Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial

Background Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges. Methods We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented). Results At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points. Conclusion In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes

Evaluation of the measurement properties of the Manchester foot pain and disability index

BACKGROUND: The Manchester Foot Pain and Disability Index (MFPDI, 19 items) was developed to measure functional limitations, pain and appearance for patients with foot pain and is frequently used in both observational studies and randomised controlled trials. A Dutch version of the MFPDI was developed. The aims of this study were to evaluate all the measurement properties for the Dutch version of the MFPDI and to evaluate comparability to the original version. METHOD: The MFPDI was translated into Dutch using a forward/backward translation process. The dimensionality was evaluated using exploratory and confirmatory factor analysis. Measurement properties were evaluated per subscale according to the COSMIN taxonomy consisting of: reliability (internal consistency, test-retest reliability and measurement error), validity (structural validity, content validity and cross-cultural validity comparing the Dutch version to the English version) responsiveness and interpretation. RESULTS: The questionnaire consists of three scales, measuring foot function, foot pain and perception. The reliability of the foot function scale is acceptable (Cronbach’s α > 0.7, ICC = 0.7, SEM = 2.2 on 0-18 scale). The construct validity of the function and pain scale was confirmed and only the pain scale contains one item with differential item functioning (DIF). The responsiveness of the function and pain scale is moderate when compared to anchor questions. CONCLUSION: Results using the Dutch MFPDI version can be compared to results using the original version. The foot function sub-scale (items 1-9) is a reliable and valid sub-scale. This study indicates that the use of the MFPDI as a longitudinal instrument might be problematic for measuring change in musculoskeletal foot pain due to moderate responsiveness

The COSMIN checklist for evaluating the methodological quality of studies on measurement properties: A clarification of its content

<p>Abstract</p> <p>Background</p> <p>The COSMIN checklist (COnsensus-based Standards for the selection of health status Measurement INstruments) was developed in an international Delphi study to evaluate the methodological quality of studies on measurement properties of health-related patient reported outcomes (HR-PROs). In this paper, we explain our choices for the design requirements and preferred statistical methods for which no evidence is available in the literature or on which the Delphi panel members had substantial discussion.</p> <p>Methods</p> <p>The issues described in this paper are a reflection of the Delphi process in which 43 panel members participated.</p> <p>Results</p> <p>The topics discussed are internal consistency (relevance for reflective and formative models, and distinction with unidimensionality), content validity (judging relevance and comprehensiveness), hypotheses testing as an aspect of construct validity (specificity of hypotheses), criterion validity (relevance for PROs), and responsiveness (concept and relation to validity, and (in) appropriate measures).</p> <p>Conclusions</p> <p>We expect that this paper will contribute to a better understanding of the rationale behind the items, thereby enhancing the acceptance and use of the COSMIN checklist.</p

Inter-observer reproducibility of measurements of range of motion in patients with shoulder pain using a digital inclinometer

BACKGROUND: Reproducible measurements of the range of motion are an important prerequisite for the interpretation of study results. The digital inclinometer is considered to be a useful instrument because it is inexpensive and easy to use. No previous study assessed inter-observer reproducibility of range of motion measurements with a digital inclinometer by physical therapists in a large sample of patients. METHODS: Two physical therapists independently measured the passive range of motion of the glenohumeral abduction and the external rotation in 155 patients with shoulder pain. Agreement was quantified by calculation of the mean differences between the observers and the standard deviation (SD) of this difference and the limits of agreement, defined as the mean difference ± 1.96*SD of this difference. Reliability was quantified by means of the intraclass correlation coefficient (ICC). RESULTS: The limits of agreement were 0.8 ± 19.6 for glenohumeral abduction and -4.6 ± 18.8 for external rotation (affected side) and quite similar for the contralateral side and the differences between sides. The percentage agreement within 10° for these measurements were 72% and 70% respectively. The ICC ranged from 0.28 to 0.90 (0.83 and 0.90 for the affected side). CONCLUSIONS: The inter-observer agreement was found to be poor. If individual patients are assessed by two different observers, differences in range of motion of less than 20–25 degrees can not be distuinguished from measurement error. In contrast, acceptable reliability was found for the inclinometric measurements of the affected side and the differences between the sides, indicating that the inclimeter can be used in studies in which groups are compared

Prediction of persistent shoulder pain in general practice: Comparing clinical consensus from a Delphi procedure with a statistical scoring system

<p>Abstract</p> <p>Background</p> <p>In prognostic research, prediction rules are generally statistically derived. However the composition and performance of these statistical models may strongly depend on the characteristics of the derivation sample. The purpose of this study was to establish consensus among clinicians and experts on key predictors for persistent shoulder pain three months after initial consultation in primary care and assess the predictive performance of a model based on clinical expertise compared to a statistically derived model.</p> <p>Methods</p> <p>A Delphi poll involving 3 rounds of data collection was used to reach consensus among health care professionals involved in the assessment and management of shoulder pain.</p> <p>Results</p> <p>Predictors selected by the expert panel were: symptom duration, pain catastrophizing, symptom history, fear-avoidance beliefs, coexisting neck pain, severity of shoulder disability, multisite pain, age, shoulder pain intensity and illness perceptions. When tested in a sample of 587 primary care patients consulting with shoulder pain the predictive performance of the two prognostic models based on clinical expertise were lower compared to that of a statistically derived model (Area Under the Curve, AUC, expert-based dichotomous predictors 0.656, expert-based continuous predictors 0.679 vs. 0.702 statistical model).</p> <p>Conclusions</p> <p>The three models were different in terms of composition, but all confirmed the prognostic importance of symptom duration, baseline level of shoulder disability and multisite pain. External validation in other populations of shoulder pain patients should confirm whether statistically derived models indeed perform better compared to models based on clinical expertise.</p

Prevalence of complaints of arm, neck and shoulder among computer office workers and psychometric evaluation of a risk factor questionnaire

<p>Abstract</p> <p>Background</p> <p>Complaints of Arm Neck and Shoulder (CANS) represent a wide range of complaints, which can differ in severity from mild, periodic symptoms to severe, chronic and debilitating conditions. They are thought to be associated with both physical and psychosocial risk factors. The measurement and identification of the various risk factors for these complaints is an important step towards recognizing (a) high risk subgroups that are relevant in profiling CANS; and (b) also for developing targeted and effective intervention plans for treatment. The purpose of the present study was to investigate the prevalence of CANS in a Dutch population of computer workers and to develop a questionnaire aimed at measuring workplace physical and psychosocial risk factors for the presence of these complaints.</p> <p>Methods</p> <p>To examine potential workplace risk factors for the presence of CANS, the Maastricht Upper Extremity Questionnaire (MUEQ), a structured questionnaire, was developed and tested among 264 computer office workers of a branch office of the national social security institution in the Netherlands. The MUEQ holds 95 items covering demographic characteristics, in addition to seven main domains assessing potential risk factors with regard to (1) work station, (2) posture during work, (3) quality of break time, (4) job demands, (5) job control, and (6) social support. The MUEQ further contained some additional questions about the quality of the work environment and the presence of complaints in the neck, shoulder, upper and lower arm, elbow, hand and wrist. The prevalence rates of CANS in the past year were computed. Further, we investigated the psychometric properties of the MUEQ (i.e. factor structure and reliability).</p> <p>Results</p> <p>The one-year prevalence rate of CANS indicated that 54% of the respondents reported at least one complaint in the arm, neck and/or shoulder. The highest prevalence rates were found for neck and shoulder symptoms (33% and 31% respectively), followed by hand and upper arm complaints (11% to 12%) and elbow, lower arm and wrist complaints (6% to 7%). The psychometric properties of the MUEQ were assessed using exploratory factor analysis which resulted in the identification of 12 factors. The calculation of internal consistency and cross validation provided evidence of reliability and lack of redundancy of items.</p> <p>Conclusion</p> <p>Neck and shoulder complaints are more frequently reported among Dutch computer workers than arm, elbow and hand complaints. The results further indicate that the MUEQ has satisfactory reliability and internal consistency when used to document CANS among computer workers in the Netherlands.</p

Cost-effectiveness of an intensive group training protocol compared to physiotherapy guideline care for sub-acute and chronic low back pain: design of a randomised controlled trial with an economic evaluation. [ISRCTN45641649]

BACKGROUND: Low back pain is a common disorder in western industrialised countries and the type of treatments for low back pain vary considerably. METHODS: In a randomised controlled trial the cost-effectiveness and cost-utility of an intensive group training protocol versus physiotherapy guideline care for sub-acute and chronic low back pain patients is evaluated. Patients with back pain for longer than 6 weeks who are referred to physiotherapy care by their general practitioner or medical specialist are included in the study. The intensive group training protocol combines exercise therapy with principles of behavioural therapy ("graded activity") and back school. This training protocol is compared to physiotherapy care according to the recently published Low Back Pain Guidelines of the Royal Dutch College for Physiotherapy. Primary outcome measures are general improvement, pain intensity, functional status, work absenteeism and quality of life. The direct and indirect costs will be assessed using cost diaries. Patients will complete questionnaires at baseline and 6, 13, 26 and 52 weeks after randomisation. DISCUSSION: No trials are yet available that have evaluated the effect of an intensive group training protocol including behavioural principles and back school in a primary physiotherapy care setting and no data on cost-effectiveness and cost-utility are available

Variable selection under multiple imputation using the bootstrap in a prognostic study

Background: Missing data is a challenging problem in many prognostic studies. Multiple imputation (MI) accounts for imputation uncertainty that allows for adequate statistical testing. We developed and tested a methodology combining MI with bootstrapping techniques for studying prognostic variable selection. Method: In our prospective cohort study we merged data from three different randomized controlled trials (RCTs) to assess prognostic variables for chronicity of low back pain. Among the outcome and prognostic variables data were missing in the range of 0 and 48.1%. We used four methods to investigate the influence of respectively sampling and imputation variation: MI only, bootstrap only, and two methods that combine MI and bootstrapping. Variables were selected based on the inclusion frequency of each prognostic variable, i.e. the proportion of times that the variable appeared in the model. The discriminative and calibrative abilities of prognostic models developed by the four methods were assessed at different inclusion levels. Results: We found that the effect of imputation variation on the inclusion frequency was larger than the effect of sampling variation. When MI and bootstrapping were combined at the range of 0% (full model) to 90% of variable selection, bootstrap corrected c-index values of 0.70 to 0.71 and slope values of 0.64 to 0.86 were found. Conclusion: We recommend to account for both imputation and sampling variation in sets of missing data. The new procedure of combining MI with bootstrapping for variable selection, results in multivariable prognostic models with good performance and is therefore attractive to apply on data sets with missing values

Information and feedback to improve occupational physicians’ reporting of occupational diseases: a randomised controlled trial

To assess the effectiveness of supplying occupational physicians (OPs) with targeted and stage-matched information or with feedback on reporting occupational diseases to the national registry in the Netherlands. In a randomized controlled design, 1076 OPs were divided into three groups based on previous reporting behaviour: precontemplators not considering reporting, contemplators considering reporting and actioners reporting occupational diseases. Precontemplators and contemplators were randomly assigned to receive stage-matched, stage-mismatched or general information. Actioners were randomly assigned to receive personalized or standardized feedback upon notification. Outcome measures were the number of OPs reporting and the number of reported occupational diseases in a 180-day period before and after the intervention. Precontemplators were significantly more male and self-employed compared to contemplators and actioners. There was no significant effect of stage-matched information versus stage-mismatched or general information on the percentage of reporting OPs and on the mean number of notifications in each group. Receiving any information affected reporting more in contemplators than in precontemplators. The mean number of notifications in actioners increased more after personalized feedback than after standardized feedback, but the difference was not significant. This study supports the concept that contemplators are more susceptible to receiving information but could not confirm an effect of stage-matching this information on reporting occupational diseases to the national registr