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Abstract Welcome to a new age in publishing systematic reviews. We hope the launch of Systematic Reviews will resonate with a broad spectrum of readers interested in using them in a variety of ways, such as providing comprehensive and up to date evidence for patient management, informing health policy, and developing rigorous practice guidelines. Systematic reviews are increasingly popular. Our journal is committed to publishing a wide variety of well conducted and transparently reported systematic reviews and associated research. We are open access and electronic and not confined by space and so offer scope for publishing reviews in detail and providing a modern and innovative approach to publishing. We look forward to participating in the voyage with all of our readers.

Background Hospitals have implemented diverse quality improvement (QI) interventions to reduce rates of catheter- associated urinary tract infections (CAUTIs). The economic value of these QI interventions is uncertain. Objective To systematically review economic evaluations of QI interventions designed to prevent CAUTI in acute care hospitals. Methods A search of Ovid MEDLINE, Econlit, Centre for Reviews & Dissemination, New York Academy of Medicine's Grey Literature Report, WorldCat, IDWeek conference abstracts and prior systematic reviews was conducted from January 2000 to October 2020. We included English- language studies of any design that evaluated organisational or structural changes to prevent CAUTI in acute care hospitals, and reported programme and infection- related costs. Dual reviewers assessed study design, effectiveness, costs and study quality. For each eligible study, we performed a cost- consequences analysis from the hospital perspective, estimating the incidence rate ratio (IRR) and incremental net cost/savings per hospital over 3 years. Unadjusted weighted regression analyses tested predictors of these measures, weighted by catheter days per study. Results Fifteen unique economic evaluations were eligible, encompassing 74 hospitals. Across 12 studies amenable to standardisation, QI interventions were associated with a 43% decline in infections (mean IRR 0.57, 95% CI 0.44 to 0.70) and wide ranges of net costs (mean US$52 000, 95% CI -$288 000 to $392 000), relative to usual care. Conclusions QI interventions were associated with large declines in infection rates and net costs to hospitals that varied greatly but that, on average, were not significantly different from zero over 3 years. Future research should examine specific practices associated with cost- savings and clinical effectiveness, and examine whether or not more comprehensive interventions offer hospitals and patients the best value. [ABSTRACT FROM AUTHOR]

Background: Bedside "sitters" are often used for patients at high risk for falls, but they are expensive and their effectiveness is unclear.Purpose: To review evidence about the effect of sitters and alternatives to sitters on patient falls in acute care hospitals.Data Sources: PubMed searches to 8 October 2019, other databases from inception to December 2018, citation searches on key articles, and a Google search (22 October 2019).Study Selection: English-language studies of any design that assessed the effect of adding sitters to usual care or compared alternatives to sitters (for example, video monitors or "close observation units") for adult patients on general wards of acute care hospitals and reported falls as a primary outcome.Data Extraction: Dual-reviewer extraction of study data and risk of bias; single reviewer with group discussion for GRADE (Grading of Recommendations Assessment, Development and Evaluation) certainty of evidence.Data Synthesis: Of 20 studies meeting inclusion criteria, 2 added sitters to usual care and 18 compared alternatives to sitters. There were no randomized trials, 11 time-series studies, 1 retrospective quasi-experimental study, and 8 pre-post studies. All studies had at least 1 methodological limitation. Two studies provided very-low-certainty evidence that adding sitters reduced falls. Eight studies provided moderate-certainty evidence that interventions that included video monitoring reduced sitter use and either did not affect or reduced the number of falls. Very-low-certainty evidence suggested that interventions that included nurse assessment tools (3 studies) or a close observation unit (2 studies) were effective alternatives to sitters.Limitation: No studies had low risk of bias, publication bias is likely, and studies may have been missed.Conclusion: Despite a compelling rationale, evidence is scant that adding sitters to usual care reduces falls.Primary Funding Source: Veterans Affairs Quality Enhancement Research Initiative. (PROSPERO: CRD42019127424). [ABSTRACT FROM AUTHOR]

Objectives: Massage therapy has been proposed for painful conditions, but it can be difficult to understand the breadth and depth of evidence, as various painful conditions may respond differently to massage. The authors conducted an evidence mapping process and generated an "evidence map" to visually depict the distribution of evidence available for massage and various pain indications to identify gaps in evidence and to inform future research priorities. Design: The authors searched PubMed, Embase, and Cochrane for systematic reviews reporting pain outcomes for massage therapy. The authors assessed the quality of each review using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) criteria. The authors used a bubble plot to depict the number of included articles, pain indication, effect of massage for pain, and strength of findings for each included systematic review. Results: The authors identified 49 systematic reviews, of which 32 were considered high quality. Types of pain frequently included in systematic reviews were cancer pain, low back pain, and neck pain. High quality reviews concluded that there was low strength of evidence of potential benefits of massage for labor, shoulder, neck, low back, cancer, arthritis, postoperative, delayed onset muscle soreness, and musculoskeletal pain. Reported attributes of massage interventions include style of massage, provider, co-interventions, duration, and comparators, with 14 high-quality reviews reporting all these attributes in their review. Conclusion: Prior reviews have conclusions of low strength of evidence because few primary studies of large samples with rigorous methods had been conducted, leaving evidence gaps about specific massage type for specific pain. Primary studies often do not provide adequate details of massage therapy provided, limiting the extent to which reviews are able to draw conclusions about characteristics such as provider type. [ABSTRACT FROM AUTHOR]

Background: Cranial electrical stimulation (CES) is increasingly popular as a treatment, yet its clinical benefit is unclear.Purpose: To review evidence about the benefits and harms of CES for adult patients with chronic painful conditions, depression, anxiety, and insomnia.Data Sources: Several databases from inception to 10 October 2017 without language restrictions and references from experts, prior reviews, and manufacturers.Study Selection: Randomized controlled trials of CES versus usual care or sham CES that reported pain, depression, anxiety, or sleep outcomes in any language.Data Extraction: Single-reviewer extraction checked by another; dual independent quality assessment; strength-of-evidence grading by the first author with subsequent group discussion.Data Synthesis: Twenty-eight articles from 26 randomized trials met eligibility criteria. The 2 trials that compared CES with usual care were small, and neither reported a statistically significant benefit in pain or anxiety outcomes for patients with fibromyalgia or anxiety, respectively. Fourteen trials with sham or placebo controls involving patients with painful conditions, such as headache, neuromuscular pain, or musculoskeletal pain, had conflicting results. Four trials done more than 40 years ago and 1 from 2014 provided low-strength evidence of a possible modest benefit compared with sham treatments in patients with anxiety and depression. Trials in patients with insomnia (n = 2), insomnia and anxiety (n = 1), or depression (n = 3) had inconclusive or conflicting results. Low-strength evidence suggested that CES does not cause serious side effects.Limitation: Most trials had small sample sizes and short durations; all had high risk of bias due to inadequate blinding.Conclusion: Evidence is insufficient that CES has clinically important effects on fibromyalgia, headache, neuromusculoskeletal pain, degenerative joint pain, depression, or insomnia; low-strength evidence suggests modest benefit in patients with anxiety and depression.Primary Funding Source: Veterans Affairs Quality Enhancement Research Initiative. (PROSPERO: CRD42016023951). [ABSTRACT FROM AUTHOR]

Background: Several risk factors are associated with multiple sclerosis (MS) progression and may be amenable to intervention. Objective: To systematically review the evidence for interventions targeting risk factors for MS progression. Methods: We searched six databases and existing reviews till March 2015 and consulted with experts to identify randomized controlled trials (RCTs) of interventions targeting MS risk factors (PROSPERO 2015:CRD42015016461). Results: In total, 37 RCTs met inclusion criteria. Expanded Disability Status Scale (EDSS) scores after exercise interventions did not differ compared with untreated controls (standardized mean differences (SMDs): 0.02; confidence interval (CI): -0.40, 0.44; I2: 0%; seven RCTs; very low quality of evidence (QoE)). Dietary interventions did not show a statistically significant effect on the relative risk (RR) of progression (RR: 0.86; CI: 0.67, 1.05; I2: 0%; four RCTs; moderate QoE) compared to placebo. EDSS scores after vitamin D supplementation were not significantly different from placebo (SMD: -0.15; CI: -0.33, 0.02; I2: 0%; five RCTs; very low QoE). Conclusion: We did not identify any risk factor interventions with significant effects on MS progression, but the overall QoE was limited. More adequately powered trials are needed on vitamin D supplementation, long-term exercise, and smoking cessation. [ABSTRACT FROM AUTHOR]

Background: The need for systematic methods for reviewing evidence is continuously increasing. Evidence mapping is one emerging method. There are no authoritative recommendations for what constitutes an evidence map or what methods should be used, and anecdotal evidence suggests heterogeneity in both. Our objectives are to identify published evidence maps and to compare and contrast the presented definitions of evidence mapping, the domains used to classify data in evidence maps, and the form the evidence map takes. Methods: We conducted a systematic review of publications that presented results with a process termed "evidence mapping" or included a figure called an "evidence map." We identified publications from searches of ten databases through 8/21/2015, reference mining, and consulting topic experts. We abstracted the research question, the unit of analysis, the search methods and search period covered, and the country of origin. Data were narratively synthesized. Results: Thirty-nine publications met inclusion criteria. Published evidence maps varied in their definition and the form of the evidence map. Of the 31 definitions provided, 67 % described the purpose as identification of gaps and 58 % referenced a stakeholder engagement process or user-friendly product. All evidence maps explicitly used a systematic approach to evidence synthesis. Twenty-six publications referred to a figure or table explicitly called an "evidence map," eight referred to an online database as the evidence map, and five stated they used a mapping methodology but did not present a visual depiction of the evidence. Conclusions: The principal conclusion of our evaluation of studies that call themselves "evidence maps" is that the implied definition of what constitutes an evidence map is a systematic search of a broad field to identify gaps in knowledge and/or future research needs that presents results in a user-friendly format, often a visual figure or graph, or a searchable database. Foundational work is needed to better standardize the methods and products of an evidence map so that researchers and policymakers will know what to expect of this new type of evidence review. Systematic review registration: Although an a priori protocol was developed, no registration was completed; this review did not fit the PROSPERO format. [ABSTRACT FROM AUTHOR]

Background: The purpose of this review is to study the effect of school-based interventions on smoking prevention for girls. Methods: We performed a systematic review of articles published since 1992 on school-based tobacco-control interventions in controlled trials for smoking prevention among children. We searched the databases of PubMed, Embase, Web of Science, The Cochrane Databases, CINAHL, Social Science Abstracts, and PsycInfo. Two reviewers independently assessed trials for inclusion and quality and extracted data. A pooled random-effects estimate was estimated of the overall relative risk. Results: Thirty-seven trials were included, of which 16 trials with 24,210 girls were included in the pooled analysis. The overall pooled effect was a relative risk (RR) of 0.96 (95 % confidence interval (CI) 0.86-1.08; I² =75 %). One study in which a school-based intervention was combined with a mass media intervention showed more promising results compared to only school-based prevention, and four studies with girl-specific interventions, that could not be included in the pooled analysis, reported statistically significant benefits for attitudes and intentions about smoking and quit rates. Conclusions: There was no evidence that school-based smoking prevention programs have a significant effect on preventing adolescent girls from smoking. Combining school-based programs with mass media interventions, and developing girl-specific interventions, deserve additional study as potentially more effective interventions compared to school-based-only intervention programs. Systematic review registration: PROSPERO CRD42012002322 [ABSTRACT FROM AUTHOR]

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the screening, monitoring, and treatment of adults with stage 1 to 3 chronic kidney disease. Methods: This guideline is based on a systematic evidence review evaluating the published literature on this topic from 1985 through November 2011 that was identified by using MEDLINE and the Cochrane Database of Systematic Reviews. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, chronic heart failure, composite vascular outcomes, composite renal outcomes, end-stage renal disease, quality of life, physical function, and activities of daily living. This guideline grades the evidence and recommendations by using ACP's clinical practice guidelines grading system. Recommendation 1: ACP recommends against screening for chronic kidney disease in asymptomatic adults without risk factors for chronic kidney disease. (Grade: weak recommendation, low-quality evidence) Recommendation 2: ACP recommends against testing for proteinuria in adults with or without diabetes who are currently taking an angiotensin-converting enzyme inhibitor or an angiotensin II-receptor blocker. (Grade: weak recommendation, low-quality evidence) Recommendation 3: ACP recommends that clinicians select pharmacologic therapy that includes either an angiotensin-converting enzyme inhibitor (moderate-quality evidence) or an angiotensin II-receptor blocker (high-quality evidence) in patients with hypertension and stage 1 to 3 chronic kidney disease. (Grade: strong recommendation) Recommendation 4: ACP recommends that clinicians choose statin therapy to manage elevated low-density lipoprotein in patients with stage 1 to 3 chronic kidney disease. (Grade: strong recommendation, moderate-quality evidence) [ABSTRACT FROM AUTHOR]

A small percentage of patients die during hospitalization or shortly thereafter, and it is widely believed that more or better nursing care could prevent some of these deaths. The author systematically reviewed the evidence about nurse staffing ratios and in-hospital death through September 2012. From 550 titles, 87 articles were reviewed and 15 new studies that augmented the 2 existing reviews were selected. The strongest evidence supporting a causal relationship between higher nurse staffing levels and decreased inpatient mortality comes from a longitudinal study in a single hospital that carefully accounted for nurse staffing and patient comorbid conditions and a meta-analysis that found a "dose- response relationship" in observational studies of nurse staffing and death. No studies reported any serious harms associated with an increase in nurse staffing. Limiting any stronger conclusions is the lack of an evaluation of an intervention to increase nurse staffing ratios. The formal costs of increasing the nurse-patient ratio cannot be calculated because there has been no evaluation of an intentional change in nurse staffing to improve patient outcomes. INSET: Key Summary Points. [ABSTRACT FROM AUTHOR]

Objective. To review and characterize existing health care efficiency measures in order to facilitate a common understanding about the adequacy of these methods. Data Sources. Review of the MedLine and EconLit databases for articles published from 1990 to 2008, as well as search of the “gray” literature for additional measures developed by private organizations. Study Design. We performed a systematic review for existing efficiency measures. We classified the efficiency measures by perspective, outputs, inputs, methods used, and reporting of scientific soundness. Principal Findings. We identified 265 measures in the peer-reviewed literature and eight measures in the gray literature, with little overlap between the two sets of measures. Almost all of the measures did not explicitly consider the quality of care. Thus, if quality varies substantially across groups, which is likely in some cases, the measures reflect only the costs of care, not efficiency. Evidence on the measures' scientific soundness was mostly lacking: evidence on reliability or validity was reported for six measures (2.3 percent) and sensitivity analyses were reported for 67 measures (25.3 percent). Conclusions. Efficiency measures have been subjected to few rigorous evaluations of reliability and validity, and methods of accounting for quality of care in efficiency measurement are not well developed at this time. Use of these measures without greater understanding of these issues is likely to engender resistance from providers and could lead to unintended consequences. [ABSTRACT FROM AUTHOR]

The article presents a systematic review which was designed to estimate bariatric surgery rates among women aged 18 to 45 years. An assessment of published literature on fertility after surgery and pregnancy outcomes is included. Articles published between 1985 and February 2008 on bariatric surgery among women of reproductive age were identified through a search of the Nationwide Inpatient Sample and multiple electronic databases. Findings showed lower rates of maternal complication after bariatric surgery than for obese women without bariatric surgery. There were no differences found in neonatal outcomes between the two groups. Researchers note that rigorously designed studies are needed.

Systematic reviewers increasingly must decide whether and how to incorporate existing systematic reviews into complex systematic reviews that are commissioned to support clinical guideline development or for other health policy uses. To date, however, this issue has been largely unexamined. Reviewers seeking to incorporate existing reviews into new reviews face a set of important questions: Can this practice adhere to systematic review principles? Will it save time? When should it be avoided? Will it produce valid results and be acceptable to users? Drawing from their collective experience, the authors outline a series of steps that can help reviewers reach reasoned decisions about the incorporation of existing systematic reviews and enumerate potential hazards to consider in doing so. They highlight issues surrounding the main steps reviewers must undertake, including locating existing reviews; assessing their relevance to the new review; assessing the quality of relevant reviews; determining how to incorporate high-quality, relevant existing systematic reviews; and clearly reporting the methods used and the results from this process. Further specification of methods, including the development of reporting standards for this approach, is needed. [ABSTRACT FROM AUTHOR]

The article presents a clinical practice guideline on diagnosis and management of stable chronic obstructive pulmonary disease (COPD) from the American College of Physicians in the U.S. The target audience is physicians, and adults with COPD as the target patient population. The recommendations presented are based on the systematic evidence review by T. J. Wilt and colleagues and the Agency for Healthcare Research and Quality-sponsored Minnesota Evidence-based Practice Center evidence report.

Objective: To evaluate the evidence of the supplements vitamin C and vitamin E for treatment and prevention of cancer.Methods: Systematic review of trials and meta-analysis. DATA SOURCES AND MAIN RESULTS: Thirty-eight studies showed scant evidence that vitamin C or vitamin E beneficially affects survival. In the ATBC Cancer Prevention Study Group, no statistically significant effect of treatment was seen for any cancer individually, and our pooled relative risk (regardless of tumor type) for alpha-tocopherol alone was 0.91 (95% confidence interval [CI]: 0.74, 1.12). All cause mortality was not significant. In the Linxian General Population Trial, the relative risks for cancer death for vitamin C (combined with molybdenum) was 1.06 (95% CI: 0.92, 1.21) and for vitamin E (combined with beta-carotene and selenium) was 0.87 (95% CI: 0.76, 1.00). We identified only 3 studies that reported statistically significant beneficial results: vitamin C (in combination with BCG) was found to be beneficial in a single trial of bladder cancer and vitamin E (in combination with omega-3 fatty acid) increased survival in patients with advanced cancer. In the ATBC trial, in analyses of 6 individual cancers, the prevention of prostate cancer in subjects treated with alpha-tocopherol was statistically significant (RR=0.64, 95% CI: 0.44, 0.94).Conclusions: The systematic review of the literature does not support the hypothesis that the use of supplements of vitamin C or vitamin E in the doses tested helps prevent and/or treat cancer in the populations tested. There were isolated findings of benefit, which require confirmation. [ABSTRACT FROM AUTHOR]

The use of complementary and alternative medicine (CAM) continues to grow in the United States. The Agency for Healthcare Research and Quality has devoted a substantial proportion of the Evidence-based Practice Center (EPC) program to systematic reviews of CAM. Such syntheses present different challenges from those conducted on western medicine topics, and in many ways are more difficult. We discuss 3 challenges: identifying evidence about CAM, assessing the quality of individual studies, and addressing rare serious adverse events. We use illustrations from EPC evidence reports to show readers approaches to the 3 areas and then present specific recommendations for each issue. [ABSTRACT FROM AUTHOR]

Endoscopic band ligation (EBL) is the community-accepted standard therapy for the secondary prophylaxis of esophageal variceal hemorrhage. Recent data indicate that combination EBL and sclerotherapy may be a more effective therapy than EBL alone. Yet existing data are conflicting. We therefore performed a meta-analysis to compare the efficacy and safety of EBL and sclerotherapy versus EBL alone for the secondary prophylaxis of esophageal variceal hemorrhage. We performed a systematic review of two computerized databases (MEDLINE and EMBASE) along with manual-searching of published abstracts to identify relevant citations without language restrictions from 1990 to 2002. Eight studies met explicit inclusion criteria. We performed meta-analysis of these studies to pool the relative risk for the following outcomes: esophageal variceal rebleeding, death, number of endoscopic sessions to achieve variceal obliteration, and therapeutic complications. There were no significant differences between EBL and sclerotherapy versus EBL alone in the risk of esophageal variceal rebleeding (RR = 1.05; 95% CI = 0.67-1.64; P = 0.83), death (RR = 0.99; 95% CI = 0.68-1.44; P = 0.96), or number of endoscopic sessions to variceal obliteration (RR = 0.23; 95% CI = 0.055-0.51; P = 0.11). However, the incidence of esophageal stricture formation was significantly higher in the EBL group than in the sclerotherapy group. There is no evidence that the addition of sclerotherapy to endoscopic band ligation changes clinically relevant outcomes (variceal rebleeding, death, time to variceal obliteration) in the secondary prophylaxis of esophageal variceal hemorrhage. Moreover, combination EBL and sclerotherapy had more esophageal stricture formation than EBL alone. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the publication of clinical guidelines and systematic review on screening for osteoporosis in men by the American College of Physicians.

The article discusses a systematic review protocol called Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) as a tool for reporting guidelines in the review process for clinical trials.

A chart is presented that shows the items contained in the preferred reporting items for systematic reviews and meta-analyses protocol (PRISMA-P) such as identification, registration and eligibility criteria.

An abstract of the study "An Evidence Map of the Effects of Acupuncture" by Stephanie Taylor and colleagues is presented.

In response to concerns about healthcare access and long wait times within the Veterans Health Administration (VA), Congress passed the Choice Act of 2014 and the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act of 2018 to create a program for patients to receive care in non-VA sites of care, paid by VA. Questions remain about the quality of surgical care between these sites in specific and between VA and non-VA care in general. This review synthesizes recent evidence comparing surgical care between VA and non-VA delivered care across the domains of quality and safety, access, patient experience, and comparative cost/efficiency (2015 to 2021). Eighteen studies met the inclusion criteria. Of 13 studies reporting quality and safety outcomes, 11 reported that quality and safety of VA surgical care were as good as or better than non-VA sites of care. Six studies of access did not have a preponderance of evidence favoring care in either setting. One study of patient experience reported VA care as about equal to non-VA care. All 4 studies of cost/efficiency outcomes favored non-VA care. Based on limited data, these findings suggest that expanding eligibility for veterans to get care in the community may not provide benefits in terms of increasing access to surgical procedures, will not result in better quality, and may result in worse quality of care, but may reduce inpatient length of stay and perhaps cost less. [ABSTRACT FROM AUTHOR]

Objectives: To assess the reliability of the Cochrane Risk of Bias (ROB) tool between individual raters and across consensus agreements of pairs of reviewers and examine the impact of study-level factors on reliability. Study Design and Setting: Two reviewers assessed risk of bias for 154 randomized controlled trials (RCTs). For 30 RCTs, two reviewers from each of four centers assessed risk of bias and reached consensus. We assessed interrater agreement using kappas and the impact of study-level factors through subgroup analyses. Results: Reliability between two reviewers was fair for most domains (k = 0.24 - 0.37), except sequence generation (k = 0.79, substantial). Reliability results across reviewer pairs: sequence generation, moderate (k = 50 - 60); allocation concealment and ''other sources of bias,'' fair (k = 0.37 - 0.27); and other domains, slight (k = 0.05 - 0.09). Reliability was influenced by the nature of the outcome, nature of the intervention, study design, trial hypothesis, and funding source. Variability resulted from different interpretation of the tool rather than different information identified in the study reports. Conclusion: Low agreement has implications for interpreting systematic reviews. These findings suggest the need for detailed guidance in assessing the risk of bias. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Apply and compare two methods that identify signals for the need to update systematic reviews, using three Evidence-based Practice Center reports on omega-3 fatty acids as test cases. Study Design and Setting: We applied the RAND method, which uses domain (subject matter) expert guidance, and a modified Ottawa method, which uses quantitative and qualitative signals. For both methods, we conducted focused electronic literature searches of recent studies using the key terms from the original reports. We assessed the agreement between the methods and qualitatively assessed the merits of each system. Results: Agreement between the two methods was “substantial” or better (kappa>0.62) in three of the four systematic reviews. Overall agreement between the methods was “substantial” (kappa=0.64, 95% confidence interval [CI] 0.45–0.83). Conclusion: The RAND and modified Ottawa methods appear to provide similar signals for the possible need to update systematic reviews in this pilot study. Future evaluation with a broader range of clinical topics and eventual comparisons between signals to update reports and the results of full evidence review updates will be needed. We propose a hybrid approach combining the best features of both methods, which should allow efficient review and assessment of the need to update. [Copyright &y& Elsevier]

Abstract: Objective: Systematic reviewers disagree about the ability of observational studies to answer questions about the benefits or intended effects of pharmacotherapeutic, device, or procedural interventions. This study provides a framework for decision making on the inclusion of observational studies to assess benefits and intended effects in comparative effectiveness reviews (CERs). Study Design and Setting: The conceptual model and recommendations were developed using a consensus process by members of the methods workgroup of the Effective Health Care Program of the Agency for Healthcare Research and Quality. Results: In considering whether to use observational studies in CERs for addressing beneficial effects, reviewers should answer two questions: (1) Are there gaps in the evidence from randomized controlled trials (RCTs)? (2) Will observational studies provide valid and useful information? The latter question involves the following: (a) refocusing the study questions on gaps in the evidence from RCTs, (b) assessing the risk of bias of the body of evidence of observational studies, and (c) assessing whether available observational studies address the gap review questions. Conclusions: Because it is unusual to find sufficient evidence from RCTs to answer all key questions concerning benefit or the balance of benefits and harms, comparative effectiveness reviewers should routinely assess the appropriateness of inclusion of observational studies for questions of benefit. Furthermore, reviewers should explicitly state the rationale for inclusion or exclusion of observational studies when conducting CERs. [Copyright &y& Elsevier]