scholarly journals Covariate adjustment in subgroup analyses of randomized clinical trials: A propensity score approach

2021 ◽  
pp. 174077452110285
Author(s):  
Siyun Yang ◽  
Fan Li ◽  
Laine E Thomas ◽  
Fan Li
Keyword(s):  
Clinical Trials ◽  
Propensity Score ◽  
Exercise Training ◽  
Randomized Clinical Trials ◽  
Analysis Of Covariance ◽  
Covariate Adjustment ◽  
Operating Characteristics ◽  
Propensity Score Model ◽  
Propensity Score Weighting ◽  
Subgroup Analyses

Background: Subgroup analyses are frequently conducted in randomized clinical trials to assess evidence of heterogeneous treatment effect across patient subpopulations. Although randomization balances covariates within subgroups in expectation, chance imbalance may be amplified in small subgroups and adversely impact the precision of subgroup analyses. Covariate adjustment in overall analysis of randomized clinical trial is often conducted, via either analysis of covariance or propensity score weighting, but covariate adjustment for subgroup analysis has been rarely discussed. In this article, we develop propensity score weighting methodology for covariate adjustment to improve the precision and power of subgroup analyses in randomized clinical trials. Methods: We extend the propensity score weighting methodology to subgroup analyses by fitting a logistic regression propensity model with pre-specified covariate–subgroup interactions. We show that, by construction, overlap weighting exactly balances the covariates with interaction terms in each subgroup. Extensive simulations were performed to compare the operating characteristics of unadjusted estimator, different propensity score weighting estimators and the analysis of covariance estimator. We apply these methods to the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training trial to evaluate the effect of exercise training on 6-min walk test in several pre-specified subgroups. Results: Standard errors of the adjusted estimators are smaller than those of the unadjusted estimator. The propensity score weighting estimator is as efficient as analysis of covariance, and is often more efficient when subgroup sample size is small (e.g. <125), and/or when outcome model is misspecified. The weighting estimators with full-interaction propensity model consistently outperform the standard main-effect propensity model. Conclusion: Propensity score weighting is a transparent and objective method to adjust chance imbalance of important covariates in subgroup analyses of randomized clinical trials. It is crucial to include the full covariate–subgroup interactions in the propensity score model.

Comparative effectiveness of treatment options in elderly patients with colon cancer receiving adjuvant chemotherapy.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 470-470
Author(s):  
Sacha Satram-Hoang ◽  
Devi Ramanan ◽  
Luen F. Lee ◽  
Shui Yu ◽  
Carolina M. Reyes ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Clinical Trials ◽  
Propensity Score ◽  
Elderly Patients ◽  
Older Patients ◽  
Randomized Clinical Trials ◽  
Cohort Analysis ◽  
Risk Of Death ◽  
Morbidity Score ◽  
Co Morbidity

470 Background: While colon cancer (CC) is predominantly a disease of the elderly, older patients are underrepresented in clinical trials. We sought to evaluate whether the treatment patterns and benefits realized by trial participants pertain to older patients in the real-world setting. Methods: Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we conducted a retrospective cohort analysis of 3390 stage II and III CC patients diagnosed between 1/1/ 2004 to 12/31/2007, who were >66 years, enrolled in Medicare Parts A and B, and received adjuvant treatment with 5FU/LV (n=1368), FOLFOX (n=1398), CAP (capecitabine; n=507), and CAPOX (CAP + oxaliplatin; n=117) within 3 months after surgery. Date of last follow-up was 12/31/2007. Chi-square test and ANOVA or t-test assessed differences in patient and disease characteristics by treatment. Propensity score weighted Cox regression assessed the relative risk of death by treatment. Results: Patients treated with CAP were older (mean age 77 years; p<.0001), more likely female (61%; p<.05), more likely non-white (19%; p<.05) and had higher co-morbidity score (p<.0001) compared to the other treatment groups. The mean time to chemo initiation after surgery were similar between the groups (mean 46-49 days) while mean duration of treatment were longer for 5FU/LV (149 days) and FOLFOX (144 days), compared to CAP (121 days) and CAPOX (111 days); p<.0001. The incidence of adverse events (AEs) within 180 days after initiation of treatment were higher in patients treated with FOLFOX (82%) and 5FU/LV (78%) compared to CAP (74%) and CAPOX (71%); p=0.0002. Propensity score adjusted multivariate analysis demonstrated comparable survival for CAP-based regimens vs. 5-FU/LV- based regimens ( table ). Conclusions: Treatment outcomes for elderly patients observed in routine clinical practice were comparable between CAP-based and 5FU/LV-based regimens and consistent with results reported in randomized clinical trials. AEs associated with medical resource utilization were less frequent with CAP-based regimens. [Table: see text]

scholarly journals Effect of Isometric Exercise on Blood Pressure in Pre-Hypertensive and Hypertensive Individuals: Protocol for a Systematic Review and Meta-analysis of Randomized Clinical Trials

2021 ◽  
Author(s):  
Patricia Caetano Oliveira ◽  
Alexandre Machado Lehnen ◽  
Gustavo Waclawovsky
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Clinical Trials ◽  
Exercise Training ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Isometric Exercise ◽  
Lifestyle Changes ◽  
Dynamic Resistance ◽  
Isometric Handgrip

Abstract BackgroundSystemic arterial hypertension (HTN) is the leading risk factor of cardiovascular disease death. Lifestyle changes are key for the prevention and management of HTN. Regular aerobic exercise training is recommended as part of the management of HTN; and dynamic resistance exercise should be prescribed as an adjuvant to aerobic training. Recent evidence points to potential benefits of isometric resistance training in reducing blood pressure (BP). Yet, the hypotensive effect of isometric exercise in pre-hypertensive and hypertensive individuals is not fully understood. Thus, we will examine the effect of isometric exercise in pre-hypertensive and hypertensive individuals through a systematic review and meta-analysis. MethodsOur systematic review study will include randomized clinical trials (RCTs) selected from the electronic databases MEDLINE (PubMed), Cochrane, LILACS, EMBASE and PEDro published in English, Spanish and Portuguese language. We will follow the PRISMA guidelines and PICOS framework. Our search will involve studies with both male and female participants aged 18 years or more diagnosed with prehypertension or HTN performing one session of isometric exercise (acute effect) or isometric exercise training (chronic effect) compared to a control group (no exercise). We will use Cochrane Risk of Bias 2 (RoB 2) tool to evaluate the quality of the studies and RStudio software (v1.3.959 for Windows) for statistical analyses. DiscussionA meta-analysis of a homogeneous sample of pre-hypertensive and hypertensive individuals involving isometric handgrip exercise alone can further support previous findings and improve our understanding and recommendations for the management of these populations. Systematic review registrationThe study protocol for this review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD 42020213081).

Clinical Adverse Events of High-Dose vs Low-Dose Sodium–Glucose Cotransporter 2 Inhibitors in Type 2 Diabetes: A Meta-Analysis of 51 Randomized Clinical Trials

2020 ◽  
Vol 105 (11) ◽  
Author(s):  
Fang-Hong Shi ◽  
Hao Li ◽  
Jiang Yue ◽  
Yi-Hong Jiang ◽  
Zhi-Chun Gu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trials ◽  
Adverse Events ◽  
Low Dose ◽  
Randomized Clinical Trials ◽  
Sglt2 Inhibitors ◽  
High Dose ◽  
Sodium Glucose Cotransporter ◽  
Subgroup Analyses

Abstract Aims The aims of this work are to assess the clinical adverse events (AEs) of high-dose vs low-dose sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors) in patients with type 2 diabetes mellitus (T2DM). Methods We searched MEDLINE, EMBASE, and Cochrane Library from January 1, 2006 to March 10, 2020, for identifying eligible randomized clinical trials (RCTs) that reported AEs by high-dose and low-dose SGLT2 inhibitors in T2DM patients. Random-effects models was used to obtain summary relative risks (RRs) with associated 95% CIs. Prespecified subgroup analyses according to individual SGLT2 inhibitors and follow-up duration, and leave-one-out sensitivity analysis were conducted. Results A total of 51 RCTs involving 24 371 patients (12 208 received high-dose and 12 163 received low-dose SGLT2 inhibitors) were included. Overall, the heterogeneity among included studies was relatively low (I2 &lt; 50% for each outcome). No significant differences between high-dose and low-dose SGLT2 inhibitors were observed for overall safety (including any AEs, serious AEs, AEs leading to discontinuation, and death) and specified safety (including infections and infestations, musculoskeletal disorders, gastrointestinal disorders, osmotic diuresis-related AEs, volume-related AEs, renal-related AEs, and metabolism and nutrition), except for a mild increase in risk for AEs related to study drugs (RR: 1.08; 95% CI, 1.01-1.16) that mainly derived from canagliflozin (RR: 1.17; 95% CI, 1.05-1.30). Subgroup analyses were consistent with the primary outcomes. Conclusions This study provided substantial evidence that AEs of SGLT2 inhibitors were not dose related.

Exercise training and cognitive performance in persons with multiple sclerosis: A systematic review and multilevel meta-analysis of clinical trials

2020 ◽  
pp. 135245852091793 ◽  
Author(s):  
Reza Gharakhanlou ◽  
Leonie Wesselmann ◽  
Annette Rademacher ◽  
Amit Lampit ◽  
Raoof Negaresh ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Exercise Training ◽  
Cognitive Performance ◽  
Randomized Clinical Trials ◽  
Selection Process ◽  
Meta Analysis ◽  
Training Dose ◽  
Domain Specific ◽  
Positive Effects

Background: Cognitive impairment is common, debilitating, and poorly managed in persons with multiple sclerosis (pwMS). Exercise training might have positive effects on cognitive performance in pwMS, yet the overall magnitude, heterogeneity, and potential moderators remain unclear. Objective: This three-level meta-analysis aims to identify the effects of exercise training and those of exercise modalities on global and domain-specific cognitive performance in pwMS. Methods: MEDLINE, PsycInfo, SportDiscus, CENTRAL, and EMBASE were screened for randomized and non-randomized clinical trials from inception to 27 January 2020, yielding 3091 articles. Based on titles and abstracts, 75 articles remained in the selection process. After full-text evaluation, 13 studies were finally selected (PROSPERO pre-registered). Results: The pooled effect of exercise training on the global cognitive performance was null ( g = 0.04, 95% confidence interval (CI): –0.11 to 0.18) and no significant differences were displayed among domains. Heterogeneity within studies was null ([Formula: see text]= 0.0%) and between studies was low ([Formula: see text]= 25.1%). None of the moderators (exercise modalities, age, Expanded Disability Status Scale (EDSS), supervision, cognitive domains) reached significance. However, the exercise volume explained most of the overall heterogeneity (slope = 4.651 × 10−5, [Formula: see text] = 100%, [Formula: see text] = 52.34%). Conclusion: These results do not support the efficacy of exercise training on global or domain-specific cognitive performance in pwMS. Future studies are needed to determine whether higher training dose are beneficial.

Propensity score analysis methods with balancing constraints: A Monte Carlo study

2021 ◽  
pp. 096228022098351
Author(s):  
Yan Li ◽  
Liang Li
Keyword(s):  
Monte Carlo ◽  
Propensity Score ◽  
Propensity Scores ◽  
Probability Weighting ◽  
Inverse Probability ◽  
Propensity Score Model ◽  
Propensity Score Weighting ◽  
Estimation Performance ◽  
Score Model ◽  
Weighting Methods

The inverse probability weighting is an important propensity score weighting method to estimate the average treatment effect. Recent literature shows that it can be easily combined with covariate balancing constraints to reduce the detrimental effects of excessively large weights and improve balance. Other methods are available to derive weights that balance covariate distributions between the treatment groups without the involvement of propensity scores. We conducted comprehensive Monte Carlo experiments to study whether the use of covariate balancing constraints circumvent the need for correct propensity score model specification, and whether the use of a propensity score model further improves the estimation performance among methods that use similar covariate balancing constraints. We compared simple inverse probability weighting, two propensity score weighting methods with balancing constraints (covariate balancing propensity score, covariate balancing scoring rule), and two weighting methods with balancing constraints but without using the propensity scores (entropy balancing and kernel balancing). We observed that correct specification of the propensity score model remains important even when the constraints effectively balance the covariates. We also observed evidence suggesting that, with similar covariate balance constraints, the use of a propensity score model improves the estimation performance when the dimension of covariates is large. These findings suggest that it is important to develop flexible data-driven propensity score models that satisfy covariate balancing conditions.

Sign in / Sign up

Export Citation Format

Share Document