Adoption of Decentralization: Are Our Perceptions Holding Us Back?

Incorporating decentralized approaches into clinical trials is a critical innovation with potential implications for improved accessibility and diversity, as well as lower burden for participants and caregivers. As we move forward in a collective effort to modernize clinical trials, we consistently hear of hurdles that interfere with the adoption of decentralized approaches. But are these hurdles really the impediments we think they are? In this commentary, we offer three perceptions that are commonly heard as impediments to the adoption of digital and decentralized clinical trials. Leveraging the Clinical Trial Transformation Initiative's Digital Health Trial hub of work, interactions with members and regulators, and observations related to adoption, we address those perceptions and note some resources that exist to overcome them. In working through these barriers, we can instill confidence in sponsors and designers to leverage all the clinical trial design tools available to them to advance the use of decentralized approaches.

Investigator Experiences Using Mobile Technologies in Clinical Research: Qualitative Descriptive Study.

BACKGROUND: The successful adoption of mobile technology for use in clinical trials relies on positive reception from key stakeholders, including clinical investigators; however, little information is known about the perspectives of investigators using mobile technologies in clinical trials. OBJECTIVE: The aim of this study was to seek investigators' insights on the advantages and challenges of mobile clinical trials (MCTs); site-level budgetary, training, and other support needs necessary to adequately prepare for and implement MCTs; and the advantages and disadvantages for trial participants using mobile technologies in clinical trials. METHODS: Using a qualitative descriptive study design, we conducted in-depth interviews with investigators involved in the conduct of MCTs. Data were analyzed using applied thematic analysis. RESULTS: We interviewed 12 investigators who represented a wide variety of clinical specialties and reported using a wide range of mobile technologies. Investigators most commonly cited 3 advantages of MCTs over traditional clinical trials: more streamlined study operations, remote data capture, and improvement in the quality of studies and data collected. Investigators also reported that MCTs can be designed around the convenience of trial participants, and individuals may be more willing to participate in MCTs because they can take part from their homes. In addition, investigators recognized that MCTs can also involve additional burden for participants and described that operational challenges, technology adoption barriers, uncertainties about data quality, and time burden made MCTs more challenging than traditional clinical trials. Investigators stressed that additional training and dedicated staff effort may be needed to select a particular technology for use in a trial, helping trial participants learn and use the technology, and for staff troubleshooting the technology. Investigators also expressed that sharing data collected in real time with investigators and trial participants is an important aspect of MCTs that warrants consideration and potentially additional training and education. CONCLUSIONS: Investigator perspectives can inform the use of mobile technologies in future clinical trials by proactively identifying and addressing potential challenges.

Real-World Data for Planning Eligibility Criteria and Enhancing Recruitment: Recommendations from the Clinical Trials Transformation Initiative.

The growing availability of real-world data (RWD) creates opportunities for new evidence generation and improved efficiency across the research enterprise. To varying degrees, sponsors now regularly use RWD to make data-driven decisions about trial feasibility, based on assessment of eligibility criteria for planned clinical trials. Increasingly, RWD are being used to support targeted, timely, and personalized outreach to potential trial participants that may improve the efficiency and effectiveness of the recruitment process. This paper highlights recommendations and resources, including specific case studies, developed by the Clinical Trials Transformation Initiative (CTTI) for applying RWD to planning eligibility criteria and recruiting for clinical trials. Developed through a multi-stakeholder, consensus- and evidence-driven process, these actionable tools support researchers in (1) determining whether RWD are fit for purpose with respect to study planning and recruitment, (2) engaging cross-functional teams in the use of RWD for study planning and recruitment, and (3) understanding patient and site needs to develop successful and patient-centric approaches to RWD-supported recruitment. Future considerations for the use of RWD are explored, including ensuring full patient understanding of data use and developing global datasets.

Development and Application of a Patient Group Engagement Prioritization Tool for Use in Medical Product Development.

INTRODUCTION: Patient group engagement is increasingly used to inform the design, conduct, and dissemination of clinical trials and other medical research activities. However, the priorities of industry sponsors and patient groups differ, and there is currently no framework to help these groups identify mutually beneficial engagement activities. METHODS: We conducted 28 qualitative, semi-structured interviews with representatives from research sponsor organizations (n = 14) and patient groups (n = 14) to determine: (1) how representatives define benefits and investments of patient group engagement in medical product development, and (2) to refine a list of 31 predefined patient group engagement activities. RESULTS: Patient group and sponsor representatives described similar benefits: engagement activities can enhance the quality and efficiency of clinical trials by improving patient recruitment and retention, reduce costs, and help trials meet expectations of regulators and payers. All representatives indicated that investments include both dedicated staff time and expertise, and financial resources. Factors to consider when evaluating benefits and investments were also identified as were suggestions for clarifying the list of engagement activities. DISCUSSION: Using these findings, we refined the 31 engagement activities to 24 unique activities across the medical product development lifecycle. We also developed a web-based prioritization tool ( https://prioritizationtool.ctti-clinicaltrials.org/ ) to help clinical research sponsors and patient groups identify high-priority engagement activities. Use of this tool can help sponsors and patient groups identify the engagement activities that they believe will provide the most benefit for the least investment and may lead to more meaningful and mutually beneficial partnerships in medical product development.

Learning from patient and site perspectives to develop better digital health trials: Recommendations from the Clinical Trials Transformation Initiative.

In order to harness the potential of digital health technologies to enhance the quality of clinical research, it is critical to first understand how to engage patients and research sites when planning and conducting digital health trials. To pave the way for the more effective use of digital health technologies in trials, the Clinical Trials Transformation Initiative has developed the first comprehensive, evidence-based set of recommendations for incorporating patient and site perspectives in digital health trials. While directed primarily at sponsors, these recommendations are expected to be valuable for all stakeholders including investigators.

Patient preferences for using mobile technologies in clinical trials.

The use of mobile technologies to collect participant data in clinical trials offers a number of scientific and logistical advantages. However, little is known about potential research participant preferences about how to incorporate mobile technologies into the design and conduct of a trial. Using a web-based survey which described hypothetical mobile clinical trial and traditional clinical trial scenarios, we explored patients' perceptions of and willingness to participate in mobile and traditional clinical trials, their preferred trial procedures related to the use of mobile technologies, and the preferred attributes of mobile technologies. The majority of survey respondents reported that they would prefer participating in a clinical trial that used mobile technology than a traditional trial that relied on standard in-clinic assessments. They expressed that mobile clinical trials offered greater convenience, a reduction of in-person clinic visits, and greater data collection accuracy. Respondents also reported preferences for the frequency of in-clinic visits during mobile clinical trials, device training and troubleshooting, data privacy and confidentiality, the location of data storage, and user access to data collected by the trial device. As research participants become more involved in capturing their own data to inform trial endpoints, their user-preferences of mobile technology, such as those described here, should be considered in the design and conduct of mobile clinical trials.

The Clinical Trials Transformation Initiative: Methodology supporting the mission.

The mission of the Clinical Trials Transformation Initiative, a public-private partnership co-founded by the U.S. Food and Drug Administration and Duke University, is to develop and drive adoption of practices that will increase the quality and efficiency of clinical trials. The Clinical Trials Transformation Initiative works collaboratively with key stakeholders, implements "fit-for-purpose" evidence-gathering projects, and develops actionable recommendations and tools to address the challenges faced by the clinical trials enterprise. In pursuit of its mission, The Clinical Trials Transformation Initiative follows an innovative and collaborative, five-step methodology: (1) state the problem and identify impediments to research, (2) gather evidence to identify gaps and barriers, (3) explore results by analyzing and interpreting findings, (4) finalize solutions by developing recommendations and tools, and (5) drive adoption through disseminating and implementing recommendations and tools. This article describes each step of the Clinical Trials Transformation Initiative's methodology, with a specific focus on describing the evidence-gathering activities.

Informed consent in clinical research: Consensus recommendations for reform identified by an expert interview panel.

BACKGROUND: Informed consent is the cornerstone for protection of human subjects in clinical trials. However, a growing body of evidence suggests that reform of the informed consent process in the United States is needed. METHODS: The Clinical Trials Transformation Initiative conducted interviews with 25 experienced observers of the informed consent process to identify limitations and actionable recommendations for change. RESULTS: There was broad consensus that current practices often fail to meet the ethical obligation to inform potential research participants during the informed consent process. The most frequent single recommendation, which would affect all participants in federally regulated clinical research, was reform of the informed consent document. The interviews also identified the need for reform of clinical research review by institutional review boards, including transitioning to a single institutional review board for multi-site trials. CONCLUSION: The consensus recommendations from the interviewees provide a framework for meaningful change in the informed consent process. Although some proposed changes are feasible for rapid implementation, others such as substantive reform of the informed consent document may require change in federal regulations.

Meeting the obligation to communicate clinical trial results to study volunteers.

Although the overwhelming majority of study volunteers want to receive information on the results of their participation in clinical trials, research suggests that most study volunteers never do. CISCRP - an independent nonprofit organization - in collaboration with Pfizer, conducted a study evaluating the feasibility and impact of a new process to inform study volunteers of the results of their clinical trials. Two process components were evaluated via surveys, focus groups, and interviews with volunteers and investigative site staff: a series of ongoing post-trial communications to set expectations for when trial results would be received; and routine development and delivery of the lay language trial results summary. The results of this assessment show that study volunteers and investigative site staff are extremely receptive to receiving clinical trial results and that the process of preparing and disseminating clinical trial results is feasible and generally easy to execute. The results also indicate that study volunteer comprehension of basic facts about their clinical trial pre- and post-test increased by as much as 65.6 percentage points, and suggest that this communication initiative may positively impact volunteer recruitment, retention and long-term trust in the clinical research enterprise.