OBJECTIVE:There is growing interest in evaluating new strategies to delay or prevent posttraumatic osteoarthritis (PTOA) in individuals who have sustained anterior cruciate ligament (ACL) injury. This study sought to determine characteristics of potential treatments that are acceptable to patients with ACL injury. METHODS:Participants with a history of ACL injury were recruited from Reddit, Facebook, and ResearchMatch.org. After consent and eligibility confirmation, participants completed a survey comprising questions on (1) demographics, (2) PTOA perceptions, (3) perceived PTOA risk, and (4) a discrete choice experiment (DCE) task. The DCE assessed treatment attributes including risk reduction, side effects, benefits, and out-of-pocket costs. In several scenarios, participants chose between two hypothetical treatments with various attributes or no treatment. The data were analyzed with multinomial logit, mixed logit, and latent class models. RESULTS:We enrolled 273 participants (median age 30.6 years [interquartile range 27-33]; 63% female; mean body mass index = 25.5 kg/m2). Of these, 29% experienced daily knee pain, and 35% reported being very or extremely worried about knee OA. The two most influential attributes affecting treatment acceptability were monthly cost and potential mild side effects. Two preference phenotypes emerged: Class 1 members (n = 162, 59%) generally favored treatment, prioritizing effectiveness and injections but were deterred by high cost. Class 2 members (n = 111, 41%) were less inclined to use treatments with potential mild side effects and high cost. CONCLUSION:These results can be used to develop tailored recruitment messaging for future trials. Messaging should emphasize how to manage side effects and out-of-pocket costs.

OBJECTIVE:Despite receiving physical therapy (PT), some patients with meniscal tear still experience persistent knee pain. Understanding their treatment preferences is essential for clinicians to engage in shared decision-making. Self-reported questionnaires are often used to gauge patients' experiences and preferences, but questionnaires may not fully capture their attitudes. We conducted a mixed-methods study to compare patients' treatment preferences collected from closed-ended questionnaires and open-ended interviews. METHODS:Participants included 20 patients with physician-suspected meniscal tear and persistent knee pain following a course of PT. Participants participated in interviews and completed questionnaires that assessed their preferences for five treatment modalities such as PT, arthroscopic partial meniscectomy (APM), injections, medications, and educational support. Subsequently, we scored the qualitative data from interviews and compared the qualitative and questionnaire responses. RESULTS:Although most participants indicated a preference to avoid APM in the questionnaires, many expressed a conditional willingness to receive APM in the interviews, particularly if their physician recommended it. Many participants endorsed a preference to receive injections, medications, and additional PT in written questionnaires, but several expressed a conditional willingness to receive these modalities in interviews. For example, some participants described cost and location as important factors to consider before agreeing to additional PT, whereas others voiced a preference to avoid frequent medication use in the interviews. CONCLUSION:Our results suggest that closed-ended questionnaires may not fully capture patient attitudes. Supplementation of questionnaires with qualitative interviews or open-ended questions may allow researchers and clinicians to fully understand the nuances of patient concerns and preferences.

OBJECTIVE:Symptomatic meniscal tear and knee osteoarthritis (OA) are commonly accompanied by pain, which may arise from nociceptive mechanisms and from processes, referred to as sensitization, that alter and amplify pain perception. Sensitization may be assessed objectively with quantitative sensory testing (QST). There is a paucity of data on the magnitude of associations between QST measures and subjective and objective outcome measures. DESIGN:We assessed cross-sectional associations between QST measures and pain, muscle strength, and performance measures in participants in the TeMPO trial of nonoperative therapies for meniscal tear and OA. QST measures included pain pressure thresholds (PPT), temporal summation (TS) and conditioned pain modulation (CPM). We derived standardized mean differences in each outcome between the lowest vs. highest tercile of each QST measure using linear regression, adjusted for age, body mass index (BMI), and Kellgren-Lawrence (KL) radiographic grade. RESULTS:The sample included 317 participants with mean age 59.1 years, 58% female. Correlations between QST measures and pain, catastrophizing, widespread pain, strength (gluteus medius, quadriceps, hamstring), 40-meter timed walk, 30-second sit to stand, and timed single-leg stand were generally < 0.20. The adjusted standardized mean difference in each outcome between the lowest vs. highest tercile of each QST measure generally differed by <0.30 standard deviations. CONCLUSIONS:In this cross-sectional assessment of individuals with meniscal tear and OA, associations between QST measures and measures of pain, strength and performance were generally weak, suggesting pain sensitization makes minor contributions to these objective and subjective outcomes.

Objective Glucagon‐like peptide 1 receptor agonists (GLP‐1RAs) facilitate weight loss and reduce pain among individuals with knee osteoarthritis (OA). We investigated attitudes and barriers influencing GLP‐1RA use among individuals with knee OA and excess weight to draw distinctions in perspectives between patients with and without GLP‐1RA experience. Methods In this cross‐sectional qualitative study guided by the Framework Analysis method, we conducted structured interviews with persons with knee OA and excess weight. The moderator's guide included questions about health, weight loss history, and thoughts and experiences related to GLP‐1RAs. Of the 286 patients prescreened, 30 completed an interview, after which saturation was reached. Interview transcripts were coded by research assistants using Dedoose software, and themes were identified using inductive analysis, charting, and memo writing. Results The 30 individuals interviewed were majority female and most self‐identified as White. Fifteen participants had current or prior GL‐P1RA use, and fifteen had never taken GLP‐1RAs. We identified four major themes: (1) health care providers were the primary GLP‐1RA information source; (2) most participants recognized that weight loss could contribute to knee pain relief; (3) “ever users” reported overall positive experiences and found GLPA‐1RAs helped facilitate healthy lifestyle changes, whereas “never users” more often described medications as a last resort after lifestyle changes fail; and (4) cost was the most significant barrier to GLP‐1RA use. Conclusion We found that perceptions both differed and overlapped among participants with and without prior GLP‐1RA use. Clinicians should address potential concerns regarding GLP‐1RAs when discussing treatment options with patients with excess weight and knee OA.

We aimed to conduct a qualitative prospective preference assessment (PPA) to assess participants’ willingness to enroll in a planned randomized controlled trial (RCT). The planned RCT would enroll participants with meniscal tear with persistent knee pain following a course of physical therapy (PT) and would compare outcomes of arthroscopic partial meniscectomy (APM) vs. enhanced conservative care. We identified participants 45–85 years old with suspected meniscal tear who were referred to PT. After 10 weeks of PT, participants were sent a questionnaire that assessed knee pain. We asked participants reporting persistent knee pain to participate in a follow-up interview. We conducted semi-structured interviews and coded and analyzed transcripts to identify themes related to enrollment in our planned RCT. We analyzed transcripts from twenty participants (mean age (SD): 61.6 (6.16); 60

Objective Prognostic enrichment in clinical trials aims to target potential participants at high risk for events of interest, such as disease progression or incident osteoarthritis (OA). The objective of this work is to describe and investigate key parameters that should inform the decision to implement an enrichment strategy. Design We apply the framework of the Biomarker Prognostic Enrichment Tool (BioPET) to develop the Research-Based Enrichment for Arthritis Clinical Trials (REACT) tool. REACT takes into consideration the cost of screening and enrichment accuracy to determine whether an enrichment strategy is cost- and time-saving as compared with no enrichment. Results Modestly accurate prognostic enrichment can yield cost-savings if the costs of enrichment are low; we show cost-savings for a scenario with a prognostic enrichment algorithm with an area under the curve (AUC) of 0.6 and a cost of enrichment of $25 per potential participant screened. The increased number of potential participants needed to screen in order to enroll an enriched sample may present logistical and/or feasibility challenges. While the example with a prognostic enrichment algorithm AUC of 0.6 is indeed cost-saving from a monetary perspective, enrichment in this scenario requires screening 1.7 times more potential participants than a strategy with no enrichment. Conclusions REACT is a user-friendly tool to assess the value of incorporating an enrichment algorithm into clinical trial design. It could assist investigators in evaluating enrollment strategies to critically evaluate enrichment trade-offs, consider operational feasibility, in addition to qualitative factors such as generalizability and acceptability by participants.

BACKGROUND:Physical therapy is routinely recommended for knee pain attributed to a degenerative meniscal tear, but its efficacy has not been established. METHODS:We randomly assigned participants 45 to 85 years of age with knee pain, osteoarthritis, and meniscal tear to one of four groups: home exercise (3-month home-exercise program), home exercise plus text messages to encourage exercise adherence, home exercise plus text messages plus sham physical therapy (in-clinic sham manual therapy and sham ultrasound therapy), and home exercise plus text messages plus standard physical therapy (supervised strengthening, functional, and stretching exercises and manual therapy). The primary outcome was the change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain subscore (range, 0 to 100, with higher scores indicating more pain) between baseline and 3 months, with adjustment for trial site, baseline KOOS pain subscore, and radiographic grade. RESULTS:A total of 879 participants underwent randomization (mean [±SD] age, 59.2±7.8 years). The difference in the 3-month change in the KOOS pain subscore between home exercise and home exercise plus text messages was -0.1 points (98.3% confidence interval [CI], -3.8 to 3.7) and between home exercise and home exercise plus text messages plus standard physical therapy was 2.5 points (98.3% CI, -1.3 to 6.2); the difference between home exercise plus text messages and home exercise plus text messages plus standard physical therapy was 2.5 points (98.3% CI, -1.4 to 6.5). Adverse events were generally nonserious and evenly distributed overall across groups. CONCLUSIONS:For patients with degenerative meniscal tear and knee pain, the addition of physical therapy or text messages to encourage adherence to home exercises was not superior in reducing pain to a home-exercise program alone. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and others; TeMPO ClinicalTrials.gov number, NCT03059004.).

[This corrects the article DOI: 10.1016/j.ocarto.2024.100563.].

Background: Total knee arthroplasty (TKA) is commonly performed to relieve pain in persons with severe knee osteoarthritis. Despite substantial pain reduction and functional improvements, physical activity (PA) does not necessarily increase post TKA. The premise for this randomized trial is that a behavioral intervention invoking internal and external motivators could lead to improvement in PA uptake post TKA. Methods: KArAT (the Knee Arthroplasty Activity Trial) is a three-arm multi-center randomized controlled trial designed to establish the efficacy and sustainability of a personalized behavioral intervention in improving PA among TKA recipients with a primary diagnosis of knee osteoarthritis. The three arms include: 1) usual care, 2) attention control with Fitbit activity trackers, and 3) health coaching and financial incentives for reaching personalized PA goals. The primary outcome is defined as the proportion of participants engaged in at least 150 min of moderate-to-vigorous physical activity over a given week after the 6-month intervention. We also plan to conduct a cost-effectiveness analysis to establish the value and affordability of the KArAT interventions. Discussion: This paper aims to outline the rationale, study design, and implementation of KArAT. Trial Registration: Clinicaltrials.gov NCT04107649.

ObjectivePosttraumatic osteoarthritis (PTOA) accounts for nearly 12% of osteoarthritis incidences and often occurs after anterior cruciate ligament (ACL) tear. Ensuring the uptake of preventive treatments for PTOA requires that investigators and clinicians understand factors influencing patients to seek preventive therapies. This qualitative, descriptive study aimed to assess individuals' willingness to adopt a medication therapy for PTOA prevention following ACL injury.MethodsWe enrolled participants who had an ACL tear within two years of enrollment. Study individuals participated in a semistructured interview or focus group. We reviewed audio transcriptions for accuracy, and then organized the data inductively, beginning with open coding of audio transcriptions using NVivo 12. Finally, using a qualitative content analysis approach, we identified, revised, and constructed themes and subthemes.ResultsTwenty-five individuals (mean age 25 years, 60% women) participated. Participants were an average of 10 months after injury (mean 310 days, 95% confidence interval [CI] 249-371) and reported a mean Knee Injury and Osteoarthritis Outcome Score pain score of 80.3 (95% CI 74.5-86.2). We identified three main themes related to general treatment for PTOA (eg, unwanted side effects), medication treatment for PTOA (eg, concern about pill size and dose frequency), and clinical trial attributes (eg, time commitment).ConclusionAlthough participants expressed great interest in trying medication therapy for PTOA prevention, there was variability in which components of treatment mattered to them. Our results stress the importance of using qualitative approaches such as this one to inform the design of trials and treatments that real-world patients will pursue with enthusiasm.

Objective: Randomized controlled trials (RCTs) frequently fail to meet sample size requirements within their proposed timeline. Prospective preference assessments (PPAs) estimate the number of eligible individuals likely to enroll. The COSMIC Trial (Conservative care or Surgery for Meniscal tear after IneffeCtive physical therapy), currently in planning stages, will compare arthroscopic partial meniscectomy (APM) to non-operative treatment among those with meniscal tear who experience knee pain following a course of physical therapy (PT). We conducted a PPA to estimate willingness to enroll in the hypothetical trial and identify factors associated with willingness. Method: We invited eligible patients 45–85 years old with meniscal tear who were prescribed PT to participate in the PPA. Participants completed up to two questionnaires: one prior to a course of PT (Baseline questionnaire), and another following 10 weeks of PT (End of PT questionnaire). Both questionnaires assessed willingness to enroll in the COSMIC trial and knee treatment preferences. Results: In total, 94 participants completed both questionnaires, and 50 completed the End of PT questionnaire only. For those who completed both questionnaires, willingness to enroll in the hypothetical COSMIC RCT fell from 62 ​% at Baseline to 46 ​% in the End of PT questionnaires. Respondents’ strongest preference was to avoid APM (47 ​%). Preference for APM at baseline was associated with willingness to enroll. Conclusions: Our findings suggest that about half of eligible patients would be willing to participate in the COSMIC RCT and that, except for APM, participants’ preference for treatments was not strongly related to willingness to participate.

BACKGROUND:Glucagon-like peptide-1 receptor agonists (GLP1RAs) lead to substantial weight loss and pain reduction in persons with knee osteoarthritis and obesity. OBJECTIVE:To evaluate the cost-effectiveness of 2 GLP1RAs, semaglutide and tirzepatide, for patients with osteoarthritis and obesity. DESIGN:Osteoarthritis Policy Model, a validated microsimulation model of knee osteoarthritis, to estimate lifetime benefits and costs of weight loss strategies. DATA SOURCES:Published data to derive treatment-related weight loss, pain reduction, and costs of GLP1RAs from the U.S. Office of Health Policy. TARGET POPULATION:Persons with knee osteoarthritis and obesity in the United States. The base-case cohort had a Western Ontario and McMaster Universities Osteoarthritis Index pain score of 71 (0 to 100, 100 worst) and a mean body mass index (BMI) of 40 kg/m2. TIME HORIZON:Lifetime. PERSPECTIVE:Health care, societal. INTERVENTION:Semaglutide, tirzepatide, laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), and diet and exercise. OUTCOME MEASURES:Quality-adjusted life-years (QALYs), cost, and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS:Tirzepatide provided greater health benefits at lower costs than semaglutide and yielded a $57 400 per QALY ICER versus diet and exercise. For those eligible, RYGB provided greater health benefits at lower costs than the 2 GLP1RAs and had a $30 700 per QALY ICER versus LSG. RESULTS OF SENSITIVITY ANALYSIS:Tirzepatide's ICER was most sensitive to changes in medication costs, treatment efficacy, and cohort baseline BMI. Tirzepatide had a 64% and semaglutide had a 34% probability of being cost-effective at a $100 000 per QALY threshold. LIMITATION:Data from multiple sources. CONCLUSION:Both tirzepatide and semaglutide would be widely considered cost-effective when compared directly with usual care. Tirzepatide would offer the most favorable return on investment to decision makers whose cost-effectiveness thresholds exceed $57 400 per QALY. PRIMARY FUNDING SOURCE:The Arthritis Foundation and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Background: Clinician equipoise-indifference between treatment arms-provides an ethical foundation for clinician participation in randomized controlled trials (RCTs). In preparation for an RCT comparing arthroscopic partial meniscectomy versus enhanced nonoperative therapy for patients with a meniscal tear and knee osteoarthritis (OA) who remain symptomatic after a course of physical therapy, we conducted a mixed-methods study to assess equipoise among potential enrolling clinicians. Methods:Fifteen clinicians with experience managing meniscal tears assessed 29 vignettes of hypothetical patients who met trial eligibility criteria. We randomly varied 13 vignette features (e.g., age, sex, radiographic severity, tear morphology). Clinicians expressed their willingness to enroll each hypothetical patient. After polling, we recorded and transcribed a moderated discussion to document clinician thought processes. We performed a quantitative analysis to identify clinical features associated with the likelihood of enrollment and an exploratory thematic analysis of the transcribed discussion to explicate the quantitative findings. Results:The 15 orthopaedic surgeons and physician assistants assessed 29 vignettes describing hypothetical patients. Eight votes were missing, leaving 427 vignettes, of which the clinicians were willing to enroll 302 (71%) (range, 24% to 100%) in the trial. Three clinicians were willing to enroll <50% of vignettes. Clinicians were willing to enroll just 39% of vignettes with bucket-handle tears. In logistic regression analyses, a bucket-handle tear (adjusted odds ratio [aOR], 0.12; 95% confidence interval [CI], 0.04 to 0.37) and Kellgren-Lawrence 3 radiographs (aOR, 0.54; 95% CI, 0.36 to 0.82) were independently associated with clinician unwillingness to randomize. The qualitative analysis confirmed that clinicians believed that bucket-handle tears should be managed operatively, whereas combinations of greater age, severe OA, inability to walk 200 yards, and higher body mass index (BMI) pushed clinicians toward nonoperative therapy. Conclusions: This methodology can be used to identify clinicians who should be engaged in discussions and interventions to support equipoise. It can also inform development of exclusion criteria (e.g., exclude bucket-handle tears) to increase the proportion of eligible subjects referred for enrollment. Clinical Relevance:Orthopedic surgeons play crucial roles in randomized controlled trials, the foundation of clinical practice guidelines, by enrolling patients from their practices. This article examines clinician equipoise, a key determinant of the willingness of clinicians to enroll eligible patients in trials.

Background:Understanding the factors contributing to willingness to participate in randomized clinical trials (RCTs) after anterior cruciate ligament reconstruction (ACLR) is crucial to optimizing recruitment and understanding whether interested participants represent the patient population that may benefit from the studied treatment. Purpose:To understand patients' willingness to participate in a future RCT of an oral medication to prevent posttraumatic osteoarthritis (PTOA) after ACLR. Study Design:Cross-sectional study; Level of evidence, 3. Methods:A total of 103 patients aged 18 to 45 years who were either planning to undergo ACLR in the next 4 months or had undergone ACLR within 1 year of the screening date were recruited from 2 institutions. The patients viewed a video explaining the trial and completed a questionnaire that included demographic characteristics, pain intensity, activity level, willingness to participate in the hypothetical trial, and their perceived risk (on a scale of 0%-100%) of developing knee PTOA (next 10 years or lifetime). Results:Within the cohort, 31% stated they were "definitely willing," 38% were "probably willing," 17% were "unsure," and 14% were "unwilling" to participate in a hypothetical trial. Willingness did not differ by pain or activity level; however, younger patients stated they were less willing to participate. The most common reasons for unwillingness to participate included not wanting to take a medication daily (59%) and concerns about medication risks or side effects (59%). Respondents who indicated a definite willingness to participate in the trial had higher perceptions of their own PTOA risk over the next 10 years than those who indicated they would not participate (70% vs 50%). Conclusion:In this prospective preference assessment, 69% of survey respondents expressed a willingness to participate in an RCT involving an oral medication to potentially alter the progression of PTOA after ACLR. The results suggest that an RCT in this study should include clear and concise information on the risk of developing PTOA after ACLR and the safety and tolerability of study medications in the recruitment materials.

Objective: The success of a randomized controlled trial (RCT) depends, in part, on the willingness to participate (WTP) of eligible subjects. Prospective preference assessments (PPA) offer insights into future RCT enrollment by evaluating eligible individuals’ WTP in the RCT. We sought to summarize the methods and findings of published PPAs and to compare the WTP estimates of published PPAs to the actual enrollment rates from these trials. Design: We performed a systematic literature search using PubMed for studies that assessed eligible participants’ WTP in a hypothetical trial. We abstracted sample size, proposed interventions, WTP response options, WTP percentage, presence of qualitative analyses, and assessment of trial feasibility from each publication. We defined WTP as a response of “probably” or “definitely” willing in the PPA; in sensitivity analyses, we included only “definitely” willing responses. We searched for registered and published RCTs connected to each PPA and extracted enrollment data from the corresponding trial publications where available. Results: We identified 40 PPAs. The median WTP across all PPAs was 54.9 ​% (range: 13 ​%–92.4 ​%), and 42.1 ​% (range: 7 ​%–90.2 ​%) when including only “definitely willing” responses. We found ten registered RCTs; five are completed and one is ongoing. Four PPAs with a RCT provided both “definitely willing” and “total willing” estimates. In three of these four RCTs, the actual enrollment fell between the “definitely willing” and “total willing” PPA estimates. Conclusion: “Definitely willing” and “total willing” findings in a PPA may provide useful upper and lower boundaries on participation for future trial planning.