Indirect comparisons of competing interventions. A multicentre, double-blind, randomised, controlled, parallel-group study of the effectiveness of a pharmacist-acquired medication history in an emergency department Do randomized clinical trials with inadequate blinding report enhanced placebo effects for intervention groups and nocebo effects for placebo groups? Comparison of Population-Based Observational Studies With Randomized Trials in Oncology. Decision tree analyses of key patient characteristics in Middle Eastern/North African and Latin American men treated with long-acting and short-acting PDE5 inhibitors for erectile dysfunction Acceptability of the method of administration of a patient-reported outcome measure (PROM) with stroke survivors, a randomised controlled trial protocol A randomised controlled trial to compare the clinical and cost-effectiveness of prism glasses, visual search training and standard care in patients with hemianopia following stroke: a protocol An Approach to Assess Generalizability in Comparative Effectiveness Research Simple randomization did not protect against bias in smaller trials. A randomised controlled trial of clinics in secondary schools for adolescents with asthma. Indirect comparison in evaluating relative efficacy illustrated by antimicrobial prophylaxis in colorectal surgery. Adaptive trials in paediatric development: dealing with heterogeneity and uncertainty in pharmacokinetic differences in children. Optimizing polypharmacy among elderly hospital patients with chronic diseases—study protocol of the cluster randomized controlled POLITE-RCT trial Translating comparative effectiveness of depression medications into practice by comparing the depression medication choice decision aid to usual care: study protocol for a randomized controlled trial The YOU CALL–WE CALL Randomized Clinical Trial: Impact of a Multimodal Support Intervention After a Mild Stroke Improving medication use in newly admitted home healthcare patients: a randomized controlled trial. Randomized, placebo-controlled study of a selective PDE4 inhibitor in the treatment of asthma.
OBJECTIVES To survey the frequency of use of indirect comparisons in systematic review s and evaluate the methods used in their analysis and interpretation . Also to identify alternative statistical approaches for the analysis of indirect comparisons , to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within review s. DATA SOURCES Electronic data bases . REVIEW METHODS The Data base of Abstract s of Review s of Effects ( DARE ) was search ed for systematic review s involving meta- analysis of r and omised controlled trials ( RCTs ) that reported both direct and indirect comparisons , or indirect comparisons alone . A systematic review of MEDLINE and other data bases was carried out to identify published methods for analysing indirect comparisons . Study design s were created using data from the International Stroke Trial . R and om sample s of patients receiving aspirin , heparin or placebo in 16 centres were used to create meta-analyses , with half of the trials comparing aspirin and placebo and half heparin and placebo . Methods for indirect comparisons were used to estimate the contrast between aspirin  and  heparin . The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results . Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken . RESULTS Of the review s identified through DARE , 31/327 ( 9.5 % ) included indirect comparisons . A further five review s including indirect comparisons were identified through electronic search ing . Few review s carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest . Few method ological papers were identified . Some valid approaches for aggregate data that could be applied using st and ard software were found : the adjusted indirect comparison , meta-regression and , for binary data only , multiple logistic regression ( fixed effect models only ) . Simulation studies showed that the naive method is liable to bias and also produces over-precise answers . Several methods provide correct answers if strong but unverifiable assumptions are fulfilled . Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly r and omised comparisons . Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies , but the direction of such discrepancy is unpredictable . CONCLUSIONS Direct evidence from good- quality RCTs should be used wherever possible . Without this evidence , it may be necessary to look for indirect comparisons from RCTs . However , the results may be susceptible to bias . When making indirect comparisons within a systematic review , an adjusted indirect comparison method should ideally be used employing the r and om effects model . If both direct and indirect comparisons are possible within a review , it is recommended that these be done separately before considering whether to pool data . There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect . Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons . Research into how evidence from indirect comparisons compares to that from non-r and omised studies may also be warranted . Investigations using individual patient data from a meta- analysis of several RCTs using different protocol s and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful Background Admission to an emergency department ( ED ) is a key vulnerable moment when patients are at increased risk of medication discrepancies and medication histories are an effective way of ensuring that fewer errors are made . This study measured whether a pharmacist-acquired medication history in an ED focusing on a patient ’s current home medication regimen , and available to be used by a doctor when consulting in the ED , would reduce the number of patients having at least 1 medication discrepancy related to home medication . Methods This multicentre , double-blind , r and omised , controlled parallel-group study was conducted at 3 large teaching hospitals . Two hundred and seventy participants were r and omly allocated to an intervention ( n = 134 ) or a st and ard care ( n = 136 ) arm . All consecutive patients > 18 years old admitted through the ED were eligible . The intervention consisted of pharmacists conducting a st and ardised comprehensive medication history interview focusing on a patient ’s current home medication regimen , prior to being seen by a doctor . Data recorded on the admission medication order form was available to be used by a doctor during consultation in the ED . The admission medication order form was given to doctors at a later stage in the control arm for them to amend prescriptions . The effect of the intervention was assessed primarily by comparing the number of patients having at least 1 admission medication discrepancy regarding medication being taken at home . Secondary outcomes concerned the characteristics and clinical severity of such medication discrepancies . Results The intervention reduced discrepancies occurring by 33 % ( p < 0.0001 ; 0.1055 odds ratio , 0.05 - 0.24 95 % confidence interval ) , despite recall bias . Regarding total discrepancies , omitting medication occurred most frequently ( 55.1 % ) and most discrepancies ( 42.7 % ) were judged to have the potential to cause moderate discomfort or clinical deterioration . Conclusions A pharmacist-acquired medication history in an ED focusing on a patient ’s current home medication regimen available to be used by a doctor at the time of consulting in the ED reduced the number of patients having at least 1 home medication-related discrepancy . Trial registration Current Controlled Trials IS RCT N63455839 Background Studies suggest that expectations powerfully shape clinical outcomes . For subjective outcomes in adequately blinded trials , health improvements are substantial and largely explained by non-specific factors . The objective of this study was to investigate if unblinding in r and omized controlled trials ( RCTs ) is associated with enhanced placebo effects for intervention groups and nocebo effects for placebo groups . For these effects , a secondary objective was to explore potential moderating factors . Methods We included RCTs that investigated the efficacy of phosphodiesterase-5 ( PDE-5 ) inhibitors  for male erectile dysfunction by comparing one PDE-5 inhibitor to placebo . In addition , to be included studies must have reported scores for change from baseline , or baseline and final International Index of Erectile Functioning-Erectile Functioning domain score ( IIEF-EF )  , and be published in either English , French , Dutch , or German . We search ed for both published and unpublished relevant trials using PUBMED , EMBASE , the Cochrane Central Register of Controlled Trials , a clinical trials register ( clinical trials.gov ) and the Food and Drug Administration clinical review s through March 2012.We evaluated the blinding status of trials with the Cochrane Risk of Bias Tool , using the domains of allocation sequence concealment , blinding of participants , healthcare providers and outcome assessors . Across these four domains , studies that scored low risk of bias were judged to be adequately blinded and studies that scored unclear or high risk of bias were judged to be inadequately blinded . Results We included 110 studies ( 205 journal publications and 2 unpublished sources ) that involved 23,877 participants ; 93 ( 85 % ) , 51 ( 46 % ) , 93 ( 85 % ) and 93 ( 85 % ) studies were assessed with an unclear risk of bias for allocation concealment , blinding of participant , blinding of caregiver and blinding of outcome assessor , respectively . None of the studies reported testing of blinding . None of the 205 journal publications provided sufficient details to assess allocation concealment , blinding of participants , caregivers and outcome assessors . After contacting authors for additional information , we judged five studies to be adequately ( n = 1,202 ) and 16 to be inadequately ( n = 3,006 ) blinded . The IIEF-EF score for placebo groups in adequately blinded trials versus inadequately blinded trials was 1.92 points ( 95 % CI , 0.64 to 3.20 ) versus 1.56 ( 95 % CI , 0.93 to 2.20 ) , respectively . The IIEF-EF score for intervention groups in adequately blinded trials versus inadequately blinded trials was 9.40 ( 95 % CI , 6.96 to 11.83 ) versus 8.33 ( 95 % CI , 7.29 to 9.37 ) , respectively . In a secondary analysis , prior experience with the drug affected the scores ; in placebo groups with participants naïve to the intervention the score was 2.89 ( 95 % CI , 2.33 to 3.45 ) versus -0.11 ( 95 % CI , -2.06 to 1.84 ) with participants having prior experience . In the intervention groups , these scores were 7.99 ( 95 % CI , 6.85 to 9.14 ) versus 8.33 ( 95 % CI , 7.51 to 9.16 ) , respectively . Unblinding lowered placebo scores ( creating a nocebo effect ) by 19 % ( 0.33 points ; 95 % CI , -0.96 to 1.62 ) . Unblinding lowered intervention scores by 11 % ( 1.0 ; 95 % CI , -1.35 to 3.47 ) . The results provided no conclusive evidence for nocebo or enhanced placebo effects .  Patients taking a PDE-5 inhibitor for the first time experience a larger placebo effect that accounts for 35 % of the total effect . Conclusions Given the overall poor reporting of blinding in clinical trial reports and the small number of trials that could be rated as adequately or inadequately blinded , we could not draw any robust conclusions about the existence or absence of nocebo and enhanced placebo effects . A large placebo effect was found for patients taking PDE-5 inhibitors for the first time . It was not clear if previous exposure to the drug impacted trial blinding . We found clear evidence that studies assessing a subjective continuous outcome fail to report on measures taken to secure double blinding . Although we observed a trend for the presence of a nocebo effect , there was insufficient evidence to quantify its impact on expectations . RCTs with patients with no prior experience with PDE-5 inhibitors reported larger placebo effects and possibly these studies were better blinded . Future research should further investigate the factors that contribute to blinding and their impact on health outcomes in r and omized trials of subjectively assessed conditions . This research is part of a PhD project and has no external funding . The authors have no competing interests to declare PURPOSE Comparative efficacy research performed using population registries can be subject to significant bias . There is an absence of objective data demonstrating factors that can sufficiently reduce bias and provide accurate results . METHODS MEDLINE was search ed from January 2000 to October 2016 for observational studies comparing two treatment regimens for any diagnosis of cancer , using SEER , SEER-Medicare , or the National Cancer Data base . Reporting quality and statistical methods were assessed using components of the STROBE criteria . R and omized trials comparing the same treatment regimens were identified . Primary outcome was correlation between survival hazard ratio ( HR ) estimates provided by the observational studies and r and omized trials . Secondary outcomes included agreement between matched pairs and predictors of agreement . RESULTS Of 3,657 studies review ed , 350 treatment comparisons met eligibility criteria and were matched to 121 r and omized trials . There was no significant correlation between the HR estimates reported by observational studies and r and omized trials ( concordance correlation coefficient , 0.083 ; 95 % CI , -0.068 to 0.230 ) . Forty percent of matched studies were in agreement regarding treatment effects ( κ , 0.037 ; 95 % CI , -0.027 to 0.1 ) , and 62 % of the observational study HRs fell within the 95 % CIs of the r and omized trials . Cancer type , data source , reporting quality , adjustment for age , stage , or comorbidities , use of propensity weighting , instrumental variable or sensitivity analysis , and well-matched study population did not predict agreement . CONCLUSION We were unable to identify any modifiable factor present in population -based observational studies that improved agreement with r and omized trials . There was no agreement beyond what is expected by chance , regardless of reporting quality or statistical rigor of the observational study . Future work is needed to identify reliable methods for conducting population -based comparative efficacy research Abstract Background : Phosphodiesterase type 5 ( PDE5 ) inhibitors have discontinuation rates as high as 60 % in men with erectile dysfunction . Treatment satisfaction has been significantly associated with treatment continuation . Underst and ing key characteristics in terms of treatment preference , relationship , and lifestyle issues could provide direction on how to improve compliance with PDE5 inhibitor treatment globally . Objective : The objective was to identify subgroups of interest in the pooled data base of two observational studies conducted in Latin America ( LA ) and Middle East/North Africa ( MENA ) exploring patient characteristics and prescription of either a long- or short-acting PDE5 inhibitor at baseline . Methods : Two identical prospect i ve , non-interventional , observational , studies in MENA ( N = 493 ) and LA ( N = 511 ) treated men with an ‘ on dem and ’ ( pro re nata , PRN ) PDE5 inhibitor ( sildenafil , tadalafil , vardenafil , or lodenafil ) during 6 months . In this post-hoc meta- analysis of two observational studies with equal design , pooled data were analyzed to determine patient characteristics and PDE5 inhibitor prescribed/used most likely to be associated with patient expectations , satisfaction , self-esteem , and patient – partner relationships . Decision tree analyses , with and without weighting , were used to identify and describe key features . Results : In each analysis of patient expectations , patient – partner relationship , and self-esteem , we describe the two major subgroups at baseline for each decision tree . Analyses of patient expectations and sexual self-esteem revealed that patients prescribed long-acting PDE5 inhibitors ( 59 % ) highlighted the importance of treatment effect duration , second to partner satisfaction with treatment , while patients prescribed short-acting PDE5 inhibitors ( 32 % ) placed less importance on treatment effect duration but considerable importance on treatment effect lasting until intercourse completion . Further insights regarding patients , partner relationship characteristics , and treatment expectations were identified . Conclusion : Our analyses have described key characteristics , such as self- and partner perceptions , sexual attitudes , and treatment expectations in relation to the patients ’ country and prescribed treatment , which might guide treatment decisions in MENA and LA men with ED Background UK-wide national clinical guidelines promote routine 6-month post-stroke follow-up assessment . However , as part of this 6-month assessment little information is gathered from the patient ’s perspective . The means of collecting this patient-centred information might be served best by a patient-reported outcome measure ( PROM ) at the 6-month assessment time point . Currently , four different methods of 6-month follow-up assessment occur ; the most common being face-to-face interview followed by telephone interview , postal question naire and online question naire . Therefore , this study will investigate if the acceptability of telephone , online or postal administration of a PROM at the 6-month post-stoke time point is not inferior to face-to-face administration . Methods / design A UK multicentre , blinded ( analyst and research er ) , pragmatic , non-inferiority study , with 80 % power using a 2.5 % non-inferiority margin was design ed to compare the acceptability of three modes of administration ( telephone interview , postal question naire and online question naire ) compared with face-to-face interview administration of a PROM . We plan to approach and r and omise a minimum of 808 potentially eligible participants , 202 participants per group . Discussion The aim of this ongoing research is to underst and if there is a difference between face-to-face administration and the other three methods of administering a PROM as a patient-centred supplement to the 6-month review for stroke survivors . In utilising a pragmatic design , it is believed that this study will offer UK wide generalisable results , of the acceptability of the methods under investigation , to inform clinicians and commissioners of stroke services . Trials registration Clinical Trials.gov : NCT03177161 . Registered on 6 June 2017 Introduction Homonymous hemianopia is a common and disabling visual problem after stroke . Currently , prism glasses and visual scanning training are proposed to improve it . The aim of this trial is to determine the effectiveness of these interventions compared to st and ard care . Methods and analysis The trial will be a multicentre three arm individually r and omised controlled trial with independent assessment at 6 week , 12 week and 26 week post-r and omisation . Recruitment will occur in hospital , outpatient and primary care setting s in UK hospital trusts . A total of 105 patients with homonymous hemianopia and without ocular motility impairment , visual inattention or pre-existent visual field impairment will be r and omised to one of three balanced groups . R and omisation lists will be stratified by site and hemianopia level ( partial or complete ) and created using simple block r and omisation by an independent statistician . Allocations will be disclosed to patients by the treating clinician , maintaining blinding for outcome assessment . The primary outcome will be change in visual field assessment from baseline to 26 weeks . Secondary measures will include the Rivermead Mobility Index , Visual Function Question naire 25/10 , Nottingham Extended Activities of Daily Living , Euro Qual-5D and Short Form-12 question naires . Analysis will be by intention to treat . Ethics and dissemination This study has been developed and supported by the UK Stroke Research Network Clinical Studies Group working with service users . Multicentre ethical approval was obtained through the North West 6 Research ethics committee ( Reference 10/H1003/119 ) . The trial is funded by the UK Stroke Association . Trial Registration : Current Controlled Trials IS RCT N05956042 . Dissemination will consider usual scholarly options of conference presentation and journal publication in addition to patient and public dissemination with lay summaries and articles . Trial Registration Current Controlled Trials IS RCT N05956042 Background . Policy makers require estimates of comparative effectiveness that apply to the population of interest , but there has been little research on quantitative approaches to assess and extend the generalizability of r and omized controlled trial ( RCT ) –based evaluations . We illustrate an approach using observational data . Methods . Our example is the Whole Systems Demonstrator ( WSD ) trial , in which 3230 adults with chronic conditions were assigned to receive telehealth or usual care .  First , we used novel placebo tests to assess whether outcomes were similar between the RCT control group and a matched subset of non participants who received usual care . We matched on 65 baseline variables obtained from the electronic medical record . Second , we conducted sensitivity analysis to consider whether the estimates of treatment effectiveness were robust to alternative assumptions about whether “ usual care ” is defined by the RCT control group or non participants . Thus , we provided alternative estimates of comparative effectiveness by contrasting the outcomes of the RCT telehealth group and matched non participants . Results . For some endpoints , such as the number of outpatient attendances , the placebo tests passed , and the effectiveness estimates were robust to the choice of comparison group . However , for other endpoints , such as emergency admissions , the placebo tests failed and the estimates of treatment effect differed markedly according to whether telehealth patients were compared with RCT controls or matched non participants . Conclusions . The proposed placebo tests indicate those cases when estimates from RCTs do not generalize to routine clinical practice and motivate complementary estimates of comparative effectiveness that use observational data . Future RCTs are recommended to incorporate these placebo tests and the accompanying sensitivity analyses to enhance their relevance to policy making OBJECTIVES By removing systematic differences across treatment groups , simple r and omization is assumed to protect against bias . However , r and om differences may remain if the sample size is insufficiently large . We sought to determine the minimal sample size required to eliminate r and om differences , thereby allowing an unbiased estimation of the treatment effect . STUDY DESIGN AND SETTING We reanalyzed two published multicenter , large , and simple trials : the International Stroke Trial ( IST ) and the Coronary Artery Bypass Grafting ( CABG ) Off- or On-Pump Revascularization Study  ( CORONARY ) . We reiterated 1,000 times the analysis originally reported by the investigators in r and om sample s of varying size . We measured the covariates balance across the treatment arms . We estimated the effect of aspirin and heparin on death or dependency at 30 days after stroke ( IST ) , and the effect of off-pump CABG on a composite primary outcome of death , nonfatal stroke , nonfatal myocardial infa rct ion , or new renal failure requiring dialysis at 30 days ( CORONARY ) . In addition , we conducted a series of Monte Carlo simulations of r and omized trials to supplement these analyses . RESULTS R and omization  removes r and om differences between treatment groups when including at least 1,000 participants , thereby result ing in minimal bias in effects estimation . Later , substantial bias is observed . In a short review , we show such an enrollment is achieved in 41.5 % of phase 3 trials published in the highest impact medical journals . CONCLUSIONS Conclusions drawn from completely r and omized trials enrolling a few participants may not be reliable . In these circumstances , alternatives such as minimization or blocking should be considered for allocating the treatment AIM To compare a nurse-led clinic in schools versus care in general practice for adolescents with asthma .  DESIGN OF STUDY R and omised controlled trial in four schools ; parallel observational study in two schools . SETTING Six comprehensive schools . METHOD In the r and omised trial , pupils were invited to attend asthma review  at a  nurse-led clinic  either in school , or in general practice . The parallel observational study compared pupils invited to practice care within and outside the r and omised trial . Primary outcome measures were attendance for asthma review , symptom control , and quality of life . Secondary outcomes were knowledge , attitudes , inhaler technique , use of steroids , school absence , peak flow rate , preference for future care , health service utilisation , and costs . RESULTS School clinic pupils were more likely to attend an asthma review than those r and omised to practice care ( 90.8 % versus 51.0 % overall [ P < 0.001 , not consistent across schools ] ) . No differences were observed in symptom control ( P = 0.42 ) or quality of life ( P = 0.63 ) . Pupils attending school clinics had greater knowledge of asthma ( difference = + 0.38 , 95 % CI = 0.19 to 0.56 ) , more positive attitudes ( difference = + 0.21 , 95 % CI = 0.05 to 0.36 ) , and better inhaler technique ( P < 0.001 , not consistent across all schools ) . No differences were observed in school absence or peak flow rate . A majority ( 63 % ) of those who had received care at school preferred this model in future . Median costs of providing care at school and at the practice were 32.10 Pounds and 19.80 Pounds , respectively . No differences were observed between the groups in the observational comparison on any outcome . CONCLUSIONS The schools asthma clinic increased uptake of asthma review s. There were improvements in various process measures , but not in clinical outcomes This paper aims to explore the potential usefulness and limitations of indirect comparisons in evaluating the relative efficacy of interventions . From a systematic review of antimicrobial prophylaxis in colorectal surgery , we identified 11 sets of r and omized trials that can be used to compare antibiotics both directly and indirectly . The discrepancy between the direct and the indirect comparison is defined as the absolute value of difference in log odds ratio . The adjusted indirect comparison has the advantages that the prognostic factors of participants in different trials can be partially taken into account and more uncertainty be incorporated into its result by providing a wider confidence interval . However , considerable discrepancies exist between the direct and the adjusted indirect comparisons . When there is no direct comparison , the adjusted indirect method may be used to obtain some evidence about the relative efficacy of competing interventions , although such indirect results should be interpreted with great caution . Further empirical and method ologic research is needed to explore the validity and generalizability of the adjusted indirect comparison for evaluating different interventions AIMS To assess whether an adaptive design in early clinical trials based on the paradigm of variable dosing and controlled exposure can provide better dosing recommendations compared with the st and ard fixed dose approach . METHODS In a clinical trial simulation setting , a paediatric study was simulated using a pharmacokinetic model previously developed for abacavir .  Plasma concentrations following the current recommended dose ( 8 mg kg⁻¹ ) were taken at st and ard sampling times , exposures ( AUC ) were calculated and doses individually adapted to reach the target exposure ( i.e. effective exposure in adults ) . A second round of simulations followed with the adapted doses , and the result ing concentrations were fitted again with the same model . Exposure distributions in both conditions ( i.e. fixed dose and controlled exposure ) were compared with the target exposure . RESULTS The AUC distribution after the current dose result ed in a median exposure of 6.43 mg h l⁻¹ ( 90th percentile 3.13 - 10.67 mg h l⁻¹ ) . A total of 61 of 128 subjects  showed AUC values either too low or to high compared with the target exposure . After dose adjustment , the median exposure was 6.94 mg h l⁻¹ ( 5.57 - 8.25 mg h l⁻¹ ) , and only 14 subjects deviated from the target range . CONCLUSIONS Adaptive r and omization can be used to optimize dosing regimens in early paediatric clinical trials . The r and omization of patients to target exposure rather than dose increases the probability of demonstrating efficacy ( i.e. study power ) compared with dose-controlled trials . Furthermore , it contributes to further underst and ing of the role of dose on the total heterogeneity in clinical response Background Treatment of patients with multimorbidity is challenging . A rational reduction of long-term drugs can lead to decreased mortality , less acute hospital treatment , and a reduction of costs . Simplification of drug treatment schemes is also related to higher levels of patient satisfaction and adherence . The POLITE- RCT trial will test the effectiveness of an intervention aim ing at reducing the number of prescribed long-term drugs among multimorbid and chronically ill patients . The intervention focuses on the interface between primary and secondary health care and includes a pharmacist-based , patient-centered medication review prior to the patient 's discharge from hospital . Methods The POLITE- RCT trial is a cluster r and omized controlled trial . Two major secondary health care providers of Mecklenburg-Western Pomerania , Germany , take part in the study . Clusters are wards of both medical centers . All wards where patients with chronic diseases and multimorbidity are regularly treated will be included . Patients aged 65 + years who take five or more prescribed long-term drugs and who are likely to spend at least 5 days in the participating hospitals will be recruited and included consecutively . Cluster-r and omization takes place after a six-month baseline data collection period . Patients of the control group receive care as usual . The independent two main primary outcomes are ( 1 ) health-related quality of life ( EQ-5D ) and ( 2 ) the difference in the number of prescribed long-term pharmaceutical agents  between intervention and control group . The secondary outcomes are appropriateness of prescribed medication ( PRISCUS list , Beers Criteria , MAI ) , patient satisfaction ( TSQM ) , patient empowerment ( PEF-FB-9 ) , patient autonomy ( IADL ) , falls , re-hospitalization , and death . The points of measurement are at admission to ( T0 ) and discharge from hospital ( T1 ) as well as 6 and 12 months after discharge from the hospital ( T2 and T3 ) . In 42 wards , 1,626 patients will be recruited . Discussion In case of positive evaluation , the proposed study will provide evidence for a sustainable reduction of polypharmacy by enhancing patient-centeredness and patient autonomy . Trial registration Current Controlled Trials IS RCT Background Comparative effectiveness research ( CER ) documents important differences in antidepressants in terms of efficacy , safety , cost , and burden to the patient . Decision aids can adapt this evidence to help patients participate in making informed choices . In turn , antidepressant therapy will more likely reflect patients ’ values and context , leading to improved adherence and mood outcomes . Methods / Design The objective of this study is to develop the Depression Medication Choice decision aid for use during primary care encounters , and to test its efficacy by conducting a clustered practical r and omized trial comparing the decision aid to usual depression care in primary care practice s . We will use a novel practice -based , patient-centered approach based on participatory action research that involves a multidisciplinary team of design ers , investigators , clinicians , patient representatives , and other stakeholders for the development of the decision aid . We will then conduct a clustered practical r and omized trial enrolling clinicians and their patients ( n = 300 ) with moderate to severe depression from rural , suburban and inner city primary care practice s ( n = 10 ) . The intervention will consist of the use of the depression medication choice decision aid during the clinical encounter . This trial will generate preliminary evidence of the relative impact of the decision aid on patient involvement in decision making , decision making quality , patient knowledge , and 6-month measures of medication adherence and mental health compared to usual depression care . Discussion Upon completion of the proposed research , we will have developed and evaluated the efficacy of the decision aid depression medication choice as a novel translational tool for CER in depression treatment , engaged patients with depression in their care , and refined the process by which we conduct practice -based trials with limited research footprint . Trial registration Clinical Trials.gov : Background — Comparison of a multimodal intervention WE CALL ( study initiated phone support/information provision ) versus a passive intervention YOU CALL ( participant can contact a re source person ) in individuals with first mild stroke . Methods and Results — This study is a single-blinded r and omized clinical trial . Primary outcome includes unplanned use of health services ( participant diaries ) for adverse events and quality of life ( Euroquol-5D , Quality of Life Index ) . Secondary outcomes include planned use of health services ( diaries ) , mood ( Beck Depression Inventory II ) , and participation ( Assessment of Life Habits [ LIFE-H ] ) . Blind assessment s were done at baseline , 6 , and 12 months . A mixed model approach for statistical analysis on an intention-to-treat basis was used where the group factor was intervention type and occasion factor time , with a significance level of 0.01 . We enrolled 186 patients ( WE=92 ; YOU=94 ) with a mean age of 62.5±12.5 years , and 42.5 % were women . No significant differences were seen between groups at 6 months for any outcomes with both groups improving from baseline on all measures ( effect sizes ranged from 0.25 to 0.7 ) . The only significant change for both groups from 6 months to 1 year ( n=139 ) was in the social domains of the LIFE-H ( increment in score , 0.4/9±1.3 [ 95 % confidence interval , 0.1–0.7 ] ; effect size , 0.3 ) . Qualitatively , the WE CALL intervention was perceived as reassuring , increased insight , and problem solving while decreasing anxiety . Only 6 of 94 ( 6.4 % ) YOU CALL participants availed themselves of the intervention . Conclusions — Although the 2 groups improved equally over time , WE CALL intervention was perceived as helpful , whereas YOU CALL intervention was not used . Clinical Trial Registration — URL : http://www.controlled-trials.com . Unique identifier : IS RCT N95662526 OBJECTIVES To test the efficacy of a medication use improvement program developed specifically for home health agencies . The program addressed four medication problems identified by an expert panel : unnecessary therapeutic duplication , cardiovascular medication problems , use of psychotropic drugs in patients with possible adverse psychomotor or adrenergic effects , and use of nonsteroidal antiinflammatory drugs ( NSAIDs ) in patients at high risk of peptic ulcer complications . It used a structured collaboration between a specially trained clinical pharmacist and the patients ' home-care nurses to improve medication use . DESIGN Parallel-group , r and omized controlled trial . SETTING Two of the largest home health agencies in the United States . PARTICIPANTS Study subjects were consenting Medicare patients aged 65 and older admitted to participating agency offices from October 1996 through September 1998 , with a projected home healthcare duration of at least 4 weeks and at least one study medication problem . INTERVENTION Qualifying patients were r and omized to usual care or usual care with the medication improvement program .  MEASUREMENTS Medication use was measured during an in-home interview , with container inspection at baseline and at follow-up ( between 6 and 12 weeks ) by interviewers unaware of treatment assignment . The trial endpoint was the proportion of patients with medication use improvement  according to predefined criteria at follow-up . RESULTS There were 259 r and omized patients with completed follow-up interviews : 130 in the intervention group and 129 with usual care . Medication use improved for 50 % of intervention patients and 38 % of control patients , an attributable improvement of 12 patients per 100 ( 95 % confidence interval ( CI ) = 0.0 - 24.0 , P = .051 ) . The intervention effect was greatest for therapeutic duplication , with improvement for 71 % of intervention and 24 % of control patients , an attributable improvement of 47 patients per 100 ( 95 % CI = 20 - 74 , P = .003 ) . Use of cardiovascular medications also improved more frequently in intervention patients : 55 % vs 18 % , attributable improvement 37 patients per 100 ( 95 % CI = 9 - 66 , P = .017 ) . There were no significant improvements for the psychotropic medication or NSAID problems . There was no evidence of adverse intervention effects : new medication problems , more agency nurse visits , or increased duration of home health care . CONCLUSIONS A program congruent with existing personnel and practice s of home health agencies improved medication use in a vulnerable population and was particularly effective in reducing therapeutic duplication BACKGROUND Phosphodiesterase-4 ( PDE4 ) inhibitors have potential utility as a new therapeutic approach to improving symptoms and pulmonary function in asthma and COPD . This study evaluated the efficacy and safety of MK-0359 , a selective and potent oral PDE4 inhibitor , in chronic asthma . METHODS Adults ( N=88 ) with > or = 1 year asthma history and an FEV(1 ) 50 - 80 % predicted were r and omized to double-blind treatment with MK-0359 ( 15mg/day ) or placebo for 14 days , then crossed-over to the other treatment for 14 days . The primary endpoint was the change from baseline in FEV(1 ) at the end of each 2-week treatment period . Secondary and other endpoints included the changes from baseline in Daytime asthma symptom score , Nighttime asthma symptom score , Total daily beta-agonist use ( puffs/day ) , AM and PM peak expiratory flow ( PEF ) and overall asthma-specific quality -of-life . Safety and tolerability were assessed by clinical adverse experiences . RESULTS MK-0359 significantly improved the primary endpoint ( versus placebo ) : the least-squares mean difference in change from baseline in FEV(1 ) ( L ) was 0.09L ( 95 % CI 0.01 , 0.18 ) . Endpoints of Daytime asthma symptom score , Nighttime asthma symptom score , Total daily beta-agonist use , AM PEF , PM PEF , and quality -of-life were also significantly improved . Nineteen patients ( 24.1 % ) on MK-0359 and 8 patients ( 10.4 % ) on placebo reported gastrointestinal clinical adverse experiences . Serious gastrointestinal clinical adverse experiences were reported in 3 patients while receiving MK-0359 . CONCLUSION Over a 14-day treatment period , the oral PDE4 inhibitor MK-0359 improved lower airway function , symptoms and rescue medication use in chronic asthma , although at the expense of gastrointestinal adverse experiences . ( Clinical trial registry number : NCT00482898 . )
For common outcomes there was similar efficacy between PDE-5 inhibitors
Background There are no r and omised and properly blinded trials directly comparing one PDE-5 inhibitor with another in a normal home setting .
Valid indirect comparisons with a common comparator must examine equivalent doses , similar duration , similar population s , with the same outcomes reported in the same way .