Azithromycin distribution and childhood mortality in compliance-related subgroups in Niger: complier average causal effect and spillovers in a cluster-randomized, placebo-controlled trial

2021 ◽  
Author(s):  
Kieran S O’Brien ◽  
Ahmed M Arzika ◽  
Ramatou Maliki ◽  
Abdou Amza ◽  
Farouk Manzo ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Rate Ratio ◽  
Incidence Rate Ratio ◽  
Causal Effect ◽  
Controlled Trial ◽  
Effect Analysis ◽  
Intention To Treat ◽  
Average Causal Effect ◽  
Cluster Randomized ◽  
Complier Average Causal Effect

Abstract Background Biannual azithromycin distribution to children 1–59 months old reduced all-cause mortality by 18% [incidence rate ratio (IRR) 0.82, 95% confidence interval (CI): 0.74, 0.90] in an intention-to-treat analysis of a randomized controlled trial in Niger. Estimation of the effect in compliance-related subgroups can support decision making around implementation of this intervention in programmatic settings. Methods The cluster-randomized, placebo-controlled design of the original trial enabled unbiased estimation of the effect of azithromycin on mortality rates in two subgroups: (i) treated children (complier average causal effect analysis); and (ii) untreated children (spillover effect analysis), using negative binomial regression. Results In Niger, 594 eligible communities were randomized to biannual azithromycin or placebo distribution and were followed from December 2014 to August 2017, with a mean treatment coverage of 90% [standard deviation (SD) 10%] in both arms. Subgroup analyses included 2581 deaths among treated children and 245 deaths among untreated children. Among treated children, the incidence rate ratio comparing mortality in azithromycin communities to placebo communities was 0.80 (95% CI: 0.72, 0.88), with mortality rates (deaths per 1000 person-years at risk) of 16.6 in azithromycin communities and 20.9 in placebo communities. Among untreated children, the incidence rate ratio was 0.91 (95% CI: 0.69, 1.21), with rates of 33.6 in azithromycin communities and 34.4 in placebo communities. Conclusions As expected, this analysis suggested similar efficacy among treated children compared with the intention-to-treat analysis. Though the results were consistent with a small spillover benefit to untreated children, this trial was underpowered to detect spillovers.

Paracetamol bei Rückenschmerzen nicht empfohlen

2020 ◽  
Vol 24 (02) ◽  
pp. 54-55
Author(s):  
Arne Vielitz
Keyword(s):  
Randomized Controlled Trial ◽  
Low Back Pain ◽  
Causal Effect ◽  
Controlled Trial ◽  
Low Back ◽  
Effect Analysis ◽  
Acute Low Back Pain ◽  
Randomized Controlled ◽  
Average Causal Effect ◽  
Complier Average Causal Effect

Schreijenberg M, Lin CC, McLachlan AJ et al. Paracetamol is Ineffective for Acute Low Back Pain even for Patients Who Comply with Treatment: Complier Average Causal Effect Analysis of a Randomized Controlled Trial. Pain 2019; 160: 2848–2854. doi: 10.1097/j.pain.0000000000001685

scholarly journals The Effectiveness of a Community-Based Mentoring Program for Children Aged 5–11 Years: Results from a Randomized Controlled Trial

2020 ◽  
Vol 22 (1) ◽  
pp. 100-112 ◽  
Author(s):  
Nick Axford ◽  
Gretchen Bjornstad ◽  
Justin Matthews ◽  
Laura Whybra ◽  
Vashti Berry ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Causal Effect ◽  
Controlled Trial ◽  
Well Being ◽  
Mentoring Program ◽  
Post Intervention ◽  
Intention To Treat ◽  
Randomized Controlled ◽  
Average Causal Effect ◽  
Superiority Trial

AbstractThe study, a two-arm, randomized controlled, parallel group, superiority trial, aimed to evaluate the implementation and effectiveness of a 12-month one-to-one volunteer mentoring program designed to improve behavioral and emotional outcomes in children aged 5 to 11 years who have teacher- and parent/carer-reported behavioral difficulties. Participants were 246 children (123 intervention, 123 control; mean age 8.4 years; 87% boys) in five sites in London, UK, scoring in the “abnormal” range on the teacher-rated Strengths and Difficulties Questionnaire (SDQ) Total Difficulties measure and in the “borderline” or abnormal range on the parent-rated SDQ Total Difficulties measure. Randomization on a 1:1 ratio took place using a computer-generated sequence and stratifying by site. Data collectors and statisticians were blind to participant allocation status. Outcome measures focused on parent- and teacher-rated child behavior and emotions, and child-rated self-perception and hope. Intention-to-treat analysis on all 246 randomized participants (using imputed data where necessary) showed that at post-intervention (16 months after randomization), there were no statistically significant effects on the primary outcome—parent-rated SDQ Total Difficulties (adjusted standardized mean difference = − 0.12; 95% CI: −0.38 to 0.13; p = 0.33)—or any secondary outcomes. Results from complier average causal effect (CACE) analysis using the primary outcome indicated the intervention was not effective for children who received the recommended duration of mentoring. Exploratory analyses found no sub-group effects on the primary outcome. The article concludes that the mentoring program had no effect on children’s behavior or emotional well-being, and that program content needs revising to satisfactorily address key risk and protective factors.

scholarly journals A complier average causal effect analysis of the Stimulant Reduction Intervention using dosed exercise study

2018 ◽  
Vol 10 ◽  
pp. 1-8 ◽  
Author(s):  
Thomas Carmody ◽  
Tracy L. Greer ◽  
Robrina Walker ◽  
Chad D. Rethorst ◽  
Madhukar H. Trivedi
Keyword(s):  
Causal Effect ◽  
Effect Analysis ◽  
Average Causal Effect ◽  
Complier Average Causal Effect

scholarly journals Hospital ward design and prevention of hospital-acquired infections: A prospective clinical trial

2014 ◽  
Vol 25 (5) ◽  
pp. 265-270 ◽  
Author(s):  
Jennifer Ellison ◽  
Danielle Southern ◽  
Donna Holton ◽  
Elizabeth Henderson ◽  
Jean Wallace ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Rate Ratio ◽  
Incidence Rate Ratio ◽  
Controlled Trial ◽  
Care Facility ◽  
Hospital Ward ◽  
Incidence Density ◽  
Medical Patients ◽  
Hospital Acquired Infections ◽  
Hospital Acquired

BACKGROUND: Renovation of a general medical ward provided an opportunity to study health care facility design as a factor for preventing hospital-acquired infections.OBJECTIVE: To determine whether a hospital ward designed with predominantly single rooms was associated with lower event rates of hospital-acquired infection and colonization.METHODS: A prospective controlled trial with patient allocation incorporating randomness was designed with outcomes on multiple ‘historic design’ wards (mainly four-bed rooms with shared bathrooms) compared with outcomes on a newly renovated ‘new design’ ward (predominantly single rooms with private bathrooms).RESULTS: Using Poisson regression analysis and adjusting for time at risk, there were no differences (P=0.18) in the primary outcome (2.96 versus 1.85 events/1000 patient-days, respectively). After adjustment for age, sex, Charlson score, admitted from care facility, previous hospitalization within six months, isolation requirement and the duration on antibiotics, the incidence rate ratio was 1.44 (95% CI 0.71 to 2.94) for the new design versus the historic design wards. A restricted analysis on the numbers of events occurring in single-bed versus multibed wings within the new design ward revealed an event incidence density of 1.89 versus 3.47 events/1000 patient-days, respectively (P=0.18), and an incidence rate ratio of 0.54 (95% CI 0.15 to 1.30).CONCLUSIONS: No difference in the incidence density of hospital-acquired infections or colonizations was observed for medical patients admitted to a new design ward versus historic design wards. A restricted analysis of events occurring in single-bed versus multibed wings suggests that ward design warrants further study.

The Complier Average Causal Effect Parameter for Multiarmed RCTs

2020 ◽  
pp. 0193841X2097920
Author(s):  
Peter Z. Schochet
Keyword(s):  
Causal Effect ◽  
Control Group ◽  
Multiple Treatment ◽  
Intention To Treat ◽  
Treatment Services ◽  
Average Causal Effect ◽  
Key Issues ◽  
Effect Parameter ◽  
Complier Average Causal Effect ◽  
And Control

In randomized controlled trials, the complier average causal effect (CACE) parameter is often of policy interest because it pertains to intervention effects for study units that comply with their research assignments and receive a meaningful dose of treatment services. Causal inference methods for identifying and estimating the CACE parameter using an instrumental variables (IV) framework are well established for designs with a single treatment and control group. This article uses a parallel IV framework to discuss and build on the much smaller literature on estimation of CACE parameters for designs with multiple treatment groups. The key finding is that the conditions to identify and estimate CACE parameters are much more complex for multiarmed designs and may not be tractable in some cases. Practical steps are provided on how to proceed, and a case study demonstrates key issues. The results suggest that ensuring compliance is particularly important in multiarmed trials so that intention-to-treat estimates on the offer of intervention services (which can be identified) can provide meaningful information on the CACE parameters.

Contrasting approaches for addressing non-adherence in randomized controlled trials: An illustration from the REFLUX trial

2021 ◽  
pp. 174077452110568
Author(s):  
Luke Keele ◽  
Richard Grieve
Keyword(s):  
Randomized Controlled Trials ◽  
Causal Effect ◽  
Controlled Trial ◽  
Treatment Protocol ◽  
Analytical Framework ◽  
Controlled Trials ◽  
Intention To Treat ◽  
Randomized Controlled ◽  
Average Causal Effect ◽  
Study Context

Background: In many randomized controlled trials, a substantial proportion of patients do not comply with the treatment protocol to which they have been randomly assigned. Randomized controlled trials are required to report results according to the intention-to-treat estimand, but recent methodological guidance recognizes the importance of estimating other causal quantities. Methods: This article outlines an analytical framework for randomized controlled trials with non-compliance. We apply the ICH E9 (R1) addendum and combine it with the potential outcomes framework to define key estimands, outline the major assumptions for identification of each estimand, and highlight the assumptions that cannot be verified from the randomized controlled trial data. We contrast the assumptions and estimates in a re-analysis of the REFLUX trial. We report alternative estimates for the effectiveness of receipt of laparoscopic surgery versus medical management for patients with gastro-intestinal reflux disease. Results: The article finds that adjusted as-treated and per-protocol estimates were similar in magnitude to those based intention-to-treat methods. Instrumental variable estimates of the complier average causal effect were larger, with wider confidence intervals. Conclusion: We recommend that in randomized controlled trials with non-compliance, studies should outline which estimand is most relevant to the study context, evaluate key assumptions, and present estimates from a range of methods as a sensitivity analysis.

scholarly journals 688. Marginal Structure Models to Estimate the Effect of Cytomegalovirus Infection on Hospitalization Among Children Undergoing Allogeneic Hematopoietic Cell Transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S397-S398
Author(s):  
Yun Li ◽  
Arman Oganisian ◽  
Craig L K Boge ◽  
Molly Hayes ◽  
Alexander Newman ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Generalized Estimating Equations ◽  
Rate Ratio ◽  
Incidence Rate Ratio ◽  
Causal Effect ◽  
Time Varying ◽  
Cmv Infection ◽  
Research Support ◽  
Post Transplant ◽  
Cmv Reactivation

Abstract Background Children receiving an allogeneic hematopoietic cell transplant (HCT) are at risk for cytomegalovirus (CMV) infection in the post-transplant period, necessitating routine surveillance for CMV. Some patients will not have CMV detected while others will have intermittent or persistent CMV detection. Prior analyses assessing the association of CMV infection on hospitalization in the post-transplant period have been limited by methods that did not consider the time-varying nature of the exposure (CMV reactivation) and its confounders or aim to obtain causal effect estimates. We aimed to assess the causal effect of CMV reactivation on hospitalization using a causal modeling approach. The Effect of CMV Infection on Hospitalization Using Generalized Estimating Equations and Marginal Structural Models Methods A cohort of allogeneic HCT patients transplanted at Children’s Hospital of Philadelphia January 2004–April 2017 was assembled and followed for 100 days after transplant. Eligible patients included those under CMV surveillance, defined as having ≥2 CMV whole blood polymerase chain reaction tests in the first month after HCT. All information was abstracted from medical charts. The association of CMV reactivation on the rate of hospitalization was estimated using traditional generalized estimating equations and repeated using a marginal structural model that accounted for time-varying exposure, confounders and non-random drop-out and obtained effects with causal interpretations. Results The study cohort included 340 pediatric allogeneic HCT recipients under CMV surveillance testing. 46.5% were female and the median age was 9 (range: 0 to 26). The CMV infection rate was 33.9%, with a median time to CMV detection of 23.5 days (range: 4-100). CMV infection was common in Donor+/Recipient+ (58.9%) and Donor-/Recipient+ (34.6%) patients. A traditional model estimates an additional week of CMV infection was associated with a 22% increase in average weekly hospitalization (Incidence rate ratio: 1.22, 95%: 1.12 -1.34). A marginal structure model estimates an additional week of CMV infection is associated with 3% increase in average weekly hospitalization incidence (Incidence rate ratio: 1.03, 95%: 0.91-1.16). Conclusion Our research showed the effect of CMV on hospitalization diminished after properly considering the time-varying nature of the CMV infection status and its confounders. Disclosures Brian T. Fisher, DO, MPH, MSCE, Astellas (Advisor or Review Panel member)Merck (Grant/Research Support)Pfizer (Grant/Research Support)

Inflammatory Bowel Disease and Risk of Major Bleeding During Anticoagulation for Venous Thromboembolism

2021 ◽  
Author(s):  
Susanna Scharrer ◽  
Christian Primas ◽  
Sabine Eichinger ◽  
Sebastian Tonko ◽  
Maximilian Kutschera ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Venous Thromboembolism ◽  
Incidence Rate ◽  
Rate Ratio ◽  
Incidence Rate Ratio ◽  
Fatal Bleeding ◽  
Adjusted Incidence Rate ◽  
Inflammatory Bowel ◽  
Adjusted Incidence

Abstract Background Little is known about the bleeding risk in patients with inflammatory bowel disease (IBD) and venous thromboembolism (VTE) treated with anticoagulation. Our aim was to elucidate the rate of major bleeding (MB) events in a well-defined cohort of patients with IBD during anticoagulation after VTE. Methods This study is a retrospective follow-up analysis of a multicenter cohort study investigating the incidence and recurrence rate of VTE in IBD. Data on MB and IBD- and VTE-related parameters were collected via telephone interview and chart review. The objective of the study was to evaluate the impact of anticoagulation for VTE on the risk of MB by comparing time periods with anticoagulation vs those without anticoagulation. A random-effects Poisson regression model was used. Results We included 107 patients (52 women, 40 with ulcerative colitis, 64 with Crohn disease, and 3 with unclassified IBD) in the study. The overall observation time was 388 patient-years with and 1445 patient-years without anticoagulation. In total, 23 MB events were registered in 21 patients, among whom 13 MB events occurred without anticoagulation and 10 occurred with anticoagulation. No fatal bleeding during anticoagulation was registered. The incidence rate for MB events was 2.6/100 patient-years during periods exposed to anticoagulation and 0.9/100 patient-years during the unexposed time. Exposure to anticoagulation (adjusted incidence rate ratio, 3.7; 95% confidence interval, 1.5-9.0; P = 0.003) and ulcerative colitis (adjusted incidence rate ratio, 3.5; 95% confidence interval, 1.5-8.1; P = 0.003) were independent risk factors for MB events. Conclusion The risk of major but not fatal bleeding is increased in patients with IBD during anticoagulation. Our findings indicate that this risk may be outweighed by the high VTE recurrence rate in patients with IBD.

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