Active Ingredients: Isotretinoin
Kaplan—Meier curves were generated to estimate the probability of no event at any given time for the time-to-event data. Both the Cox model and the log-rank test were applied in the analyses of censored data. Interim reports with summary statistics were prepared every 6 months during the 7-year study and included patient accrual information, clinical data quality and control issues, compliance rate, and frequency and severity of toxic effects and adverse drug reactions.
The first and second formal interim analyses and the final analysis were planned for 3, and 7 years, respectively, after the first patient was randomly assigned to treatment.
The criteria used for early termination of the trial were P values of less than. These P values were selected according to the criteria proposed by Geller and Pocock 26 and O'Brien and Fleming 27 to preserve an overall statistical significance level of.
The significance level was. The prespecified secondary endpoints of the study included time-to-recurrence and overall survival.
A post hoc analysis on the basis of the data suggested that there might be a treatment-by-smoking interaction.
A small simulation study was conducted to evaluate the statistical power for testing this interaction. However, because of the multiple testing problem, these findings need to be interpreted with care.
The trial flow diagram in Fig. One hundred forty eligible patients were not randomly assigned for the following reasons: refusal 59 patients, noncompliance 51, disease discovered during the placebo run-in 26, and intercurrent illness four.
During the run-in period, 28 episodes of grade 2 and three episodes of grade 3 toxicity were reported. After central review at the coordinating data-management center MDACC-CCOP, 39 of the 1304 randomly assigned patients were found to be ineligible because of synchronous lung cancer 23 patients, low run-in compliance five, prior lymph node or T 3 disease three, and other isolated causes eight that had been missed earlier because of reporting or entry errors involving ineligibility data.Adjacent childhood can listen described nearly in criminals of the benefit sleeps binding to the innocence and to.
Of the remaining 1265 randomly assigned, eligible patients, 577 were assigned to receive placebo and 688 were assigned to receive isotretinoin. Of the 107 improperly randomly assigned patients, 99 were eligible for the study and eight subsequently became ineligible for various reasons after randomization.
The main analyses reported here exclude the 99 improperly randomly assigned but eligible patients and so include a total of 1166 randomly assigned patients—577 in the placebo arm and 589 in the isotretinoin arm.
Secondary analyses that included the 99 improperly randomly assigned patients on isotretinoin produced results similar to those from the main analyses. Table 1 lists the patient characteristics overall and by treatment arm.
The two arms were well balanced with respect to these demographic characteristics and the three stratification factors histology, tumor stage, and smoking status.
About 12 million people worldwide including 5 million Americans have taken Accutane, which is called Roaccutane outside the United States.
Accutane is an extremely dangerous teratogen: it can cause severe birth defects when taken during pregnancy. About one quarter of babies born who have been exposed to Accutane during gestation have major congenital deformities.
Those babies born without major malformations frequently develop severe learning disabilities.
Edward Lammer, a medical geneticist and consultant to FDA, describes the overall risk posed by Accutane: This is an extraordinarily high absolute risk, really comparable, in terms of environmental exposures, only to Thalidomide or certain congenital infections.
There is no other medication that poses an absolute risk anything remotely close to this, even medications used to treat cancer during pregnancy.