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Megatrials for Clinical Decision Making
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
TO THE EDITOR:
In their article on meta-analyses, Borzak and Ridker [1] comment on a perplexing issue. Why did a reasonably large trial (LIMIT-2 [Second Leicester Intravenous Magnesium Intervention Trial]) [2] show a therapeutic benefit for magnesium in patients who had had acute myocardial infarction when a megatrial (ISIS-4 [Fourth International Study of Infarct Survival]) [3] did not? If the difference is the timing with which the drug was given, another trial can be done. If the results of LIMIT-2 were wrong, however, and magnesium has no benefit in the treatment of acute myocardial infarction under any circumstances, some serious questions must be asked about the sample sizes needed to correctly determine therapeutic efficacy. All of the trials discussed by Borzak and Ridker are in the field of cardiology, where trials enrolling tens of thousands of patients are becoming increasingly common.
LIMIT-2 was a randomized, double-blind trial of 2316 patients. In any other specialty, this trial would be considered very large. If this sample size is inadequate, how are we to conduct trials to evaluate diseases less common than acute myocardial infarction? In many cases, it would be impossible to enroll 10 000 patients in a reasonable time frame. Should multiple trials be done for all therapies? If 10 000 patients are required to show a treatment effect, is this effect clinically relevant? If megatrials are required for every therapy or alteration in therapy, evidence-based medicine may be facing serious difficulties.
Heather L. Horton, MD, PhD
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
