Abstract
Objective
Recruitment and retention in trials may bias the results and subsequently complicate their interpretation and validity. The aim of this study is to evaluate the impact of recruitment and retention on all-cause mortality in a large all-comers trial.
Methods
The recruitment rate in each investigating center of the GLOBAL LEADERS trial was assessed and the 130 centers were subdivided into low and high recruiters according to the median, with all-cause mortality then compared between the two groups. Vital status was obtained from public records in patients with incomplete follow-up.
Results
The trial randomized 15,991 (7.86%) of 203,483 eligible patients with percutaneous coronary intervention during the recruitment period, of whom 15,267 (95.47%) completed follow-up, 23 (0.14%) patients withdrew consent and formally requested to be deleted from the database; 183 (1.14%) withdrew consent but only objected to future data collection; 303 (1.89%) discontinued the study; and 215 (1.34%) were lost to follow-up. Vital status was finally obtained in all but 31 patients (99.81%). Patients from low recruiters had a significantly lower all-cause mortality than high ones (2.26% vs. 3.24%; hazard ratio: 0.69; 95% confidence interval: 0.55–0.87; p = 0.002). There was a significant difference in all-cause mortality among the incomplete follow-up groups (log-rank p < 0.001) with a significantly higher mortality in the 183 patients who withdrew consent than those who completed follow-up (7.38% vs. 2.99%, p = 0.002).
Conclusions
Recruitment and retention significantly impacted all-cause mortality. Search for vital status through public domains is of paramount importance in the interpretation and validity of large clinical trials.
Graphic abstract
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Funding
The GLOBAL LEADERS trial was conducted under the support of the unrestricted resource from AstraZeneca, Biosensors, and The Medicines Company.
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Dr. Liebetrau reports personal fees from Astra Zeneca, outside the submitted work. Dr. Hamm reports personal fees from AstraZeneca, outside the submitted work. Dr. Steg reports Grants and personal fees from Bayer/Janssen, Grants and personal fees from Merck, Grants and personal fees from Sanofi, Grants and personal fees from Amarin, personal fees from Amgen, personal fees from Bristol Myers Squibb, personal fees from Boehringer-Ingelheim, personal fees from Pfizer, personal fees from Novartis, personal fees from Regeneron, personal fees from Lilly, personal fees from AstraZeneca, Grants and personal fees from Servier, outside the submitted work. Dr. Valgimigli reports Grants and personal fees from Abbott, personal fees from Chiesi, personal fees from Bayer, personal fees from Daiichi Sankyo, personal fees from Amgen, Grants and personal fees from Terumo, personal fees from Alvimedica, Grants from Medicure, Grants and personal fees from Astrazeneca, personal fees from Biosensors, outside the submitted work. Dr. Vranckx has received personal fees from AstraZeneca and the Medicines Company during the conduct of the study and personal fees from Bayer Health Care, Terumo, and Daiichi-Sankyo outside the submitted work. Dr. Windecker reports Grants from Amgen, Grants from Abbott, Grants from Boston Scientific, Grants from Biotronik, Grants from Bayer, Grants from Medtronic, Grants from Edwards Lifesciences, Grants from St Jude, Grants from Terumo, outside the submitted work. Dr. Serruys reports personal fees from Abbott Laboratories, personal fees from Biosensors, personal fees from Medtronic, personal fees from Micel Technologies, personal fees from Sinomedical Sciences Technology, personal fees from Stentys, personal fees from Svelte Medical Systems, personal fees from Philips/Volcano, personal fees from Xeltis, personal fees from StentIt and personal fees from HeartFlow outside the submitted work. All other authors declare no competing interests.
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Takahashi, K., Kogame, N., Tomaniak, M. et al. Impact of recruitment and retention on all-cause mortality in a large all-comers randomised controlled trial: insights from the GLOBAL LEADERS trial. Clin Res Cardiol 109, 918–929 (2020). https://doi.org/10.1007/s00392-019-01585-w
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Keywords
- All-cause mortality
- All-comers
- Recruitment
- Retention
- Randomised controlled trial