Janelle Guirguis-Blake

Update on the Methods of the U.S. Preventive Services Task Force: Estimating Certainty and Magnitude of Net Benefit

The major goal of the U.S. Preventive Services Task Force (USPSTF) is to provide clinicians and policymakers with a reliable and accurate source of evidence-based recommendations on a wide range of preventive services. To accomplish this goal, the USPSTF systematically reviews the evidence concerning both the benefits and harms of widespread implementation of a preventive service. It then assesses the certainty of the evidence and the magnitude of the benefits and harms. On the basis of this assessment, the USPSTF assigns a letter grade to each preventive service signifying its recommendation about provision of the service (Table 1). Table 1. U.S. Preventive Services Task Force Recommendation Grid* An important, but often challenging, step is determining the balance between benefits and harms to estimate net benefit (that is, benefits minus harms). In this issue, the Task Force reports an update to its recommendation for carotid artery stenosis screening (1, 2). Because carotid artery stenosis screening has both known benefits and harms, estimating net benefit was critical in the final USPSTF recommendation that clinicians not provide carotid artery stenosis screening in asymptomatic people (recommendation letter grade D). Release of this recommendation provides an opportunity for the Task Force to update and explain to a clinical audience the process by which it evaluates evidence, determines the certainty and magnitude of net benefit, and gives a letter grade to the recommendation. We will do this by considering 3 questions: 1) What evidence does the Task Force consider to estimate net benefit? 2) How does the Task Force estimate the certainty of net benefit? and 3) How does the Task Force estimate the magnitude of net benefit? What Evidence Does the Task Force Consider to Estimate Net Benefit? The overarching question that the Task Force seeks to answer for every preventive service is whether evidence suggests that provision of the service would improve health outcomes if implemented in a general primary care population. For screening topics, this standard could be met by a large randomized, controlled trial (RCT) in a representative asymptomatic population with follow-up of all members of both the group invited for screening and the group not invited for screening. For example, the Multicentre Aneurysm Screening Study (3) was a population-based RCT of screening for abdominal aortic aneurysm in which 67800 asymptomatic men age 65 to 74 years in the United Kingdom were randomly assigned to be invited or not to be invited for screening. Both groups were followed for a mean of 4.1 years, and abdominal aortic aneurysmrelated mortality and all-cause mortality were compared. No RCTs of carotid artery stenosis screening have been published; however, RCTs comparing carotid endarterectomy to medical management of asymptomatic carotid artery stenosis are available. The distinction between RCTs that randomly assign people to undergo screening versus RCTs that randomly assign people known to have a condition to an intervention is important. In contrast to the latter, RCTs of screening take into account the false-positive and false-negative rates of the screening test, the possibility of adverse events from the test, the accuracy and potential for adverse events of any subsequent confirmatory diagnostic tests, and the inevitable failure to follow through on the test or any subsequent steps needed before the therapeutic intervention is delivered. In addition, conditions detected by screening may have different biological characteristics than those detected in other ways. The benefits of treating screened individuals, therefore, cannot be assumed to be the same as those of treating symptomatic individuals. Screening trials directly answer a simple question important to the primary care setting: Does screening for a certain condition improve health outcomes? Direct RCT evidence about screening is often unavailable, so the Task Force considers indirect evidence. To guide its selection of indirect evidence, the Task Force constructs a chain of evidence within an analytic framework. Figure 1 of the evidence update (2) in this issue (page 861) shows the analytic framework for the Task Force assessment of carotid artery stenosis screening. Each arrow in the framework defines a key question, and each key question represents a link in the chain of evidence. Rectangles in the framework represent the intermediate outcomes (rounded corners) or the health outcomes (square corners); ovals represent harms. To form an unbroken chain, evidence must support each link in the chain, thereby connecting the target population (far left side of the framework) to the improved health outcome (far right side of the framework). For each key question, the body of pertinent literature is critically appraised, focusing on 6 questions (Table 2). The USPSTF will now describe its judgment about the evidence for each key question as convincing, adequate, or inadequate. Evidence may be considered convincing when derived from several high-quality studies with consistent, logical results that are generalizable to the U.S. primary care population and setting. Evidence may be deemed adequate when, on the basis of judgment, most but not all of these 6 questions are answered favorably. When evidence is conflicting or the studies are of poor quality individually or in aggregate, the evidence for a key question is considered inadequate. Inadequate evidence may create a critical gap in the evidence chain. Table 2. Questions Considered by the U.S. Preventive Services Task Force for Evaluating Evidence Related Both to Key Questions and to the Overall Certainty of the Evidence of Net Benefit for the Preventive Service How Does the Task Force Estimate the Certainty of Net Benefit? The next step in the Task Force process is to use the evidence from the key questions to assess whether there would be net benefit if the service were implemented. In 2001, the USPSTF published an article that documented its systematic processes of evidence evaluation and recommendation development (4). At that time, the Task Forces overall assessment of evidence was described as good, fair, or poor. The Task Force realized that this rating seemed to apply only to how well studies were conducted and did not fully capture all of the issues that go into an overall assessment of the evidence about net benefit. To avoid confusion, the USPSTF has changed its terminology. Whereas individual study quality will continue to be characterized as good, fair, or poor, the term certainty will now be used to describe the Task Forces assessment of the overall body of evidence about net benefit of a preventive service and the likelihood that the assessment is correct. Certainty will be determined by considering all 6 questions in Table 2; the judgment about certainty will be described as high, moderate, or low. In making its assessment of certainty about net benefit, the evaluation of the evidence from each key question plays a primary role. It is important to note that the Task Force makes recommendations for real-world medical practice in the United States and must determine to what extent the evidence for each key questioneven evidence from screening RCTs or treatment RCTscan be applied to the general primary care population. Frequently, studies are conducted in highly selected populations under special conditions. The Task Force must consider differences between the general primary care population and the populations studied in RCTs and make judgments about the likelihood of observing the same effect in actual practice. For carotid artery stenosis screening, the Task Force searched for evidence about the true prevalence of high-grade carotid artery stenosis in the general population, the generalizability of treatment effectiveness estimates based on RCTs conducted in selected populations, and the complication rate from carotid endarterectomy in asymptomatic individuals if performed in nontrial settings (for example, community hospitals). It is also important to note that 1 of the key questions in the analytic framework refers to the potential harms of the preventive service. The Task Force considers the evidence about the benefits and harms of preventive services separately and equally. Data about harms are often obtained from observational studies because harms observed in RCTs may not be representative of those found in usual practice and because some harms are not completely measured and reported in RCTs. For example, the surgeons who enrolled patients in RCTs of carotid artery stenosis were selected on the basis of their low postoperative stroke and mortality rates. Widespread screening for carotid artery stenosis would invariably lead to surgical treatment provided in hospitals (or by surgeons) with higher rates of complications. The harms of screening for carotid artery stenosis, including the harms from carotid angiography to confirm the diagnosis of carotid artery stenosis in patients screening positive by carotid ultrasonography, were not captured in some treatment RCTs. Putting the body of evidence for all key questions together as a chain, the Task Force assesses the certainty of net benefit of a preventive service by asking the 6 major questions in Table 2. The Task Force would rate a body of convincing evidence about the benefits of a service that, for example, derives from several RCTs of screening in which the estimate of benefits can be generalized to the general primary care population as high certainty (Table 3). The Task Force would rate a body of evidence that was not clearly applicable to general practice or has other defects in quality, research design, or consistency of studies as moderate certainty. Certainty is low when, for example, there are gaps in the evidence linking parts of the analytic framework, when evidence to determine the harms of treatment is unavailable, or when

Current Processes of the U.S. Preventive Services Task Force: Refining Evidence-Based Recommendation Development

The U.S. Preventive Services Task Force (USPSTF) is an internationally recognized, independent panel of nonfederal experts in primary care, prevention, and research methods that makes evidence-based recommendations to guide the delivery of clinical preventive services. Convened and supported by the Agency for Healthcare Research and Quality (AHRQ), the USPSTF is charged by the U.S. Congress to review the scientific evidence for clinical preventive services and to develop evidence-based recommendations for their delivery to the health care community. The disciplines of USPSTF members include family medicine, internal medicine, geriatrics, preventive medicine, pediatric and adolescent medicine, obstetrics and gynecology, nursing, psychology and behavioral medicine, public health, and health policy. Since its inception more than 20 years ago, the USPSTF has worked to fulfill its mission by 1) evaluating the benefits and harms of preventive services in apparently healthy persons on the basis of age, sex, and known risk factors for disease and 2) making recommendations about which preventive services should be provided routinely in primary care practice and which should not. The USPSTF recommendations are intended to improve both clinical practice and the health of patients. The scope of the Task Force is specific: Its recommendations address primary or secondary preventive services targeting conditions of substantial burden in the United States and are provided in primary care settings (or are available through primary care referral). Although the main audience for USPSTF recommendations is the primary care clinician, these recommendations also have relevance for and are widely used by policymakers, managed care organizations, public and private payers, quality improvement organizations, research institutions, professional medical organizations, specialist physicians, and patients. The USPSTF is distinct from other groups that provide recommendations for preventive services. It does not create guidelines based on expert opinion, as do many nonprofit advocacy organizations and professional groups. The Task Force does not advocate for prevention, perform decision analysis to routinely standardize the personal preferences and values of patients, consider medicolegal issues or the cost or coverage of services in making recommendations, or set clinical standards or health policy. Instead, the Task Force follows a unique and explicit methodology to develop recommendations that pass a rigorous evidence-based standard (1). Table 1 shows the Task Forces current procedures for developing recommendations. The USPSTF stands as an independent arbiter of the evidence and, as such, has set the standard for evidence-based recommendations for the delivery of clinical preventive services. Table 1. Procedures for Developing a Recommendation Statement* The process of making evidence-based recommendations occurs in an environment in which many stakeholders, often with competing interests, have their own preferences for or ideas about the delivery of preventive services. In such an environment, in which outside organizations maintain a keen interest in what the Task Force recommends, it is especially important for the USPSTF to maintain transparency, accountability, and consistency to ensure the independence and the integrity of their process and recommendations. This paper is 1 in a series presenting the refinements that the USPSTF has undergone since its methodology was last published in 2001. The Task Force processes of selecting topics, synthesizing evidence, deliberating and voting on recommendations, soliciting peer review, and finalizing recommendations have evolved over time. The purpose of this refinement is to continually improve the methods of evidence-based review, to maintain transparency and objectivity, and to increase USPSTF efficiency. Table 2 summarizes the ways in which the USPSTF has refined its processes to meet these and other aims. Table 2. Aims and Processes of the U.S. Preventive Services Task Force to Ensure Integrity* Types of Recommendations New Topics The Task Force solicits new topics for consideration from the field through a periodic notice in the Federal Register and solicitation of professional liaison organizations. Task Force members may also generate new topics for consideration. The USPSTF first considers whether newly nominated topics are within the scope of the USPSTF (that is, a primary or secondary preventive service that is relevant to primary care and addresses a disease with a substantial health burden) and then prioritizes the topics by using specific criteria: 1) the public health importance of the condition to be prevented (burden of suffering and expected effectiveness of preventive services to reduce that burden) and 2) the potential for the USPSTF to affect clinical practice (based on existing controversy or the belief that a gap exists between evidence and practice). The USPSTF secondarily considers the need to balance the portfolio of topics to address diverse groups, types of conditions, and types of preventive services (for example, screening, counseling, and preventive medication). The USPSTF recommendation statement on routine use of aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer, which appeared in the 6 March 2007 issue of Annals of Internal Medicine, represents a new topic nominated by the Centers for Disease Control and Prevention (CDC) (2). Updated Recommendations To efficiently utilize available resources, the Task Force has implemented new procedures to review previous topics and update recommendations for continued inclusion in the current Task Force library. To be consistent with the standards of the National Guidelines Clearinghouse (www.ngc.gov), the process of revisiting and updating a previous USPSTF recommendation begins approximately 3.5 years after that recommendation was released, or earlier if a landmark study is published that could change a current recommendation. The USPSTF screens topics under consideration to identify emerging scientific issues and current clinical relevance, and then prioritizes them by using the criteria described above, in addition to considering the potential for new, recent evidence to change a previous recommendation. The USPSTF then recommends a targeted evidence update or a full evidence update. A full evidence update systematically examines a complete analytic framework of key questions by using recent evidence, taking into account any need to reframe the topic or focus of the recommendation since it was last considered, whereas a targeted evidence update systematically examines a subset of the key questions from the original analytic framework. Reaffirmation Recommendations Some clinical preventive services, such as screening for hypertension, have a strong, well-established evidence base and are a routine part of clinical practice. Because it is unlikely that new evidence will change USPSTF recommendations for such services, the USPSTF reviews the evidence for them in an expedited manner by conducting literature searches that address benefits and harms and consulting experts. Some recommendations for clinical preventive services fall within the scope of not only the USPSTF but also other federal agencies. For example, adult and childhood immunizations are addressed by the CDC Advisory Committee on Immunization Practices (ACIP). In a few select cases, the Task Force chooses to refer to such recommendations. Although the USPSTF considers these recommendations part of its portfolio of recommended clinical preventive services, it refers clinicians to the ACIP active evidence review process and recommendations for 2 reasons: The USPSTF does not have adequate resources to keep such recommendations current, and it does not wish to duplicate the efforts of the ACIP. Inactive Recommendations The USPSTF considers some recommendations made in previous years (for example, those for electronic fetal monitoring, home uterine monitoring, and counseling for dental disease) to be no longer current or priority topics. These topics are regarded as inactive for various reasons. First, the USPSTF may consider such recommendations now to be outside its scope of work. Second, such recommendations may be judged to be no longer clinically relevant, because of changes in technology or clinical practice or because of new understanding of disease etiology or natural history. Finally, the topic of a recommendation may be judged to have low priority because it has limited potential to influence public health burden or clinical practice. Currently inactive recommendations are identified on the USPSTF Web site (www.preventiveservices.ahrq.gov). Types of Evidence Reviews The USPSTF bases its recommendations on systematic evidence reviews, which form the critical underpinnings of its deliberations and decision making. The USPSTF members are intensively involved in the conceptualization, content, and interpretation of these reviews. The reviews are products of a partnership between members of the USPSTF and Evidence-based Practice Center (EPC), which conducts, synthesizes, and produces them. The process is facilitated and coordinated by the staff of the AHRQ, and in some cases, the AHRQ staff conducts targeted evidence updates. The USPSTF now uses 4 types of reviews to support its recommendations: full evidence reviews, staged evidence reviews, targeted evidence updates, and reaffirmation updates. Recommendations for new topics are informed by full evidence reviews (which may be, in rare instances, staged evidence reviews). Updates of previous recommendations are informed by 1 of 3 types of reviews: full evidence updates, targeted evidence updates, or reaffirmation updates. These 3 updated reviews represent a new methodology for the USPSTF process. Table 3 provides descriptions and examples of the types of reviews.

Screening for Carotid Artery Stenosis: An Update of the Evidence for the U.S. Preventive Services Task Force

Cerebrovascular disease is the third leading cause of death in the United States (1). Approximately 500000 people in the United States each year experience a first stroke (1). The mortality rate for cerebrovascular disease has declined by nearly 70% since 1950 (2). Much of the decrease is probably due to reduced cigarette smoking and improved control of hypertension. Carotid artery stenosis (CAS) is pathologic atherosclerotic narrowing of the extracranial carotid arteries. The contribution of CAS to overall stroke burden is difficult to approximate. Eighty-eight percent of strokes are ischemic, and 20% or fewer of these are due to large-artery stenosis (39). A subgroup of patients have large-artery stenosis due to stenosis of the carotid bifurcation or proximal carotid artery that is approachable by carotid endarterectomy; some of these patients are asymptomatic. A clinically important degree of CAS is defined as the percentage of stenosis that corresponds to a substantially increased risk for stroke. Because stroke risk depends on more than the degree of carotid artery narrowing, it is difficult to define categories of CAS that are associated with various risk levels of stroke in asymptomatic people. Most studies of treatment for CAS consider stenosis of 50% or greater or 60% or greater to be clinically important. The most important risk factor is previous cerebrovascular disease. Other risk factors include hemodynamic factors; atrial fibrillation; collateral circulation; patient age (>65 years); male sex; comorbid conditions; and cardiovascular risk factors, such as hypertension, cigarette smoking, clotting mechanisms, and plaque structure (1016). The presence of the strongest reported risk factors, smoking or heart disease, approximately doubles the risk for CAS (14, 15). However, no single risk factor or clinically useful risk model incorporating multiple factors clearly discriminates people who have clinically important CAS from people who do not. Several population-based cohort and cross-sectional studies have examined the prevalence of CAS. These prevalence estimates are based on a positive result on a screening carotid ultrasonography. Estimates of the prevalence of CAS from population-based studies range from 0.5% to 8% (5, 10, 1719). On the basis of population-based studies and the accuracy of ultrasonography, we estimate the actual prevalence of clinically important CAS (60% to 99%) to be approximately 1% or less in the general primary care population and about 1% in persons age 65 years or older. A detailed discussion on the prevalence of CAS is available in a larger report at www.ahrq.gov/clinic/uspscacas.htm (20). Carotid endarterectomy has been proposed as a strategy for reducing the burden of suffering due to stroke, in addition to controlling such risk factors as tobacco use and hypertension. Randomized, controlled trials (RCTs) have shown that carotid endarterectomy effectively reduces stroke among people who have severe CAS and have had a transient ischemic attack or minor stroke. It is not clear, however, whether screening asymptomatic people (those who have never had a transient ischemic attack) to detect CAS and treatment with carotid endarterectomy are effective in reducing stroke. Before carotid endarterectomy, cerebral angiography after ultrasonography may be used to confirm CAS. A small percentage of patients will be harmed by the angiographic procedure itself. In an RCT of carotid endarterectomy in asymptomatic patients, 1.2% of patients who had angiography had a nonfatal stroke. Prospective studies of cerebral angiography have found rates of persistent neurologic complications of 0.1% to 0.5% (2123). Because of the increased risk for stroke, there is disagreement on whether cerebral angiography should be used to confirm a positive ultrasonography screening result. Current practice varies widely: Some surgeons do other confirmatory tests, such as magnetic resonance angiography (MRA) or computed tomographic angiography (CTA), whereas others request angiography before carotid endarterectomy. In 1996, the U.S. Preventive Services Task Force (USPSTF) concluded that evidence was insufficient to recommend for or against screening of asymptomatic persons for CAS by using physical examination or carotid ultrasonography (24). This recommendation was based on new evidence at the time, including data from ACAS (Asymptomatic Carotid Atherosclerosis Study), an RCT involving 1662 persons with asymptomatic stenosis greater than 60%. Results of ACAS suggested that the overall benefit of treatment with carotid endarterectomy depends greatly on the perioperative complications. At that time, information was limited about carotid endarterectomy complications in the general population. Since the previous Task Force review, the largest RCT of carotid endarterectomy versus medical treatment for asymptomatic CAS, the ACST (Asymptomatic Carotid Surgery Trial), and several large studies on actual harms of carotid endarterectomy have been published. This review updates the 1996 USPSTF review of screening for CAS, focusing on duplex ultrasonography as the screening test (with various confirmatory tests) and carotid endarterectomy as the treatment for clinically important CAS. Medical interventions and screening with carotid auscultation were not reviewed in this report. The USPSTF has reviewed screening for several known risk factors of carotid artery stenosis and stroke, including hyperlipidemia, hypertension, aspirin prophylaxis, and smoking. The evidence reports and recommendations are available at the Agency for Healthcare Research and Quality Web site at www.preventiveservices.ahrq.gov . Figure 1 shows the analytic framework for this review, which was developed by following USPSTF methods (25). The USPSTF developed 4 key questions from the analytic framework to guide its consideration of the benefits and harms of screening with ultrasonography for CAS. The key questions were as follows: Figure 1. Analytic framework for screening for carotid artery stenosis ( CAS ). CEA = carotid endarterectomy; KQ = key question. Key question 1: Is there direct evidence that screening adults with duplex ultrasonography for asymptomatic CAS reduces fatal or nonfatal stroke? Key question 2: What is the accuracy and reliability of duplex ultrasonography to detect clinically important CAS? Key question 3: For people with asymptomatic CAS 60% to 99%, does intervention with carotid endarterectomy reduce CAS-related morbidity or mortality? Key question 4: Does screening or carotid endarterectomy for asymptomatic CAS 60% to 99% result in harm? Methods The USPSTF designated key questions 1, 2, and 3 as subsidiary questions for which they requested nonsystematic reviews to assist them in updating their recommendations. Key question 4 was the only key question for which the USPSTF requested a systematic evidence review. Data Sources and Searches We searched MEDLINE for English-language articles published between 1 January 1994 and 2 April 2007 that addressed key questions 1, 2, and 3. We identified additional studies by examining the reference lists of major review articles and by consulting experts. For key question 3, we performed a MEDLINE search for RCTs, systematic reviews, and meta-analyses that compared carotid endarterectomy with medical therapy for asymptomatic people with CAS. We identified 1 in-process RCT by its inclusion in a systematic review, and we included it once it was published. For key question 4, we performed a systematic search of MEDLINE for English-language articles published between 1 January 1994 and 2 April 2007 by using the focused Medical Subject Heading terms endarterectomy, carotid, and outcome and process assessment. We also selected a key study from this search and identified related articles through MEDLINE. Additional studies were identified through a search of the Cochrane database, discussions with experts, and hand-searching of reference lists from major review articles and studies. Study Selection Titles and abstracts of articles retrieved for key questions 1, 2, and 3 were nonsystematically selected and reviewed by 2 reviewers. The process was considered nonsystematic because articles were selected for review and abstracted by 1 reviewer. Articles for key question 1 were selected for inclusion if they were RCTs; compared screened versus nonscreened groups; used ultrasonography, MRA, or CTA as screening methods; reported outcomes of strokes or death in asymptomatic persons; and were performed in a population generalizable to the United States. For key question 2, we included systematic reviews that compared screening tests (ultrasonography, MRA, or CTA) with angiography in asymptomatic persons and were performed in a population generalizable to the United States. Articles for key question 3 were included if they were RCTs of carotid endarterectomy comparing surgical treatment with medical treatment, reported 30-day complication rates (stroke and death) of carotid endarterectomy, included only asymptomatic patients, and were performed in a population generalizable to the United States. For key question 4, three reviewers independently reviewed the abstracts and selected articles from titles and abstracts on the basis of inclusion and exclusion criteria. In general, studies were selected if they were large, multi-institution, prospective studies that reported 30-day mortality or stroke outcomes for asymptomatic patients undergoing carotid endarterectomy. Studies were excluded if they did not report outcomes by symptom status, included patients receiving carotid endarterectomy combined with other major surgeries, were not performed in the United States, included patients with restenosis, or covered patients at extremely high risk. Appendix Table 1 shows detailed search terms and inclusion and exclusion criteria. Abstracts that were chosen by fewer than 3 reviewers were discussed and selected on t

Ultrasonography Screening for Abdominal Aortic Aneurysms: A Systematic Evidence Review for the U.S. Preventive Services Task Force

An abdominal aortic aneurysm (AAA) is a weakening in the wall of the infrarenal aorta that results in an anteroposterior diameter of 3 cm or greater (1). Abdominal aortic aneurysms are often undiagnosed because a large proportion are asymptomatic until the development of rupture, which is generally acute and often fatal (59% to 83% of patients die before hospitalization) (2). Significant risk factors for the development of AAA include advanced age (3), male sex (4), smoking (1, 5, 6), and family history of AAAs (1, 7, 8). Other potential risk factors include a history of other vascular aneurysms (9), coronary artery disease (10), cerebrovascular disease (9), atherosclerosis (10), hypercholesterolemia (10), and hypertension (1, 10). Protective factors include black race, female sex, and diabetes mellitus (11). Smoking is the most important modifiable risk factor for AAA development (1214) and aneurysm growth (15). Older age, female sex, smoking, and higher blood pressure are associated with increased risk for rupture in patients with small (3.0 to 5.4 cm) AAAs (15). Although several screening methods exist, ultrasonography is accepted as the standard screening imaging method for AAA because it has a high sensitivity (94% to 100%) and specificity (98% to 100%) (1, 2, 1619). Ultrasonography is noninvasive, can be conducted at a low cost, and does not involve radiation exposure. Computed tomography scans are highly sensitive and specific in detecting AAAs but are not recommended for first-line screening because of high cost and radiation exposure (1, 20). In 2005, the U.S. Preventive Services Task Force (USPSTF) found good evidence to recommend 1-time screening for AAA by ultrasonography in men aged 65 to 75 years who have ever smoked (B recommendation). The USPSTF concluded that the benefits of screening did not clearly outweigh the harms and did not make a general recommendation for or against screening for AAA in men aged 65 to 75 years who have never smoked (C recommendation). The USPSTF recommended against routine screening for AAA in women (D recommendation) (21). This systematic review includes newly identified literature and all trials from the previous review that meet current inclusion criteria to provide updated evidence on the effectiveness of 1-time and repeated ultrasonography screening for AAAs (6). Supplement. Original Version (PDF) Methods Detailed methods are publicly available in our full evidence report and its appendices (www.uspreventiveservicestaskforce.org) (22). This review addressed the following key questions: the effect of 1-time screening for AAAs of all sizes (3.0 cm) and repeated screening for initially normal-sized aortas (<3.0 cm) on health outcomes and the harms related to 1-time and repeated screening for AAAs (Appendix Figure). Of note, our detailed critique of treatment evidence for AAAs identified through screening that did not meet the currently accepted treatment threshold of 5 cm is presented in the full evidence report. Appendix Figure. Analytic framework and key questions. AAA = abdominal aortic aneurysm; COPD = chronic obstructive pulmonary disease; EVAR = endovascular aneurysm repair; QOL = quality of life. Data Sources and Searches We searched MEDLINE, the Database of Abstracts of Reviews of Effects, and the Cochrane Central Register of Controlled Trials for relevant English-language studies published between January 2004 and January 2013. We searched for screening trials through September 2013 in MEDLINE. We supplemented searches with suggestions from experts and considered all articles included in the previous review for the USPSTF. We also reviewed reference lists of relevant systematic reviews and meta-analyses. Study Selection Two investigators independently reviewed abstracts and full-text articles for inclusion according to predetermined criteria. We resolved discrepancies through consensus with a third investigator. We considered randomized, controlled trials (RCTs) and large cohort studies (1000 participants) of asymptomatic adult populations for key questions examining the effectiveness of 1-time and repeated screening. For the key question examining the harms of screening for AAAs, we considered RCTs and observational studies. Ultrasonography was the only screening method we considered. For all bodies of evidence, we excluded studies that we rated as poor-quality on the basis of the USPSTF quality rating standards (23). Data Extraction and Quality Assessment One investigator extracted data, and a second investigator reviewed these data. Two investigators completed independent critical appraisals of all relevant studies by using the USPSTFs design-specific criteria (23), the National Institute for Health and Care Excellence method checklists (24), the Quality Assessment of Diagnostic Accuracy Studies (25) tool, and the Newcastle-Ottawa Scale (26). According to the USPSTF criteria, a good-quality study met all prespecified standards. A fair-quality study did not meet (or it was unclear whether it met) at least 1 criterion, but it also had no known limitation that could invalidate its results. A poor-quality study had a single fatal flaw or several important limitations that would likely bias results. Data Synthesis and Analysis We qualitatively synthesized data for each key question by summarizing relevant details and results for each included study. Although we decided a priori to pool studies for all outcomes using DerSimonianLaird random-effects models, we report quantitative analyses only for all-cause mortality. When we pooled AAA-related mortality and screening harms, the summary effects showed high statistical heterogeneity at the longest follow-up. Thus, we present forest plots with no pooled summaries. In addition, we did not pool studies examining the effectiveness of rescreening because of substantial differences in patient population, length of follow-up, and reported outcomes. For all pooled results using the DerSimonianLaird random-effects models, see the full evidence report (22). For all-cause mortality, we conducted planned random-effects analyses using the DerSimonianLaird method (27). We conducted sensitivity analyses using a fixed-effects model as well as the profile likelihood method because there were only 3 trials and the DerSimonianLaird method can underestimate uncertainty when the number of trials is small (27, 28). The 2 methods resulted in identical effect estimates and CIs. We examined heterogeneity across trials with the I 2 statistic and chi-square test for heterogeneity. Role of the Funding Source This study was funded by the Agency for Healthcare Research and Quality (AHRQ) under a contract to support the work of the USPSTF. Members of the USPSTF and the AHRQ medical officer assisted in the development of the reviews scope. Approval from AHRQ was required before the manuscript could be submitted for publication, but the authors are solely responsible for its content and the decision to submit it for publication. Results We reviewed 2723 abstracts and 204 full-text articles and identified 4 trials addressing the benefits of 1-time screening, 10 studies on the effectiveness of rescreening, 7 studies addressing the harms of 1-time and repeated screening, 15 trials examining the benefits of treating small AAAs, and 15 studies on the harms associated with treating small AAAs (Figure 1). The evidence related to the treatment of small AAAs is discussed in our full evidence report (22), along with detailed study-level and summary results of the evidence related to AAA screening. Figure 1. Summary of evidence search and selection. AAA = abdominal aortic aneurysm; KQ = key question. * Evidence related to the treatment of small AAAs is included in the full evidence report (22). One study was excluded for study design and outcomes. AAA Screening in Men We identified 2 fair-quality and 2 good-quality population-based screening RCTs (137214 participants) that assessed the efficacy of AAA screening in population-based settings: MASS (Multicentre Aneurysm Screening Study) (2932); the Chichester, United Kingdom screening trial (3336); the Viborg County, Denmark screening trial (3741); and the western Australian screening trial (42) (Table 1). All trials used population registries or regional health directories to identify potential participants aged 64 or 65 years or older. The Chichester trial (33) was the only trial that included women (34). No trial reported outcomes by demographic characteristics other than age and sex. Three of the 4 trials described adequate randomization (30, 33, 37). Three had no trial exclusions, whereas MASS excluded patients who were identified as being too high-risk to be screened by their primary care physicians, were terminally ill, or had other serious health problems or previous AAA repair (30). All trials randomly assigned participants to usual care or invitation for 1-time ultrasonography screening. Three specified postscreening ultrasonography surveillance protocols for AAAs measuring 3.0 cm or greater (30, 33, 39), whereas the western Australian trial sent initial ultrasound results to primary care physicians for further management (42). Table 1. Methodological and Intervention Characteristics of the 4 Included Population-Based AAA Screening Randomized, Controlled Trials All trials used intention-to-treat analysis. Adherence to screening varied from the lowest in the western Australian trial (62.5% of invited attended screening) to the greatest in MASS (80.2% adherence). Less than 1% of the control group crossed over in any trial to receive elective surgery, even at the longest follow-up of 13 to 15 years. The primary trial outcome was AAA-specific mortality (defined as all AAA deaths plus all deaths within 30 days of AAA surgical repair). Trials also reported AAA rupture and all-cause mortality rates. Deaths and their causes were ascertained from death certificates in all studies, and 3 used a blinded ad

Translating research into improved outcomes in comprehensive cancer control.

A key question in moving comprehensive cancer control (CCC) plans into action is, to what extent should the knowledge gained from investments in cancer prevention and control research influence the actions taken by states, tribes, and territories during implementation? Underlying this ‘should’ is the assumption that evidence-based approaches (i.e., a public health or clinical intervention or policy that has resulted in improved outcomes when scientifically tested), when implemented in a real-world setting, will increase the likelihood of improved outcomes. This article elucidates the barriers and opportunities for integrating science with practice across the cancer control continuum. However, given the scope of CCC and the substantial investment in generating new knowledge through science, it is difficult for any one agency, on its own, to make a sufficient investment to ensure new knowledge is translated and implemented at a national, state, or local level. Thus, if greater demand for evidence-based interventions and increased resources for adopting them are going to support the dissemination initiatives described herein, new interagency partnerships must be developed to ensure that sufficient means are dedicated to integrating science with service. Furthermore, for these collaborations to increase both in size and in frequency, agency leaders must clearly articulate their support for these collaborative initiatives and explicitly recognize those collaborative efforts that are successful. In this way, the whole (in this context, comprehensive cancer control) can become greater than the sum of its parts.

Developing a Practice-Based Research Network by Integrating Quality Improvement: Challenges and Ingredients for Success

Improving patient outcomes in community‐based settings is the goal of both the Clinical Translational Science Award program and practice‐based quality improvement (QI) programs. Given this common goal, integrating QI and outcomes research is a promising strategy for developing, implementing, and evaluating clinical interventions. This article describes the challenges and strengths illuminated by the conduct of a combined research/QI study in a nascent practice‐based research network. Challenges include researchs exclusion of clinic patients who might benefit from the intervention; QI programs’ less uniform approach to intervention implementation; and the need for both academic and clinically relevant products and publications. A major strength is the increased likelihood of both engaging clinical practices in research and developing successful clinical interventions. Required elements for success include identification of enthusiastic clinical research “champions,” involvement of researchers with clinical experience, and adequate funding to support both research and clinical resources and dissemination. Combined Ql/research projects in the practice‐based research environment have the potential to improve and shorten the cycle from good idea to improved clinical outcomes in real‐world settings. Clin Trans Sci 2012; Volume 5: 351–355

Screening for familial hypercholesterolaemia

Insufficient evidence exists to support universal screening

An approach to addressing subpopulation considerations in systematic reviews: the experience of reviewers supporting the U.S. Preventive Services Task Force

BackgroundGuideline developers and other users of systematic reviews need information about whether a medical or preventive intervention is likely to benefit or harm some patients more (or less) than the average in order to make clinical practice recommendations tailored to these populations. However, guidance is lacking on how to include patient subpopulation considerations into the systematic reviews upon which guidelines are often based. In this article, we describe methods developed to consistently consider the evidence for relevant subpopulations in systematic reviews conducted to support primary care clinical preventive service recommendations made by the U.S. Preventive Services Task Force (USPSTF).Proposed approachOur approach is grounded in our experience conducting systematic reviews for the USPSTF and informed by a review of existing guidance on subgroup analysis and subpopulation issues. We developed and refined our approach based on feedback from the Subpopulation Workgroup of the USPSTF and pilot testing on reviews being conducted for the USPSTF. This paper provides processes and tools for incorporating evidence-based identification of important sources of potential heterogeneity of intervention effects into all phases of systematic reviews. Key components of our proposed approach include targeted literature searches and key informant interviews to identify the most important subpopulations a priori during topic scoping, a framework for assessing the credibility of subgroup analyses reported in studies, and structured investigation of sources of heterogeneity of intervention effects.ConclusionsFurther testing and evaluation are necessary to refine this proposed approach and demonstrate its utility to the producers and users of systematic reviews beyond the context of the USPSTF. Gaps in the evidence on important subpopulations identified by routinely applying this process in systematic reviews will also inform future research needs.

Using the diffusion of innovations theory to assess socio-technical factors in planning the implementation of an electronic health record alert across multiple primary care clinics

Background Adverse drug events (ADEs) are a leading cause of death in the United States. Patients with stage 3 and 4 chronic kidney disease (CKD) are at particular risk because many medications are cleared by the kidneys. Alerts in the electronic health record (EHR) about drug appropriateness and dosing at the time of prescription have been shown to reduce ADEs for patients with stage 3 and 4 CKD in inpatient settings, but more research is needed about the implementation and effectiveness of such alerts in outpatient settings. Objective To explore factors that might inform the implementation of an electronic drug–disease alert for patients with CKD in primary care clinics, using Rogers’ diffusion of innovations theory as an analytic framework. Methods Interviews were conducted with key informants in four diverse clinics using various EHR systems. Interviews were audio recorded and transcribed. Results Although all clinics had a current method for calculating glomerular filtration rate (GFR), clinics were heterogeneous with regard to current electronic decision support practices, quality improvement resources, and organizational culture and structure. Conclusion Understanding variation in organizational culture and infrastructure across primary care clinics is important in planning implementation of an intervention to reduce ADEs among patients with CKD.

Contraceptive Methods and Informed Consent among Women Receiving Medications with Potential for Adverse Fetal Effects: A Washington, Wyoming, Alaska, Montana, Idaho (WWAMI) Region Study

Background: Increasing diabetes, hypertension, and hypercholesterolemia rates expose some young women to medications with potential adverse fetal effects, such as angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and statins. This study examined whether quality improvement (QI) interventions promote informed consent and contraception to minimize risks with use of ACE-I/ARB/statins. Methods: This longitudinal cohort study at 7 clinics abstracted medical records of 328 women aged 18 to 44 with ≥1 prescription for ACE-I/ARB/statins and ≥1 visit for hypertension, diabetes, or hypercholesterolemia during the previous year. We measured informed consent documentation and contraceptive methods before and after QI interventions in which providers contacted their patients to discuss medication risks and benefits. Results: Of 179 women who were not surgically sterilized, only 11.7% had documented informed consent related to the risks of ACE-I/ARB/statin use. One hundred fifty-eight women were eligible for the QI intervention (not surgically sterilized, no documented informed consent); only 76 (48.1%) received the intervention. Before the intervention, 23.7% of these 76 were “at risk” of an adverse fetal effect. After the intervention, only 7.9% (P ≤ .001) were “at risk” because some women started contraception, discontinued ACE-I/ARB/statins, or changed drug class. Conclusions: Women prescribed ACE-I/ARB/statins were not consistently using contraception or were not consistently informed of the risks. Provider-implemented QI interventions improved care but were difficult to accomplish, suggesting that new interventions are needed.