Article type
Year
Abstract
Background: More than 25% of planned randomized controlled trials (RCTs) are prematurely discontinued. Most discontinuations are not reported to research ethics committees (RECs) and most discontinued RCTs remain unpublished. This raises serious ethical concerns, including waste of scarce resources, loss of collected patient data, and missed opportunities to learn from failure. Similar concerns apply to other prospective studies (non-RCTs) such as non-randomized controlled trials, uncontrolled trials, or cohort studies. However, the prevalence of discontinuation of non-RCTs and the reasons thereof are unknown.
Objectives: To assess the prevalence of and the reasons for discontinuation in non-RCTs, and to compare the results to those in RCTs.
Methods: Systematically we surveyed studies that were approved by six RECs (Germany, Switzerland, Canada) from 2000 to 2003, enrolled patients or healthy volunteers, and collected outcome data prospectively after study initiation. We had access to study protocols of non-RCTs at one REC (Freiburg, Germany) and to RCT protocols at all six RECs. We will collect study characteristics such as medical area, type of participants, sample size, collaboration, and funding source. We will identify subsequent publications and survey investigators to elucidate whether a study was discontinued and, if so, why. Since some reasons such as benefit or harm only apply to experimental studies, we will stratify the results by study design.
Results: An initial screen of study protocols suggests that about 1000 studies were RCTs, 150 uncontrolled trials, 60 non-randomized controlled trials, 25 cohort studies, and 217 ineligible retrospective or cross-sectional studies. We will present data on non-RCTs compared to RCTs regarding the prevalence of discontinuation and the reasons thereof.
Conclusions: Compared to RCTs, typical features of non-RCTs likely increase the risk for discontinuation (e.g. first in human study) while others may decrease this risk (e.g. explorative character). Non-RCTs are increasingly included in systematic reviews, so that a a better understanding of their premature discontinuation is warranted.
Objectives: To assess the prevalence of and the reasons for discontinuation in non-RCTs, and to compare the results to those in RCTs.
Methods: Systematically we surveyed studies that were approved by six RECs (Germany, Switzerland, Canada) from 2000 to 2003, enrolled patients or healthy volunteers, and collected outcome data prospectively after study initiation. We had access to study protocols of non-RCTs at one REC (Freiburg, Germany) and to RCT protocols at all six RECs. We will collect study characteristics such as medical area, type of participants, sample size, collaboration, and funding source. We will identify subsequent publications and survey investigators to elucidate whether a study was discontinued and, if so, why. Since some reasons such as benefit or harm only apply to experimental studies, we will stratify the results by study design.
Results: An initial screen of study protocols suggests that about 1000 studies were RCTs, 150 uncontrolled trials, 60 non-randomized controlled trials, 25 cohort studies, and 217 ineligible retrospective or cross-sectional studies. We will present data on non-RCTs compared to RCTs regarding the prevalence of discontinuation and the reasons thereof.
Conclusions: Compared to RCTs, typical features of non-RCTs likely increase the risk for discontinuation (e.g. first in human study) while others may decrease this risk (e.g. explorative character). Non-RCTs are increasingly included in systematic reviews, so that a a better understanding of their premature discontinuation is warranted.