Background Traditional clinical trials are often expensive, inefficient, include selected populations, and can create significant participant burden via travel and other logistical demands. Using new technologies and methodologies to promote a decentralized approach has the potential to improve the efficiency of clinical trials. The Clinical Trials Transformation Initiative (CTTI)-a public-private partnership to improve clinical trials-launched a multi-stakeholder Decentralized Clinical Trials (DCTs) Project to provide recommendations on addressing the actual and perceived legal, regulatory, and practical challenges with DCT design and conduct in the United States. Methods Informed by qualitative group interviews and an expert meeting, CTTI engaged stakeholders to identify key challenges to implementing DCTs and possible solutions. Results The CTTI DCT project team used the interview findings and expert feedback to develop recommendations that will drive broader use of DCTs. Conclusions CTTI's recommendations cover protocol design, use of telemedicine and mobile healthcare providers, medical product supply chain, investigator delegation and oversight, and safety monitoring considerations. By implementing these recommendations, sponsors, contract research organizations, and others can help advance successful medical product development using mobile technologies and methodologies in DCTs.

Ethically sound clinical research requires that prospective study participants provide voluntary informed consent before any study procedures begin. The original intent was to provide the participant with clear, accurate information about study specifics (e.g., risks/benefits) to aid in the decision to participate. Broad consensus among sponsors, research staff, study participants, and advocates indicate that the current process could be improved to enhance participants' understanding of study-related information and meet the needs of individuals. The Clinical Trials Transformation Initiative (CTTI) convened a project to identify problems in the current process and to formulate recommendations for improvement. A literature review, expert interviews, and multi-stakeholder meeting were conducted to identify barriers and develop solutions for a more effective informed consent process. Four key topics were the foundation of the recommendations: 1) defining an effective informed consent process, 2) training research staff, 3) improving the informed consent document, and 4) exploring the use of electronic consent. The ideal informed consent process involves an ongoing, interactive conversation between the participant and knowledgeable, responsive research staff who were trained in best practices. The informed consent process should be supported by a tiered informed consent document that provides critically relevant information to aid in the decision to participate in a study. Adoption of the CTTI informed consent recommendations should lead to a more participant-centric informed consent process. Participant involvement better meets the needs of participants and benefits the clinical trial enterprise by promoting a research culture that encourages informed participation in clinical studies.

BackgroundInformed 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.MethodsThe Clinical Trials Transformation Initiative conducted interviews with 25 experienced observers of the informed consent process to identify limitations and actionable recommendations for change.ResultsThere 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.ConclusionThe 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.

Background/aimsUse of data monitoring committees to oversee clinical trials was first proposed nearly 50 years ago. Since then, data monitoring committee use in clinical trials has increased and evolved. Nonetheless, there are no well-defined criteria for determining the need for a data monitoring committee, and considerable variability exists in data monitoring committee composition and conduct. To understand and describe the role and function of data monitoring committees, and establish best practices for data monitoring committee trial oversight, the Clinical Trials Transformation Initiative—a public–private partnership to improve clinical trials—launched a multi-stakeholder project.MethodsThe data monitoring committee project team included 16 individuals charged with (1) clarifying the purpose of data monitoring committees, (2) identifying best practices for independent data monitoring committee conduct, (3) describing effective communication practices, and (4) developing strategies for training data monitoring committee members. Evidence gathering included a survey, a series of focus group discussions, and a 2-day expert meeting aimed at achieving consensus opinions that form the foundation of our data monitoring committee recommendations.ResultsWe define the role of the data monitoring committee as an advisor to the research sponsor on whether to continue, modify, or terminate a trial based on periodic assessment of trial data. Data monitoring committees should remain independent from the sponsor and be composed of members with no relevant conflicts of interest. Representation on a data monitoring committee generally should include at least one clinician with expertise in the therapeutic area being studied, a biostatistician, and a designated chairperson who has experience with clinical trials and data monitoring. Data monitoring committee meetings are held periodically to evaluate the unmasked data from ongoing trials, but the content and conduct of meetings may vary depending on specific goals or topics for deliberation. To guide data monitoring committee conduct and communication plans, a charter consistent with the protocol’s research design and statistical analysis plan should be developed and agreed upon by the sponsor and the data monitoring committee prior to patient enrollment. We recommend concise and flexible charters that explain roles, responsibilities, operational issues, and how data monitoring committee recommendations are generated and communicated. The demand for data monitoring committee members appears to exceed the current pool of qualified individuals. To prepare a new generation of trained data monitoring committee members, we encourage a combination of didactic educational programs, practical experience, and skill development through apprenticeships and mentoring by experienced data monitoring committee members.ConclusionOur recommendations address data monitoring committee use, conduct, communication practices, and member preparation and training. Furthermore recommendations form th...

Mobile technologies offer the potential to reduce the costs of conducting clinical trials by collecting high-quality information on health outcomes in real-world settings that are relevant to patients and clinicians. However, widespread use of mobile technologies in clinical trials has been impeded by their perceived challenges. To advance solutions to these challenges, the Clinical Trials Transformation Initiative (CTTI) has issued best practices and realistic approaches that clinical trial sponsors can now use. These include CTTI recommendations on technology selection; data collection, analysis, and interpretation; data management; protocol design and execution; and US Food and Drug Administration submission and inspection. The scientific principles underpinning the clinical trials enterprise continue to apply to studies using mobile technologies. These recommendations provide a framework for including mobile technologies in clinical trials that can lead to more efficient assessment of new therapies for patients.