Urogenital Symptoms and Pain History as Precursors of Vulvodynia: A Longitudinal Study

Abstract Background: We sought to assess vulvodynia incidence and risk factors among those with and without premorbid urogenital symptoms. Methods: Women's Health Registry members who completed a baseline assessment in 2004 were sent a 2-year and 4-year follow-up survey containing a validated screen for vulvodynia. Subgroup analysis of vulvodynia incidence rates was performed, and risk factors associated with incidence were assessed. Results: Of 1037 original enrollees, 723 (69.7%) completed consecutive surveys (initial and 2-year or initial, 2-year, and 4-year), 660 of whom did not have current or past vulvodynia at baseline. Of these 660, 71 (10.8%) first met criteria for vulvodynia within the 4-year period, for an annual incidence rate of 3.1% (95% confidence interval [CI] 2.5-4.0). Baseline strict controls were less likely to develop criteria for vulvodynia diagnosis (annual incidence rate of 1.4%) compared to those with an intermediate phenotype (presence of dyspareunia or history of short-term vulvar pain), for whom the incidence rate was 5.6% (p<0.001). Risk factors for incident vulvodynia differed between these two groups. Among the strict controls, an increased risk was noted among younger women (incidence rate ratio) [IRR] 3.6). For those with an intermediate phenotype, risk was increased among nonwhite women and those reporting pain with or after intercourse (IRR 2.2, 3.4, and 3.1, respectively). In both control groups, incident vulvodynia risk increased among those reporting urinary burning at enrollment (IRR 4.2 and 2.8 for strict and intermediate phenotype controls, respectively). Conclusions: The annual incidence of vulvodynia is substantial (3.1%) and is greater among women reporting a history of dyspareunia or vulvar pain that did not meet criteria for vulvodynia compared to those without this history, suggesting that generalized urogenital sensitivity may be a common underlying mechanism predating the clinical presentation of vulvodynia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98465/1/jwh%2E2012%2E3566.pd

Clinical trialist perspectives on the ethics of adaptive clinical trials: a mixed-methods analysis

Abstract Background In an adaptive clinical trial (ACT), key trial characteristics may be altered during the course of the trial according to predefined rules in response to information that accumulates within the trial itself. In addition to having distinguishing scientific features, adaptive trials also may involve ethical considerations that differ from more traditional randomized trials. Better understanding of clinical trial experts’ views about the ethical aspects of adaptive designs could assist those planning ACTs. Our aim was to elucidate the opinions of clinical trial experts regarding their beliefs about ethical aspects of ACTs. Methods We used a convergent, mixed-methods design employing a 22-item ACTs beliefs survey with visual analog scales and open-ended questions and mini-focus groups. We developed a coding scheme to conduct thematic searches of textual data, depicted responses to visual analog scales on box-plot diagrams, and integrated findings thematically. Fifty-three clinical trial experts from four constituent groups participated: academic biostatisticians (n = 5); consultant biostatisticians (n = 6); academic clinicians (n = 22); and other stakeholders including patient advocacy, National Institutes of Health, and U.S. Food and Drug Administration representatives (n = 20). Results The respondents recognized potential ethical benefits of ACTs, including a higher probability of receiving an effective intervention for participants, optimizing resource utilization, and accelerating treatment discovery. Ethical challenges voiced include developing procedures so trial participants can make informed decisions about taking part in ACTs and plausible, though unlikely risks of research personnel altering enrollment patterns. Conclusions Clinical trial experts recognize ethical advantages but also pose potential ethical challenges of ACTs. The four constituencies differ in their weighing of ACT ethical considerations based on their professional vantage points. These data suggest further discussion about the ethics of ACTs is needed to facilitate ACT planning, design and conduct, and ultimately better allow planners to weigh ethical implications of competing trial designs.http://deepblue.lib.umich.edu/bitstream/2027.42/111302/1/12910_2015_Article_22.pd

Reflections on the adaptive designs accelerating promising trials into treatments (ADAPT-IT) process—Findings from a qualitative study

ContextThe context for this study was the Adaptive Designs Advancing Promising Treatments Into Trials (ADAPT-IT) project, which aimed to incorporate flexible adaptive designs into pivotal clinical trials and to conduct an assessment of the trial development process. Little research provides guidance to academic institutions in planning adaptive trials.ObjectivesThe purpose of this qualitative study was to explore the perspectives and experiences of stakeholders as they reflected back about the interactive ADAPT-IT adaptive design development process, and to understand their perspectives regarding lessons learned about the design of the trials and trial development.Materials and methodsWe conducted semi-structured interviews with ten key stakeholders and observations of the process. We employed qualitative thematic text data analysis to reduce the data into themes about the ADAPT-IT project and adaptive clinical trials.ResultsThe qualitative analysis revealed four themes: education of the project participants, how the process evolved with participant feedback, procedures that could enhance the development of other trials, and education of the broader research community.Discussion and conclusionsWhile participants became more likely to consider flexible adaptive designs, additional education is needed to both understand the adaptive methodology and articulate it when planning trials

The life cycles of six multi-center adaptive clinical trials focused on neurological emergencies developed for the Advancing Regulatory Science initiative of the National Institutes of Health and US Food and Drug Administration: Case studies from the Adaptive Designs Accelerating Promising Treatments Into Trials Project

Objectives: Clinical trials are complicated, expensive, time-consuming, and frequently do not lead to discoveries that improve the health of patients with disease. Adaptive clinical trials have emerged as a methodology to provide more flexibility in design elements to better answer scientific questions regarding whether new treatments are efficacious. Limited observational data exist that describe the complex process of designing adaptive clinical trials. To address these issues, the Adaptive Designs Accelerating Promising Treatments Into Trials project developed six, tailored, flexible, adaptive, phase-III clinical trials for neurological emergencies, and investigators prospectively monitored and observed the processes. The objective of this work is to describe the adaptive design development process, the final design, and the current status of the adaptive trial designs that were developed. Methods: To observe and reflect upon the trial development process, we employed a rich, mixed methods evaluation that combined quantitative data from visual analog scale to assess attitudes about adaptive trials, along with in-depth qualitative data about the development process gathered from observations. Results: The Adaptive Designs Accelerating Promising Treatments Into Trials team developed six adaptive clinical trial designs. Across the six designs, 53 attitude surveys were completed at baseline and after the trial planning process completed. Compared to baseline, the participants believed significantly more strongly that the adaptive designs would be accepted by National Institutes of Health review panels and non-researcher clinicians. In addition, after the trial planning process, the participants more strongly believed that the adaptive design would meet the scientific and medical goals of the studies. Conclusion: Introducing the adaptive design at early conceptualization proved critical to successful adoption and implementation of that trial. Involving key stakeholders from several scientific domains early in the process appears to be associated with improved attitudes towards adaptive designs over the life cycle of clinical trial development

A conceptual model for the development process of confirmatory adaptive clinical trials within an emergency research network

BackgroundAdaptive clinical trials use accumulating data from enrolled subjects to alter trial conduct in pre-specified ways based on quantitative decision rules. In this research, we sought to characterize the perspectives of key stakeholders during the development process of confirmatory-phase adaptive clinical trials within an emergency clinical trials network and to build a model to guide future development of adaptive clinical trials.MethodsWe used an ethnographic, qualitative approach to evaluate key stakeholders' views about the adaptive clinical trial development process. Stakeholders participated in a series of multidisciplinary meetings during the development of five adaptive clinical trials and completed a Strengths-Weaknesses-Opportunities-Threats questionnaire. In the analysis, we elucidated overarching themes across the stakeholders' responses to develop a conceptual model.ResultsFour major overarching themes emerged during the analysis of stakeholders' responses to questioning: the perceived statistical complexity of adaptive clinical trials and the roles of collaboration, communication, and time during the development process. Frequent and open communication and collaboration were viewed by stakeholders as critical during the development process, as were the careful management of time and logistical issues related to the complexity of planning adaptive clinical trials.ConclusionThe Adaptive Design Development Model illustrates how statistical complexity, time, communication, and collaboration are moderating factors in the adaptive design development process. The intensity and iterative nature of this process underscores the need for funding mechanisms for the development of novel trial proposals in academic settings

Reflections on the adaptive designs accelerating promising trials into treatments (ADAPT-IT) process—Findings from a qualitative study

CONTEXT: The context for this study was the Adaptive Designs Advancing Promising Treatments Into Trials (ADAPT-IT) project, which aimed to incorporate flexible adaptive designs into pivotal clinical trials and to conduct an assessment of the trial development process. Little research provides guidance to academic institutions in planning adaptive trials. OBJECTIVES: The purpose of this qualitative study was to explore the perspectives and experiences of stakeholders as they reflected back about the interactive ADAPT-IT adaptive design development process, and to understand their perspectives regarding lessons learned about the design of the trials and trial development. MATERIALS AND METHODS: We conducted semi-structured interviews with ten key stakeholders and observations of the process. We employed qualitative thematic text data analysis to reduce the data into themes about the ADAPT-IT project and adaptive clinical trials. RESULTS: The qualitative analysis revealed four themes: education of the project participants, how the process evolved with participant feedback, procedures that could enhance the development of other trials, and education of the broader research community. DISCUSSION AND CONCLUSIONS: While participants became more likely to consider flexible adaptive designs, additional education is needed to both understand the adaptive methodology and articulate it when planning trials

Correlates of putting condoms on after sex has begun and of removing them before sex ends: a study of men attending an urban public STD clinic

This study aimed to identify possible correlates of putting condoms on after sex has begun and taking them off before sex has ended among male patients of an urban, public sexually transmitted disease clinic. Participants responded to a questionnaire and were largely African American men, 18 to 35 years old, who had used a condom during penile-vaginal intercourse at least three times in the past 3 months. In controlled analyses, men who were not highly motivated to use condoms correctly were nearly twice as likely to put a condom on after sex had begun. Men who reported erection loss during sex were about twice as likely to remove condoms before sex ended. Men reporting difficulties with the fit and feel of condoms were 2.5 times more likely to remove condoms early. Identified correlates may be amenable to clinic-based education and counseling augmented by offering a variety of condom brands and sizes to patients. <br/