Assessment of industry data on pulmonary and immunosuppressive effects of IQOS.
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ABSTRACT:
SUBMITTER: Moazed F
PROVIDER: S-EPMC6252496 | biostudies-other | 2018 Nov
REPOSITORIES: biostudies-other
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Project description:To investigate whether adverse effects data for the sponsor's product are presented more favourably in pharmaceutical industry-funded studies than in non-industry-funded studies.We conducted a systematic review of methodological evaluations that had assessed the relationship between industry funding and the reported risk of adverse effects. Searches were undertaken in 10 databases and supplemented with other sources of information such as handsearching, citation searching, checking conference proceedings and discussion with experts. Two reviewers independently screened the records and carried out data extraction for potentially relevant papers. We included studies that compared the results and interpretation of the adverse effects data according to funding source (e.g. adverse effects data in pharmaceutical industry research vs. data from nonprofit organizations, or from one manufacturer vs. another). Methodological evaluations were excluded if categories of funding source were not explicitly specified by the researchers, and if we were uncertain that industry-funded studies were present in the evaluation.The search strategy yielded 4,069 hits, of which six methodological evaluations met our inclusion criteria. One survey of 370 trials covering a wide range of topics found that trials with industry sponsors had more complete reporting of adverse effects compared with non-industry-funded trials, whereas another survey of 504 inhaled corticosteroid studies showed no apparent difference after confounding factors were adjusted for. In contrast, we found evidence from post hoc subgroup analyses involving two products where the likelihood of harm was of a lower magnitude in manufacturer-funded studies compared with nonmanufacturer-funded studies. There is also evidence from four methodological evaluations that authors with industry funding were more likely than authors without pharmaceutical funding to interpret and conclude that a drug was safe, even among studies that did find a statistically significant increase in adverse effects for the sponsored product.Our review indicates that industry funding may not be a major threat to bias in the reporting of the raw adverse effects data. However, we are concerned about potential bias in the interpretation and conclusions of industry-funded authors and studies.
| S-EPMC2675760 | biostudies-literature
Project description:This paper aims to identify the regional potential of Industry 4.0 (I4.0). Although the regional background of a company significantly determines how the concept of I4.0 can be introduced, the regional aspects of digital transformation are often neglected with regard to the analysis of I4.0 readiness. Based on the analysis of the I4.0 readiness models, the external regional success factors of the implementation of I4.0 solutions are determined. An I4.0+ (regional Industry 4.0) readiness model, a specific indicator system is developed to foster medium-term regional I4.0 readiness analysis and foresight planning. The indicator system is based on three types of data sources: (1) open governmental data; (2) alternative metrics like the number of I4.0-related publications and patent applications; and (3) the number of news stories related to economic and industrial development. The indicators are aggregated to the statistical regions (NUTS 2), and their relationships analyzed using the Sum of Ranking Differences (SRD) and Promethee II methods. The developed I4.0+ readiness index correlates with regional economic, innovation and competitiveness indexes, which indicates the importance of boosting regional I4.0 readiness.
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Project description:The data article presents a dataset suitable to measure regional Industry 4.0 (I4.0+) readiness. The I4.0+ dataset includes 101 indicators with 248 958 observations, aggregated to NUTS 2 statistical level) based on open data in the field of education (ETER, Erasmus), science (USPTO, MA-Graph, GRID), government (Eurostat) and media coverage (GDELT). Indicators consider the I4.0-specific domain of higher education and lifelong learning, innovation, technological investment, labour market and technological readiness as indicators. A composite indicator, the I4.0+ index was constructed by the Promethee method, to identify regional rank regarding their I4.0 performance. The index is validated with economic (GDP) and innovation indexes (Regional Innovation Index).
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Project description:Rationale: Immunosuppression was associated with adverse events for patients with idiopathic pulmonary fibrosis (IPF) in the PANTHER-IPF (Evaluating the Effectiveness of Prednisone, Azathioprine and N-Acetylcysteine in Patients with IPF) clinical trial. The reason why some patients with IPF experience harm is unknown.Objectives: To determine whether age-adjusted leukocyte telomere length (LTL) was associated with the harmful effect of immunosuppression in patients with IPF.Methods: LTL was measured from available DNA samples from PANTHER-IPF (interim analysis, n = 79; final analysis, n = 118). Replication cohorts included ACE-IPF (Anticoagulant Effectiveness in Idiopathic Pulmonary Fibrosis) (n = 101) and an independent observational cohort (University of Texas Southwestern Medical Center-IPF, n = 170). LTL-stratified and medication-stratified survival analyses were performed using multivariable Cox regression models for composite endpoint-free survival.Measurements and Main Results: Of the subjects enrolled in the PANTHER-IPF and ACE-IPF, 62% (49/79) and 56% (28/50) had an LTL less than the 10th percentile of normal, respectively. In PANTHER-IPF, exposure to prednisone/azathioprine/N-acetylcysteine was associated with a higher composite endpoint of death, lung transplantation, hospitalization, or FVC decline for those with an LTL less than the 10th percentile (hazard ratio, 2.84; 95% confidence interval, 1.02-7.87; P = 0.045). This finding was replicated in the placebo arm of ACE-IPF for those exposed to immunosuppression (hazard ratio, 7.18; 95% confidence interval, 1.52-33.84; P = 0.013). A propensity-matched University of Texas Southwestern Medical Center IPF cohort showed a similar association between immunosuppression and composite endpoints (death, lung transplantation, or FVC decline) for those with an LTL less than the 10th percentile (hazard ratio, 3.79; 95% confidence interval, 1.73-8.30; P = 0.00085). An interaction was found between immunosuppression and LTL for the combined PANTHER-IPF and ACE-IPF clinical trials (Pinteraction = 0.048), and the University of Texas Southwestern Medical Center IPF cohort (Pinteraction = 0.00049).Conclusions: LTL is a biomarker that may identify patients with IPF at risk for poor outcomes when exposed to immunosuppression.
| S-EPMC6680304 | biostudies-literature
Project description:BackgroundClinical trial transparency is important to participants, trialists, publishers, and regulators, and there have been recent major policy changes by the pharmaceutical industry regarding clinical study data sharing. However, it is unknown if these changes are enabling independent researchers to access participant-level data from prominent contemporary clinical trials sponsored by the pharmaceutical industry 2 years after publication of the primary results.Main textPubMed and ClinicalTrials.gov were searched to identify clinical trials of medicines sponsored by the pharmaceutical industry and first published between 1 July 2015 and 31 December 2015 in the top 10 general and internal medical journals by impact factor. For each clinical trial, the eligibility of independent researchers to request participant-level data was identified via the sponsor having a data sharing policy/process and a positive response to an enquiry. Fifty-six publications reporting on 61 industry-sponsored clinical trials were identified, of which 32 (52%) had a public data sharing policy/process and 9 (15%) were confirmed eligible for data sharing. Industry sponsors within the top 25 by global sales were more likely to have a data sharing policy (93% vs 10%), and there was a trend towards increased data sharing eligibility (23% vs 4%). Twenty-six studies were explicitly confirmed as ineligible for data sharing. The two most common data sharing policy conditions that prevented sharing of data for published results were the exclusion of studies that had ongoing follow-up of the published results and the exclusion of studies of medicines that have not yet achieved regulatory approval in the USA and the European Union.ConclusionsFifteen percent of the sampled clinical trials were available for data sharing 2 years after publication of primary results of the trial. Key issues limiting data sharing include a large proportion of industry sponsors who do not have a data sharing policy/process, and data sharing policy conditions that exclude access on the basis of ongoing follow-up and regulatory activity.
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Project description:BackgroundBenefit-risk assessments for medicinal products and devices have advanced significantly over the past decade. The purpose of this study was to characterize the extent to which the life sciences industry is utilizing quantitative benefit-risk assessment (qBRA) methods.MethodsSemi-structured interviews were conducted with a sample of industry professionals working in drug and/or medical device benefit-risk assessments (n = 20). Questions focused on the use, timing, and impact of qBRA; implementation challenges; and future plans. Interviews were recorded, transcribed, and coded for thematic analysis.ResultsWhile most surveyed companies had applied qBRA, application was limited to a small number of assets-primarily to support internal decision-making and regulatory submissions. Positive impacts associated with use included improved team decision-making and communication. Multi-criteria decision analysis and discrete choice experiment were the most frequently utilized qBRA methods. A key challenge of qBRA use was the lack of clarity regarding its value proposition. Championing by senior company leadership and receptivity of regulators to such analyses were cited as important catalysts for successful adoption of qBRA. Investment in qBRA methods, via capability building and pilot studies, was also under way in some instances.ConclusionqBRA application within this sample of life sciences companies was widespread, but concentrated in a small fraction of assets. Its use was primarily for internal decision-making or regulatory submissions. While some companies had plans to build further capacity in this area, others were waiting for further regulatory guidance before doing so.
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Project description:Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response of the host during several pathologies such as chronic infections or cancer. In fact, manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of tuberculosis (TB). However, very limited information regarding the PGE2 pathway in patients with active TB is currently available. In the present work, we demonstrated that PGE2 exerts a potent immunosuppressive action during the immune response of the human host against Mycobacterium tuberculosis (Mtb) infection. Actually, we showed that PGE2 significantly reduced the surface expression of several immunological receptors, the lymphoproliferation and the production of proinflammatory cytokines. In addition, PGE2 promoted autophagy in monocytes and neutrophils cultured with Mtb antigens. These results suggest that PGE2 might be attenuating the excessive inflammatory immune response caused by Mtb, emerging as an attractive therapeutic target. Taken together, our findings contribute to the knowledge of the role of PGE2 in the human host resistance to Mtb and highlight the potential of this lipid mediator as a tool to improve anti-TB treatment.
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Project description:Immunosuppression in elderly recipients has been underappreciated in clinical trials. Here, we assessed age-specific effects of the calcineurin inhibitor tacrolimus (TAC) in a murine transplant model and assessed its clinical relevance on human T cells. Old recipient mice exhibited prolonged skin graft survival compared with young animals after TAC administration. More important, half of the TAC dose was sufficient in old mice to achieve comparable systemic trough levels. TAC administration was able to reduce proinflammatory interferon-γ cytokine production and promote interleukin-10 production in old CD4+ T cells. In addition, TAC administration decreased interleukin-2 secretion in old CD4+ T cells more effectively while inhibiting the proliferation of CD4+ T cells in old mice. Both TAC-treated murine and human CD4+ T cells demonstrated an age-specific suppression of intracellular calcineurin levels and Ca2+ influx, two critical pathways in T cell activation. Of note, depletion of CD8+ T cells did not alter allograft survival outcome in old TAC-treated mice, suggesting that TAC age-specific effects were mainly CD4+ T cell mediated. Collectively, our study demonstrates age-specific immunosuppressive capacities of TAC that are CD4+ T cell mediated. The suppression of calcineurin levels and Ca2+ influx in both old murine and human T cells emphasizes the clinical relevance of age-specific effects when using TAC.
| S-EPMC5395364 | biostudies-literature
Project description:We assessed the CT attenuation density of the pulmonary tissue adjacent to the heart in patients with acute non-ST segment elevation myocardial infarction (J.T. Kuhl, T.S. Kristensen, A.F. Thomsen et al., 2016) [1]. This data was related to the level of ground-glass opacification evaluated by a radiologist, and data on the interobserver variability of semi-automated assessment of pulmonary attenuation density was provided.
| S-EPMC5133651 | biostudies-literature
Project description:BackgroundIn March, 2016, the UK Government proposed a tiered levy on sugar-sweetened beverages (SSBs; high tax for drinks with >8 g of sugar per 100 mL, moderate tax for 5-8 g, and no tax for <5 g). We estimate the effect of possible industry responses to the levy on obesity, diabetes, and dental caries.MethodsWe modelled three possible industry responses: reformulation to reduce sugar concentration, an increase of product price, and a change of the market share of high-sugar, mid-sugar, and low-sugar drinks. For each response, we defined a better-case and worse-case health scenario. We developed a comparative risk assessment model to estimate the UK health impact of each scenario on prevalence of obesity and incidence of dental caries and type 2 diabetes. The model combined data for sales and consumption of SSBs, disease incidence and prevalence, price elasticity estimates, and estimates of the association between SSB consumption and disease outcomes. We drew the disease association parameters from a meta-analysis of experimental studies (SSBs and weight change), a meta-analysis of prospective cohort studies (type 2 diabetes), and a prospective cohort study (dental caries).FindingsThe best modelled scenario for health is SSB reformulation, resulting in a reduction of 144 383 (95% uncertainty interval 5102-306 743; 0·9%) of 15 470 813 adults and children with obesity in the UK, 19 094 (6920-32 678; incidence reduction of 31·1 per 100 000 person-years) fewer incident cases of type 2 diabetes per year, and 269 375 (82 211-470 928; incidence reduction of 4·4 per 1000 person-years) fewer decayed, missing, or filled teeth annually. An increase in the price of SSBs in the better-case scenario would result in 81 594 (3588-182 669; 0·5%) fewer adults and children with obesity, 10 861 (3899-18 964; 17·7) fewer incident cases of diabetes per year, and 149 378 (45 231-262 013; 2·4) fewer decayed, missing, or filled teeth annually. Changes to market share to increase the proportion of low-sugar drinks sold in the better-case scenario would result in 91 042 (4289-204 903; 0·6%) fewer adults and children with diabetes, 1528 (4414-21 785; 19·7) fewer incident cases of diabetes per year, and 172 718 (47 919-294 499; 2·8) fewer decayed, missing, or filled teeth annually. The greatest benefit for obesity and oral health would be among individuals aged younger than 18 years, with people aged older than 65 years having the largest absolute decreases in diabetes incidence.InterpretationThe health impact of the soft drinks levy is dependent on its implementation by industry. Uncertainty exists as to how industry will react and about estimation of health outcomes. Health gains could be maximised by substantial product reformulation, with additional benefits possible if the levy is passed on to purchasers through raising of the price of high-sugar and mid-sugar drinks and activities to increase the market share of low-sugar products.FundingNone.
| S-EPMC5543265 | biostudies-literature