Optimal design of clinical trials with biologics using dose-time-response models

The commentary by Drs Abman and Kinsella entitled "Inhaled Nitric Oxide for Persistent Pulmonary Hypertension of the Newborn: The Physiology Matters!" provides one important and valid viewpoint concerning the optimal design of clinical trials in this area of neonatology. The approach that they advocate involves individualized and meticulous care of persistent pulmonary hypertension of the newborn (PPHN) patients depending on their underlying disease, using whatever conventional or rescue therapy (before extracorporeal membrane oxygenation [ECMO] is needed to support the patient, while testing the efficacy of inhaled nitric oxide (I-NO).

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Commentary on “Optimal design of clinical trials for drugs designed to slow the course of Alzheimer's disease”

Alzheimer s & Dementia ◽

10.1016/j.jalz.2006.03.017 ◽

2006 ◽

Vol 2 (3) ◽

pp. 140-142 ◽

Cited By ~ 3

Author(s):

Eric R. Siemers

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Optimal Design

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Towards the optimal design of a minimum set of clinical trials for the identification and characterization of VWD

13th International Symposium on Process Systems Engineering (PSE 2018) - Computer Aided Chemical Engineering ◽

10.1016/b978-0-444-64241-7.50345-1 ◽

2018 ◽

pp. 2101-2106

Author(s):

Beatrice Taverna ◽

Alessandra Casonato ◽

Fabrizio Bezzo ◽

Federico Galvanin

Keyword(s):

Clinical Trials ◽

Optimal Design ◽

Identification And Characterization

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Optimal design of clinical trials with computer simulation based on results of earlier trials, illustrated with a lipodystrophy trial in HIV patients

Journal of Biomedical Informatics ◽

10.1016/j.jbi.2008.04.008 ◽

2008 ◽

Vol 41 (6) ◽

pp. 1053-1061 ◽

Cited By ~ 7

Author(s):

Ismail Abbas ◽

Joan Rovira ◽

Josep Casanovas ◽

Tony Greenfield

Keyword(s):

Computer Simulation ◽

Clinical Trials ◽

Optimal Design ◽

Hiv Patients ◽

Simulation Based

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Diarrhea events in cancer patients (pts) treated with lapatinib

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.9125 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 9125-9125 ◽

Cited By ~ 2

Author(s):

M. Koehler ◽

S. Chan ◽

B. O. Newstat ◽

A. Preston ◽

H. A. Burris

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Kinase Inhibitor ◽

Median Number ◽

Low Grade ◽

Cancer Clinical Trials ◽

Dose Time ◽

Delayed Onset ◽

Gastrointestinal Adverse Events ◽

Time To Onset

9125 Introduction: Lapatinib (L) is an oral dual ErbB1/ErbB2 tyrosine kinase inhibitor administered to > 5,000 pts in clinical trials. Low grade gastrointestinal adverse events: diarrhea, nausea and vomiting were recorded. We characterize here the diarrhea events related to L. Methods: Diarrhea events were recorded in 1,514 pts from 8 completed MBC and non-breast cancer clinical trials. Non-L treated pts in these trials were the comparator for analysis of toxicity grades, relationship to dose, time to onset, duration, required interventions and outcomes. Results: The L dose ranged from 1,000–1,500mg daily as monotherapy (n=928) or in combination with chemotherapy (n=198). Capecitabine alone (n=191)and tamoxifen alone (n=197) pts served as controls. For L and non-L groups the per pt diarrhea rates were: any grade 50%v33%; of those G1 54%v53%; G2 30%v30%; G3 15%v17%; G4 <1%v0% and SAEs 3% v 3%; respectively. There were no fatal L-related SAEs. For L, early diarrhea presentation <6 days(d) was 2x more frequent (44%v21%). In the non-L grp, diarrhea presented at 6–14 d in 30% pts. Delayed onset (>28 d) was similar: 22% on L v 26%, non-L. Initial G3 diarrhea or progression from G1/G2 to G3 was similar (Lv non-L): 4%v 3% and 4% v3%, respectively. The median number of events/pt (2) was the same for both groups and median duration was 5d (L) v 6d (non-L). Events (L v non-L) resolved in 89%v93%; and resolved with sequelae <1% v 1%; resolution was not recorded in 7%v4%. Events were managed in approximately 30% of pts with standard anti-diarrhea medications (loperimide and lomitil) and when more sever with hydration, octreotide & antibiotics. Majority of G1/G2 events were not treated. Most pts (85%) did not have L interrupted or dose adjusted and both group only 2% (L)v 2% (non-L) discontinued therapy due to diarrhea. Conclusions: Diarrhea related to L therapy (mostly used as monotherapy in this analysis) is usually mild to moderate, frequently does not require intervention, but pts monitoring is crucial. Importantly, L-related diarrhea appears as early events (before day 6) and is generally responsive to standard interventions. Analyses are ongoing to further identify its natural history, characteristics and pts at risk for serious events. No significant financial relationships to disclose.

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