Below you will find brief descriptions of our published research projects. See the Oapol Portfolio for additional information about the OAPol Model and select results from publications. To learn more about our ongoing research, please refer to the Ongoing Research page.
Model-based evaluation of cost-effectiveness of nerve growth factor inhibitors in knee osteoarthritis: impact of drug cost, toxicity, and means of administration. Losina et al., Osteoarthritis and Cartilage, 2015: Published literature suggests that nerve growth factor inhibitors (NGFi) relieve pain but could lead to accelerated disease progression in OA patients. Using the OAPol Model, we evaluated cost and toxicity thresholds under which NGFi would be a cost-effective option for knee OA treatment. We found that the setting of drug administration and cost per dose of the drug play important roles in the cost-effectiveness of NGFi treatments. Our analyses further suggest that NGFi treatments have the potential to decrease total knee replacement utilization by over 50%. The cost-effectiveness of this treatment will depend heavily on how the drugs are priced and identifying the appropriate patients to receive the treatment.
Cost-effectiveness of nonsteroidal anti-inflammatory drugs and opioids in the treatment of knee osteoarthritis in older patients with multiple comorbidities. Katz et al., Osteoarthritis and Cartilage, 2015: Patients with multiple comorbidities are often contraindicated to first-line OA treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs). While the addition of stronger analgesics may offer greater pain relief, they are also associated with substantial adverse events. Using the OAPol Model, we examined the long-term clinical and economic outcomes of using NSAIDs and opioids to treat knee OA pain in patients with multiple comorbid conditions. WE founds that, in this cohort, non-selective NSAID-based strategies were more effective and cost-effective in managing OA pain than opioids or selective NSAIDs.
Risk and risk perception of knee osteoarthritis in the US: a population-based study. Michl et al., Osteoarthritis and Cartilage, 2015: Although knee OA is traditionally associated with aging, it is increasingly diagnosed in younger adults, suggesting that prevention efforts should be directed to a younger population. Using Amazon’s Mechanical Turk, we recruited a cohort of US adults aged 25-44 years with no history of knee OA and asked participants to estimate their risk of developing knee OA. We compared participants’ perceptions of knee OA development with their risks derived from an OA risk calculator (OA Risk C), an online tool built and validated by the OAPol Model. We found that knee OA risk factors are prevalent in a younger population, and persons consistently overestimate their risk of knee OA development. These data suggest a lack of knowledge about the timing and incidence of knee OA and offer insights for awareness and risk interventions for younger persons.
Development and feasibility of a personalized, interactive risk calculator for knee osteoarthritis. Losina et al., BMC MSK, 2015: Several factors are associated with knee osteoarthritis; however, these risk factors are not well known among those at risk for OA. Risk calculators have been developed for other chronic conditions but not for OA. Using estimates from the OAPol Model, we built an interactive, personalized, computer-based knee OA risk calculator (OA Risk C) and subsequently conducted a pilot study to evaluate its acceptability and feasibility. We found that our risk calculator was easy to use and depicted risk estimates in a clear and comprehensible fashion. OA Risk C could be used to estimate individual risks and deliver educational interventions focused on knee OA risk reduction.
Defining the value of future research to identify the preferred treatment of meniscal tear in the presence of knee osteoarthritis. Losina et al., PLoS One, 2015: While arthroscopic partial meniscectomy (APM) is frequently used to relieve pain in patients with concomitant meniscal tear and knee osteoarthritis, no recent studies have shown the superiority of APM compared to other treatments for this diagnosis. We built a simulation model evaluating whether the current literature is sufficient to reject the use of APM as a cost-effective treatment for patients with mensical tears and knee OA. We found that delaying APM until patients fail conservative therapy was cost-effective more than 50% of the time. Our results suggest substantial uncertainty in several important parameters and, therefore, do not support the rejection of APM for the treatment of patients with meniscal tear and knee OA.
Lifetime medical costs of knee osteoarthritis management in the United States: Impact of extending indications for total knee arthroplasty. Losina et al., Arthritis Care & Research, 2015: As the only currently available effective treatment for knee osteoarthritis (OA), total knee arthroplasty (TKA) has seen a dramatic expansion in uptake to match the growing number of patients suffering from knee OA. Using the OAPol Model, we estimated total lifetime costs and TKA utilization under a range of eligibility criteria. Average direct medical costs for persons with knee OA were $129,600, and 10% of costs were attributable to knee OA. Persons spent an average of 13 years waiting for TKA after non-surgical treatment options failed to control pain. We estimated OA-related direct medical costs increased to $16,000 when eligibility for TKA was expanded.
Trends in Prescription of Opioids from 2003-2009 in Persons with Knee Osteoarthritis. Wright et al., Arthritis Care & Research, 2014: In the past decade, awareness of potential adverse effects due to NSAID use has grown; simultaneously, there has been an increase in consideration of opioid use for the treatment of pain. We examined how prescription NSAID and opioid use has changed over the past decade using data from MCBS 2003, 2006, and 2009 and identified trends in their utilization. There was a significant increase in opioids prescriptions between 2003 and 2009. We determined that functional limitation, poor self-reported health status, chronic obstructive pulmonary disease, and other musculoskeletal diseases are associated with greater opioid use.
Pharmacologic regimens for knee osteoarthritis prevention: can they be cost-effective. Losina et al., Osteoarthritis and Cartilage, 2014: We examined the clinical and economic implications of using hypothetical drug-based regimens to prevent the onset of symptomatic knee OA. Using the OAPol Model, we evaluated the use of a prevention regimen in cohorts at varying risk for the development of knee OA while varying the characteristics of the pharmacologic agent itself, including the annual cost of the drug, its risk of toxicity, and its effectiveness at OA prevention. We determined that drug-based prevention regimens demonstrated cost-effectiveness levels comparable to commonly used prophylactic therapies for other chronic conditions when used in a high-risk population and when priced below $2,000 per year.
Studies of pain management in osteoarthritis: bedside to policy. Losina et al., Osteoarthritis and Cartilage, 2013: We evaluated the current landscape of research investigating OA-related pain management by characterizing studies registered to ClinicalTrials.gov with respect to their intervention focus, trial duration, enrollment, outcome measures, and sources of funding. We identified 287 studies on the registry, of which 69% investigated pharmacologic interventions, 11% behavioral interventions, 5% surgical procedures or devices, and 15% other interventions such as electrotherapy and acupuncture. The average study duration was 7.4 months, where 52% of all studies used trial durations less than or equal to 3 months. Industry funded trials were more likely to report using these short term durations in their protocols.
Disease-modifying drugs for knee osteoarthritis: Can they be cost-effective? Losina et al.,Osteoarthritis and Cartilage, 2013: Disease-modifying osteoarthritis drugs (DMOADs) which could suspend progression of knee OA are currently under investigation. In anticipation of DMOAD development, we sought to identify threshold values for cost, toxicity, and efficacy under which DMOADs could be a cost-effective addition to standard knee OA care. Using the OAPol model, we found that, given 50% likelihood of suspending OA progression, 30% likelihood of relieving pain, and 0.5% annual risk of major adverse event, DMOADs carried incremental cost-effectiveness ratios below $100,000 per quality-adjusted life year gained. DMOAD cost-effectiveness was highly sensitive to the level of pain relief conferred, and DMOADs that provided pain relief below 30% annually were unlikely to be cost-effective.
Estimating the burden of total knee replacement in the United States. Weinstein et al., Journal of Bone and Joint Surgery, 2013: We estimated the prevalence of total knee replacement (TKR) in the United States population aged 50 years and older. Using data on national TKR utilization from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) alongside demographic data from the National Health and Nutrition Examination Survey (2005-2008), we estimated that 11.5% of US adults 50 years or older had been diagnosed with symptomatic knee OA and that 4.2% of US adults in this age group had had a knee replacement. The lifetime risk of undergoing a primary TKR surgery by the age of 60 years was estimated to be 2.0% for men and 2.8% for women.
Lifetime risk and age of diagnosis of symptomatic knee osteoarthritis in the US. Losina et al.,Arthritis Care and Research, 2013: We estimated the incidence and lifetime risk of diagnosed symptomatic knee OA using information on sex, race, and obesity prevalence from the National Health Interview Survey (NHIS) and disease duration estimates derived from the OAPol Model. The overall lifetime risk of having diagnosed symptomatic knee OA from age 25 was estimated to be 13.83%, with a 9.29% risk of having diagnosed symptomatic knee OA by the age of 60. The mean and median ages for knee OA diagnosis were estimated at 53.5 and 55 years, respectively. Obese women demonstrated the highest estimations of OA prevalence and incidence, with estimates of OA incidence ranging from 0.04% per year in non-obese men aged >85 years to 1.02% per year in obese women aged 55–64 years.
Placing a price on medical device innovation: The example of total knee arthroplasty. Suter et al.,PLoS ONE, 2013: Using the OAPol model, we performed a cost-effectiveness analysis to compare projected total knee arthroplasty implant survival, quality-adjusted life expectancy, lifetime costs, and cost-effectiveness of standard versus innovative implants. Implants offering at least a 50% decrease in long-term TKA at no more than 50% increased cost offered incremental cost-effectiveness ratios of under $100,000 regardless of age or baseline comorbidity at time of surgery. Innovative implants must decrease actual TKA failure, rather than radiographic wear, by 50-55% or more over standard implants to be broadly cost-effective. Age and comorbidity significantly affect innovative implant cost-effectiveness and should be considered in the development, approval, and implementation of novel technologies.
Studies of pain management in osteoarthritis: bedside to policy. Losina et al., Osteoarthritis and Cartilage, In Press: We examined how clinical research studies evaluate strategies in nonsurgical pain management of OA by looking at trends among clinical trials registered to ClinicalTrials.gov in the last fifteen years. We focused on the sources of funding, trial designs, trial durations, and types of nonsurgical pain management methods employed in over 280 trials. We found that 69% of trials listed on the registry evaluated pharmacologic interventions for OA, 64% were funded at least in part by industry, and 52% evaluated patients over durations of 3 months or less. Studies examining on pharmacologic interventions and funded by industry were more likely to evaluate interventions over the short-term, investigate opioids, and be conducted in the United States.
The cost-effectiveness of total joint arthroplasty: A systematic review of published literature. Daigle et al., Best Practice & Research Clinical Rheumatology, 2012: We conducted a systematic review of literature evaluating the cost-effectiveness of total knee and hip arthroplasty (TKA and THA). We included studies that were published between 1980 and 2012 and that reported incremental cost-effectiveness ratios. Among 13 studies meeting our review criteria, we found three which evaluated cohorts aged younger than 65, and one study for each THA and TKA that evaluated cost-effectiveness over the lifetime horizon and from the societal perspective. THA and TKA have both been found to be highly cost-effective, however future evaluations should address expanding indication of THA and TKA to younger, more physically active individuals.
The dramatic increase in total knee replacement utilization rates in the United States cannot be fully explained by growth in population size and the obesity epidemic. Losina et al., Journal of Bone and Joint Surgery: American Volume, 2012: Using data from the Nationwide Inpatient Sample, we estimated that the number of knee replacements performed in the US more than doubled from 1999 to 2008. We concluded that changes in obesity and population growth over the last 10 years fail to account for the dramatic increases in total knee replacement use. This suggests that other factors, such as a growing number of knee injuries and expanding indications for the procedure, must also be involved.
Medical device innovation–is “better” good enough? Suter LG et al., New England Journal of Medicine, 2011: Using the OAPol model, we found that a novel total knee replacement implant that reduces long-term failure by 70% compared to current implants would reduce cumulative revision risk by 11% among healthy 50-59-year-olds and by 6% among 70-79-year-olds with coexisting conditions. We suggest that there is no one-size-fits-all approach to the use of innovative devices in total knee replacement and that a model-based approach is a valuable way of determining the circumstances under which the use of a novel device is clinically and economically justified.
Impact of obesity and knee osteoarthritis on morbidity and mortality in older Americans. Losina et al., Annals of Internal Medicine, 2011: Using the OAPol Model and data from the US Census and the National Health and Nutrition Examination Survey (2005-2008), we estimated that 86 million quality-adjusted life-years (QALY) are lost due to obesity and/or knee OA among Americans aged 50-84. Seventy-four percent (74%) of these are attributable to obesity and 26% to knee OA. Black females comprise 5% of the population but experience 9% of QALY losses. This paper received wide [media coverage], including by US News and World Report, the Wall Street Journal: MarketWatch, and Arthritis Today.
Differences in self-reported health in the Osteoarthritis Initiative (OAI) and Third National Health and Nutrition Examination Survey (NHANES-III). Reichmann et al., PLoS One, 2011: Symptomatic knee OA is a debilitating disorder affecting approximately 12-16% of US adults older than 60 years of age. There is a growing body of evidence suggesting that obesity works in concert with other risk factors to exacerbate OA incidence. We sought to estimate the 10-year cumulative incidence and progression rates of knee OA in a population aged 60-64 years. Using the OAPol Model, we projected that 13% of adults 60-64 years old have prevalent symptomatic knee OA and another 600,000 will develop OA over the next decade. Incidence will be approximately 4 times greater among obese persons. More sensitive imaging tools, such as MRI, may increase the prevalence of diagnosed OA up to 47%.
Forecasting the burden of advanced knee osteoarthritis over a 10-year period in a cohort of 60-64 year-old US adults. Holt et al., Osteoarthritis and Cartilage, 2011: Symptomatic knee OA is a debilitating disorder affecting approximately 12-16% of US adults older than 60 years of age. There is a growing body of evidence suggesting that obesity works in concert with other risk factors to exacerbate OA incidence. We sought to estimate the 10-year cumulative incidence and progression rates of knee OA in a population aged 60-64 years. Using the OAPol Model, we projected that 13% of adults 60-64 years old have prevalent symptomatic knee OA and another 600,000 will develop OA over the next decade. Incidence will be approximately 4 times greater among obese persons. More sensitive imaging tools, such as MRI, may increase the prevalence of diagnosed OA up to 47%.
Impact of knee osteoarthritis on health care resource utilization in a US population-based national sample. Wright et al., Medical Care, 2010: Though previous research has examined health care utilization among arthritis patients in various settings, only a few studies have compared utilization of OA patients with non-OA patients while controlling for important confounding factors. We identified a knee OA cohort from Medicare Current Beneficiary Survey participants and found that the knee OA cohort had an average of 6 more physician office visits and 2.8 more non-physician office visits than the non-OA cohort. In this population-based, controlled study of health care utilization in persons with knee OA, we documented substantial excess utilization attributable to knee OA, independent of comorbidities and other patient factors.
Cost-effectiveness of total knee arthroplasty in the United States: patient risk and hospital volume. Losina et al., Archives of Internal Medicine, 2009: Total knee replacement (TKR) is highly effective in relieving pain and improving quality of life for persons with advanced knee OA. Using the OAPol Model, we projected lifetime costs and quality-adjusted life expectancy for patients undergoing TKR. We found TKR to be a cost-effective treatment, at $18,300 per QALY. This paper was accompanied by an editorial and also received [wide press coverage] including by Reuters, Forbes, and the Wall Street Journal.
Medical decision making in patients with knee pain, meniscal tear, and osteoarthritis. Suter et al.,Arthritis and Rheumatism, 2009: Mensical tears are often treated via non-operative therapy or arthroscopic partial meniscectomy (APM). Though meniscal tears often coexist with knee OA, there are no data identifying patients who will benefit from each treatment approach in this population. Using a decision-analytic approach, we found that easily-obtained clinical data can differentiate patients who are more likely to benefit from APM among individuals with degenerative meniscal tears and OA.
Ambulatory visit utilization in a national, population-based sample of adults with osteoarthritis. Cisternas et al., Arthritis Care and Research, 2009: We used data from the Medical Expenditures Panel Survey (MEPS) to estimate the proportion of persons with OA seen by OA specialists in a one-year period. We found that 92% of symptomatic OA patients see clinicians, 25% see an orthopedist, 11% see a physical therapist, and 6% see a rheumatologist. While most adults with OA do not visit OA specialists, those without insurance and with lower levels of education are less likely to visit these specialists.
Determinants of self-reported health status in a population-based sample of persons with radiographic knee osteoarthritis. Reichmann et al., Arthritis Care and Research, 2009: Patients with radiographic knee OA often experience substantial pain and functional limitations, which lead to diminished health statuses. Using National Health and Nutrition Examination Survey (NHANES) data, we found that non-White race, lower income, greater number of comorbidities, and functional limitation were associated with worse self-reported health status. This study has quantified the role of clinical, radiographic, and socioeconomic factors associated with self-reported health status in a population-based sample of patients with radiographic knee OA.
Joint space narrowing and Kellgren-Lawrence progression in knee osteoarthritis: an analytic literature synthesis. Emrani et al., Osteoarthritis and Cartilage, 2008: The measurement of radiographic joint space width on plain radiographs remains the standard method for evaluating the progression of knee OA; however, other common metrics of OA progression exist, including the Kellgren-Lawrence scale. We conducted a systematic review to identify factors that explain variability in published estimates of radiographic progression of knee OA. In a synthesis of 34 studies, we estimated a joint-space-narrowing rate of 0.13 + 0.15 mm/year and annual risk of progression by at least one Kellegren-Lawrence grade of 5.6 + 4.9%. Radiographic approach and study designed were associated with joint space narrowing, while OA definition, cohort composition, and study duration were associated with increased K-L progression.