A danger advantage examination of celecoxib for the aversion of colorectal tumor

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A hazard advantage investigation of celecoxib for the avoidance of colorectal malignancy James Cross, MS Pharmaceutical Outcomes Research and Policy Program University of Washington - Biobehavioral Cancer Fellows Day April 20, 2007

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The system & choice issue Nonsteroidal antiinflammatories (NSAIDs)  danger of colorectal adenoma. NSAIDs  danger of gastrointestinal & cardiovascular antagonistic occasions. What is the hazard advantage profile of these medications for colorectal disease chemoprevention?

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Colorectal malignancy: US gauges for 2006 1 Lifetime hazard: 1 in 18 analyzed with CRC. Analyze: 148,610 Deaths: 55,170 1 Ries L et al . Diviner Cancer Statistics Review, 1975-2003 , NCI. Bethesda MD. http://seer.cancer.gov/csr/1975_2003/Based on November 2005 SEER information accommodation.

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Polyps: antecedents to adenocarcinoma Standard Colonoscopy : current reconnaissance technique among "high-hazard" patients. Zielinski SL. JNCI 2004.

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NSAIDs Non-particular inhibitors Ibuprofen, naproxen, diclofenac Aspirin COX-2 specific inhibitors Celecoxib

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Inflammation in colorectal growth Ulrich C, Nat Rev Cancer 2006

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Evidence of advantage: NSAID versus fake treatment at 3 years 1 Baron JA, NEJM 2003 2 Bertagnolli MM, NEJM 2006 3 Arber N, NEJM 2006.

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Evidence of hazard (CV, GI) GI drain chance for ASA : OR: 1.59 (1.40-1.81) 1 OR: 1.77 (1.07-2.94) 2 CV chance for Celecoxib : 1 Derry L BMJ 2000. (RCT meta-examination, n=66,000) 2 USPhysician Health Study NEJM 1989. 3 Solomon SD Circulation 2006.

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Current supposition of celecoxib … Due to the expanded danger of CV occasions connected with their utilization, COX-2 inhibitors are not suggested routinely for sporadic adenomas. - Practice Guideline in Oncology v1.2007 , Nat'l Comprehensive Cancer Network … It is sensible to infer that celecoxib has no part as a chemopreventive operator either in patients with nonfamilial colonic adenomas or the all inclusive community. - Psaty and Potter NEJM 2006

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Reasons for doing a hazard advantage examination Proposed dangers: Cardiovascular (celecoxib) Gastrointestinal (headache medicine) Proposed benefits: Colonoscopies not superbly delicate Slows carcinogenesis handle Decreases # of adenomas Decision issues: Efficacy information in light of surrogate endpoint No orderly, quantitative evaluation

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R isk advantage investigation: techniques Objective : look at the net wellbeing results (chance & advantage) between 3 CRC counteractive action systems ASA versus celecoxib versus colonoscopy alone Perspective : societal point of view, 20 years Population : 60 years, earlier finding of adenoma Approach : wellbeing state move display measuring wellbeing results more than 20 year time frame

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Health-state move model of CRC aversion Polyp free (Post-polypectomy) Advanced adenoma Death CRC GI Tox Discontinue ASA/COX CV Tox

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Methods: Model suppositions GI/CV genuine unfavorable occasions require sedate suspension. The individuals who stop sedate accept wellbeing state moves just as they were getting just colonoscopy.

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Results: Net wellbeing sway # malignancy case/passing + # cardiovascular occasion/demise = net wellbeing sway COMPARATOR [net wellbeing sway – REFERENCE [net wellbeing impact] For an associate of 100,000 (undiscounted):

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Limitations Scarcity of information: relationship between's surrogate endpoints and results utilized as a part of basic leadership. In what manner ought to this be taken care of here, & all in all? ASA utilize: How best to demonstrate cardioprotective impact of ASA utilize, which celecoxib clients may likewise take? For estimations, 1 tumor case/demise = 1 GI/CV occasion.

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Acknowledgments Dissertation board of trustees: Lou Garrison (UW, seat) Scott Ramsey (UW & FHCRC) Dave Veenstra (UW) Funding: Biobehavioral Cancer Prevention & Control Training Program (NCI & UW)

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