Efficacy and safety of electronic cigarettes as a smoking cessation intervention: A systematic review and network meta-analysis.

INTRODUCTION: This systematic review of randomized controlled trials (RCTs) evaluated the efficacy and safety of electronic cigarettes (e-cigarettes, ENDS) in helping people who smoke to achieve abstinence compared with electronic non-nicotine delivery systems (ENNDS, no nicotine) or any smoking cessation comparator treatment or combination of treatments at 24-26 weeks and at 52 weeks. METHODS: Systematic review techniques involved searches of three databases in February 2020 with update searches run on 14 May 2021, two-person independent screening, two-person independent assessment of bias, formal extraction of data with verification by a second person, a feasibility assessment to decide if meta-analysis was appropriate, and network meta-analysis (NMA) of data at 24-26 weeks. Data at 52 weeks were narratively summarized. RESULTS: Ten RCTs met the inclusion criteria, eight for efficacy and ten for safety. Eight of the nine RCTs were assessed as at high risk of bias. The sample sizes of the RCTs were 30-2012. Using nicotine replacement therapy (NRT) as the reference treatment, the incidences of smoking cessation at 24-26 weeks were comparable between ENDS and NRT groups (RR=1.17; 95% CrI: 0.66-1.86). Three sensitivity analyses were carried out indicating the main findings for 24-26 weeks were robust to assumptions. The findings at 52 weeks were inconclusive. CONCLUSIONS: This systematic review and NMA indicates that there is no clear evidence of a difference in effect between nicotine containing e-cigarettes and NRT on incidences of smoking cessation at 24-26 weeks, and substantial uncertainty remains.

Critical appraisal of nonrandomized studies-A review of recommended and commonly used tools.

RATIONALE, AIMS, AND OBJECTIVES: When randomized controlled trial data are limited or unavailable, or to supplement randomized controlled trial evidence, health technology assessment (HTA) agencies may rely on systematic reviews of nonrandomized studies (NRSs) for evidence of the effectiveness of health care interventions. NRS designs may introduce considerable bias into systematic reviews, and several methodologies by which to evaluate this risk of bias are available. This study aimed to identify tools commonly used to assess bias in NRS and determine those recommended by HTA bodies. METHODS: Appraisal tools used in NRS were identified through a targeted search of systematic reviews (January 2013-March 2017; MEDLINE and EMBASE [OVID SP]). Recommendations for the critical appraisal of NRS by expert review groups and HTA bodies were reviewed. RESULTS: From the 686 studies included in the narrative synthesis, 48 critical appraisal tools were identified. Commonly used tools included the Newcastle-Ottawa Scale, the methodological index for NRS, and bespoke appraisal tools. Neither the Cochrane Handbook nor the Centre for Reviews and Dissemination recommends a particular instrument for the assessment of risk of bias in NRS, although Cochrane has recently developed their own NRS critical appraisal tool. Among HTA bodies, only the Canadian Agency for Drugs and Technologies in Health recommends use of a specific critical appraisal tool-SIGN 50 (for cohort or case-control studies). Several criteria including reporting, external validity, confounding, and power were examined. CONCLUSION: There is no consensus between HTA groups on the preferred appraisal tool. Reviewers should select from a suite of tools on the basis of the design of studies included in their review.

A practical approach to predict expansion of evidence networks: a case study in treatment-naive advanced melanoma.

Network meta-analysis (NMA) is a statistical method used to produce comparable estimates of efficacy across a range of treatments that may not be compared directly within any single trial. NMA feasibility is determined by the comparability of the data and presence of a connected network. In rapidly evolving treatment landscapes, evidence networks can change substantially in a short period of time. We investigate methods to determine the optimum time to conduct or update a NMA based on anticipated available evidence. We report the results of a systematic review conducted in treatment-naive advanced melanoma and compare networks of evidence available at retrospective, current, and prospective time points. For included publications, we compared the primary completion date of trials from clinical trials registries (CTRs) with the date of their first available publication to provide an estimate of publication lag. Using CTRs we were able to produce anticipated networks for future time points based on projected study completion dates and average publication lags which illustrated expansion and strengthening of the initial network. We found that over a snapshot of periods between 2015 and 2018, evidence networks in melanoma changed substantively, adding new comparators and increasing network connectedness. Searching CTRs for ongoing trials demonstrates it is possible to anticipate future networks at a certain time point. Armed with this information, sensible decisions can be made over when best to conduct or update a NMA. Incorporating new and upcoming interventions in a NMA enables presentation of a complete, up-to-date and evolving picture of the evidence.

Relative efficacy and safety of simeprevir and telaprevir in treatment-naïve hepatitis C-infected patients in a Japanese population: A Bayesian network meta-analysis.

AIM: Simeprevir (SMV) is an oral, once-daily protease inhibitor for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection. In phase II/III randomized controlled trials (RCT) conducted in Japan, SMV, in combination with peginterferon-α and ribavirin (PEG IFN/RBV), demonstrated potent efficacy in HCV genotype 1-infected patients relative to PEG IFN/RBV and was generally well tolerated. Telaprevir (TVR) in combination with PEG IFN/RBV is licensed for the treatment of HCV in Japan. In the absence of head-to-head comparisons of TVR and SMV in a Japanese population, we undertook a network meta-analysis (NMA) to examine the relative efficacy and safety of SMV and TVR in combination with PEG IFN/RBV. METHODS: A systematic review identified SMV and TVR RCT in Japanese treatment-naïve patients. Bayesian NMA was performed assuming fixed study effects. RESULTS: Three studies met our inclusion criteria: two SMV and one TVR. SMV showed a higher mean odds ratio (OR) of achieving SVR versus TVR (OR, 1.68 (95% credible interval 0.66-4.26)). SMV showed a lower mean OR of discontinuation: overall, 0.35 (0.12-1.00); and due to AE, 0.87 (0.23-3.34) versus TVR. SMV showed a lower mean OR of experiencing anemia 0.20 (0.07-0.56) and rash 0.41 (0.17-0.99) but a higher mean OR of experiencing pruritus 1.26 (0.46-3.47) versus TVR. CONCLUSION: In this indirect treatment comparison, SMV, in combination with PEG IFN/RBV, showed a favorable risk-benefit profile compared with TVR with PEG IFN/RBV in Japanese treatment-naïve HCV patients.