Interventions to reduce contaminated aerosols produced during dental procedures for preventing infectious diseases.

BACKGROUND: Many dental procedures produce aerosols (droplets, droplet nuclei and splatter) that harbour various pathogenic micro-organisms and may pose a risk for the spread of infections between dentist and patient. The COVID-19 pandemic has led to greater concern about this risk. OBJECTIVES: To assess the effectiveness of methods used during dental treatment procedures to minimize aerosol production and reduce or neutralize contamination in aerosols. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases on 17 September 2020: Cochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library, 2020, Issue 8), MEDLINE Ovid (from 1946); Embase Ovid (from 1980); the WHO COVID-19 Global literature on coronavirus disease; the US National Institutes of Health Trials Registry (ClinicalTrials.gov); and the Cochrane COVID-19 Study Register. We placed no restrictions on the language or date of publication. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on aerosol-generating procedures (AGPs) performed by dental healthcare providers that evaluated methods to reduce contaminated aerosols in dental clinics (excluding preprocedural mouthrinses). The primary outcomes were incidence of infection in dental staff or patients, and reduction in volume and level of contaminated aerosols in the operative environment. The secondary outcomes were cost, accessibility and feasibility. DATA COLLECTION AND ANALYSIS: Two review authors screened search results, extracted data from the included studies, assessed the risk of bias in the studies, and judged the certainty of the available evidence. We used mean differences (MDs) and 95% confidence intervals (CIs) as the effect estimate for continuous outcomes, and random-effects meta-analysis to combine data. We assessed heterogeneity. MAIN RESULTS: We included 16 studies with 425 participants aged 5 to 69 years. Eight studies had high risk of bias; eight had unclear risk of bias. No studies measured infection. All studies measured bacterial contamination using the surrogate outcome of colony-forming units (CFU). Two studies measured contamination per volume of air sampled at different distances from the patient's mouth, and 14 studies sampled particles on agar plates at specific distances from the patient's mouth. The results presented below should be interpreted with caution as the evidence is very low certainty due to heterogeneity, risk of bias, small sample sizes and wide confidence intervals. Moreover, we do not know the 'minimal clinically important difference' in CFU. High-volume evacuator Use of a high-volume evacuator (HVE) may reduce bacterial contamination in aerosols less than one foot (~ 30 cm) from a patient's mouth (MD -47.41, 95% CI -92.76 to -2.06; 3 RCTs, 122 participants (two studies had split-mouth design); very high heterogeneity I² = 95%), but not at longer distances (MD -1.00, -2.56 to 0.56; 1 RCT, 80 participants). One split-mouth RCT (six participants) found that HVE may not be more effective than conventional dental suction (saliva ejector or low-volume evacuator) at 40 cm (MD CFU -2.30, 95% CI -5.32 to 0.72) or 150 cm (MD -2.20, 95% CI -14.01 to 9.61). Dental isolation combination system One RCT (50 participants) found that there may be no difference in CFU between a combination system (Isolite) and a saliva ejector (low-volume evacuator) during AGPs (MD -0.31, 95% CI -0.82 to 0.20) or after AGPs (MD -0.35, -0.99 to 0.29). However, an 'n of 1' design study showed that the combination system may reduce CFU compared with rubber dam plus HVE (MD -125.20, 95% CI -174.02 to -76.38) or HVE (MD -109.30, 95% CI -153.01 to -65.59). Rubber dam One split-mouth RCT (10 participants) receiving dental treatment, found that there may be a reduction in CFU with rubber dam at one-metre (MD -16.20, 95% CI -19.36 to -13.04) and two-metre distance (MD -11.70, 95% CI -15.82 to -7.58). One RCT of 47 dental students found use of rubber dam may make no difference in CFU at the forehead (MD 0.98, 95% CI -0.73 to 2.70) and occipital region of the operator (MD 0.77, 95% CI -0.46 to 2.00). One split-mouth RCT (21 participants) found that rubber dam plus HVE may reduce CFU more than cotton roll plus HVE on the patient's chest (MD -251.00, 95% CI -267.95 to -234.05) and dental unit light (MD -12.70, 95% CI -12.85 to -12.55). Air cleaning systems One split-mouth CCT (two participants) used a local stand-alone air cleaning system (ACS), which may reduce aerosol contamination during cavity preparation (MD -66.70 CFU, 95% CI -120.15 to -13.25 per cubic metre) or ultrasonic scaling (MD -32.40, 95% CI - 51.55 to -13.25). Another CCT (50 participants) found that laminar flow in the dental clinic combined with a HEPA filter may reduce contamination approximately 76 cm from the floor (MD -483.56 CFU, 95% CI -550.02 to -417.10 per cubic feet per minute per patient) and 20 cm to 30 cm from the patient's mouth (MD -319.14 CFU, 95% CI - 385.60 to -252.68). Disinfectants ‒ antimicrobial coolants Two RCTs evaluated use of antimicrobial coolants during ultrasonic scaling. Compared with distilled water, coolant containing chlorhexidine (CHX), cinnamon extract coolant or povidone iodine may reduce CFU: CHX (MD -124.00, 95% CI -135.78 to -112.22; 20 participants), povidone iodine (MD -656.45, 95% CI -672.74 to -640.16; 40 participants), cinnamon (MD -644.55, 95% CI -668.70 to -620.40; 40 participants). CHX coolant may reduce CFU more than povidone iodine (MD -59.30, 95% CI -64.16 to -54.44; 20 participants), but not more than cinnamon extract (MD -11.90, 95% CI -35.88 to 12.08; 40 participants). AUTHORS' CONCLUSIONS: We found no studies that evaluated disease transmission via aerosols in a dental setting; and no evidence about viral contamination in aerosols. All of the included studies measured bacterial contamination using colony-forming units. There appeared to be some benefit from the interventions evaluated but the available evidence is very low certainty so we are unable to draw reliable conclusions. We did not find any studies on methods such as ventilation, ionization, ozonisation, UV light and fogging. Studies are needed that measure contamination in aerosols, size distribution of aerosols and infection transmission risk for respiratory diseases such as COVID-19 in dental patients and staff.

Designing clinical trials for future space missions as a pathway to changing how clinical trials are conducted on Earth.

OBJECTIVE: The project aims to build a framework for conducting clinical trials for long-term interplanetary missions to contribute to innovation in clinical trials on Earth, especially around patient involvement and ownership. METHODS: We conducted two workshops in which participants were immersed in the speculative scenario of an interplanetary mission in which health problems emerged that required medical trials to resolve. The workshops used virtual reality and live simulation to mimic a zero-gravity environment and visual perception shifts and were followed by group discussion. RESULTS: Some key aspects for the framework that emerged from the workshops included: (a) approaches to be inclusive in the management of the trial, (b) approaches to be inclusive in designing the research project (patient preference trials, n-of-1 trials, designing clinical trials to be part of a future prospective meta-analysis, etc), (c) balancing the research needs and the community needs (eg, allocation of the participants based on both research and community need), (d) ethics and partnerships (ethics and consent issues and how they relate to partnerships and relationships). CONCLUSION: In identifying some key areas that need to be incorporated in future planning of clinical trials for interplanetary missions, we also identified areas that are relevant to engaging patients in clinical trials on Earth. We will suggest using the same methodology to facilitate more in-depth discussions on specific aspects of clinical trials in aerospace medicine. The methodology can be more widely used in other areas to open new inclusive conversations around innovating research methodology.

Global health trials methodological research agenda: results from a priority setting exercise.

BACKGROUND: Methodological research into the design, conduct, analysis and reporting of trials is essential to optimise the process. UK specialists in the field have established a set of top priorities in aid of this research. These priorities, however, may not be reflected in the needs of similar research in low- to middle-income countries (LMICs) with different healthcare provision, resources and research infrastructure. The aim of the study was to identify the top priorities for methodological research in LMICs to inform further research and ultimately to improve clinical trials in these regions. METHODS: An online, two-round survey was conducted from December 2016 to April 2017 amongst researchers and methodologists working on trials in LMICs. The first round required participants to suggest between three and six topics which they felt were priorities for trial methodological research in LMICs. The second round invited participants to grade the importance of a compulsory list of topics suggested by four or more individuals, and an optional list of the remaining topics. FINDINGS: Rounds 1 and 2 were completed by 412 and 314 participants, respectively. A wide spread of years of experience, discipline, current country of residence, origin of trials training and area of involvement in trials was reported. The topics deemed most important for methodological research were: choosing appropriate outcomes to measure and training of research staff. CONCLUSION: By presenting these top priorities we have the foundations of a global health trials methodological research agenda which we hope will foster future research in specific areas in order to increase and improve trials in LMICs.

Physical activity and the prevention, reduction, and treatment of alcohol and/or substance use across the lifespan (The PHASE review): protocol for a systematic review.

BACKGROUND: Alcohol and substance use results in significant human and economic cost globally and is associated with economic costs of £21 billion and £15billion within the UK, respectively, and trends for use are not improving. Pharmacological interventions are well researched, but relapse rates across interventions for substance and alcohol use disorders are as high as 60-90%. Physical activity may offer an alternative or adjunct approach to reducing rates of alcohol and substance use that is associated with few adverse side effects, is easily accessible, and is potentially cost-effective. Through psychological, behavioural, and physiological mechanisms, physical activity may offer benefits in the prevention, reduction, and treatment of alcohol and substance use across the lifespan. Whilst physical activity is widely advocated as offering benefit, no systematic review exists of physical activity (in all forms) and its effects on all levels of alcohol and substance use across all ages to help inform policymakers, service providers, and commissioners. METHODS: The objectives of this mixed methods systematic review are to describe and evaluate the quantitative and qualitative research obtained by a diverse search strategy on the impact of physical activity and its potential to: 1. Reduce the risk of progression to alcohol and/or substance use (PREVENTION) 2. Support individuals to reduce alcohol and/or substance use for harm reduction (REDUCTION), and 3. Promote abstinence and relapse prevention during and after treatment for an alcohol and/or substance use disorder (TREATMENT). With the input of key stakeholders, we aim to assess how what we know can be translated into policy and practice. Quantitative, qualitative, service evaluations, and economic analyses will be brought together in a final narrative synthesis that will describe the potential benefits of physical activity for whom, in what conditions, and in what form. DISCUSSION: This review will provide details of what is known about physical activity and the prevention, reduction, and treatment of alcohol and/or substance use. The synthesised findings will be disseminated to policymakers, service providers, and commissioners in the UK. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number: CRD42017079322 .

Identifying gaps for research prioritisation: Global burden of external causes of injury as reflected in the Cochrane Database of Systematic Reviews.

IMPORTANCE: Burden of disease should impact research prioritisation. OBJECTIVE: To analyse the Cochrane Database of Systematic Reviews (CDSR) and determine whether systematic reviews and protocols accurately represent disease burden, as measured by disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2010 Study. METHODS: Two investigators collected GBD disability metrics for 12 external causes of injury in the GBD 2010 Study. These external causes were then assessed for systematic review and protocol representation in CDSR. Data was collected during the month of April 2015. There were no study participants aside from the researchers. Percentage of total 2010 DALYs, 2010 DALY rank, and median DALY percent change from 1990 to 2010 of the 12 external causes of injury were compared with CDSR representation of systematic reviews and protocols. Data were analysed for correlation using Spearman rank correlation. RESULTS: Eleven of the 12 causes were represented by at least one systematic review or protocol in CDSR; the category collective violence and legal intervention had no representation in CDSR. Correlation testing revealed a strong positive correlation that was statistically significant. Representation of road injury; interpersonal violence; fire, heat, and hot substances; mechanical forces; poisonings, adverse effect of medical treatment, and animal contact was well aligned with respect to DALY. Representation of falls was greater compared to DALY, while self-harm, exposure to forces of nature, and other transport injury representation was lower compared to DALY. CONCLUSIONS AND RELEVANCE: CDSR representation of external causes of injury strongly correlates with disease burden. The number of systematic reviews and protocols was well aligned for seven out of 12 causes of injury. These results provide high-quality and transparent data that may guide future prioritisation decisions.

Ethics and equity in research priority-setting: stakeholder engagement and the needs of disadvantaged groups.

A transparent and evidence-based priority-setting process promotes the optimal use of resources to improve health outcomes. Decision-makers and funders have begun to increasingly engage representatives of patients and healthcare consumers to ensure that research becomes more relevant. However, disadvantaged groups and their needs may not be integrated into the priority-setting process since they do not have a "political voice" or are unable to organise into interest groups. Equitable priority-setting methods need to balance patient needs, values, experiences with population-level issues and issues related to the health system.

Identifying otolaryngology systematic review research gaps: comparing Global Burden of Disease 2010 results with Cochrane Database of Systematic Review content.

IMPORTANCE: Burden of disease should inform research prioritization. OBJECTIVE: To determine whether systematic reviews and protocols published in the Cochrane Database of Systematic Reviews (CDSR) appropriately reflect disease burden for otolaryngologic conditions as measured by the Global Burden of Disease (GBD) 2010 project. DESIGN: Two investigators independently assessed 10 otolaryngologic conditions in CDSR for systematic review and protocol representation from March to June 2014. The otolaryngologic diseases were matched to their respective GBD 2010 disability-adjusted life-years (DALYs) to assess their correlation. MAIN OUTCOMES AND MEASURES: Relationship of CDSR representation (based on systematic reviews and protocols) with percentage of total 2010 DALYs, 2010 DALY rank, and DALY percentage change from 1990 to 2010 for 10 otolaryngologic conditions. RESULTS: All 10 otolaryngologic conditions were represented by at least 1 systematic review in CDSR. The number of reviews and protocols in CDSR was well matched with GBD 2010 disability metrics for only 1 disease, mouth cancer. Upper respiratory infections, otitis media, thyroid cancer, and cleft lip and cleft palate were overrepresented in CDSR, and esophageal cancer, "other hearing loss," nasopharynx cancer, larynx cancer, and "cancer of other part of pharynx and oropharynx" were underrepresented. CONCLUSIONS AND RELEVANCE: The representation of otolaryngologic conditions in CDSR correlates poorly with DALY metrics. The results of this study may guide future research prioritization and allocation of funds.

Global burden of skin disease as reflected in Cochrane Database of Systematic Reviews.

IMPORTANCE: Research prioritization should be guided by impact of disease. OBJECTIVE: To determine whether systematic reviews and protocol topics in Cochrane Database of Systematic Reviews (CDSR) reflect disease burden, measured by disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2010 project. DESIGN, SETTING, AND PARTICIPANTS: Two investigators independently assessed 15 skin conditions in the CDSR for systematic review and protocol representation from November 1, 2013, to December 6, 2013. The 15 skin diseases were matched to their respective DALYs from GBD 2010. An official publication report of all reviews and protocols published by the Cochrane Skin Group (CSG) was also obtained to ensure that no titles were missed. There were no study participants other than the researchers, who worked with databases evaluating CDSR and GBD 2010 skin condition disability data. MAIN OUTCOMES AND MEASURES: Relationship of CDSR topic coverage (systematic reviews and protocols) with percentage of total 2010 DALYs, 2010 DALY rank, and DALY percentage change from 1990 to 2010 for 15 skin conditions. RESULTS: All 15 skin conditions were represented by at least 1 systematic review in CDSR; 69% of systematic reviews and 67% of protocols by the CSG covered the 15 skin conditions. Comparing the number of reviews/protocols and disability, dermatitis, melanoma, nonmelanoma skin cancer, viral skin diseases, and fungal skin diseases were well matched. Decubitus ulcer, psoriasis, and leprosy demonstrated review/protocol overrepresentation when matched with corresponding DALYs. In comparison, acne vulgaris, bacterial skin diseases, urticaria, pruritus, scabies, cellulitis, and alopecia areata were underrepresented in CDSR when matched with corresponding DALYs. CONCLUSIONS AND RELEVANCE: Degree of representation in CDSR is partly correlated with DALY metrics. The number of published reviews/protocols was well matched with disability metrics for 5 of the 15 studied skin diseases, while 3 skin diseases were overrepresented, and 7 were underrepresented. Our results provide high-quality and transparent data to inform future prioritization decisions.

GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation's direction and strength.

In the GRADE approach, the strength of a recommendation reflects the extent to which we can be confident that the composite desirable effects of a management strategy outweigh the composite undesirable effects. This article addresses GRADE's approach to determining the direction and strength of a recommendation. The GRADE describes the balance of desirable and undesirable outcomes of interest among alternative management strategies depending on four domains, namely estimates of effect for desirable and undesirable outcomes of interest, confidence in the estimates of effect, estimates of values and preferences, and resource use. Ultimately, guideline panels must use judgment in integrating these factors to make a strong or weak recommendation for or against an intervention.

An equity lens can ensure an equity-oriented approach to agenda setting and priority setting of Cochrane Reviews.

OBJECTIVES: This study aimed to develop and pilot an equity lens that could help researchers in developing a more equity-oriented approach toward priority setting and agenda setting in systematic reviews. STUDY DESIGN AND SETTING: We developed an equity lens to guide the development and evaluation of a prioritization process and evaluate its outcomes based on the information derived from a discussion workshop and a comparison with the existing literature on the topic. We piloted the process section of the equity lens across the 13 structured priority-setting approaches in the Cochrane Collaboration. RESULTS: We devised an equity lens with two checklists: one to guide the process of priority setting (nine questions) and the other to evaluate the outcomes of priority setting (eight questions). Of the nine questions, seven questions were partially addressed by at least one of the prioritization projects. Two questions were not considered in any of them. The prioritization projects did not report sufficient outcome data, thus we could not explore the eight question on evaluating outcomes. CONCLUSION: Currently, there are few strategies in the Cochrane Collaboration that explicitly address the research priorities of individuals from different sociodemographic groups. The equity lens for priority setting and agenda setting can help project teams to develop a more equity-oriented approach to set a research agenda and/or prioritize research topics. However, further studies are needed to evaluate its impact on the prioritization process.

Generalizability of systematic reviews of the effectiveness of health care interventions to primary health care: concepts, methods and future research.

BACKGROUND: There is a push to make clinical decision making more evidence based and patient oriented. However, current systematic reviews are limited by the lack of consideration of generalizability. OBJECTIVE: To develop a guide for investigators (systematic reviewers) on how to adapt the methodology of a systematic review to facilitate the exploration of the results to primary care. METHODS: We reviewed the method guidelines of five organizations and working groups. Then, we conducted a search of literature in PubMed for articles on external validity of systematic. Based on the literature, we developed general steps to incorporate generalizability in systematic reviews and then integrated main primary care themes as outlined in WONCA definition of primary care and the definition of person-centred medicine across those steps. RESULTS: We identified a wide variety of approaches to address the issue of generalizability in systematic reviews. We extracted four major primary care themes from the two definitions of primary care and person-centred medicine that we mapped across the methods of generalizability. We suggested a two-step approach: Step 1 planning the scope of a review using four-layer schematic model and Step 2 to follow four steps to incorporate the concept of generalizability to primary care in the review. CONCLUSIONS: Systematic reviewers can take several steps to improve the generalizability of their review to primary care. However, more research is needed to determine which approach provides better results than others.

Choosing health technology assessment and systematic review topics: the development of priority-setting criteria for patients' and consumers' interests.

BACKGROUND: The Institute for Quality and Efficiency in Health Care (IQWiG) was established in 2003 by the German parliament. Its legislative responsibilities are health technology assessment, mostly to support policy making and reimbursement decisions. It also has a mandate to serve patients' interests directly, by assessing and communicating evidence for the general public. OBJECTIVES: To develop a priority-setting framework based on the interests of patients and the general public. METHODS: A theoretical framework for priority setting from a patient/consumer perspective was developed. The process of development began with a poll to determine level of lay and health professional interest in the conclusions of 124 systematic reviews (194 responses). Data sources to identify patients' and consumers' information needs and interests were identified. RESULTS: IQWiG's theoretical framework encompasses criteria for quality of evidence and interest, as well as being explicit about editorial considerations, including potential for harm. Dimensions of "patient interest" were identified, such as patients' concerns, information seeking, and use. Rather than being a single item capable of measurement by one means, the concept of "patients' interests" requires consideration of data and opinions from various sources. CONCLUSIONS: The best evidence to communicate to patients/consumers is right, relevant and likely to be considered interesting and/or important to the people affected. What is likely to be interesting for the community generally is sufficient evidence for a concrete conclusion, in a common condition. More research is needed on characteristics of information that interest patients and consumers, methods of evaluating the effectiveness of priority setting, and methods to determine priorities for disinvestment.

GRADE guidelines: 8. Rating the quality of evidence--indirectness.

Direct evidence comes from research that directly compares the interventions in which we are interested when applied to the populations in which we are interested and measures outcomes important to patients. Evidence can be indirect in one of four ways. First, patients may differ from those of interest (the term applicability is often used for this form of indirectness). Secondly, the intervention tested may differ from the intervention of interest. Decisions regarding indirectness of patients and interventions depend on an understanding of whether biological or social factors are sufficiently different that one might expect substantial differences in the magnitude of effect. Thirdly, outcomes may differ from those of primary interest-for instance, surrogate outcomes that are not themselves important, but measured in the presumption that changes in the surrogate reflect changes in an outcome important to patients. A fourth type of indirectness, conceptually different from the first three, occurs when clinicians must choose between interventions that have not been tested in head-to-head comparisons. Making comparisons between treatments under these circumstances requires specific statistical methods and will be rated down in quality one or two levels depending on the extent of differences between the patient populations, co-interventions, measurements of the outcome, and the methods of the trials of the candidate interventions.

Evidence summary: is smoking cessation an effective and cost-effective service to be introduced in NHS dentistry?

Since August 2009, members of the Primary Care Dentistry Research Forum (www.dentistryresearch.org) have taken part in an online vote to identify questions in day-to-day practice that they felt most needed to be answered with conclusive research. The question that receives the most votes each month forms the subject of a critical appraisal of the relevant literature. Each month a new round of voting takes place to decide which further questions will be reviewed. Dental practitioners and dental care professionals are encouraged to take part in the voting and submit their own questions to be included in the vote by joining the website. The paper below details a summary of the findings of the eighth critical appraisal. In order to address the question raised by the primary care dentistry research forum, first any international study was included that evaluated the effectiveness smoking cessation in dental practice. The aim was to understand whether smoking cessation in dental practice is an effective treatment strategy to increase tobacco cessation and abstinence. Moreover, this rapid assessment intended to identify whether there are certain types of smoking cessation intervention (or components of an intervention) in dental settings that are more effective than the others. In order to determine the applicability of the results to the NHS, we also looked for studies evaluating the cost-effectiveness of these interventions in NHS dentistry, studies reporting the current practice in NHS dentistry and finally qualitative and quantitative studies describing and evaluating the experience and views of dentists in the UK regarding implementing smoking cessation interventions in dental settings. The latter studies would help us to identify the possible barriers and facilitators in implementing these interventions in a dental setting. In conclusion, the critical appraisal of the international literature suggests that behavioural intervention for smoking cessation involving oral health professionals is an effective method of reducing tobacco use in smokers and users of smokeless tobacco and preventing uptake in non-smokers. There is not enough evidence available to assess whether these interventions are cost-effective and the effectiveness of one intervention (or component of the intervention) over another is not clear. The evaluation of the UK-related literature shows that private dental practices deliver more smoking cessation activities than their NHS counterparts. NHS practitioners report lack of reimbursement from the NHS, lack of time and training and fears over patient response as barriers to delivering smoking cessation interventions. We did not find studies evaluating the cost-effectiveness of the intervention in the UK.

Institute for Quality and Efficiency in Health Care: Germany.

The Institute for Quality and Efficiency in Health Care (IQWiG) was established in 2004 to provide Germany's Federal Joint Committee with evidence-based evaluations of the benefits and cost benefits of health services, and functions in an advisory role. IQWiG reviews available evidence and produces recommendations after an extensive process of consultation with experts and stakeholders. IQWiG's recommendations are then considered by the Joint Committee in issuing coverage and payment directives. Under German law, insurance funds must cover any service that is medically necessary, which means that cost-effectiveness analysis can only be used to exclude a treatment from coverage if at least one equivalent alternative exists.

Comparative effectiveness research and evidence-based health policy: experience from four countries.

CONTEXT: The discussion about improving the efficiency, quality, and long-term sustainability of the U.S. health care system is increasingly focusing on the need to provide better evidence for decision making through comparative effectiveness research (CER). In recent years, several other countries have established agencies to evaluate health technologies and broader management strategies to inform health care policy decisions. This article reviews experiences from Britain, France, Australia, and Germany. METHODS: This article draws on the experience of senior technical and administrative staff in setting up and running the CER entities studied. Besides reviewing the agencies' websites, legal framework documents, and informal interviews with key stakeholders, this analysis was informed by a workshop bringing together U.S. and international experts. FINDINGS: This article builds a matrix of features identified from the international models studied that offer insights into near-term decisions about the location, design, and function of a U.S.-based CER entity. While each country has developed a CER capacity unique to its health system, elements such as the inclusiveness of relevant stakeholders, transparency in operation, independence of the central government and other interests, and adaptability to a changing environment are prerequisites for these entities' successful operation. CONCLUSIONS: While the CER entities evolved separately and have different responsibilities, they have adopted a set of core structural, technical, and procedural principles, including mechanisms for engaging with stakeholders, governance and oversight arrangements, and explicit methodologies for analyzing evidence, to ensure a high-quality product that is relevant to their system.