Brief interventions to prevent sexually transmitted infections suitable for in-service use: A systematic review

BackgroundSexually transmitted infections (STIs) are more common in young people and men who have sex with men (MSM) and effective in-service interventions are needed.MethodsA systematic review of randomized controlled trials (RCTs) of waiting-room-delivered, self-delivered and brief healthcare-provider-delivered interventions designed to reduce STIs, increase use of home-based STI testing, or reduce STI-risk behavior was conducted. Six databases were searched between January 2000 and October 2014.Results17,916 articles were screened. 23 RCTs of interventions for young people met our inclusion criteria. Significant STI reductions were found in four RCTs of interventions using brief one-to-one counselling (2 RCTs), video (1 RCT) and a STI home-testing kit (1 RCT). Increase in STI test uptake was found in five studies using video (1 RCT), one-to-one counselling (1 RCT), home test kit (2 RCTs) and a web-based intervention (1 RCT). Reduction in STI-risk behavior was found in seven RCTs of interventions using digital online (web-based) and offline (computer software) (3 RCTs), printed materials (1 RCT) and video (3 RCTs). Ten RCTs of interventions for MSM met our inclusion criteria. Three tested for STI reductions but none found significant differences between intervention and control groups. Increased STI test uptake was found in two studies using brief one-to-one counselling (1 RCT) and an online web-based intervention (1 RCT). Reduction in STI-risk behavior was found in six studies using digital online (web-based) interventions (4 RCTs) and brief one-to-one counselling (2 RCTs).ConclusionA small number of interventions which could be used, or adapted for use, in sexual health clinics were found to be effective in reducing STIs among young people and in promoting self-reported STI-risk behavior change in MSM.     

Aggregating single patient (n-of-1) trials in populations where recruitment and retention was difficult: the case of palliative care

Randomized controlled trials (RCTs) are the gold standard for evaluating new interventions. Different RCT designs apply depending on the patient population, clinical setting, and intervention being evaluated. A design that may help to generate evidence in some clinical areas where recruitment is a challenge is aggregated n-of-1 trials.N-of-1 trials are randomized, double-blind, and multiple crossover comparisons of an intervention and a control treatment. Methodologically robust n-of-1 trials provide an objective means of testing the effectiveness of treatments within individual participants. Aggregation of multiple cycle identically conducted n-of-1 trials yield a population estimate of effect, which potentially commensurate with that derived from other RCT designs. Trial participants contribute data for both intervention and control treatments creating matched data sets while using generally smaller sample sizes than conventional RCT trials.Careful choice of symptoms and medications are required for n-of-1 trials to be feasible. A validated and reliable outcome measure sensitive to change is still required.This article reviews the utility and limitations of aggregated n-of-1 trials to gather evidence in populations where conducting formal RCTs is difficult because of the low prevalence of the underlying condition or the clinical condition making recruitment and retention difficult. The article examines a proposed palliative care trial as a test case.     

The multiple baseline design for evaluating population-based research

There is a need for pragmatic and rigorous research designs to evaluate the effectiveness of population-based health interventions. The randomized controlled trial (RCT) has limitations in its practicality, ethical appropriateness, and cost when evaluating population-based interventions. Like RCTs, the multiple baseline design can demonstrate that a change in behavior has occurred, the change is a result of the intervention, and the change is significant. Especially important practical advantages over the RCT are that this design requires fewer population groups and communities may act as their own controls. Advantages and methodologic limitations of the multiple baseline design are discussed, and where feasible, strategies to minimize the impact of its limitations are suggested. Recommendations for future research are included.     

A systematic review of comparisons of effect sizes derived from randomised and non-randomised studies

BACKGROUND: There is controversy about the value of evidence about the effectiveness of healthcare interventions from non-randomised study designs. Advocates for quasi-experimental and observational (QEO) studies argue that evidence from randomised controlled trials (RCTs) is often difficult or impossible to obtain, or is inadequate to answer the question of interest. Advocates for RCTs point out that QEO studies are more susceptible to bias and refer to published comparisons that suggest QEO estimates tend to find a greater benefit than RCT estimates. However, comparisons from the literature are often cited selectively, may be unsystematic and may have failed to distinguish between different explanations for any discrepancies observed. OBJECTIVES: The aim was to investigate the association between methodological quality and the magnitude of estimates of effectiveness by comparing systematically estimates of effectiveness derived from RCTs and QEO studies. Quantifying any such association should help healthcare decision-makers to judge the strength of evidence from non-randomised studies. Two strategies were used to minimise the influence of differences in external validity between RCTs and QEO studies: a comparison of the RCT and QEO study estimates of effectiveness of any intervention, where both estimates were reported in a single paper a comparison of the RCT and QEO study estimates of effectiveness for specified interventions, where the estimates were reported in different papers. The authors also sought to identify study designs that have been proposed to address one or more of the problems often found with conventional RCTs. METHODS: DATA SOURCES: Relevant literature was identified from: The Cochrane Library, MEDLINE, EMBASE, DARE, and the Science Citation Index. References of relevant papers already identified experts. Electronic searches were very difficult to design and yielded few papers for the first strategy and when identifying study designs. CHOICE OF INTERVENTIONS TO REVIEW FOR STRATEGIES 1 AND 2: For strategy 1, any intervention was eligible. For strategy 2, interventions for which the population, intervention and outcome investigated were anticipated to be homogeneous across studies were selected for review: Mammographic screening (MSBC) of women to reduce mortality from breast cancer. Folic acid supplementation (FAS) to prevent neural tube defects in women trying to conceive. DATA EXTRACTION AND QUALITY ASSESSMENT: Data were extracted by the first author and checked by the second author. Disagreements were negotiated with reference to the paper concerned. For strategy 1, study quality was scored using a checklist to assess whether the RCT and QEO study estimates were derived from the same populations, whether the assessment of outcomes was 'blinded', and the extent to which the QEO study estimate took account of possible confounding. For strategy 2, a more detailed instrument was used to assess study quality on four dimensions: the quality of reporting, the generalisability of the results, and the extent to which estimates of effectiveness may have been subject to bias or confounding. All quality assessments were carried out by three people. DATA SYNTHESIS AND ANALYSIS: For strategy 1, pairs of comparisons between RCT and QEO study estimates were classified as high or low quality. Seven indices of the size of discrepancies between estimates of effect size and outcome frequency were calculated, where possible, for each comparison. Distributions of the size and direction of discrepancies were compared for high- and low-quality comparisons. FOR STRATEGY 2, THREE ANALYSES WERE CARRIED OUT: Attributes of the instrument were described by k statistics, percentage agreement, and Cronbach's a values. Regression analyses were used to investigate -variations in study quality. (ABSTRACT TRUNCATED)     

Realist RCTs of complex interventions – An oxymoron

Bonell et al. discuss the challenges of carrying out randomised controlled trials (RCTs) to evaluate complex interventions in public health, and consider the role of realist evaluation in enhancing this design (Bonell, Fletcher, Morton, Lorenc, & Moore, 2012). They argue for a “synergistic, rather than oppositional relationship between realist and randomised evaluation” and that “it is possible to benefit from the insights provided by realist evaluation without relinquishing the RCT as the best means of examining intervention causality.” We present counter-arguments to their analysis of realist evaluation and their recommendations for realist RCTs.Bonell et al. are right to question whether and how (quasi-)experimental designs can be improved to better evaluate complex public health interventions. However, the paper does not explain how a research design that is fundamentally built upon a positivist ontological and epistemological position can be meaningfully adapted to allow it to be used from within a realist paradigm. The recommendations for “realist RCTs” do not sufficiently take into account important elements of complexity that pose major challenges for the RCT design. They also ignore key tenets of the realist evaluation approach.We propose that the adjective ‘realist’ should continue to be used only for studies based on a realist philosophy and whose analytic approach follows the established principles of realist analysis. It seems more correct to call the approach proposed by Bonell and colleagues ‘theory informed RCT’, which indeed can help in enhancing RCTs.     

Neighborhood effects in a behavioral randomized controlled trial

Randomized controlled trials (RCTs) of interventions intended to modify health behaviors may be influenced by neighborhood effects which can impede unbiased estimation of intervention effects. Examining a RCT designed to increase colorectal cancer (CRC) screening (N=5628), we found statistically significant neighborhood effects: average CRC test use among neighboring study participants was significantly and positively associated with individual patient’s CRC test use. This potentially important spatially-varying covariate has not previously been considered in a RCT. Our results suggest that future RCTs of health behavior interventions should assess potential social interactions between participants, which may cause intervention arm contamination and may bias effect size estimation.     

Primary school interventions to promote fruit and vegetable consumption: a systematic review and meta-analysis

ObjectiveThe consumption of fruits and vegetables (FV) may contribute to the prevention of many diseases. However, children at school age do not eat an enough amount of those foods. We have systematically reviewed the literature to assess the effectiveness of school interventions for promoting the consumption of FV.MethodsWe performed a search in MEDLINE, EMBASE, CINAHL and CENTRAL. We pooled results and stratified the analysis according to type of intervention and study design.ResultsNineteen cluster studies were included. Most studies did not describe randomization method and did not take the cluster's effect into account. Pooled results of two randomized controlled trials (RCTs) of computer-based interventions showed effectiveness in improving consumption of FV [Standardized Mean Difference (SMD) 0.33 (95% CI 0.16, 0.50)]. No significant differences were found in pooled analysis of seven RCTs of multicomponent interventions or pooling results of two RCTs evaluating free/subsidized FV interventions.ConclusionsMeta-analysis shows that computer-based interventions were effective in increasing FV consumption. Multicomponent interventions and free/subsidized FV interventions were not effective. Improvements in methodology are needed in future cluster studies. Although these results are preliminary, computer-based interventions could be considered in schools, given that they are effective and cheaper than other alternatives.     

Network meta‐analysis of longitudinal data using fractional polynomials

Network meta‐analysis of randomized controlled trials (RCTs) are often based on one treatment effect measure per study. However, many studies report data at multiple time points. Furthermore, not all studies measure the outcomes at the same time points. As an alternative to a network meta‐analysis based on a synthesis of the results at one time point, a network meta‐analysis method is presented that allows for the simultaneous analysis of outcomes at multiple time points. The development of outcomes over time of interventions compared in an RCT is modeled with fractional polynomials, and the differences between the parameters of these polynomials within a trial are synthesized across studies with a Bayesian network meta‐analysis. The proposed models are illustrated with an analysis of RCTs evaluating interventions for osteoarthritis of the knee. Fixed and random effects second order fractional polynomials were applied to the case study. Network meta‐analysis with models that represent the treatment effects in terms of several parameters using fractional polynomials can be considered a useful addition to models for network meta‐analysis of repeated measures previously proposed. When RCTs report treatment effects at multiple follow‐up times, these models can be used to synthesize the results even if reporting times differ across the studies. Copyright © 2015 John Wiley & Sons, Ltd.     

Systematic Review of Interdisciplinary Interventions in Nursing Homes

BackgroundThe role of interdisciplinary interventions in the nursing home (NH) setting remains unclear. We conducted a systematic evidence review to study the benefits of interdisciplinary interventions on outcomes of NH residents. We also examined the interdisciplinary features of successful trials, including those that used formal teams.Data SourcesMedline was searched from January 1990 to August 2011. Search terms included residential facilities, long term care, clinical trial, epidemiologic studies, epidemiologic research design, comparative study, evaluation studies, meta-analysis and guideline.Study SelectionWe included randomized controlled trials (RCTs) evaluating the efficacy of interdisciplinary interventions conducted in the NH setting.MeasurementsWe used the Cochrane Collaboration tools to appraise each RCT, and an RCT was considered positive if its selected intervention had a significant positive effect on the primary outcome regardless of its effect on any secondary outcome. We also extracted data from each trial regarding the participating disciplines; for trials that used teams, we studied the reporting of various team elements, including leadership, communication, coordination, and conflict resolution.ResultsWe identified 27 RCTs: 7 had no statistically significant effect on the targeted primary outcome, 2 had a statistically negative effect, and 18 demonstrated a statistically positive effect. Participation of residents’ own primary physicians (all 6 trials were positive) and/or a pharmacist (all 4 trials were positive) in the intervention were common elements of successful trials. For interventions that used formal team meetings, presence of communication and coordination among team members were the most commonly observed elements.ConclusionOverall interdisciplinary interventions had a positive impact on resident outcomes in the NH setting. Participation of the residents’ primary physician and/or a pharmacist in the intervention, as well as team communication and coordination, were consistent features of successful interventions.     

Physical interventions for the treatment of trauma and stressor-related disorders: A comprehensive systematic review

BackgroundCognitive behavioral therapies for posttraumatic stress disorder (PTSD) are evidence-based and effective for many. However, the reach and impact of these interventions are limited. Physical interventions hold potential to bridge a gap in the unmet treatment of trauma and stressor-related disorders.MethodThis systematic review examined 84 studies from four decades of research on physical interventions for trauma and stressor-related disorders to: 1) describe the state of the field and 2) summarize the best available evidence. Reviewed studies were described in terms of measured sample characteristics and assessed outcomes. Treatment effect patterns were analyzed by intervention content and study design.ResultsThe majority of studies (65.9%) reported statistically significant reductions in posttraumatic stress symptoms; 40.9% used a randomized controlled trial (RCT) design. Among RCTs, one performed rigorous, statistically powered analyses in an intention-to-treat sample.LimitationsHigh variability in reporting strategies among reviewed studies precludes analysis of variables such as intervention length, frequency, and dropout.ConclusionPreliminary evidence for the efficacy of physical interventions for trauma and stressor-related disorders is promising. Larger scale RCTs powered and designed to identify mediators and moderators of these interventions are warranted.     

大型公共卫生项目评价研究设计的有关问题探讨

对源于临床医疗领域的随机对照试验(RCT)在大型公共卫生干预尤其是社区干预中拓展应用存在的外部效度和内部效度方面的局限性进行了重点阐释,认为外部效度受到社会和行为效应修饰问题的严重制约,且其传统的内部效度优势也因公共卫生项目因果路径长等特征而不能充分发挥,并指出一系列限制其现实可行性的因素。建议在大型公共卫生干预项目中,主要根据评价结论的用途并结合现实条件来确定合适的评价研究设计。针对意在检验因果关系的探索性项目,建议采用更广泛意义上的实验设计,包括整群随机试验设计、分阶渐进随机试验设计和N-of-1设计等,以改善传统RCT的现实可行性问题,同时,应发挥定性研究方法的优势,尽可能开展过程评价和项目监测以弥补内部效度方面存在的缺陷;对于因果关系已得到验证的示范项目或应用型项目,建议采用准实验设计,如时间序列设计或多重基线设计等,以及流行病学观察性研究方法,以保证充分的外部效度。     

Should structural interventions be evaluated using RCTs? The case of HIV prevention

Structural interventions addressing macro-social determinants of risk have been suggested as potentially important adjuncts to biomedical and behavioural interventions for the prevention of HIV and other diseases. A few interventions of this type have been evaluated using randomised controlled trials (RCTs), the most rigorous design to evaluate the effects of biomedical and behavioural interventions. The appropriateness of applying RCTs to structural interventions is however debated. This paper considers whether issues of ethics, feasibility and utility preclude the use of RCTs in evaluations of structural interventions for HIV prevention. We conclude there is nothing particular to this category of interventions prohibiting use of RCTs. However, we suggest that RCTs may prove unacceptable, unfeasible or not useful in certain circumstances, such as where an intervention brings important benefits other than HIV prevention (such as increased income); where leaders of clusters do not allow decisions about macro-social policies to be determined randomly; where the unit of social organization addressed by an intervention is so large that recruitment of adequate numbers of clusters is impossible; and where the period required to trial interventions extends beyond practical decision-making time-scales. In such cases, alternative evaluative designs must be assessed for their ability to provide evidence of intervention effectiveness.     

The one-person randomized controlled trial

Currently, the gold standard for collection of clinical evidence is the randomized controlled trial (RCT), preferably with large, multicenter samples of subjects. Although this approach provides valuable information, many clinicians find it difficult to translate RCT results to the individual patient level. In this report, a statistical approach called Design of Experiments (DOE) is described as a method of applying the principles of RCTs one person at a time. An overview of the method, with a simple clinical example, is presented. As shown, DOE is a more efficient method than the sequential approach often taken by clinicians and their patients when evaluating various treatment choices. Further, the effect of multiple interventions can be assessed, alone or in combination with each other. In this way, DOE can be an important addition to the field of evidence-based medicine, although further studies are needed.     

Interventions to increase the uptake of seasonal influenza vaccination among pregnant women: A systematic review

BackgroundPregnant women and their infants under 6 months of age infected with influenza have a high risk of serious morbidity and mortality. Influenza vaccine during pregnancy offers 3-for-1 benefits to pregnant women, fetuses and newborn infants. Current vaccination uptake rates during pregnancy, however, are often lower than other high-risk groups and the general population.MethodsWe systematically reviewed evidence on the effectiveness of interventions to improve influenza vaccination coverage in pregnant women. Risk differences (RDs) were calculated from the included studies.ResultsEleven studies were included in the review, of which four were randomized controlled trials (RCTs). Three cohort studies assessed provider-focused interventions while four RCTs and one cohort study evaluated pregnant women-focused interventions. Two cohort studies and a prospective intervention study assessed the effectiveness of bundled interventions. No study solely assessed the effectiveness of interventions to enhance access to influenza vaccination. One moderate quality RCT showed that an influenza pamphlet, with or without a verbalized benefit statement, improved the vaccination rate (RD = 0.26; RD = 0.39). The other reviewed RCTs showed discordant results, with RDs ranging from −0.15 to 0.03. Although all observational studies significantly improved vaccination rates (RDs ranged from 0.03 to 0.44), the quality of the evidence varied.ConclusionsThere is a lack of effective interventions to increase the influenza vaccination rate in pregnant women. Based on the existing research, we recommend that clinicians provide influenza pamphlets to pregnant women with a verbalized statement about the benefits of influenza vaccine to newborns. Further high-quality RCTs are needed to develop successful maternal influenza vaccination programs. Increased clarity in reporting the content of interventions would help to improve the comparability and generalizability of the published studies.     

Evaluación de la efectividad en salud pública: Fundamentos conceptuales y metodológicos

In the last few years, interest has markedly increased in evaluating health programs, especially their social utility and economic efficiency. However, consensus on key issues in evaluation, such as terminology, goals and methods is still a long way off. In this context, we review the main definitions and classifications of evaluation applied to public health programs and policies. We describe the main evaluation designs and their components, focusing on outcome evaluation. Threats to the internal validity of the results of weak evaluation designs are also discussed. The characteristics of public health interventions that limit evaluation with traditional designs are also analyzed. These limitations include the complexity of interventions, usually with multiple components, and the difficulty of forming an equivalent control group with no intervention, especially through random assignment. Finally, a two-step approach to evaluation through weak designs, which takes into account adequacy and plausibility, is described. Adequacy consists of the observation of a change in the selected indicators after the intervention, and would be sufficient to take decisions under certain conditions; at other times, plausibility would need to be analyzed, defined as attribution of the results to the program or intervention.     

Effectiveness assessment in public health: conceptual and methodological foundations

In the last few years, interest has markedly increased in evaluating health programs, especially their social utility and economic efficiency. However, consensus on key issues in evaluation, such as terminology, goals and methods is still a long way off. In this context, we review the main definitions and classifications of evaluation applied to public health programs and policies. We describe the main evaluation designs and their components, focusing on outcome evaluation. Threats to the internal validity of the results of weak evaluation designs are also discussed. The characteristics of public health interventions that limit evaluation with traditional designs are also analyzed. These limitations include the complexity of interventions, usually with multiple components, and the difficulty of forming an equivalent control group with no intervention, especially through random assignment. Finally, a two-step approach to evaluation through weak designs, which takes into account adequacy and plausibility, is described. Adequacy consists of the observation of a change in the selected indicators after the intervention, and would be sufficient to take decisions under certain conditions; at other times, plausibility would need to be analyzed, defined as attribution of the results to the program or intervention.     

Omega-3 fatty acids and cancers: a systematic update review of epidemiological studies

Experimental models showed consistently a modulation of carcinogenesis by omega 3 polyunsaturated fatty acids (ω3 PUFA). Fish intake is often described as part of a beneficial dietary pattern. However, observational epidemiological studies on the relationship between ω3 PUFA reported conflicting results. The objective of this systematic review is to determine whether there exists any progress in the evaluation of the causal relationship between dietary ω3 PUFA and cancers since the previous FAO/OMS expert consultation and whether it is possible to propose preventive and/or adjuvant therapeutic recommendations. Prospective and case-control observational studies published since 2007 and meeting validity criteria were considered together with RCT. Experimental studies are mentioned to provide for biological plausibility. When evaluating the level of evidence, a portfolio approach was used, weighted by a hierarchy giving higher importance to prospective studies followed by RCT if any. There is a probable level of evidence that ALA per se is neither a risk factor nor a beneficial factor with regards to cancers. Observational studies on colorectal, prostate and breast cancers only provided limited evidence suggesting a possible role of LC-ω3PUFA in cancer prevention because insufficient homogeneity of the observations. Explanation for heterogeneity might be the inherent difficulties associated with epidemiology (confounding and dietary pattern context, measurement error, level of intake, genetic polymorphism). The role of LC-ω3PUFA as adjuvant, might be considered of possible use, in view of the latest RCT on lung cancers even if RCT on other cancers still need to be undertaken.     

Mediators, moderators, and modulators of causal effects in clinical trials––Dynamically Modified Outcomes (DYNAMO) in health-related quality of life

Purpose  There is more than one effect of a randomized intervention, and more than one response to a treatment. The mean group difference in the pre-specified outcome of a randomized controlled trial (RCT) estimates the average causal effect of treatment across causal mechanisms that may be distinct. To understand the comprehensive impact of an intervention, we propose identifying and separating the direct causal effects of the intervention from mediating, moderating, and modulating (individual differences) influences of uncontrolled variables. Methods   Relational outcomes and moderated interventions describe two common mechanisms by which treatment interactions with uncontrolled variables expand or qualify the causal inferences to be drawn from an RCT, signifying treatment impact beyond that captured by conventional mean differences. Relational outcomes are associations between post-randomization measures. The treatment intervention may affect relational outcomes, and individual differences may modulate them. With moderated interventions, the effect of treatment on the outcome of interest depends on personal attributes or pre-randomization uncontrolled variables. Results   Awareness and measurement of both types of mechanisms can greatly improve interpretation of the results of a clinical trial. Conclusion  The integrated formal system of Dynamically Modified Outcomes (DYNAMO) provides comprehensive analysis of the diverse causal influences and interactions operating in a clinical trial.