REPRINT OF: Current Methods of the U.S. Preventive Services Task Force: A Review of the Process.

Editor's Note: This article is a reprint of a previously published article. For citation purposes, please use the original publication details: Harris RP, Helfand M, Woolf SH, et al. Current methods of the U.S. Preventive Services Task Force: a review of the process. Am J Prev Med. 2001;20(3S):21-35. The U.S. Preventive Services Task Force (USPSTF/Task Force) represents one of several efforts to take a more evidence-based approach to the development of clinical practice guidelines. As methods have matured for assembling and reviewing evidence and for translating evidence into guidelines, so too have the methods of the USPSTF. This paper summarizes the current methods of the third USPSTF, supported by the Agency for Healthcare Research and Quality (AHRQ) and two of the AHRQ Evidence-based Practice Centers (EPCs). The Task Force limits the topics it reviews to those conditions that cause a large burden of suffering to society and that also have available a potentially effective preventive service. It focuses its reviews on the questions and evidence most critical to making a recommendation. It uses analytic frameworks to specify the linkages and key questions connecting the preventive service with health outcomes. These linkages, together with explicit inclusion criteria, guide the literature searches for admissible evidence. Once assembled, admissible evidence is reviewed at three strata: (1) the individual study, (2) the body of evidence concerning a single linkage in the analytic framework, and (3) the body of evidence concerning the entire preventive service. For each stratum, the Task Force uses explicit criteria as general guidelines to assign one of three grades of evidence: good, fair, or poor. Good or fair quality evidence for the entire preventive service must include studies of sufficient design and quality to provide an unbroken chain of evidence-supported linkages, generalizable to the general primary care population, that connect the preventive service with health outcomes. Poor evidence contains a formidable break in the evidence chain such that the connection between the preventive service and health outcomes is uncertain. For services supported by overall good or fair evidence, the Task Force uses outcomes tables to help categorize the magnitude of benefits, harms, and net benefit from implementation of the preventive service into one of four categories: substantial, moderate, small, or zero/negative. The Task Force uses its assessment of the evidence and magnitude of net benefit to make a recommendation, coded as a letter: from A (strongly recommended) to D (recommend against). It gives an I recommendation in situations in which the evidence is insufficient to determine net benefit. The third Task Force and the EPCs will continue to examine a variety of methodologic issues and document work group progress in future communications.

Defining treatment-resistant depression.

BACKGROUND: Varying conceptualizations of treatment-resistant depression (TRD) have made translating research findings or systematic reviews into clinical practice guidelines challenging and inconsistent. METHODS: We conducted a review for the Centers for Medicare & Medicaid Services and the Agency for Healthcare Research and Quality to clarify how experts and investigators have defined TRD and to review systematically how well this definition comports with TRD definitions in clinical trials through July 5, 2019. RESULTS: We found that no consensus definition existed for TRD. The most common TRD definition for major depressive disorder required a minimum of two prior treatment failures and confirmation of prior adequate dose and duration. The most common TRD definition for bipolar disorder required one prior treatment failure. No clear consensus emerged on defining adequacy of either dose or duration. Our systematic review found that only 17% of intervention studies enrolled samples meeting the most frequently specified criteria for TRD. Depressive outcomes and clinical global impressions were commonly measured; functional impairment and quality-of-life tools were rarely used. CONCLUSIONS: Two key steps are critical to advancing TRD research: (a) Developing a consensus definition of TRD that addresses how best to specify the number of prior treatment failures and the adequacy of dose and duration; and (b) identifying a core package of outcome measures that can be applied in a standardized manner. Our recommendations about stronger approaches to designing and conducting TRD research will foster better evidence to translate into clearer guidelines for treating patients with this serious condition.

Primary Care Interventions to Prevent Child Maltreatment: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Child maltreatment, also referred to as child abuse and neglect, can result in lifelong negative consequences. Objective: To update the evidence on interventions provided in or referable from primary care to prevent child maltreatment for the US Preventive Services Task Force. Data Sources: PubMed, Cochrane Library, EMBASE, and trial registries through December 18, 2017; references; experts; literature surveillance through July 17, 2018. Study Selection: English-language fair- and good-quality randomized clinical trials that (1) included children with no known exposure to maltreatment and no signs or symptoms of current or past maltreatment, (2) evaluated interventions feasible in a primary care setting or that could result from a referral from primary care, and (3) reported abuse or neglect outcomes or proxies for abuse or neglect (eg, injury with a specificity for abuse, visits to the emergency department, hospitalization). Data Extraction and Synthesis: Two reviewers independently assessed titles/abstracts, full-text articles, and study quality; a third resolved conflicts when needed. When at least 3 similar trials were available, random-effects meta-analyses were conducted. Main Outcomes and Measures: Direct measures (including reports to child protective services and removal of the child from the home) or proxy measures of abuse or neglect; behavioral, emotional, mental, or physical well-being; and harms. Results: Twenty-two trials (33 publications) were included (N = 11 132). No significant association was found between interventions and reports to child protective services within 1 year of intervention completion (10.6% vs 11.9%; pooled odds ratio [OR], 0.94 [95% CI, 0.72-1.23]; 10 trials [n = 2444]) or removal of the child from the home within 1 to 3 years of follow-up (3.5% vs 3.7%; pooled OR, 1.09 [95% CI, 0.16-7.28]; 4 trials [n = 609]). No statistically significant associations were observed between interventions and outcomes for emergency department visits in the short term (<2 years), hospitalizations, child development, school performance, and prevention of death. Nonsignificant results from single trials led to a conclusion of insufficient evidence for injuries, failure to thrive, failure to immunize, school attendance, and other measures of abuse or neglect. Inconsistent results led to a conclusion of insufficient evidence for long-term (≥2 years) outcomes for reports to child protective services (ORs range from 0.48 to 1.13; 3 trials [n = 1690]), emergency department visits (1 of 2 trials reported significant differences) and internalizing and externalizing behavior symptoms (3 of 6 trials reported reductions in behavior difficulties). No eligible trials on harms of interventions were identified. Conclusions and Relevance: Interventions provided in or referable from primary care did not consistently prevent child maltreatment. No evidence on harms is available.

Comparative Benefits and Harms of Complementary and Alternative Medicine Therapies for Initial Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis.

OBJECTIVES: To report the comparative benefits and harms of exercise and complementary and alternative medicine (CAM) treatments with second-generation antidepressants (SGA) for major depressive disorder (MDD). DESIGN: Systematic review and meta-analysis. SETTINGS: Outpatient clinics. SUBJECTS: Adults, aged 18 years and older, with MDD receiving an initial treatment attempt with SGA. INTERVENTIONS: Any CAM or exercise intervention compared with an SGA. OUTCOME MEASURES: Treatment response, remission, change in depression rating, adverse events, treatment discontinuation, and treatment discontinuation due to adverse events. RESULTS: We found 22 randomized controlled trials for direct comparisons and 127 trials for network meta-analyses, including trials of acupuncture, omega-3 fatty acids, S-adenosyl methionine, St. John's wort, and exercise. For most treatment comparisons, we found no differences between treatment groups for response and remission. However, the risk of bias of these studies led us to conclude that the strength of evidence for these findings was either low or insufficient. The risk of treatment harms and treatment discontinuation attributed to adverse events was higher for selective serotonin receptor inhibitors than for St. John's wort. CONCLUSIONS: Although we found little difference in the comparative efficacy of most CAM therapies or exercise and SGAs, the overall poor quality of the available evidence base tempers any conclusions that we might draw from those trials. Future trials should incorporate patient-oriented outcomes, treatment expectancy, depressive severity, and harms assessments into their designs; antidepressants should be administered over their full dosage ranges; and larger trials using methods to reduce sampling bias are needed.

Quality improvement, implementation, and dissemination strategies to improve mental health care for children and adolescents: a systematic review.

BACKGROUND: Some outcomes for children with mental health problems remain suboptimal because of poor access to care and the failure of systems and providers to adopt established quality improvement strategies and interventions with proven effectiveness. This review had three goals: (1) assess the effectiveness of quality improvement, implementation, and dissemination strategies intended to improve the mental health care of children and adolescents; (2) examine harms associated with these strategies; and (3) determine whether effectiveness or harms differ for subgroups based on system, organizational, practitioner, or patient characteristics. METHODS: Sources included MEDLINE®, the Cochrane Library, PsycINFO, and CINAHL, from database inception through February 17, 2017. Additional sources included gray literature, additional studies from reference lists, and technical experts. Two reviewers selected relevant randomized controlled trials (RCTs) and observational studies, extracted data, and assessed risk of bias. Dual analysis, synthesis, and grading of the strength of evidence for each outcome followed for studies meeting inclusion criteria. We also used qualitative comparative analysis to examine relationships between combinations of strategy components and improvements in outcomes. RESULTS: We identified 18 strategies described in 19 studies. Eleven strategies significantly improved at least one measure of intermediate outcomes, final health outcomes, or resource use. Moderate strength of evidence (from one RCT) supported using provider financial incentives such as pay for performance to improve the competence with which practitioners can implement evidence-based practices (EBPs). We found inconsistent evidence involving strategies with educational meetings, materials, and outreach; programs appeared to be successful in combination with reminders or providing practitioners with newly collected clinical information. We also found low strength of evidence for no benefit for initiatives that included only educational materials or meetings (or both), or only educational materials and outreach components. Evidence was insufficient to draw conclusions on harms and moderators of interventions. CONCLUSIONS: Several strategies can improve both intermediate and final health outcomes and resource use. This complex and heterogeneous body of evidence does not permit us to have a high degree of confidence about the efficacy of any one strategy because we generally found only a single study testing each strategy. TRIAL REGISTRATION: PROSPERO, CRD42015024759 .

Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews.

OBJECTIVES: This study aims to summarise the evidence on more than 140 pharmacological and non-pharmacological treatment options for major depressive disorder (MDD) and to evaluate the confidence that patients and clinicians can have in the underlying science about their effects. DESIGN: This is a review of systematic reviews. DATA SOURCES: This study used MEDLINE, Embase, Cochrane Library, PsycINFO and Epistemonikos from 2011 up to February 2017 for systematic reviews of randomised controlled trials in adult patients with acute-phase MDD. METHODS: We dually reviewed abstracts and full-text articles, rated the risk of bias of eligible systematic reviews and graded the strength of evidence. RESULTS: Nineteen systematic reviews provided data on 28 comparisons of interest. For general efficacy, only second-generation antidepressants were supported with high strength evidence, presenting small beneficial treatment effects (standardised mean difference: -0.35; 95% CI -0.31 to -0.38), and a statistically significantly higher rate of discontinuation because of adverse events than patients on placebo (relative risk (RR) 1.88; 95% CI 1.0 to 3.28).Only cognitive behavioural therapy is supported by reliable evidence (moderate strength of evidence) to produce responses to treatment similar to those of second-generation antidepressants (45.5% vs 44.2%; RR 1.10; 95% CI 0.93 to 1.30). All remaining comparisons of non-pharmacological treatments with second-generation antidepressants either led to inconclusive results or had substantial methodological shortcomings (low or insufficient strength of evidence). CONCLUSIONS: In contrast to pharmacological treatments, the majority of non-pharmacological interventions for treating patients with MDD are not evidence based. For patients with strong preferences against pharmacological treatments, clinicians should focus on therapies that have been compared directly with antidepressants. TRIAL REGISTRATION NUMBER: International Prospective Register of Systematic Reviews (PROSPERO) registration number: 42016035580.

Comparative Effectiveness of Treatments for Binge-Eating Disorder: Systematic Review and Network Meta-Analysis.

Psychological and pharmacological interventions for binge-eating disorder have previously demonstrated efficacy (compared with placebo or waitlist control); thus, we aimed to expand that literature with a review of comparative effectiveness. We searched MEDLINE,® EMBASE,® Cochrane Library, Academic OneFile, CINAHL® for binge-eating disorder treatment articles and selected studies using predetermined inclusion and exclusion criteria. Data were sufficient for network meta-analysis comparing two pharmacological interventions; psychological interventions were analysed qualitatively. In all, 28 treatment comparisons were included in this review: one pharmacological comparison (second-generation antidepressants versus lisdexamfetamine) and 26 psychological comparisons. Only three statistically significant differences emerged: lisdexamfetamine was better at increasing binge abstinence than second-generation antidepressants; therapist-led cognitive behavioural therapy was better at reducing binge-eating frequency than behavioural weight loss, but behavioural weight loss was better at reducing weight. The majority of other treatment comparisons revealed few significant differences between groups. Thus, patients and clinicians can choose from several effective treatment options. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Preventing and De-escalating Aggressive Behavior Among Adult Psychiatric Patients: A Systematic Review of the Evidence.

OBJECTIVE: The project goal was to compare the effectiveness of strategies to prevent and de-escalate aggressive behaviors among psychiatric patients in acute care settings, including interventions for reducing use of seclusion and restraint. METHODS: Relevant databases were systematically reviewed for comparative studies of violence prevention and de-escalation strategies involving adult psychiatric patients in acute care settings. Studies (trials and cohort studies) were required to report on aggression or seclusion or restraint outcomes. Both risk of bias, an indicator of quality of individual studies, and strength of evidence (SOE) for each outcome were independently assessed by two study personnel. RESULTS: Seventeen primary studies met inclusion criteria. Evidence was limited for benefits and harms; information about characteristics that might modify the interventions' effectiveness, such as race or ethnicity, was especially limited. All but one study had a medium or high risk of bias and thus presented worrisome limitations. For prevention, risk assessment reduced both aggression and use of seclusion and restraint (low SOE), and multimodal interventions reduced the use of seclusion and restraint (low SOE). SOE for all other interventions, whether aimed at preventing or de-escalating aggression, and for modifying characteristics was insufficient. CONCLUSIONS: Available evidence about strategies for preventing and de-escalating aggressive behavior among psychiatric patients is very limited. Two preventive strategies, risk assessment and multimodal interventions consistent with the Six Core Strategies principles, may effectively lower aggressive behavior and use of seclusion and restraint, but more research is needed on how best to prevent and de-escalate aggressive behavior in acute care settings.

Binge-Eating Disorder in Adults: A Systematic Review and Meta-analysis.

BACKGROUND: The best treatment options for binge-eating disorder are unclear. PURPOSE: To summarize evidence about the benefits and harms of psychological and pharmacologic therapies for adults with binge-eating disorder. DATA SOURCES: English-language publications in EMBASE, the Cochrane Library, Academic OneFile, CINAHL, and ClinicalTrials.gov through 18 November 2015, and in MEDLINE through 12 May 2016. STUDY SELECTION: 9 waitlist-controlled psychological trials and 25 placebo-controlled trials that evaluated pharmacologic (n = 19) or combination (n = 6) treatment. All were randomized trials with low or medium risk of bias. DATA EXTRACTION: 2 reviewers independently extracted trial data, assessed risk of bias, and graded strength of evidence. DATA SYNTHESIS: Therapist-led cognitive behavioral therapy, lisdexamfetamine, and second-generation antidepressants (SGAs) decreased binge-eating frequency and increased binge-eating abstinence (relative risk, 4.95 [95% CI, 3.06 to 8.00], 2.61 [CI, 2.04 to 3.33], and 1.67 [CI, 1.24 to 2.26], respectively). Lisdexamfetamine (mean difference [MD], -6.50 [CI, -8.82 to -4.18]) and SGAs (MD, -3.84 [CI, -6.55 to -1.13]) reduced binge-eating-related obsessions and compulsions, and SGAs reduced symptoms of depression (MD, -1.97 [CI, -3.67 to -0.28]). Headache, gastrointestinal upset, sleep disturbance, and sympathetic nervous system arousal occurred more frequently with lisdexamfetamine than placebo (relative risk range, 1.63 to 4.28). Other forms of cognitive behavioral therapy and topiramate also increased abstinence and reduced binge-eating frequency and related psychopathology. Topiramate reduced weight and increased sympathetic nervous system arousal, and lisdexamfetamine reduced weight and appetite. LIMITATIONS: Most study participants were overweight or obese white women aged 20 to 40 years. Many treatments were examined only in single studies. Outcomes were measured inconsistently across trials and rarely assessed beyond end of treatment. CONCLUSION: Cognitive behavioral therapy, lisdexamfetamine, SGAs, and topiramate reduced binge eating and related psychopathology, and lisdexamfetamine and topiramate reduced weight in adults with binge-eating disorder. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

The Effectiveness of Total Worker Health Interventions: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.

BACKGROUND: The Total Worker Health (TWH) program of the National Institute for Occupational Safety and Health aims to advance worker well-being by integrating injury and illness prevention efforts with work-related safety and health hazard efforts. PURPOSE: To evaluate evidence on the benefits and harms of integrated TWH interventions. DATA SOURCES: MEDLINE, Cochrane Library, and PsycINFO (January 1990 through September 2015); clinical trial registries; and reference lists. STUDY SELECTION: English-language studies that enrolled employed adults and compared integrated interventions with usual work practice, no intervention, or another intervention. DATA EXTRACTION: Dual abstraction and risk-of-bias (ROB) assessment. DATA SYNTHESIS: Ten of the 15 included studies had high ROB, primarily because of selection and attrition bias. Findings graded as having low strength of evidence (SOE) supported the effectiveness of TWH interventions for improving smoking cessation, as measured by self-reported 7-day abstinence over 22 to 26 weeks (2 randomized, controlled trials [RCTs]; n = 737), and increasing consumption of fruits and vegetables over 26 to 104 weeks (3 RCTs; n = 6056); results apply to populations of blue-collar manufacturing and construction workers. Findings graded as having low SOE supported the effectiveness of TWH interventions for reducing sedentary work behavior in office workers over 16 to 52 weeks (2 RCTs; n = 262). Evidence was insufficient or lacking for other outcomes of interest, such as rates of work injuries, quality of life, and harms. LIMITATION: Small, diverse body of evidence with many methodological limitations; possible publication bias. CONCLUSION: Integrated TWH interventions might improve health behaviors (for example, reduce tobacco use and sedentary behavior and improve diet) of workers, but effects of these interventions on injuries and overall quality of life are not known. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Respiratory Syncytial Virus Hospitalizations in Healthy Preterm Infants: Systematic Review.

BACKGROUND: Studies have explored the risk for and impact of respiratory syncytial virus (RSV) infection requiring hospitalization among healthy preterm infants born at 29-35 weeks of gestational age not given RSV immunoprophylaxis. We performed a systematic review and qualitative synthesis of these studies. METHODS: Two experienced reviewers used prespecified inclusion/exclusion criteria to screen titles/abstracts and full-text studies using MEDLINE, Embase, BIOSIS and Cochrane Library (January 1, 1985, to November 6, 2014). We abstracted data on risk factors for RSV hospitalization, incidence and short- and long-term outcomes of RSV hospitalization. Using standard procedures, we assessed study risk of bias and graded strength of evidence (SOE). RESULTS: We identified 4754 records and reviewed 27. Important risk factors for RSV hospitalization included young age during the RSV season, having school-age siblings and day-care attendance, with odds ratios >2.5 in at least one study (high SOE). Incidence rates for RSV hospitalizations ranged from 2.3% to 10% (low SOE). Length of hospital stays ranged from 3.8 to 6.1 days (low SOE). Recurrent wheezing rates ranged from 20.7% to 42.8% 1 to 2 years after RSV hospitalization (low SOE). CONCLUSIONS: Young chronological age and some environmental risk factors are important clinical indicators of an increased risk of RSV hospitalization in healthy preterm infants 32 to 35 weeks of gestational age. SOE was low for estimates of incidence of RSV hospitalizations, in-hospital resource use and recurrent wheezing in this population. Studies were inconsistent in study characteristics, including weeks of gestational age, age during RSV season and control for confounding factors.

Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatments for Major Depression: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians.

BACKGROUND: Primary care patients and clinicians may prefer options other than second-generation antidepressants for the treatment of major depressive disorder (MDD). The comparative benefits and harms of antidepressants and alternative treatments are unclear. PURPOSE: To compare the benefits and harms of second-generation antidepressants and psychological, complementary and alternative medicine (CAM), and exercise treatments as first- and second-step interventions for adults with acute MDD. DATA SOURCES: English-, German-, and Italian-language studies from multiple electronic databases (January 1990 to September 2015); trial registries and gray-literature databases were used to identify unpublished research. STUDY SELECTION: Two investigators independently selected comparative randomized trials of at least 6 weeks' duration on health outcomes of adult outpatients; nonrandomized studies were eligible for harms. DATA EXTRACTION: Reviewers abstracted data on study design, participants, interventions, and outcomes; rated the risk of bias; and graded the strength of evidence. A senior reviewer confirmed data and ratings. DATA SYNTHESIS: 45 trials met inclusion criteria. On the basis of moderate-strength evidence, cognitive behavioral therapy (CBT) and antidepressants led to similar response rates (relative risk [RR], 0.90 [95% CI, 0.76 to 1.07]) and remission rates (RR, 0.98 [CI, 0.73 to 1.32]). In trials, antidepressants had higher risks for adverse events than most other treatment options; no information from nonrandomized studies was available. The evidence was too limited to make firm conclusions about differences in the benefits and harms of antidepressants compared with other treatment options as first-step therapies for acute MDD. For second-step therapies, different switching and augmentation strategies provided similar symptom relief. LIMITATION: High dropout rates, dosing inequalities, small sample sizes, and poor assessment of adverse events limit confidence in the evidence. CONCLUSION: Given their similar efficacy, CBT and antidepressants are both viable choices for initial treatment of MDD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

The predictive validity of quality of evidence grades for the stability of effect estimates was low: a meta-epidemiological study.

OBJECTIVE: To determine the predictive validity of the U.S. Evidence-based Practice Center (EPC) approach to GRADE (Grading of Recommendations Assessment, Development and Evaluation). STUDY DESIGN AND SETTING: Based on Cochrane reports with outcomes graded as high quality of evidence (QOE), we prepared 160 documents which represented different levels of QOE. Professional systematic reviewers dually graded the QOE. For each document, we determined whether estimates were concordant with high QOE estimates of the Cochrane reports. We compared the observed proportion of concordant estimates with the expected proportion from an international survey. To determine the predictive validity, we used the Hosmer-Lemeshow test to assess calibration and the C (concordance) index to assess discrimination. RESULTS: The predictive validity of the EPC approach to GRADE was limited. Estimates graded as high QOE were less likely, estimates graded as low or insufficient QOE more likely to remain stable than expected. The EPC approach to GRADE could not reliably predict the likelihood that individual bodies of evidence remain stable as new evidence becomes available. C-indices ranged between 0.56 (95% CI, 0.47 to 0.66) and 0.58 (95% CI, 0.50 to 0.67) indicating a low discriminatory ability. CONCLUSION: The limited predictive validity of the EPC approach to GRADE seems to reflect a mismatch between expected and observed changes in treatment effects as bodies of evidence advance from insufficient to high QOE.

Average effect estimates remain similar as evidence evolves from single trials to high-quality bodies of evidence: a meta-epidemiologic study.

OBJECTIVES: The objective of our study was to use a diverse sample of medical interventions to assess empirically whether first trials rendered substantially different treatment effect estimates than reliable, high-quality bodies of evidence. STUDY DESIGN AND SETTING: We used a meta-epidemiologic study design using 100 randomly selected bodies of evidence from Cochrane reports that had been graded as high quality of evidence. To determine the concordance of effect estimates between first and subsequent trials, we applied both quantitative and qualitative approaches. For quantitative assessment, we used Lin's concordance correlation and calculated z-scores; to determine the magnitude of differences of treatment effects, we calculated standardized mean differences (SMDs) and ratios of relative risks. We determined qualitative concordance based on a two-tiered approach incorporating changes in statistical significance and magnitude of effect. RESULTS: First trials both overestimated and underestimated the true treatment effects in no discernible pattern. Nevertheless, depending on the definition of concordance, effect estimates of first trials were concordant with pooled subsequent studies in at least 33% but up to 50% of comparisons. The pooled magnitude of change as bodies of evidence advanced from single trials to high-quality bodies of evidence was 0.16 SMD [95% confidence interval (CI): 0.12, 0.21]. In 80% of comparisons, the difference in effect estimates was smaller than 0.5 SMDs. In first trials with large treatment effects (>0.5 SMD), however, estimates of effect substantially changed as new evidence accrued (mean change 0.68 SMD; 95% CI: 0.50, 0.86). CONCLUSION: Results of first trials often change, but the magnitude of change, on average, is small. Exceptions are first trials that present large treatment effects, which often dissipate as new evidence accrues.

Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis.

STUDY QUESTION: What are the benefits and harms of second generation antidepressants and cognitive behavioral therapies (CBTs) in the initial treatment of a current episode of major depressive disorder in adults? METHODS: This was a systematic review including qualitative assessment and meta-analyses using random and fixed effects models. Medline, Embase, the Cochrane Library, the Allied and Complementary Medicine Database, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from January 1990 through January 2015. The 11 randomized controlled trials included compared a second generation antidepressant CBT. Ten trials compared antidepressant monotherapy with CBT alone; three compared antidepressant monotherapy with antidepressant plus CBT. SUMMARY ANSWER AND LIMITATIONS: Meta-analyses found no statistically significant difference in effectiveness between second generation antidepressants and CBT for response (risk ratio 0.91, 0.77 to 1.07), remission (0.98, 0.73 to 1.32), or change in 17 item Hamilton Rating Scale for Depression score (weighted mean difference, -0.38, -2.87 to 2.10). Similarly, no significant differences were found in rates of overall study discontinuation (risk ratio 0.90, 0.49 to 1.65) or discontinuation attributable to lack of efficacy (0.40, 0.05 to 2.91). Although more patients treated with a second generation antidepressant than receiving CBT withdrew from studies because of adverse events, the difference was not statistically significant (risk ratio 3.29, 0.42 to 25.72). No conclusions could be drawn about other outcomes because of lack of evidence. Results should be interpreted cautiously given the low strength of evidence for most outcomes. The scope of this review was limited to trials that enrolled adult patients with major depressive disorder and compared a second generation antidepressant with CBT, and many of the included trials had methodological shortcomings that may limit confidence in some of the findings. WHAT THIS STUDY ADDS: Second generation antidepressants and CBT have evidence bases of benefits and harms in major depressive disorder. Available evidence suggests no difference in treatment effects of second generation antidepressants and CBT, either alone or in combination, although small numbers may preclude detection of small but clinically meaningful differences. Funding, competing interests, data sharing This project was funded under contract from the Agency for Healthcare Research and Quality by the RTI-UNC Evidence-based Practice Center. Detailed methods and additional information are available in the full report, available at http://effectivehealthcare.ahrq.gov/.

Screening for Speech and Language Delay in Children 5 Years Old and Younger: A Systematic Review.

BACKGROUND AND OBJECTIVES: No recommendation exists for or against routine use of brief, formal screening instruments in primary care to detect speech and language delay in children through 5 years of age. This review aimed to update the evidence on screening and treating children for speech and language since the 2006 US Preventive Services Task Force systematic review. METHODS: Medline, the Cochrane Library, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and reference lists. We included studies reporting diagnostic accuracy of screening tools and randomized controlled trials reporting benefits and harms of treatment of speech and language. Two independent reviewers extracted data, checked accuracy, and assigned quality ratings using predefined criteria. RESULTS: We found no evidence for the impact of screening on speech and language outcomes. In 23 studies evaluating the accuracy of screening tools, sensitivity ranged between 50% and 94%, and specificity ranged between 45% and 96%. Twelve treatment studies improved various outcomes in language, articulation, and stuttering; little evidence emerged for interventions improving other outcomes or for adverse effects of treatment. Risk factors associated with speech and language delay were male gender, family history, and low parental education. A limitation of this review is the lack of well-designed, well-conducted studies addressing whether screening for speech and language delay or disorders improves outcomes. CONCLUSIONS: Several screening tools can accurately identify children for diagnostic evaluations and interventions, but evidence is inadequate regarding applicability in primary care settings. Some treatments for young children identified with speech and language delays and disorders may be effective.

Grading the strength of a body of evidence when assessing health care interventions: an EPC update.

OBJECTIVES: To revise 2010 guidance on grading the strength of evidence (SOE) of the effectiveness of drugs, devices, and other preventive and therapeutic interventions in systematic reviews produced by the Evidence-based Practice Center (EPC) program, established by the US Agency for Healthcare Research and Quality (AHRQ). STUDY DESIGN AND SETTING: A cross-EPC working group reviewed authoritative systems for grading SOE [primarily the approach from the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group] and conducted extensive discussions with GRADE and other experts. RESULTS: Updated guidance continues to be conceptually similar to GRADE. Reviewers are to evaluate SOE separately for each major treatment comparison for each major outcome. We added reporting bias as a required domain and retained study limitations (risk of bias), consistency, directness, and precision (and three optional domains). Additional guidance covers scoring consistency, precision, and reporting bias, grading bodies of evidence with randomized controlled trials and observational studies, evaluating single study bodies of evidence, using studies with high risk of bias, and presenting findings with greater clarity and transparency. SOE is graded high, moderate, low, or insufficient, reflecting reviewers' confidence in the findings for a specific treatment comparison and outcome. CONCLUSION: No single approach for grading SOE suits all reviews, but a more consistent and transparent approach to reporting summary information will make reviews more useful to the broad range of audiences that AHRQ's work aims to reach. EPC working groups will consider ongoing challenges and modify guidance as needed, on issues such as combining trials and observational studies in bodies of evidence, weighting domains, and combining qualitative and quantitative syntheses.