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Multiple analyses in clinical trials: sound science or data dredging?

Sarah J Lord, Val J Gebski and Anthony C Keech
Med J Aust 2004; 181 (8): . || doi: 10.5694/j.1326-5377.2004.tb06376.x
Published online: 18 October 2004

Clinical trials typically require the collection of many data to describe the participants and for measuring their response to an intervention. In addition to the primary analysis of treatment effect, investigators can use these data to perform multiple analyses, but there are important pitfalls with their use.1,2 Here, we discuss three common types of secondary analyses: analyses of multiple outcome variables; analyses of trial outcomes that account for prognostic factors (adjusted analyses); and using trial data to answer secondary research questions (see definitions in Box 1). The use of trial data for population subgroup analyses has been discussed earlier in this series.3,4


  • NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW.


Correspondence: 

Acknowledgements: 

We thank Rhana Pike for expert assistance in preparation of this manuscript.

Competing interests:

None identified.

  • 1. Pocock SJ. Clinical trials with multiple outcomes: a statistical perspective on their design, analysis, and interpretation. Control Clin Trials 1997; 18: 530-545.
  • 2. Tukey JW. Some thoughts on clinical trials, especially problems of multiplicity. Science 1977; 198: 679-684.
  • 3. Cook DI, Gebski VJ, Keech AC. Subgroup analysis in clinical trials. Med J Aust 2004; 180: 289-291. www.mja.com.au/public/issues/180_06_150304/coo10086_fm.html
  • 4. Simes RJ, Gebski VJ, Keech AC. Subgroup analysis: application to individual patient decisions. Med J Aust 2004; 180: 467-469. <eMJA full text>
  • 5. Chan AW, Hrobjartsson A, Haahr MT, et al. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. JAMA 2004; 291: 2457-2465.
  • 6. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 2001; 357: 1191-1194.
  • 7. Sledge GW, Neuberg D, Bernardo P, et al. Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial. J Clin Oncol 2003; 21: 588-592.
  • 8. Keech A, Colquhoun D, Best J, et al. Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose: results from the LIPID trial. Diabetes Care 2003; 26: 2713-2721.
  • 9. Stone GWM, Ellis SGM, Cox DAM, et al. One-year clinical results with the slow-release, polymer-based, paclitaxel-eluting TAXUS stent: The TAXUS-IV trial. Circulation 2004; 109: 1942-1947.
  • 10. Beller EM, Gebski V, Keech AC. Randomisation in clinical trials. Med J Aust 2002; 177: 565-567. <eMJA full text>
  • 11. White H. and Hirulog and Early Reperfusion or Occlusion (HERO) Trial Investigators. Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial. Lancet 2001; 358: 1855-1863.
  • 12. Steyerberg EW, Bossuyt PM, Lee KL. Clinical trials in acute myocardial infarction: should we adjust for baseline characteristics? Am Heart J 2000; 139: 745-751.
  • 13. Pocock SJ, Assmann SE, Enos LE, Kasten LE. Subgroup analysis, covariate adjustment and baseline comparisons in clinical trial reporting: current practice and problems. Stat Med 2002; 21: 2917-2930.
  • 14. Assmann SF, Pocock SJ, Enos LE, Kasten LE. Subgroup analysis and other (mis)uses of baseline data in clinical trials. Lancet 2000; 355: 1064-1069.
  • 15. Shumaker SA, Reboussin BA, Espeland MA, et al. The Women’s Health Initiative Memory Study (WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Control Clin Trials 1998; 19: 604-621.
  • 16. Barron HV, Cannon CP, Murphy SA, et al. Association between white blood cell count, epicardial blood flow, myocardial perfusion, and clinical outcomes in the setting of acute myocardial infarction: a thrombolysis in myocardial infarction 10 substudy. Circulation 2000; 102: 2329-2334.
  • 17. O’Connor FF, Shields DC, Fitzgerald A, et al. Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes. Blood 2001; 98: 3256-3260.

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