase II proof‐of‐concept studies have played a key role in determining whether or not to advance to a confirmatory phase III trial. With the increasing number of immunotherapies, efficient design strategies are crucial in moving successful drugs quickly to market. Our research examines drug development decision making under the framework of maximizing resource investment, characterized by benefit cost ratios (BCRs). In general, benefit represents the likelihood that a drug is successful, and cost is characterized by the risk adjusted total sample size of the phases II and III studies. Phase III studies often include a futility interim analysis; this sequential component can also be incorporated into BCRs. Under this framework, multiple scenarios can be considered. For example, for a given drug and cancer indication, BCRs can yield insights into whether to use a randomized control trial or a single‐arm study. Importantly, any uncertainty in historical control estimates that are used to benchmark single‐arm studies can be explicitly incorporated into BCRs. More complex scenarios, such as restricted resources or multiple potential cancer indications, can also be examined. Overall, BCR analyses indicate that single‐arm trials are favored for proof‐of‐concept trials when there is low uncertainty in historical control data and smaller phase III sample sizes. Otherwise, especially if the most likely to succeed tumor indication can be identified, randomized controlled trials may be a better option. While the findings are consistent with intuition, we provide a more objective approach.     

The Therapeutic Misconception: A Threat to Valid Parental Consent for Pediatric Neuroimaging Research

Neuroimaging research has brought major advances to child health and well-being. However, because of the vulnerabilities associated with neurological and developmental conditions, the parental need for hope, and the expectation of parents that new medical advances can benefit their child, pediatric neuroimaging research presents significant challenges to the general problem of consent in the context of research involving children. A particular challenge in this domain is created by the presence of therapeutic misconception on the part of parents and other key research stakeholders. This article reviews the concept of therapeutic misconception and its role in pediatric neuroimaging research. It argues that this misconception can compromise consent given by parents for the involvement of their children in research as healthy controls or as persons with neurological and developmental conditions. The article further contends that therapeutic misconception can undermine the research ethics review process for proposed and ongoing neuroimaging studies. Against this backdrop, the article concludes with recommendations for mitigating the effects of therapeutic misconception in pediatric neuroimaging research.     

Defining estimands for efficacy assessment in single arm phase 1b or phase 2 clinical trials in oncology early development

The addendum of the ICH E9 guideline on the statistical principles for clinical trials introduced the estimand framework. The framework is designed to strengthen the dialog between different stakeholders, to introduce greater clarity in the clinical trial objectives and to provide alignment between the estimand and statistical analysis. Estimand framework related publications thus far have mainly focused on randomized clinical trials. The intention of the Early Development Estimand Nexus (EDEN), a task force of the cross-industry Oncology Estimand Working Group ( www.oncoestimand.org ), is to apply it to single arms Phase 1b or Phase 2 trials designed to detect a treatment-related efficacy signal, typically measured by objective response rate. Key recommendations regarding the estimand attributes include that in a single arm early clinical trial, the treatment attribute should start when the first dose is received by the participant. Focusing on the estimation of an absolute effect, the population-level summary measure should reflect only the property used for the estimation. Another major component introduced in the ICH E9 addendum is the definition of intercurrent events and the associated possible ways to handle them. Different strategies reflect different clinical questions of interest that can be answered based on the journeys an individual subject can take during a trial. We provide detailed strategy recommendations for intercurrent events typically seen in early-stage oncology. We highlight where implicit assumptions should be made transparent as whenever follow-up is suspended, a while-on-treatment strategy is implied.     

Testing drugs in pediatric populations: The FDA mandate

On November 27, 1998 the Food and Drug Administration (FDA) issued a new rule requiring that drugs and biological products be tested in pediatric populations. Since voluntary testing in pediatric populations had not resulted in a significant increase in pediatric labeling of drugs, stronger measures were needed to ensure that infants and children would receive the benefits of properly tested drugs and biologies. The mandate for pediatric testing raises a core ethical question: How should the need for validated treatments that benefit children as a group be weighed against the obligation to protect individual child subjects of research? The preamble to the new rule claims that adherence to Department of Health and Human Services (DHHS) and American Academy of Pediatrics (AAP) guidelines will provide adequate protection to individual subjects. Yet the special protections provided to children in these guidelines are not required by the new FDA rule, and have never been obligatory for research that is regulated by the FDA. While the new rule does not necessitate or encourage violation of these standards, the rule does not pay adequate attention to them nor clarify what role they should play in IRB review of protocols under FDA regulation.     

儿科教学多媒体课件设计与学习心理初探

多媒体课件设计是影响课件质量和教学效果的关键环节,各专业学科有其各自的特点。本文主要从认知心理学角度,对多媒体课件的总体设计、各种媒体的设计、界面的设计等方面进行了分析,提出了一些儿科教学课件制作的有效方式。