title: Influence of body mass index on the response to asthma controller agents External validity of randomised controlled trials in asthma: to whom do the results of the trials apply? Leukotriene antagonists as first-line or add-on asthma-controller therapy. Good research practices for comparative effectiveness research: analytic methods to improve causal inference from nonrandomized studies of treatment effects using secondary data sources: the ISPOR Good Research Practices for Retrospective Database Analysis Task Force Report--Part III. Complementing the randomized controlled trial evidence base. Evolution not revolution. 1-year prospective real life monitoring of asthma control and quality of life in Italy Effectiveness of inhaler types for real-world asthma management: retrospective observational study using the GPRD Improving the reporting of pragmatic trials: an extension of the CONSORT statement Small-particle Inhaled Corticosteroid as First-line or Step-up Controller Therapy in Childhood Asthma. Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size. Adherence to inhaled therapy, mortality and hospital admission in COPD Good research practices for comparative effectiveness research: approaches to mitigate bias and confounding in the design of nonrandomized studies of treatment effects using secondary data sources: the International Society for Pharmacoeconomics and Outcomes Research Good Research Practices for Retr A questionnaire to assess the relevance and credibility of observational studies to inform health care decision making: an ISPOR-AMCP-NPC Good Practice Task Force report. Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma A pragmatic–explanatory continuum indicator summary (PRECIS): a tool to help trial designers Quality standards for real-world research. Focus on observational database studies of comparative effectiveness. Pharmaceutical care for patients with persistent asthma: assessment of treatment compliance and use of inhaled medications. Prescribing practices and asthma control with hydrofluoroalkane-beclomethasone and fluticasone: a real-world observational study. Real-life prospective study on asthma control in Italy: cross-sectional phase results. Impact of asthma controller medications on clinical, economic, and patient-reported outcomes. Impact of a short-term educational intervention on adherence to asthma treatment and on asthma control. Increased Dose of Inhaled Corticosteroid versus Add-On Long-acting β-Agonist for Step-Up Therapy in Asthma. Are pharmacological randomised controlled clinical trials relevant to real-life asthma populations? A protocol for an UNLOCK study from the IPCRG Real life clinical study design supporting the effectiveness of extra-fine inhaled beclomethasone/formoterol at the level of small airways of asthmatics. Inhaler technique and asthma: feasability and acceptability of training by pharmacists. Predictors of adherence to treatment in patients with severe asthma treated at a referral center in Bahia, Brazil. Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant. CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials The REal Life EVidence AssessmeNt Tool (RELEVANT): development of a novel quality assurance asset to rate observational comparative effectiveness research studies Interventions to improve inhaler technique for people with asthma
abstract: The incidence of asthma has been positively associated with obesity . Asthma comprises diverse “ phenotypes ” reflecting heterogeneity in a number of characteristics , including response to therapy . The present authors examined whether body mass index ( BMI ) influenced the response to placebo , as well as to two asthma controller medications . A post hoc analysis was performed , pooling data from four double-blind , placebo-controlled studies r and omising 3,073 moderate asthmatic adults to montelukast ( n = 1,439 ) , beclomethasone ( n = 894 ) or placebo ( n = 740 ) . The primary end point was asthma control days ; other end points were forced expiratory volume in one second , β-agonist use and nocturnal awakening . Analyses were conducted using BMI classification into normal ( < 25.0 kg·m−2 ; 52 % of patients ) , overweight ( 25–29.9 kg·m−2 ; 32 % ) and obese ( ≥30.0 kg·m−2 ; 16 % ) categories , as well as BMI as a continuous variable . The treatment groups were balanced for BMI , demographic characteristics and parameters of asthma control .  The placebo response for all end points was generally lower with increasing BMI . Similarly , the response to the inhaled corticosteroid decreased , whereas the response to the leukotriene antagonist remained stable . In conclusion , post hoc data from the present study suggested that body mass index may influence the natural history of asthma control ( as reflected by response to placebo ) and may differentially influence response to the two active agents , warranting explicit testing in future prospect i ve studies Background : Asthma is a heterogeneous disease with a wide range of clinical phenotypes , not all of which may be encompassed in the subjects included in r and omised controlled trials ( RCTs ) . This makes it difficult for clinicians to know to what extent the evidence derived from RCTs applies to a given patient . Aim : To calculate the proportion of  individuals with asthma who would have been eligible for the major asthma RCTs from the data of a r and om community survey of respiratory health . Methods : A postal survey was sent to 3500 r and omly selected individuals aged 25–75 years . Respondents were invited to complete a detailed respiratory question naire and pulmonary function testing . Participants with current asthma were assessed against the eligibility criteria of the 17 major asthma RCTs cited in the Global Initiative for Asthma ( GINA ) guidelines . Findings : A total of 749 participants completed the full survey , of whom 179 had current asthma . A median 4 % of participants with current asthma ( range 0–36 % ) met the eligibility criteria for the included RCTs . A median 6 % ( range 0–43 % ) of participants with current asthma on treatment met the eligibility criteria . Interpretation : This study shows that the major asthma RCTs on which the GINA guidelines are based may have limited external validity as they have been performed on highly selected patient population s. Most of the participants with current asthma on treatment in the community would not have been eligible for these RCTs BACKGROUND Most r and omized trials of treatment for asthma study highly selected patients under idealized conditions . METHODS We conducted two parallel , multicenter , pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist ( LTRA ) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist ( LABA ) as add-on therapy in patients already receiving inhaled glucocorticoid therapy . Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life ( Mini Asthma Quality of Life Question naire [ MiniAQLQ ] score ≤6 ) or inadequate asthma control ( Asthma Control Question naire [ ACQ ] score ≥1 ) . We r and omly assigned patients to 2 years of open-label therapy , under the care of their usual physician , with LTRA ( 148 patients ) or an inhaled glucocorticoid ( 158 patients ) in the first-line controller therapy trial and LTRA ( 170 patients ) or LABA ( 182 patients ) added to an inhaled glucocorticoid in the add-on therapy trial . RESULTS Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials . At 2 months , differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence ( 95 % confidence interval [ CI ] for an adjusted mean difference , -0.3 to 0.3 ) . At 2 years , mean MiniAQLQ scores approached equivalence , with an adjusted mean difference between treatment groups of -0.11 ( 95 % CI , -0.35 to 0.13 ) in the first-line controller therapy trial and of -0.11 ( 95 % CI , -0.32 to 0.11 ) in the add-on therapy trial . Exacerbation rates and ACQ scores did not differ significantly between the two groups . CONCLUSIONS Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients . Equivalence was not proved at 2 years . The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group . ( Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others ; Controlled Clinical Trials number , IS RCT N99132811 . ) OBJECTIVES Most contemporary epidemiologic studies require complex analytical methods to adjust for bias and confounding . New methods are constantly being developed , and older more established methods are yet appropriate . Careful application of statistical analysis techniques can improve causal inference of comparative treatment effects from nonr and omized studies using secondary data bases . A Task Force was formed to offer a review of the more recent developments in statistical control of confounding . METHODS The Task Force was commissioned and a chair was selected by the ISPOR Board of Directors in October 2007 . This Report , the third in this issue of the journal , addressed methods to improve causal inference of treatment effects for nonr and omized studies . RESULTS The Task Force Report recommends general analytic techniques and specific best practice s where consensus is reached including : use of stratification analysis before multivariable modeling , multivariable regression including model performance and diagnostic testing , propensity scoring , instrumental variable , and structural modeling techniques including marginal structural models , where appropriate for secondary data . Sensitivity analyses and discussion of extent of residual confounding are discussed . CONCLUSIONS Valid findings of causal therapeutic benefits can be produced from nonr and omized studies using an array of state-of-the-art analytic techniques . Improving the quality and uniformity of these studies will improve the value to patients , physicians , and policymakers worldwide Observational studies and pragmatic trials can complement classical r and omized controlled trials ( RCTs ) by providing data more relevant to the circumstances under which medicine is routinely practice d , thereby providing practical guidance for clinicians . The bearing of RCT findings on day-to-day practice can be weighted and the data more meaningfully interpreted by practicing clinicians if evidence is integrated from a variety of different study design s and method ologies . The advent of observational studies and pragmatic trials , often referred to as " real-life studies , " has met with a degree of cynicism , but their role and value is gaining widespread recognition and support among clinicians . This article discusses where observational studies and pragmatic trials have utility , namely : in addressing clinical questions that are unanswered and /or unanswerable by RCTs ; in testing new hypotheses and possible license extensions ; and in helping to differentiate between available therapies for a given indication . Moreover , it seeks to highlight how the different approaches fit within a conceptual framework of evidence relevant to clinical practice , a step-change in the traditional view of medical evidence Objectives The study aim ed at prospect ively evaluating the evolution of asthma control in Italy , to evaluate the reasons for lack of asthma control , perceived quality of life ( QoL ) and association with level of asthma control , the impact of pharmacological treatment , the number of exacerbations and the healthcare re source consumption . Methods PRISMA ( PRospect I ve Study on asthMA control ) was an observational study performed in asthmatic patients including a cross-sectional phase and a 12-month prospect i ve phase . Asthma control was assessed with the  Asthma Control Test ™ ( ACT ) and QoL was evaluated with  EuroQoL-5D question naire filled in and collected during 5 clinic visits together with all the other data . Results The prospect i ve phase included 1017 patients with uncontrolled ( 55.7 % ) or partly controlled asthma ( 44.3 % ) . Out of the 739 patients evaluable after 12 months , 22.2 % achieved full asthma control ( ACT score = 25 ) and 58.7 % reached a good control ( ACT score : 20–24 ) . The improvement in asthma control was associated with improved QoL and reduced hospital visits . The main reasons for lack of asthma control were comorbidities , continued exposure to irritants/triggers and poor adherence to therapy . The frequency of exacerbations was lower in patients with controlled asthma . A fixed combination therapy with an inhaled corticosteroid and a long-acting β2 agonist was reported by 77.0 % of patients . A better asthma control and improved QoL were achieved with extrafine beclomethasone/formoterol compared to either budesonide/formoterol or fluticasone/salmeterol . Conclusions An improvement in asthma control and QoL can be achieved during a 1-year monitoring in a real life setting . Extrafine beclomethasone/formoterol was associated with significant benefit in terms of asthma control and QoL compared to large-particles combinations . Clinical Trials.gov number NCT01110460 Purpose : Results of r and omized controlled trials may not predict effectiveness of inhaled corticosteroids ( ICS ) in real-world clinical practice , where inhaler technique and device characteristics can influence effectiveness . We compared asthma outcomes for ICS delivered via three different inhaler devices : pressurized metered-dose inhaler ( pMDI ) , breath-actuated MDI ( BAI ) , and dry powder inhaler ( DPI ) . Patients and methods : This retrospective data base study evaluated 1-year outcomes for primary care patients with asthma aged 5–60 years prescribed their first ICS ( initiation population ) by pMDI ( n = 39,746 ) , BAI ( n = 9809 ) , or DPI ( n = 6792 ) , or their first ICS dose increase ( step-up population ) by pMDI ( n = 6245 ) , BAI ( n = 1388 ) , or DPI ( n = 1536 ) . Co- primary outcome measures were composite proxy measures of asthma control ( no hospital attendance for asthma , oral corticosteroids , or antibiotics for lower respiratory infection ) and severe exacerbations ( unscheduled hospital admission , emergency room attendance , or oral corticosteroids ) . Outcomes were adjusted for potential confounding factors identified during a baseline year . Results : In the initiation population , adjusted odds ratios ( 95 % confidence intervals [ CI ] ) for asthma control , as compared with pMDIs , were significantly better for BAIs ( 1.08 [ 1.02–1.14 ] ) and DPIs ( 1.13 [ 1.06–1.21 ] ) , while adjusted exacerbation rate ratios ( 95 % CI ) were 1.00 ( 0.93–1.08 ) and 0.88 ( 0.81–0.95 ) , respectively . In the step-up population , adjusted odds of asthma control were 1.21 ( 1.05–1.39 ) for BAIs and 1.13 ( 0.99–1.29 ) for DPIs ; adjusted exacerbation rate ratios were 0.83 ( 0.71–0.98 ) for BAIs and 0.85 ( 0.74–0.98 ) for DPIs , compared with pMDIs . Conclusion : Inhaler device selection may have a bearing on clinical outcomes . Differences in real-world effectiveness among these devices require closer evaluation in well- design ed prospect i ve trials Background The CONSORT statement is intended to improve reporting of r and omised controlled trials and focuses on minimising the risk of bias ( internal validity ) . The applicability of a trial ’s results ( generalisability or external validity ) is also important , particularly for pragmatic trials . A pragmatic trial ( a term first used in 1967 by Schwartz and Lellouch ) can be broadly defined as a r and omised controlled trial whose purpose is to inform decisions about practice . This extension of the CONSORT statement is intended to improve the reporting of such trials and focuses on applicability . Methods At two , two-day meetings held in Toronto in 2005 and 2008 , we review ed the CONSORT statement and its extensions , the literature on pragmatic trials and applicability , and our experiences in conducting pragmatic trials . Recommendations We recommend extending eight CONSORT checklist items for reporting of pragmatic trials : the background , participants , interventions , outcomes , sample size , blinding , participant flow , and generalisability of the findings . These extensions are presented , along with illustrative examples of reporting , and an explanation of each extension . Adherence to these reporting criteria will make it easier for decision makers to judge how applicable the results of r and omised controlled trials are to their own conditions . Empirical studies are needed to ascertain the usefulness and comprehensiveness of these CONSORT checklist item extensions . In the meantime we recommend that those who support , conduct , and report pragmatic trials should use this extension of the CONSORT statement to facilitate the use of trial results in decisions about health care . Pragmatic trials are design ed to inform decisions about practice , but poor reporting can reduce their usefulness . The CONSORT and Practihc groups describe modifications to the CONSORT guidelines to help readers assess the applicability of the BACKGROUND Because r and omized controlled trials of established pediatric asthma therapies are expensive and difficult to perform , observational studies may fill gaps in the evidence base . OBJECTIVES To compare the effectiveness of representative small-particle inhaled corticosteroid ( ICS ) with that of st and ard size-particle ICS for children initiating or stepping up ICS therapy for asthma ( analysis 1 ) and to compare the effectiveness of ICS dose step-up using small-particle ICS with adding long-acting β2-agonist ( LABA ) to the ICS ( analysis 2 ) . METHODS These historical matched cohort analyses drew on electronic medical records of children with asthma aged 5 to 11 years . Variables measured during 2 consecutive years ( 1 baseline year for confounder definition and 1 outcome year ) included risk-domain asthma control ( no hospital attendance for asthma , acute oral corticosteroids , or lower respiratory tract infection requiring antibiotics ) and rate of severe exacerbations ( asthma-related emergency , hospitalization , or oral corticosteroids ) . RESULTS In the initiation population ( n = 797 in each cohort ) , children prescribed small-particle ICS versus st and ard size-particle ICS experienced greater odds of asthma control ( adjusted odds ratio , 1.49 ; 95 % CI , 1.10 - 2.02 ) and lower severe exacerbation rate ( adjusted rate ratio , 0.56 ; 95 % CI , 0.35 - 0.88 ) . Step-up outcomes ( n = 206 in each cohort ) were also significantly better for small-particle ICS , with asthma control adjusted odds ratio of 2.22 ( 95 % CI , 1.23 - 4.03 ) and exacerbations adjusted rate ratio of 0.49 ( 95 % CI , 0.27 - 0.89 ) . The number needed to treat with small-particle ICS to achieve 1 additional child with asthma control was 17 ( 95 % CI , 9 - 107 ) for the initiation population and 5 ( 95 % CI , 3 - 78 ) for the step-up population . Outcomes were not significantly different for stepped-up small-particle ICS dose versus ICS/LABA combination ( n = 185 in each cohort ) . CONCLUSIONS Initiating or stepping up the ICS dose with small-particle ICS rather than with st and ard size-particle ICS is more effective and shows similar effectiveness to add-on LABA in childhood asthma RATIONALE Aerosol particle size influences the extent , distribution , and site of inhaled drug deposition within the airways . OBJECTIVES We hypothesized that targeting albuterol to regional airways by altering aerosol particle size could optimize inhaled bronchodilator delivery . METHODS In a r and omized , double-blind , placebo-controlled study , 12 subjects with asthma ( FEV1 , 76.8 + /- 11.4 % predicted ) inhaled technetium-99m-labeled monodisperse albuterol aerosols ( 30-microg dose ) of 1.5- , 3- , and 6-microm mass median aerodynamic diameter , at slow ( 30 - 60 L/min ) and fast ( > 60 L/min ) inspiratory flows . Lung and extrathoracic radioaerosol deposition were quantified using planar gamma-scintigraphy . Pulmonary function and tolerability measurements were simultaneously assessed . Clinical efficacy was also compared with unlabeled monodisperse albuterol ( 15-microg dose ) and 200 microg metered-dose inhaler ( MDI ) albuterol . RESULTS Smaller particles achieved greater total lung deposition ( 1.5 microm [ 56 % ] , 3 microm [ 50 % ] , and 6 microm [ 46 % ] ) , farther distal airways penetration ( 0.79 , 0.60 , and 0.36 , respective penetration index ) , and more peripheral lung deposition ( 25 , 17 , and 10 % , respectively ) . However , larger particles ( 30-microg dose ) were more efficacious and achieved greater bronchodilation than 200 microg MDI albuterol ( deltaFEV1 [ ml ] : 6 microm [ 551 ] , 3 microm [ 457 ] , 1.5 microm [ 347 ] , MDI [ 494 ] ) . Small particles were exhaled more ( 1.5 microm [ 22 % ] , 3 microm [ 8 % ] , 6 microm [ 2 % ] ) , whereas greater oropharyngeal deposition occurred with large particles ( 15 , 31 , and 43 % , respectively ) . Faster inspiratory flows decreased total lung deposition and increased oropharyngeal deposition for the larger particles , with less bronchodilation . A shift in aerosol distribution to the proximal airways was observed for all particles . CONCLUSIONS Regional targeting of inhaled beta2-agonist to the proximal airways is more important than distal alveolar deposition for bronchodilation . Altering intrapulmonary deposition through aerosol particle size can appreciably enhance inhaled drug therapy and may have implication s for developing future inhaled treatments Background : Little is known about adherence to inhaled medication in chronic obstructive pulmonary disease ( COPD ) and the impact on mortality and morbidity . Methods : Data on drug adherence from a r and omised double-blind trial comparing inhaled salmeterol 50 μg + fluticasone propionate 500 μg twice daily with placebo and each drug individually in 6112 patients with moderate to severe COPD over 3 years in the TORCH study were used  . All-cause mortality and exacerbations leading to hospital admission were primary and secondary end points . The study of adherence was not specified a priori as an ancillary study . Results : Of the 4880 patients ( 79.8 % ) with good adherence defined as > 80 % use of study medication  , 11.3 % died compared with 26.4 % of the 1232 patients ( 20.2 % ) with poor adherence .  The annual rates of hospital admission for exacerbations were 0.15 and 0.27 , respectively . The association between adherence and mortality remained unchanged and statistically significant after adjusting for other factors related to prognosis ( hazard ratio 0.40 ( 95 % CI 0.35 to 0.46 ) , p<0.001 ) . The association was even stronger when analysing on-treatment deaths only . Similarly , the association between adherence and hospital admission remained unchanged and significant in a multivariate analysis ( rate ratio 0.58 ( 95 % CI 0.44 to 0.73 , p<0.001 ) . The association between increased adherence and improved mortality and reduction in hospital admission was independent of study treatment . The effect of treatment was more pronounced in patients with good adherence than in those with poor adherence . Conclusion : Adherence to inhaled medication is significantly associated with reduced risk of death and admission to hospital due to exacerbations in COPD . Further research is needed to underst and these strong associations OBJECTIVES The goal of comparative effectiveness analysis is to examine the relationship between two variables , treatment , or exposure and effectiveness or outcome . Unlike data obtained through r and omized controlled trials , research ers face greater challenges with causal inference with observational studies . Recognizing these challenges , a task force was formed to develop a guidance document on method ological approaches to addresses these biases . METHODS The task force was commissioned and a Chair was selected by the International Society for Pharmacoeconomics and Outcomes Research Board of Directors in October 2007 . This report , the second of three reported in this issue of the Journal , discusses the inherent biases when using secondary data sources for comparative effectiveness analysis and provides method ological recommendations to help mitigate these biases . RESULTS The task force report provides recommendations and tools for research ers to mitigate threats to validity from bias and confounding in measurement of exposure and outcome . Recommendations on design of study included : the need for data analysis plan with causal diagrams ; detailed attention to classification bias in definition of exposure and clinical outcome ; careful and appropriate use of restriction ; extreme care to identify and control for confounding factors , including time-dependent confounding . CONCLUSIONS Design of nonr and omized studies of comparative effectiveness face several daunting issues , including measurement of exposure and outcome challenged by misclassification and confounding . Use of causal diagrams and restriction are two techniques that can improve the theoretical basis for analyzing treatment effects in study population s of more homogeneity , with reduced loss of generalizability Evidence -based health care decisions are best informed by comparisons of all relevant interventions used to treat conditions in specific patient population s.  Observational studies are being performed to help fill evidence gaps . Widespread adoption of evidence from observational studies , however , has been limited because of various factors , including the lack of consensus regarding accepted principles for their evaluation and interpretation . Two task forces were formed to develop question naires to assist decision makers in evaluating observational studies  , with one Task Force addressing retrospective research and the other Task Force addressing prospect i ve research . The intent was to promote a structured approach to reduce the potential for subjective interpretation of evidence and drive consistency in decision making . Separately developed question naires were combined into a single question naire consisting of 33 items . These were divided into two domains : relevance and credibility . Relevance addresses the extent to which findings , if accurate , apply to the setting of interest to the decision maker . Credibility addresses the extent to which the study findings accurately answer the study question . The question naire provides a guide for assessing the degree of confidence that should be placed from observational studies and promotes awareness of the subtleties involved in evaluating those Background : Although inhaled corticosteroids have an established role in the treatment of asthma , studies have tended to concentrate on non-smokers and little is known about the possible effect of cigarette smoking on the efficacy of treatment with inhaled steroids in asthma . A study was undertaken to investigate the effect of active cigarette smoking on responses to treatment with inhaled corticosteroids in patients with mild asthma . Methods : The effect of treatment with inhaled fluticasone propionate ( 1000 μg daily ) or placebo for 3 weeks was studied in a double blind , prospect i ve , r and omised , placebo controlled study of 38 steroid naïve adult asthmatic patients ( 21 non-smokers ) . Efficacy was assessed using morning and evening peak expiratory flow ( PEF ) readings , spirometric parameters , bronchial hyperreactivity , and sputum eosinophil counts . Comparison was made between responses to treatment in non-smoking and smoking asthmatic patients . Results : There was a significantly greater increase in mean morning PEF in non-smokers than in smokers following inhaled fluticasone ( 27 l/min v –5 l/min ) . Non-smokers had a statistically significant increase in mean morning PEF ( 27 l/min ) , mean forced expiratory volume in 1 second ( 0.17 l ) , and geometric mean PC20 ( 2.6 doubling doses ) , and a significant decrease in the proportion of sputum eosinophils ( –1.75 % ) after fluticasone compared with placebo . No significant changes were observed in the smoking asthmatic patients for any of these parameters . Conclusions : Active cigarette smoking impairs the efficacy of short term inhaled corticosteroid treatment in mild asthma . This finding has important implication s for the management of patients with mild asthma who smoke CMAJ • MAY 12 , 2009 • 180(10 ) © 2009 Canadian Medical Association or its licensors E47 R and omized trials have traditionally been broadly categorized as either an effectiveness trial or an efficacy trial , although we prefer the terms “ pragmatic ” and “ explanatory . ” Schwartz and Lellouch described these 2 approaches toward clinical trials in 1967 . These authors coined the term “ pragmatic ” to describe trials that help users choose between options for care , and “ explanatory ” to describe trials that test causal research hypotheses ( i.e. , that a given intervention causes a particular benefit ) . We take the view that , in general , pragmatic trials are primarily design ed to determine the effects of an intervention under the usual conditions in which it will be applied , whereas explanatory trials are primarily design ed to determine the effects of an intervention under ideal circumstances . Thus , these terms refer to a trial ’s purpose and , in turn , structure . The degree to which this purpose is met depends on decisions about how the trial is design ed and , ultimately , conducted . Very few trials are purely pragmatic or explanatory . For example , in an otherwise explanatory trial , there may be some aspect of the intervention that is beyond the investigator ’s control . Similarly , the act of conducting an otherwise pragmatic trial may impose some control result ing in the setting being not quite usual . For example , the very act of collecting data required for a trial that would not otherwise be collected in usual practice could be a sufficient trigger to modify participant behaviour in unanticipated ways . Further , several aspects of a trial are relevant , relating to choices of trial participants , health care practitioners , interventions , adherence to protocol and analysis . Thus , we are left with a multidimensional continuum rather than a dichotomy , and a particular trial may display varying levels of pragmatism across these dimensions . In this article , we describe an effort to develop a tool to assess and display the position of any given trial within the pragmatic – explanatory continuum . The primary aim of this tool is to help trialists assess the degree to which design decisions align with the trial ’s stated purpose ( decision-making v. explanation ) . Our tool differs , therefore , from that of Gartlehner and associates in that it is intended to inform trial design rather than provide a method of classifying trials for the purpose of systematic review s. It can , however , also be used by research funders , ethics committees , trial registers and journal editors to make the same assessment , provided trialists declare their intended purpose and adequately report their design decisions . Hence , reporting of pragmatic trials is addressed elsewhere Real-world research can use observational or clinical trial design s , in both cases putting emphasis on high external validity , to complement the classical efficacy r and omized controlled trials ( RCTs ) with high internal validity . Real-world research is made necessary by the variety of factors that can play an important a role in modulating effectiveness in real life but are often tightly controlled in RCTs , such as comorbidities and concomitant treatments , adherence , inhalation technique , access to care , strength of doctor-caregiver communication , and socio-economic and other organizational factors . Real-world studies belong to two main categories : pragmatic trials and observational studies , which can be prospect i ve or retrospective . Focusing on comparative data base observational studies , the process aim ed at ensuring high- quality research can be divided into three parts : preparation of research , analyses and reporting , and discussion of results . Key points include a priori planning of data collection and analyses , identification of appropriate data base(s ) , proper outcomes definition , study registration with commitment to publish , bias minimization through matching and adjustment processes accounting for potential confounders , and sensitivity analyses testing the robustness of results . When these conditions are met , observational data base studies can reach a sufficient level of evidence to help create guidelines ( i.e. , clinical and regulatory decision-making ) OBJECTIVE To evaluate treatment compliance and use of inhaled medications of patients with asthma receiving complementary pharmaceutical care . METHODS A controlled prospect i ve parallel study involving a study group and a control group . We selected 60 patients with persistent asthma and using metered-dose inhalers ( MDIs ) , dry powder inhalers ( DPIs ) or both .  The patients were evaluated three times over 60 days . Instructions were provided to the patients in the study group at all visits but only at the first visit to those in the control group . The patients using < 80 % or > 120 % of the total number of prescribed doses were classified as noncompliant . The inhalation technique was quantified by a scoring system . A satisfactory technique was defined as a score higher than 7 ( maximum , 9 ) for MDIs and higher than 4 ( maximum , 5 ) for DPIs . RESULTS The final study sample comprised 28 study group patients and 27 control group patients , of whom 18 ( 64.3 % ) and 20 ( 74.7 % ) , respectively , were considered treatment compliant . From the first to the third visits , there were increases , in the study and control groups , in the median MDI-use score ( from 3 [ range , 0 - 5 ] to 8 [ range , 8 - 9 ] ; p < 0.001 ; and from 5 [ range , 2 - 6 ] to 7 [ range , 6 - 8 ] ) , as well as in the median DPI-use score ( from 3 [ range , 2 - 4 ] to 5 [ range , 4 - 5 ] and from 3 [ range , 2 - 4 ] to 4 [ range , 3 - 5 ] ) . CONCLUSIONS The counseling provided by the pharmacist to the patient was important to assist in the implementation of the appropriate inhalation technique , especially for MDI use BACKGROUND Long-term r and omized trials comparing asthma outcomes between inhaled corticosteroids in real-world population s are lacking . As such , rigorously conducted observational studies to complement the findings of r and omized trials are needed . OBJECTIVE We sought to compare asthma-related outcomes over 1 year as recorded in a large primary care data base for patients aged 5 to 60 years receiving a first prescription ( initiation population ) or dose increase ( step-up population ) of hydrofluoroalkane (HFA)-beclomethasone or fluticasone .  METHODS We used a retrospective matched cohort study in which patients were matched on baseline demographic and disease severity measures . Co primary outcomes were asthma control ( a composite measure comprising no unplanned visit or hospitalization for asthma , oral corticosteroids , or antibiotics for lower respiratory tract infection ) and exacerbation rate . RESULTS More than 80 % of patients in each population achieved asthma control ; 10 % and 16 % of patients in the initiation and step-up population s , respectively , received add-on or combination therapy during the year . Fluticasone was prescribed at significantly higher doses than HFA-beclomethasone for both population s ( P < or= .001 ) . In the initiation population ( n = 1319 in each cohort ) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.30 ( 95 % CI , 1.02 - 1.65 ) relative to fluticasone . In the step-up population ( cohorts : n = 250 ) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.22 ( 95 % CI , 0.66 - 2.26 ) . Exacerbation rates were similar between cohorts . CONCLUSIONS In a real-world setting patients receiving HFA-beclomethasone had a similar or better chance of achieving asthma control at lower prescribed doses than with fluticasone OBJECTIVES To estimate the prevalence of partly controlled and uncontrolled asthmatic patients , to evaluate quality of life and healthcare re source consumption . METHODS Cross-sectional phase followed by a 12-month prospect i ve phase . Asthma Control Test and the EQ-5D were used . RESULTS 2853 adult patients recruited in 56 Hospital Respiratory Units in Italy were evaluated : 64.4 % had controlled asthma , 15.8 % partly controlled asthma and 19.8 % were uncontrolled . The mean ( SD ) EQ-5D score was 0.86 ( 0.17 ) in controlled , 0.75 ( 0.20 ) in partly controlled and 0.69 ( 0.23 ) in uncontrolled patients ( p<0.001 between groups ) . The number of patients requiring hospitalization or emergency room visits was lower in controlled ( 1.8 % and 1.6 % , respectively ) than in partly controlled ( 5.1 % and 11.5 % ) and uncontrolled ( 6.4 % and 18.6 % ) . A combination of an inhaled corticosteroid and a long-acting beta-2 agonist was the reported therapy by 56.0 % of patients , with the rate of controlled asthma and improved quality of life being higher in patients on extrafine beclomethasone/formoterol compared to budesonide/formoterol ( p<0.05 ) and fluticasone/salmeterol ( p<0.05 for quality of life ) . CONCLUSIONS Asthma control is achieved in a good proportion of Italian patients . Differences may be detected in a real-life setting in favor of extrafine beclomethasone/formoterol combination OBJECTIVE To comprehensively evaluate clinical , economic , and patient-reported outcomes associated with various therapeutic classes of asthma controller medications . PATIENTS AND METHODS This observational study , which used administrative cl aims data from US commercial health plans , included patients with asthma aged 18 through 64 years who filled a prescription for at least 1 asthma controller medication from September 1 , 2003 , through August 31 , 2005 . Outcome metrics included the use of short-acting beta-agonists ( SABAs ) , the use of oral corticosteroids , inpatient (INP)/emergency department ( ED ) visits , and asthma-related health care costs .  A subset of 5000 patients was r and omly selected for a survey using the Mini-Asthma Quality of Life Question naire , the Work Productivity and Activity Impairment question naire , and the Asthma Therapy Assessment Question naire . RESULTS Of 56,168 eligible patients , 823 returned completed question naires . Compared with inhaled corticosteroids ( ICSs ) , leukotriene modifiers ( LMs ) were associated with lower odds of INP/ED visits ( odds ratio [ OR ] , 0.80 ; P<.001 ) , lower odds of using 6 or more SABA canisters ( OR , 0.81 ; P<.001 ) , and higher annual cost ( $ 193 ; P<.001 ) . In the subgroup analysis of adherent patients , LMs were associated with higher odds of INP/ED visits ( OR , 1.74 ; P=.04 ) , lower odds of using 6 or more SABA canisters ( OR , 0.46 ; P<.001 ) , and higher annual cost ( $ 235 ; P<.001 ) . Inhaled corticosteroids and LMs had a comparable impact on all patient-reported outcomes . For combination therapy , ICS plus a long-acting beta-agonist consistently showed at least equivalent or better outcomes in the use of SABAs and oral corticosteroids , the risk of INP/ED visits , cost , asthma control level , quality of life , and impairment in productivity and activity . CONCLUSION Inhaled corticosteroids were associated with a lower risk of INP/ED visits , and a lower cost if adherence was achieved . When adherence can not be achieved , LMs may be a reasonable alternative . Combination therapy with ICS plus a long-acting beta-agonist was associated with better or equivalent clinical , economic , and patient-reported outcomes OBJECTIVE To evaluate the effect of a short-term individualized education program on adherence to asthma treatment , inhalation techniques , and asthma control . METHODS A prospect i ve study involving patients aged 14 years or older , with a confirmed diagnosis of asthma and recruited from the asthma outpatient clinic of a university hospital in the city of Porto Alegre , Brazil . The study was conducted in two phases ( before and after the educational intervention ) . At a routine medical visit , the participants completed a  general question naire in order to assess the level of asthma control and inhalation techniques . The participants also underwent pulmonary function testing . Subsequently , they participated in an asthma education program , which consisted of one individualized session . The participants were reevaluated after three months . RESULTS Of the 174 patients recruited , 115 completed the study . Between the first and second evaluations , there was a significant improvement in the effective use of inhaled corticosteroids ( 90.4 % vs. 93.3 % ; p = 0.003 ) , the effective use of long-acting β2 agonists ( 57.4 % vs. 63.5 % ; p < 0.0001 ) , the effective use of a combined regimen with these two medications ( 57.4 % vs. 62.6 % ; p < 0.0001 ) , and the self-reported adherence to corticosteroid therapy ( p = 0.001 ) . There was a significant decrease in the proportion of patients visiting ERs ( 30.4 % vs. 23.5 % ; p = 0.012 ) . However , the level of asthma control and the inhalation technique did not improve significantly ( p = 0.095 and p = 0.512 , respectively ) . CONCLUSIONS This short-term asthma education program result ed in an improvement in the use of medications for asthma control and a decrease in the number of ER visits , although it had no significant effect on the inhalation technique RATIONALE Guidelines advocate adding long-acting β-agonist ( LABA ) to inhaled corticosteroid as the preferred step-up therapy to increasing inhaled corticosteroid dose for patients with uncontrolled asthma on inhaled corticosteroid monotherapy . However , less than 5 % of patients with asthma qualify for the r and omized controlled trials on which guidelines are based . Thus , real-world data are needed to complement the results of r and omized trials with narrow entry criteria . OBJECTIVES To compare the effectiveness of stepping up asthma therapy with an increased dose of various types of inhaled corticosteroid as compared with add-on LABA . METHODS We performed a historical matched cohort study using large primary care data bases to compare asthma step-up therapy with small- and st and ard size-particle inhaled corticosteroid versus added LABA for patients 12 - 80 years old . As outcomes , we examined a composite of asthma control and rates of severe exacerbations . MEASUREMENTS AND MAIN RESULTS The odds of asthma control and rates of severe exacerbations over one outcome year were comparable with increased inhaled corticosteroid dose versus added LABA . The adjusted odds ratios ( 95 % confidence interval ) for achieving asthma control with increased inhaled corticosteroid dose versus inhaled corticosteroid/LABA were 0.99 ( 0.88 - 1.12 ) for small-particle inhaled corticosteroid ( n = 3,036 per cohort ) and 0.85 ( 0.67 - 1.07 ) for st and ard size-particle inhaled corticosteroid ( n = 809 per cohort ) . The adjusted rate ratios ( 95 % confidence interval ) for severe exacerbations , compared with inhaled corticosteroid/LABA combination inhaler , were 1.04 ( 0.91 - 1.20 ) and 1.18 ( 0.92 - 1.54 ) , respectively . The results were not affected by smoking status . CONCLUSIONS When applied to a broad primary care population , antiinflammatory therapy using increased doses of small- or st and ard size-particle inhaled corticosteroid is as effective as adding LABA , as measured by outcomes important to both patients and providers . Real-world population s and outcomes need to be taken into consideration when formulating treatment recommendations Are pharmacological r and omised controlled clinical trials relevant to real-life asthma population s ? : A protocol for an UNLOCK study from the BACKGROUND In an attempt to establish how treatment with inhaled extra-fine beclomethasone/formoterol ( I-EF-BDP/F ) formulation differs from other combinations of inhaled corticosteroid ( ICS ) and long acting beta-agonist ( LABA ) , we studied lung function and markers of airway inflammation upon switching to the extra-fine formulation and after 8 weeks of treatment with it . METHODS We carried out a real-life clinical observation of undercontrolled asthmatic patients switched over from dry powder inhalers of fluticasone/salmeterol and budesonide/formoterol to I-EF-BDP/F  ( Foster ( ® ) , Chiesi Farmaceutici S.p . A. , Italy ) . The effects of 8-weeks of treatment were documented by means of visual analog scale ( VAS ) , quality of life by Asthma Quality of Life Question naire ( AQLQ ) , spirometry and markers of airway or systemic inflammation : exhaled breath temperature ( EBT ) , blood eosinophils ( Eos ) , and high sensitivity C-reactive protein ( CRP ) . Before/after treatment differences between forced vital capacity percent of predicted ( % FVC ) , a simple indicator of small airways involvement , were calculated and subjects were ranked accordingly to reflect the magnitude of the therapeutic response . Subjects above the 75th percentile ( n = 15 ) , " top responders " , were then compared with those below the 25th percentile ( n = 15 ) " poor responders " . RESULTS On average , the 59 patients completing the study ( mean age ± SD 51 ± 12 years , 38 women ) had significant improvement in VAS and QLQ scores at the end of the treatment period ( 49.1 ± 2.4 vs. 73.1 ± 2.05 and 146.1 ± 2.7 vs. 176.7.1 ± 3.4 respectively , P < 0.001 ) , but not in the inflammatory indicators ( EBT , CRP and Eos ) . However , when comparing the " top responders " with the " poor responders " , significant improvement in these inflammatory indicators was observed : EBT significantly decreased from 34.04/mean/± 0.30/s.e.m./[ ° C ] to 33.57 ± 0.33 , P = 0.003 , Eos in blood fell from 381.7 ± 91.2 [ cells/μL ] to 244.2 ± 43.2 , P = 0.02 . Before/after treatment differences in hsCRP decreased significantly in the top responders compared with the poor responders ( Mann-Whitney test , P = 0.04 ) . CONCLUSION Asthmatic subjects who had the most improvement in FVC after transition to  I-EF-BDP/F  from other combined ICS/LABA preparations also demonstrated a significant decrease in some indicators of airway/systemic inflammation . These results support the notion that I-EF-BDP/F exerts an effect also at the level of the small airways through a reduction of the level of air trapping . Patients in whom inflammation of the small airways plays an important clinical role are the ones to derive most benefit from this small airways tailored treatment . However , improved compliance due to the " promise of a new drug " effect should also be considered as contributing to the treatment results Poor inhaler technique is frequent in asthma , but its long-term consequences have been seldom assessed . Pharmacists are ideally positioned to teach inhaler technique . This prospect i ve observational study evaluated the feasibility of inhaler training by pharmacists in patients receiving inhaled corticosteroids by pressurised metered-dose inhaler ( pMDI ) or breath-actuated MDI . In parallel , the relationships between inhaler technique , adherence , and asthma control , and their modulation one month after training were assessed . Of 727 patients receiving training at pharmacies ( n=123 ) , 61 % were prescribed a pMDI ; 35 % , an Autohaler ( ® ) ; and 5 % , an Easi-Breathe ( ® ) inhaler .  Poor asthma control ( Asthma Control Question naire score ≥ 1.5 ) at baseline was significantly ( p<0.05 ) and independently associated with poor inhaler technique and poor self-reported adherence ( Morisky score ≥ 3 ) . The percentage of patients with optimal inhaler technique rose from 24 % before to 79 % after training ( p<0.001 ) . Median training session length was 6 min . At 1 month , mean ( SD ) ACQ score had improved from a baseline score of 1.8 ( 1.2 ) to 1.4 ( 1.1 ) , ( p<0.001 ) . Importantly , greater change was observed in patients with improved inhaler technique versus those without . Similar results were observed for Morisky score . Inhaler technique is associated with adherence and influences asthma control  . Inhaler training by pharmacists is feasible and seams to improve inhaler technique , asthma control and adherence OBJECTIVE To determine the rate of adherence to treatment with inhaled corticosteroids in patients with severe asthma , to identify predictive factors for adherence and to evaluate the relationship between adherence to treatment and parameters of clinical and functional response . METHODS Prospect i ve cohort study of patients enrolled in the Program for the Control of Asthma and Allergic Rhinitis in the state of Bahia , Brazil . The study comprised 160 patients with severe asthma , monitored for 180 days in order to evaluate adherence ( dependent variable ) to the prescribed inhaled corticosteroid . Independent variables were assessed at baseline and for a six-month follow-up period by means of interviews and the completion of a st and ardized question naire . Patients recorded the missed doses in a diary . RESULTS Of the 160 patients . 158 completed the study .  Adherence rate was 83.8 % . Of the 158 patients , 112 ( 70.9 % ) were considered adherent ( cut-off point : 80 % of prescribed doses administered ) . There was a significant association between asthma control and adherence to treatment . Predictors of poor adherence were adverse effects , living far from the referral center , limited re sources to pay for transportation and dose schedule . Other factors , such as depressive symptoms , religion and economic status , were not associated with poor adherence . CONCLUSIONS Adherence to asthma treatment was high and was associated with the clinical response to treatment , in a sample of patients with severe asthma enrolled in a public program that provides free medication and the assistance of a multiprofessional specialized team in a referral center BACKGROUND This study tested the hypothesis that there would be improved asthma control with increasing doses of beclomethasone dipropionate ( BDP ) formulated in hydrofluoroalkane-134a ( HFA-BDP ) and the st and ard chlorofluorocarbon propellants ( CFC-BDP ) . Because HFA-BDP has improved lung deposition compared with CFC-BDP , this study also tested the hypothesis that HFA-BDP would provide more effective control of asthma than CFC-BDP . METHODS In this multicenter , r and omized , parallel-group blinded study , asthmatic subjects who had deterioration in asthma control after discontinuation of inhaled corticosteroids were r and omized to receive one of 6 possible treatments : 100 microg/d , 400 microg/d , or 800 microg/d of HFA-BDP or 100 microg/d , 400 microg/d , or 800 microg/d of CFC-BDP for 6 weeks . Changes in spirometry , daytime asthma symptom and nighttime asthma-related sleep disturbance scores , morning and evening peak expiratory flows , and daily use of inhaled beta-agonist for symptom control on diary cards were assessed over 6 weeks of treatment . RESULTS Three hundred twenty-three patients were r and omized to the 6 treatment groups , which had similar demographics and baseline lung function . There were significantly larger changes from baseline at week 6 in FEV(1 ) percent predicted with increasing doses of both HFA-BDP and CFC-BDP . The FEV(1 ) percent predicted dose-response curve for HFA-BDP was shifted to the left compared with the dose-response curve for CFC-BDP . By using the Finney bioassay method , it was calculated that 2.6 times as much CFC-BDP would be required to achieve the same improvement in FEV(1 ) percent predicted as HFA-BDP ( 95 % confidence interval , 1.1 - 11.6 ) . All treatment groups except the 100 microg/d CFC-BDP group tolerated study drug well . Ten ( 17 % ) of 59 patients in this group reported an acute asthma episode , increased asthma symptoms ( 6 of the 8 reports of increased asthma symptoms were classified as severe ) , or both , and 8 patients withdrew from the study ( 3 for adverse events related to asthma ) . CONCLUSIONS Increasing doses of inhaled corticosteroids lead to improved lung function and asthma control . Moreover , the reformulation of BDP in HFA enables effective asthma control at much lower doses than CFC-BDP Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Abstract Background Evidence from observational comparative effectiveness research ( CER ) is ranked below that from r and omized controlled trials in traditional evidence hierarchies . However , asthma observational CER studies represent an important complementary evidence source answering different research questions and are particularly valuable in guiding clinical decision making in real-life patient and practice setting s. Tools are required to assist in quality appraisal of observational CER to enable identification of and confidence in high- quality CER evidence to inform guideline development . Methods The REal Life EVidence AssessmeNt Tool ( RELEVANT ) was developed through a step-wise approach . We conducted an iterative refinement of the tool based on Task Force member expertise and feedback from pilot testing the tool until reaching adequate inter-rater agreement percentages . Two distinct pilots were conducted — the first involving six members of the Respiratory Effectiveness Group ( REG ) and European Academy of Allergy and Clinical Immunology ( EAACI ) joint Task Force for quality appraisal of observational asthma CER ;  the second involving 22 members of REG and EAACI membership . The final tool consists of 21 quality sub-items distributed across seven methodology domains : Background , Design , Measures , Analysis , Results , Discussion /Interpretation , and Conflict of Interest . Eleven of these sub-items are considered critical and named “ primary sub-items ” . Results Following the second pilot , RELEVANT showed inter-rater agreement ≥ 70 % for 94 % of all primary and 93 % for all secondary sub-items tested across three rater groups . For observational CER to be classified as sufficiently high quality for future guideline consideration , all RELEVANT primary sub-items must be fulfilled . The ten secondary sub-items further qualify the relative strengths and weaknesses of the published CER evidence . RELEVANT could also be applicable to general quality appraisal of observational CER across other medical specialties . Conclusions RELEVANT is the first quality checklist to assist in the appraisal of published observational CER developed through iterative feedback derived from pilot implementation and inter-rater agreement evaluation . Developed for a REG-EAACI Task Force quality appraisal of recent asthma CER , RELEVANT also has wider utility to support appraisal of CER literature in general ( including pre-publication ) . It may also assist in manuscript development and in educating relevant stakeholders about key quality markers in observational CER This Cochrane review contains 29 r and omised controlled trials ( RCT ) involving 2210 participants ( range 21–201 ) ( Normansell et al. , 2017 ) . Included studies targeted adults and adolescents ( aged 12 years and over ) and children ( aged under 12 years ) with asthma . Follow-up ranged from 2 to 26 weeks . Participants with other respiratory comorbidities , including chronic obstructive pulmonary disease and bronchiectasis , were excluded . Studies examined interventions conducted in hospital , primary care , community or outpatient care setting s. These included interventions aim ed at  improving inhaler technique compared with usual care with no additional intervention , or with alternative interventions such as asthma education only or a different type/intensity of inhaler technique intervention . Twelve studies evaluated enhanced face-to-face training , nine used multimedia-delivered training and the rest used  technique feedback devices . Studies were conducted in Europe ( n= 11 , of which 6 were in UK and 1 each in Belgium , Denmark , France , Irel and and Italy ) , USA ( n= 7 ) , Australia ( n= 4 ) , Asia ( n= 3 ) , Africa ( n= 1 ) and 3 were of unknown origin . Interventions were delivered by trained health care professionals including nurses , respiratory or physiotherapists , pharmacists and physicians
target: Results Although highlighting a general lack of high- quality real-life effectiveness observational research on these clinical ly important topics , the analysis provided insights into how identified observational studies might inform asthma guidelines developers and clinicians .
  Overall , RELEVANT appeared reliable and easy to use by expert review ers .
  Conclusions Using such quality appraisal tools is m and atory to assess whether specific observational real-life effectiveness studies can be used to inform guideline development and /or decision-making in clinical practice
background: Abstract Introduction A Task Force was commissioned jointly by the European Academy of Allergy and Clinical Immunology ( EAACI ) and the Respiratory Effectiveness Group ( REG ) to develop a  quality assessment tool for real-life observational research to identify high- quality real-life asthma studies that could be considered within future guideline development .