Choosing Appropriate Estimands in Clinical Trials

Therapeutic Innovation and Regulatory Science

Volumn 49, Issue 4, 2015, Pages 584-592

  Leuchs, Ann Kristin ^a   Zinserling, Jörg ^a   Brandt, Andreas ^a   Wirtz, Dorothee ^a   Benda, Norbert ^a  

^a Federal Institute for Drugs and Medical Devices BfArM   (Germany)

Author keywords

clinical trials; effectiveness; efficacy; estimands; missing data; nonadherence

Indexed keywords

ARTICLE; CEREBROVASCULAR ACCIDENT; CLINICAL PRACTICE; CLINICAL TRIAL (TOPIC); DEPRESSION; HUMAN; LONGITUDINAL STUDY; PATIENT COMPLIANCE; PRIORITY JOURNAL; SENSITIVITY ANALYSIS; STUDY DESIGN; TREATMENT PLANNING;

EID: 84936766668     PISSN: 21684790     EISSN: 21684804     Source Type: Journal    
DOI: 10.1177/2168479014567317     Document Type: Article

References (32)

1. C.H.Mallinckrodt. Preventing and Treating Missing Data in Longitudinal Clinical Trials: A Practical Guide. New York: Cambridge University Press; 2013.
2. National Research Council: Panel on Handling Missing Data in Clinical Trials. The Prevention and Treatment of Missing Data in Clinical Trials. Washington, DC: National Academies Press; 2010.
3. R.J.A.LittleD.B.Rubin. Statistical Analysis With Missing Data. New York: John Wiley & Sons; 1987.
4. G.MolenberghsM.G.Kenward. Missing Data in Clinical Studies. New York: John Wiley & Sons; 2007.
5. G.Molenberghs. Incomplete data in clinical studies: analysis, sensitivity, and sensitivity analysis. Drug Inf J. 2009;43:409-429.
6. J.R.CarpenterM.G.Kenward. Multiple Imputation and Its Application. New York: John Wiley & Sons; 2013.
7. International Conference on Harmonisation. Statistical Principles for Clinical Trials E9: 1998. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E9/Step4/E9_Guideline.pdf. Accessed February 2014.
8. European Medicines Agency. EMA/CPMP/EWP/1776/99 Rev. 1 Guideline on Missing Data in Confirmatory Clinical Trials. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/09/WC500096793.pdf. Published2011. Accessed June 2013.
9. C.H.MallinckrodtJ.RogerC.Chuang-Stein. Recent developments in the prevention and treatment of missing data. Therapeutic Innovation & Regulatory Science. 2014;48:68-80.
10. R.T.O’NeillR.Temple. The prevention and treatment of missing data in clinical trials: an FDA perspective on the importance of dealing with it. Clin Pharmacol Ther. 2012;91:550-554.
11. M.G.Kenward. The handling of missing data in clinical trials. Clin Invest. 2013;3:241-250.
12. C.H.MallinckrodtM.G.Kenward. Conceptual considerations regarding endpoints, hypotheses, and analyses for incomplete longitudinal clinical trial data. Drug Inf J. 2009;43:449-458.
13. J.R.CarpenterJ.H.RogerM.G.Kenward. Analysis of longitudinal trials with protocol deviation: a framework for relevant, accessible assumptions, and inference via multiple imputation. J Biopharm Stat. 2013;23:1352-1371.
14. C.H.MallinckrodtQ.LinI.LipkovichG.Molenberghs. A structural approach to choosing estimands and estimators in longitudinal clinical trials. Pharm Stat. 2012;11:456-461.
15. T.R.Fleming. Addressing missing data in clinical trials. Ann Internal Med. 2011;154:113-117.
16. European Medicines Agency. CPMP/EWP/1080/00 Rev. 1 Guideline on Clinical Investigation of Medicinal Products in the Treatment or Prevention of Diabetes Mellitus. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500129256.pdf. Published2012. Accessed February 2014.
17. R.D.GibbonsD.HedekerI.Elkin. Some conceptual and statistical issues in analysis of longitudinal psychiatric data. Arch Gen Psychiatry. 1993;50:739-750.
18. C.H.MallinckrodtW.S.ClarkS.R.David. Type 1 error rates from mixed effects model repeated measures versus fixed effects ANOVA with missing values imputed via last observation carried forward. Drug Inf J. 2001;35:1215-1225.
19. C.H.MallinckrodtS.W.ClarkR.J.CarrollG.Molenberghs. Assessing response profiles from incomplete longitudinal clinical trial data under regulatory considerations. J Biopharm Stat. 2003;13:179-190.
20. C.H.MallinckrodtC.J.KaiserJ.G.WatkinG.MolenberghsR.J.Carroll. The effect of correlation structure on treatment contrasts estimated from incomplete clinical trial data with likelihood-based repeated measures compared with last observation carried forward ANOVA. Clin Trials. 2004;1:477-489.
21. C.H.MallinckrodtT.M.SangerS.Dube. Assessing and interpreting treatment effects in longitudinal clinical trials with missing data. Biol Psychiatry. 2003;53:754-760.
22. G.MolenberghsH.ThijsI.Jansen. Analyzing incomplete longitudinal clinical trial data. Biostatistics. 2004;5:445-464.
23. C.H.MallinckrodtP.W.LaneD.SchnellY.PengJ.P.Mancuso. Recommendations for the primary analysis of continuous endpoints in longitudinal clinical trials. Drug Inf J. 2007;42:303-319.
24. B.TeshomeI.LipkovichG.MolenberghsC.H.Mallinckrodt. A multiple-imputation-based approach to sensitivity analyses and effectiveness assessments in longitudinal clinical trials. J Biopharm Stat. 2014;24:211-228.
25. B.RatitchM.O’KellyR.Tosiello. Missing data in clinical trials: from clinical assumptions to statistical analysis using pattern mixture models. Pharm Stat. 2013;12:337-347.
26. R.J.A.LittleL.Yau. Intention-to-treat analysis for longitudinal studies with drop-outs. Biometrics. 1996;52:1324-1333.
27. A.K.LeuchsJ.ZinserlingG.Schlosser-WeberM.BerresM.NeuhäuserN.Benda. Estimation of the treatment effect in the presence of non-compliance and missing data. Stat Med. 2014;33:193-208.
28. N.BendaM.BransonW.MaurerT.Friede. Aspects of modernizing drug development using clinical scenario planning and evaluation. Drug Inf J. 2010;44:297-315.
29. C.H.MallinckrodtQ.LinG.Molenberghs. A structured framework for assessing sensitivity to missing data assumptions in longitudinal clinical trials. Pharm Stat. 2013;12:1-6.
30. European Medicines Agency. EMA/CHMP/185423/2010, Rev 2 Previously (CPMP/EWP/518/97, Rev. 1) Guideline on Clinical Investigation of Medicinal Products in the Treatment of Depression. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/05/WC500143770.pdf. Published2013. Accessed June 2014.
31. European Medicines Agency. EMA/CHMP/623942/2013 Guideline on Clinical Investigation of Medicinal Products for Prevention of Stroke and Systemic Embolic Events in Patients With Non-valvular Atrial Fibrillation. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/11/WC500154227.pdf. Published2013. Accessed June 2014.
32. M.O’KellyI.Lipkovich. Using multiple imputation and delta adjustment to implement sensitivity analyses for time-to-event data. Presentation at: PSI 2014 conference; May 11-14, 2014; London.