Interim efficacy analyses

Interim efficacy analyses usually make a mess These analyses require either that the overall size of the trial has to be greater than if no interim analysis was performed, or that a smaller a must be accepted as indicating statistical significance at the end of the whole study. 

All four trials currently ongoing have successfully passed preplanned interim safety analyses. Intergroup and NSABP trials were granted FDA approval for a joint interim efficacy analysis including 3351 patients. The HERA trial performed a pre-planned interim efficacy analysis at 475 events including 3387 evaluable patients. These analyses, presented during AS CO 2005, showed a reduction in the risk of recurrent disease of 52% (joint interim analysis) and 46% (HERA interim... 

Jacobson IM, Everson GT, Gordon SC, Kauffman R, McNair L, Muir A, McHutchison JG (2007) Interim analysis results from a phase 2 study of telaprevir with peginterferon alfa-2A and ribavirin in treatment-naive subjects with hepatitis C. AASLD 58th Annual Meet, Abstract 177 Johnson M (2006) Response to Atazanavir/ritonavir versus lopinavir/ritonavir equivalent or different efficacy profiles by HUl. AIDS 20 1987... 

De Angelo, D.J. et al.. Interim analysis of a phase If study of the safety and efficacy of gemtuzumab ozogamycin (Mylotarg) given in combination with cytarabine and daunorubicin in patients <60 years old with untreated acute myeloid leukemia, Proc. Am. Soc. Hem., 100,198a, Abstr. 745, 2002. 

It is also possible to stop trials for reasons other than overwhelming efficacy, for example for futility, where at an interim stage it is clear that if the trial were to continue it would have little chance of giving a positive result. We will say more about interim analysis in a later chapter and in particular consider the practical application of these methods. 

In addition to looking for overwhelming efficacy there is also the possibility of stopping the trial for futility at an interim stage. It may be, for example, that the analysis of the interim data is not at all in favour of the test treatment and were the trial to continue there would simply be no real possibility of obtaining a... 

It is not a requirement that a trial must have an interim analysis, either for efficacy or for futility. In most long-term trials, however, where there is the opportunity for an interim evaluation then it may be something worth putting in place. The interim can involve only efficacy, only futility, or both and may indeed involve some other things as well, such as a re-evaluation of sample size (see Section 8.5.3). 

In line with this, the interim analysis plan was revised and only one interim was to be conducted for both efficacy and futility after 40 per cent of the patients had completed 3 months of follow-up. Since the two proposed analyses were not equally spaced, a spending functions were needed to revise the adjusted significance levels and these turned out to be 0.0007 and 0.0497. 

Review of interim analysis of efficacy data (if planned)... 

S.L. Rogers, L.T. Friedhoff, Long-term efficacy and safety of donepezil in the treatment of Alzheimer s disease an interim analysis of the results of a US multicentre open label extension study, Eur. Neuropsychopharmacol. 8 (1998) 67-75. 

A modified-release formulation (Carbolithium Once-A-Day) produced a reduction in peak/trough lithium ratio compared with a standard formulation (519), and an interim analysis of an open switch to the modified-release formulation suggested better tolerability and efficacy at 4 weeks (n = 27) and 6 weeks (n = 15) (520). A paucity of detail, however, prevents firm conclusions. 

Durbano F, Mencacci C, Dorigo D, Riva M, Buffa G. The long-term efficacy and tolerability of carbolithium once a day an interim analysis at 6 months. Chn Ter 2002 153(3) 161-6. 

D Amico DJ, Goldberg MF, Hudson H, et al. Anecortave acetate as monotherapy for the treatment of subfoveal lesions in patients with exudative age-related macular degeneration (AMD) interim (month 6) analysis of clinical safety and efficacy. Anecortave Acetate Clinical Smdy Group. Retina 2003 23 14. 

A trial of the efficacy of D-sotalol in patients with left ventricular dysfunction (8) was discontinued early when an interim analysis of 2762 patients showed an overall mortality of 3.9% in the D-sotalol group, compared with 2% in the placebo group (9). 

Paavonen J, Jenkins D, Bosch FX et al. (2007) Efficacy of a prophylactic adjuvanted bivalent LI virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women an interim analysis of a phase III double-blind, randomised controlled trial. Lancet 369 2161-2170. Erratum in Lancet 370 1414... 

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