The Role of Socioeconomic Conditions and Psychological Factors in the Willingness to Volunteer for Phase I Studies

2008 ◽  
Vol 22 (6) ◽  
pp. 367-374 ◽  
Author(s):  
Luis Almeida ◽  
Amílcar Falcão ◽  
Rui Coelho ◽  
António Albino-Teixeira ◽  
Patrício Soares-da-Silva
2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Georg Ferber ◽  
Ulrike Lorch ◽  
Jörg Täubel

Concentration-effect (CE) models applied to early clinical QT data from healthy subjects are described in the latest E14 Q&A document as promising analysis to characterise QTc prolongation. The challenges faced if one attempts to replace a TQT study by thorough ECG assessments in Phase I based on CE models are the assurance to obtain sufficient power and the establishment of a substitute for the positive control to show assay sensitivity providing protection against false negatives. To demonstrate that CE models in small studies can reliably predict the absence of an effect on QTc, we investigated the role of some key design features in the power of the analysis. Specifically, the form of the CE model, inclusion of subjects on placebo, and sparse sampling on the performance and power of this analysis were investigated. In this study, the simulations conducted by subsampling subjects from 3 different TQT studies showed that CE model with a treatment effect can be used to exclude small QTc effects. The number of placebo subjects was also shown to increase the power to detect an inactive drug preventing false positives while an effect can be underestimated if time points aroundtmaxare missed.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3029-3029 ◽  
Author(s):  
T. Z. Zaks ◽  
A. Akkari ◽  
L. Briley ◽  
M. Mosteler ◽  
A. G. Stead ◽  
...  

3029 Background: Rash and diarrhea are a class effect of ERBB1 inhibitors. These events are relatively mild with Lapatinib (a dual ERBB1/ERBB2 kinase inhibitor). Finding a genetic basis for patients who may be predisposed to these adverse events, from the outset of clinical development, may improve the understanding of the mechanisms of these side effects and may have implications for use and dosing. Methods: DNA was isolated from peripheral blood of 107 Caucasian subjects from eight monotherapy phase I studies including 73 healthy volunteers and 34 cancer patients, 100 of whom had associated pharmacokinetic data. 284 single nucleotide polymorphisms (SNPs) from five candidate genes of transporters (ABCB1, ABCG2) and enzymes (CYP 3A4 and 3A5, and 2C19) for which lapatinib is a substrate were genotyped and examined for associations with pharmacokinetic variables (dose-normalized AUC, Cmax, and Tmax) as well as rash (15 cases) and diarrhea (18 cases). Results: Skin rash and diarrhea in this phase I cohort were only mild, (i.e. grade I or II). Statistically significant associations were observed between 34 SNPs in CYP2C19, rash (22 SNPs) and diarrhea (6 SNPs), and between 15 SNPs in ABCB1 and Tmax. Notably, 3/3 subjects (2 healthy volunteers, one patient) homozygous for the CYP2C19*2 allele experienced both mild rash and diarrhea. Extensive linkage disequilibrium was observed among these associated SNPs. Conclusions: Our results suggest that it is possible to determine pharmacogenetic associations with side effect phenotypes during the earliest phase of clinical drug development. These results are currently being validated on a larger cohort of patients from phase II lapatinib clinical trials. [Table: see text]


BMJ ◽  
2015 ◽  
pp. h3889
Author(s):  
Nathan J Brendish ◽  
Diane F Gbesemete ◽  
Hans de Graaf ◽  
Christopher J Edwards ◽  
Saul N Faust

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yudong Wang ◽  
Filip Janku ◽  
Sarina Piha-Paul ◽  
Kenneth Hess ◽  
Russell Broaddus ◽  
...  
Keyword(s):  
Phase I ◽  

ORL ro ◽  
2016 ◽  
Vol 4 (1) ◽  
pp. 40-42
Author(s):  
Alexandra Boloș ◽  
Sebastian Cozma ◽  
Andreea Silvana Szalontay

Tinnitus is a common otologic symptom and probably the most troublesome. Tinnitus causes a number of physical and psychological consequences, that interfere with the quality of life of the patient. Many authors believe that the presence of tinnitus in children is a matter of lesser importance than in adults because it is met less frequently and would be a fleeting symptom, inoffensive for them (Graham, 1981). In addition, the prevalence of tinnitus during adolescence and even in young adults is increasing, possibly as a consequence of the increased ambient noise (Bulbul SF, Shargorodsky J). Various therapeutic approaches have generated different results, which led us to consider the role of psychological factors, hence the need to underline the particularities of this symptom in childhood.  


2020 ◽  
Author(s):  
Robert Pellegrino ◽  
Curtis Luckett

Texture is a prominent feature in foods and consequently can be the reason a food is accepted or rejected. However, other sensory attributes, such as flavor/taste, aroma, sound and appearance may also lead to the rejection of food and motivations other than unpleasantness exist in unacceptance. To date, these motivations for food rejection have been studied in isolation and their relationships with psychological factors have not been tested. This study measured reasons people reject a food and probed into the specifics of texture rejection. A large U.S. sample (N=473) was asked to rate their motivations for rejecting a food, list foods that were disliked due to unpleasant sensory attributes, specify the unpleasant sensory attribute(s), and complete an assessment of general touch sensitivity. Results showed 94% of individuals reject a food due to its texture, a rate comparable to flavor-based rejection. Looking at the number of foods being rejected, flavor was the most common food attribute, followed by texture and then aroma. From a linguistic standpoint, aversive textures encompass a large vocabulary, larger than liked textures, and the same food may be rejected due to a single or combination of texture terms. Viscosity (e.g. slimy) and hardness (e.g. mushy) are the most common aversive texture types, but through cluster analysis subsets of individuals were identified that are more aversive to other textures. This study emphasizes the role of aversive textures in food rejection and provides many avenues for future investigations.


Author(s):  
Neha Mehta‐Shah ◽  
Matthew A. Lunning ◽  
Alison J. Moskowitz ◽  
Adam M. Boruchov ◽  
Jia Ruan ◽  
...  

Ergonomics ◽  
2013 ◽  
Vol 56 (12) ◽  
pp. 1928-1939 ◽  
Author(s):  
Martina Kotzé ◽  
Leon Steyn

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