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Optimization, refinement and reduction of murine in vivo experiments to assess therapeutic approaches for hemophilia A.

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Optimization, refinement and reduction of murine in vivo experiments to assess therapeutic approaches for hemophilia A. / Baumgartner, Bernhard; Jaki, Thomas; Wolfsegger, Martin J. et al.
In: Laboratory Animals, Vol. 44, No. 3, 07.2010, p. 211-217.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Baumgartner, B, Jaki, T, Wolfsegger, MJ, Eder, B, Schiviz, A, Schwarz, HP & Muchitsch, EM 2010, 'Optimization, refinement and reduction of murine in vivo experiments to assess therapeutic approaches for hemophilia A.', Laboratory Animals, vol. 44, no. 3, pp. 211-217. https://doi.org/10.1258/la.2010.009113

APA

Baumgartner, B., Jaki, T., Wolfsegger, M. J., Eder, B., Schiviz, A., Schwarz, H. P., & Muchitsch, E. M. (2010). Optimization, refinement and reduction of murine in vivo experiments to assess therapeutic approaches for hemophilia A. Laboratory Animals, 44(3), 211-217. https://doi.org/10.1258/la.2010.009113

Vancouver

Baumgartner B, Jaki T, Wolfsegger MJ, Eder B, Schiviz A, Schwarz HP et al. Optimization, refinement and reduction of murine in vivo experiments to assess therapeutic approaches for hemophilia A. Laboratory Animals. 2010 Jul;44(3):211-217. doi: 10.1258/la.2010.009113

Author

Baumgartner, Bernhard ; Jaki, Thomas ; Wolfsegger, Martin J. et al. / Optimization, refinement and reduction of murine in vivo experiments to assess therapeutic approaches for hemophilia A. In: Laboratory Animals. 2010 ; Vol. 44, No. 3. pp. 211-217.

Bibtex

@article{275c3a234b1d4c57bda676807e222f89,
title = "Optimization, refinement and reduction of murine in vivo experiments to assess therapeutic approaches for hemophilia A.",
abstract = "The tail cut bleeding model (CUT) is routinely used in factor VIII-deficient mice to assess pharmacodynamic effects of therapeutic strategies for haemophilia A. Results from this model are highly variable, many modifications to the model are reported and at times the animals' wellbeing may be compromised by recording survival as an endpoint. We therefore investigated if the ferric chloride carotid occlusion model (COM) used for thrombosis research can be applied to enhance data quality and animal welfare in haemophilia A research. Relative dose effects and relative dose variations were calculated for the CUT and COM. The requisite sample sizes were estimated and the importance of survival rates to assess rebleeds during recovery was evaluated by correlating initial blood loss to mortality. Relative dose effects increased with higher doses in both models. The COM was more sensitive at lower doses than the CUT, had up to 82% less variation across doses and clearly showed superior accuracy. Only 5% of the sample size required for the CUT would be needed to establish non-inferiority between a specific therapeutic dose in haemophilia A mice and healthy wild-type animals. A strong statistically significant correlation was found between initial blood loss and mortality within 24 h. Our findings clearly suggest that the COM is a valid tool for assessing haemophilia A treatment in vivo. The highly reproducible data means that significantly fewer animals are required and a more humane endpoint can be used by directly assessing clot stability instead of survival rate.",
keywords = "Animal model , haemophilia , rodents , reduction , refinement",
author = "Bernhard Baumgartner and Thomas Jaki and Wolfsegger, {Martin J.} and B. Eder and A. Schiviz and Schwarz, {H. P.} and Muchitsch, {E. M.}",
year = "2010",
month = jul,
doi = "10.1258/la.2010.009113",
language = "English",
volume = "44",
pages = "211--217",
journal = "Laboratory Animals",
issn = "0023-6772",
publisher = "SAGE Publications Ltd",
number = "3",

}

RIS

TY - JOUR

T1 - Optimization, refinement and reduction of murine in vivo experiments to assess therapeutic approaches for hemophilia A.

AU - Baumgartner, Bernhard

AU - Jaki, Thomas

AU - Wolfsegger, Martin J.

AU - Eder, B.

AU - Schiviz, A.

AU - Schwarz, H. P.

AU - Muchitsch, E. M.

PY - 2010/7

Y1 - 2010/7

N2 - The tail cut bleeding model (CUT) is routinely used in factor VIII-deficient mice to assess pharmacodynamic effects of therapeutic strategies for haemophilia A. Results from this model are highly variable, many modifications to the model are reported and at times the animals' wellbeing may be compromised by recording survival as an endpoint. We therefore investigated if the ferric chloride carotid occlusion model (COM) used for thrombosis research can be applied to enhance data quality and animal welfare in haemophilia A research. Relative dose effects and relative dose variations were calculated for the CUT and COM. The requisite sample sizes were estimated and the importance of survival rates to assess rebleeds during recovery was evaluated by correlating initial blood loss to mortality. Relative dose effects increased with higher doses in both models. The COM was more sensitive at lower doses than the CUT, had up to 82% less variation across doses and clearly showed superior accuracy. Only 5% of the sample size required for the CUT would be needed to establish non-inferiority between a specific therapeutic dose in haemophilia A mice and healthy wild-type animals. A strong statistically significant correlation was found between initial blood loss and mortality within 24 h. Our findings clearly suggest that the COM is a valid tool for assessing haemophilia A treatment in vivo. The highly reproducible data means that significantly fewer animals are required and a more humane endpoint can be used by directly assessing clot stability instead of survival rate.

AB - The tail cut bleeding model (CUT) is routinely used in factor VIII-deficient mice to assess pharmacodynamic effects of therapeutic strategies for haemophilia A. Results from this model are highly variable, many modifications to the model are reported and at times the animals' wellbeing may be compromised by recording survival as an endpoint. We therefore investigated if the ferric chloride carotid occlusion model (COM) used for thrombosis research can be applied to enhance data quality and animal welfare in haemophilia A research. Relative dose effects and relative dose variations were calculated for the CUT and COM. The requisite sample sizes were estimated and the importance of survival rates to assess rebleeds during recovery was evaluated by correlating initial blood loss to mortality. Relative dose effects increased with higher doses in both models. The COM was more sensitive at lower doses than the CUT, had up to 82% less variation across doses and clearly showed superior accuracy. Only 5% of the sample size required for the CUT would be needed to establish non-inferiority between a specific therapeutic dose in haemophilia A mice and healthy wild-type animals. A strong statistically significant correlation was found between initial blood loss and mortality within 24 h. Our findings clearly suggest that the COM is a valid tool for assessing haemophilia A treatment in vivo. The highly reproducible data means that significantly fewer animals are required and a more humane endpoint can be used by directly assessing clot stability instead of survival rate.

KW - Animal model

KW - haemophilia

KW - rodents

KW - reduction

KW - refinement

U2 - 10.1258/la.2010.009113

DO - 10.1258/la.2010.009113

M3 - Journal article

VL - 44

SP - 211

EP - 217

JO - Laboratory Animals

JF - Laboratory Animals

SN - 0023-6772

IS - 3

ER -