Showing papers on "Subgroup analysis published in 2007"

Effect of High-Dose Atorvastatin on Hospitalizations for Heart Failure. Subgroup Analysis of the Treating to New Targets (TNT) Study

Abstract: Background— Statins reduce the rate of major cardiovascular events in high-risk patients, but their potential benefit as treatment for heart failure (HF) is less clear. Methods and Results— Patient...

Do baseline characteristics predict response to treatment for low back pain? Secondary analysis of the UK BEAM dataset [ISRCTN32683578]

Abstract: Objectives. To identify characteristics of randomized controlled trial participants which predict greater benefits from physical treatments for low back pain. If successful, this would allow more appropriate selection of patients for different treatments. Methods. We did a secondary analysis of the UK Back pain Exercise And Manipulation trial (UK BEAM n ¼1334) dataset to identify baseline characteristics predicting response to manipulation, exercise and manipulation followed by exercise (combined treatment). Rather than simply identifying factors associated with overall outcome, we tested for the statistical significance of the interaction between treatment allocation, baseline characteristics and outcome to identify factors that predicted response to treatment. We also did a post-hoc subgroup analysis to present separate results for trial participants with subacute and chronic low back pain to inform future evidence synthesis. Results. Age, work status, age of leaving school, ‘pain and disability’, ‘quality of life’ and ‘beliefs’ at baseline all predicted overall outcome. None of these predicted response to treatment. In those allocated to combined treatment, there was a suggestion that expecting treatment to be helpful might improve outcome at 1yr. Episode length at study entry did not predict response to treatment. Conclusion. Baseline participant characteristics did not predict response to the UK BEAM treatment packages. Using recognized prognostic variables to select patients for different treatment packages, without first demonstrating that these factors affect response to treatment, may be inappropriate. In particular, this analysis suggests that the distinction between subacute and chronic low back pain may not be useful when considering treatment choices.

A method for testing a prespecified subgroup in clinical trials

Abstract: In clinical trials, investigators are often interested in the effect of a given study treatment on a subgroup of patients with certain clinical or biological attributes in addition to its effect on the overall study population. Such a subgroup analysis would become even more important to the study sponsor if an efficacy claim can be made for the subgroup when the test for the overall study population fails at a prespecified alpha level. In practice, such a claim is often dependent on prespecification of the subgroup and certain implicit or explicit requirements placed on the study results due to ethical or regulatory concerns. By carefully considering these requirements, we propose a general statistical methodology for testing both the overall and subgroup hypotheses, which has optimal power and strongly controls the familywise Type I error rate.

Prevalence and predictors of epoetin hyporesponsiveness in chronic kidney disease patients

Abstract: Background. The required erythropoiesis-stimulating agent (ESA) dose varies when correcting anaemia in chronic kidney disease (CKD) patients. This analysis was performed to identify the prevalence of and factors associated with ESA hyporesponsiveness. Methods. This analysis was a post hoc evaluation of epoetin alfa dosage requirements in a subgroup of patients from the Effect of early Correction of Anemia on the Progression of CKD study. The patients in this subgroup were randomly assigned to the high haemoglobin target group (14–15 g/dl for men and 13–14 g/dl for women) and completed a 4-month haemoglobin stabilization phase with complete epoetin dosage data. The relationship of demographics, disease characteristics and laboratory measures with epoetin dosage were evaluated using Pearson’s correlation, association measures and analysis of covariance (ANCOVA) models. Results. Of the 93 patients evaluated in this subgroup analysis, 14 (15%) were hyporesponsive to epoetin (maximum dosage >100 IU/kg/week during stabilization). An ANCOVA analysis showed that 52% of the observed variability in epoetin dosage at completion of the stabilization phase could be accounted for by diabetes as the primary cause of kidney disease, angiotensin-converting enzyme (ACE) inhibitor/ angiotensin receptor blocker (ARB) use, proteinuria, transferrin saturation, age, pre-treatment haemoglobin, geographical region, serum iron and body mass index (BMI). Unidentified patient characteristics accounted for an additional 16% of the dosage variance. Conclusions. Older age, higher BMI, anaemia, ACE inhibitor/ARB use and diabetes as the primary cause of kidney disease are associated with increased epoetin requirements when normalizing haemoglobin in anaemic CKD patients.

A meta-analysis on depression and subsequent cancer risk.

Abstract: The authors tested the hypothesis that depression is a possible factor influencing the course of cancer by reviewing prospective epidemiological studies and calculating summary relative risks. Studies were identified by computerized searches of Medline, Embase and PsycINFO. as well as manual searches of reference lists of selected publications. Inclusion criteria were cohort design, population-based sample, structured measurement of depression and outcome of cancer known for depressed and non-depressed subjects Thirteen eligible studies were identified. Based on eight studies with complete crude data on overall cancer, our summary relative risk (95% confidence interval) was 1.19 (1.06–1.32). After adjustment for confounders we pooled a summary relative risk of 1.12 (0.99–1.26). No significant association was found between depression and subsequent breast cancer risk, based on seven heterogeneous studies, with or without adjustment for possible confounders. Subgroup analysis of studies with a follow-up of ten years or more, however, resulted in a statistically significant summary relative risk of 2.50 (1.06–5.91). No significant associations were found for lung, colon or prostate cancer. This review suggests a tendency towards a small and marginally significant association between depression and subsequent overall cancer risk and towards a stronger increase of breast cancer risk emerging many years after a previous depression.

Targeted stent use in clinical practice based on evidence from the BAsel Stent Cost Effectiveness Trial (BASKET)

Abstract: We thank Agostini Pierfranco and colleagues for their interest in our analysis of the 18-month BASKET subgroup analysis. We are well aware that the subgroup of patients with percutaneous …

An analysis of mortality rates with dual-antiplatelet therapy in the primary prevention population of the CHARISMA trial

Abstract: Aims To examine the unanticipated, excess mortality observed in patients randomized to clopidogrel and aspirin vs. aspirin alone in the prespecified ‘asymptomatic’ subgroup of CHARISMA, we investigated whether dual-antiplatelet therapy may be associated with adverse cardiovascular (CV) events in a primary prevention population. Methods and results Of 15 603 patients enrolled, 3284 were initially categorized as asymptomatic with CV risk factors, but 995 had a prior CV event, leaving 2289 patients to represent the primary prevention cohort. This subset was compared with 13 148 symptomatic patients with established vascular disease and both were evaluated for CV death and bleeding. A multivariate analysis analysed predictors of CV death in this group. No post mortem data were available. Compared with aspirin alone, a significant increase in CV death (P ¼ 0.01) was observed in patients receiving dual-antiplatelet therapy in the asymptomatic population. Within the primary prevention cohort, this excess CV death was not significant (P ¼ 0.07). Multivariate analysis of the primary prevention group showed a trend towards excess CV death (P ¼ 0.054; HR 1.72; CI 0.99–2.97) with dual-antiplatelet therapy (aspirin plus clopidogrel). Other independent predictors of CV death included increasing age, hypertension, atrial fibrillation, and a history of heart failure. There was a non-significant increase in moderate or severe bleeding (P ¼ 0.218) with dual-antiplatelet therapy; thus, bleeding was an unlikely explanation for the excess event rate. Conclusion These findings do not support the use of dual-antiplatelet therapy with clopidogrel and aspirin in a primary prevention population. In this subgroup analysis, CV death occurred more frequently than anticipated. The cause of this apparent harm is not elucidated, may represent play of chance, but requires further prospective evaluation.

The effect of beta-blocker therapy on quality of life in heart failure patients : a systematic review and meta-analysis

Abstract: Purpose To assess the impact of beta-blocker therapy on quality of life (QoL) in chronic heart failure (CHF) patients receiving optimal standard medication. Methods Randomised controlled trials (RCT) assessing QoL with a generic or disease specific instrument were identified by searching Medline, Embase, Pascual, Cochrane Controlled Trial database, and the bibliographies of the published articles. Studies published between 1985 and 2002 were included, regardless of language of publication. Cochrane Review Manager 4.2 software was used to analyse the data and standardised mean difference (SMD) was calculated to assess the effect on QoL. Results A total of 9 trials involving 1954 patients fit into the inclusion criteria for the analysis. QoL improved more in the beta-blocker group compared to the control arm, but the SMD did not reach statistical significance (SMD, 0.07; 95%CI [-0.16, 0.021; p=0.13). Subgroup analysis, per type of beta-blocker and various treatment follow-up showed similar results. Conclusions In this meta-analysis there is evidence that beta-blocker therapy, on top of standard medication, does not impair QoL. Clinicians may add beta-blockers to standard therapy without concerns of impairing QoL in patients with CHF. Copyright (c) 2006 John Wiley & Sons, Ltd.

Effect of Multivitamin and Mineral Supplementation on Episodes of Infection in Nursing Home Residents: A Randomized, Placebo-Controlled Study

Abstract: OBJECTIVES: To evaluate the effect of vitamin and mineral supplementation on infections in an elderly institutionalized population. DESIGN: Eighteen-month, randomized, placebo-controlled trial. SETTING: Twenty-one long-term care facilities. PARTICIPANTS: Seven hundred sixty-three subjects from 21 long-term care facilities. INTERVENTION: Participants were randomized to receive one multivitamin and mineral supplementation daily or placebo. MEASUREMENTS: The primary outcome was number of infections per subject. Secondary outcomes were antibiotic use and hospitalization rates. Infection control surveillance was conducted over 18 months using standardized criteria. RESULTS: Outcome data from 748 subjects, mean age 85, were included in the intention-to-treat analysis. Using univariate analyses, there was no difference in infectious episodes between the supplemented and placebo groups (3.5 infections per 1,000 resident-days vs 3.8 infections per 1,000 resident-days, odds ratio (OR)=0.92, 95% confidence interval (CI)=0.82–1.03, P=.12). There was a reduction in antibiotic usage in the supplementation group, but this was not significant in the multivariate model. There was no difference in the number of hospital visits. In the multivariate analysis, the effect of multivitamin use on total number of infections was not significant (OR=0.77, 95% CI=0.54–1.1). Subjects without dementia had a greater rate of infections than those with dementia (OR=1.44, 95% CI=1.19–1.76). In post hoc subgroup analysis, subjects without dementia who received supplementation had a significantly lower rate of infections than those who received placebo (relative risk=0.81, 95% CI=0.66–0.99). CONCLUSION: Overall, multivitamin and mineral supplementation does not have a significant effect on the incidence of infections in institutionalized seniors, although the subgroup of residents in long-term care without dementia may benefit from supplementation. Further research is needed to determine its effect in high-risk subgroups within the nursing home population.

Time-dependent benefit of initial thrombosuction on myocardial reperfusion in primary percutaneous coronary intervention.

Abstract: BACKGROUND: In ST-segment elevation acute myocardial infarction (STEMI), dislodgement of thrombus within the culprit artery during primary percutaneous coronary intervention (PCI) may cause distal embolisation and impaired myocardial reperfusion. Clinical results of thromboembolic protection strategies have been controversial. We conducted this study to investigate whether the benefit of thrombus removal is time dependent. METHODS: Seventy-four STEMI patients within 12 h from onset were randomised to receive either primary PCI with initial thrombosuction (IT) or standard strategy. Results were analysed in subgroups according to the onset-to-lab time intervals (subgroup 1: 0-240 min, subgroup 2: 241-480 min and subgroup 3: 481-720 min). RESULTS: The primary end-points were improvements in thrombolysis in myocardial infarction flow (DeltaTIMI) and myocardial blush grade (DeltaMBG) postprocedure. Better DeltaTIMI (2.2 +/- 1.1 vs. 1.5 +/- 1.3, p = 0.014) and DeltaMBG (2.3 +/- 1.1 vs. 1.0 +/- 1.5, p < 0.001) were observed in IT patients, compared with standard PCI patients. In onset-to-lab time subgroup analysis, the difference between IT and standard PCI is significant only in subgroup 2 (DeltaTIMI 2.6 +/- 1.0 vs. 1.3 +/- 1.2, p = 0.007; DeltaMBG 2.6 +/- 0.9 vs. 1.0 +/- 1.1, p = 0.010), but not in the other two subgroups. CONCLUSIONS: This prospective randomised study shows that primary PCI with IT may improve epicardial flow and myocardial reperfusion in patients with STEMI, and this benefit is the most significant in patients treated within 4-8 h after symptom onset.

Meta-Analysis of Effect of Statin Treatment on Risk of Sudden Death

Abstract: Despite significant progress in the prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) is a major public health problem. Statins showed consistent benefits on cardiovascular events, but scant data were available about their effects on SCD. This meta-analysis aimed to assess the effect of statins on SCD. Additional analyses were carried out to evaluate lipid reduction as a possible mediator of the effect. Randomized controlled trials from January 1966 to July 2006 were retrieved by searching the MEDLINE database. Inclusion criteria were outcome focusing on the incidence of SCD, statin treatment compared with placebo or no treatment, randomized design, ≥100 patients enrolled, and follow-up ≥6 months. Data were independently abstracted by 2 investigators using a standardized protocol. Ten randomized controlled trials enrolling a total of 22,275 patients were included in the meta-analysis. Risks of SCD were 3% in patients receiving statins and 3.8% in control patients. Statin treatment was associated with a significant 19% risk reduction for SCD (odds ratio 0.81, 95% confidence interval 0.71 to 0.93, p = 0.003). In subgroup analysis, the benefit of statins was independent from the main characteristics of the studies and changes in patient lipid levels during the study. In conclusion, our results suggest that statins decrease the risk of SCD.

Additional exercise for older subacute hospital inpatients to prevent falls: benefits and barriers to implementation and evaluation

Abstract: Objective: To evaluate the clinical effectiveness and implementation of a falls prevention exercise programme for preventing falls in the subacute hospital setting.Design: Randomized controlled trial, subgroup analysis.Participants: Patients of a metropolitan subacute/aged rehabilitation hospital who were recommended for a falls prevention exercise programme when enrolled in a larger randomized controlled trial of a falls prevention programme.Methods: Participants in both the control and intervention groups who were recommended for the exercise programme intervention were followed for the duration of their hospital stay to determine if falls occurred. Participants had their balance, strength and mobility assessed upon referral for the exercise programme and then again prior to discharge. Participation rates in the exercise programme were also recorded.Results: Intervention group participants in this subgroup analysis had a significantly lower incidence of falls than their control group counterparts (contr...

Meta-analysis of randomised controlled trials comparing latanoprost with brimonidine in the treatment of open-angle glaucoma, ocular hypertension or normal-tension glaucoma

Abstract: Aim: To compare the efficacy and tolerability of latanoprost versus brimonidine in the treatment of open-angle glaucoma, ocular hypertension or normal-tension glaucoma. Method: Systematic review of randomised controlled trials comparing latanoprost and brimondine, identified by searches including Medline, Embase and Cochrane Controlled Trials Register. Two reviewers independently assessed trials for eligibility and quality and extracted data. Data were synthesised (random effects model) and expressed as the absolute mean intraocular pressure (IOP) reduction difference from baseline to end point for efficacy and relative risk for adverse events. Subgroup analysis and regression were used to explore heterogeneity according to patient characteristics, trial design and quality. Results: 15 publications reporting on 14 trials (1784 participants) were included for meta-analysis. IOP reduction favoured latanoprost (weighted mean difference (WMD) = 1.10 mm Hg (95% confidence interval (CI) 0.57 to 1.63)). Significant heterogeneity was present (χ213 = 38.29, p = 0.001, I2 = 66.0%). Subgroup analysis showed greater WMD for studies where data were analysed from end points >6 months duration, cross-over design, open-angle glaucoma or ocular hypertension and monotherapy. Multiple regression showed no significant association of WMD with trial duration (t9 = 1.92, p = 0.09), trial design (t9 = 1.79, p = 0.11), trial quality (t9 = −0.46, p = 0.66), or monotherapy or adjunctive therapy (t9 = −2.14, p = 0.06). Fatigue was less commonly associated with latanoprost (RR = 0.27, 95% CI 0.08 to 0.88). Publication bias was not evident on visual inspection of a funnel plot. Conclusion: Latanoprost is more effective than brimonidine as monotherapy in lowering IOP. Brimonidine is associated with a higher rate of fatigue.

Sex and gender subgroup analyses of randomized trials.

Abstract: Introduction and background Subgroup analyses by sex or gender can raise potential differences in response to medical interventions which require further investigation. However, sex/gender-based SGA have the potential to be misleading if their results are overinterpreted and may incorrectly influence medical management. Objectives We sought to assess the frequency of subgroup analysis (SGA) by sex/gender in randomized controlled trials (RCTs) of cardiovascular disease (CVD), to determine the comprehensiveness of these analyses, and to determine the proportion of SGA considered proper using predefined criteria. Methods Using the terms “cardiovascular disease,” “randomized controlled trial,” and “sex” or “gender,” the EMBASE, Medline and Cochrane Central Register of Controlled Trials databases were searched from January 1990 to April 2006. Studies were excluded if they were review articles, not randomized controlled trials, or included 1 sex only. This search yielded 169 eligible studies. All RCTs including a sex/gender SGA were scored for comprehensiveness using predefined criteria and assessed for completing a proper SGA. Two individuals performed the data extraction with Cohen’s kappa coefficient of 0.81 for interrater agreement. Results The number of studies performing a SGA by sex/gender increased from 1990 to 2005. Of the 169 studies, 53% (n = 89) performed a sex/gender SGA. Of those with a SGA, 35% (n = 31) completed a proper SGA and 38% (n = 34) received comprehensive scores of ≥3 (out of 4). Conclusions Performing sex/gender SGA is common in CVD RCTs. However, many SGAs are not properly conducted and their results should be viewed cautiously. Investigators should follow guidelines to ensure the proper conduct of SGA to prevent misleading conclusions from becoming adopted by clinicians.

Primer: the fallacy of subgroup analysis.

Abstract: The identification of subgroups of patients from randomized clinical trials that are of specific interest for guiding clinical decisions can be an attractive idea; however, since such trials are designed for the comparison of groups of patients, performing subgroup analyses can result in misinterpretation of the data. Such analyses must, therefore, be performed and evaluated with caution: these should be pre-planned and included in the design of a suitably powered trial. Data obtained should be analyzed using formal statistical tests of interaction on proper subgroups rather than improper subgroups of patients, the results obtained should be delineated carefully, and details of how these analyses were performed, and how the data should be interpreted, should be reported in the trial paper. The caveats associated with this approach, such as the occurrence of false positive or false negative effects, chance differences in observed effects, lack of power to perform the analysis, floor or ceiling effects, issues relating to multiple statistical testing, and over-reporting and under-reporting are discussed in this review. Subgroup analyses can, however, provide valuable, albeit predominantly exploratory, information on which to base clinical decisions if they are performed in accordance with recommendations and guidelines, and do, therefore, have a legitimate place in rheumatology clinical trials.

The Probability of Observing Negative Subgroup Results When the Treatment Effect is Positive and Homogeneous across All Subgroups

Abstract: Subgroup analysis is an important part in the design and analysis of clinical trials. The importance arises from the scientific and commercial implications of such analysis. The predominant concerns about subgroup analysis relate to the increased false-positive and false-negative rates. Much of the existing literature on subgroup analysis focuses on the former. In this article, we will concentrate on the false-negative aspect. Using theoretical derivation and simulations, we investigate factors that affect the probability of observing at least one negative subgroup result (ie, numerically negative treatment effect estimate) even though the true treatment effect is positive (ie, the new treatment is more efficacious than the comparator) and homogeneous across all subgroups. This probability, conditioning or unconditioning on a statistically significant overall treatment effect, is assessed for design scenarios that are commonly encountered in practice. In addition, we assess the probability of observing at...

Interpretive subgroup analysis extends modified grounded theory research findings in oncologic music therapy.

Abstract: Following an investigation into oncologic patients' experiences of the helpfulness of music therapy (O'Callaghan & McDermott, 2004), it was considered that examining relationships between specific patient characteristics and their responses could yield further interesting understandings. "Interpretative subgroup analysis" is introduced, which adapts principles of subgroup analysis in quantitative research to textual data analysis. Anonymous written responses from 128 oncologic patients were analyzed to compare responses from (a) those that had one music therapy session with those who had more than one session, (b) males and females, and (c) middle and older aged respondents. The number of music therapy sessions had scant effect on reported music therapy experiences, and males were much more likely to return questionnaires but much less likely to participate. Unlike some females, males always described positive affective responses when experiencing both sad and positive memories. Variations in the middle and older aged subgroups were evident in type of affective response, and emphases in descriptions of memories and music therapy's effect. Implications of these findings for music therapy practice are considered. Interpretive subgroup analysis is recommended for extending understanding of subjective within group experiences in music therapy research incorporating a grounded theory approach and large enough samples.

Contrast set mining through subgroup discovery applied to brain ischaemina data

Abstract: Contrast set mining aims at finding differences between different groups. This paper shows that a contrast set mining task can be transformed to a subgroup discovery task whose goal is to find descriptions of groups of individuals with unusual distributional characteristics with respect to the given property of interest. The proposed approach to contrast set mining through subgroup discovery was successfully applied to the analysis of records of patients with brain stroke (confirmed by a positive CT test), in contrast with patients with other neurological symptoms and disorders (having normal CT test results). Detection of coexisting risk factors, as well as description of characteristic patient subpopulations are important outcomes of the analysis.

FDA and CPMP rulings on subgroup analyses.

Abstract: The extent to which subgroup analyses should affect the interpretation and conclusions in a trial report is a contentious matter, and guidelines regarding this issue have been established by the US Fo

Subgroup analysis of efficacy and safety analysis of a randomized, double-blinded controlled phase II study of STA-4783 in combination with paclitaxel in patients with metastatic melanoma

Abstract: 8528 Background: STA-4783 (S), an inducer of heat shock protein 70 (hsp70) is a bis-thiobenzoylhydrazide compound S leads to up-regulation of hsp70 in tumor cell lines Xenograft models of solid t

Subgroup analysis of GEICAM 9906 trial comparing six cycles of FE90C (FEC) to four cycles of FE90C followed by 8 weekly paclitaxel administrations (FECP): Relevance of HER2 and hormonal status (HR)

Abstract: 10598 Background: GEICAM 9906 interim analysis showed FECP improved disease-free survival (DFS) compared to FEC (SABCS 2005, abstract #39). As a secondary objective, predictive markers were central...