Furthermore, TKR is a very efficacious treatment option for knee OA70, and societys willingness to pay for Tanezumab may be limited by the existence of a very efficacious and cost-effective surgical alternate. Tanezumab provides an additional pharmacological routine that can delay the need for surgical treatment and ARQ 197 (Tivantinib) improve QALE. life expectancy of 11.15 QALYs, a lifetime risk of TKR of 74%, and cumulative discounted direct medical costs of $148,700. Adding Tanezumab improved QALYs to 11.42, reduced ARQ 197 (Tivantinib) main TKR utilization to 63%, and increased costs to between $155,400 and $199,500. In the base-case analysis, Tanezumab at $600/dose was cost-effective when delivered outside of a hospital. At $1,000/dose, Tanezumab was not cost-effective in all but the most optimistic scenario. Only at rates of accelerated OA progression of 10% or more (10-fold higher than reported ideals) did Tanezumab decrease QALYs and fail to represent a viable option. Conclusions At $100,000/QALY, Tanezumab would be cost effective if priced $400/dose in all settings except IV hospital delivery. is defined as failure of a routine that provided initial relief to provide pain relief in subsequent periods. The subjects remain on the routine until the failure is observed by a clinician. Subjects observed GLURC to fail (pain returned to pre-treatment levels) are removed from the routine. For the base case, we assumed a late failure rate of 10% per year (analogizing from data on biologics for rheumatoid arthritis)51 We carried out these analyses having a validated model (OAPol) of the organic history and management of knee OA that has been used to examine the cost-effectiveness of opioids in OA, for any premarket evaluation of DMOADs, and to project lifetime costs in individuals with knee OA11, 54, 55. We adapted the existing model to capture the essential medical and economic overall performance attributes of Tanezumab. We added one structural feature, which offered the capacity to recognize those who experienced quick ARQ 197 (Tivantinib) joint destruction, an important Tanezumab-related complication. We estimated a 1% chance of accelerated OA progression (major toxicity) in the 1st yr and 0.5% in subsequent years based on findings from an independent adjudication committee18, 56. Accelerated OA progression was characterized by termination of Tanezumab treatment and immediate TKR. We assumed a worst-case scenario, and we reduced the durability and effectiveness of TKR by 50% among those with joint destruction in order to reflect the bone damage associated with this complication. TKR acceptance rates were based on data from your Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) and were calibrated so that all cause TKR rate in the 1st yr of treatment matched those observed in large Tanezumab tests (~5%)18 For revision TKR, we used data from Paxton et al, since revision data were not reported due to short trial duration57 To assure the model output is definitely concordant with trial-based input data, we present the results of the internal model validation. The model estimated the pain reduction due to Tanezumab at 37.8 WOMAC points, which is similar to the 33.7 (SD 19.5) point reduction seen in the clinical trial (an average across dosages ranging from 10 g/kg to 100 g/kg)17. Further, the trial reported that 5% of those on Tanezumab received TKR by the end of one yr with 1% having TKR due to joint damage. The model derived ideals were 4% and 1% respectively. Costs Tanezumab costs were broken into three groups: administration, drug, and monitoring. Administration costs refer to the cost associated with delivery of the drug and varied depending on the establishing (self-administered subcutaneous (SC) vs intravenous (IV); non-hospital vs IV outpatient) as well as the type of process billed (non-chemotherapeutic IV vs chemotheraputic IV)58, 59. While published tests of Tanezumab for knee OA have focused on IV delivery, Tanezumab has been delivered via SC injection in additional diseases, so both of these modes of delivery were included in this analysis60, 61. All SC injections were assumed to be self-administered, while IV infusions were delivered by a healthcare provider. Administration costs assorted from $0/injection (self-administered SC) to $433/injection. For the purposes of this analysis, drug cost refers to the price of one dose of Tanezumab and, in the absence of current pricing, was assorted from $200 to $1000, consistent with costs of additional biologic regimens for additional conditions62. Based on published studies, we assumed that Tanezumab doses were delivered once every 8 weeks15, 17, 19. Monitoring costs for IV infusions were fixed at $277 and included semi-annual physicians visits, yearly blood checks, and x-rays to.