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Monitoring Committee (monitoring + committee)

Distribution by Scientific Domains

Medical Sciences	60%
Mathematics and Statistics	40%

Selected Abstracts

Data and Safety Monitoring Committees in Clinical Trials by HERSON, J.

BIOMETRICS, Issue 1 2010
Roger F. Liddle
No abstract is available for this article. [source]

Intravenous lacosamide as short-term replacement for oral lacosamide in partial-onset seizures

EPILEPSIA, Issue 6 2010
Gregory Krauss
Summary Purpose:, Lacosamide is a new antiepileptic drug effective for adjunctive treatment of partial-onset seizures. We evaluated the safety and tolerability of an intravenous (i.v.) formulation of lacosamide (200,800 mg/day) infused over 10, 15, and 30 min as short-term replacement for oral lacosamide in patients with partial-onset seizures. Methods:, This multicenter, open-label, inpatient trial enrolled 160 patients from ongoing open-label, long-term trials who were taking stable doses of oral lacosamide and up to three concomitant antiepileptic drugs (AEDs). Serial cohorts of patients were converted from oral lacosamide treatment to the same intravenous doses infused over progressively shorter infusion durations: 30, 15, and 10 min for 2,5 days. A data monitoring committee (DMC) reviewed safety data for each cohort. The safety of intravenous lacosamide was assessed from adverse events (AEs), laboratory variables, electrocardiography findings, and physical/neurologic examinations. Results:, A total of 160 patients received lacosamide 200,800 mg/day, i.v., for 2,5 days, of which 69% received 400,800 mg/day doses. The most common AEs (reported by ,10% of patients) were headache, dizziness, and somnolence. There was no increase in frequency or severity of AEs with shorter durations of infusion or increased days of exposure. AEs were similar, but more frequent, with higher doses (,400 mg/day). Injection-site events were rare and did not appear to be linked to infusion doses or rates. Lacosamide plasma concentrations were linearly related to dose across the cohorts. Discussion:, This comprehensive evaluation supports the safety of an intravenous lacosamide infusion duration as short as 15 min for short-term (2,5 days) replacement for patients temporarily unable to take oral lacosamide. [source]

An Adaptive Hierarchical Test Procedure for Selecting Safe and Efficient Treatments

BIOMETRICAL JOURNAL, Issue 4 2006
Franz König
Abstract We consider the situation where during a multiple treatment (dose) control comparison high doses are truncated because of lack of safety and low doses are truncated because of lack of efficacy, e.g., by decisions of a data safety monitoring committee in multiple interim looks. We investigate the properties of a hierarchical test procedure for the efficacy outcome in the set of doses carried on until the end of the trial, starting with the highest selected dose group to be compared with the placebo at the full level ,. Left truncation, i.e., dropping doses in a sequence starting with the lowest dose, does not inflate the type I error rate. It is shown that right truncation does not inflate the type I error if efficacy and toxicity are positively related and dose selection is based on monotone functions of the safety data. A positive relation is given e.g. in the case where the efficacy and toxicity data are normally distributed with a positive pairwise correlation. A positive relation also applies if the probability for an adverse event is increasing with a normally distributed efficacy outcome. The properties of such truncation procedures are investigated by simulations. There is a conflict between achieving a small number of unsafely treated patients and a high power to detect safe and efficient doses. We also investigated a procedure to increase power where a reallocation of the sample size to the truncated treatments and the control remaining at the following stages is performed. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

Pitfalls in the design and analysis of paediatric clinical trials: a case of a ,failed' multi-centre study, and potential solutions

ACTA PAEDIATRICA, Issue 2 2009
Johanna H Van Der Lee
Abstract Aim: To increase awareness of possible pitfalls in the design and analysis of a multi-centre randomized clinical trial and to give an overview of alternative study designs and their consequences for power analyses in case of limited availability of trial participants. Methods: Investigation of the assumptions in the power calculation and re-analysis of the original data of a ,failed' trial on the effect of dexamethasone on the duration of mechanical ventilation in young children with respiratory syncytial virus infection. Use of ,boundaries approach' is explored using the data from this trial. A comprehensive overview of the various modern solutions for the design of a subsequent trial in this field is given. Results: Two frequent major deficiencies of trial design and data analysis are reviewed in depth, i.e. too optimistic assumptions for the sample size calculation and failure to adjust for centre effects. Conclusion: Critical review of trial assumptions and if necessary sample size recalculation based on an internal pilot by a data monitoring committee is recommended to maximize the probability of obtaining conclusive results. [source]

Where are clinical trials going?

JOURNAL OF INTERNAL MEDICINE, Issue 2 2004
Society, clinical trials
Abstract. Clinical trials now increasingly impinge on society at large. First there is growing emphasis from health organizations on the need for unbiased evidence about the effectiveness of promoted remedies. Second, as most novel treatments accrue increased costs to society, these need to be evaluated in terms of value for money. Third, there has been confusion and concern about the resolution of conflicting evidence, especially the role of advertising and commercial pressures from a powerful pharmaceutical industry motivated by profit. Fourth, there is concern about research fraud and the ethics of clinical trials. Fifth, there is increasing suspicion of political advice, which sometimes has sought to reassure an anxious public on the basis of complex and possibly inadequate scientific information. Some of these issues are addressed by truly independent and properly constituted data and safety monitoring committees, which are of particular importance when academic investigators or universities have a large financial conflict of interest. This is now more problematic with the current encouragement of investigator-led spin-off companies. These issues are best resolved by independent financial support (from government or other institutions) rather than relying on the commercial sponsor. [source]