Mobilizing Public Will For Social Change

Examines the theory and strategies of "public will" campaigns and offers tangible criteria for their evaluation. It provides a rich inventory of strategies for use in mobilizing the public will through an integration of models of agenda building, social problem construction, issues management, social movements, media advocacy, and social capital. In addition, the paper provides cases and examples of public will campaigns directed at various social problems, along with criteria for evaluating these campaigns at various stages of a social problem's life cycle

Agreements and Discrepancies between FDA Reports and Journal Papers on Biologic Agents Approved for Rheumatoid Arthritis:<i>A Meta-Research Project</i>

BACKGROUND:Sponsors that seek to commercialize new drugs apply to the Food and Drug Administration (FDA) which independently analyzes the raw data and reports the results on its website. OBJECTIVES:This study sought to determine if there are differences between the FDA assessments and journal reports on biologic agents developed for the treatment of rheumatoid arthritis. METHODS:Available data on FDA-approved drugs were extracted from the website, and a systematic literature search was conducted to identify matching studies in peer-reviewed medical journals. Outcome measures were the American College of Rheumatology response criteria ACR20 (efficacy) and withdrawal due to adverse events (safety). As effect size odds ratios were estimated for each active trial arm vs. control arm (i.e. for both sources: FDA and journal report), followed by calculation of the ratios of the FDA and journal report odds ratios. A ratio of odds ratios not equal to 1 was categorized as a discrepancy. RESULTS:FDA reports were available for 8 of 9 FDA-approved biologic agents for rheumatoid arthritis; all identified trials (34) except one were published in peer-reviewed journals. Overall, discrepancies were noted for 20 of the 33 evaluated trials. Differences in the apparent benefit reporting were found in 39% (24/61) pairwise comparisons and in 11 cases these were statistically significant; the FDA report showed greater benefit than the journal publication in 15 comparisons and lesser benefit in 9. Differences in the reported harms were found in 51% (28/55) pairwise comparisons and were statistically significant in 5. The "signal" in FDA reports showed a less harmful effect than the journal publication in 17 comparisons whereas a more harmful effect in 11. The differences were attributed to differences in analytic approach, patient inclusion, rounding effect, and counting discrepancies. However, no differences were categorized as critical. CONCLUSION:There was no empirical evidence to suggest biased estimates between the two sources. Increased and detailed transparency in publications would improve the understanding and credibility of published results. Further, the FDA report was found to be a useful source when data are missing in the published report (i.e. reporting bias)

Test-retest of computerized health status questionnaires frequently used in the monitoring of knee osteoarthritis: a randomized crossover trial

<p>Abstract</p> <p>Background</p> <p>To compare data based on touch screen to data based on traditional paper versions of questionnaires frequently used to examine patient reported outcomes in knee osteoarthritis patients and to examine the impact of patient characteristics on this comparison</p> <p>Methods</p> <p>Participants were recruited from an ongoing trial (<url>http://ClinicalTrials.Gov</url> Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00655941">NCT00655941</a>). 20 female participants, mean age 67 (SD 7), completed KOOS, VAS pain, function and patient global, SF-36, Physical Activity Scale, painDETECT, and the ADL Taxonomy. Patients were randomly assigned to one of two subgroups, completing either the paper or touch screen version first. Mean, mean differences (95% CI), median, median differences and Intraclass Correlation Coefficients (ICCs) were calculated for all questionnaires.</p> <p>Results</p> <p>ICCs between data based on computerized and paper versions ranged from 0.86 to 0.99. Analysis revealed a statistically significant difference between versions of the ADL Taxonomy, but not for the remaining questionnaires. Age, computer experience or education-level had no significant impact on the results. The computerized questionnaires were reported to be easier to use.</p> <p>Conclusion</p> <p>The computerized questionnaires gave comparable results to answers given on paper. Patient characteristics did not influence results and implementation was feasible.</p

Measuring cognitive assessment and intervention burden in patients with acquired brain injured: Development of the "How Much is Too Much" questionnaire

Objective: To design and preliminarily test a questionnaire intended to measure patient treatment burden resulting from participation in cognitive assessments and interventions. Methods: An expert consensus process was used to develop the concept of patient treatment burden and to determine the first set of questionnaire items and administration protocol. The pilot questionnaire was administered to 20 patients with mild to severe acquired brain injuries on completion of a 2-h or longer neuropsychological assessment. Following preliminary testing, the questionnaire was revised and re-evaluated by a second expert panel and content validity was assessed. Results: Burden was defined as psychologically and/or physically aversive symptoms in response to cognitive assessment or intervention. The first questionnaire contained 21 items assigned to 3 categories: physical, cognitive, and emotional. Eightyfive percent of patients endorsed symptom level increases, with "tired/fatigued" the most frequently endorsed item (80% of patients). Instructions and test items were easily understood, and the questionnaire was quick to administer. Content validity ratio (CVR) of the revised questionnaire yielded 23 acceptable items and a subset met the highest CVR threshold (>0.78). Conclusion: This patient-reported outcome will ultimately help patients give voice to aversive experiences, and help clinicians and researchers to monitor and adapt assessments/treatments appropriately. Future steps in development are described

Defining the optimal biological monotherapy in rheumatoid arthritis: a systematic review and meta-analysis of randomised trials

Objectives To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. Methods We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800. Results The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included “DMARD-naïve”, and 20 “DMARD-Inadequate responder” (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068). Conclusions Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice

Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis

OBJECTIVES: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA.METHODS: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).RESULTS: A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI: 1.18, 2.14), adalimumab (1.36, 95% CI: 1.02, 1.81), etanercept (1.60, 95% CI: 1.18, 2.17), golimumab (1.45, 95% CI: 1.00, 2.08), rituximab (1.63, 95% CI: 1.16, 2.30), tofacitinib (1.44, 95% CI: 1.03, 2.02) and control (1.45, 95% CI: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI: 1.03, 1.65), etanercept (1.31, 95% CI: 1.04, 1.67) and rituximab (1.34, 95% CI: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates.CONCLUSION: Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs. OBJECTIVES: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA.METHODS: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).RESULTS: A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI: 1.18, 2.14), adalimumab (1.36, 95% CI: 1.02, 1.81), etanercept (1.60, 95% CI: 1.18, 2.17), golimumab (1.45, 95% CI: 1.00, 2.08), rituximab (1.63, 95% CI: 1.16, 2.30), tofacitinib (1.44, 95% CI: 1.03, 2.02) and control (1.45, 95% CI: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI: 1.03, 1.65), etanercept (1.31, 95% CI: 1.04, 1.67) and rituximab (1.34, 95% CI: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates.CONCLUSION: Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs.SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42014014842

Assessing the effect of interventions for axial spondyloarthritis according to the endorsed ASAS/OMERACT core outcome set: a meta-research study of trials included in Cochrane reviews.

The Assessment of SpondyloArthritis international Society (ASAS) has defined core sets for (i) symptom-modifying anti-rheumatic drugs (SM-ARD), (ii) clinical record keeping, and (iii) disease-controlling anti-rheumatic therapy (DC-ART). These include the following domains for all three core sets: physical function, pain, spinal mobility, spinal stiffness, and patient\u27s global assessment (PGA). The core set for clinical record keeping further includes the domains peripheral joints/entheses and acute phase reactants, and the core set for DC-ART further includes the domains fatigue and spine radiographs/hip radiographs. The Outcome Measures in Rheumatology (OMERACT) endorsed the core sets in 1998.Using empirical evidence from axSpA trials, we investigated the efficacy (i.e., net benefit) according to the ASAS/OMERACT core outcome set for axSpA across all interventions tested in trials included in subsequent Cochrane reviews. For all continuous scales, we combined data using the standardized mean difference (SMD) to meta-analyze outcomes involving the same domains. Also, through meta-regression analysis, we examined the effect of the separate SMD measures (independent variables) on the primary endpoint (log [OR], dependent variable) across all trials.Based on 11 eligible Cochrane reviews, from these, 85 articles were screened; we included 43 trials with 63 randomized comparisons. Mean (SD) number of ASAS/OMERACT core outcome domains measured for SM-ARD/physical therapy trials was 4.2 (1.7). Six trials assessed all proposed domains. Mean (SD) for number of core outcome domains for DC-ART trials was 5.8 (1.7). No trials assessed all nine domains. Eight trials (16%) were judged to have inadequate (i.e., high risk of) selective outcome reporting bias. The most responsible core domains for achieving success in meeting the primary objective per trial were pain, OR (95% CI) 5.19 (2.28, 11.77), and PGA, OR (95% CI) 1.87 (1.14, 3.07). In conclusion, selective outcome reporting (and missing data ) should be reduced by encouraging the use of the endorsed ASAS/OMERACT outcome domains in clinical trials. Overall outcome reporting was good for SM-ARD/physical therapy trials and poor for DC-ART trials. Our findings suggest that both PGA and pain provide a valuable holistic construct for the assessment of improvement beyond more objective measures of spinal inflammation