Fundamentals of osteoarthritis: outcome evaluation with patient-reported measures and functional tests.

Evaluating outcome in osteoarthritis (OA) clinical research and practice requires reliable, valid and responsive patient-reported outcome measures (PROMs) and functional tests that reflect important problems experienced by people with OA. The goal of this work is to provide information to start to guide the reader in selecting measures for people with OA. In this narrative review, we begin by providing an overview of measurement properties that can help clinicians and researchers in making decisions about whether a measure might be appropriate for use in their research or clinical context. We then report evidence supporting the use of measures of pain (e.g., Pain Visual Analogue (VAS), Numeric Pain Rating Scale (NPRS), Intermittent and Constant Osteoarthritis Pain, PROMIS Pain Interference, and, for screening in research, the painDETECT and the Self-report Leeds Assessment of Neuropathic Symptoms and Signs) and fatigue (e.g., PROMIS-Fatigue) at a group level in clinical research. Several multi-dimensional joint-specific measures (e.g., Western Ontario McMaster Universities' Osteoarthritis Outcomes Scale, Knee/Hip Injury and Osteoarthritis Outcome Score, Oxford Hip/Knee Scale) also have evidence for group-level use. Functional tests (e.g., timed walk tests, 30 Second Chair Stand, Timed Up and Go, etc.) have measurement properties supporting their use at the group level in clinical research and at the individual patient level as do the pain VAS and NPRS. Other generic and disease-specific PROMs have been used in or could be used in OA studies but their measurement properties require further evaluation in people with OA.

Development and validation of the Flare-OA questionnaire for measuring flare in knee and hip osteoarthritis.

OBJECTIVE: Ability to assess flares in osteoarthritis (OA) of the knee and hip (KHOA) is important in clinical care and research. Using mixed methods, we developed a self-reported instrument measuring flare and assessed its psychometric properties. METHODS: We constructed questionnaire items from semi-structured interviews and a focus group (patients, clinicians) by using a dual-language (English-French) approach. A Delphi consensus method was used to select the most relevant items. Patients with OA from Australia, France and the United States completed the preliminary Flare-OA, HOOS, KOOS and Mini-OAKHQOL questionnaires online. We used a factor analysis and content approach to reduce items and determine structural validity. We tested the resulting questionnaire (score 0-100) for internal consistency, convergent and known-groups validity. RESULTS: Initially, 180 statements were generated and reduced to 33 items in five domains (response 0 = not at all, to 10 = absolutely) by Delphi consensus (50 patients, 116 professionals) and an expert meeting. After 398 patients (mean [SD] age 64 [8.5] years, 70.4% female, 86.7% knee OA) completed the questionnaire, it was reduced to 19 items by factor analysis and a content approach (RMSEA = 0.06; CFI = 0.96; TLI = 0.94). The Cronbach's alpha was >0.9 for the five domains and the whole questionnaire. Correlation coefficients between Flare-OA and other instrument scores were as predicted, supporting construct validity. The difference in Flare-OA score between patients with and without flare (31.8) largely exceeded 2 SEM (10.2). CONCLUSION: Flare-OA is a valid and reliable patient-reported instrument for assessing the occurrence and severity of flare in patients with KHOA in clinical research.

Long-term effect of patient decision aids on use of joint replacement and health care costs.

OBJECTIVE: Shared decision-making supported by patient decisions aids may improve care and reduce healthcare costs for persons considering total joint replacement. Observational studies and randomized controlled trials (RCTs) have evaluated the short-term impact of decision aids on uptake of surgery and costs, however the long-term effects are unclear. This analysis aimed to evaluate the effect of patient decision aids on 1) use of joint replacement up to 7-years of follow-up, and 2) osteoarthritis-related health system costs. METHODS: 324 participants in a Canadian RCT with 2-years follow-up who were randomized to either a decision aid (n = 161) or usual care (n = 163) had their trial and health administrative data linked. The proportion undergoing surgery up to 7-years were compared using cumulative incidence plots and competing risk regression. Mean per-patient costs were compared using two sample t-tests. RESULTS: At 2-years, 119 of 161 (73.9%) patients in the decision aid arm and 129 of 163 (79.1%) patients in the usual care arm had surgery. Between two and 7-years, 17 additional patients in both the decision aid (of 42, 40.4%) and usual care (of 34, 50.0%) arms underwent surgery. At 7-years, patients exposed to decision aids had a similar likelihood of undergoing surgery (HR = 0.92, 95% CI:0.73 to 1.17, p = 0.49) and mean per-patient costs ($21,965 vs $23,681, incremental cost: -$1,717, 95% CI:-$5,631 to $2,198) compared to those in usual care. CONCLUSIONS: This is the first study to assess the long-term impact of decision aids on use of joint replacement and healthcare costs. These results are not conclusive but can inform future trial design. CLINICAL TRIAL REGISTRATION: The full trial protocol is available at ClinicalTrials.Gov (NCT00911638).

Are medical comorbidities contributing to the use of opioid analgesics in patients with knee osteoarthritis?

BACKGROUND: Although opioid analgesics are not generally recommended for treatment of knee osteoarthritis (OA), they are frequently used. We sought to determine the association between medical comorbidities and self-reported opioid analgesic use in these patients. METHODS: This cross-sectional study recruited patients referred to two provincial hip and knee clinics in Alberta, Canada for consideration of total knee arthroplasty. Standardized questionnaires assessed demographic (age, gender, income, education, social support, smoking status) and clinical (pain, function, total number of troublesome joints) characteristics, comorbid medical conditions, and non-surgical OA management participants had ever used or were currently using. Multivariable Poisson regression with robust estimate of the standard errors assessed the association between comorbid medical conditions and current opioid use, controlling for potential confounders. RESULTS: 2,127 patients were included: mean age 65.4 (SD 9.1) years and 59.2% female. Currently used treatments for knee OA were: 57.6% exercise and/or physiotherapy, 61.1% NSAIDs, and 29.8% opioid analgesics. In multivariable regression, controlling for potential confounders, comorbid hypertension (RR 1.18, 95% CI 1.02-1.37), gastrointestinal disease (RR 1.31, 95% CI 1.07-1.60), depressed mood (RR 1.25, 95% CI 1.05-1.48) and a higher number of troublesome joints (RR 1.04 per joint, 95% CI 1.00-1.09) were associated with opioid use, with no association found with having ever used recommended non-opioid pharmacological or non-pharmacological treatments. CONCLUSIONS: In a large cohort of patients with knee OA, of 12 comorbidities assessed, comorbid hypertension, gastrointestinal disease, and depressed mood were associated with current use of opioid analgesics, in addition to total burden of troublesome joints. Improved guidance on the management of painful OA in the setting of common comorbidities is warranted.

Few fragility fracture patients perceive that their bone health is affected by their comorbidities and medications.

We examined fragility fracture patients' perceptions of associations between bone health and other chronic conditions and medications. Awareness of the associations between bone health and these conditions and medications was low. Providers should increase patients' awareness of these associations in order to minimize the risk of future fracture. INTRODUCTION: Among patients with a fragility fracture presenting with at least one other chronic health condition, we examined (1) perceptions of the association between bone health and their other health conditions, and (2) perceptions of the association between bone health and prescribed medications taken for other health conditions. METHODS: We identified fragility fracture patients presenting to a Canadian urban fracture clinic with at least one self-reported chronic health condition (in addition to bone fragility). In-depth interviews, 60-90 min in duration, were conducted. Our qualitative methodology was informed by saliency analysis. RESULTS: We interviewed 26 patients (21 females, 5 males) aged 45 to 84 years old. Participants were taking 1-13 medications each and presented with a variety of comorbidities (range 1-7). All participants described at least one condition or medication they were currently taking for which there existed evidence of a negative effect on bone health (increased risk of fracture, bone loss, falling). Two participants perceived a correct association between their other health conditions and compromised bone health, and four participants perceived a correct association between their medications and compromised bone health. CONCLUSION: All patients reported a chronic health condition and/or were taking at least one medication that potentially compromised their bone health. Patient awareness of the association between bone health and other health conditions and prescribed medications was low. Health care providers should increase patients' awareness of the bone health significance of their chronic conditions and medications in order to minimize the risk of future fracture.

Lifetime risk of knee and hip replacement following a GP diagnosis of osteoarthritis: a real-world cohort study.

OBJECTIVE: The aim of this study was to estimate lifetime risk of knee and hip replacement following a GP diagnosis of osteoarthritis and assess how this risk varies with patient characteristics. METHODS: Routinely collected data from Catalonia, Spain, covering 2006 to 2015, were used. Study participants had a newly recorded GP diagnosis of knee or hip osteoarthritis. Parametric survival models were specified for risk of knee/hip replacement and death following diagnosis. Survival models were combined using a Markov model and lifetime risk estimated for the average patient profile. The effects of age at diagnosis, sex, comorbidities, socioeconomic status, body mass index (BMI), and smoking on risk were assessed. RESULTS: 48,311 individuals diagnosed with knee osteoarthritis were included, of whom 2,561 underwent knee replacement. 15,105 individuals diagnosed with hip osteoarthritis were included, of whom 1,247 underwent hip replacement. The average participant's lifetime risk for knee replacement was 30% (95% CI: 25-36%) and for hip replacement was 14% (10-19%). Notable patient characteristics influencing lifetime risk were age at diagnosis for knee and hip replacement, sex for hip replacement, and BMI for knee replacement. BMI increasing from 25 to 35 was associated with lifetime risk of knee replacement increasing from 24% (20-28%) to 32% (26-37%) for otherwise average patients. CONCLUSION: Knee and hip replacement are not inevitable after an osteoarthritis diagnosis, with average lifetime risks of less than a third and a sixth, respectively. Patient characteristics, most notably BMI, influence lifetime risks.

How do patients trade-off surgeon choice and waiting times for total joint replacement: a discrete choice experiment.

OBJECTIVE: Patients face significant waiting times for hip and knee total joint replacement (TJR) in publicly funded healthcare systems. We aimed to assess how surgeon selection and reputation affect patients' willingness to wait for TJR. DESIGN: We assessed patient preferences using a discrete choice experiment questionnaire with 12 choice scenarios administered to patients referred for TJR. Based on qualitative research, pre- and pilot-testing, we characterized each scenario by five attributes: surgeon reputation, surgeon selection, waiting time to surgeon visit (initial consultation), waiting time to surgery, and travel time to hospital. Preferences were assessed using hierarchical Bayes (HB) analysis and evaluated for goodness-of-fit. We conducted simulation analyses to understand how patients value surgeon reputation and surgeon selection in terms of willingness to wait for surgeon visit and surgery. RESULTS: Of 422 participants, 68% were referred for knee TJR. The most important attribute was surgeon reputation followed by waiting times, surgeon selection process and travel time. Patients appear willing to wait 10 months for a visit with an excellent reputation surgeon before switching to a good reputation surgeon. Patients in the highest pain category were willing to wait 7.3 months before accepting the next available surgeon, compared to 12 months for patients experiencing the least pain. CONCLUSIONS: Our findings confirm that patients value surgeon reputation in the context of wait times and surgeon selection. We suggest opportunities to reduce wait times by explicitly offering the next available surgeon to increase patient choice, and by reporting surgeon performance to reduce potential misinformation about reputation.

Factors associated with the orthopaedic surgeon's decision to recommend total joint replacement in hip and knee osteoarthritis: an international cross-sectional study of 1905 patients.

OBJECTIVE: To determine factors associated with orthopaedic surgeons' decision to recommend total joint replacement (TJR) in people with knee and hip osteoarthritis (OA). DESIGN: Cross-sectional study in eleven countries. For consecutive outpatients with definite hip or knee OA consulting an orthopaedic surgeon, the surgeon's indication of TJR was collected, as well as patients' characteristics including comorbidities and social situation, OA symptom duration, pain, stiffness and function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), joint-specific quality of life, Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) radiographic grade (0-4), and surgeons' characteristics. Univariable and multivariable logistic regressions were performed to identify factors associated with the indication of TJR, adjusted by country. RESULTS: In total, 1905 patients were included: mean age was 66.5 (standard deviation [SD], 10.8) years, 1082 (58.0%) were women, mean OA symptom duration was 5.0 (SD 7.0) years. TJR was recommended in 561/1127 (49.8%) knee OA and 542/778 (69.7%) hip OA patients. In multivariable analysis on 516 patients with complete data, the variables associated with TJR indication were radiographic grade (Odds Ratio, OR for one grade increase, for knee and hip OA, respectively: 2.90, 95% confidence interval [1.69-4.97] and 3.30 [2.17-5.03]) and WOMAC total score (OR for 10 points increase: 1.65 [1.32-2.06] and 1.38 [1.15-1.66], respectively). After excluding radiographic grade from the analyses, on 1265 patients, greater WOMAC total score was the main predictor for knee and hip OA; older age was also significant for knee OA. CONCLUSION: Radiographic severity and patient-reported pain and function play a major role in surgeons' recommendation for TJR.

The longitudinal relationship between hand, hip and knee osteoarthritis and cardiovascular events: a population-based cohort study.

OBJECTIVE: In this population-based cohort study, we examined the association between the presence of symptomatic osteoarthritis (OA) and risk for cardiovascular (CV) events. METHOD: A cohort aged ≥55 years recruited from 1996 to 98 was followed through provincial health administrative data to 2014. Demographics, joint complaints and functional limitations were collected. Hip, knee and hand OA were defined using a validated definition. Using Cox-regressions, the relationship between OA and a composite CV outcome (myocardial infarction (MI), stroke, angina, heart failure, revascularization) was assessed controlling for age, body mass index (BMI), sex, pre-existing metabolic factors, comorbidities, income status, primary care exposure and functional limitations. RESULTS: 18,490 participants were included: median age was 68 years, 60.3% were female; 24.4% met criteria for OA (10.0% hip, 15.3% knee, 16.0% hand), 16.3% self-reported limitation in grip and 25.4% in walking. Over a median 13.4 years, 31.9% experienced a CV event. Controlling for all but walking limitation, a dose-response relationship was observed between number of joints affected by knee/hip OA and CV risk (HR 2 hips/knees vs none: 1.13, 95% CI 1.03-1.23; 3+ hips/knees: 1.22, 95% CI 1.09-1.36). This relationship became non-significant additionally controlling for difficulty walking. Self-reported difficulty walking was associated with a 30% increased hazard for CV events. The effect of hand OA was not significant. CONCLUSION: In a large population cohort, a greater burden of hip/knee OA was associated with higher CV risk; the relationship was explained by OA-related difficulty walking. Increased attention to management of OA with a view to improving mobility has potential to reduce CV events.

Decision aids for patients considering total joint replacement: a cost-effectiveness analysis alongside a randomised controlled trial.

BACKGROUND: Shared decision-making (SDM) is a key priority to improve patient-centred care, and can play an important role in helping patients decide whether to undergo total joint arthroplasty (TJA). Patient decision aids can support SDM; however, they may incur an upfront cost. We aimed to estimate the health and economic effects of patient decision aids for TJA. METHODS: A cost-effectiveness analysis of a randomised controlled trial (RCT) with 2-year follow-up. 343 patients were recruited from two orthopedic screening clinics in Ottawa, Canada. Patients were randomized to either a patient decision aid plus surgeon preference report (decision aid) or usual care. Primary outcomes were costs (in 2014 CAD$), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). Costs were calculated by multiplying self-reported resource use by unit costs. QALYs were calculated by mapping the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) to EuroQol 5-Dimension (EQ-5D) health utilities. Costs and QALYs were discounted at 5%. Multiple imputation was used to handle missing data, and bootstrapping was used to estimate uncertainty. RESULTS: The sample comprised 167 intervention and 167 control group patients. The decision aid arm had fewer surgeries over the 2-year period thereby incurring a negative incremental cost of -$560 (95% CI: -$1358 to $426) per patient while providing 0.05 (95% CI: -0.04 to 0.13) additional QALYs per patient. Consequently, the decision aid arm was dominant. CONCLUSION: The use of a patient decision aid was associated with fewer health care costs, while producing similar health outcomes. CLINICAL TRIAL REGISTRATION NUMBER: CT00911638 (clinicaltrials.gov).

Osteoarthritis-related difficulty walking and risk for diabetes complications.

OBJECTIVES: To examine the effect of Osteoarthritis (OA)-related difficulty walking on risk for diabetes complications in persons with diabetes and OA. DESIGN: A population cohort aged 55+ years with symptomatic hip and knee OA was recruited 1996-98 and followed through provincial administrative data to 2015 (n = 2,225). In those with confirmed OA (examination and radiographs) and self-reported diabetes at baseline (n = 359), multivariate Cox regression modeling was used to examine the relationship between baseline difficulty walking (Health Assessment Questionnaire (HAQ) difficulty walking score; use of walking aid) and time to first diabetes-specific complication (hospitalization for hypo- or hyperglycemia, infection, amputation, retinopathy, or initiation of chronic renal dialysis) and cardiovascular (CV) events. RESULTS: Participants' mean baseline age was 71.4 years; 66.9% were female, 77.7% had hypertension, 54.0% had pre-existing CV disease, 42.9% were obese and 15.3% were smokers. Median HAQ difficulty walking score was 2/3 indicating moderate to severe walking disability; 54.9% used a walking aid. Over a median 6.1 years, 184 (51.3%) experienced one or more diabetes-specific complications; 191 (53.2%) experienced a CV event over a median 5.7 years. Greater baseline difficulty walking was associated with shorter time to the first diabetes-specific complication (adjusted HR per unit increase in HAQ walking 1.24, 95% CI 1.04-1.47, P = 0.02) and CV event (adjusted HR for those using a walking aid 1.35, 95% CI 1.00-1.83, P = 0.04). CONCLUSIONS: In a population cohort with OA and diabetes, OA-related difficulty walking was a significant - and potentially modifiable - risk factor for diabetes complications.

Primary care physicians' perceptions about and confidence in deciding which patients to refer for total joint arthroplasty of the hip and knee.

OBJECTIVE: The purpose of this study is to examine the perceptions of primary care physicians (PCPs) regarding indications, contraindications, risks and benefits of total joint arthroplasty (TJA) and their confidence in selecting patients for referral for TJA. DESIGN: PCPs recruited from among those providing care to participants in an established community cohort with hip or knee osteoarthritis (OA). Self-completed questionnaires were used to collect demographic and practice characteristics and perceptions about TJA. Confidence in referring appropriate patients for TJA was measured on a scale from 1 to 10; respondents scoring in the lowest tertile were considered to have 'low confidence'. Descriptive analyses were conducted and multiple logistic regression was used to determine key predictors of low confidence. RESULTS: 212 PCPs participated (58% response rate) (65% aged 50+ years, 45% female, 77% >15 years of practice). Perceptions about TJA were highly variable but on average, PCPs perceived that a typical surgical candidate would have moderate pain and disability, identified few absolute contraindications to TJA, and overestimated both the effectiveness and risks of TJA. On average, PCPs indicated moderate confidence in deciding who to refer. Independent predictors of low confidence were female physicians (OR = 2.18, 95% confidence interval (CI): 1.06-4.46) and reporting a 'lack of clarity about surgical indications' (OR = 3.54, 95% CI: 1.87-6.66). CONCLUSIONS: Variability in perceptions and lack of clarity about surgical indications underscore the need for decision support tools to inform PCP - patient decision making regarding referral for TJA.

Impact of patient decision aids on appropriate and timely access to hip or knee arthroplasty for osteoarthritis: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of patient decision aids (PtDA) compared to usual education on appropriate and timely access to total joint arthroplasty in patients with osteoarthritis. METHOD: A randomized controlled trial (RCT) with patients undergoing orthopedic screening. Control and intervention arms received usual education; intervention arm also received a PtDA and a surgeon preference report. Wait times (primary outcome) were described using stratified Kaplan-Meier survival curves with patients censored at the time of death or loss to follow-up, and multivariable Cox proportional hazards regression. Secondary outcomes were compared using stratified Cochran-Mantel-Haenszel chi-squared tests. RESULTS: 343 patients were randomized to intervention (n = 174) or control (n = 169). The typical patient was 66 years old, retired, living with someone, and 51% had high school education or less. The intervention was associated with a trend towards reduction in wait time (hazard ratio (HR) 1.25, 95% confidence interval (CI) 0.99-1.60, P = 0.0653). Median wait times were 3 weeks shorter in intervention than in control at the community site with no difference at the academic site. Good decision quality was reached by 56.1% intervention and 44.5% control (Relative risk (RR) 1.25; 95% CI 1.00-1.56, P = 0.050). Surgery rates were 73.2% intervention and 80.5% controls (RR 0.91: 95% CI 0.81-1.03) with 12 intervention (7.3%) and eight control participants (4.9%) returning to have surgery within 2 years (P = 0.791). CONCLUSION: Compared to controls, decision aid recipients had shorter wait times at one site, fewer surgeries, and were more likely to reach good decision quality, but overall effect was not statistically significant. TRIALS REGISTRATION: The full trial protocol is available at ClinicalTrials.Gov (NCT00911638).

Cross-cultural validation of the ICOAP and physical function short forms of the HOOS and KOOS in a multi-country study of patients with hip and knee osteoarthritis.

OBJECTIVE: To evaluate the internal consistency and construct validity of the Physical Function short-forms for the Hip and Knee Injury Osteoarthritis Outcome Scores (HOOS-PS/KOOS-PS) and the Intermittent and Constant Osteoarthritis Pain (ICOAP) in a nine country study of patients consulting for total hip or knee replacement (THR or TKR). METHODS: Patients completed HOOS-PS or KOOS-PS, ICOAP and Western Ontario and McMaster Universities' Osteoarthritis Index (WOMAC) pain and physical function subscales at their consultation visit. Internal consistency was calculated using Cronbach's alpha. The association of HOOS-PS/KOOS-PS and ICOAP with WOMAC pain and function subscales was calculated with Spearman correlation coefficients with 95% confidence intervals. RESULTS: HOOS-PS/KOOS-PS and ICOAP demonstrated high internal consistency across countries (alpha 0.75-0.96 (hip) and 0.76-0.95 (knee)). Both HOOS-PS and KOOS-PS demonstrated high correlations (0.76-0.90 and 0.75-0.91, respectively) with WOMAC function in all countries. ICOAP exhibited moderate to high correlations with WOMAC pain and function subscales (0.53-0.84 (hip) and 0.43-0.84 (knee)). CONCLUSION: The psychometric properties of the HOOS-PS/KOOS-PS, and ICOAP were maintained across all countries.

Patients do not have a consistent understanding of high risk for future fracture: a qualitative study of patients from a post-fracture secondary prevention program.

UNLABELLED: We examined fracture patients' understanding of "high" fracture risk after they were screened through a post-fracture secondary prevention program and educated about their risk verbally, numerically, and graphically. Our findings suggest that messages about fracture risk are confusing to patients and need to be modified to better suit patients' needs. INTRODUCTION: The aim of this study was to examine fracture patients' understanding of high risk for future fracture. METHODS: We conducted an in-depth qualitative study in patients who were high risk for future fracture. Patients were screened through the Osteoporosis Exemplary Care Program where they were educated about fracture risk: verbally told they were "high risk" for future fracture, given a numerical prompt that they had a >20 % chance of future fracture over the next 10 years, and given a visual graph highlighting the "high risk" segment. This information about fracture risk was also relayed to patients' primary care physicians (PCPs) and specialists. Participants were interviewed at baseline (within six months of fracture) and follow-up (after visit with a PCP and/or specialist) and asked to recall their understanding of risk and whether it applied to them. RESULTS: We recruited 27 patients (20 females, 7 males) aged 51-87 years old. Fractures were sustained at the wrist (n = 7), hip (n = 7), vertebrae (n = 2), and multiple or other locations (n = 11). While most participants recalled they had been labeled as "high risk" (verbal cue), most were unable to correctly recall the other elements of risk (numerical, graphical). Further, approximately half of the patients who recalled they were high risk did not believe that high risk applied, or had meaning, to them. Participants also had difficulty explaining what they were at risk for. CONCLUSIONS: Our results suggest that health care providers' messages about fracture risk are confusing to patients and that these messages need to be modified to better suit patients' needs.

OARSI Clinical Trials Recommendations: Design and conduct of implementation trials of interventions for osteoarthritis.

Rigorous implementation research is important for testing strategies to improve the delivery of effective osteoarthritis (OA) interventions. The objective of this manuscript is to describe principles of implementation research, including conceptual frameworks, study designs and methodology, with specific recommendations for randomized clinical trials of OA treatment and management. This manuscript includes a comprehensive review of prior research and recommendations for implementation trials. The review of literature included identification of seminal articles on implementation research methods, as well as examples of previous exemplar studies using these methods. In addition to a comprehensive summary of this literature, this manuscript provides key recommendations for OA implementation trials. This review concluded that to date there have been relatively few implementation trials of OA interventions, but this is an emerging area of research. Future OA clinical trials should routinely consider incorporation of implementation aims to enhance translation of findings.