Financial conflicts of interest and their association with outcome and quality of fibromyalgia drug therapy randomized controlled trials.

AIMS: To evaluate the association of financial conflicts of interest (FCOI) with the characteristics, outcome and reported methodological quality of fibromyalgia drug therapy randomized controlled trials (FM-RCTs). METHODS: A cross-sectional study of original, parallel-group, drug therapy FM-RCTs published between 1997 and 2011 from Medline and Cochrane Central Register of Controlled Trials was conducted. Two reviewers independently assessed each RCT for funding source, authors' FCOI(s), study characteristics, reporting of methodological measures important for internal validity and outcome (positive [statistically significant result favoring experimental drug for the primary outcome] or non-positive). RESULTS: Forty-seven RCTs were eligible with funding source as: 26 (55.3%) industry; eight (17%) non-profit source(s); five (10.6%) mixed; and eight (17%) unspecified. Industry-funded RCTs were more likely to be multicenter and enroll greater number of patients. Reporting of key methodological measures was suboptimal; however, industry and non-profit funded RCTs did not differ in their reporting. Thirty (63.8%) RCTs had ≥ one author who disclosed an FCOI (receipt of research grant [21, 44.7%], industry sponsor employee [20, 42.6%], receipt of consultancy fee/honorarium [16, 34%] and stock ownership [11, 23.4%]). Although industry funding and certain authors' FCOIs (employment and receipt of consultancy fee/honorarium) were univariately associated with positive outcome, such association was not observed after adjusting for study sample size. CONCLUSIONS: The majority of FM-RCTs were industry-sponsored, and had at least one author with an FCOI. Reporting of key methodological measures was suboptimal. After adjusting for study sample size, no association of industry funding or author's FCOI with study outcome was seen.

The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program.

OBJECTIVES: The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). METHODS: Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10=worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score [HAQ]) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. RESULTS: Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. CONCLUSIONS: Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.

Disease activity assessment and patient-reported outcomes in patients with early rheumatoid arthritis.

Quantitative assessment of disease activity and patient-reported outcomes are recognized as valuable in the management of rheumatoid arthritis (RA). Complexities of assessment of RA include challenges concerning measures themselves, as a gold standard measure for disease status does not exist. This article discusses the hurdles in the implementation of quantitative assessment of RA in usual clinical care and also provides an example to monitor patients with early RA.

Association of industry funding with the outcome and quality of randomized controlled trials of drug therapy for rheumatoid arthritis.

OBJECTIVE: To assess the association of industry funding with the characteristics, outcome, and reported quality of randomized controlled trials (RCTs) of drug therapy for rheumatoid arthritis (RA). METHODS: The Medline and Cochrane Central Register of Controlled Trials databases were searched to identify original RA drug therapy RCTs published in 2002-2003 and 2006-2007. Two reviewers independently assessed each RCT for the funding source, characteristics, outcome (positive [statistically significant result favoring experimental drug for the primary outcome] or not positive), and reporting of methodologic measures whose inadequate performance may have biased the assessment of treatment effect. RCTs that were registered at ClinicalTrials.gov and completed during the study years were assessed for publication bias. RESULTS: Of the 103 eligible RCTs identified, 58 (56.3%) were funded by industry, 19 (18.4%) were funded by nonprofit sources, 6 (5.8%) had mixed funding, and funding for 20 (19.4%) was not specified. Industry-funded RCTs had significantly more study centers and subjects, while nonprofit agency-funded RCTs had longer duration and were more likely to study different treatment strategies. Outcome could be assessed for 86 (83.5%) of the 103 RCTs studied. The funding source was not associated with a higher likelihood of positive outcomes favoring the sponsored experimental drug (75.5% of industry-funded RCTs had a positive outcome, compared with 68.8% of non-industry-funded RCTs, 40% of RCTs with mixed funding, and 81.2% of RCTs for which funding was not specified). Industry-funded RCTs showed a trend toward a higher likelihood of nonpublication (P=0.093). Industry-funded RCTs were more frequently associated with double-blinding, an adequate description of participant flow, and performance of an intent-to-treat analysis. CONCLUSION: Industry funding was not associated with a higher likelihood of positive outcomes of published RCTs of drug therapy for RA, and industry-funded RCTs performed significantly better than non-industry-funded RCTs in terms of reporting the use of some key methodologic quality measures.

Reevaluation of the role of duration of morning stiffness in the assessment of rheumatoid arthritis activity.

OBJECTIVE: To evaluate the utility of the duration of morning stiffness (MS), as a patient-reported outcome (PRO), in assessing rheumatoid arthritis (RA) disease activity. METHODS: We acquired information on 5439 patients in QUEST-RA, an international database of patients with RA evaluated by a standard protocol. MS duration was assessed from time of waking to time of maximal improvement. Ability of MS duration to differentiate RA activity states, based on Disease Activity Score (DAS)28, was assessed by analysis of variance; and a receiver-operating characteristic (ROC) curve was plotted for discriminating clinically active (DAS28 > 3.2) from less active (DAS28 3.2). CONCLUSION: MS duration has a moderate correlation with RA disease activity. Assessment of MS duration may be clinically helpful in patients with low RAPID3 scores.

Clinical trials and public trust: the geographical shift to the Asia-Pacific region.

Multiple issues surrounding the publication of clinical trials and the conduct of clinical trials, especially those that are industry-sponsored, have raised doubts regarding the integrity of their results, and of the integrity of the medical profession. An appreciation of the historical and economic changes in the relationship between physicians and industry is crucial to the understanding of these issues. Increasingly, as healthcare professionals and centers in the Asia-Pacific region become involved in corporate-funded multi-center drug trials, these ethical issues similarly come into play. It is imperative for medical leaders to take actions ensuring rights of subjects participating in these clinical trials, and to ensure the integrity of physicians and authors of clinical trials from this region of the world.