Robert W. Harrison, MD; Daniel Wojdyla , MS; Kenneth W. Mahaffey, MD

1. Lost to follow-up in contemporary global cardiovascular randomized clinical trials Robert W. Harrison, MD; Daniel Wojdyla, MS; Kenneth W. Mahaffey, MD Duke Clinical Research Institute, Durham, NC Results Table 1: Study Characteristics Table 2: Reporting of LTFU and Withdrawn Consent Background Disclosures: Harrison, RW: None Wojdyla, D: None Mahaffey, KW: Consulting fees/honoraria: Johnson&Johnson, AstraZeneca, Exeter Group, Orexigan, Biotronik, Amgen, Genentech, Sun Pharma, Forest, Adolor, WebMD, Ortho/McNeill, Haemonetics, Daiichi Sankyo, Pfizer, South East Area Health Education Center, Elsevier (AHJ), Eli Lilly, Gilead Science, Bristol Myers Squibb, Glaxo Smith Kline, Novartis Pharmaceutical, Medtronic, Merck, Sanofi-Aventis, BoehringerIngleheim, Bayer, Polymedix; Research Grants: INC Research, Eli Lilly, Medtronic, Merck , Pozen, Baxter, Cordis, BoehringerIngelheim, Luitpold, AstraZeneca, Edwards Lifesciences, Bristol Myers Squibb, Abbott Vascular, Portola, Daiichi Sankyo, Sanofi, Guidant , Bayer, Amgen, Glaxo Smith Kline, Johnson & Johnson, Roche Diagnostic, Novartis Pharmaceutical, Amylin, Schering Plough Research Institute, Ikaria, The Medicines Company, Regado, Springer Publishing, KAI • Subjects in clinical trials may choose to withdrawal their consent (WDC) to participate, or become lost to follow-up (LTFU) prior to study completion • High rates of LTFU may introduce uncertainty around the validity of the results of clinical trials • Incomplete follow-up data may lead to increased scrutiny on behalf of regulatory agencies, and may threaten approval of investigational products 1 • Currently, there is no standard method for reporting LTFU and WDC Figure: Proportion of subjects with LTFU or WDC Objectives • Review the methods for reporting LTFU and WDC in large contemporary global cardiovascular clinical trials • Determine the rates of LTFU and WDC in large contemporary global cardiovascular clinical trials Methods • PubMed was searched for randomized clinical trials published between 2007 and 2012 in the New England Journal of Medicine (NEJM) • Trials were included if they enrolled at least 5,000 patients and had a cardiovascular primary endpoint • Rates of LTFU and WDC were determined from the primary manuscripts and online supplementary material when necessary WDC LTFU Reference: 1FDA Briefing Document for the Cardiovascular and Renal Drugs Advisory Committee (CRDAC). http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM304755.pdf. May 23, 2012; Accessed March 1, 2013 • Conclusions • There is great variability in the manner in which LTFU and WDC are reported • 40% of studies did not contain a CONSORT diagram, and 40% of studies did not describe LTFU or WDC by treatment arm • Overall, the proportions of LTFU were low, but in some trials over 100 patients had LTFU • WDC occurred more frequently 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 Contact Robert W. Harrison, MD Duke Clinical Research Institute 2400 Pratt St. Durham, NC 27705 Robert.w.harrison@duke.edu