Table 4 Process area 1, informativeness-centric. An informative CT includes a hypothesis that addresses an important and unresolved scientific, medical, or policy question; is designed to provide meaningful evidence related to this question; must have a realistic plan for recruiting sufficient participants; must be conducted and analyzed in a scientifically valid manner; and reports methods and results accurately, completely, and promptly [27]. An alternate definition is that an informative CT is designed to have the best chance to complete on time, answer its research questions definitively, and effect policy change or a regulatory process, through special commitment to (a) siting the CT based on epidemiology and impact rather than convenience, (b) completing a statistical analysis plan concurrently with the CT protocol, (c) using accepted endpoints and conservative effect and prevalence/incidence estimates, and (d) utilizing contemporary techniques, such as statistical simulation, innovative CT designs, and software to monitor recruitment

ML5

Innovating

Review organization is efficiently applying artificial intelligence, digital innovation, and novel data to each review to surface informativeness risk. New research, based on studies that end informatively, is being performed to identify true drivers of informativeness. Innovations are invested in that make drivers to informativeness more clearly identified by reviewers. Improvements to continuing education for reviewers have occurred. Uncovering new drivers to uninformativeness happens through convenings of peers, talks from visionaries and researchers, and other engagement. Methods of innovative, effective continuing education for expert reviewers who are not pure CT methodologists are explored. Because of the pace of technology improvement and new inventions in the space, not all innovations can be adequately captured and described here.

ML4

Predictable

Informativeness information in the public domain specific to the design to be reviewed is collected and provided to reviewers along with the review materials: review-specific ‘benchmarks’ of similar CTs crafted just in time. Statistics on historical coverage of informativeness review variables are collected and provided to reviewers to ensure more complete reviews. As each review progresses, at interim points early indicators of trending areas of concern amongst reviewers, and/or other-generated risk scores are provided to all reviewers.

ML3

Standardized

The review organization selects the most appropriate definition of informativeness.  A list of common drivers of uninformativeness is made, referred to, and used to educate and orient reviewers. This list is sourced empirically and reinforced with clinical study exemplars. The primacy of informativeness over good clinical practice, regulatory, ethical, or other types of recommendations is mentioned often and debated. The large majority of review recommendations tie to informativeness rather than Good Clinical Practice, regulatory, reducing bias, or other areas of interest. All stakeholders beyond reviewers are prompted to understand informativeness and its drivers.

ML2

Managed

Across reviewers, there is a mix of education level on uninformativeness and what causes it. There is variation in review output based on varying levels of CT experience and other variables. Some reviews have documented recommendations with rich meta-information, others have limited context, others have no documented output other than a discussion. Informativeness is specified as the most important quality of a CT, and the purpose of the review only sometimes focuses on informativeness. Sometimes reviewers ignore the informativeness focus and default to their own focus preferences (regulatory, ethics, clinops, equity, other). Reviews may miss obvious PI shortcuts that increase risk of uninformativeness.

ML1

Initial

Focus on informativeness varies often. Many reviewers believe the word informativeness refers to the traditional definition, rather than being a term of art tied to CT design rigor. Review comments optimize the study design for items unrelated to informativeness, such as safety, ethics, or clinical operations. There is no clear, written statement that the review is about informativeness. There is no discussion or education about the fact that a CT could fail to be informative. PIs can avoid being reviewed if desired. Presence of specific reviewer roles decides whether certain informativeness levers are reviewed.