VCCEP Pilot: Progress on Evaluating Children''s Risks and Data Needs

The Voluntary Children's Chemical Evaluation Program (VCCEP) is designed to provide information to the public on children's potential health risks associated with chemical exposures. The key question of the VCCEP is whether the potential hazards, exposures, and risks to children have been adequately characterized, and, if not, what additional data are necessary. To answer this question, manufacturers or importers of 23 chemicals were asked by the U. S. Environmental Protection Agency (U.S. EPA) to sponsor their chemicals in the first tier of a pilot program. These chemicals were selected for evaluation because they have been found as contaminants in human tissue or fluids (adipose tissue, blood, breath, breast milk, or urine); food and water children may eat and drink; or air children may breathe (including residential or school air). Under the VCCEP framework, sponsoring companies agree to prepare Tier 1 hazard, exposure, and risk assessments on the individual chemicals, and identify the need for additional data. These assessment documents are submitted to the U.S. EPA and subsequently undergo review by experts in an independent peer consultation meeting that is open to the public. Following this peer consultation process, the U.S. EPA reviews each submission and makes a data-needs determination, which may include requesting further data collection or generation by the sponsor. Sponsoring companies then decide whether to volunteer for the next tier and collect or generate the requested data. The purpose of this article is to describe the VCCEP process and to review and present the key findings from the first set of chemicals that have been fully or partially evaluated under the pilot program (vinylidene chloride, decabromodiphenyl ether, pentabromodiphenyl ether, octabromodiphenyl ether, acetone, methyl ethyl ketone, decane, undecane, and dodecane). Specifically, we provide a brief summary of the sponsors' submissions, the peer consultation panels' discussions, and the U.S. EPA's data-needs decisions. Although we do not attempt to conduct independent analyses of the underlying data, we do identify a number of common themes that have emerged during implementation of the pilot program and discuss several key issues that could become important in the future. The information presented here should be useful for various parties interested in the progress of the VCCEP and the results of the initial (Tier 1) children's assessments.     

Design Improvements for Message Propagation in Malleable Social Networks

This study presents the formal problem definition and computational analysis of the network design improvements for idea and message propagation in both enterprise and consumer social networks (ESN and CSN, respectively). Message propagation in social networks is impacted by how messages are seeded in the network, and by propagation characteristics of the network topology itself. It has been recognized that the propagation properties of these networks can be actively influenced by network design interventions, such as the deliberate creation of new connections. We address the problem of finding cost‐effective message seeding, and identifying potential new network connections that allow improved propagation in social networks with cascade propagation. We use the hop‐constrained minimum spanning tree (HMST) model to find the seeds and possible new connections that result in networks with improved propagation properties. Moreover, we present new heuristic algorithms that substantially improve the solution quality for the HMST problem. Computational results posit that the design improvements proposed by the HMST approach can greatly improve cascade propagation performance of the networks at low cost.     

Bioequivalence and the pharmaceutical industry

Since the early 1990s, average bioequivalence (ABE) studies have served as the international regulatory standard for demonstrating that two formulations of drug product will provide the same therapeutic benefit and safety profile when used in the marketplace. Population (PBE) and individual (IBE) bioequivalence have been the subject of intense international debate since methods for their assessment were proposed in the late 1980s and since their use was proposed in United States Food and Drug Administration guidance in 1997. Guidance has since been proposed and finalized by the Food and Drug Administration for the implementation of such techniques in the pioneer and generic pharmaceutical industries. The current guidance calls for the use of replicate design and of cross‐over studies (cross‐overs with sequences TRTR, RTRT, where T is the test and R is the reference formulation) for selected drug products, and proposes restricted maximum likelihood and method‐of‐moments techniques for parameter estimation. In general, marketplace access will be granted if the products demonstrate ABE based on a restricted maximum likelihood model. Study sponsors have the option of using PBE or IBE if the use of these criteria can be justified to the regulatory authority. Novel and previously proposed SAS^®‐based approaches to the modelling of pharmacokinetic data from replicate design studies will be summarized. Restricted maximum likelihood and method‐of‐moments modelling results are compared and contrasted based on the analysis of data available from previously performed replicate design studies, and practical issues involved in the application of replicate designs to demonstrate ABE are characterized. It is concluded that replicate designs may be used effectively to demonstrate ABE for highly variable drug products. Statisticians should exercise caution in the choice of modelling procedure. Copyright © 2002 John Wiley & Sons, Ltd.     

Process evaluation of the midwifery initiated oral health-dental service program: Perceptions of midwives in Greater Western Sydney,Australia

Background

Despite links between poor maternal oral health, adverse pregnancy outcomes and early childhood decay there is limited emphasis on maternal oral health in Australia. To address this, the Midwifery Initiated Oral Health Dental Service (MIOH-DS) program was developed in collaboration with the Australian College of Midwives.

Sexual Orientation,Relationships with Parents,Stress, and Depressive Symptoms among Adults

Disparities in depressive symptoms as a function of sexual orientation have been well documented, but less is known about their origins. This study examines whether, even in adulthood, less favorable parental relationships are associated with disparities in depressive symptoms as a function of sexual orientation. Cross-sectional data were drawn from Wave IV of the National Longitudinal Study of Adolescent to Adult Health. Gay, lesbian, and bisexual (GLB) participants reported lower quality parental relationships, greater stress, and more depressive symptoms than did heterosexual participants. Lower quality parental relationships were associated with higher stress. Higher stress and lower quality parental relationships were associated with more depressive symptoms. GLB individuals reported lower father relationship quality and higher stress, which partially mediated the association of sexuality and depressive symptoms. Lesbian and bisexual women reported lower mother relationship quality and higher stress, which fully mediated the association of sexuality and depressive symptoms. While no differences in mother relationship quality existed for men, mother relationship quality was more strongly associated with depressive symptoms for gay and bisexual men than for heterosexual men. Even in adulthood, greater stress and depressive symptoms among GLB individuals were at least partially accounted for by less favorable parental relationships.     

Supervising family therapy trainees in primary care medical settings: context matters

The purpose of this article is to identify and describe four essential skills for effective supervision of family therapy trainees in primary care medical settings. The supervision skills described include: (1) Understand medical culture; (2) Locate the trainee in the treatment system; (3) Investigate the biological/health issues; and (4) Be attentive to the self-of-the-therapist. Recommendations are also made to help supervisors become better prepared for the questions medical family therapy trainees bring to supervision.     

Viewpoint: observations on scaled average bioequivalence

The two one-sided test procedure (TOST) has been used for average bioequivalence testing since 1992 and is required when marketing new formulations of an approved drug. TOST is known to require comparatively large numbers of subjects to demonstrate bioequivalence for highly variable drugs, defined as those drugs having intra-subject coefficients of variation greater than 30%. However, TOST has been shown to protect public health when multiple generic formulations enter the marketplace following patent expiration. Recently, scaled average bioequivalence (SABE) has been proposed as an alternative statistical analysis procedure for such products by multiple regulatory agencies. SABE testing requires that a three-period partial replicate cross-over or full replicate cross-over design be used. Following a brief summary of SABE analysis methods applied to existing data, we will consider three statistical ramifications of the proposed additional decision rules and the potential impact of implementation of scaled average bioequivalence in the marketplace using simulation. It is found that a constraint being applied is biased, that bias may also result from the common problem of missing data and that the SABE methods allow for much greater changes in exposure when generic-generic switching occurs in the marketplace.     

UPPER BOUNDS FOR EFFICIENCY FACTORS IN BLOCK DESIGNS

Upper bounds are derived for efficiency factors in block designs with particular types of variety or block concurrence matrices. These bounds compare favorably with existing upper bounds.