The Ethics of Early Stopping Rules

2 and as chair of the Data Safety Monitoring Committee for one of the trials (the Intergroup MA17 trial of letrozole) he criticizes, we are concerned that this article has the potential to impair significantly the conduct of future trials in breast cancer adjuvant endocrine therapy and consequently be harmful to patients.Our major issues with the article are: (1) Dr Cannistra repeats some of the misunderstandings about MA17 that we have previously addressed.3 Most important in this context is the implication that disease-free survival (DFS) was not the sole primary end point around which the study was designed and that the difference in DFS targeted was at a specific point in time, rather than, as was actually the case, a hazard ratio measured over time.(2) A one-size-fits-all approach to choosing end points in cancer clinical trials is wrong.The proper choice of end point is context (disease, stage, and therapy) -specific.DFS is an appropriate outcome in trials of endocrine therapy in early breast cancer.(3) The title and tone of the article implies that stopping MA17 "early" meant the goals of the trial had not been achieved because of the intervention of a Data Safety Monitoring Board (DSMB).On the contrary, the study question was answered sooner than we expected because the treatment effect was larger than anticipated.(4) The value of Dr Cannistra's comments and recommendations regarding DSMB's are undermined by an apparent lack of familiarity with how these bodies function under the auspices of a National Cancer Institute cooperative group program.Because of their importance, we will expand briefly on points 2 and 4 in the following paragraphs: 2. Disease-free survival is commonly chosen as the end point of US Food and Drug Administration-and NCIapproved trials of adjuvant endocrine therapy in breast cancer.We feel strongly that this is appropriate, not only because the accumulated experience to date suggests that DFS is a surrogate for overall survival in this setting, 4 but also because preventing breast cancer recurrence has value in itself.Women who suffer an in-breast recurrence often require the mastectomy their initial management was intended to avoid; women who develop new breast cancer repeat the trauma of their initial diagnosis and treatment; and women with distant recurrence inevitably die of their disease.Even in the absence of data that formally quantify

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