PMID- 27793353 OWN - NLM STAT- MEDLINE DCOM- 20170922 LR - 20190318 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 38 IP - 11 DP - 2016 Nov TI - Cost-effectiveness of Low-dose Submicron Diclofenac Compared With Generic Diclofenac. PG - 2418-2429 LID - S0149-2918(16)30736-6 [pii] LID - 10.1016/j.clinthera.2016.09.013 [doi] AB - PURPOSE: NSAIDs are commonly prescribed for the treatment of pain and inflammation. Despite the effectiveness of NSAIDs, concerns exist regarding their tolerability. Worldwide health authorities, including the European Medicines Agency, Health Canada, and the US Food and Drug Administration, have advised that NSAIDs be prescribed at the lowest effective dosage and for the shortest duration. Effective lowering of NSAID dosage without compromising pain relief has been demonstrated in randomized, controlled trials of the recently approved NSAID lower-dose submicron diclofenac. Building on previously published work from an independently published systematic review and meta-analysis, a linear dose-toxicity relationship between diclofenac dose and serious gastrointestinal (GI) events was recently demonstrated, indicating that reductions in adverse events (AEs) may be seen even with modest dose reductions in many patients. The objective of the present study was to estimate the potential reduction in risk for NSAID dose-related AEs, corresponding savings in health care costs, and the incremental cost-effectiveness of submicron diclofenac compared with generic diclofenac in the United States. METHODS: Our decision-analytic cost-effectiveness model considered a subset of potential AEs that may be avoided by lowering NSAID dosage. To estimate the expected reductions in upper GI bleeding/perforation and major cardiovascular events with submicron diclofenac, our model used prediction equations estimated by meta-regressions using data from systematic literature reviews. Utilities, lifetime costs, and health outcomes associated with AEs were estimated using data from the literature. The face validity of the model structure and inputs was confirmed by clinical experts in the United States. Results were evaluated in 1-way and probabilistic sensitivity analyses. FINDINGS: The model predicted that submicron diclofenac versus generic diclofenac could reduce the occurrence of modeled GI events (by 18.0%), cardiovascular events (by 6.9%), and acute renal failure (by 18.8%), leading to a 9.8% reduction in costs of treating AEs. Submicron diclofenac was predicted to be cost-saving, with results relatively insensitive to parameter uncertainty. IMPLICATIONS: Submicron diclofenac has the potential to provide clinical and economic value to patients using NSAIDs in the United States. Further investigation regarding the potential effects of submicron diclofenac on the risks for additional NSAID dose-related toxicities should be explored. CI - Copyright (c) 2016 Elsevier HS Journals, Inc. All rights reserved. FAU - Mladsi, Deirdre AU - Mladsi D AD - School Of Medicine, RTI Health Solutions, Research Triangle Park, North Carolina. Electronic address: dmladsi@rti.org. FAU - Ronquest, Naoko AU - Ronquest N AD - School Of Medicine, RTI Health Solutions, Research Triangle Park, North Carolina. FAU - Odom, Dawn AU - Odom D AD - School Of Medicine, RTI Health Solutions, Research Triangle Park, North Carolina. FAU - Miles, LaStella AU - Miles L AD - School Of Medicine, RTI Health Solutions, Research Triangle Park, North Carolina. FAU - Saag, Kenneth AU - Saag K AD - University of Alabama, Birmingham, Alabama. LA - eng PT - Comparative Study PT - Journal Article DEP - 20161026 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Drugs, Generic) RN - 144O8QL0L1 (Diclofenac) SB - IM MH - Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/economics MH - Cost-Benefit Analysis MH - Diclofenac/*administration & dosage/economics MH - Drugs, Generic/*administration & dosage/economics MH - Humans MH - Pain/drug therapy MH - United States OTO - NOTNLM OT - *NSAIDs OT - *cardiovascular risk OT - *cost-effectiveness OT - *diclofenac OT - *gastrointestinal risk OT - *nonsteroidal anti-inflammatory drugs EDAT- 2016/10/30 06:00 MHDA- 2017/09/25 06:00 CRDT- 2016/10/30 06:00 PHST- 2016/07/29 00:00 [received] PHST- 2016/09/12 00:00 [revised] PHST- 2016/09/03 00:00 [accepted] PHST- 2016/10/30 06:00 [pubmed] PHST- 2017/09/25 06:00 [medline] PHST- 2016/10/30 06:00 [entrez] AID - S0149-2918(16)30736-6 [pii] AID - 10.1016/j.clinthera.2016.09.013 [doi] PST - ppublish SO - Clin Ther. 2016 Nov;38(11):2418-2429. doi: 10.1016/j.clinthera.2016.09.013. Epub 2016 Oct 26.