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Abstract Background Docetaxel, pemetrexed, erlotinib, and gefitinib are recommended as second-line treatment for advanced non-small cell lung cancer (NSCLC) with wild-type or unknown status for epidermal growth factor receptor (EGFR). However, the number of published randomized clinical trials (RCTs) on this topic is increasing. Our objective was to assess the comparative effectiveness and tolerability of all second-line treatments for advanced NSCLC with wild-type or unknown status for EGFR by a systematic review and network meta-analysis. Methods MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and the US Food and Drug Administration website, as well as other sources, were searched for available reports up to June 6, 2017. Two reviewers independently selected published and unpublished reports of RCTs comparing any second-line treatments, extracted data and assessed the risk of bias of all included trials. We performed a Bayesian network meta-analysis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response (ObR), the number of serious adverse events, and quality of life. Results We included 102 RCTs involving 36,058 patients (62% male, median age 61 years, 81% with stage IV cancer, 80% smokers, and 92% with performance status 0–1). We revealed a differential reporting of outcomes between efficacy and safety outcomes. Half of the trials reported safety outcomes and less than 20% quality of life. For OS, nivolumab was more effective than docetaxel (hazard ratio (HR) 0.69, 95% credible interval (CrI) 0.56–0.83), pemetrexed (0.67, 0.52–0.83), erlotinib (0.68, 0.53–0.86), and gefitinib (0.66, 0.53–0.83). Pembrolizumab, atezolizumab, and pemetrexed plus erlotinib were also significantly more effective than docetaxel, pemetrexed, erlotinib, and gefitinib. For PFS, erlotinib plus cabozantinib was more effective than docetaxel (HR 0.39, 95% CrI 0.18–0.84), pemetrexed (0.38, 0.18–0.82), erlotinib (0.37, 0.18–0.78), and gefitinib (0.38, 0.18–0.82). Cabozantinib and pemetrexed plus erlotinib were also significantly more effective than the four recommended treatments. For ObR, no treatment was significantly more effective. The effectiveness of the four recommended treatments was similar and they were ranked among the 25 less-effective treatments. For safety, evidence is insufficient to draw certain conclusions. Conclusions Nivolumab, pembrolizumab, atezolizumab, and pemetrexed plus erlotinib may be the most effective second-line treatments for NSCLC in terms of OS. The four recommended treatments seem to have relatively poor performance. However, the impact on life expectancy of immunotherapy versus other treatments should be further explored by future analyses, and more trials comparing the novel treatments are needed to reduce uncertainty in these results. Trial registration Registration number: PROSPERO (CRD42015017592)

Background: Docetaxel, pemetrexed, erlotinib, and gefitinib are recommended as second-line treatment for advanced non-small cell lung cancer (NSCLC) with wild-type or unknown status for epidermal growth factor receptor (EGFR). However, the number of published randomized clinical trials (RCTs) on this topic is increasing. Our objective was to assess the comparative effectiveness and tolerability of all second-line treatments for advanced NSCLC with wild-type or unknown status for EGFR by a systematic review and network meta-analysis.Methods: MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and the US Food and Drug Administration website, as well as other sources, were searched for available reports up to June 6, 2017. Two reviewers independently selected published and unpublished reports of RCTs comparing any second-line treatments, extracted data and assessed the risk of bias of all included trials. We performed a Bayesian network meta-analysis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response (ObR), the number of serious adverse events, and quality of life.Results: We included 102 RCTs involving 36,058 patients (62% male, median age 61 years, 81% with stage IV cancer, 80% smokers, and 92% with performance status 0-1). We revealed a differential reporting of outcomes between efficacy and safety outcomes. Half of the trials reported safety outcomes and less than 20% quality of life. For OS, nivolumab was more effective than docetaxel (hazard ratio (HR) 0.69, 95% credible interval (CrI) 0.56-0.83), pemetrexed (0.67, 0.52-0.83), erlotinib (0.68, 0.53-0.86), and gefitinib (0.66, 0.53-0.83). Pembrolizumab, atezolizumab, and pemetrexed plus erlotinib were also significantly more effective than docetaxel, pemetrexed, erlotinib, and gefitinib. For PFS, erlotinib plus cabozantinib was more effective than docetaxel (HR 0.39, 95% CrI 0.18-0.84), pemetrexed (0.38, 0.18-0.82), erlotinib (0.37, 0.18-0.78), and gefitinib (0.38, 0.18-0.82). Cabozantinib and pemetrexed plus erlotinib were also significantly more effective than the four recommended treatments. For ObR, no treatment was significantly more effective. The effectiveness of the four recommended treatments was similar and they were ranked among the 25 less-effective treatments. For safety, evidence is insufficient to draw certain conclusions.Conclusions: Nivolumab, pembrolizumab, atezolizumab, and pemetrexed plus erlotinib may be the most effective second-line treatments for NSCLC in terms of OS. The four recommended treatments seem to have relatively poor performance. However, the impact on life expectancy of immunotherapy versus other treatments should be further explored by future analyses, and more trials comparing the novel treatments are needed to reduce uncertainty in these results.Trial Registration: Registration number: PROSPERO ( CRD42015017592 ). [ABSTRACT FROM AUTHOR]

Despite a shift from institutional services toward more home and community-based services (HCBS) for older adults who need long-term services and supports (LTSS), the effects of HCBS have yet to be adequately synthesized in the literature. This review of literature from 1995 to 2012 compares the outcome trajectories of older adults served through HCBS (including assisted living [AL]) and in nursing homes (NHs) for physical function, cognition, mental health, mortality, use of acute care, and associated harms (e.g., accidents, abuse, and neglect) and costs. NH and AL residents did not differ in physical function, cognition, mental health, and mortality outcomes. The differences in harms between HCBS recipients and NH residents were mixed. Evidence was insufficient for cost comparisons. More and better research is needed to draw robust conclusions about how the service setting influences the outcomes and costs of LTSS for older adults. Future research should address the numerous methodological challenges present in this field of research and should emphasize studies evaluating the effectiveness of HCBS. [ABSTRACT FROM PUBLISHER]

Objectives: Systematic reviews should provide balanced assessments of benefits and harms, while focusing on the most important outcomes. Selection of harms to be reviewed can be a challenge due to the potential for large numbers of diverse harms., Study Design and Setting: A workgroup of methodologists from Evidence-based Practice Centers (EPCs) developed consensus-based guidance on selection and prioritization of harms in systematic reviews. Recommendations were informed by a literature scan, review of Evidence-based Practice Center reports, and interviews with experts in conducting reviews or assessing harms and persons representing organizations that commission or use systematic reviews., Results: Ten recommendations were developed on selection and prioritization of harms, including routinely focusing on serious as well as less serious but frequent or bothersome harms; routinely engaging stakeholders and using literature searches and other data sources to identify important harms; using a prioritization process (formal or less formal) to inform selection decisions; and describing the methods used to select and prioritize harms., Conclusion: We provide preliminary guidance for a more structured approach to selection and prioritization of harms in systematic reviews., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: The number of systematic reviews that aim to compare multiple interventions using network meta-analysis is increasing. In this study, we highlight aspects of a standard systematic review protocol that may need modification when multiple interventions are to be compared., Study Design and Setting: We take the protocol format suggested by Cochrane for a standard systematic review as our reference and compare the considerations for a pairwise review with those required for a valid comparison of multiple interventions. We suggest new sections for protocols of systematic reviews including network meta-analyses with a focus on how to evaluate their assumptions. We provide example text from published protocols to exemplify the considerations., Conclusion: Standard systematic review protocols for pairwise meta-analyses need extensions to accommodate the increased complexity of network meta-analysis. Our suggested modifications are widely applicable to both Cochrane and non-Cochrane systematic reviews involving network meta-analyses., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: We compared the effectiveness of PCA3 (prostate cancer antigen 3) and select comparators for improving initial or repeat biopsy decision making in men at risk for prostate cancer, or treatment choices in men with prostate cancer., Materials and Methods: MEDLINE®, EMBASE®, Cochrane Database and gray literature were searched from January 1990 through May 2012. Included studies were matched, and measured PCA3 and comparator(s) within a cohort. No matched analyses were possible. Differences in independent performance estimates between PCA3 and comparators were computed within studies. Studies were assessed for quality using QUADAS (Quality Assessment of Diagnostic Accuracy Studies) and for strength of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria., Results: Among 1,556 publications identified, 34 observational studies were analyzed (24 addressed diagnostic accuracy and 13 addressed treatment decisions). Most studies were conducted in opportunistic cohorts of men referred for procedures and were not designed to answer key questions. Two study biases (partial verification and sampling) were addressed by analyses, allowing some conclusions to be drawn. PCA3 was more discriminatory than total prostate specific antigen increases (eg at an observed 50% specificity, summary sensitivities were 77% and 57%, respectively). Analyses indicated that this finding holds for initial and repeat biopsies, and that the markers were independent predictors. For all other biopsy decision making comparisons and associated health outcomes, strength of evidence was insufficient. For treatment decision making, strength of evidence was insufficient for all outcomes and comparators., Conclusions: PCA3 had a higher diagnostic accuracy than total prostate specific antigen increases, but strength of evidence was low (limited confidence in effect estimates). Strength of evidence was insufficient to conclude that PCA3 testing leads to improved health outcomes. For all other outcomes and comparators, strength of evidence was insufficient., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)