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Oligodeoxynucleotides containing CpG motifs (CpG ODNs) display a strong immunostimulating activity and drive the immune response toward the Th1 (T helper type 1) phenotype. These ODNs have shown promising efficacy in preclinical studies when injected locally in several cancer models. We conducted a phase 1 trial to define the safety profile of CpG-28, a(More)
The continual reassessment method (CRM) provides a Bayesian estimation of the maximum tolerated dose (MTD) in phase I clinical trials and is also used to estimate the minimal efficacy dose (MED) in phase II clinical trials. In this paper we propose Bayesian stopping rules for the CRM, based on either posterior or predictive probability distributions that(More)
Haematopoietic stem cell transplantation (HSCT) has been proposed for refractory autoimmune diseases, including systemic sclerosis (SSc). A sequential Bayesian phase I-II clinical trial was conducted in SSc patients to assess the feasibility, the tolerance and the efficacy of autologous HSCT. Peripheral blood stem cells (PBSC) were collected using(More)
We review the rationale behind the statistical design of dose-finding studies as used in phase I and phase I/II clinical trials. We underline what the objectives of such dose-finding studies should be and why the widely used standard design fails to meet any of these objectives. The standard design is a "memoryless" design and we discuss how this impacts on(More)
OBJECTIVE Intravenous ibuprofen (IBU) has been found to be as effective as indomethacin for the treatment of patent ductus arteriosus (PDA) in preterm infants and has been associated with fewer adverse effects in comparative phase III studies. The dose regimen used (10-5-5 mg/kg/day) was based on limited pharmacokinetic data and no phase II study was(More)
The aim of phase II single-arm clinical trials of a new drug is to determine whether it has sufficient promising activity to warrant its further development. For the last several years Bayesian statistical methods have been proposed and used. Bayesian approaches are ideal for earlier phase trials as they take into account information that accrues during a(More)
OBJECTIVE To determine the minimal effective dose (MED) of intravenous midazolam, required for appropriate sedation in 95% of patients, 1 h after drug administration. METHODS A double-blind dose-finding study using the continual reassessment method, a Bayesian sequential design. Twenty-three newborn infants hospitalized in intensive care unit(More)
To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of semisynthetic homoharringtonine (ssHHT), given as a twice daily subcutaneous (s.c.) injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this sequential Bayesian phase I dose-finding(More)
We study model sensitivity of the continual reassessment method (CRM). The context is that of dose-finding designs where certain design parameters are fixed by the investigator. Although our focus is on the CRM (O'Quigley et al., 1990), the essential ideas can be applied to any sequential dose-finding method. It is expected that different choices of a model(More)
For a dose finding study in cancer, the most successful dose (MSD), among a group of available doses, is that dose at which the overall success rate is the highest. This rate is the product of the rate of seeing non-toxicities together with the rate of tumor response. A successful dose finding trial in this context is one where we manage to identify the MSD(More)