Understanding the null hypothesis (H 0) in non-inferiority trials

Repeat transurethral resection for patients with T1 tumors achieves diagnostic, prognostic, and therapeutic benefit. From a diagnostic standpoint, disease understaging is common for these patients; therefore, a second resection provides a more thorough interrogation for the presence of muscle-invasive disease. Upstaging at repeat resection to muscle-invasive disease has been reported in approximately 30% of patients with T1 tumors.115 The risk of upstaging is related to the presence or absence of muscularis propria on the initial resection specimen, with rates of upstaging varying from 40-50% among patients without muscle present on the first TURBT specimen to 15-20% in patients with muscle present at the first TURBT.115 Repeat resection is recommended even when the initial TURBT demonstrates the presence of muscularis propria given the noted risk of upstaging in that setting. Additionally, the pathology at repeat resection contains prognostic value that may guide subsequent clinical management. Patients found to have muscle-invasive disease may be offered neoadjuvant chemotherapy and radical cystectomy as well as tri-modality definitive local treatment. The presence of residual T1 disease at the time of repeat resection is associated with subsequent progression risk approaching 80%. As such, these patients should be counseled regarding the potential benefit of early cystectomy.120 Alternatively, patients with non-invasive disease at repeat resection may be considered for initial bladder preservation with intravesical therapy.

10/12/2012 · Non-inferiority clinical trials: Practical issues and ..

Clinicians should avoid prescribing additional BCG instillations to patients who are not likely to benefit from further BCG therapy. Various definitions have been put forth to more specifically classify patients in which disease continues or recurs quickly after BCG.192,205-207 Historical evidence has demonstrated the lack of clinical benefit of additional BCG in patients who have continued disease after two prior BCG induction courses,190,194 while a short time interval between completion of BCG treatment and subsequent tumor detection has been identified as an adverse prognostic feature.53,197,205 Recently, separate consensus panels have put forth similar defining characteristics of patients not likely to benefit from additional BCG; specifically, patients with high-grade non-muscle invasive disease who have received two induction courses of BCG or induction plus maintenance within six months, as well as those who are intolerant of BCG.208,209 The intention of such a definition as put forth in the statement here is to avoid patients receiving treatments from which they are unlikely to benefit, as well as to aid in future clinical trial design by establishing appropriate eligibility criteria for studies of novel therapies for patients with persistent or recurrent tumor despite BCG treatment.


the non-inferiority margin in this study was 15% .

Non-inferiority trial

Moreover, the non-inferiority margin in this study was 15% []. However, the authors did not provide any justification as to why they chose 15 rather than 10% as used in a previous trial [].