Primary mitochondrial myopathy: 12-month follow-up results of an Italian cohort

ObjectiveTo determine whether a set of functional tests, clinical scales, patient-reported questionnaires, and specific biomarkers can be considered reliable outcome measures in patients with primary mitochondrial myopathy (PMM), we analyzed a cohort of Italian patients.MethodsBaseline data were collected from 118 patients with PMM, followed by centers of the Italian network for mitochondrial diseases. We used the 6-Minute Walk Test (6MWT), Timed Up-and-Go Test (x3) (3TUG), Five-Times Sit-To-Stand Test (5XSST), Timed Water Swallow Test (TWST), and Test of Masticating and Swallowing Solids (TOMASS) as functional outcome measures; the Fatigue Severity Scale and West Haven-Yale Multidimensional Pain Inventory as patient-reported outcome measures; and FGF21, GDF15, lactate, and creatine kinase (CK) as biomarkers.ResultsA total of 118 PMM cases were included. Functional outcome measures (6MWT, 3TUG, 5XSST, TWST, and TOMASS) and biomarkers significantly differed from healthy reference values and controls. Moreover, functional measures correlated with patients' perceived fatigue and pain severity. Patients with either mitochondrial or nuclear DNA point mutations performed worse in functional measures than patients harboring single deletion, even if the latter had an earlier age at onset but similar disease duration. Both the biomarkers FGF21 and GDF15 were significantly higher in the patients compared with a matched control population; however, there was no relation with severity of disease.ConclusionsWe characterized a large cohort of PMM by evaluating baseline mitochondrial biomarkers and functional scales that represent potential outcome measures to monitor the efficacy of treatment in clinical trials; these outcome measures will be further reinvestigated longitudinally to define the natural history of PMM.

27. Achievement of minimum clinically important differences in patient reported outcomes does not imply outright improvements in objective functional outcome measures for surgical treatment of adult spinal deformities

P4. Minimum clinically important differences in degenerative lumbar patient-reported outcomes are not indicative of widespread improvements in objective functional outcome measures

Clinically important postoperative changes can be best evaluated through the minimal clinically important difference (MCID). Our study aims to evaluate risk factors associated with failure to achieve MCID following lumbar decompression (LD). Demographics, perioperative characteristics, and patient-reported outcome measures (PROM) for pain, disability, and physical function were retrospectively reviewed and collected for patients undergoing LD. MCID achievement was calculated using established values. Relative risk of demographic and perioperative characteristics with failure to meet MCID for all PROMs was calculated. Least absolute shrinkage and selection operator (LASSO) was used to estimate individual risk factors, and postestimation logistic regression was performed. The study cohort included 811 patients. Comorbidity burden was associated with failed MCID for visual analog scale (VAS) back and leg pain and Oswestry Disability Index (ODI). Operative levels or duration was associated with failed MCID for VAS leg pain, 12-item short form physical component summary (SF-12 PCS), and the patient-reported outcomes measurement information system physical function (PROMIS PF). Preoperative spinal pathology was associated with failed MCID for VAS leg pain, ODI, SF-12 PCS, and PROMIS PF. Additional risk factors included the type of operation, insurance, age, and body mass index. LASSO selected insurance, age, comorbidity burden, blood loss, operative duration, and type of spinal pathology as significant risk factors for failure to reach MCID. Failure to reach MCID was greatest for VAS back. Age, comorbidity burden, and prolonged procedures were significantly associated with risk for failure to reach MCID for a majority of PROMs. Comorbidity burden combined with operative outcomes may place patients at increased risk for failure to reach MCID for pain, disability, and physical function following LD. Establishes risk factors for failing to reach the threshold of meaningful difference in symptoms after LD surgery.

BackgroundAs previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing nuclear DNA (nDNA) pathogenic variants receiving elamipretide experienced an improvement in the six-minute walk test (6MWT), while the cohort of subjects with mitochondrial DNA (mtDNA) pathogenic variants showed no difference versus placebo. These published findings prompted additional genotype-specific post hoc analyses of the MMPOWER-3 trial. Here, we present these analyses to further investigate the findings and to seek trends and commonalities among those subjects who responded to treatment, to build a more precise Phase 3 trial design for further investigation in likely responders.ResultsSubjects with mtDNA pathogenic variants or single large-scale mtDNA deletions represented 74% of the MMPOWER-3 population, with 70% in the mtDNA cohort having either single large-scale mtDNA deletions or MT-TL1 pathogenic variants. Most subjects in the nDNA cohort had pathogenic variants in genes required for mtDNA maintenance (mtDNA replisome), the majority of which were in POLG and TWNK. The mtDNA replisome post-hoc cohort displayed an improvement on the 6MWT, trending towards significant, in the elamipretide group when compared with placebo (25.2 ± 8.7 m versus 2.0 ± 8.6 m for placebo group; p = 0.06). The 6MWT results at week 24 in subjects with replisome variants showed a significant change in the elamipretide group subjects who had chronic progressive external ophthalmoplegia (CPEO) (37.3 ± 9.5 m versus − 8.0 ± 10.7 m for the placebo group; p = 0.0024). Pharmacokinetic (exposure–response) analyses in the nDNA cohort showed a weak positive correlation between plasma elamipretide concentration and 6MWT improvement.ConclusionsPost hoc analyses indicated that elamipretide had a beneficial effect in PMM patients with mtDNA replisome disorders, underscoring the importance of considering specific genetic subtypes in PMM clinical trials. These data serve as the foundation for a follow-up Phase 3 clinical trial (NuPOWER) which has been designed as described in this paper to determine the efficacy of elamipretide in patients with mtDNA maintenance-related disorders.Classification of evidenceClass IClinicalTrials.gov identifierNCT03323749

The minimum clinically important difference (MCID) has not been established in lateral lumbar interbody fusion (LLIF). Our study aims to establish MCID for patient-reported outcome measures (PROMs) of physical function and pain for LLIF through anchor-based and distribution-based approaches. Patients undergoing LLIF with preoperative and 6-month postoperative Oswestry Disability Index (ODI) scores were identified. PROMs of Patient-Reported Outcome Measurement Information System Physical Function (PROMIS-PF), 12-Item Short Form Physical Component Score (SF-12 PCS), Veterans RAND 12-Item Short Form Physical Component Score (VR-12 PCS), visual analog scale (VAS) back, and VAS leg were collected at preoperative and 6-month postoperative time points. Anchor-based MCID calculations were average change, minimal detectable change, change difference, receiver operating characteristic curve, and cross-sectional analysis using ODI as the anchor. Distribution-based calculations were standard error of measurement, reliable change index, effect size, and 0.5 ∗ ΔSD. Fifty patients were included. Anchor-based approaches MCID ranges were PROMIS-PF 1.1-9.6, SF-12 PCS 6.4-16.5, VR-12 PCS 5.9-12.9, VAS Back 1.4-4.6, and VAS Leg 1.3-4.3. The area under curve for receiver operating characteristics (ROC) analysis ranged from 0.63 to 0.71. Distribution-based MCID ranges were PROMIS-PF 1.4-4.5, SF-12 PCS 1.9-12.7, VR-12 PCS 2.0-6.6, VAS Back 0.4-1.4, and VAS Leg 0.5-2.0. MCID thresholds varied widely depending on the calculation method. The closest to (0,1) ROC approach was the most clinically appropriate MCID calculation. The corresponding MCID values for LLIF were PROMIS-PF at 7.8, SF-12 PCS at 6.4, VR-12 PCS at 9.3, VAS Back at 4.6, and VAS Leg at 4.3.

BackgroundThis study aims to evaluate the effect of subcutaneous (SC) elamipretide dosing on exercise performance using the 6 min walk test (6MWT), patient‐reported outcomes measuring fatigue, functional assessments, and safety to guide the development of the Phase 3 trial.MethodsMMPOWER‐2 was a randomized, double‐blind, placebo‐controlled, crossover trial that enrolled participants (N = 30) with genetically confirmed primary mitochondrial myopathy. Participants were randomly assigned (1:1) to 40 mg/day SC elamipretide for 4 weeks followed by placebo SC for 4 weeks, separated by a 4‐week washout period, or the opposite sequence. The primary endpoint was the distance walked on the 6MWT.ResultsThe distance walked on the 6MWT by the elamipretide‐treated participants was 398.3 (±134.16) meters compared with 378.5 (±125.10) meters in the placebo‐treated group, a difference of 19.8 m (95% confidence interval, −2.8, 42.5; P = 0.0833). The results of the Primary Mitochondrial Myopathy Symptom Assessment Total Fatigue and Total Fatigue During Activities scores showed that participants treated with elamipretide reported less fatigue and muscle complaints compared with placebo (P = 0.0006 and P = 0.0018, respectively). Additionally, the Neuro‐QoL Fatigue Short Form and Patient Global Assessment showed reductions in symptoms (P = 0.0115 and P = 0.0421, respectively). In this 4‐week treatment period, no statistically significant change was observed in the Physician Global Assessment (P = 0.0636), the Triple Timed Up and Go (P = 0.8423) test, and wrist/hip accelerometry (P = 0.9345 and P = 0.7326, respectively). Injection site reactions were the most commonly reported adverse events with elamipretide (80%), the majority of which were mild. No serious adverse events or deaths were reported.ConclusionsParticipants who received a short‐course treatment of daily SC elamipretide for 4 weeks experienced a clinically meaningful change in the 6MWT, which did not achieve statistical significance as the primary endpoint of the study. Secondary endpoints were suggestive of an elamipretide treatment effect compared with placebo. Nominal statistically significant and clinically meaningful improvements were seen in patient‐reported outcomes. The results of this trial provided an efficacy signal and data to support the initiation of MMPOWER‐3, a 6‐month long, Phase 3 treatment trial in patients with primary mitochondrial myopathy.

Discordance Abounds in Minimum Clinically Important Differences in THA: A Systematic Review.

Perioperative Predictors in Patients Undergoing Lateral Lumbar Interbody Fusion for Minimum Clinically Important Difference Achievement

Retrospective review. To determine postoperative clinical outcomes in patients undergoing minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF) for isthmic spondylolisthesis (IS). Few studies have examined the postoperative clinical trajectory in patients undergoing MIS-TLIF specifically for IS. Patients were separated into two cohorts based on the previously defined Visual Analog Scale (VAS) back pain (BP) for severe pain: VAS-BP <7 and VAS-BP ≥7. Patient-reported outcome measures (PROMs) of Patient-Reported Outcomes Measurement Information System-physical function (PF), 12-item Short Form (SF-12) Physical/Mental Component Score, Patient Health Questionnaire-9, VAS-BP, VAS leg pain, and Oswestry Disability Index were collected preoperatively and up to 2-year postoperatively. Minimum clinically important difference (MCID) was calculated through previously defined thresholds. A total of 160 patients were recorded, with 58 patients in the VAS-BP <7 cohort. The VAS-BP <7 cohort demonstrated significant improvement in all PROMs at one or more postoperative time points. The VAS-BP ≥7 demonstrated significant improvement at 3 or more postoperative time points in all PROMs except for SF-12 Mental Component Score. The VAS-BP <7 cohort reported significantly superior preoperative and postoperative PROMs in all domains, except for SF-12 Physical Component Score. The VAS-BP ≥7 cohort had higher MCID achievement rates at one or more time points in multiple PROMs. Patients undergoing MIS-TLIF for IS demonstrated significant postoperative improvement in PF, mental function, pain, and disability outcomes independent of preoperative severity of BP. Patients with lower preoperative BP demonstrated superior outcomes in PF, mental function, pain, and disability. However, patients with greater preoperative BP achieved higher rates of MCID in mental function, BP, and disability outcomes. Patients with greater severity of preoperative BP undergoing MIS-TLIF for IS may experience greater rates of clinically relevant improvement in mental function, BP, and disability outcomes.

As the value of patient-reported outcomes becomes increasingly recognized, minimum clinically important difference (MCID) thresholds have seen greater use in shoulder arthroplasty. However, MCIDs are unique to certain populations, and variation in the modes of calculation in this field may be of concern. With the growing utilization of MCIDs within the field and value-based care models, a detailed appraisal of the appropriateness of MCID use in the literature is necessary and has not been systematically reviewed. We performed a systematic review of MCID quantification in existing studies on shoulder arthroplasty to answer the following questions: (1) What is the range of values reported for the MCID in commonly used shoulder arthroplasty patient-reported outcome measures (PROMs)? (2) What percentage of studies use previously existing MCIDs versus calculating a new MCID? (3) What techniques for calculating the MCID were used in studies where a new MCID was calculated? The Embase, PubMed, and Ovid/MEDLINE databases were queried from December 2008 through December 2020 for total shoulder arthroplasty and reverse total shoulder arthroplasty articles reporting an MCID value for various PROMs. Two reviewers (DAK, MAM) independently screened articles for eligibility, specifically identifying articles that reported MCID values for PROMs after shoulder arthroplasty, and extracted data for analysis. Each study was classified into two categories: those referencing a previously defined MCID and those using a newly calculated MCID. Methods for determining the MCID for each study and the variability of reported MCIDs for each PROM were recorded. The number of patients, age, gender, BMI, length of follow-up, surgical indications, and surgical type were extracted for each article. Forty-three articles (16,408 patients) with a mean (range) follow-up of 20 months (0.75 to 68) met the inclusion criteria. The median (range) BMI of patients was 29.3 kg/m2 (28.0 to 32.2 kg/m2), and the median (range) age was 68 years (53 to 84). There were 17 unique PROMs with MCID values. Of the 112 MCIDs reported, the most common PROMs with MCIDs were the American Shoulder and Elbow Surgeons (ASES) (23% [26 of 112]), the Simple Shoulder Test (SST) (17% [19 of 112]), and the Constant (15% [17 of 112]). The ranges of MCID values for each PROM varied widely (ASES: 6.3 to 29.5; SST: 1.4 to 4.0; Constant: -0.3 to 12.8). Fifty-six percent (24 of 43) of studies used previously established MCIDs, with 46% (11 of 24) citing one study. Forty-four percent (19 of 43) of studies established new MCIDs, and the most common technique was anchor-based (37% [7 of 19]), followed by distribution (21% [4 of 19]). There is substantial inconsistency and variability in the quantification and reporting of MCID values in shoulder arthroplasty studies. Many shoulder arthroplasty studies apply previously published MCID values with variable ranges of follow-up rather than calculating population-specific thresholds. The use of previously calculated MCIDs may be acceptable in specific situations; however, investigators should select an anchor-based MCID calculated from a patient population as similar as possible to their own. This practice is preferable to the use of distribution-approach MCID methods. Alternatively, authors may consider using substantial clinical benefit or patient-acceptable symptom state to assess outcomes after shoulder arthroplasty. Although MCIDs may provide a useful effect-size based alternative to the traditional p value, care must be taken to use an MCID that is appropriate for the particular patient population being studied.

Primary mitochondrial myopathies (PMMs), a group of genetic mitochondrial oxidative phosphorylation disorders, primarily affect skeletal muscle function. No approved treatments for PMM exist, and patient information is limited. The international RePOWER registry (NCT03048617) assessed genotypic and phenotypic relationships in PMM and identified patients for MMPOWER-3 (elamipretide Phase 3 study). RePOWER enrolled screened and ambulatory patients aged 16-80 years. With signs and/or symptoms of PMM (N = 376; 60.4% female; mean [SD] age 42.6 [14.4] years; ~75% with an mtDNA variant and ~25% with an nDNA variant). Baseline information, current symptoms, qualityoflife, and functional assessments (6-Minute Walk Test [6MWT], Triple-Timed Up-and-Go [3TUG] Test, and 5-Times Sit-to-Stand Test [5XSST]) were captured. Accredited laboratory and genetic testing methods were available to most patients. The majority of enrolled PMM patients presented with progressive external ophthalmoplegia and fatigue. US patients were observed to use more medical interventions. Compared to non-US patients, US patients did not perform as well on the 6MWT (mean 364.6 vs. 375.2 m) and 5XSST (mean 21.6 vs. 18.6 s); US patients performed better on the 3TUG test (mean 40.2 vs. 45.0 s). The RePOWER registry provided data on patients with genetically confirmed PMM, thereby improving our understanding of PMM diagnosis and treatment and the differences in global mitochondrial clinical practice.

ObjectiveThe American Society of Anesthesiologists (ASA) physical status classification has been used to risk stratify surgical candidates. Our study compares outcomes of minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) procedures based on preoperative ASA physical status classification. MethodsA surgical registry was reviewed for primary, single-level MIS TLIF patients. Patients were categorized by preoperative ASA physical status classification: ASA I, ASA II, ASA III+. Perioperative complications were compared among groups. Patient-reported outcome measures (PROMs) for back pain, leg pain, physical function, and disability were recorded preoperatively and at 6-week, 12-week, 6-month, 1-year, and 2-year postoperative timepoints. PROM improvement from baseline (ΔPROM) and minimum clinically important difference (MCID) achievement was calculated for each timepoint and compared among groups. MCID achievement was determined as ΔPROMs that surpassed previously established MCID values. ResultsOf the 487 patients, 64 had an ASA classification of I, whereas 336 had an ASA of II, and 87 had an ASA of III or greater. Rates of complications were not associated with ASA classification (all p>0.050). Neither mean PROM scores nor ΔPROM scores were significantly associated with ASA classification at any timepoint (all p>0.050). MCID achievement was significantly associated with ASA classification for back pain at 1 year only (p=0.041). Overall MCID achievement was not significantly associated with ASA classification for any PROM (p>0.050). ConclusionWhile ASA classification has been commonly used to risk stratify surgical candidates for spinal procedures, patients with an ASA of III or greater may be able to achieve similar long-term outcomes following MIS TLIF given proper selection criteria.

Objectives:The field of orthopaedic surgery continues to transition towards using patient-reported outcome measures (PROMs) to measure treatment success. Metrics such as the minimum clinically important difference (MCID) can help define treatment success, but there is no clear consensus on the methodology or application of scores in clinical medicine. MCID calculations can vary significantly based on cohort size, methodology (e.g. anchor-based versus distribution-based methods), follow-up time point, and patient-specific factors. Anterior cruciate ligament reconstruction (ACLR) is a highly prevalent procedure that provides high patient satisfaction according to PROMs such as the Knee Injury & Osteoarthritis Outcome Score (KOOS) and the Single Assessment Numerical Evaluation (SANE). Both scales have MCID values reported in the ACLR literature. The purpose of this study was to identify patients that reached the literature-reported MCID values for KOOS and SANE. The secondary aim was to identify if there were any differences in demographic, injury, and treatment characteristics among patients that reach MCID for KOOS and/or SANE and those that do not.Methods:The PROM database of a single ambulatory surgical center was queried for ACLR procedures from 2009-2016. Revision procedures, concomitant ligament repairs/reconstructions, and patients without outcome data at baseline and two-year follow-up were excluded from the study. Demographic, injury, and surgical characteristics were extracted via chart review. Demographics included age, sex, and diagnosis of anxiety and/or depression. Injury characteristics included acuity of injury (≥6 months considered chronic) and presence of meniscal injuries. Surgical characteristics included body mass index (BMI), operative time, American Society of Anesthesiologists (ASA) Score, graft type, implant type, and concomitant meniscal procedures. Outcomes evaluated were KOOS and SANE after two years of ACLR. Patients were grouped according to whether they did or did not meet literature-reported MCIDs for KOOS and/or SANE. One-way analysis of variance and chi-square tests were conducted to identify group differences, with p=0.05 set as the threshold for significance.Results:A total of 322 patients were included. Most were female (62.1%) and had an average age of 28. Average BMI and operative time were 25.3 and 108.3 minutes, respectively. Most patients had an ASA score of 1 (84.1%). A total of 20.5% of patients had a mental health diagnosis of anxiety and/or depression. Most patients received a bone-tendon-bone autograft (49.1%). Only 6.8% of patients presented with a chronic injury. The proportion of patients that achieved MCID at two years for KOOS and SANE were 73.6% and 45.7%, respectively (p<0.00001). The majority of patients achieving SANE MCID achieved KOOS MCID (89.8%), while just 55.7% of patients achieving KOOS MCID achieved SANE MCID. 41.0% of patients achieved MCID for both KOOS and SANE, while 21.7% of patients did not achieve MCID for any scale. Compared to patients that achieved MCID in at least one PROM, there was a significantly higher proportion of patients that underwent ACLR for chronic injuries among those that did not meet MCID (11.4% vs 5.6%, p=0.004). Surgical technique did not statistically differ among patients that achieved MCID and those that did not.Conclusions:The rates of achieving literature-reported MCID values for KOOS and SANE were significantly different within the same cohort of ACLR patients (73.6% for KOOS vs 45.7% for SANE). Only 41.0% of patients achieved MCID for both PROMs. A higher percentage of patients that did not meet MCID had chronic injuries compared to those that met at least one MCID. Treatment success in ACLR as determined by PROMs is thus a function of the tool employed and the injury/patient undergoing treatment rather than the surgery performed. This study particularly found that the timing from injury to presentation was associated with likelihood of achieving MCID. As orthopaedics continues to incorporate PROM data to determine treatment success as well as prior authorization and reimbursement policies, it is important to refine these PROMs and tailor them to patient-specific factors in order to adequately capture a successful treatment.

Patient-reported outcome measures (PROMs), including the Patient-reported Outcomes Measurement Information System (PROMIS), are increasingly used to measure healthcare value. The minimum clinically important difference (MCID) is a metric that helps clinicians determine whether a statistically detectable improvement in a PROM after surgical care is likely to be large enough to be important to a patient or to justify an intervention that carries risk and cost. There are two major categories of MCID calculation methods, anchor-based and distribution-based. This variability, coupled with heterogeneous surgical cohorts used for existing MCID values, limits their application to clinical care. In our study, we sought (1) to determine MCID thresholds and attainment percentages for PROMIS after common orthopaedic procedures using distribution-based methods, (2) to use anchor-based MCID values from published studies as a comparison, and (3) to compare MCID attainment percentages using PROMIS scores to other validated outcomes tools such as the Hip Disability and Osteoarthritis Outcome Score (HOOS) and Knee Disability and Osteoarthritis Outcome Score (KOOS). This was a retrospective study at two academic medical centers and three community hospitals. The inclusion criteria for this study were patients who were age 18 years or older and who underwent elective THA for osteoarthritis, TKA for osteoarthritis, one-level posterior lumbar fusion for lumbar spinal stenosis or spondylolisthesis, anatomic total shoulder arthroplasty or reverse total shoulder arthroplasty for glenohumeral arthritis or rotator cuff arthropathy, arthroscopic anterior cruciate ligament reconstruction, arthroscopic partial meniscectomy, or arthroscopic rotator cuff repair. This yielded 14,003 patients. Patients undergoing revision operations or surgery for nondegenerative pathologies and patients without preoperative PROMs assessments were excluded, leaving 9925 patients who completed preoperative PROMIS assessments and 9478 who completed other preoperative validated outcomes tools (HOOS, KOOS, numerical rating scale for leg pain, numerical rating scale for back pain, and QuickDASH). Approximately 66% (6529 of 9925) of patients had postoperative PROMIS scores (Physical Function, Mental Health, Pain Intensity, Pain Interference, and Upper Extremity) and were included for analysis. PROMIS scores are population normalized with a mean score of 50 ± 10, with most scores falling between 30 to 70. Approximately 74% (7007 of 9478) of patients had postoperative historical assessment scores and were included for analysis. The proportion who reached the MCID was calculated for each procedure cohort at 6 months of follow-up using distribution-based MCID methods, which included a fraction of the SD (1/2 or 1/3 SD) and minimum detectable change (MDC) using statistical significance (such as the MDC 90 from p < 0.1). Previously published anchor-based MCID thresholds from similar procedure cohorts and analogous PROMs were used to calculate the proportion reaching MCID. Within a given distribution-based method, MCID thresholds for PROMIS assessments were similar across multiple procedures. The MCID threshold ranged between 3.4 and 4.5 points across all procedures using the 1/2 SD method. Except for meniscectomy (3.5 points), the anchor-based PROMIS MCID thresholds (range 4.5 to 8.1 points) were higher than the SD distribution-based MCID values (2.3 to 4.5 points). The difference in MCID thresholds based on the calculation method led to a similar trend in MCID attainment. Using THA as an example, MCID attainment using PROMIS was achieved by 76% of patients using an anchor-based threshold of 7.9 points. However, 82% of THA patients attained MCID using the MDC 95 method (6.1 points), and 88% reached MCID using the 1/2 SD method (3.9 points). Using the HOOS metric (scaled from 0 to 100), 86% of THA patients reached the anchor-based MCID threshold (17.5 points). However, 91% of THA patients attained the MCID using the MDC 90 method (12.5 points), and 93% reached MCID using the 1/2 SD method (8.4 points). In general, the proportion of patients reaching MCID was lower for PROMIS than for other validated outcomes tools; for example, with the 1/2 SD method, 72% of patients who underwent arthroscopic partial meniscectomy reached the MCID on PROMIS Physical Function compared with 86% on KOOS. MCID calculations can provide clinical correlation for PROM scores interpretation. The PROMIS form is increasingly used because of its generalizability across diagnoses. However, we found lower proportions of MCID attainment using PROMIS scores compared with historical PROMs. By using historical proportions of attainment on common orthopaedic procedures and a spectrum of MCID calculation techniques, the PROMIS MCID benchmarks are realizable for common orthopaedic procedures. For clinical practices that routinely collect PROMIS scores in the clinical setting, these results can be used by individual surgeons to evaluate personal practice trends and by healthcare systems to quantify whether clinical care initiatives result in meaningful differences. Furthermore, these MCID thresholds can be used by researchers conducting retrospective outcomes research with PROMIS. Level III, therapeutic study.