Utilization of opt-out registries in emergency clinical research

Background: Emergency clinical research aims to study and develop new treatments for acute injuries and illnesses such as stroke, traumatic brain injury, seizures, and meningitis. While the regulations require that researchers provide information about ways in which individuals wishing to be excluded from a study may indicate this preference, they do not require emergency clinical research investigators to provide specific resources to members of the public who may wish to opt out of the research. Objectives: We investigated the methods which potential research subjects at a Midwest US university community might use to opt out of emergency clinical researcher. The primary aim of this research was to determine the method which potential emergency research subjects would prefer to use to opt out of emergency clinical research (e.g. by being listed online in a registry, by wearing a bracelet, or through direct communication with the research team). Methods: Students and staff at Eastern Michigan University in Ypsilanti, Michigan, were asked to respond to an online survey. Findings: 218 respondents participated in the survey. The data showed that 43.1% of respondents preferred to opt out by talking to the study team in person, while 39.2% of study respondents preferred opting out online. Findings: 218 respondents participated in the survey. The data showed that 43.1% of respondents preferred to opt out by talking to the study team in person, while 39.2% of study respondents preferred opting out online

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

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

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

Additional file 1: of Attitudes and opinions regarding confirmatory adaptive clinical trials: a mixed methods analysis from the Adaptive Designs Accelerating Promising Trials into Treatments (ADAPT-IT) project

ADAPT-IT general-coreq-FINAL. Consolidated criteria for reporting qualitative research (COREQ) checklist contents: responses to the 32-item COREQ checklist as applicable to the current research study. (DOCX 26 kb

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