RECURRENT MISCARRIAGE (REMIS) STUDY - HOW SHOULD DATA FROM WOMEN WHO DO NOT BECOME PREGNANT BE HANDLED

The Recurrent Miscarriage (REMIS) study is a double-blind, multicenter , randomized clinical trial designed to evaluate the efficacy of immun ization with paternal leukocytes in the prevention of miscarriages in women who have had three or more unexplained pregnancy losses. Women e ntering the study are immunized with their husband's leukocytes or wit h a saline control before they become pregnant. After becoming pregnan t, they receive weekly ultrasound examinations and psychological suppo rt during the first trimester and are followed until a successful deli very or a miscarriage occurs. The primary analysis for the study will be an intent-to-treat analysis in which we shall compare the proportio n of successes in the two groups, defining a ''success'' as a pregnanc y achieved within 12 months of randomization that results in a viable offspring. We shall count both miscarriages and nonpregnancies as fail ures, owing to the possibility of very early losses prior to the detec tion of pregnancy. In a secondary analysis, we shall exclude women who do not become pregnant within the alloted 12 month period. We compare d the test size and power of these two approaches under various config urations for the true rates of nonpregnancy, miscarriage, and delivery in the two groups. Although the analysis excluding nonpregnant women achieves greater power for alternatives in which pregnancy rates are e qual and Live birth rates higher in the treated group, the rejection r ate is not adequately controlled when pregnancy rates differ but Live birth rates are unaffected by treatment. It can also lead to a reducti on in power if the treatment prevents early as well as later losses. W e conclude that the intent-to-treat analysis should remain the primary analysis for the trial. (C) Elsevier Science Inc. 1998.