Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Background: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium–glucose co-transporter 2 (SGLT2) inhibitors. Objective: To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin. Sources: MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions. Methods: Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers. Results: We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP). Limitations: There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking. Conclusions: Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK). Funding: The National Institute for Health Research Health Technology Assessment programme

Leveraging first principles modeling and cross-product process monitoring to improve process design robustness

Thesis: M.B.A., Massachusetts Institute of Technology, Sloan School of Management, 2015. In conjunction with the Leaders for Global Operations Program at MIT.Thesis: S.M., Massachusetts Institute of Technology, Engineering Systems Division, 2015. In conjunction with the Leaders for Global Operations Program at MIT.Cataloged from PDF version of thesis.Includes bibliographical references (pages 88-89).Abstract The vision of the Operations Technology Group at Amgen is to enable a robust pipeline through focused and efficient operations research studies. Process design is traditionally developed by performing experiments, but other approaches can be used to improve cost, efficiency, and robustness. The scope of this internship included the use of First Principles, Computational Fluid Dynamics (CFD), and Cross-Product Process Monitoring (CPPM) to improve process design robustness with reduced testing and faster development cycle. The project focused specifically on the drug product development network, which included the development of processes from formulation to filling and finishing, clinical manufacturing, and technology transfer to commercial manufacturing The goal of this internship was to explore opportunities to utilize First Principles, CFD, and CPPM in drug product process design space. First Principles and CFD modeling tools were used to look into the physics of drug product filling process (specifically parameters influencing two key filling issues - drying during line stoppage and dripping between fills). Criteria for analyzing cost and benefits for the use of First Principles were also provided as strategic recommendations on where the new approach should be utilized. Clinical data were leveraged, with multivariate statistical data analysis, to determine inspection reject limit for the purpose of process monitoring and root cause analysis.by Nahathai Srivali.M.B.A.S.M

Ankylosing spondylitis and risk of venous thromboembolism: A systematic review and meta-analysis

Background: Several immune-mediated inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus have been linked to an increased risk of venous thromboembolism (VTE). However, the data on ankylosing spondylitis (AS) are limited. Methods: We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing the risk of VTE and possible pulmonary embolism (PE) in patients with AS versus non-AS participants. Pooled risk ratio and 95% confidence intervals were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Results: Of 423 potentially relevant articles, three studies met our inclusion criteria and thus, were included in the data analysis. The pooled risk ratio of VTE in patients with AS was 1.60 (95% confidence interval: 1.05–2.44). The statistical heterogeneity of this study was high with an I2 of 93%. Conclusion: Our study demonstrated a statistically significant increased VTE risk among patients with AS

Risk of Parkinson's disease among patients with psoriasis: A systematic review and meta-analysis

Background: Patients with psoriasis might be at a higher risk of developing Parkinson's disease (PD) as a result of the detrimental effect of chronic inflammation on the neuronal tissue. This meta-analysis aimed to investigate this risk by comprehensively reviewing all available data. Methods: We conducted a systematic review and meta-analysis of cohort and case–control studies that reported relative risk, hazard ratio, odds ratio, or standardized incidence ratio comparing the risk of PD in patients with psoriasis versus subjects without psoriasis. Pooled risk ratio and 95% confidence interval (CI) were calculated using random-effect, generic inverse variance methods of DerSimonian and Laird. Results: Three retrospective studies and one case–control study met our eligibility criteria and were included in this meta-analysis. The pooled risk ratio of PD in patients with psoriasis versus participants without psoriasis was 1.38 (95% CI, 1.15–1.66). The statistical heterogeneity was low with an I2of 35%. Conclusions: Our meta-analysis demonstrated a statistically significant increased risk of PD among patients with psoriasis

Association between psoriasis and chronic obstructive pulmonary disease: A systematic review and meta-analysis

<p>Psoriasis has been linked to an increased risk of several co-morbidities. However, its association with chronic obstructive pulmonary disease (COPD) remains unclear. To further characterize this relationship, we conducted a systematic review and meta-analysis of case–control and cross-sectional studies that compared the risk of COPD in patients with psoriasis versus non-psoriasis participants. Generic inverse variance method of DerSimonian and Laird was used to combine all the point estimates. Out of 502 potentially relevant articles, seven studies met our inclusion criteria and were included in the data analysis. The pooled odds ratio of COPD in patients with psoriasis versus control was 1.45 (95% CI, 1.21–1.73). The statistical heterogeneity was high with an <i>I</i>² of 91%. Therefore, our study provided evidence to support the increased risk of COPD among patients with psoriasis.</p

Systemic sclerosis and risk of venous thromboembolism: A systematic review and meta-analysis

<p><i>Background</i>. Several chronic inflammatory disorders, such as rheumatoid arthritis, inflammatory myositis, and systemic vasculitides, have been linked to an increased risk of venous thromboembolism (VTE). However, the data on systemic sclerosis (SSc) remains unclear.</p> <p><i>Methods</i>. We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of VTE in patients with SSc versus non-SSc participants. Pooled risk ratio and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird.</p> <p><i>Results</i>. Out of 776 potentially relevant articles, five eligible studies were identified and included in the data analysis. The pooled risk ratio of VTE in patients with SSc was 2.51 (95% CI, 1.79–3.54). The statistical heterogeneity of this study was high with an I² of 90%.</p> <p><i>Conclusions</i>. Our study demonstrated a statistically significant increased VTE risk among patients with SSc.</p