Bias and Loss to Follow‐Up in Cardiovascular Randomized Trials: A Systematic Review
Background Loss to follow‐up (LTFU) is common in randomized controlled trials. However, its potential impact on primary outcomes from cardiovascular randomized controlled trials is not known. Methods and Results We conducted a prospective systematic review (PROSPERO: CRD42019121959) for randomized c...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-07-01
|
| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.119.015361 |
| _version_ | 1818251633847435264 |
|---|---|
| author | Lucas Chun Wah Fong Thomas J. Ford Bruno R. da Costa Peter Jüni Colin Berry |
| author_facet | Lucas Chun Wah Fong Thomas J. Ford Bruno R. da Costa Peter Jüni Colin Berry |
| author_sort | Lucas Chun Wah Fong |
| collection | DOAJ |
| description | Background Loss to follow‐up (LTFU) is common in randomized controlled trials. However, its potential impact on primary outcomes from cardiovascular randomized controlled trials is not known. Methods and Results We conducted a prospective systematic review (PROSPERO: CRD42019121959) for randomized controlled trials published in 8 leading journals over 5 years from January 2014 to December 2018. Extent, reporting, and handling of LTFU data were recorded, and the proportion of a trial's primary outcome results that lose statistical significance was calculated after making plausible assumptions for the intervention and control arms. These assumptions could drive differential treatment effects between the groups considering relative event incidence between LTFU participants and those included in the primary outcome. We identified 117 randomized controlled trials of which 91 (78%) trials reported LTFU, 23 (20%) reported no LTFU, and 3 (3%) trials did not report on whether LTFU occurred. The median percentage of study participants lost to follow‐up was 2% (interquartile range, 0.33%–5.3%). Only 10 trials (9%) had a low cluster of risk factors for impairment in trial quality. The percentage of trials losing statistical significance varied from 2% when the relative event incidence for LTFU between the randomized groups was 1 for the intervention arm and 1.5 for the control arm to 16% when the relative event incidence was 3 for the intervention arm and 1 for the control arm. Conclusions Almost 1 in 6 (16%) cardiovascular randomized trials published in leading journals may have a change in the primary outcome if plausible assumptions are made about differential event rates of participants lost to follow up. There is scope for improvement arising from LTFU in randomized trials in cardiovascular medicine. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42019121959. |
| first_indexed | 2024-12-12T16:11:23Z |
| format | Article |
| id | doaj.art-7535949eba25445dbb2b9d0226a4e137 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-12T16:11:23Z |
| publishDate | 2020-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-7535949eba25445dbb2b9d0226a4e1372022-12-22T00:19:11ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802020-07-0191410.1161/JAHA.119.015361Bias and Loss to Follow‐Up in Cardiovascular Randomized Trials: A Systematic ReviewLucas Chun Wah Fong0Thomas J. Ford1Bruno R. da Costa2Peter Jüni3Colin Berry4West of Scotland Heart and Lung Centre Golden Jubilee National Hospital Glasgow ScotlandBritish Heart Foundation Glasgow Cardiovascular Research Centre Institute of Cardiovascular and Medical Sciences University of Glasgow United KingdomInstitute of Health Policy, Management, and Evaluation Dalla Lana School of Public Health University of TorontoDepartment of Medicine University of Toronto CanadaWest of Scotland Heart and Lung Centre Golden Jubilee National Hospital Glasgow ScotlandBackground Loss to follow‐up (LTFU) is common in randomized controlled trials. However, its potential impact on primary outcomes from cardiovascular randomized controlled trials is not known. Methods and Results We conducted a prospective systematic review (PROSPERO: CRD42019121959) for randomized controlled trials published in 8 leading journals over 5 years from January 2014 to December 2018. Extent, reporting, and handling of LTFU data were recorded, and the proportion of a trial's primary outcome results that lose statistical significance was calculated after making plausible assumptions for the intervention and control arms. These assumptions could drive differential treatment effects between the groups considering relative event incidence between LTFU participants and those included in the primary outcome. We identified 117 randomized controlled trials of which 91 (78%) trials reported LTFU, 23 (20%) reported no LTFU, and 3 (3%) trials did not report on whether LTFU occurred. The median percentage of study participants lost to follow‐up was 2% (interquartile range, 0.33%–5.3%). Only 10 trials (9%) had a low cluster of risk factors for impairment in trial quality. The percentage of trials losing statistical significance varied from 2% when the relative event incidence for LTFU between the randomized groups was 1 for the intervention arm and 1.5 for the control arm to 16% when the relative event incidence was 3 for the intervention arm and 1 for the control arm. Conclusions Almost 1 in 6 (16%) cardiovascular randomized trials published in leading journals may have a change in the primary outcome if plausible assumptions are made about differential event rates of participants lost to follow up. There is scope for improvement arising from LTFU in randomized trials in cardiovascular medicine. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42019121959.https://www.ahajournals.org/doi/10.1161/JAHA.119.015361biasloss to follow‐upoutcomeoutcome and process assessmentpatient dropoutrandomized controlled trials |
| spellingShingle | Lucas Chun Wah Fong Thomas J. Ford Bruno R. da Costa Peter Jüni Colin Berry Bias and Loss to Follow‐Up in Cardiovascular Randomized Trials: A Systematic Review Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease bias loss to follow‐up outcome outcome and process assessment patient dropout randomized controlled trials |
| title | Bias and Loss to Follow‐Up in Cardiovascular Randomized Trials: A Systematic Review |
| title_full | Bias and Loss to Follow‐Up in Cardiovascular Randomized Trials: A Systematic Review |
| title_fullStr | Bias and Loss to Follow‐Up in Cardiovascular Randomized Trials: A Systematic Review |
| title_full_unstemmed | Bias and Loss to Follow‐Up in Cardiovascular Randomized Trials: A Systematic Review |
| title_short | Bias and Loss to Follow‐Up in Cardiovascular Randomized Trials: A Systematic Review |
| title_sort | bias and loss to follow up in cardiovascular randomized trials a systematic review |
| topic | bias loss to follow‐up outcome outcome and process assessment patient dropout randomized controlled trials |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.119.015361 |
| work_keys_str_mv | AT lucaschunwahfong biasandlosstofollowupincardiovascularrandomizedtrialsasystematicreview AT thomasjford biasandlosstofollowupincardiovascularrandomizedtrialsasystematicreview AT brunordacosta biasandlosstofollowupincardiovascularrandomizedtrialsasystematicreview AT peterjuni biasandlosstofollowupincardiovascularrandomizedtrialsasystematicreview AT colinberry biasandlosstofollowupincardiovascularrandomizedtrialsasystematicreview |