Utility of Circulating Tumor DNA Assessment in Characterizing Recurrence Sites after Optimal Resection for Metastatic Colorectal Cancer.

BACKGROUND: Plasma circulating tumor DNA (ctDNA) is a promising biomarker for metastatic colorectal cancer (mCRC); however, its role in characterizing recurrence sites after mCRC resection remains poorly understood. This single-institution study investigated the timing of ctDNA detection and its levels in the context of recurrence at different sites after mCRC resection. STUDY DESIGN: Patients who underwent optimal resection of CRC metastases involving the peritoneum, distant lymph nodes, or liver, with serial postoperative tumor-informed ctDNA assessments (Signatera) were included. Recurrence sites, as defined by surveillance imaging or laparoscopy, were categorized as peritoneal-only and other distant sites (liver, lung, lymph nodes, or body wall). RESULTS: Among the 31 included patients, ctDNA was detected in all 26 (83.4%) patients with postoperative recurrence and was persistently undetectable in 5 patients who did not experience recurrence. At 3 months postsurgery, ctDNA was detected in 2 (25%) of 8 patients with peritoneal-only recurrence and 17 (94.4%) of 18 patients with distant recurrence (p < 0.001). Beyond 3 months, ctDNA was detected in the remaining 6 patients with peritoneal-only disease and 1 patient with distant disease. ctDNA detection preceded the clinical diagnosis of recurrence by a median of 9 weeks in both groups. At recurrence, peritoneal-only recurrent cases exhibited lower ctDNA levels (median 0.4 mean tumor molecules/mL, interquartile range 0.1 to 0.8) compared with distant recurrence (median 5.5 mean tumor molecules/mL, interquartile range 0.8 to 33.3, p = 0.004). CONCLUSIONS: Peritoneal-only recurrence was associated with delayed ctDNA detection and low levels of ctDNA after optimal resection for mCRC. ctDNA testing may effectively characterize recurrence sites and may help guide subsequent treatments specific to the disease sites involved.

Does gabapentin provide benefit for patients with knee OA? A benefit-harm and cost-effectiveness analysis.

OBJECTIVE: Gabapentin can treat neuropathic pain syndromes and has increasingly been prescribed to treat nociplastic pain. Some patients with knee osteoarthritis (OA) suffer from both nociceptive and nociplastic pain. We examined the cost-effectiveness of adding gabapentin to knee OA care. METHOD: We used the Osteoarthritis Policy Model, a validated Monte Carlo simulation of knee OA, to examine the value of gabapentin in treating knee OA by comparing three strategies: 1) usual care, gabapentin sparing (UC-GS); 2) targeted gabapentin (TG), which provides gabapentin plus usual care for those who screen positive for nociplastic pain on the modified PainDETECT questionnaire (mPD-Q) and usual care only for those who screen negative; and 3) universal gabapentin plus usual care (UG). Outcomes included cumulative quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. We derived model inputs from published literature and national databases and varied key input parameters in sensitivity analyses. RESULTS: UC-GS dominated both gabapentin-containing strategies, as it led to lower costs and more QALYs. TG resulted in a cost increase of $689 and a cumulative QALY reduction of 0.012 QALYs. UG resulted in a further $1,868 cost increase and 0.036 QALY decrease. The results were robust to plausible changes in input parameters. The lowest TG strategy ICER of $53,000/QALY was reported when mPD-Q specificity was increased to 100% and AE rate was reduced to 0%. CONCLUSION: Incorporating gabapentin into care for patients with knee OA does not appear to offer good value.

A Systematic Review of Operative Team Familiarity on Metrics of Efficiency, Patient Outcomes, Cost, and Team Satisfaction.

OBJECTIVE: This study seeks to systematically review the current literature on how surgical team familiarity relates to metrics of operative efficiency. BACKGROUND: The operating room (OR) is a complex environment involving numerous multidisciplinary interactions that must interface precisely to achieve a successful outcome. METHODS: A systematic search of the PubMed database was prospectively registered in the National Institute for Health Research PROSPERO database (CRD 42020181046) and performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Exposure variable was team familiarity and outcome measures included operative efficiency, patient outcomes, costs, and/or team satisfaction. RESULTS: Of 1123 articles screened, 15 studies involving 24,340 operations met inclusion criteria. All studies were limited to an individual specialty, procedure, or both. The effects of more familiar teams were most pronounced in decreasing operative times [standardized mean difference of -0.51 (95% confidence interval: -1.00, -0.02), P =0.04], whereas the reported impacts on patient clinical outcomes, material waste, and team satisfaction were much more heterogenous. CONCLUSIONS: Improving OR team familiarity is associated with superior operative efficiency and may be associated with other favorable measures. Further inferences are limited by literature heterogeneity, yet could be a novel focus for improving OR performance.

The art and science of priority-setting: assessing the value of Public Health England's Prioritization Framework.

BACKGROUND: Findings are presented from the evaluation of Public Health England's (PHE) Prioritization Framework (PF) aimed to assist local authority commissioners with their public health investment and disinvestment decisions. The study explored the take up of the PF in three early adopter local authority settings. METHODS: Semi-structured interviews (n = 30) across three local authorities supplemented by participant observation of workshops. RESULTS: Participants acknowledged that the PF provided a systematic means of guiding priority-setting and one that encouraged transparency over investment and disinvestment decisions. The role performed by PHE and its regional teams in facilitating the process was especially welcomed and considered critical to the adoption process. However, uptake of the PF required a significant investment of time and commitment from public health teams at a time when resources were stretched. The impact of the political environment in the local government was a major factor determining the likely uptake of the PF. Ensuring committed leadership and engagement from senior politicians and officers was regarded as critical to success. CONCLUSIONS: The study assessed the value and impact of PHE's PF tool in three early adopter local authorities. Further research could explore the value of the tool in aiding investment and disinvestment decisions and its impact on spending.

Cost-effectiveness of duloxetine for knee OA subjects: the role of pain severity.

OBJECTIVE: Establish the impact of pain severity on the cost-effectiveness of generic duloxetine for knee osteoarthritis (OA) in the United States. DESIGN: We used a validated computer simulation of knee OA to compare usual care (UC) - intra-articular injections, opioids, and total knee replacement (TKR) - to UC preceded by duloxetine in those no longer achieving pain relief from non-steroidal anti-inflammatory drugs (NSAIDs). Outcomes included quality-adjusted life years (QALYs), lifetime medical costs, and incremental cost-effectiveness ratios (ICERs). We considered cohorts with mean ages 57-75 years and Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain 25-55 (0-100, 100-worst). We derived inputs from published data. We discounted costs and benefits 3% annually. We conducted sensitivity analyses of duloxetine efficacy, duration of pain relief, toxicity, and costs. RESULTS: Among younger subjects with severe pain (WOMAC pain = 55), duloxetine led to an additional 9.6 QALYs per 1,000 subjects (ICER = $88,500/QALY). The likelihood of duloxetine being cost-effective at willingness-to-pay (WTP) thresholds of $50,000/QALY and $100,000/QALY was 40% and 54%. Offering duloxetine to older patients with severe pain led to ICERs >$150,000/QALY. Offering duloxetine to subjects with moderate pain (pain = 25) led to ICERs <$50,000/QALY, regardless of age. Among knee OA subjects with severe pain (pain = 55) who are unwilling or unable to undergo TKR, ICERs were <$50,600/QALY, regardless of age. CONCLUSIONS: Duloxetine is a cost-effective addition to knee OA UC for subjects with moderate pain or those with severe pain unable or unwilling to undergo TKR. Among younger subjects with severe pain, duloxetine is cost-effective at WTP thresholds >$88,500/QALY.

Long-term clinical and economic outcomes of a short-term physical activity program in knee osteoarthritis patients.

OBJECTIVE: Physical activity (PA) in the US knee osteoarthritis (OA) population is low, despite well-established health benefits. PA program implementation is often stymied by sustainability concerns. We sought to establish parameters that would make a short-term (3-year efficacy) PA program a cost-effective component of long-term OA care. METHOD: Using a validated computer microsimulation (Osteoarthritis Policy Model), we examined the long-term clinical (e.g., comorbidities averted), quality of life (QoL), and economic impacts of a 3-year PA program, based upon the SPARKS (Studying Physical Activity Rewards after Knee Surgery) Trial, for inactive knee OA patients. We determined the cost, efficacy, and impact of PA on QoL and medical costs that would make a PA program a cost-effective addition to OA care. RESULTS: Among the 14 million with knee OA in the US, >4 million are inactive. Participation of 10% in the modeled PA program could save 200 cases of cardiovascular disease, 400 cases of diabetes, and 6,800 quality-adjusted life-years (QALYs). The program had an incremental cost-effectiveness ratio (ICER) of $16,100/QALY. Tripling PA program cost ($860/year) raised the ICER to $108,300/QALY; varying QoL benefits from PA yielded ICERs of $8,800/QALY-$99,900/QALY; varying background cost savings from PA did not qualitatively impact ICERs. Offering the PA program to any adults with knee OA (not only inactive) yielded $31,000/QALY. CONCLUSION: A PA program with 3-year efficacy in the knee OA population carried favorable long-term clinical and economic benefits. These results offer justification for policymakers and payers considering a PA intervention incorporated into knee OA care.

Capacity for evidence-informed policymaking across Europe: development and piloting of a multistakeholder survey.

OBJECTIVES: Evidence-informed policymaking (EIP) is increasingly viewed as a complex endeavour that requires integration of research evidence with available resources and the preferences of those affected by the policy. The first technical expert meeting to enhance EIP in the World Health Organization (WHO) European Region identified the scope to develop and conduct a survey to gather insights into the generation, translation and application of research evidence across the region. This article describes the process of developing and piloting a multistakeholder survey (promoted and technically supported by WHO/Europe) on the topic of capacity for EIP. STUDY DESIGN: Rapid review and pilot cross-sectional survey. METHODS: A survey instrument was developed based on findings from the published literature and refined with input from EIP experts/champions. The online survey was then piloted using various recruitment strategies designed to maximise its reach among the key target groups (senior researchers, knowledge brokers and members of civil society). RESULTS: The rapid review revealed a clear gap in the evidence base in relation to broader surveys of capacity for EIP, as opposed to evidence-based practice at an individual level. Thirteen responses to the pilot survey were received from individuals in 10 European countries. Reported barriers to EIP included a lack of understanding among policymakers and a lack of interaction with researchers. There were examples of efforts to enhance capacity for EIP, both at region or country level and through membership of international networks and collaborations. However, few examples were given of the application and impact of research evidence on the policymaking process. CONCLUSION: This research has demonstrated the feasibility of developing and piloting a multicountry, multistakeholder survey to generate better understanding of evidence use in health policymaking. Next steps include incorporating the lessons learned into a revised version of the survey to be implemented with all 53 WHO/Europe Member States.

Cost-effectiveness of generic celecoxib in knee osteoarthritis for average-risk patients: a model-based evaluation.

OBJECTIVE: The cost-effectiveness of the recently-introduced generic celecoxib in knee OA has not been examined. METHOD: We used the Osteoarthritis Policy (OAPol) Model, a validated computer simulation of knee OA, to evaluate long-term clinical outcomes, costs, and cost-effectiveness of generic celecoxib in persons with knee OA. We examined eight treatment strategies consisting of generic celecoxib, over-the-counter (OTC) naproxen, or prescription naproxen, with or without prescription or OTC proton-pump-inhibitors (PPIs) to reduce gastrointestinal (GI) toxicity. In the base case, we assumed that annual cost was $130 for OTC naproxen, $360 for prescription naproxen, and $880 for generic celecoxib. We considered a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) and discounted costs and benefits at 3% annually. In sensitivity analyses we varied celecoxib toxicity, discontinuation, cost, and pain level. RESULTS: In the base case analysis of the high pain cohort (WOMAC 50), celecoxib had an incremental cost-effectiveness ratio (ICER) of $284,630/QALY compared with OTC naproxen. Only under highly favorable cost, toxicity, and discontinuation assumptions (e.g., annual cost below $360, combined with a reduction in the cardiovascular (CV) event rates below baseline values) was celecoxib likely to be cost-effective. Celecoxib might also be cost-effective at an annual cost of $600 if CV toxicity were eliminated completely. In subjects with moderate pain (WOMAC 30), at the base case CV event rate of 0.2%, generic celecoxib was only cost-effective at the lowest plausible cost ($190). CONCLUSION: In knee OA patients with no comorbidities, generic celecoxib is not cost-effective at its current price.

Assessing the Use of Loupes and Lights in Dental Hygiene Educational Programs.

Purpose: The purpose of this study was to explore the use of loupes and lights in dental hygiene programs, to assess why they are being used, and to evaluate at what point in time they are introduced to students within the curriculum.Methods: A 20 question survey was developed and pilot tested. The survey was disseminated electronically to 335 dental hygiene program directors in the United States. Frequency distributions were analyzed to provide an overview of the data and Fisher's Exact Test was used to investigate differences between technical/community college programs and university-based programs.Results: Out of the 335 electronic surveys, 143 were completed for a response rate of 47%. Prevention of musculoskeletal disorders, ergonomics, and enhanced vision for instrumentation remain the top three advantages of using loupes. Ninety-six percent of respondents indicated students use loupes and over 50% of faculty use loupes. Fifty-seven percent of dental hygiene programs encourage students to purchase loupes with a light. Fifty percent of students pay $601-$900 for loupes and 47% pay $300-$600 for a light.Conclusion: Student and faculty use of loupes and lights are increasing in educational programs. Future research should focus on the longitudinal impact of using loupes/lights, the prevention of musculoskeletal disorders, and an investigation of the continued use of loupes in a professional setting post-graduation.

Model-based evaluation of cost-effectiveness of nerve growth factor inhibitors in knee osteoarthritis: impact of drug cost, toxicity, and means of administration.

OBJECTIVE: Studies suggest nerve growth factor inhibitors (NGFi) relieve pain but may accelerate disease progression in some patients with osteoarthritis (OA). We sought cost and toxicity thresholds that would make NGFi a cost-effective treatment for moderate-to-severe knee OA. DESIGN: We used the Osteoarthritis Policy (OAPol) model to estimate the cost-effectiveness of NGFi compared to standard of care (SOC) in OA, using Tanezumab as an example. Efficacy and rates of accelerated OA progression were based on published studies. We varied the price/dose from $200 to $1000. We considered self-administered subcutaneous (SC) injections (no administration cost) vs provider-administered intravenous (IV) infusion ($69-$433/dose). Strategies were defined as cost-effective if their incremental cost-effectiveness ratio (ICER) was less than $100,000/quality-adjusted life year (QALY). In sensitivity analyses we varied efficacy, toxicity, and costs. RESULTS: SOC in patients with high levels of pain led to an average discounted quality-adjusted life expectancy of 11.15 QALYs, a lifetime risk of total knee replacement surgery (TKR) of 74%, and cumulative discounted direct medical costs of $148,700. Adding Tanezumab increased QALYs to 11.42, reduced primary 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 $1000/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 values) 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.

Cost-effectiveness of nonsteroidal anti-inflammatory drugs and opioids in the treatment of knee osteoarthritis in older patients with multiple comorbidities.

OBJECTIVE: To evaluate long-term clinical and economic outcomes of naproxen, ibuprofen, celecoxib or tramadol for OA patients with cardiovascular disease (CVD) and diabetes. DESIGN: We used the Osteoarthritis Policy Model to examine treatment with these analgesics after standard of care (SOC) - acetaminophen and corticosteroid injections - failed to control pain. NSAID regimens were evaluated with and without proton pump inhibitors (PPIs). We evaluated over-the-counter (OTC) regimens where available. Estimates of treatment efficacy (pain reduction, occurring in ∼57% of patients on all regimens) and toxicity (major cardiac or gastrointestinal toxicity or fractures, risk ranging from 1.09% with celecoxib to 5.62% with tramadol) were derived from published literature. Annual costs came from Red Book Online(®). Outcomes were discounted at 3%/year and included costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios (ICERs). Key input parameters were varied in sensitivity analyses. RESULTS: Adding ibuprofen to SOC was cost saving, increasing QALYs by 0.07 while decreasing cost by $800. Incorporating OTC naproxen rather than ibuprofen added 0.01 QALYs and increased costs by $300, resulting in an ICER of $54,800/QALY. Using prescription naproxen with OTC PPIs led to an ICER of $76,700/QALY, while use of prescription naproxen with prescription PPIs resulted in an ICER of $252,300/QALY. Regimens including tramadol or celecoxib cost more but added fewer QALYs and thus were dominated by several of the naproxen-containing regimens. CONCLUSIONS: In patients with multiple comorbidities, naproxen- and ibuprofen-containing regimens are more effective and cost-effective in managing OA pain than opioids, celecoxib or SOC.

Systematic review of the use of data from national childhood obesity surveillance programmes in primary care: a conceptual synthesis.

This study reviewed the use in primary care of national surveillance data for children to determine the data's potential utility to inform policy and practice decisions on how to prevent and treat childhood obesity. We reviewed the 28 countries identified by the World Obesity Federation as having high-quality comparable body mass index data for children. Literature published from any period up to December 2013 was included. Peer review literature was searched using Web of Science (Core Collection, MEDLINE). Grey literature was searched using the Internet by country name, programme name and national health and government websites. We included studies that (i) use national surveillance obesity data in primary care, or (ii) explore practitioner or parent perspectives about the use of such data. The main uses of national surveillance data in primary care were to identify and recruit obese children and their parents to participate in school and general practice-based research and/or interventions, and to inform families of children's measurements. Findings indicate a need for school staff and practitioners to receive additional training and support to sensitively communicate with families. Translation of these findings into policy and practice could help to improve current uses of national child obesity surveillance data in primary care.

The return of public health to local government in England: changing the parameters of the public health prioritization debate?

OBJECTIVES: To explore the influence of values and context in public health priority-setting in local government in England. STUDY DESIGN: Qualitative interview study. METHODS: Decision-makers' views were identified through semi-structured interviews and prioritization tools relevant for public health were reviewed. Interviews (29) were carried out with Health and Wellbeing Board members and other key stakeholders across three local authorities in England, following an introductory workshop. RESULTS: There were four main influences on priorities for public health investment in our case study sites: an organizational context where health was less likely to be associated with health care and where accountability was to a local electorate; a commissioning and priority-setting context (plan, do, study, act) located within broader local authority priority-setting processes; different views of what counts as evidence and, in particular, the role of local knowledge; and debates over what constitutes a public health intervention, triggered by the transfer of a public health budget from the NHS to local authorities in England. CONCLUSIONS: The relocation of public health into local authorities exposes questions over prioritizing public health investment, including the balance across lifestyle interventions and broader action on social determinants of health and the extent to which the public health evidence base influences local democratic decision-making. Action on wider social determinants reinforces not only the art and science but also the values and politics of public health.

Whole joint MRI assessment of surgical cartilage repair of the knee: cartilage repair osteoarthritis knee score (CROAKS).

OBJECTIVE: To develop a magnetic resonance imaging (MRI) scoring system for follow-up of knee cartilage repair procedures integrating assessment of the repair site and the whole joint called Cartilage Repair OsteoArthritis Knee Score (CROAKS), and to assess its reliability. DESIGN: MRI examinations of 20 patients that had undergone matrix-associated autologous chondrocyte transplantation (MACT) of the knee 12 months before were semi-quantitatively assessed for the repair site using features of the magnetic resonance observation of cartilage repair tissue (MOCART) system and for the whole joint based on experiences with the MRI Osteoarthritis Knee Score (MOAKS) instrument. Intra- and inter-observer reliability was calculated using weighted (w) kappa statistics for plates (medial/lateral tibia, medial/lateral femur, trochlea, patella), compartments (medial tibio-femoral, lateral tibio-femoral, patello-femoral) and the whole joint. For certain features with low prevalence the overall percent agreement was calculated in addition. RESULTS: For cartilage, reliability on a plate level ranged between 0.48 (lateral femur) and 1.00 (medial femur). BML assessment showed comparable results ranging on a plate level between 0.46 and 1.00 with overall percent agreement between 83.3% and 100%. Meniscal morphology assessment ranged between 0.62 and 0.94. For repair site assessment reliability ranged from 0.41 (signal intensity inter-observer) to 1.00 (several features). Overall percent agreement was above 80% for 17 of 22 features assessed (intra- and inter-observer results combined). CONCLUSIONS: Combined scoring of the repair site and whole joint assessment for common osteoarthritis features using CROAKS, which is based on experience with two established semi-quantitative scoring tools, is feasible and may be performed with good to excellent reliability.

Pharmacologic regimens for knee osteoarthritis prevention: can they be cost-effective?

OBJECTIVE: We sought to determine the target populations and drug efficacy, toxicity, cost, and initiation age thresholds under which a pharmacologic regimen for knee osteoarthritis (OA) prevention could be cost-effective. DESIGN: We used the Osteoarthritis Policy (OAPol) Model, a validated state-transition simulation model of knee OA, to evaluate the cost-effectiveness of using disease-modifying OA drugs (DMOADs) as prophylaxis for the disease. We assessed four cohorts at varying risk for developing OA: (1) no risk factors, (2) obese, (3) history of knee injury, and (4) high-risk (obese with history of knee injury). The base case DMOAD was initiated at age 50 with 40% efficacy in the first year, 5% failure per subsequent year, 0.22% major toxicity, and annual cost of $1,000. Outcomes included costs, quality-adjusted life expectancy (QALE), and incremental cost-effectiveness ratios (ICERs). Key parameters were varied in sensitivity analyses. RESULTS: For the high-risk cohort, base case prophylaxis increased quality-adjusted life-years (QALYs) by 0.04 and lifetime costs by $4,600, and produced an ICER of $118,000 per QALY gained. ICERs >$150,000/QALY were observed when comparing the base case DMOAD to the standard of care in the knee injury only cohort; for the obese only and no risk factors cohorts, the base case DMOAD was less cost-effective than the standard of care. Regimens priced at $3,000 per year and higher demonstrated ICERs above cost-effectiveness thresholds consistent with current US standards. CONCLUSIONS: The cost-effectiveness of DMOADs for OA prevention for persons at high risk for incident OA may be comparable to other accepted preventive therapies.

Perceptions of risk from workers in high risk industries with work related musculoskeletal disorders.

BACKGROUND: Work-related musculoskeletal disorders (WMSDs) remain a major occupational health problem, despite decades of research, outreach, and intervention. OBJECTIVE: The aim of this study is to promote early identification and prevention of WMSDs by developing education and outreach materials grounded in interview data collected from workers that have recently filed for workers compensation (WC) for WMSDs. PROCEDURES: We conducted semi-structured telephone interviews with WC claimants (n=66) from high risk industries identified through the use of a Prevention Index (PI) in Washington state with WMSDs of the back, shoulder, hand/wrist, or knee. RESULTS: Perceptions regarding the degree of exposure to WMSD risk factors, the social construction of pain, and the potential to implement injury-prevention measures varied widely. Many workers dismissed their injuries as the result of "fluke" or "freak" occurrences and framed their exposure to risk factors for WMSDs as either inevitable or "just part of the job." CONCLUSIONS: Workers in high-risk industries for WMSDs described their work conditions in ways that suggested: (1) a lack of awareness of the potential for developing a WMSD, (2) a view of work-related pain as normal, and/or (3) a pattern of self-blame for WMSD onset. A paradigm that either asserts the inevitability of WMSDs or dismisses potential control measures presents both a significant barrier to injury prevention efforts as well as a major opportunity for future occupational health research.

Disease-modifying drugs for knee osteoarthritis: can they be cost-effective?

OBJECTIVE: Disease-modifying osteoarthritis drugs (DMOADs) are under development. Our goal was to determine efficacy, toxicity, and cost thresholds under which DMOADs would be a cost-effective knee OA treatment. DESIGN: We used the Osteoarthritis Policy Model, a validated computer simulation of knee OA, to compare guideline-concordant care to strategies that insert DMOADs into the care sequence. The guideline-concordant care sequence included conservative pain management, corticosteroid injections, total knee replacement (TKR), and revision TKR. Base case DMOAD characteristics included: 50% chance of suspending progression in the first year (resumption rate of 10% thereafter) and 30% pain relief among those with suspended progression; 0.5%/year risk of major toxicity; and costs of $1,000/year. In sensitivity analyses, we varied suspended progression (20-100%), pain relief (10-100%), major toxicity (0.1-2%), and cost ($1,000-$7,000). Outcomes included costs, quality-adjusted life expectancy, incremental cost-effectiveness ratios (ICERs), and TKR utilization. RESULTS: Base case DMOADs added 4.00 quality-adjusted life years (QALYs) and $230,000 per 100 persons, with an ICER of $57,500/QALY. DMOADs reduced need for TKR by 15%. Cost-effectiveness was most sensitive to likelihoods of suspended progression and pain relief. DMOADs costing $3,000/year achieved ICERs below $100,000/QALY if the likelihoods of suspended progression and pain relief were 20% and 70%. At a cost of $5,000, these ICERs were attained if the likelihoods of suspended progression and pain relief were both 60%. CONCLUSIONS: Cost, suspended progression, and pain relief are key drivers of value for DMOADs. Plausible combinations of these factors could reduce need for TKR and satisfy commonly cited cost-effectiveness criteria.