Background: To demonstrate bioequivalence between two drug formulations, a pilot trial is often conducted prior to a pivotal trial to assess feasibility and gain preliminary information about the treatment effect. Due to the limited sample size, it is not recommended to perform significance tests at the conventional 5% level using pilot data to determine if a pivotal trial should take place. Whilst some authors suggest to relax the significance level, a Bayesian framework provides an alternative for informing the decision-making. Moreover, a Bayesian approach also readily permits possible incorporation of pilot data in priors for the parameters that underpin the pivotal trial.
Methods: We consider two-sequence, two-period crossover designs that compare test (T) and reference (R) treatments. We propose a robust Bayesian hierarchical model, embedded with a scaling factor, to elicit a Go/No-Go decision using predictive probabilities. Following a Go decision, the final analysis to formally establish bioequivalence can leverage both the pilot and pivotal trial data jointly. A simulation study is performed to evaluate trial operating characteristics.
Results: Compared with conventional procedures, our proposed method improves the decision-making to correctly allocate a Go decision in scenarios of bioequivalence. By choosing an appropriate threshold, the probability of correctly (incorrectly) making a No-Go (Go) decision can be ensured at a desired target level. Using both pilot and pivotal trial data in the final analysis can result in a higher chance of declaring bioequivalence. The false positive rate can be maintained in situations when T and R are not bioequivalent.
Conclusions: The proposed methodology is novel and effective in different stages of bioequivalence assessment. It can greatly enhance the decision-making process in bioequivalence trials, particularly in situations with a small sample size.
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http://dx.doi.org/10.1186/s12874-023-02120-2 | DOI Listing |
Ann Hematol
January 2025
Division of Hematology-Oncology, Hanyang University Seoul Hospital, Seoul, Republic of Korea.
Ravulizumab is a second-generation complement component 5 (C5) inhibitor (C5i) approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) following positive results from two pivotal trials in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH. In both trials, after the 26week primary evaluation period, all patients received ravulizumab for up to 6 years. To report ravulizumab treatment outcomes in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH treated for up to 6 years.
View Article and Find Full Text PDFTher Adv Urol
January 2025
UT Southwestern Department of Urology, Dallas, TX, USA.
Background: The Optilume paclitaxel drug-coated balloon (DCB) is a relatively new-to-market alternative in the management of male anterior urethral stricture disease. The pivotal trial excluded patients with a history of urethroplasty, although these strictures may be amenable to endoscopic management. Therefore, we sought to assess the efficacy of the DCB in the management of recurrent strictures following urethroplasty.
View Article and Find Full Text PDFOpen Respir Med J
November 2024
New Drug Discovery Research, Mankind Research Centre, Mankind Pharma Limited, Plot No 191-E, Sector 4-II, IMT Manesar, Gurugram, India-122051.
Chronic Obstructive Pulmonary Disease (COPD) is associated with cough, sputum production, and a reduction in lung function, quality of life, and life expectancy. Currently, bronchodilator combinations (β2-agonists and muscarinic receptor antagonists, dual therapy) and bronchodilators combined with inhaled corticosteroids (ICS), triple therapy, are the mainstays for the management of COPD. However, the use of ICS in triple therapy has been shown to increase the risk of pneumonia in some patients.
View Article and Find Full Text PDFCancer Med
January 2025
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Introduction: Avelumab, an anti-programmed death ligand 1 antibody, was approved in combination with axitinib for curatively unresectable or metastatic renal cell carcinoma (RCC) in Japan in December 2019. Because the pivotal JAVELIN Renal 101 study included a limited number of Japanese patients, post-marketing surveillance (PMS) was required to evaluate outcomes (safety and effectiveness) in patients with RCC who received avelumab + axitinib treatment in clinical practice in Japan.
Materials And Methods: We report data from prospective, noncomparative, multicenter, observational PMS in patients with RCC who received ≥ 1 dose of avelumab.
Drug Dev Ind Pharm
January 2025
Guangxi Key Laboratory of Drug Discovery and Optimization, School of Pharmacy, Guilin Medical University, Guilin 541199, Guangxi, China.
Objective: Amid the escalating global cancer incidence, the development of effective and safe anticancer drugs is a critical priority in medical research. Addressing the clinical shortcomings of ruthenium-based anticancer drugs are currently a prominent focus of research.
Significance And Methods: Since the pioneering work with platinum derivatives, significant progress has been made in the fundamental studies of metal complexes for the treatment of a wide range of cancers, and there has been a growing interest in their properties and biomedical applications.
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