The minimal clinically important difference raised the significance of outcome effects above the statistical level, with methodological implications for future studies

OBJECTIVE To illustrate and discuss current and proposed new concepts of effect size (ES) quantification and significance, with a focus on statistical and clinical/subjective interpretation and supported by empirical examples. STUDY DESIGN AND SETTINGS Different methods for determining minimal clinically important differences (MCIDs) are reviewed, applied to practical examples (pain score differences in knee osteoarthritis), and further developed. Their characteristics, advantages, and disadvantages are illustrated and discussed. RESULTS Empirical score differences between verum and placebo become statistically significant if sample sizes are sufficiently large. MCIDs, by contrast, are defined by patients' perceptions. MCIDs obtained by the most common "mean change method" can be expressed as absolute or relative scores, as different ES parameters, and as the optimal cutoff point on the receiver operating characteristic curve. They can further be modeled by linear and logistic regression, adjusting for potential confounders. CONCLUSION Absolute and relative MCIDs are easy to interpret and apply to data of investigative studies. MCIDs expressed as effect sizes reduce bias, which mainly results from dependency on the baseline score. Multivariate linear and logistic regression modeling further reduces bias. Anchor-based methods use clinical/subjective perception to define MCIDs and should be clearly differentiated from distribution-based methods that provide statistical significance only

Multidimensional minimal clinically important differences in knee osteoarthritis after comprehensive rehabilitation: a prospective evaluation from the Bad Zurzach Osteoarthritis Study

OBJECTIVE To determine minimal clinically important differences (MCIDs) for improvement and worsening in various health dimensions in knee osteoarthritis under conservative therapy. METHODS Health, symptoms and function were assessed by the generic Short Form 36 and the condition-specific Western Ontario and McMaster Universities Osteoarthritis Index in n=190 patients with knee osteoarthritis before and after comprehensive rehabilitation intervention (3-month follow-up). By means of construct-specific transition questions, MCIDs were defined as the difference between the 'slightly better/worse' and the 'almost equal' transition response categories according to the 'mean change method'. The bivariate MCIDs were adjusted for sex, age and baseline score to obtain adjusted MCIDs by multivariate linear regression. They were further standardised as (baseline) effect sizes (ESs), standardised response means (SRMs) and standardised mean differences (SMDs) and compared with the minimal detectable change with 95% confidence (MDC95). RESULTS Multivariate, adjusted MCIDs for improvement ranged from 2.89 to 16.24 score points (scale 0-100), corresponding to ES=0.14 to 0.63, SRM=0.17 to 0.61 and SMD=0.18 to 0.72. The matching results for worsening were -5.80 to -12.68 score points, ES=-0.30 to -0.56, SRM=-0.35 to -0.52 and SMD=-0.35 to -0.58. Almost all MCIDs were larger than the corresponding MDC95s. CONCLUSIONS This study presents MCIDs quantified according to different methods over a comprehensive range of health dimensions. In most health dimensions, multivariate adjustment led to higher symmetry between the MCID levels of improvement and worsening. MCIDs expressed as standardised effect sizes (ES, SRM, SMD) and adjusted by potential confounders facilitate generalisation to the results of other studies

Responsiveness of five condition-specific and generic outcome assessment instruments for chronic pain

<p>Abstract</p> <p>Background</p> <p>Changes of health and quality-of-life in chronic conditions are mostly small and require specific and sensitive instruments. The aim of this study was to determine and compare responsiveness, i.e. the sensitivity to change of five outcome instruments for effect measurement in chronic pain.</p> <p>Methods</p> <p>In a prospective cohort study, 273 chronic pain patients were assessed on the Numeric Rating Scale (NRS) for pain, the Short Form 36 (SF-36), the Multidimensional Pain Inventory (MPI), the Hospital Anxiety and Depression Scale (HADS), and the Coping Strategies Questionnaire (CSQ). Responsiveness was quantified by effect size (ES) and standardized response mean (SRM) before and after a four week in-patient interdisciplinary pain program and compared by the modified Jacknife test.</p> <p>Results</p> <p>The MPI measured pain more responsively than the SF-36 (ES: 0.85 vs 0.72, p = 0.053; SRM: 0.72 vs 0.60, p = 0.027) and the pain NRS (ES: 0.85 vs 0.62, p < 0.001; SRM: 0.72 vs 0.57, p = 0.001). Similar results were found for the dimensions of role and social interference with pain. Comparison in function was limited due to divergent constructs. The responsiveness of the MPI and the SF-36 was equal for affective health but both were better than the HADS (e.g. MPI vs HADS depression: ES: 0.61 vs 0.43, p = 0.001; SF-36 vs HADS depression: ES: 0.54 vs 0.43, p = 0.004). In the "ability to control pain" coping dimension, the MPI was more responsive than the CSQ (ES: 0.46 vs 0.30, p = 0.011).</p> <p>Conclusion</p> <p>The MPI was most responsive in all comparable domains followed by the SF-36. The pain-specific MPI and the generic SF-36 can be recommended for comprehensive and specific bio-psycho-social effect measurement of health and quality-of-life in chronic pain.</p

Comprehensiveness and validity of a multidimensional assessment in patients with chronic low back pain: a prospective cohort study

Background: Chronic low back pain is a multidimensional syndrome affecting physical activity and function, health-related quality of life and employment status. The aim of the study was to quantify the cross-sectional and longitudinal validity of single measurement scales in specific construct domains and to examine how they combine to build a comprehensive outcome, covering the complex construct of chronic low back pain before and after a standardized interdisciplinary pain program. Methods: This prospective cohort study assessed 177 patients using the Short Form 36 (SF-36), the Multidimensional Pain Inventory (MPI), the Symptom Checklist-90-Revised (SCL-90-R), the Oswestry Disability Index (ODI), and 2 functional performance tests, the Back Performance Scale (BPS) and the 6-Minute Walking Distance (6MWD). The comprehensiveness and overlap of the constructs used were quantified cross-sectionally and longitudinally by bivariate correlations, exploratory factor analysis, and effect sizes. Results: The mean age of the participants was 48.0 years (+/− 12.7); 59.3% were female. Correlations of baseline scores ranged from r = − 0.01 (BPS with MPI Life control) to r = 0.76 (SF-36 Mental health with MPI Negative mood). SF-36 Physical functioning correlated highest with the functional performance tests (r = 0.58 BPS, 0.67 6MWD) and ODI (0.56). Correlations of change scores (difference of follow-up – baseline score) were consistent but weaker. Factor analysis revealed 2 factors: “psychosocial” and “pain & function” (totally explained variance 44.0–60.9%). Psychosocial factors loaded strongest (up to 0.89 SCL-90-R) on the first factor, covering 2/3 of the explained variance. Pain and function (ing) loaded more strongly on the second factor (up to 0.81 SF-36 Physical functioning at follow-up). All scales showed improvements, with effect sizes ranging from 0.16–0.67. Conclusions: Our results confirm previous findings that the chronic low back pain syndrome is highly multifactorial and comprises many more dimensions of health and quality of life than merely back-related functioning. A comprehensive outcome measurement should include the predominant psychosocial domain and a broad spectrum of measurement constructs in order to assess the full complexity of the chronic low back syndrome. Convergence and divergence of the scales capture the overlapping contents and nuances within the constructs

Mortality of 403 patients with mood disorders 48 to 52years after their psychiatric hospitalisation

The purpose is to analyse differences in mortality among patients with major depressive disorders (MDD), bipolar-II (BP-II), bipolar-I (BP-I) disorders and mania with or without minor depressive disorders and to identify risk factors of mortality. The sample represents all admissions for depression or mania over 5years (1959-1963) to the Psychiatric Hospital of Zurich University, serving a large area. 403 patients were included and followed up every 5years until 1985; thereafter, mortality data were collected repeatedly until 2009 when 352 (87%) patients had died. Standardised mortality ratios (SMRs) were computed and survival analyses applied. With the exception of BP-II disorder, the three other diagnostic groups showed elevated SMRs. The group with mania had the highest SMR for cardiovascular deaths and the group with MDD the highest for deaths by suicide. Mortality was also high among patients with late-onset MDD. Across the diagnostic spectrum, we found differences in risk factors for mortality, such as a family history of suicides and personality type: more anxious patients with MDD lived longer, and among patients with BP disorders, more tense (aggressive) types had shorter lives. Long-term medication had a protective effect against mortality in patients with MDD during years 1-9 and in patients with BP disorders during years 1-19 after admission. We found marked differences in causes of death and risk factors between subgroups of mood disorders. For the purpose of further research, it would be recommendable to distinguish pure mania from bipolar disorder

Mortality of 403 patients with mood disorders 48 to 52 years after their psychiatric hospitalisation

The purpose is to analyse differences in mortality among patients with major depressive disorders (MDD), bipolar-II (BP-II), bipolar-I (BP-I) disorders and mania with or without minor depressive disorders and to identify risk factors of mortality. The sample represents all admissions for depression or mania over 5 years (1959-1963) to the Psychiatric Hospital of Zurich University, serving a large area. 403 patients were included and followed up every 5 years until 1985; thereafter, mortality data were collected repeatedly until 2009 when 352 (87 %) patients had died. Standardised mortality ratios (SMRs) were computed and survival analyses applied. With the exception of BP-II disorder, the three other diagnostic groups showed elevated SMRs. The group with mania had the highest SMR for cardiovascular deaths and the group with MDD the highest for deaths by suicide. Mortality was also high among patients with late-onset MDD. Across the diagnostic spectrum, we found differences in risk factors for mortality, such as a family history of suicides and personality type: more anxious patients with MDD lived longer, and among patients with BP disorders, more tense (aggressive) types had shorter lives. Long-term medication had a protective effect against mortality in patients with MDD during years 1-9 and in patients with BP disorders during years 1-19 after admission. We found marked differences in causes of death and risk factors between subgroups of mood disorders. For the purpose of further research, it would be recommendable to distinguish pure mania from bipolar disorders

Relationship between subjectively-rated and objectively-tested physical function across six different medical diagnoses

Objective: To quantify and compare associations and relationships between self-rated and tested assessments of mainly mobility-related physical function in different diagnoses. Design: Six longitudinal cohort studies before and after inpatient rehabilitation. Patients: Patients with whiplash-associated disorder (n = 71), low back pain (n = 121), fibromyalgia (n = 84), lipoedema (n = 27), lymphoedema (n = 78), and post-acute coronary syndrome (n = 64). Methods: Physical function was measured with the self-rated Short-Form 36 Physical functioning (SF-36 PF) and with the tested 6-Min Walk Distance (6MWD) and assessed by correlation coefficients. Across the 6 cohorts, the relationship between the 2 scores was compared using the ratio between them. Results: The correlations between the 2 scores were mostly moderate to strong at baseline (up to r = 0.791), and weak to moderate for the changes to follow-up (up to r = 0.408). The ratios SF-36 PF to 6MWD were 1.143–1.590 at baseline and 0.930–3.310 for the changes, and depended on pain and mental health. Conclusion: Moderate to strong cross-sectional and moderate to weak longitudinal correlations were found between the 6MWD and the SF-36 PF. Pain and mental health should be considered when interpreting physical function. For a comprehensive assessment in clinical practice and research, the combination of self-rated and tested physical function measures is recommended

The new COSMIN guidelines confront traditional concepts of responsiveness

The recently published "COSMIN" guidelines aim to rate properties of outcome instruments and state two issues with regard to responsiveness which is the instrument's ability to detect change over time. These issues are comparison of score changes with change of an external criterion using correlations and the judgement of traditional methods as inappropriate. The latter are the "transition" concept, a global rating of change, and parametric measures of responsiveness, for example, effect sizes. It can be shown that the methodology proposed by the guidelines has important weaknesses and that denunciation of traditional methods is not appropriate. Some claims of the guidelines about responsiveness do not match the demands of clinical reality and confront findings of numerous epidemiological studies