Conceptual model for the health technology assessment of current and novel interventions in rheumatoid arthritis

The objective of this study was to evaluate current approaches to economic modeling in rheumatoid arthritis (RA) and propose a new conceptual model for evaluation of the cost-effectiveness of RA interventions. We followed recommendations from the International Society of Pharmacoeconomics and Outcomes Research-Society of Medical Decision Making (ISPOR-SMDM) Modeling Good Research Practices Task Force-2. The process involved scoping the decision problem by a working group and drafting a preliminary cost-effectiveness model framework. A systematic literature review (SLR) of existing decision-analytic models was performed and analysis of an RA registry was conducted to inform the structure of the draft conceptual model. Finally, an expert panel was convened to seek input on the draft conceptual model. The proposed conceptual model consists of three separate modules: 1) patient characteristic module, 2) treatment module, and 3) outcome module. Consistent with the scope, the conceptual model proposed six changes to current economic models in RA. These changes proposed are to: 1) use composite measures of disease activity to evaluate treatment response as well as disease progression (at least two measures should be considered, one as the base case and one as a sensitivity analysis); 2) conduct utility mapping based on disease activity measures; 3) incorporate subgroups based on guideline-recommended prognostic factors; 4) integrate realistic treatment patterns based on clinical practice/registry datasets; 5) assimilate outcomes that are not joint related (extra-articular outcomes); and 6) assess mortality based on disease activity. We proposed a conceptual model that incorporates the current understanding of clinical and real-world evidence in RA, as well as of existing modeling assumptions. The proposed model framework was reviewed with experts and could serve as a foundation for developing future cost-effectiveness models in RA

Non-pharmacological interventions to promote work participation in people with rheumatic and musculoskeletal diseases: a systematic review and meta-analysis from the EULAR taskforce on healthy and sustainable work participation

Objective To summarise the evidence on effectiveness of non-pharmacological (ie, non-drug, non-surgical) interventions on work participation (sick leave, work status and presenteeism) in people with rheumatic and musculoskeletal diseases (RMDs). Methods A systematic review of randomised controlled trials (RCTs) and longitudinal observational studies (LOS) was performed. Qualitative (RCTs/LOS) and quantitative (RCTs) evidence syntheses were conducted. Mixed-effects restricted maximum likelihood models were used to combine effect estimates, using standardised mean differences (SMDs) as the summary measure for each outcome domain separately, with a negative SMD favouring the intervention over comparator. Subgroup analyses were performed for type of RMD, risk status at baseline regarding adverse work outcomes and intervention characteristics. Results Of 10 153 records, 64 studies (37 RCTs and 27 LOS; corresponding to k=71 treatment comparisons) were included. Interventions were mostly conducted in clinical settings (44 of 71, 62%). Qualitative synthesis suggested clear beneficial effects of 7 of 64 (11%) interventions for sick leave, 1 of 18 (6%) for work status and 1 of 17 (6%) for presenteeism. Quantitative synthesis (37 RCTs; k=43 treatment comparisons) suggested statistically significant but only small clinical effects on each outcome (SMDsick leave (95% CI)=−0.23 (−0.33 to −0.13; k=42); SMDwork status=−0.38 (−0.63 to −0.12; k=9); SMDpresenteeism=−0.25 (−0.39 to −0.12; k=13)). Conclusion In people with RMDs, empirical evidence shows that non-pharmacological interventions have small effects on work participation. Effectiveness depends on contextual factors such as disease, population risk status, intervention characteristics and outcome of interest, highlighting the importance of tailoring interventions

De Nederlandse 'health assessment questionnaire': consensus bereikt.

Contains fulltext : 50377.pdf (publisher's version ) (Open Access

In patients with early rheumatoid arthritis, the new ACR/EULAR definition of remission identifies patients with persistent absence of functional disability and suppression of ultrasonographic synovitis

To test the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and disease activity score in 44 and 28 joints (DAS, DAS28) definitions of remission in early rheumatoid arthritis (RA), against disability and ultrasound-detectable synovitis.In an observational study of early RA patients, remission rates were determined and compared in 166 patients. The remission definitions included the simplified disease activity index (SDAI 643.3), ACR/EULAR (categorical), DAS28 (<2.6) and DAS (<1.6). The health assessment questionnaire (HAQ) was completed at baseline and 12 months, power Doppler-positive synovitis (PDPS) was assessed at baseline, 6 and 12 months. Cross-sectionally, the outcomes were low functional disability (HAQ 640.5) or absent PDPS in all joints, while longitudinally the outcomes were stable low functional disability and persistent absent PDPS in all joints.At baseline, 33.7% of patients achieved DAS28 remission, 43.37% DAS remission, 16.8% SDAI remission, 13.8% ACR/EULAR remission. DAS28, SDAI and ACR/EULAR remission was cross-sectionally associated with low functional disability and absent PDPS. All definitions were longitudinally associated with low functional disability: positive likelihood ratios (LR+) of 3.24 for DAS28, 2.14 for DAS, 4.86 for SDAI, 5.67 for ACR/EULAR criteria, and with absent PDPS for DAS28 (LR+ 1.66), SDAI (LR+ 6.46), ACR/EULAR (LR+ 5.07).The new remission definitions confirmed their validity in an observational setting and identify patients with better disease control

External beam radiotherapy with endocavitary boost for nasopharyngeal cancer: treatment results and late toxicity after extended follow-up.

PURPOSE: To evaluate the long-term outcome after treatment of nasopharyngeal carcinoma and assess late toxicity in a multidisciplinary clinic. METHODS AND MATERIALS: A retrospective analysis of 117 patients treated for nasopharyngeal cancer in a single institute between 1985 and 2002 was performed. Fifty-one long-term survivors were evaluated for late toxicity by a multidisciplinary team comprising a radiation oncologist, otolaryngologist, neurologist, and oral and maxillofacial surgeon. RESULTS: The 5-year local control rate for T1 to T2 and T3 to T4 tumors was 97% and 76%, respectively. Five-year disease-free survival and overall survival were 82% and 88% for Stage I to IIb disease and 46% and 52% for Stage III to IVb, respectively. Late morbidity evaluation revealed Radiation Therapy Oncology Group (RTOG) Grade III to IV toxicity in 71% of patients. A high incidence of cranial nerve palsies (47%) and mandibular osteolysis (82%) was found, although these complications had limited clinical impact. CONCLUSIONS: The multidisciplinary late morbidity clinic revealed an unexpected high incidence of cranial nerve palsies and mandibular osteolysis and overall an RTOG Grade III to IV toxicity in 71% of patients treated for nasopharyngeal cancer. External beam radiotherapy with endocavitary brachytherapy produces excellent rates of local control for T1 to T2 tumors, but the high incidence of late toxicity suggests an overtreatment

Can FDG-PET assist in radiotherapy target volume definition of metastatic lymph nodes in head-and-neck cancer?

Contains fulltext : 80379.pdf (publisher's version ) (Closed access)BACKGROUND AND PURPOSE: The role of FDG-PET in radiotherapy target volume definition of the neck was evaluated by comparing eight methods of FDG-PET segmentation to the current CT-based practice of lymph node assessment in head-and-neck cancer patients. MATERIALS AND METHODS: Seventy-eight head-and-neck cancer patients underwent coregistered CT- and FDG-PET scans. Lymph nodes were classified as "enlarged" if the shortest axial diameter on CT was 10mm, and as "marginally enlarged" if it was 7-10mm. Subsequently, lymph nodes were assessed on FDG-PET applying eight segmentation methods: visual interpretation (PET(VIS)), applying fixed thresholds at a standardized uptake value (SUV) of 2.5 and at 40% and 50% of the maximum signal intensity of the primary tumor (PET(SUV), PET(40%), PET(50%)) and applying a variable threshold based on the signal-to-background ratio (PET(SBR)). Finally, PET(40%N), PET(50%N) and PET(SBRN) were acquired using the signal of the lymph node as the threshold reference. RESULTS: Of 108 nodes classified as "enlarged" on CT, 75% were also identified by PET(VIS), 59% by PET(40%), 43% by PET(50%) and 43% by PET(SBR). Of 100 nodes classified as "marginally enlarged", only a minority were visualized by FDG-PET. The respective numbers were 26%, 10%, 7% and 8% for PET(VIS), PET(40%), PET(50%) and PET(SBR). PET(40%N), PET(50%N) and PET(SBRN), respectively, identified 66%, 82% and 96% of the PET(VIS)-positive nodes. CONCLUSIONS: Many lymph nodes that are enlarged and considered metastatic by standard CT-based criteria appear to be negative on FDG-PET scan. Alternately, a small proportion of marginally enlarged nodes are positive on FDG-PET scan. However, the results are largely dependent on the PET segmentation tool used, and until proper validation FDG-PET is not recommended for target volume definition of metastatic lymph nodes in routine practice

Comparison of the risks of hospitalisation for cardiovascular events in patients with rheumatoid arthritis treated with tocilizumab and etanercept

Objective. To verify if tocilizumab (TCZ) is associated with an increased risk of cardiovascular (CV) events compared with etanercept (ETN) in rheumatoid arthritis (RA). Methods. This is a retrospective cohort study on administrative healthcare databases (AHD) in Italy. Patients were identified using a validated algorithm based on AHD. Exposure to specific drugs was estimated by the drug prescription recorded in the AHD. The occurrence of acute CV events (myocardial infarction, stroke, other CV events) was derived from the hospital discharge forms. The association between TCZ or ETN and CV events was estimated using competing risk models, adjusting for pre-specified confounders. Results. We identified 1,752 subjects with RA, 1,086 treated with ETN and 666 with TCZ. TCZ did not increase the overall risk of acute CV events, even when adjusted for pre-specified confounders (hazard ratio HR 0.95, 95% confidence interval 95%CI 0.54-1.66), specifically of acute myocardial infarction (HR 0.39, 95%CI 0.15-1.06), stroke (HR 1.44, 95%CI 0.24-8.68) or other CV event (1.07, 95%CI 0.59-1.92). Conclusion. RA patients with TCZ do not have a medium-term excess of CV risk in patients compared with ETN

Which outcomes should always be measured in intervention studies for improving work participation for people with a health problem? An international multistakeholder Delphi study to develop a core outcome set for Work participation (COS for Work)

OBJECTIVE: Synthesising evidence of the effects of interventions to improve work participation among people with health problems is currently difficult due to heterogeneity in outcome measurements. A core outcome set for work participation is needed. STUDY DESIGN AND SETTING: Following the Core Outcome Measures in Effectiveness Trials methodology, we used a five-step approach to reach international multistakeholder consensus on a core outcome set for work participation. Five subgroups of stakeholders took part in two rounds of discussions and completed two Delphi voting rounds on 26 outcomes. A consensus of ≥80% determined core outcomes and 50%-80% consensus was required for candidate outcomes. RESULTS: Fifty-eight stakeholders took part in the Delphi rounds. Core outcomes were: 'any type of employment including self-employment', 'proportion of workers that return to work after being absent because of illness' and 'time to return to work'. Ten candidate outcomes were proposed, among others: 'sustainable employment', 'work productivity' and 'workers' perception of return to work'. CONCLUSION: As a minimum, all studies evaluating the impact of interventions on work participation should include one employment outcome and two return to work outcomes if workers are on sick leave prior to the intervention