Estimating a Minimal Important Difference for the EQ-5D-5L Utility Index in Dialysis Patients.

OBJECTIVES: The EQ-5D-5L is a commonly used health-related quality of life instrument for evaluating interventions in patients receiving dialysis; however, the minimal important difference (MID) that constitutes a meaningful treatment effect for this population has not been established. This study aims to estimate the MID for the EQ-5D-5L utility index in dialysis patients. METHODS: 6-monthly EQ-5D-5L measurements were collected from adult dialysis patients between April 2017 and November 2020 at a renal network in Sydney, Australia. EQ-VAS and Integrated Palliative care Outcome Scale Renal symptom burden scores were collected simultaneously and used as anchors. MID estimates for the EQ-5D-5L utility index were derived using anchor-based and distribution-based methods. RESULTS: A total of 352 patients with ≥1 EQ-5D-5L observation were included, constituting 1127 observations. Mean EQ-5D-5L utility index at baseline was 0.719 (SD ± 0.267), and mean EQ-5D-5L utility decreased over time by -0.017 per year (95% CI -0.029 to -0.006, P = .004). Using cross-sectional anchor-based methods, MID estimates ranged from 0.073 to 0.107. Using longitudinal anchor-based methods, MID for improvement and deterioration ranged from 0.046 to 0.079 and -0.111 to -0.048, respectively. Using receiver operating characteristic curves, MID for improvement and deterioration ranged from 0.037 to 0.122 and -0.074 to -0.063, respectively. MID estimates from distribution-based methods were consistent with anchor-based estimates. CONCLUSIONS: Anchor-based and distribution-based approaches provided EQ-5D-5L utility index MID estimates ranging from 0.034 to 0.134. These estimates can inform the target difference or "effect size" for clinical trial design among dialysis populations.

The minimal important difference of patient-reported outcome measures related to female urinary incontinence: a systematic review.

BACKGROUND: The minimal important difference is a valuable metric in ascertaining the clinical relevance of a treatment, offering valuable guidance in patient management. There is a lack of available evidence concerning this metric in the context of outcomes related to female urinary incontinence, which might negatively impact clinical decision-making. OBJECTIVES: To summarize the minimal important difference of patient-reported outcome measures associated with urinary incontinence, calculated according to both distribution- and anchor-based methods. METHODS: This is a systematic review conducted according to the PRISMA guidelines. The search strategy including the main terms for urinary incontinence and minimal important difference were used in five different databases (Medline, Embase, CINAHL, Web of Science, and Scopus) in 09 June 2021 and were updated in January 09, 2024 with no limits for date, language or publication status. Studies that provided minimal important difference (distribution- or anchor-based methods) for patient-reported outcome measures related to female urinary incontinence outcomes were included. The study selection and data extraction were performed independently by two different researchers. Only studies that reported the minimal important difference according to anchor-based methods were assessed by credibility and certainty of the evidence. When possible, absolute minimal important differences were calculated for each study separately according to the mean change of the group of participants that slightly improved. RESULTS: Twelve studies were included. Thirteen questionnaires with their respective minimal important differences reported according to distribution (effect size, standard error of measurement, standardized response mean) and anchor-based methods were found. Most of the measures for anchor methods did not consider the smallest difference identified by the participants to calculate the minimal important difference. All reports related to anchor-based methods presented low credibility and very low certainty of the evidence. We pooled 20 different estimates of minimal important differences using data from primary studies, considering different anchors and questionnaires. CONCLUSIONS: There is a high variability around the minimal important difference related to patient-reported outcome measures for urinary incontinence outcomes according to the method of analysis, questionnaires, and anchors used, however, the credibility and certainty of the evidence to support these is still limited.

Measuring what matters to older persons for active living: part II cross-sectional validity evidence for OPAL measure across four countries.

INTRODUCTION: Through interviews with 148 older persons from four countries and in four languages, the content for a 17-item measure of active living was developed. The purpose of this paper is to present further evidence of the extent to which this new measure, Older Persons Active Living (OPAL), is "fit-for-purpose" for measuring the extent of active living at one point in time. METHODS: A cross-sectional study was carried out on a population aged 65 + and living independently, drawn from a participant panel, HostedinCanada, sampling people from Canada, United States, United Kingdom, and Netherlands. The survey instrument comprised the OPAL questionnaire rated on importance and frequency, sociodemographics, and information on physical and mental function. The argument-based approach to validity framed the analyses. Logistic regression, structural equation modeling, ordinary least-squares regression, and correlation were used to generate estimates for parameters underpinning validity evidence. RESULTS: A total of 1612 people completed the survey, 100 to 400 people across the 6 country-language strata. The proportion of people rating the items as extremely or quite important ranged from 60 to 90%, with no important differences between men and women and few differences between strata. A single-factor structure was supported. The ordinality of the response options justified an additive total score yielding a near normal distribution (mean: 33.1; SD: 11.5; range 0-51). Correlations with other measures of converging constructs were of moderate strength (~ 0.50), and differences across groups known to affect functioning and health were observed, suggesting a Miminal Important Difference (MID) of 6 out of 51. CONCLUSION: The results of this study provide evidence that the 17-item OPAL measure is fit for the purpose of estimating the extent to which older persons are living actively at one point in time.

Anchor-based minimal important difference values are often sensitive to the distribution of the change score.

PURPOSE: Anchor-based studies are today the most popular approach to determine a minimal important difference value for an outcome variable. However, a variety of construction methods for such values do exist. This constitutes a challenge to the field. In order to distinguish between more or less adequate construction methods, meaningful minimal requirements can be helpful. For example, minimal important difference values should not reflect the intervention(s) the patients are exposed to in the study used for construction, as they should later allow to compare interventions. This requires that they are not sensitive to the distribution of the change score observed. This study aims at investigating to which degree established construction methods fulfil this minimal requirement. METHODS: Six constructions methods were considered, covering very popular and recently suggested methods. The sensitivity of MID values to the distribution of the change score was investigated in a simulation study for these six construction methods. RESULTS: Five out of six construction methods turned out to yield MID values which are sensitive to the distribution of the change score to a degree that questions their usefulness. Insensitivity can be obtained by using construction methods based solely on an estimate of the conditional distribution of the anchor variable given the change score. CONCLUSION: In future the computation of MID values should be based on construction methods avoiding sensitivity to the distribution of the change score.

Minimal important difference in postoperative morphine consumption after hip and knee arthroplasty using nausea, vomiting, sedation and dizziness as anchors.

BACKGROUND: Morphine-sparing effects are often used to evaluate non-opioid analgesic interventions. The exact effect that would warrant the implementation of these interventions in clinical practice (a minimally important difference) remains unclear. We aimed to determine this with anchor-based methods. METHODS: This was a post hoc analysis of three studies investigating pain management after hip or knee arthroplasty (PANSAID [NCT02571361], DEX-2-TKA [NCT03506789] and Pain Map [NCT02340052]). The overall population was median aged 70, median ASA 2, 54% female. We examined the correlation between 0 and 24 h postoperative iv morphine equivalent consumption and the severity of nausea, vomiting, sedation and dizziness. The anchor was different severity degrees of these opioid-related adverse events. The primary outcome was the difference in morphine consumption between patients experiencing no versus only mild events. Secondary outcomes included the difference in morphine consumption between patients with mild versus moderate and moderate versus severe events. We used Hodges-Lehmann median differences, exact Wilcoxon-Mann-Whitney tests and quantile regression. RESULTS: The difference in iv morphine consumption was 6 mg (95% confidence interval: 4-8) between patients with no versus only mild events, 5 mg (2-8) between patients with mild versus moderate events and 0 mg (-4 to 4) between patients with moderate versus severe events. CONCLUSIONS: In populations comparable to this post-hoc analysis (orthopaedic surgery, median age 70 and ASA 2), we suggest a minimally important difference of 5 mg for 0-24 h postoperative iv morphine consumption.

The minimal important difference in orthodontic treatment duration: a survey across adult patients.

BACKGROUND: The minimal important difference (MID) is defined as the smallest difference that the patient perceives as important. Furthermore, the smallest worthwhile effect (SWE) is the important change measured with the benefit-harm trade-off method. The aim of this study was to evaluate the MID in orthodontic treatment duration to inform the decision regarding seeking procedures to accelerate orthodontic tooth movement and reduce treatment duration. METHODS: We constructed a survey eliciting views of the MID from adult participants from four countries undergoing orthodontic treatment. Ten questions addressed reduction in the treatment duration for both durations 12 and 24 months, and four questions were related to the reduction in treatment duration that the patients would require to undergo surgical or non-surgical adjunctive procedures. We applied a univariable random effects logistic regression model to examine the association between the participants' characteristics and the MID. Then, we fitted a multivariable logistic random effects regression including significant predictors. RESULTS: Four hundred and fifty adults, with a median age of 21 (interquartile range: 19-24), undergoing orthodontic treatment participated in the survey. Of the respondents, 60% considered 15 days as a trivial reduction from 12 months duration of therapy and 70% considered 15 days a trivial reduction from 24 months. Of the respondents, 48% considered the period of 2 months a moderate reduction from 12 months, and 60% considered 2 months a moderate reduction from 24 months. From these results, we inferred that patients considered reductions of approximately 1 month as the MID in the treatment duration for both 12 and 24 months. However, SWE was considerably more than the MID for most of the participants to decide undergoing surgical adjunctive procedures to reduce the time of therapy. The participants required smaller SWE to undergo non-surgical procedures compared to surgical procedures. CONCLUSION: The MID in the treatment duration is one month for both treatment durations 12 and 24 months. Patients require a greater SWE than the MID to undergo adjunctive procedures to shorten the duration, particularly for surgical procedures.

The oral and systemic health impact profile for periodontal disease (OSHIP-Perio)-Part 2: Responsiveness and minimal important difference.

OBJECTIVES: The Oral and Systemic Health Impact Profile for Periodontal Disease (OSHIP-Perio) was developed to measure health-related quality of life (HRQoL) and oral health-related quality of life (OHRQoL). This study aimed to determine the responsiveness and minimal importance difference (MID) of the OSHIP-Perio. METHODS: Subjects with periodontal disease completed the OSHIP-Perio at baseline and six to ten weeks after non-surgical periodontal therapy. Comparisons of the clinical variables and the OSHIP-Perio scores before and after treatment were analysed using the Wilcoxon signed-rank test, together with the Oral Health Impact Profile (OHIP-49, OHIP-14 and OHIP-5) scores. The MIDs for all the instruments were calculated using distribution-based methods. RESULTS: Fifty-one case subjects who completed periodontal treatment and the OSHIP-Perio instrument were included for analysis. Significant improvement in all clinical variables after treatment (p < 0.001) was observed. The OSHIP-Perio total score as well as its four-dimensional scores (periodontal, oral function, orofacial pain and psychosocial impact) were significantly reduced after treatment (p < 0.001), indicating better OHRQoL. Findings were consistent with the other OHIP instruments. In determining the MID, the percentage point change of the OSHIP-Perio was found to be lower than the shorter OHIP-5 instrument when using both effect sizes (ES) (10.71% vs. 15.0% at 0.5SD) and standard error of measurement (SEM) (5.36% vs. 10.0% at 1SEM; 8.93% vs. 20.0% at 2SEM) calculations. CONCLUSIONS: The OSHIP-Perio demonstrated good responsiveness which was comparable to the OHIP-49 and its short-form derivatives. Its required percentage point change in determining its MID is smaller than the OHIP-5.

Patient-Reported Outcome Measure Use in Guidelines Published by the American Academy of Ophthalmology: A Review.

TOPIC: We reviewed the use of patient-reported outcome measures (PROMs) in the treatment of ophthalmologic conditions as recommended by the Clinical Practice Guidelines (CPGs) published by the American Academy of Ophthalmology (AAO). CLINICAL RELEVANCE: Patient-reported outcome measures are standardized instruments that provide information regarding a patient's health status or health-related quality of life. Patient-reported outcome measures are increasingly used to inform study end points in ophthalmology studies. However, the extent to which PROMs are ultimately informing patient management recommendations in ophthalmology as part of CPGs remains an area of evidence gap. METHODS: We included all CPGs published by the AAO from inception to June 2022. We also included all primary studies and systematic reviews cited in the treatment sections of the CPGs evaluating treatment of an ophthalmic condition. The primary outcome was the frequency of PROMs discussed in CPGs and in cited studies evaluating treatment. Secondary outcomes included frequency of minimal important difference (MID) use to contextualize PROM results and percentage of strong and discretionary recommendations supported by PROMs. We published a study protocol a priori on PROSPERO (CRD42022307427). Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We assessed risk of bias using the Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. RESULTS: We identified 24 eligible CPGs, providing 2458 cited studies (2191 primary, 267 secondary) evaluating treatment of eye conditions. Ten CPGs (41.7%) reported consideration of PROMs. Of these, 31 of 94 (33%) recommendations were informed by studies evaluating a PROM as an outcome. Across all studies cited in the development of CPGs, 221 (9.0%) used PROMs as a primary or secondary outcome, of which 4 PROM results (1.8%) were interpreted using an empirically determined MID. Overall, the risk of bias was low for all CPGs. CONCLUSIONS: Overall, outcomes of PROMs are seldom used in ophthalmology CPGs published by the AAO and in cited primary and secondary research on treatments. When PROMs were considered, their interpretation was seldom based on an MID. To improve patient care, guideline developers may consider incorporating PROMs and applicable MIDs to inform key outcomes when formulating treatment recommendations. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Toward a rigorous assessment of the statistical performances of methods to estimate the Minimal Important Difference of Patient-Reported Outcomes: A protocol for a large-scale simulation study.

Interpreting observed changes over time in Patient-Reported Outcomes (PRO) measures is still considered a challenge. Indeed, concluding an observed change at group level is statistically significant does not necessarily equate this change is meaningful from the perspective of the patient. To help interpret within and/or between group changes in the measure over time, the estimation of the Minimal Important Difference (MID) of the instrument - the smallest value that patients consider as a perceived change - is useful. In the last 30 years, a plethora of methods and estimators have been proposed to derive this MID value using clinical data from sample of patients. MIDs for hundreds of PROs have been estimated, with frequently a substantial variability in the results depending on the method used. Nonetheless, a rigorous assessment of the statistical performances of numerous proposed methods for estimating MIDs by experimental design such as Monte-Carlo study has never been performed. The purpose of this paper is to thoroughly depict a protocol for a large-scale simulation study designed to investigate the statistical performances, especially bias against a true populational value, of the common proposed estimators for MID. This paper depicts how investigated methods and estimators were retained after the conduct of a systematic review, the design of a conceptual model that formally defines what is the true populational MID value and the translation of the conceptual model into a model allowing the simulation of responses of items to a hypothetical PRO at two times of measurement along with the response to a Patient Global Rating of Change at the second time under the constraint of a known true MID value. A statistical analysis plan is depicted in order to conclude if working hypotheses on what could be appropriate MID estimators will be verified. Strengths, assumptions, and limits of the simulation model are exposed. Finally, we show how this protocol could be the basis for fostering future methodological research on the issue of interpreting changes in PRO measures.

The challenges inherent with anchor-based approaches to the interpretation of important change in clinical outcome assessments.

PURPOSE: Anchor-based methods are group-level approaches used to derive clinical outcome assessment (COA) interpretation thresholds of meaningful within-patient change over time for understanding impacts of disease and treatment. The methods explore the associations between change in the targeted concept of the COA measure and the concept measured by the external anchor(s), typically a global rating, chosen as easier to interpret than the COA measure. While they are valued for providing plausible interpretation thresholds, group-level anchor-based methods pose a number of inherent theoretical and methodological conundrums for interpreting individual-level change. METHODS: This investigation provides a critical appraisal of anchor-based methods for COA interpretation thresholds and details key biases in anchor-based methods that directly influences the magnitude of the interpretation threshold. RESULTS: Five important research issues inherent with the use of anchor-based methods deserve attention: (1) global estimates of change are consistently biased toward the present state; (2) the use of static current state global measures, while not subject to artifacts of recall, may exacerbate the problem of estimating clinically meaningful change; (3) the specific anchor assessment response(s) that identify the meaningful change group usually involves an arbitrary judgment; (4) the calculated interpretation thresholds are sensitive to the proportion of patients who have improved; and (5) examination of anchor-based regression methods reveals that the correlation between the COA change scores and the anchor has a direct linear relationship to the magnitude of the interpretation threshold derived using an anchor-based approach; stronger correlations yielding larger interpretation thresholds. CONCLUSIONS: While anchor-based methods are recognized for their utility in deriving interpretation thresholds for COAs, attention to the biases associated with estimation of the threshold using these methods is needed to progress in the development of standard-setting methodologies for COAs.

Establishing thresholds for meaningful within-individual change using longitudinal item response theory.

PURPOSE: Thresholds for meaningful within-individual change (MWIC) are useful for interpreting patient-reported outcome measures (PROM). Transition ratings (TR) have been recommended as anchors to establish MWIC. Traditional statistical methods for analyzing MWIC such as mean change analysis, receiver operating characteristic (ROC) analysis, and predictive modeling ignore problems of floor/ceiling effects and measurement error in the PROM scores and the TR item. We present a novel approach to MWIC estimation for multi-item scales using longitudinal item response theory (LIRT). METHODS: A Graded Response LIRT model for baseline and follow-up PROM data was expanded to include a TR item measuring latent change. The LIRT threshold parameter for the TR established the MWIC threshold on the latent metric, from which the observed PROM score MWIC threshold was estimated. We compared the LIRT approach and traditional methods using an example data set with baseline and three follow-up assessments differing by magnitude of score improvement, variance of score improvement, and baseline-follow-up score correlation. RESULTS: The LIRT model provided good fit to the data. LIRT estimates of observed PROM MWIC varied between 3 and 4 points score improvement. In contrast, results from traditional methods varied from 2 to 10 points-strongly associated with proportion of self-rated improvement. Best agreement between methods was seen when approximately 50% rated their health as improved. CONCLUSION: Results from traditional analyses of anchor-based MWIC are impacted by study conditions. LIRT constitutes a promising and more robust analytic approach to identifying thresholds for MWIC.

Comparison of anchor-based methods for estimating thresholds of meaningful within-patient change using simulated PROMIS PF 20a data under various joint distribution characteristic conditions.

PURPOSE: To compare the performance of anchor-based methods for estimating thresholds of meaningful within-patient change (i.e., individual change) of clinical outcome assessments in conditions reflecting data characteristics of small- to medium-sized clinical trials. METHODS: Datasets were generated from the joint distributions of the PROMIS PF 20a T-score changes and a seven-point global change anchor measure. The 108 simulation conditions (1000 replications per condition) included combinations of three marginal distributions of T-score changes, three improvement percentages in the anchor measure, four levels of responsiveness correlations, and three sample sizes. Threshold estimation methods included mean change, median change, ROC curve, predictive modeling, half SD, and SEM. Relative bias, precision, accuracy, and measurement significance of the estimates were evaluated based on comparison with true thresholds and IRT-based individual reliable changes of PROMIS scores. Quantile regression models were applied to select and interpret effects of simulation conditions on estimation bias. RESULTS: When PROMIS T-score changes were distributed normally, the predictive modeling method performed best with 50% or more responders identified by the anchor; the mean and median methods were preferred with 30% responders. For skewed distributions, the median method and ROC method gained more advantages. Among the evaluated study conditions, the improvement percentage condition had the most obvious effects on estimation bias. CONCLUSION: To establish accurate and precise thresholds, clinical researchers are recommended to prioritize study designs with at least 50% anchor-defined responders and strongly responsive target endpoints with highly reliable scoring calibration and to select optimal anchor-based methods given the data characteristics.

Novel clinically meaningful scores for the ICIQ-UI-SF and ICIQ-FLUTS questionnaires in women with stress incontinence.

AIM: To establish, for the first time, the clinically important differences for the ICIQ-UI-SF and ICIQ-FLUTS questionnaires following surgical and conservative treatments for stress-predominant urinary incontinence in women. METHODS: Data from the SIMS and OPAL randomised controlled trials were analysed using an anchor-based method. Clinically important difference (CID; score change indicating a successful outcome) and minimal important difference (MID; score change indicating the smallest noticeable difference) were estimated using the PGI-I scale as the anchor. RESULTS: For ICIQ-UI-SF, following surgical management, CIDs were 5.0 (95%CI 4.3, 5.6) at 1 year and 4.9 points (95%CI 4.2, 5.5) at 3 years, while following conservative management, CIDs were 4.0 (95%CI 3.4, 4.5) at 1 year and 4.6 points (95%CI 4.0, 5.2) at 2 years. For ICIQ-FLUTS, the CID was 3.4 points (95%CI 2.9, 4.0) at 1 year for both surgical and conservative management. MIDs for ICIQ-UI-SF, after surgical treatment, were 4.7 (95% CI 3.2, 6.1) at 1 year and 1.6 points (95%CI -0.2, 3.0) at 3 years, and after conservative treatment they were 1.7 (95% CI 1.0, 2.5) at 1 year and 1.9 points (95%CI 1.1, 2.7) at 2 years. For ICIQ-FLUTS, MIDs were 1.8 (95% CI 0.6, 3.1) at 1 year and 3.2 points (95%CI 2.0, 4.4) at 2 years after surgical treatment, and 1.3 (95%CI 0.6, 1.9) at 1 year and 1.9 points (95%CI 1.1, 2.6) at 2 years after conservative treatment. CONCLUSION: Our study is the first to establish the CID for the ICIQ-UI-SF and ICIQ-FLUTS that women would associate with a successful outcome 3-years post-surgery and 2-years post-conservative treatment of stress-predominant urinary incontinence. The MID was lower following conservative compared to surgical treatment.

Minimal important difference in opioid consumption based on adverse event reduction-A study protocol.

BACKGROUND: The patient-relevant minimal important difference for opioid consumption remains undetermined, despite its frequent use as primary outcome in trials on postoperative pain management. A minimal important difference is necessary to evaluate whether significant trial results are clinically relevant. Further, it can be used as effect size to ensure that trials are powered to find clinically relevant effects. By exploring the dose-response relationship between postoperative opioid consumption and opioid-related adverse effects, we aim to approximate the minimal important difference in opioid consumption anchored to opioid-related adverse effects. METHODS: This is a post-hoc analysis of aggregated data from two clinical trials (PANSAID NCT02571361 and DEX2TKA NCT03506789) and one observational cohort study (Pain Map NCT02340052) on pain management after total hip and knee arthroplasty. The primary outcome is the Hodges-Lehmann median difference in opioid consumption between patients with no opioid-related adverse effects and patients experiencing the mildest degree of one or more opioid-related adverse effects (i.e., mild nausea, sedation and/or dizziness or vomiting). Secondary outcomes include the Hodges-Lehmann median difference in opioid consumption that corresponds to one point on a cumulated opioid-related adverse event 0-10 scale. Further, we will explore the proportion of patients that experience opioid-related adverse effects for consecutive opioid dose intervals of 2 mg iv morphine equivalents. Quantile regression will be used to assess any significant interactions with patient baseline characteristics. CONCLUSIONS: This study will hopefully bring us one step closer to determining relevant opioid reductions and thereby improve our understanding of intervention effects and planning of future trials.

Determination of the minimal important difference for inspiratory muscle strength in people with severe and very severe COPD.

OBJECTIVE: Inspiratory muscle training is recommended for people with chronic obstructive pulmonary disease (COPD) with inspiratory muscle weakness. Clinical interpretation of changes in inspiratory muscle strength could be helped by the determination of cut-off values. The aim of this study was to estimate the minimal important difference for inspiratory muscle strength assessed with maximal inspiratory pressure (MIP) in people with COPD. DESIGN: Post hoc analysis of a randomized controlled trial (EMI2 study) including people with severe to very severe COPD undergoing a pulmonary rehabilitation program was conducted. The determination of the minimal important difference was realized using both anchor-based and distribution-based methods. SETTING: The study includes patients admitted to the rehabilitation program unit of the Centre Hospitalier des Pays de Morlaix (Morlaix, France) between March 5, 2014 and September 8, 2016. PARTICIPANTS: Seventy-three people with severe to very severe COPD (age 62.2 ± 8.0 years, forced expiratory volume in 1 s 36.4 ± 9.5% of theoretical) were analyzed. INTERVENTION: Patients followed a standardized pulmonary rehabilitation program 5 days a week for 4 weeks. The program included aerobic training, ground-based outdoor walking training, and strengthening of lower and upper limb muscles. MAIN MEASURES: At the end of the pulmonary rehabilitation program, MIP improved by 14.8 ± 14.9 cmH2O (p < 0.05). Regarding the anchor-based method, only the modified Medical Research Council was selected as an appropriate anchor. The receiver operating characteristic curve analysis reported a minimal important difference of 13.5 cmH2O (sensibility: 75% specificity: 67.5%). Using distribution-based methods, the estimate of minimal important difference was 7.9 cmH2O (standard error of measurement method) and 10.9 cmH2O (size effect method). RESULTS: The estimations proposed by this study ranged from 7.9 to 13.5 cmH2O. CONCLUSIONS: The measurement of minimal important difference is a simple tool for assessing the changes of inspiratory muscle strength during a pulmonary rehabilitation program. We propose a minimal important difference of 13.5 cmH2O for the improvement of MIP. Further studies are needed to confirm this estimation.ClinicalTrials.gov identifier: NCT02074813.

Factors associated with worsening sexual function during adjuvant endocrine therapy in a prospective clinic-based cohort of women with early-stage breast cancer.

PURPOSE: Sexual function problems are common but under-reported among women receiving adjuvant endocrine therapy for breast cancer. Worsening scores on patient-reported outcomes (PROs) may identify those at risk for sexual function problems during treatment. We performed a secondary analysis of prospectively collected PROs in women receiving adjuvant endocrine therapy to identify factors associated with worsening sexual function. METHODS: Women with stage 0-III breast cancer initiating adjuvant endocrine therapy participating in a prospective cohort completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60 months. Sexual function was evaluated by the MOS-SP measure. Other measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance and the Endocrine Symptom Subscale of the FACT-ES. We evaluated associations between score worsening of at least the minimal important difference (MID) in PROMIS T-scores (4 points) and FACT-ES scores (5 points) with score worsening of at least the MID in MOS-SP scores (8 points) using logistic regression. RESULTS: Among 300 participants, 45.7% experienced ≥ 8-point worsening of MOS-SP score at any time point compared to baseline. Worsening endocrine symptoms (OR 1.34, 95% CI 1.22-1.49, p < 0.001), worsening physical function (OR 1.09, 95% CI 1.00-1.18, p = 0.06), and prior mastectomy (OR 1.45, 95% CI 0.94-2.23, p = 0.09) were associated with MOS-SP score worsening by at least the MID. CONCLUSION: Worsening endocrine symptoms and physical function identified on PROs are associated with worsening sexual function during adjuvant endocrine therapy. Routine assessment of these domains with PROs may identify women at risk for sexual function problems. TRIAL REGISTRATION NUMBER: NCT01937052; Date of Registration: 09/09/2013.

Determining the minimal important differences in the RQLQ score with grass and tree allergy immunotherapy versus placebo in adults with moderate-to-severe allergy.

BACKGROUND: Pollen from grasses and trees can trigger allergic rhinitis (AR), where the symptoms and associated consequences can negatively affect quality of life (QoL). The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) is frequently used in clinical trials of AR to assess QoL. To help interpret RQLQ data, the minimal important difference (MID) can be used to assess whether a mean difference in QoL between treatment groups is clinically meaningful. In seasonal allergy, an MID differs according to the allergen, pollen exposure, symptom severity, patient age and treatment; the same MID cannot be applied to all scenarios. METHODS: Using data from four Phase III clinical trials of SQ sublingual immunotherapy-tablets in adults with moderate-to-severe allergy, between-group MIDs were derived for the RQLQ in grass pollen allergy (during the peak [n = 501] and entire [n = 514] pollen seasons), and in tree pollen allergy (during the birch [n = 516] and tree [n = 518] pollen seasons), using anchor-based methodology, supported by distribution-based methods. RESULTS: For grass pollen allergy, anchor-based derived between-group MIDs were 0.22 for the entire pollen season (n = 343) and 0.10 for the peak pollen season (n = 335). For tree pollen allergy, anchor-based derived between-group MIDs were 0.26 for the tree pollen season (n = 306) and 0.16 for the birch pollen season (n = 305) (representative of peak season). Distribution-based derived MIDs were supportive of the anchor-based values. CONCLUSIONS: This analysis has derived between-group MIDs specific to the trial populations evaluated and to the conditions under which the data were obtained, and highlights the need for a range of MIDs to reflect the unique nature of seasonal allergic disease.

Is IQWiG's 15% Threshold Universally Applicable in Assessing the Clinical Relevance of Patient-Reported Outcomes Changes? An ISPOR Special Interest Group Report.

This article discusses a recent methodological change to assess the additional benefit of drug intervention by the German Federal Joint Committee (Gemeinsamer Bundesausschuss), a key stakeholder in EUnetHTA21 (European Network for Health Technology Assessment joint consortium for future EU HTA regulation), methodological workstream. The German Federal Joint Committee (Gemeinsamer Bundesausschuss) set a universal individual response threshold at ≥ 15% of the scale range of the measurement instrument, for all patient-reported outcomes, to achieve an additional benefit rating for a given pharmaceutical intervention. This approach is originally based on a corresponding recommendation from the Institute for Quality and Efficiency in Health Care. The merits of this approach are reviewed from various perspectives, including the evidence basis, statistical and psychometric considerations, and regulatory perspectives by the ISPOR Clinical Outcomes Assessment Special Interest Group's multistakeholder group of authors (academia, contract research organizations, and industry). Particular focus is placed on the patient perspective within the Institute for Quality and Efficiency in Health Care approach. The article development incorporated feedback from ISPOR members during well-attended ISPOR US and European conference presentations and 2 formal rounds of written review. The authors concluded that the ≥ 15% response threshold is incongruent with previously defined and scientifically established thresholds and is not well-suited for universal implementation. Further scientific evidence and discussion among all stakeholders are needed, especially should this universal rule be considered in the context of future joint clinical assessments of health technologies in the European Union scheduled from 2025 onward.

Minimal important difference and patient acceptable symptom state for the Numerical Rating Scale (NRS) for pain and the Patient-Rated Wrist/Hand Evaluation (PRWHE) for patients with osteoarthritis at the base of thumb.

BACKGROUND: The Numerical Rating Scale (NRS) and Patient-rated wrist/hand evaluation (PRWHE) are patient-reported outcomes frequently used for evaluating pain and function of the wrist and hand. The aim of this study was to determine thresholds for minimal important difference (MID) and patient acceptable symptom state (PASS) for NRS pain and PRWHE instruments in patients with base of thumb osteoarthritis. METHODS: Fifty-two patients with symptomatic base of thumb osteoarthritis wore a splint for six weeks before undergoing trapeziectomy. NRS pain (0 to 10) and PRWHE (0 to 100) were collected at the time of recruitment (baseline), after splint immobilization prior to surgery, and at 3, 6, 9 and 12 months after surgery. Four anchor-based methods were used to determine MID for NRS pain and PRWHE: the receiver operating characteristics (ROC) curve, the mean difference of change (MDC), the mean change (MC) and the predictive modelling methods. Two approaches were used to determine PASS for NRS pain and PRWHE: the 75th percentile and the ROC curve methods. The anchor question for MID was the change perceived by the patient compared with baseline; the anchor question for PASS was whether the patient would be satisfied if the condition were to stay similar. The correlation between the transition anchor at baseline and the outcome at all time points combined was calculated using the Spearman's rho analysis. RESULTS: The MID for NRS pain was 2.5 using the ROC curve method, 2.0 using the MDC method, 2.8 using the MC method, and 2.5 using the predictive modelling method. The corresponding MIDs for PRWHE were 22, 24, 10, and 20. The PASS values for NRS pain and PRWHE were 2.5 and 30 using the ROC curve method, and 2.0 and 22 using the 75th percentile method, respectively. The area under curve (AUC) analyses showed excellent discrimination for all measures. CONCLUSION: We found credible MID estimates for NRS and PRWHE (including its subscales), although the MID estimates varied depending on the method used. The estimates were 20-30% of the range of scores of the instruments. The cut-offs for MID and PASS showed good or excellent discrimination, lending support for their use in future studies. TRIAL REGISTRATION: This clinimetrics study was approved by the Helsinki University ethical review board (HUS1525/2017).

Minimal important difference and patient acceptable symptom state for common outcome instruments in patients with a closed humeral shaft fracture - analysis of the FISH randomised clinical trial data.

BACKGROUND: Two common ways of assessing the clinical relevance of treatment outcomes are the minimal important difference (MID) and the patient acceptable symptom state (PASS). The former represents the smallest change in the given outcome that makes people feel better, while the latter is the symptom level at which patients feel well. METHODS: We recruited 124 patients with a humeral shaft fracture to a randomised controlled trial comparing surgery to nonsurgical care. Outcome instruments included the Disabilities of Arm, Shoulder, and Hand (DASH) score, the Constant-Murley score, and two numerical rating scales (NRS) for pain (at rest and on activities). A reduction in DASH and pain scores, and increase in the Constant-Murley score represents improvement. We used four methods (receiver operating characteristic [ROC] curve, the mean difference of change, the mean change, and predictive modelling methods) to determine the MID, and two methods (the ROC and 75th percentile) for the PASS. As an anchor for the analyses, we assessed patients' satisfaction regarding the injured arm using a 7-item Likert-scale. RESULTS: The change in the anchor question was strongly correlated with the change in DASH, moderately correlated with the change of the Constant-Murley score and pain on activities, and poorly correlated with the change in pain at rest (Spearman's rho 0.51, -0.40, 0.36, and 0.15, respectively). Depending on the method, the MID estimates for DASH ranged from -6.7 to -11.2, pain on activities from -0.5 to -1.3, and the Constant-Murley score from 6.3 to 13.5. The ROC method provided reliable estimates for DASH (-6.7 points, Area Under Curve [AUC] 0.77), the Constant-Murley Score (7.6 points, AUC 0.71), and pain on activities (-0.5 points, AUC 0.68). The PASS estimates were 14 and 10 for DASH, 2.5 and 2 for pain on activities, and 68 and 74 for the Constant-Murley score with the ROC and 75th percentile methods, respectively. CONCLUSION: Our study provides credible estimates for the MID and PASS values of DASH, pain on activities and the Constant-Murley score, but not for pain at rest. The suggested cut-offs can be used in future studies and for assessing treatment success in patients with humeral shaft fracture. TRIAL REGISTRATION: ClinicalTrials.gov NCT01719887, first registration 01/11/2012.