Systematic review and network meta-analysis on the efficacy of evolocumab and other therapies for the management of lipid levels in hyperlipidemia

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low‐density lipoprotein cholesterol (LDL‐C) when added to statin therapy in patients who need additional LDL‐C reduction. Methods and Results: We conducted a systematic review and network meta‐analysis of randomized trials of lipid‐lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid‐lowering therapies that enrolled patients requiring further LDL‐C reduction while on maximally tolerated medium‐ or high‐intensity statin, of which 15 could be relevant for inclusion in LDL‐C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms. PCSK9 inhibitors significantly reduced LDL‐C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (−74.1%; 95% credible interval −79.81% to −68.58%), alirocumab 75 mg (−20.03%; 95% credible interval −27.32% to −12.96%), and alirocumab 150 mg (−13.63%; 95% credible interval −22.43% to −5.33%) at ≥12 weeks. Treatment differences were similar in direction and magnitude for PCSK9 inhibitor monthly dosing. Adverse events were similar between PCSK9 inhibitors and control. Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe. Conclusions: PCSK9 inhibitors added to medium‐ to high‐intensity statin therapy significantly reduce LDL‐C in patients requiring further LDL‐C reduction. The network meta‐analysis showed a significant treatment difference in LDL‐C reduction for evolocumab versus alirocumab

Which factors may determine the necessary and feasible type of effectiveness evidence?

Objectives: Reimbursement decisions require evidence of effectiveness and, in general, a blinded randomised controlled trial (RCT) is the preferred study design to provide it. However, there are situations where a cohort study, or even patient series, can be deemed acceptable. The aim of this study was to develop an instrument that first examines which study characteristics of a blinded RCT are necessary, and then, if particular characteristics are considered necessary, examines whether these characteristics are feasible. Design: We retrospectively studied 22 interventions from 20 reimbursement reports concerning medical specialist care made by the Dutch National Health Care Institute (ZIN) to identify any factors that influenced the necessity and feasibility of blinded RCTs, and their constituent study characteristics, that is, blinding, randomisation and a control group. A literature review was performed to identify additional factors. Additional expertise was included by interviewing eight experts in epidemiology, medicine and ethics. The resulting instrument was called the FIT instrument (Feasible Information Trajectory), and was prospectively validated using three consecutive reimbursement reports. Results: (Blinded) RCT evidence was lacking in 5 of 11 positive reimbursement decisions and 3 of 11 negative decisions. In the reimbursement reports, we found no empirical evidence supporting situations where a blinded RCT is unnecessary. The literature also revealed few arguments against the necessity of a blinded RCT. In contrast, many factors influen

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies

The impact of quality-of-life data in relative effectiveness assessments of new anti-cancer drugs in European countries

PURPOSE: The aim of this study is to investigate the role of health-related quality-of-life (QoL) data in relative effectiveness assessments (REAs) of new anti-cancer drugs across European jurisdictions, during health technology assessment procedures. METHODS: Comparative analysis of guidelines and publicly available REAs in six European jurisdictions of anti-cancer drugs approved by EMA between 2011 and 2013. RESULTS: Fourteen anti-cancer drugs were included, adding up to 79 REAs. Whilst all guidelines state that QoL is a relevant endpoint to determine the relative effectiveness of new cancer drugs, QoL data were included in only 54% of the 79 reports and their impact on the recommendations was limited. CONCLUSIONS: Whilst national guidelines recognize the relevance of QoL to determine the relative effectiveness of new anti-cancer drugs, this is not well-reflected in current assessments. Developing and implementing into REAs specific evidence requirements for QoL data would improve the use of this patient-centred outcome in future reimbursement and pricing decisions

Can a Joint Assessment Provide Relevant Information for National/Local Relative Effectiveness Assessments? : An In-Depth Comparison of Pazopanib Assessments

BACKGROUND: In many European jurisdictions, relative effectiveness assessments (REAs) of pharmaceuticals are performed during the reimbursement decision-making process. International collaboration in the production of these assessments may prevent the duplication of information in various jurisdictions. A first pilot of a joint REA (pazopanib for the treatment of renal cell carcinoma) was published in 2011. OBJECTIVE: The objective was to investigate how well the methods used in the joint REA match the methods used in the national/local assessments on the same topic. METHODS: National/local assessments from European jurisdictions, available in English language, were identified through a literature search and an e-mail request to health technology assessment organizations. Data were abstracted from joint and national/local assessments using a structured data abstraction form. Results were compared for differences and similarities. RESULTS: In total, five national/local reports were included (Belgium, England/Wales, France, The Netherlands, and Scotland). The general methods (indication, main comparator, main end points, main trial) were similar. The details of the assessment (e.g., exact wording of indication, additional comparators, additional trials included, and method of indirect comparison), however, varied. Despite these differences, the joint REA included nearly all comparators, end points, trials, and methods of analysis that were used in national/local REA reports. CONCLUSIONS: This study has shown overlap in the methods national/local REA bodies in Europe have chosen for a pazopanib REA for renal cell carcinoma, except for the use and methods of indirect comparisons. Although some additional comparators and outcomes differed between national/local REAs, they can be captured in a comprehensive joint REA