Predicting therapeutic efficacy - Experimental pain in human subjects. Export

@article{citeulike:4416177, abstract = {The pharmaceutical industry faces tough times. Despite tremendous advances in the science and technology of new lead identification and optimization, attrition rates for novel drug candidates making it into the clinic remain unacceptably high. A seamless boundary between basic preclinical and clinical arms of the discovery process, embodying the concept of 'translational research' is viewed by many as the way forward. The rational application of human experimental pain models in early clinical development is reviewed. Capsaicin, UV-irradiation and electrical stimulation methods have each been used to establish experimental hyperalgesia in Phase-I human volunteers and the application of these approaches is discussed in the context of several pharmacological examples. However, data generated from such studies must be integrated into a well-conceived and executed series of Phase-II efficacy trials in patients in order to derive maximal benefit. The challenges involved in optimal Phase-II/III trial design are reviewed with specific attention to the issues of sample size and placebo response. Finally, the application and potential of cortical EEG studies are discussed as an objective alternative to more conventional pain assessment tools with specific examples of how this technique has been applied to the study of NSAID and opiate-based therapeutics.}, author = {Chizh, B. A. and Priestley, T. and Rowbotham, M. and Schaffler, K.}, citeulike-article-id = {4416177}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.brainresrev.2008.12.016}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19168094}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19168094}, doi = {10.1016/j.brainresrev.2008.12.016}, issn = {0165-0173}, journal = {Brain research reviews}, keywords = {drugs, pain, prediction, vas}, month = {April}, number = {1}, pages = {243--254}, posted-at = {2009-04-28 16:48:27}, priority = {2}, title = {Predicting therapeutic efficacy - Experimental pain in human subjects.}, url = {http://dx.doi.org/10.1016/j.brainresrev.2008.12.016}, volume = {60}, year = {2009} }

TY - JOUR ID - citeulike:4416177 L3 - citeulike-article-id:4416177 N2 - The pharmaceutical industry faces tough times. Despite tremendous advances in the science and technology of new lead identification and optimization, attrition rates for novel drug candidates making it into the clinic remain unacceptably high. A seamless boundary between basic preclinical and clinical arms of the discovery process, embodying the concept of 'translational research' is viewed by many as the way forward. The rational application of human experimental pain models in early clinical development is reviewed. Capsaicin, UV-irradiation and electrical stimulation methods have each been used to establish experimental hyperalgesia in Phase-I human volunteers and the application of these approaches is discussed in the context of several pharmacological examples. However, data generated from such studies must be integrated into a well-conceived and executed series of Phase-II efficacy trials in patients in order to derive maximal benefit. The challenges involved in optimal Phase-II/III trial design are reviewed with specific attention to the issues of sample size and placebo response. Finally, the application and potential of cortical EEG studies are discussed as an objective alternative to more conventional pain assessment tools with specific examples of how this technique has been applied to the study of NSAID and opiate-based therapeutics. IS - 1 JF - Brain research reviews SN - 0165-0173 EP - 254 TI - Predicting therapeutic efficacy - Experimental pain in human subjects. VL - 60 SP - 243 KW - drugs KW - pain KW - prediction KW - vas AU - Chizh, BA AU - Priestley, T AU - Rowbotham, M AU - Schaffler, K PY - 2009/04// UR - http://dx.doi.org/10.1016/j.brainresrev.2008.12.016 ER -