AIDE: Adaptive intrapatient dose escalation designs to accelerate Phase I clinical trials.

Designing Phase I clinical trials is challenging when accrual is slow or sample size is limited. The corresponding key question is: how to efficiently and reliably identify the maximum tolerated dose (MTD) using a sample size as small as possible? We propose model-assisted and model-based designs with adaptive intrapatient dose escalation (AIDE) to address this challenge. AIDE is adaptive in that the decision of conducting intrapatient dose escalation depends on both the patient's individual safety data, as well as other enrolled patient's safety data.

Dietary management and major clinical events in patients with long-chain fatty acid oxidation disorders enrolled in a phase 2 triheptanoin study.

Background & Aims: Long-chain fatty acid oxidation disorders (LC-FAOD) are rare, life-threatening, autosomal recessive disorders that lead to energy depletion and major clinical events (MCEs), such as acute metabolic crises of hypoglycemia, cardiomyopathy, and rhabdomyolysis. The aim of this study was to report a post hoc analysis of diet diary data from the phase 2 UX007-CL201 study (NCT01886378).

Methods: In the single-arm, open-label, phase 2 UX007-CL201 study, the safety and efficacy of 78 weeks of treatment with triheptanoin, an odd-carbon, medium-chain triglyceride consisting of three 7-carbon fatty acids on a glycerol backbone, was investigated in subjects with LC-FAOD versus a retrospective 78-week period when subjects were optimally managed under published dietary guidelines.

Healthcare costs among patients with hemophilia A treated with factor replacement or bypassing agents.

To assess real-world costs for patients with hemophilia A treated with bypassing agents versus factor VIII (FVIII) replacement. Claims data from a large US health insurer during 1 January 2006-30 September 2014 were used for analysis. Treated patients with hemophilia A were identified based on ≥1 medical claim with a diagnosis code for hemophilia A (ICD-9-CM 286.

Clinical and Economic Burden of Commercially Insured Patients with Acromegaly in the United States: A Retrospective Analysis.

Background: Acromegaly is a chronic disorder characterized by excess growth hormone secretion and elevated insulin-like growth factor-1 levels most often caused by a pituitary adenoma. Clinical presentation of the disease includes coarsening of the facial features, soft-tissue swelling of the hands and feet, and overgrowth of the frontal skull and protrusion of the jaw, as well as joint symptoms. Acromegaly is associated with several comorbidities, including diabetes, cardiovascular disease, and arthropathy, which, if left untreated, can lead to early mortality.

Comparison of statistical and operational properties of subject randomization procedures for large multicenter clinical trial treating medical emergencies.

Large multicenter acute stroke trials demand a randomization procedure with a high level of treatment allocation randomness, an effective control on overall and within-site imbalances, and a minimized time delay of study treatment caused by the randomization procedure. Driven by the randomization algorithm design of A Study of the Efficacy and Safety of Activase (Alteplase) in Patients with Mild Stroke (PRISMS) (NCT02072226), this paper compares operational and statistical properties of different randomization algorithms in local, central, and step-forward randomization settings. Results show that the step-forward randomization with block urn design provides better performances over others.