A new graph and scoring system simplified analysis of changing states: disease remissions in a rheumatoid arthritis clinical trial.

BACKGROUND: In the setting of multiple remission and relapse periods of a chronic disease, simple endpoint analysis does not fully capture all relevant information, and we need methods to additionally describe both the duration of remission as well as the interruptions in this desired state. Probably the two-state continuous Markov process model comprises the best mathematical approach to data analysis. However, this approach is complex and not intuitive to clinicians. In this paper we propose a simple scoring system and a graph that can enhance the information about the remission experience in a trial or cohort study. METHODS: The continuity rewarded ('ConRew') score sums up periods in remission, and rewards extended periods by placing more value on uninterrupted periods than on interrupted periods. The 'patient vector graph' attempts to plot each patient's remission experience over time as a horizontal line (the 'vector') that is visible when the patient is in remission, but interrupted whenever relapse occurs. In this way a pattern is formed that conveys the number of patients experiencing remission, their individual total duration and interruptions, and time when these occur. RESULTS: In a dataset of a randomized trial in early rheumatoid arthritis, the graph clearly showed both early and late benefit of one group over the other. The scoring system demonstrated the main benefit was in the number of remission periods, not in their 'uninterruptedness'. CONCLUSION: Both approaches proved feasible and added extra information.

Collaborative stepped care for anxiety disorders in primary care: aims and design of a randomized controlled trial.

BACKGROUND: Panic disorder (PD) and generalized anxiety disorder (GAD) are two of the most disabling and costly anxiety disorders seen in primary care. However, treatment quality of these disorders in primary care generally falls beneath the standard of international guidelines. Collaborative stepped care is recommended for improving treatment of anxiety disorders, but cost-effectiveness of such an intervention has not yet been assessed in primary care. This article describes the aims and design of a study that is currently underway. The aim of this study is to evaluate effects and costs of a collaborative stepped care approach in the primary care setting for patients with PD and GAD compared with care as usual. METHODS/DESIGN: The study is a two armed, cluster randomized controlled trial. Care managers and their primary care practices will be randomized to deliver either collaborative stepped care (CSC) or care as usual (CAU). In the CSC group a general practitioner, care manager and psychiatrist work together in a collaborative care framework. Stepped care is provided in three steps: 1) guided self-help, 2) cognitive behavioral therapy and 3) antidepressant medication. Primary care patients with a DSM-IV diagnosis of PD and/or GAD will be included. 134 completers are needed to attain sufficient power to show a clinically significant effect of 1/2 SD on the primary outcome measure, the Beck Anxiety Inventory (BAI). Data on anxiety symptoms, mental and physical health, quality of life, health resource use and productivity will be collected at baseline and after three, six, nine and twelve months. DISCUSSION: It is hypothesized that the collaborative stepped care intervention will be more cost-effective than care as usual. The pragmatic design of this study will enable the researchers to evaluate what is possible in real clinical practice, rather than under ideal circumstances. Many requirements for a high quality trial are being met. Results of this study will contribute to treatment options for GAD and PD in the primary care setting. Results will become available in 2011. TRIAL REGISTRATION: NTR1071.

Practical guidelines for economic evaluations alongside equivalence trials.

An effective treatment already exists for many diseases. In these cases the effectiveness of a new treatment may be established by showing that the new treatment is as effective as (i.e., equivalent to) or at least as effective as (i.e., noninferior to) the old treatment. For an economic evaluation accompanying a clinical equivalence or noninferiority trial it is important to decide before the start of the study on the appropriate research question. In many cases the objective of the economic evaluation will be to show equivalence or noninferiority of the cost-effectiveness of the treatments. This has major implications for the design and analysis of the economic evaluation. In this article we propose methods for the analysis of economic equivalence and noninferiority studies that are similar to the methods applied to clinical equivalence and noninferiority trials. Furthermore, cost-effectiveness planes prove to be a valuable tool in the interpretation of the results in an economic equivalence or noninferiority trial. The concepts described in the article are illustrated using the results from an economic noninferiority trial.

Surgery is more cost-effective than splinting for carpal tunnel syndrome in the Netherlands: results of an economic evaluation alongside a randomized controlled trial.

BACKGROUND: Carpal tunnel syndrome (CTS) is a common disorder, often treated with surgery or wrist splinting. The objective of this economic evaluation alongside a randomized trial was to evaluate the cost-effectiveness of splinting and surgery for patients with CTS. METHODS: Patients at 13 neurological outpatient clinics with clinically and electrophysiologically confirmed idiopathic CTS were randomly allocated to splinting (n = 89) or surgery (n = 87). Clinical outcome measures included number of nights waking up due to symptoms, general improvement, severity of the main complaint, paraesthesia at night and during the day, and utility. The economic evaluation was performed from a societal perspective and involved all relevant costs. RESULTS: There were no differences in costs. The mean total costs per patient were in the surgery group EURO 2,126 compared to EURO 2,111 in the splint group. After 12 months, the success rate in the surgery group (92%) was significantly higher than in the splint group (72%). The acceptability curve showed that at a relatively low ceiling ratio of EURO 2,500 per patient there is a 90% probability that surgery is cost-effective. CONCLUSION: In the Netherlands, surgery is more cost-effective compared with splinting, and recommended as the preferred method of treatment for patients with CTS.

Effectiveness and cost-effectiveness of early screening and treatment of malnourished patients.

BACKGROUND: About 25-40% of hospital patients are malnourished. With current clinical practices, only 50% of malnourished patients are identified by the medical and nursing staff. OBJECTIVE: The objective of this study was to report the cost and effectiveness of early recognition and treatment of malnourished hospital patients with the use of the Short Nutritional Assessment Questionnaire (SNAQ). DESIGN: The intervention group consisted of 297 patients who were admitted to 2 mixed medical and surgical wards and who received both malnutrition screening at admission and standardized nutritional care. The control group consisted of a comparable group of 291 patients who received the usual hospital clinical care. Outcome measures were weight change, use of supplemental drinks, use of tube feeding, use of parenteral nutrition and in-between meals, number of consultations by the hospital dietitian, and length of hospital stay. RESULTS: The recognition of malnutrition improved from 50% to 80% with the use of the SNAQ malnutrition screening tool during admission to the hospital. The standardized nutritional care protocol added approximately 600 kcal and 12 g protein to the daily intake of malnourished patients. Early screening and treatment of malnourished patients reduced the length of hospital stay in malnourished patients with low handgrip strength (ie, frail patients). To shorten the mean length of hospital stay by 1 d for all malnourished patients, a mean investment of 76 euros (91 US dollars) in nutritional screening and treatment was needed. The incremental costs were comparably low in the whole group and in the subgroup of malnourished patients with low handgrip strength. CONCLUSIONS: Screening with the SNAQ and early standardized nutritional care improves the recognition of malnourished patients and provides the opportunity to start treatment at an early stage of hospitalization. The additional costs of early nutritional care are low, especially in frail malnourished patients.

Are factor analytical techniques used appropriately in the validation of health status questionnaires? A systematic review on the quality of factor analysis of the SF-36.

Factor analysis is widely used to evaluate whether questionnaire items can be grouped into clusters representing different dimensions of the construct under study. This review focuses on the appropriate use of factor analysis. The Medical Outcomes Study Short Form-36 (SF-36) is used as an example. Articles were systematically searched and assessed according to a number of criteria for appropriate use and reporting. Twenty-eight studies were identified: exploratory factor analysis was performed in 22 studies, confirmatory factor analysis was performed in five studies and in one study both were performed. Substantial shortcomings were found in the reporting and justification of the methods applied. In 15 of the 23 studies in which exploratory factor analysis was performed, confirmatory factor analysis would have been more appropriate. Cross-validation was rarely performed. Presentation of the results and conclusions was often incomplete. Some of our results are specific for the SF-36, but the finding that both the application and the reporting of factor analysis leaves much room for improvement probably applies to other health status questionnaires as well. Optimal reporting and justification of methods is crucial for correct interpretation of the results and verification of the conclusions. Our list of criteria may be useful for journal editors, reviewers and researchers who have to assess publications in which factor analysis is applied.

Indirect and total costs of early rheumatoid arthritis: a randomized comparison of combined step-down prednisolone, methotrexate, and sulfasalazine with sulfasalazine alone.

OBJECTIVE: To describe the effect of indirect costs for patients with early rheumatoid arthritis (RA) within the COBRA trial (Combinatietherapie Bij Reumatoide Artritis) on the cost-effectiveness of both therapies. Analyses of the efficacy and direct costs of the treatments have already been reported. METHODS: Patients with early RA selected for the 56-week trial were randomly assigned to prednisolone, methotrexate, and sulfasalazine (the COBRA combination) (n = 76, tapered after 28 weeks) or to sulfasalazine (SSZ; n = 79, of which 78 patients were evaluable) alone. The main efficacy outcomes were a pooled index and radiographic damage score in hands and feet, and utilities. Direct and indirect costs were measured (from a societal perspective) by means of cost diaries and interviews completed by patients during the intervention phase and the followup phase, each lasting 28 weeks. Differences in mean costs between groups and cost-utility ratios were evaluated by applying nonparametric bootstrapping techniques. RESULTS: In the first 28 weeks, indirect costs per patient totaled US $2,578 and US $3,638 for COBRA and SSZ therapy, respectively (p = 0.09). The total costs were $5,931 and $7,853, respectively (p < 0.05). These differences were lost in the second 28 weeks. For the total period the mean total costs per patient were $10,262 and $12,788, respectively (p = 0.11). Sensitivity analyses showed robustness of the data. The point estimate of the cost per quality-adjusted life-year based on the rating scale was negative at $-385, suggesting dominance of COBRA (more effect at lower cost). CONCLUSION: COBRA therapy adds additional disease control (improvements in disease activity, physical function, and rate of damage progression) at lower or equal cost compared to SSZ in early RA.

Cost effectiveness of interventions for lateral epicondylitis: results from a randomised controlled trial in primary care.

OBJECTIVE: Lateral epicondylitis is a common complaint, with an annual incidence between 1% and 3% in the general population. The Dutch College of General Practitioners in The Netherlands has issued guidelines that recommend a wait-and-see policy. However, these guidelines are not evidence based. DESIGN AND SETTING: This paper presents the results of an economic evaluation in conjunction with a randomised controlled trial to evaluate the effects of three interventions in primary care for patients with lateral epicondylitis. PATIENTS AND INTERVENTIONS: Patients with pain at the lateral side of the elbow were randomised to one of three interventions: a wait-and-see policy, corticosteroid injections or physiotherapy. MAIN OUTCOME MEASURES AND RESULTS: Clinical outcomes included general improvement, pain during the day, elbow disability and QOL. The economic evaluation was conducted from a societal perspective. Direct and indirect costs (in 1999 values) were measured by means of cost diaries over a period of 12 months. Differences in mean costs between groups were evaluated by applying non-parametric bootstrap techniques. The mean total costs per patient for corticosteroid injections were euro430, compared with euro631 for the wait-and-see policy and euro921 for physiotherapy. After 12 months, the success rate in the physiotherapy group (91%) was significantly higher than in the injection group (69%), but only slightly higher than in the wait-and-see group (83%). The differences in costs and effects showed no dominance for any of the three groups. The incremental cost-utility ratios were (approximately): euro7000 per utility gain for the wait-and-see policy versus corticosteroid injections; euro12000 per utility gain for physiotherapy versus corticosteroid injections, and euro34500 for physiotherapy versus the wait-and-see policy. CONCLUSIONS: The results of this economic evaluation provided no reason to update or amend the Dutch guidelines for GPs, which recommend a wait-and-see policy for patients with lateral epicondylitis.

Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial.

OBJECTIVE: To evaluate the cost effectiveness of physiotherapy, manual therapy, and care by a general practitioner for patients with neck pain. DESIGN: Economic evaluation alongside a randomised controlled trial. SETTING: Primary care. PARTICIPANTS: 183 patients with neck pain for at least two weeks recruited by 42 general practitioners and randomly allocated to manual therapy (n=60, spinal mobilisation), physiotherapy (n=59, mainly exercise), or general practitioner care (n=64, counselling, education, and drugs). MAIN OUTCOME MEASURES: Clinical outcomes were perceived recovery, intensity of pain, functional disability, and quality of life. Direct and indirect costs were measured by means of cost diaries that were kept by patients for one year. Differences in mean costs between groups, cost effectiveness, and cost utility ratios were evaluated by applying non-parametric bootstrapping techniques. RESULTS: The manual therapy group showed a faster improvement than the physiotherapy group and the general practitioner care group up to 26 weeks, but differences were negligible by follow up at 52 weeks. The total costs of manual therapy (447 euro; 273 pounds sterling; 402 dollars) were around one third of the costs of physiotherapy (1297 euro) and general practitioner care (1379 euro). These differences were significant: P<0.01 for manual therapy versus physiotherapy and manual therapy versus general practitioner care and P=0.55 for general practitioner care versus physiotherapy. The cost effectiveness ratios and the cost utility ratios showed that manual therapy was less costly and more effective than physiotherapy or general practitioner care. CONCLUSIONS: Manual therapy (spinal mobilisation) is more effective and less costly for treating neck pain than physiotherapy or care by a general practitioner.

Cost effectiveness and cost utility of acetylcysteine versus dimethyl sulfoxide for reflex sympathetic dystrophy.

OBJECTIVE: To determine the cost effectiveness and cost utility of acetylcysteine versus dimethyl sulfoxide (DMSO) for patients with reflex sympathetic dystrophy (RSD), from a societal viewpoint. DESIGN: An economic evaluation was conducted alongside a double-dummy, double-blind, randomised, controlled trial. Patients were followed for 1 year. The primary outcome measure was the Impairment-level Sum Score (ISS). Utilities were determined by the EuroQOL instrument (EQ-5D). Both cost-effectiveness and cost-utility analyses were performed. Differences in mean direct, indirect and total costs were estimated. Corresponding 95% confidence intervals were calculated by bootstrapping techniques. RESULTS: Both groups (DMSO, n = 64; acetylcysteine, n = 67) showed relevant improvement; no differences in effects were found. Only the total direct costs were significantly lower in the DMSO group for the period of 0-52 weeks. The incremental cost-effectiveness ratios showed that, in general, DMSO generated fewer costs and more effects compared with acetylcysteine. Post-hoc subgroup analyses on cost effectiveness suggested that patients with warm RSD could be best treated with DMSO and patients with cold RSD with acetylcysteine. These results were based on small subsamples. CONCLUSION: In general, DMSO is the preferred treatment for patients with RSD.

[Retrospective assessment of the Dutch version of the Discomfort Scale--Dementia of Alzheimer Type (DS-DAT): is estimation sufficiently valid and reliable?]. / Retrospectieve afname van de Nederlandse versie van de Discomfort Scale--Dementia of Alzheimer type (DS-DAT): is inschatten achteraf voldoende valide en betrouwbaar?

The Discomfort Scale--Dementia of Alzheimer Type (DS-DAT) measures discomfort in severely demented patients with scores on nine items with behavioral descriptors. Direct observation of behaviour is the preferred method in severely demented patients, but is not feasible for some types of research. Alternatively, a patient's score may be assessed 'retrospectively', scoring an overall picture of the patient. To assess validity and reliability of such retrospective assessments, five observers--three nursing home physicians and two paramedicals--gave a DS-DAT score for 77 nursing home patients by direct observation, and, two weeks later, retrospectively. The mean score of the five observers was not different. The Intra-class Correlation Coefficient for intra-observer reliability was 0.50 for the five observers, and 0.55 for the three nursing home physicians. Our study demonstrated the possibility of a reasonably valid, but moderately reliable retrospective assessment of the Dutch version of the DS-DAT. Appropriate training of nursing home physicians who know their patients well may be required for this.

Reliability and validity of the assessment of depression in general practice: the Short Depression Interview (SDI).

General practitioners (GPs) are recommended to use DSM-IV criteria to diagnose major depression in daily clinical practice. This implies the assessment of nine depressive symptoms and four additional criteria. A short structured interview has been developed to assess these symptoms and criteria, and a study was carried out to investigate the reliability and validity with which GPs can assess these symptoms and criteria and the DSM-IV diagnosis of major depression. In 14 general practices, 52 patients with symptoms of distress and depression were interviewed twice by their GP, with an interval of one to four days. Furthermore, the patients filled out three depression questionnaires. The reproducibility of eight symptoms and three additional criteria was moderate to good (kappa >0.40). The reproducibility of the depressive symptom count, that is necessary to arrive at a diagnosis of major depression, was such that in 75 percent of the patients the test-retest difference did not exceed one symptom. The reproducibility of the diagnosis of major depression was good (kappa 0.63). The validity of the diagnosis of major depression assessed by the GPs, as compared to results of the self-report depression questionnaires, was satisfactory (r 0.35-0.61). Diagnosing major depression in patients with depressive symptomatology just above or below the threshold of major depression warrants a certain amount of caution in general practice.