bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frailty Models
Authors: Wienke Andreas 
Published: October 2006

AbstractThe notion of frailty provides a convenient way to introduce random effects, association, and unobserved heterogeneity into models for survival data. In its simplest form, a frailty is an unobserved random proportionality factor that modifies the hazard function of an individual or related individuals. In essence, the frailty concept goes back to the work of Greenwood and Yule on “accident proneness.” The term frailty itself was introduced by Vaupel et al. in univariate survival models, and the model was substantially promoted by its application to multivariate survival data in a seminal paper by Clayton (without using the notion “frailty”) on chronic disease incidence in families.
Group Sequential Designs
Authors: Wassmer Gernot 
Published: October 2006

AbstractIn clinical research, a great interest in interim analyses exists for ethical, economical, and organizational or administrative reasons. Interim analyses are performed withinsequential designsthat offer the possibility to stop a trial early with a statistically significant test result. This trial will possibly need less patients than the trial with a fixed sample size in which a test decision can be made only at the end of the trial. A therapy that was shown to be superior can be applied earlier and the inferior therapy can be replaced by the better one. Furthermore, in interim analyses, the quality of the performance of the trial can be assessed and possibly be improved when necessary. Interim analyses are also carried out for the assessment of the safety of the treatments under consideration, and the observation of serious adverse events can lead to an early stopping of the trial.
Kaplan–Meier Plot
Authors: Holländer Norbert 
Published: October 2006

AbstractThe Kaplan–Meier plot or Kaplan–Meier curve is the standard method to describe and compare graphically the overall survival of groups of patients. This method is applied to survival time, which is defined as time from treatment start or date of randomization to death or last date of follow up, and, more general, to any type of time‐to‐event data, such as time‐to‐disease progression, time‐to‐detoriation, or time‐to‐first toxicity. Sometimes, the time‐to‐event is also called failure time. In the sequel, the term “survival time” is used as a synonym for any time‐to‐event.
Repeated Measurements
Authors: Verbeke Geert , Lesaffre Emmanuel 
Published: October 2006

AbstractRepeated measures are obtained whenever an outcome is measured repeatedly within a set of units. The fact that observations from the same unit, in general, will not be independent poses particular challenges to the statistical procedures used for the analysis of such data. The current article is dedicated to an overview of frequently used statistical models for the analysis of repeated measurements, with emphasis on model formulation and parameter interpretation.
Linear Model
Authors: Burkholder Iris , Edler Lutz 
Published: October 2006

AbstractLinear Models for simple and multiple regression, Analysis of Variance (ANOVA), and Analysis of Covariance (ANCOVA) have broad and often direct application in clinical trials. Various extensions and generalizations of the Linear Model have been developed more recently often motivated by medical research problems. Most prominent are the loglinear models for the evaluation of count data; the logistic regression model for the evaluation of the influence of clinical factors on a dichotomous outcome as, for example, cancer incidence; and, last but not least, the Cox regression model for the analysis of survival data.
Hazard Ratio
Authors: Schmoor Claudia , Graf Erika 
Published: October 2006

Abstract
Hazard ratios are useful measures to compare groups of patients with respect to a survival outcome. In the context of clinical trials “survival outcome” or “survival time” are used generically to denote the time “survived” from a specified time origin, like diagnosis of cancer, start of treatment, or first infarction, to a specific event of interest, like death, recurrence of cancer, or reinfarction. Broadly speaking, the hazard rate quantifies the risk of experiencing an event at a given point in time. The hazard ratio at that time is the ratio of this risk in one population divided by the risk in a second population chosen as reference group. The hazard ratio between two populations can vary over time. For a given point in time, hazard ratios below 1.0 indicate that the risk of the event is lower in the first group than the risk in the reference group, whereas a hazard ratio of 1.0 indicates equal risks, and values above 1.0 imply a higher risk in the first group compared with the reference population.
Interim Analyses
Authors: Todd Susan 
Published: October 2006

Abstract

Recruitment of patients to a clinical trial usually occurs over time, resulting in the steady accumulation of data throughout the trial's duration. Yet, if traditional statistical methods are implemented, the sample size of the trial should be determined in advance, and data collected on all subjects should occur before an analysis proceeds. For ethical and economic reasons, techniques of sequential testing incorporating
interim analyses
have been developed to enable the valid examination of accumulating data. The aim is to stop a study as soon as sufficient evidence exists to reach a firm conclusion. Here, the advantages and disadvantages of conducting interim analyses in phase III clinical trials are presented and the development of methodology for interim analyses is chronicled and briefly described. Examples are given of completed trials, which have been carried out incorporating interim analyses, and references to relevant software and literature are provided.
Missing Data
Authors: Molenberghs Geert , Lesaffre Emmanuel 
Published: October 2006

AbstractMissing data frequently occur in clinical trials. An important source for missing data are patients who leave the study prematurely, so‐called dropouts. We will concentrate here on the impact of dropouts on the clinical trial analysis.When patients are evaluated under treatment only once, then the presence of dropouts makes it hard to comply with the intention‐to‐treat (ITT) principle. However, when repeated measurements are taken, then one can make use of the observed portion of the data to retrieve information on dropouts. Generally, commonly used methods to analyze incomplete longitudinal clinical trial data include complete case (CC) analysis and a last observation carried forward (LOCF) analysis. However, these methods rest on strong and unverifiable assumptions about the dropout mechanism. Over the last decades, several longitudinal data analysis methods have been suggested, providing a valid estimate for, e.g., the treatment effect under less restrictive assumptions.The assumptions regarding the dropout mechanism have been classified by Rubin and co‐workers as missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR). We will argue that repeated measures analysis provide valid estimates of the treatment effect under MAR. Finally, as it is impossible to verify that the dropout mechanism is MAR, we argue that, to evaluate the robustness of the conclusion, a sensitivity analysis thereby varying the assumption on the dropout mechanism should become a standard procedure when analyzing the results of a clinical trial.
Ethical Challenges Posed by Cluster Randomization
Authors: Klar Neil , Donner Allan 
Published: October 2006

Abstract
The purpose of this article is to discuss the ethical challenges posed by cluster randomized trials, which is done by revisiting the development of ethical guidelines that have been largely developed in the context of individually randomized clinical trials. A recurring theme underlying the article is that the relative absence of ethical guidelines for cluster randomized trials appears to have created a research environment in which the choice of randomization unit may determine whether informed consent is deemed necessary before random assignment. It seems questionable, on both an ethical level and a methodological level, whether the unit of randomization should play such a critical role in obtaining informed consent. Editors should require all reports of randomized trials to include mention of Institutional Review Board (IRB) approval and to discuss subject consent. For cluster randomized trials, however, additional discussion of procedures used to obtain informed consent is warranted.
Group‐Randomized Trials
Authors: Murray David M. 
Published: October 2006

AbstractThe purpose of this article is to put group‐randomized trials (GRTs) in context in terms of other kinds of designs and in terms of the terminology used in other fields, to summarize their development in public health, to characterize the range of public health research areas that now employ GRTs, to characterize the state of practice with regard to the design and analysis of GRTs, to consider their future in public health research, and to review the steps required to plan a new GRT.
Methods for Conduct of Rigorous Group‐Randomization
Authors: Peterson Arthur V. 
Published: October 2006

Abstract

A group‐randomized trial (GRT) has two defining characteristics: (
1
) it investigates the effectiveness of a
group
‐delivered intervention, and (
2
) it includes at least one intervention condition and at least one control condition to which
groups
are
randomly
assigned.
1
The groups can be, for example, schools, worksites, clinics, neighborhoods, or even entire towns or cities. Such group‐delivered interventions have advantages of practicality and cost‐efficiency in reaching large numbers of people and, once proven effective, can be important contributions to public health strategy and policy.
Community‐Based Breast and Cervical Cancer Control Research in Asian Immigrant Populations
Authors: Taylor Victoria M. , Hislop T. Gregory , Yasui Yutaka , Tu Shin‐Ping , Jackson J. Carey 
Published: October 2006

AbstractAsian‐American women are less likely to receive mammography and Papanicolaou (Pap) testing than women from other racial/ethnic groups. Screening rates are particularly low among Asian women who are not proficient in English. This article focuses on community‐based breast and cervical cancer control research in Asian populations. First, the authors address community participatory research principles and several important program evaluation issues: sampling, survey methods, recruitment and retention, translation, data quality, and control group “contamination.” Second, the authors summarize community‐based studies that aimed to increase mammography or Pap testing levels among women of Asian descent. Overall, 9 relevant studies are identified that targeted Asian communities in Canada, the United States, and England. Overall, three of the studies randomized individual women to intervention or control status, two randomized groups of women, and four used a quasi‐experimental (two‐community) study design. These studies, which reported mixed results, highlight the methodological challenges in conducting evaluative public health research, particularly in racial/ethnic minority communities.
Pharmacovigilance
Authors: Waller Patrick , Evans Stephen 
Published: October 2006

AbstractPharmacovigilance is considered here to include all safety‐related activity beyond the point at which humans are first exposed to a new medicinal drug. It is a process of clinical risk management involving the identification, investigation, and minimization of the adverse effects of medication, in particular those that have serious clinical consequences. This article considers the purposes of pharmacovigilance, methodologies, and systems and processes in place to prevent adverse drug reactions (ADRs), which includes the reporting to regulatory authorities of serious, unexpected, and suspected adverse reactions that occur in clinical trials. We also cover some historical aspects, consider the limitations of existing approaches, and provide pointers for the future development of this discipline.
The Belmont Report
Authors: Zucker Deborah 
Published: October 2006

Abstract

The Belmont Report summarizes the basic ethical principles and guidelines identified by the commission to assist in the protection of human subjects in research. The report focuses on three main areas, (
1
) the boundaries between research and practice, (
2
) the basic ethical principles that should underlie the conduct of research (autonomy, beneficence, justice) and the protection of human subjects, and (
3
) the application of these principles into practice. The report outlines general recommendations regarding obtaining informed consent, the assessment of risk and benefit, and the recruitment of participants. The Belmont Report lays out many of the ethical considerations that, to this day, are used in formulating regulations and in ensuring the protection of human study volunteers.
Clinical Significance
Authors: Kamath Celia C. , Sloan Jeffrey A. , Cappelleri Joseph C. 
Published: October 2006

Abstract
This article defines clinical significance, as opposed to statistical significance, as it relates to health‐related quality of life measures used in clinical trials. It provides a brief history of the concept and addresses the different perspectives from which it is perceived and interpreted. It describes the current methods used to assess clinical significance and provides several examples of the different ways of measuring, validating, and using clinical significance. Recent developments on the concept are discussed. Finally, directions for future research are highlighted.
Hypothesis
Authors: Rosenkranz Gerd 
Published: October 2006

Abstract
In the following article, the authors briefly review the role of hypotheses in science before statistical hypotheses and their relevance for clinical studies are investigated. The authors explain what statistical hypotheses have in common with scientific hypotheses and how they differ. In particular, testing statistical hypotheses is somewhat different from testing scientific hypotheses, although some general ideas apply to both. Eventually, the importance of formulating testable hypotheses for clinical studies are explored and some specific topics like superiority, equivalence, non‐inferiority, and multiple hypotheses are discussed.
Genetic counselors and research: Current practices and future directions
Authors: Clark Heather M. , Gamm Jennifer , Huether Carl A. , Buncher C. Ralph , Pfau Ruthann I. Blough , Warren Nancy Steinberg 
Published: October 2006

AbstractMembers of the genetic counseling community have debated the need for doctoral degree programs to further advance the profession. However, genetic counselors' interest in conducting independent research and attitudes toward obtaining a doctoral degree in genetic counseling has not been assessed in more than a decade. We designed a comprehensive web‐based survey to characterize the current research values and practices of genetic counselors. Respondents were asked to self‐report their current research involvement, their specific role in research activities, and their interest in performing research in the future. The study showed that a significant number of genetic counselors (84.5%) have conducted previous research, and 69.4% of respondents plan to perform research in the future. These results reflect the maturation of the genetic counseling field, in that a substantial number of genetic counselors consider active involvement in research to be a core role. The study also showed that 34.1% of respondents have high interest in a hypothetical PhD in Genetic Counseling, suggesting that the profession is primed for the development of doctoral degree training options. © 2006 Wiley‐Liss, Inc.
Uncertainty and perceived personal control among parents of children with rare chromosome conditions: The role of genetic counseling
Authors: Lipinski Shawn E. , Lipinski Michael J. , Biesecker Leslie G. , Biesecker Barbara B. 
Published: October 2006

AbstractLittle is known about the impact of genetic counseling on parental uncertainty or perceived control regarding the prognosis of a child with a chromosomal disorder. By exploring the parents' concerns and needs surrounding the child's diagnosis, a genetic provider can help to facilitate effective coping. This study tested the association of measures of parental uncertainty and perceived control with the perceived helpfulness of the genetic counselor. A survey was distributed to 875 members of the Chromosome Deletion Outreach (CDO) support group. We hypothesized that parents' perceptions about the helpfulness of the genetic counselor would modify the relationship between perceived uncertainty, perceived control, and coping. Among the 363 respondents, there was a significant negative correlation of the perceived helpfulness of seeing a genetic counselor with the levels of uncertainty (rs = −0.20,P‐value < 0.001). Lower perceived helpfulness of the genetic counselor, along with less perceived personal control, less benefit of a diagnosis, and lower parental age were significant predictors of the highest perceptions of uncertainty. The Transactional Model of Stress and Coping was used as a framework for interpreting the relationships between parental uncertainty, perceived control, and outcome variables. There was a significant positive correlation between parents' perceived personal control and their reports of helpfulness of the genetic counselor (rs = 0.20,P‐value <0.0006). Genetic counseling can be enhanced for parents faced with rare disorders by using interventions focused on reducing feelings of uncertainty and enhancing feelings of control. © 2006 Wiley‐Liss, Inc.
Referral to cancer genetic counseling: Are there stages of readiness?
Authors: O'Neill Suzanne M. , Peters June A. , Vogel Victor G. , Feingold Eleanor , Rubinstein Wendy S. 
Published: October 2006

AbstractAs genetic awareness spreads among healthcare providers and the general public, and evidence mounts to show the efficacy of cancer control methods, referrals to cancer genetic counseling services for risk assessment are becoming more common. However, few studies have examined referral patterns to genetics and even less is known about referral uptake to clinical cancer genetic counseling. We investigated outcome of genetics referral in 43 affected women attending a breast cancer treatment program who were referred based on having BRCA mutation carrier risks ≥10%. Within 6 months, of the 36 women we were able to recontact, 13 (36%) came to an appointment at the cancer genetic counseling clinic (Acceptors), 10 (27%) said they intended to come in the future (Intenders), and 13 (36%) said they would not consider genetic counseling (Decliners). Referral uptake was framed by elements of the Transtheoretical model (TTM) to determine if decisional balance scores (DBSs), a summary of an individual's “Pro” and “Con” opinions related to genetic testing, correlated with their decision to follow through. Mean DBS's were strongly negative for the Decliner group (−7.4), weakly negative for the Intender group (−1.1), and positive for the Acceptor group (5.4). The difference in the DBS along the continuum was due more to the mean “Con” score decreasing, rather than the mean “Pro” score increasing. Theoretical frameworks are needed to study adherence to referral for cancer genetic counseling. Stage‐based theories may have a role to play. © 2006 Wiley‐Liss, Inc.
Ethical and clinical practice considerations for genetic counselors related to direct‐to‐consumer marketing of genetic tests
Authors: Wade Christopher H. , Wilfond Benjamin S. 
Published: October 2006

AbstractSeveral companies utilize direct‐to‐consumer (DTC) advertising for genetic tests and some, but not all, bypass clinician involvement by offering DTC purchase of the tests. This article examines how DTC marketing strategies may affect genetic counselors, using available cardiovascular disease susceptibility tests as an illustration. The interpretation of these tests is complex and includes consideration of clinical validity and utility, and the further complications of gene–environment interactions and pleiotropy. Although it is unclear to what extent genetic counselors will encounter clients who have been exposed to DTC marketing strategies, these strategies may influence genetic counseling interactions if they produce directed interest in specific tests and unrealistic expectations for the tests' capacity to predict disease. Often, a client's concern about risk for cardiovascular diseases is best addressed by established clinical tests and a family history assessment. Ethical dilemmas may arise for genetic counselors who consider whether to accept clients who request test interpretation or to order DTC‐advertised tests that require a clinician's authorization. Genetic counselors' obligations to care for clients extend to interpreting DTC tests, although this obligation may be fulfilled by referral or consultation with specialists. Genetic counselors do not have an obligation to order DTC‐advertised tests that have minimal clinical validity and utility at a client's request. This can be a justified restriction on autonomy based on consideration of risks to the client, the costs, and the implications for society. Published 2006 Wiley‐Liss, Inc.
Through the viewfinder: Positive Exposure a year later
Authors: Sutton Erica J. , Rosapep Lauren , Ball Karen , Truitt Megan , Biesecker Barbara , Guidotti Rick , McLean Diane 
Published: October 2006

AbstractPositive Exposure, a non‐profit organization founded and directed by former fashion photographer Rick Guidotti and co‐directed by psychiatrist Dr. Diane McLean, uses photography and video interviews to explore the lived experiences of people affected with genetic conditions. Positive Exposure challenges pervasive social biases and stereotypes about genetic variation and strives to broaden and enrich societal perceptions of human beauty and spirit. Presented here are the open‐ended personal reflections completed by four individuals with craniofacial differences recruited from a support group, Inner Faces. These four case studies aim to relay the professional photo‐shoot experiences of people who may be challenged by the stigma associated with craniofacial differences. Questions addressed issues of perceived self‐esteem, stigma, hopefulness, and photography experiences. These personal reflections were gathered 1 year following participation in a Positive Exposure photo‐shoot. Participants described the ways in which the photo‐shoot has been a lasting and life‐promoting experience. In addition, these individuals emphasize the integral and enduring role the photographer, Rick Guidotti, played in their personal awakening. Positive Exposure provided these individuals with renewed identification of both inner and outer sources of beauty. These four case studies suggest that Positive Exposure may serve as a sustainable intervention to bolster self‐esteem and self‐image. Published 2006 Wiley‐Liss, Inc.