Abstract Introduction CompreHensive geriAtRician-led MEdication Review (CHARMER) is a behaviour change intervention to support geriatricians and pharmacists to proactively deprescribe inappropriate medicines with older adults in hospital. The intervention comprises: formulating a deprescribing action plan, workshops, benchmarking reports and weekly briefings between geriatricians and pharmacists. We assessed feasibility and acceptability of the CHARMER intervention and study processes. Method A two-arm purposive allocation feasibility study was undertaken in four hospitals (three intervention, one control) in England in 2022. Data were collected to check completeness and quality, and assess intervention fidelity. Rapid qualitative analysis of staff and patient interviews, intervention implementation observations (action plan launch, pharmacist workshop and geriatrician videos), and study meeting minutes was undertaken. Results Study data were feasible to collect, of sufficient completeness and quality. Geriatrician and pharmacist principal investigators managed intervention implementation. They were able to implement most intervention components with ease and fidelity. Principal investigators felt that dedicated support for intervention implementation would better equip them with the resource and expertise to fidelitously implement all intervention components. Detailed instructions for preparing the action plan and how it might be delivered were desired. Geriatricians and pharmacists who received the intervention found it acceptable. Pharmacists felt that the weekly briefings encouraged them to dedicate time to review medicines and raise with geriatricians, opportunities to deprescribe. Geriatricians indicated that participating in CHARMER allowed them to focus on deprescribing conversations with patients and they involved junior doctors more in the deprescribing process. Conclusion(s) The CHARMER intervention and trial processes were feasible and acceptable. Revisions to support intervention implementation include providing a template action plan for hospitals to adapt; funds for a project manager one day a week to work with CHARMER principal investigators for three-months to oversee implementation, and support from Eastern Academic Health Science Network in the definitive trial (winter 2023).

Background Having a stammer can have a significant effect on a child’s social, emotional and educational development. With approximately 66,000 children in the UK having a stammer, there is a need to establish an adequate evidence base to inform clinical practice. We describe a feasibility trial to explore the effectiveness of a new therapy programme for children aged 8–14: Palin Stammering Therapy for School Children (Palin STSC(8–14)). Preliminary data from the Michael Palin Centre, where the programme was developed, indicate that Palin STSC(8–14) is effective in reducing stammering frequency and impact for children, with beneficial effects for parents too. We will investigate the feasibility of the methods required for a definitive randomised controlled trial to investigate the application of this therapy by NHS speech and language therapists (SLTs), compared with ‘treatment as usual’ (TAU), beyond the specialist context in which it was developed. Methods This is a two-arm feasibility cluster-randomised controlled trial of Palin STSC(8–14) with TAU control arm, and randomisation at the level of the SLT. Quantitative and qualitative data will be collected to examine the following: the recruitment and retention of therapists and families, the acceptability of the research processes and the therapeutic intervention and the appropriateness of the therapy outcome measures. Assessments will be completed by children and parents at baseline and 6 months later, including measures of stammering severity; the impact of child’s stammering on both children and parents; child temperament, behaviour and peer relations, anxiety; quality of life; and economic outcomes. There will also be a qualitative process evaluation, including interviews with parents, children, SLTs and SLT managers to explore the acceptability of both the research and therapy methods. Treatment fidelity will be examined through analysis of therapy session records and recordings. Discussion The findings of this feasibility trial will inform the decision as to whether to progress to a full-scale randomised controlled trial to explore the effectiveness of Palin STSC(8–14) when compared to Treatment as Usual in NHS SLT services. There is a strong need for an evidence-based intervention for school age children who stammer. Trial registration ISRCTN. ISRCTN17058884 . Registered on 18 December 2019.

BACKGROUND:Trials are at risk of contamination bias which can occur when participants in the control group are inadvertently exposed to the intervention. This is a particular risk in rehabilitation studies where it is easy for trial interventions to be either intentionally or inadvertently adopted in control settings. The Falls in Care Homes (FinCH) trial is used in this paper as an example of a large randomised controlled trial of a complex intervention to explore the potential risks of contamination bias. We outline the FinCH trial design, present the potential risks from contamination bias, and the strategies used in the design of the trial to minimise or mitigate against this. The FinCH trial was a multi-centre randomised controlled trial, with embedded process evaluation, which evaluated whether systematic training in the use of the Guide to Action Tool for Care Homes reduced falls in care home residents. Data were collected from a number of sources to explore contamination in the FinCH trial. Where specific procedures were adopted to reduce risk of, or mitigate against, contamination, this was recorded. Data were collected from study e-mails, meetings with clinicians, research assistant and clinician network communications, and an embedded process evaluation in six intervention care homes. During the FinCH trial, there were six new falls prevention initiatives implemented outside the study which could have contaminated our intervention and findings. Methods used to minimise contamination were: cluster randomisation at the level of care home; engagement with the clinical community to highlight the risks of early adoption; establishing local collaborators in each site familiar with the local context; signing agreements with NHS falls specialists that they would maintain confidentiality regarding details of the intervention; opening additional research sites; and by raising awareness about the importance of contamination in research among participants.CONCLUSION:Complex rehabilitation trials are at risk of contamination bias. The potential for contamination bias in studies can be minimized by strengthening collaboration and dialogue with the clinical community. Researchers should recognise that clinicians may contaminate a study through lack of research expertise.

BACKGROUND:Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. METHODS:For this multicentre, double-blind, parallel-group, randomized, placebo-controlled feasibility trial, adults with OAC (including Siewert I-II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. RESULTS:A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low-density lipoprotein cholesterol levels by 3 months (adjusted mean difference -0·83 (95 per cent c.i. -1·4 to -0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow-up. Adverse events were similar between the groups. Quality-of-life data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non-randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. CONCLUSION:This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (www.isrctn/com).

Abstract Management of metastatic TNBC remains a challenge. Chemotherapy is the mainstay of treatment but benefits are frequently short-lived with rapid development of resistance. The PI3K/AKT/mTOR pathway has been implicated in many ways in TNBC, making inhibition of AKT an attractive therapeutic target. Based on downstream pathway activation signatures, PI3K pathway activation appears higher in TNBC compared to other molecular subtypes, despite a relatively low percentage of activating PI3K mutations. Alternative means of activating the PI3K pathway have been identified in TNBC, including loss or mutation of PTEN (up to 35%) and INPP4B (up to 30%) and/or amplification of PIK3CA, AKT2 or AKT3, resulting in increased activation of AKT. Induction of AKT by chemotherapy can be an early compensatory mechanism that can be exploited therapeutically to increase the efficacy of chemotherapy. Preclinical TNBC models with activated AKT signalling have been shown to be highly sensitive to AKT inhibitors. AZD5363 is a potent pan-AKT inhibitor with good oral bioavailability. Multiple lines of investigation have demonstrated strong synergistic effects between AKT inhibition and taxane chemotherapy in models of TNBC both in vitro and in vivo, providing rationale for the combination of AZD5363 and paclitaxel in TNBC. PAKT is designed to test the hypothesis that inhibition of AKT will increase the anti-tumour activity of paclitaxel chemotherapy in TNBC. The study will try to characterize those patients who may benefit from this treatment to identify potential predictors of sensitivity. PAKT is an international investigator led and sponsored, double-blind, placebo controlled, randomised phase II trial. Patients are randomised 1:1 to receive paclitaxel weekly (90mg/m2) on days 1,8, and 15 plus AZD5363 (400mgBD) or placebo (400mgBD) on days 2-5, 9-12, 15-19 (28 day treatment cycles). Patients are stratified by the number of metastatic sites and the interval from the end of adjuvant chemotherapy. Treatment is given until disease progression (RECIST 1.1), intolerable toxicity or elective withdrawal. Tumour assessments are carried out every 8 weeks. PAKT enrols patients with histologically documented locally advanced/metastatic TNBC (ER≤Allred2, PR≤Allred2, HER2=0,1+or2+), no prior systemic therapy for advanced TNBC, ECOG PS 0-2 and measurable disease per RECIST v1.1. Patients with brain metastases, significant cardiovascular disease, motor polyneuropathy are excluded. The primary endpoint is progression-free survival. Secondary endpoints are objective response rate, change in tumour size, clinical benefit rate, overall survival, duration of response, and patient reported outcomes. Archival tumour tissue must be available to evaluate potential biomarkers associated with therapeutic response and resistance. PFS will be compared between treatment arms by the stratified log-rank test. HR for disease progression/death will be estimated using a stratified Cox proportional hazards model. Kaplan-Meier methodology will be used to estimate the median PFS for each arm. Approximately 140 patients will be enrolled at ≈65 sites in the UK, France, Hungary, Romania, Georgia & South Korea. Citation Format: Schmid P, Wheatley D, Baird R, Chan S, Abraham J, Tutt A, Kristeleit H, Patel G, Bathakur U, Bishop J, Harper-Wynne C, Sims E, Copson E, Perren T, Stein R, Poole C, Cartwright H, Sarker S-J, Mousa K, Turner N. A phase II, double blind, randomised, placebo-controlled study of the AKT Inhibitor AZD5363 in combination with paclitaxel in triple-negative advanced or metastatic breast cancer (TNBC)(NCT02423603). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-13.

Management of metastatic TNBC remains a challenge. Chemotherapy is the mainstay of treatment but benefits are frequently short-lived with rapid development of resistance. The PI3K/AKT/mTOR pathway has been implicated in many ways in TNBC, making inhibition of AKT an attractive therapeutic target. Based on downstream pathway activation signatures, PI3K pathway activation appears higher in TNBC compared to other molecular subtypes, despite a relatively low percentage of activating PI3K mutations. Alternative means of activating the PI3K pathway have been identified in TNBC, including loss or mutation of PTEN (up to 35%) and INPP4B (up to 30%) and/or amplification of PIK3CA, AKT2 or AKT3, resulting in increased activation of AKT. Induction of AKT by chemotherapy can be an early compensatory mechanism that can be exploited therapeutically to increase the efficacy of chemotherapy. Preclinical TNBC models with activated AKT signalling have been shown to be highly sensitive to AKT inhibitors. AZD5363 is a potent pan-AKT inhibitor with good oral bioavailability. Multiple lines of investigation have demonstrated strong synergistic effects between AKT inhibition and taxane chemotherapy in models of TNBC both in vitro and in vivo, providing rationale for the combination of AZD5363 and paclitaxel in TNBC. PAKT is designed to test the hypothesis that inhibition of AKT will increase the anti-tumour activity of paclitaxel chemotherapy in TNBC. The study will try to characterize those patients who may benefit from this treatment to identify potential predictors of sensitivity. PAKT is an international investigator led and sponsored, double-blind, placebo controlled, randomised phase II trial. Patients are randomised 1:1 to receive paclitaxel weekly (90mg/m 2 ) on days 1,8, and 15 plus AZD5363 (400mgBD) or placebo (400mgBD) on days 2-5, 9-12, 15-19 (28 day treatment cycles). Patients are stratified by the number of metastatic sites and the interval from the end of adjuvant chemotherapy. Treatment is given until disease progression (RECIST 1.1), intolerable toxicity or elective withdrawal. Tumour assessments are carried out every 8 weeks. PAKT enrols patients with histologically documented locally advanced/metastatic TNBC (ER≤Allred2, PR≤Allred2, HER2=0,1+or2+), no prior systemic therapy for advanced TNBC, ECOG PS 0-2 and measurable disease per RECIST v1.1. Patients with brain metastases, significant cardiovascular disease, motor polyneuropathy are excluded. The primary endpoint is progression-free survival. Secondary endpoints are objective response rate, change in tumour size, clinical benefit rate, overall survival, duration of response, and patient reported outcomes. Archival tumour tissue must be available to evaluate potential biomarkers associated with therapeutic response and resistance. PFS will be compared between treatment arms by the stratified log-rank test. HR for disease progression/death will be estimated using a stratified Cox proportional hazards model. Kaplan-Meier methodology will be used to estimate the median PFS for each arm. Approximately 140 patients will be enrolled at ≈65 sites in the UK, France, Hungary, Romania, Georgia u0026 South Korea. Citation Format: Schmid P, Wheatley D, Baird R, Chan S, Abraham J, Tutt A, Kristeleit H, Patel G, Bathakur U, Bishop J, Harper-Wynne C, Sims E, Copson E, Perren T, Stein R, Poole C, Cartwright H, Sarker S-J, Mousa K, Turner N. A phase II, double blind, randomised, placebo-controlled study of the AKT Inhibitor AZD5363 in combination with paclitaxel in triple-negative advanced or metastatic breast cancer (TNBC)(NCT02423603). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-13.

Objectives: To evaluate, under real-life practice conditions in UK primary care, asthma control and cost-effectiveness of commencing therapy with leukotriene antagonists compared with inhaled corticosteroids (ICSs) as initial controller therapy and compared with long-acting β2-agonist as add-on therapy for patients with uncontrolled asthma already receiving ICS. Comparisons were made in terms of short-term efficacy (2 months) and longer-term effectiveness (2 years). Design: The study comprised two randomised controlled trials, powered for equivalence. Incremental cost-effectiveness approaches were used to study health-economic outcomes utilising NHS and societal costs. Setting: Study visits coincided with routine patient follow-up in the patients’ own primary care practices by their normal health-care providers to obtain a ‘real-life’ setting. Participants: Enrolled patients were aged 12–80 years, with asthma uncontrolled by (1) short-acting β2-agonist or (2) ICS. Active smokers and patients with small impairment of lung function/other morbidities were included in the trial. Interventions: Leukotriene antagonists were compared with ICS, as initial controller therapy, and with long-acting β2-agonist, as add-on therapy to ICS. Main outcome measures: The primary study outcome was the Mini Asthma Quality of Life Questionnaire (MiniAQLQ). An analysis of covariance was used, with treatment as a fixed effect, and baseline value as covariate, to analyse MiniAQLQ scores at 2 months (the primary time point), examining efficacy, and 2 years, as a measure of effectiveness, using an intention-to-treat approach. Results: In total, 687 patients were randomised and 650 participants (95%) had evaluable data for the primary study outcome. Comparing leukotriene antagonists with ICSs as initial controller therapy: at 2 months, the MiniAQLQ scores met the equivalence criterion, with adjusted difference (95% CI) between leukotriene antagonist and ICS of –0.02 (–0.24 to 0.20). At 2 years, however, the 95% CIs excluded the threshold for equivalence of 0.3, favouring ICS [–0.11 (–0.35 to 0.13)]. No significant between-group differences were found in Asthma Control Questionnaire (ACQ) score at either 2 months [adjusted difference 0.01 (–0.20 to 0.22)] or 2 years [0.13 (–0.07 to 0.33)]. Comparing leukotriene antagonist with long-acting β2-agonist as add-on therapy to ICS: at 2 months, the MiniAQLQ scores met the equivalence criterion [adjusted difference –0.10 (–0.29 to 0.10)], while at 2 years, the 95% CIs for MiniAQLQ score were marginally over the equivalence threshold, favouring long-acting β2-agonist as add-on therapy [adjusted difference –0.11 (–0.32 to 0.11)]. There were no significant between-group differences in ACQ score [adjusted difference at 2 months 0.12 (–0.06 to 0.30), and at 2 years 0.04 (–0.15 to 0.22)]. Daily ICS dose did not differ between the two treatment groups. Analysis of cost-effectiveness revealed that participants receiving leukotriene antagonist had significantly higher NHS and societal costs at both 2 months and 2 years but the outcomes were not statistically significantly different. For patients receiving add-on therapy to ICS, no significant differences between leukotriene antagonist and long-acting β2-agonist in NHS or societal cost were found at 2 months, but, after 2 years, participants receiving leukotriene antagonist had higher societal costs of borderline statistical significance. Conclusions: The evidence suggests that leukotriene antagonists are unlikely to be a cost-effective alternative to ICSs, at 2005 prices, as initial asthma controller therapy at step 2. Leukotriene antagonists were clinically equivalent to ICS as initial controller therapy and to long-acting β2-agonists as add-on to ICS in terms of QOL at 2 months; equivalence was not proven at 2 years. Future research should establish, in primary care, whether leukotriene antagonists will be more or less beneficial than ICSs alone or as an add-on to ICSs in treating patients with asthma who are also active smokers; determine why the ACQ correlates more poorly with economic outcomes of asthma than the Mini AQLQ and the European Quality of life-5 Dimensions questionnaire; and understand further the reasons why patients were switched from study medication when there was no real clinical indication to do so. Trial registration: Current Controlled Trials ISRCTN99132811. Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 21. See the HTA programme website for further project information.

Thirty million people, that is 6% of the population, in the European Union have asthma (1). Improving the lives of people with asthma may require developments in policy at national or international level in terms of public health measures, legislative change and both patient and professional education (2). But progress at an individual, patient–clinician level is also necessary. The International Primary Care Respiratory Group (IPCRG) is committed to identifying reasons for poor asthma control in individuals (3, 4). The Helping Asthma in Real People (HARP) initiative, which we describe here, is a practical implementation project (not a formal academic study) which seeks to start to address some of these issues using validated clinical assessment tools in real-life clinical practice. Improvements in asthma management require an assessment of each patient that examines current asthma control, evaluates current management (against safety and outcome), addresses adherence to the prescribed treatment, exposes possible reasons for poor adherence and identifies other factors that may be responsible for poor asthma control, such as smoking or untreated rhinitis. Optimum Patient Care, a social enterprise company based in Norwich, UK, has developed a system which supports such an assessment by collecting and linking data from the patient, in the form of questionnaires, and from the practitioner in the form of extracted routinely collected clinical data from electronic patient records (see Fig. 1). HARP assessment and reporting system. A questionnaire (a composite of validated questions) is sent to people with asthma to obtain information on current asthma control, exacerbations, admissions to hospital, time off work, inhaler use, beliefs and concerns on long-term inhaled therapy use, co-morbidities (rhinitis), life style choices (smoking) and occupation. An on-line, web site based questionnaire is also available at http://www.asthmatrak.org. Useful analysis of routinely held clinical data relies on the consistency of input of this data, preferably coded in a uniform manner. The quality of routine data collection in clinical care is understandably patchy, as is patient engagement in a clinical care initiative, so a degree of innovation and pragmatism is required to achieve the desired outcomes, albeit at some loss of academic purity. In countries that have standardized electronic clinical codes (e.g. ICD9 or 10 or Read [UK primary care]) an assessment can be made solely on analysis of the data held on an electronic patient record. Given a dependable level of quality and consistency of data input, evidence of both poor asthma control and some of the potential reasons for this can be suggested. Similarly, the online questionnaire is available for patients to complete, irrespective of whether or not they have been invited to do so by their clinician. Feedback is given to both patient and clinician in the form of a summarized questionnaire together with electronic data on current treatment, adherence to therapy, level of asthma control, patient reported concerns and beliefs and asthma management considerations, based on guideline recommendations. This should enhance the consultation process between doctor and patient, hopefully leading to improved asthma control. Confidentiality of patient-identifiable data during transfer or analysis is a justifiable concern for patients, their clinicians and health systems. A robust process of linked-anonymization before transfer and de-anonymization (in the doctor’s office) at the report stage is in place. No patient-identifiable data is held outside the clinician’s office. The Republic of Ireland has the fourth highest prevalence of asthma in the world with approximately 470 000 (12%) people affected. Sub-optimal asthma control is reflected in high rates of morbidity, hospital admissions, emergency presentations to Accident & Emergency and health care costs (5). With well-developed primary care contacts, interested clinicians and the prospect of institutional and political support, together with a shared language, Ireland was chosen as IPCRG’s pilot centre for the HARP implementation project. Fifteen practices were enrolled as part of a feasibility study. Both disease codes and prescriptions for short-acting beta agonists were used to identify patients likely to have asthma. Patients with COPD were excluded as were others as designated by the physician. Response rates to the questionnaire were variable as was the substantial level of uncontrolled asthma according to the measures used. Interestingly, a high percentage of respondents cited concerns about the long-term use of inhaled corticosteroids as a reason for poor compliance. This contrasts with UK studies which suggest patients’ impressions of lack of efficacy or lack of necessity drive this behaviour, although possible selection bias cannot be ruled out (6). Both individual patients and practices (in terms of individual and aggregated data) received feedback reports. It is hoped and expected that identification and reflection on factors related to poor asthma control will lead to better appreciation of the issues, the reality of an individual patient’s status, mutual understanding of the problems and thus to dialogue, implementation or revision of an asthma management plan and ultimately better outcomes. It is anticipated that HARP will be rolled out further in Ireland. We also plan to launch this project in another European country and make the resources used available online to others who wish to implement the project. The problems of the consistent recording of high quality data by clinicians, and responses to questionnaires by patients, were as great in this pilot as was expected and will doubtless remain so in the future. These impediments were balanced by the extraordinary enthusiasm of participating clinicians and the Asthma Society of Ireland. The HARP project in Ireland has become a key part of the advocacy programme of the Asthma Society of Ireland; highlighting both sub-optimal control in a high percentage of patients and the importance of capturing standardized data in managing chronic disease in the primary care environment. The interim HARP data, as a component of a wider report on the burden of asthma, has been influential in highlighting the need for a radical review of asthma management in Ireland. The value of ‘real patient’ data in influencing policy in the context of managing chronic disease should not be underestimated. In a joint policy initiative between the Department of Health, the Health Service Executive and the Asthma Society of Ireland, the Irish Government are now looking at the acclaimed asthma programme in Finland with a view to adopting some of the Finnish strategies in their own country (7). In terms of national health strategies, the structure of latest project from Finland, addressing allergic disease, is an exemplar (8). A common consensus, clear goals, tasks, tools and evaluation methods are described. Clinicians, national institutions and patients are involved and an international perspective and support is provided through an association with the Global Alliance against Chronic Respiratory Diseases (GARD). It gives us great pleasure to see government supported ventures offering the possibility of real change, hopefully for the eventual benefit of many people with asthma and allergic disease in Europe.

RATIONALE: Short-term, highly controlled trials indicate Qvar, and other inhaled corticosteroids (ICS) e.g. CFC-beclometasone (BDP) and fluticasone propionate (FP) metered dose inhalers (pMDI), are effective. However, one longer-term trial suggests greater effectiveness with Qvar. We compared Qvar and other ICS effectiveness in a large representative, UK clinical database. METHODS: Asthma patients, aged 5-60, without other chronic respiratory diseases, receiving Qvar, CFC-BDP or FP MDIs who subsequently had ICS increase between January 1997-June 2006 were identified from UK General Practice Research Database. Multiple logistic regression, adjusted for baseline severity provided odds of successful asthma control (no asthma hospital attendances, oral steroids, consultations or hospital admissions for lower respiratory tract infections requiring antibiotics) during 12 month follow-up. Poisson regression was used to compare asthma exacerbation rates (unscheduled hospital admissions/ A&E attendances for asthma or use of oral steroids). RESULTS: Data was available for 4133 patients (8% Qvar, 15% FP, 77% BDP). Odds ratio (95% CI) for success was lower with BDP and FP compared with Qvar (0.65 (0.47-0.90) and 0.71 (0.50-1.02) respectively. Exacerbation rates (95% CI) were higher with BDP and FP 1.44 (0.94-2.21) and 1.61 (1.02-2.55) respectively. CONCLUSIONS: Patients receiving increased ICS therapy with Qvar were more likely to achieve successful asthma control and less likely to experience exacerbations. These data may support the action site of an ICS as important in real life effectiveness in asthma.