Mind the MIC: large variation among populations and methods

ObjectiveThere is no consensus on the best method to determine the minimal important change (MIC) of patient-reported outcomes. Recent publications recommend the use of multiple methods. Our aim was to assess whether different methods lead to consistent values for the MIC.Study Design and SettingWe used two commonly used anchor-based methods and three commonly used distribution-based methods to determine the MIC of the subscales: pain and physical functioning of the Western Ontario and McMaster University Osteoarthritis Index questionnaire in five different studies involving patients with hip or knee complaints. We repeated the anchor-based methods using relative change scores, to adjust for baseline scores.ResultsWe found large variation in MIC values by the same method across studies and across different methods within studies. We consider it unlikely that this variation can be explained by differences between disease groups, disease severity, or lengths of follow-up. The variation persisted when using relative change scores. It was not possible to conclude whether this variation is because of true differences in MIC values between populations or to conceptual and methodological problems of the MIC methods.ConclusionTo better disentangle these two possible explanations, the MIC methodology should be improved and standardized. In the meantime, caution is needed when interpreting and using published MIC values.     

Definition of the construct to be measured is a prerequisite for the assessment of validity. The Neck Disability Index as an example

ObjectiveTo determine the content, structural, and construct validity of the Dutch version of the Neck Disability Index (NDI).Study Design and SettingTo assess content validity, 11 neck pain experts and 10 patients commented on the construct, comprehensiveness, and relevance of the NDI. Structural validity was assessed by item factor analysis (FA) and item response theory modeling using the generalized partial credit model. Differential item functioning (DIF) analysis for gender was examined. Pearson correlation coefficient with the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was calculated to assess construct validity.ResultsIn addition to a suboptimal translation, we found a lack of consensus on the construct the NDI intends to measure. Experts and patients suggested that the NDI measures more than physical functioning. Unidimensionality of the NDI could not be confirmed. DIF analysis for gender showed DIF for the headache item. The goodness-of-fit statistics for FA with one factor were satisfactory when the item “concentration” was omitted. A correlation of 0.75 with the DASH was found supporting construct validity.ConclusionIt is questionable whether in research the NDI should be the instrument of choice for use as a primary outcome measure. Definition of the construct to be measured is a prerequisite for the assessment of validity.     

Course and prognosis of elbow complaints: a cohort study in general practice

OBJECTIVE: To describe the course of new episodes of elbow complaints in general practice, and to identify predictors of short term and long term outcome in terms of pain intensity and functional disability. METHODS: 181 patients with elbow complaints filled in questionnaires at baseline and at 3, 6, and 12 months of follow up. Baseline scores of pain and disability, characteristics of the complaint, sociodemographic and psychosocial factors, physical activity, general health, and comorbidity were investigated as possible predictors of outcome. Outcome measures were analysed separately using multiple regression analyses. RESULTS: 13% of the patients reported recovery at the 3 month follow up and 34% at 12 months. Irrespective of outcome and length of follow up, a longer duration of the complaint before consulting the general practitioner, having musculoskeletal comorbidity, and using "retreating" as coping style increased the likelihood of an unfavourable outcome. Less social support was associated with an unfavourable outcome at 3 months, and having a history of elbow complaints and using "worrying" as coping style were associated with an unfavourable outcome at 12 months. The explained variance of the models ranged from 46% to 49%. CONCLUSIONS: Recovery of patients with elbow complaints in general practice was poor. Besides characteristic of the complaint, passive coping and less social support were related to a worse prognosis. The results of this study may help general practitioners to provide patients with more accurate information about their prognosis.     

Simulated effect of pneumococcal vaccination in the Netherlands on existing rules constructed in a non-vaccinated cohort predicting sequelae after bacterial meningitis

Background  

Previously two prediction rules identifying children at risk of hearing loss and academic or behavioral limitations after bacterial meningitis were developed. Streptococcus pneumoniae as causative pathogen was an important risk factor in both. Since 2006 Dutch children receive seven-valent conjugate vaccination against S. pneumoniae. The presumed effect of vaccination was simulated by excluding all children infected by S. pneumoniae with the serotypes included in the vaccine, from both previous collected cohorts (between 1990-1995).     

Profound differences in virus population genetics correspond to protection from CD4 decline resulting from feline lentivirus coinfection

CD4 decline is a hallmark of disease onset in individuals infected with Feline Immunodeficiency Virus (FIV) or Human Immunodeficiency Virus type 1 (HIV-1). Cats that are infected with a poorly replicating, apathogenic FIV (PLV) prior to exposure to a virulent FIV strain (FIVC) maintain CD4 numbers by mechanisms that are not correlated with a measurable adaptive immune response or reduction in circulating viral load. We employed population genetic approaches based on the 3' portion of the viral genome to estimate the population structure of FIVC from single and dual infected cats. In dual infected cats, FIVC effective population size was decreased during the initial viral expansion phase, and after three weeks of infection, the population declined sharply. The FIVC population recovered to pre-bottleneck levels approximately seven weeks post-FIVC infection. However, the population emerging from the bottleneck in dual infected cats was distinct based on estimates of temporal population structure and substitution profiles. The transition to transversion rate ratio (κ) increased from early to late phases in dual infected cats due primarily to a decrease in transversions whereas in single infected cats, κ declined over time. Although one clone with extensive G to A substitutions, indicative of host cytidine deaminase editing, was recovered from a dual infected cat during the bottleneck, the post bottleneck population had an overall reduction in G to A substitutions. These data are consistent with a model of PLV-induced host restriction, putatively involving host DNA editing, that alters the dynamics of FIVC throughout the course of infection leading to disease attenuation.     

Linking measurement error to minimal important change of patient-reported outcomes

ObjectiveTo provide a practical example showing how to relate measurement error to minimal important change (MIC) to estimate sample sizes required for detecting important changes in research, and to determine the usefulness of patient-reported outcomes (PROs) in daily clinical practice.Study Design and SettingThe standard error of measurement (SEM) can be calculated as a parameter of measurement error. MIC can be determined by taking the mean change in score on the questionnaire in the subgroup of patients that reported to be “a little better” or “better” on a global rating scale minus the mean change in score in the subgroup of patients that reported to be “not changed.” Based on SEM and MIC, formulas are presented that can be used to estimate sample sizes and to determine whether the questionnaire can be used to monitor changes in individual patients in daily clinical practice.ResultsA fully worked-out example is presented, using Western Ontario and McMaster University Osteoarthritis Index data from a cohort of patients undergoing hip or knee replacement.ConclusionWe strongly recommend investigators to present the SEM and MIC of PROs and use these to estimate sample sizes for research and to determine the usefulness of these outcomes in daily clinical practice.