Fundamental deficiencies in the megatrial methodology
Tóm tắt
The fundamental methodological deficiency of megatrials is deliberate reduction of experimental control in order to maximize recruitment and compliance of subjects. Hence, typical megatrials recruit pathologically and prognostically heterogeneous subjects, and protocols typically fail to exclude significant confounders. Therefore, most megatrials do not test a scientific hypothesis, nor are they informative about individual patients. The proper function of a megatrial is precise measurement of effect size for a therapeutic intervention. Valid megatrials can be designed only when simplification can be achieved without significantly affecting experimental control. Megatrials should be conducted only at the end of a long process of therapeutic development, and must always be designed and interpreted in the context of relevant scientific and clinical information.
Tài liệu tham khảo
Charlton BG: Clinical research methods for the new millennium. J Eval Clin Pract. 1999, 5: 251-263. 10.1046/j.1365-2753.1999.00182.x.
Healy D: The Antidepressant Era. Cambridge, MA: Harvard University Press,. 1998
Charlton BG: Statistical malpractice. J Roy Coll Physicians London. 1996, 30: 112-114.
Charlton BG: The new management of scientific knowledge: a change in direction with profound implications. In NICE, CHI and the NHS Reforms: Enabling Excellence or Imposing Control? Edited by Miles A, Hampton JR, Hurwitz B. London: Aesculapius Medical Press,. 2000, 13-32.
Charlton BG: Mega-trials: methodological issues and clinical implications. J Roy Coll Physicians London. 2000, 29: 96-100.
Yusuf S, Collins R, Peto R: Why do we need some large, simple randomized trials?. Statistics Med. 1984, 3: 409-420.
Olkin I: Meta-analysis: reconciling the results of independent studies. Statistics Med. 1995, 14: 457-472.
Charlton BG: The uses and abuses of meta-analysis. Fam Pract. 1996, 13: 397-401.
Robertson JIS: Which antihypertensive classes have been shown to be beneficial? What are their benefits? A critique of hypertension treatment trials. Cardiovasc Drugs Ther. 14: 357-366. 10.1023/A:1007851913672.
Charlton BG: Megatrials are based on a methodological mistake. Brit J Gen Pract. 1996, 46: 429-431.
Julian D: Trials and tribulations. Cardiovasc Res. 1994, 28: 598-603.
Hampton JR: Evidence-based medicine, practice variations and clinical freedom. J Eval Clin Pract. 1997, 3: 123-131. 10.1046/j.1365-2753.1997.00094.x.
Gardner MJ: Statistics with Confidence: Confidence Intervals and Statistical Guidelines. London: British Medical Association,. 1989
Bradford Hill AB, Hill ID: Bradford Hill's Principles of Medical Statistics. London: Edward Arnold,. 1991
Kirkwood BR: Essentials of Medical Statistics. Oxford: Blackwell,. 1988
Charlton BG: The scope and nature of epidemiology. J Clin Epidemiol. 1996, 49: 623-626. 10.1016/0895-4356(96)00038-8.
Horvitz RI, Singer BH, Makuch , Viscoli CM: Can treatment that is helpful on average be harmful to some patients? A study of the conflicting information-needs of clinical inquiry and drug regulation. J Clin Epidemiol. 1996, 49: 395-400. 10.1016/0895-4356(95)00058-5.
Charlton BG, Walston F: Individual case studies in clinical research. J Eval Clin Pract. 1998, 4: 147-155. 10.1046/j.1365-2753.1998.00011.x.
Bernard C: An Introduction to the Study of Experimental Medicine. New York: Dover, 1865;. 1957
Marshall JC, Newcombe F: Putative problems and pure progress in neuropsychological single-case studies. J Clin Neuropsychol. 1984, 6: 65-70.
Shallice T: From Neuropsychology to Mental Structure. Cambridge: Cambridge University Press,. 1988
Charlton BG: The future of clinical research: from megatrials towards methodological rigour and representative sampling. J Eval Clin Prac. 1996, 2: 159-169.