Lost to Follow-up and Withdrawal of Consent in Contemporary Global Cardiovascular Randomized Clinical Trials.

BACKGROUND: High rates of lost to follow-up (LTFU) and withdrawal of consent (WDC) may introduce uncertainty around the validity of the results of clinical trials. We sought to better understand published proportions of LTFU and WDC in large contemporary cardiovascular clinical trials. METHODS: Large (>5000 randomized subjects) cardiovascular clinical trials published between 2007 and 2012 in N Engl J Med were systematically reviewed. Data regarding LTFU and WDC were extracted from the primary manuscripts and supplementary online material. RESULTS: Twenty-five published randomized trials were identified. Trials ranged in size from 5518 to 26449 subjects. All trials reported LTFU with 15 separately reporting WDC. The duration of follow-up ranged from 30 days to 6.2 years. The number of subjects LTFU ranged from 8 to 905, and the median proportion of subjects LTFU was 0.23% (interquartile range: 0.12%-0.58%). Individual LTFU proportions varied 300-fold, from 0.03% to 9.7%. Proportions of WDC ranged from 0.02% to 8.3%-a 400-fold difference-with a median of 1.1% (interquartile range: 0.2%-2.6%). WDC occurred more frequently than LTFU in all but 2 studies. CONCLUSION: Contemporary cardiovascular clinical trials typically have low proportions of LTFU or WDC, but some trials have approximately 10% of subjects with LTFU or WDC. WDC occurred more frequently than LTFU but was only reported in 60% of the trials. These results emphasize the need to standardize reporting of LTFU and WDC as important trial metrics of quality and to develop strategies to minimize their occurrence.

Duke Scholars

Author Robert William Harrison Medicine, Cardiology