Early Termination of Cardiovascular Trials Due to Recruitment
Early Termination of Cardiovascular Trials Due to Recruitment
Our search strategy retrieved 7,042 trials, from which we were able to identify 6,279 studies that met the inclusion criteria of cardiovascular clinical trials registered in ClinicalTrials.gov between February 29, 2000, and January 17, 2013. From the eligible trials, 5,595 (89.1%) were classified as completed and 684 (10.9%) trials as terminated.
From the total of terminated trials, 165 trials (24.1%) did not report the reason for their early termination. After performing a Medline search, we were able to reclassify 35 of these trials when a related publication with results was identified. A total of 130 studies had no clear reason for termination and were excluded from the analysis (Figure 1).
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Figure 1.
Study design—flowchart of systematic analysis of cardiovascular interventional trials registered in ClinicalTrials.gov.
From the remaining 519 trials (75.9%), the main reason for termination was low recruitment (278 trials; 54%), followed by safety or ethics issues (9%), financial or administrative reasons (8%), sponsor or business decision (6%), treatment withdrawn from the market (6%), futility (6%), replaced or study competition (2%), benefit (2%), or other reasons (8%).
Overall characteristics of included studies are shown in the Table. As compared with completed trials, studies terminated early due to low recruitment were more often of parallel design (72.7% versus 58.0%), assessed safety/efficacy end points (57.1% versus. 48.9%), were phase 4 studies (36.4% versus 27.4%), had diagnostic assessment as the primary trial objective (8.3% versus 5.0%), and were funded by mixed sources (23.0% versus 14.5%).
Our multivariate logistic regression adjustment with the variables assessed for inclusion at univariate regression (Appendix) found that mixed-source funding (OR 2.14, 95% CI 1.52–3.01; P < .001) and university/hospital funding (OR 1.52, 95% CI 1.10–2.10; P = .001) were independently associated with a higher risk of study termination due to low recruitment (Figure 2). Conversely, NIH/US federal funding (OR 0.35, 95% CI 0.14–0.89; P = .027), behavior/diet intervention (OR 0.35, 95% CI 0.19–0.65; P < .001), and single-arm design (OR 0.57, 95% CI 0.42–0.78; P < .001) were factors independently associated with lower risk for early termination due to low recruitment. The area under the receiver operating characteristic curve of our final model was 0.65 (95% CI 0.62–0.68), and the Hosmer-Lemeshow goodness-of-fit test showed a P = .1485.
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Figure 2.
Multivariable logistic regression analysis assessing predictors of early termination of cardiovascular clinical trials due to low recruitment.
Results
Our search strategy retrieved 7,042 trials, from which we were able to identify 6,279 studies that met the inclusion criteria of cardiovascular clinical trials registered in ClinicalTrials.gov between February 29, 2000, and January 17, 2013. From the eligible trials, 5,595 (89.1%) were classified as completed and 684 (10.9%) trials as terminated.
From the total of terminated trials, 165 trials (24.1%) did not report the reason for their early termination. After performing a Medline search, we were able to reclassify 35 of these trials when a related publication with results was identified. A total of 130 studies had no clear reason for termination and were excluded from the analysis (Figure 1).
(Enlarge Image)
Figure 1.
Study design—flowchart of systematic analysis of cardiovascular interventional trials registered in ClinicalTrials.gov.
From the remaining 519 trials (75.9%), the main reason for termination was low recruitment (278 trials; 54%), followed by safety or ethics issues (9%), financial or administrative reasons (8%), sponsor or business decision (6%), treatment withdrawn from the market (6%), futility (6%), replaced or study competition (2%), benefit (2%), or other reasons (8%).
Characteristics of Studies
Overall characteristics of included studies are shown in the Table. As compared with completed trials, studies terminated early due to low recruitment were more often of parallel design (72.7% versus 58.0%), assessed safety/efficacy end points (57.1% versus. 48.9%), were phase 4 studies (36.4% versus 27.4%), had diagnostic assessment as the primary trial objective (8.3% versus 5.0%), and were funded by mixed sources (23.0% versus 14.5%).
Predictors of Early Termination
Our multivariate logistic regression adjustment with the variables assessed for inclusion at univariate regression (Appendix) found that mixed-source funding (OR 2.14, 95% CI 1.52–3.01; P < .001) and university/hospital funding (OR 1.52, 95% CI 1.10–2.10; P = .001) were independently associated with a higher risk of study termination due to low recruitment (Figure 2). Conversely, NIH/US federal funding (OR 0.35, 95% CI 0.14–0.89; P = .027), behavior/diet intervention (OR 0.35, 95% CI 0.19–0.65; P < .001), and single-arm design (OR 0.57, 95% CI 0.42–0.78; P < .001) were factors independently associated with lower risk for early termination due to low recruitment. The area under the receiver operating characteristic curve of our final model was 0.65 (95% CI 0.62–0.68), and the Hosmer-Lemeshow goodness-of-fit test showed a P = .1485.
(Enlarge Image)
Figure 2.
Multivariable logistic regression analysis assessing predictors of early termination of cardiovascular clinical trials due to low recruitment.
