The proportion of randomized controlled trials that inform clinical practice

Abstract

Prior studies suggest that clinical trials are often hampered by problems in design, conduct, and reporting that limit their uptake in clinical practice. We have described 'informativeness' as the ability of a trial to guide clinical, policy, or research decisions. Little is known about the proportion of initiated trials that inform clinical practice. We created a cohort of randomized interventional clinical trials in three disease areas (ischemic heart disease, diabetes mellitus, and lung cancer) that were initiated between January 1, 2009 and December 31, 2010 using ClinicalTrials.gov. We restricted inclusion to trials aimed at answering a clinical question related to the treatment or prevention of disease. Our primary outcome was the proportion of clinical trials fulfilling four conditions of informativeness: importance of the clinical question, trial design, feasibility, and reporting of results. Our study included 125 clinical trials. The proportion meeting four conditions for informativeness was 26.4% (95% CI 18.9-35.0). Sixty-seven percent of participants were enrolled in informative trials. The proportion of informative trials did not differ significantly between our three disease areas. Our results suggest that the majority of randomized interventional trials designed to guide clinical practice possess features that may compromise their ability to do so. This highlights opportunities to improve the scientific vetting of clinical research.

Keywords: clinical trials; informative research; medicine; none; research ethics.

Figure 1.. Flow diagram – the proportion of trials meeting four conditions of informativeness.

Figure 2.. The cumulative proportion of trials meeting four conditions of informativeness by disease area.

Figure 2—figure supplement 1.. The cumulative proportion of trials meeting four conditions of informativeness by sponsor.

Of the 67 non-industry funded trials, 7 were funded by the U.S. National Institutes of Health or other U.S. Federal agencies.

Figure 3.. Flow diagram for trial inclusion.

(a) Trials overlapping more than one disease area (e.g. diabetes mellitus and ischemic heart disease) were allocated based on the disease evaluated in the primary outcome. (b) An indeterminate trial is an ongoing trial that has not surpassed twice the planned primary outcome completion date. (c) We used a random number generator (RAND function in Microsoft Excel) to create our 33% sample.

Figure 3—figure supplement 1.. Flow diagram for ischemic heart disease interventional trials.

(a) An indeterminate trial is an ongoing trial that has not surpassed twice the planned primary outcome completion date.

Figure 3—figure supplement 2.. Flow diagram for diabetes mellitus interventional trials.

(a) We used a random number generator (RAND function in Microsoft Excel) to create our 33% sample.

Figure 3—figure supplement 3.. Flow diagram for lung cancer interventional trials.