Dangers of non-specific composite outcome measures in clinical trials

BMJ (Online)

Volumn 347, Issue , 2013, Pages

  Prieto Merino, David ^a   Smeeth, Liam ^b   Van Staa, Tjeerd P ^b,c   Roberts, Ian ^a  

^a LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^b UTRECHT UNIVERSITY   (Netherlands)

^c UTRECHT UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

BETA ADRENERGIC RECEPTOR BLOCKING AGENT; PLACEBO; SIMVASTATIN; TRANEXAMIC ACID;

ARTICLE; BLEEDING; CARDIOVASCULAR DISEASE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL (TOPIC); HEART INFARCTION; HOSPITAL ADMISSION; HUMAN; HYPERCHOLESTEROLEMIA; MORTALITY; MYALGIA; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RISK ASSESSMENT; RISK BENEFIT ANALYSIS; TREATMENT OUTCOME; EPIDEMIOLOGY; METHODOLOGY; PROCEDURES; STATISTICS;

CAUSALITY; CLINICAL TRIALS AS TOPIC; HUMANS; OUTCOME ASSESSMENT (HEALTH CARE); RESEARCH DESIGN; STATISTICS AS TOPIC; TREATMENT OUTCOME;

EID: 84888145722     PISSN: None     EISSN: 17561833     Source Type: Journal    
DOI: 10.1136/bmj.f6782     Document Type: Article

References (17)

1. ICH Expert Working Group. Statistical principles for clinical trials E9. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. 1998. Technical report. www.ich.org/products/guidelines/efficacy/efficacy-single/article/ statistical-principles-for-clinical-trials.html. Accessed 26-Sept-2013.
2. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:c869.
3. Cordoba G, Schwartz L, Woloshin S, Bae H, Gotzsche PC. Definition, reporting, and interpretation of composite outcomes in clinical trials: systematic review. BMJ 2010;341:c3920.
4. Ferreira-Gonzalez I, Busse JW, Heels-Ansdell D, Montori VM, Akl EA, Bryant DM, et al. Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials. BMJ 2007;334:786.
5. Ferreira-Gonzalez I, Permanyer-Miralda G, Busse JW, Bryant DM, Montori VM, Alonso-Coello P, et al. Composite endpoints in clinical trials: the trees and the forest. J Clin Epidemiol 2007;60:660-1.
6. Ferreira-Gonzalez I, Permanyer-Miralda G, Busse JW, Bryant DM, Montori VM, Alonso-Coello P, et al. Methodologic discussions for using and interpreting composite endpoints are limited, but still identify major concerns. J Clin Epidemiol 2007;60:651-7, discussion 658-62.
7. Freemantle N, Calvert M, Wood J, Eastaugh J, Griffin C. Composite outcomes in randomized trials greater precision but with greater uncertainty? JAMA 2003;289:2554-9.
8. Freemantle N, Calvert M. Weighing the pros and cons for composite outcomes in clinical trials. J Clin Epidemiol 2007;60:658-9.
9. Montori VM, Permanyer-Miralda G, Ferreira-Gonzalez I, Busse JW, Pacheco-Huergo V, Bryant D, et al. Validity of composite end points in clinical trials. BMJ 2005;330:594-6.
10. European Network for Health Technology Assessment. Endpoints used for REA of pharmaceuticals: composite endpoints. 2013. www.eunethta.eu/outputs/ methodological-guideline-rea-pharmaceuticals-composite-endpoints.
11. Rothman KJ, Lash TL, Greenland S. Modern epidemiology. Lippincott Williams and Wilkins, 2012.
12. Kessler KM. Combining composite endpoints: counterintuitive or a mathematical impossibility? Circulation 2003;107:e70.
13. Cockburn J, Behan M, de Belder A, Clayton T, Stables R, Oldroyd K, et al. Use of troponin to diagnose periprocedural myocardial infarction: effect on composite endpoints in the British Bifurcation Coronary Study (BBC ONE). Heart 2012;98:1431-5.
14. Rodgers A, McMahon S. Systematic underestimation of treatment effects as a result of diagnostic test inaccuracy: implications for the interpretation and design of thromboprophylaxis trials. Thromb Haemost 1995;73:167-71.
15. CRASH-2 Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010;376:1-10.
16. HPS Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22.
17. Lubsen J, Kirwan B. Combined endpoints: can we use them? Stat Med 2002;21:2959-70.