• 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 Robert W. Harrison, MD; Daniel Wojdyla, MS; Kenneth W. Mahaffey, MD Duke Clinical Research Institute, Durham, NC Conclusi ons Robert W. Harrison, MD Duke Clinical Research Institute 2400 Pratt St. Durham, NC 27705 Robert.w.harrison@duk e.edu Lost to follow-up in contemporary global cardiovascular randomized clinical trials Backgroun d Objectives Methods Results Trial Acronym Year of Publicat ion Median Follow-up (days) Number of Subjects LTFU N (%) WDC N (%) ACCOMPLISH 2008 1086 11,506 117 (1.02) 5 (0.04) ACCORD-Lipid 2010 1716 5,518 56 (1.00) - ACTIVE-A 2009 1314 7,554 43 (0.57) - APPRAISE-2 2011 241 7,392 50 (0.68) 81 (1.10) ARISTOTLE 2011 657 18,201 69 (0.38) 199 (1.10) ASCEND-HF 2011 30 7,141 8 (0.11) 30 (0.42) ATLAS ACS 2 2012 398 15,526 37 (0.24) 1271 (8.30) AVERROES 2011 402 5,599 - - CHAMPION-PCI 2009 30 8,877 69 (0.78) 2 (0.02) CHAMPION- PLATFORM 2009 30 5,362 19 (0.35) 6 (0.11) CURRENT OASIS-7 2010 30 25,086 25 (0.10) - EARLY-ACS 2009 30 9,492 11 (0.12) 14 (0.15) ILLUMINATE 2007 550 15,067 39 (0.26) 283 (1.88) JUPITER 2008 694 17,802 81 (0.46) - NAVIGATOR 2010 2373 9,306 905 (9.72) 306 (3.29) ONTARGET 2008 1703 25,620 43 (0.17) - ORIGIN 2012 2263 12,536 18 (0.14) 32 (0.26) PLATO 2009 277 18,624 5 (0.03) - PRoFESS 2008 913 20,332 125 (0.61) - RE-LY 2009 730 18,113 20 (0.11) - ROCKET AF 2011 707 14,264 32 (0.22) 447 (3.10) TRA-2P 2012 912 26,449 32 (0.12) 532 (2.00) Table 1: Study Characteristics • 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 • 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 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, Boehringer Ingleheim, Bayer, Polymedix; Research Grants: INC Research, Eli Lilly, Medtronic, Merck , Pozen, Baxter, Cordis, Boehringer Ingelheim, 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 Contact Reference: 1 FDA Briefing Document for the Cardiovascular and Renal Drugs Advisory Committee (CRDAC). http://www.fda.gov/down loads/AdvisoryCommittee s/CommitteesMeetingMate rials/Drugs/ CardiovascularandRenalD rugsAdvisoryCommittee/ UCM304755.pdf. May 23, 2012; Accessed March 1, 2013 • 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 Number % Reported data on LTFU 24/25 96% Contain a CONSORT diagram 15/25 60% Separately report LTFU by treatment arm 16/25 64% Separately report WDC and LTFU 15/25 60% Table 2: Reporting of LTFU and Withdrawn Consent PLATO CURRENT OASIS-7 TRITON-TIMI 38 RE-LY ONTARGET EARLY-ACS TRILOGY-ACS ORIGIN JUPITER CHAMPION-PLATFORM ASCEND-HF ACTIVE-A PRoFESS CHAMPION-PCI ACCORD-Lipid ACCOMPLISH ARISTOTLE APPRAISE-2 TRA-2P ILLUMINATE ROCKET AF TRACER ATLAS NAVIGATOR AVERROES 0% 2% 4% 6% 8% 10% 12% 14% Proportion Not Reported Figure: Proportion of subjects with LTFU or WDC LTFU Withdrawn Consent Median (IQR) 0.23% (0.12%- 0.58%) 1.10% (0.18%-2.55%) Range 0.03% - 9.7% 0.02% - 8.3% Fold variatio n 323x 415x WDC LTFU
Robert W. Harrison, MD; Daniel Wojdyla , MS; Kenneth W. Mahaffey, MD
Feb 23, 2016
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 . - PowerPoint PPT Presentation
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
• 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
Robert W. Harrison, MD; Daniel Wojdyla, MS; Kenneth W. Mahaffey, MDDuke Clinical Research Institute, Durham, NC
Conclusions
Robert W. Harrison, MDDuke Clinical Research Institute2400 Pratt St.Durham, NC [email protected]
Lost to follow-up in contemporary global cardiovascular randomized clinical trials
Background
Objectives
Methods
Results
Trial Acronym Year of Publicat
ion
Median Follow-up
(days)
Number of Subjects
LTFU N (%)
WDCN (%)
ACCOMPLISH 2008 1086 11,506 117 (1.02) 5 (0.04)ACCORD-Lipid 2010 1716 5,518 56 (1.00) -ACTIVE-A 2009 1314 7,554 43 (0.57) -APPRAISE-2 2011 241 7,392 50 (0.68) 81 (1.10)ARISTOTLE 2011 657 18,201 69 (0.38) 199 (1.10)ASCEND-HF 2011 30 7,141 8 (0.11) 30 (0.42)ATLAS ACS 2 2012 398 15,526 37 (0.24) 1271 (8.30)AVERROES 2011 402 5,599 - -CHAMPION-PCI 2009 30 8,877 69 (0.78) 2 (0.02) CHAMPION-PLATFORM 2009 30 5,362 19 (0.35) 6 (0.11)
CURRENT OASIS-7 2010 30 25,086 25 (0.10) -EARLY-ACS 2009 30 9,492 11 (0.12) 14 (0.15)ILLUMINATE 2007 550 15,067 39 (0.26) 283 (1.88)JUPITER 2008 694 17,802 81 (0.46) -NAVIGATOR 2010 2373 9,306 905 (9.72) 306 (3.29)ONTARGET 2008 1703 25,620 43 (0.17) -ORIGIN 2012 2263 12,536 18 (0.14) 32 (0.26)PLATO 2009 277 18,624 5 (0.03) -PRoFESS 2008 913 20,332 125 (0.61) -RE-LY 2009 730 18,113 20 (0.11) -ROCKET AF 2011 707 14,264 32 (0.22) 447 (3.10)TRA-2P 2012 912 26,449 32 (0.12) 532 (2.00)TRACER 2012 502 12,944 15 (0.12) 581 (4.50)TRILOGY-ACS 2012 517 9,326 7 (0.08) 19 (0.20)TRITON-TIMI 38 2007 441 13,608 14 (0.10) -
Median (IQR)550
(277 - 913)
12,944(8877 - 18113)
0.23%(0.12 - 0.58)
1.10%(0.18 – 2.55)
Table 1: Study Characteristics• 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
• 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
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, Boehringer Ingleheim, Bayer, Polymedix; Research Grants: INC Research, Eli Lilly, Medtronic, Merck , Pozen, Baxter, Cordis, Boehringer Ingelheim, 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
Contact
Reference: 1 FDA 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
• 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
Number %
Reported data on LTFU 24/25 96%Contain a CONSORT diagram 15/25 60%Separately report LTFU by treatment arm 16/25 64%
Separately report WDC and LTFU 15/25 60%
Table 2: Reporting of LTFU and Withdrawn Consent
PLATOCURRENT OASIS-7
TRITON-TIMI 38RE-LY
ONTARGETEARLY-ACS
TRILOGY-ACSORIGINJUPITER
CHAMPION-PLATFORMASCEND-HF
ACTIVE-APRoFESS
CHAMPION-PCIACCORD-LipidACCOMPLISH
ARISTOTLEAPPRAISE-2
TRA-2PILLUMINATEROCKET AF
TRACERATLAS
NAVIGATORAVERROES
0% 2% 4% 6% 8% 10% 12% 14%
Proportion
Not Reported
Figure: Proportion of subjects with LTFU or WDC
LTFU Withdrawn Consent
Median (IQR)
0.23%(0.12%-0.58%)
1.10%(0.18%-2.55%)
Range 0.03% - 9.7%
0.02% - 8.3%
Fold variation
323x 415x
WDCLTFU
Related Documents
