scholarly journals Are morbidity and mortality estimates from randomized controlled trials externally valid? A comparison of outcomes among infants enrolled into an RCT or a cohort study in Botswana

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Neil Thivalapill ◽  
Shahin Lockman ◽  
Kathleen Powis ◽  
Rebecca Zash ◽  
Jean Leidner ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cohort Study ◽  
Lower Risk ◽  
Causal Effect ◽  
Clinical Care ◽  
Morbidity And Mortality ◽  
National Standard ◽  
Randomized Controlled ◽  
Study Setting ◽  
The U.S

Abstract Background The external validity of the randomized controlled trial (RCT) refers to the extent to which the results of the RCT apply to the relevant, non-trial population and is impacted by its eligibility criteria, its organization, and its delivery of the intervention. Here, we compared the outcomes of mortality and hospitalization between an RCT and a cohort study that concurrently enrolled HIV-exposed uninfected (HEU) newborns in Botswana. Methods The Mpepu Study (the RCT) was a clinical trial which determined that co-trimoxazole (CTX) provided no survival benefit for HEUs, allowing both arms of the RCT to be used. The Maikaelelo study (the cohort study) was a prospective observational study that enrolled HEU newborns with telephone follow-up and no in-person visits. Rates of death and hospitalization in the pooled population, were modeled using cox-proportional hazards models for time to death or time to first hospitalization, with study setting (RCT vs. cohort study) as an independent variable. The causal effect of study setting on morbidity and mortality was obtained through a treatment effects approach. Results In total, 4,010 infants were included; 1,306 were enrolled into the cohort study and 2,704 were enrolled into the RCT. No significant differences in mortality were observed between the two study settings (HR: 1.28, 95% CI: 0.76, 2.13), but RCT participants had a lower risk of hospitalization (HR: 0.72, 95% CI: 0.58, 0.89) that decreased with age. However, RCT participants had a higher risk of hospitalization within the first six months of life. The causal risk difference in hospitalizations attributable to the RCT setting was -0.03 (95% CI: -0.05, -0.01). Conclusions Children in an RCT with rigorous application of national standard of care guidelines experienced a significantly lower risk of hospitalization than children participating in a cohort study that did not alter clinical care. Future research is needed to further investigate outcome disparities when real-world results fail to mirror those achieved in a clinical trial. Trial registration The Mpepu Trial was funded by the U.S. National Institutes of Health (No. NCT01229761) and the Maikaelelo Study was funded primarily by the U.S. Centers for Disease Control and Prevention (32AI007433-21).

scholarly journals Estimating the External Validity of Randomized Controlled Trials: A Comparison of Morbidity and Mortality Between an RCT and an Observational Study in Botswana

2021 ◽  
Author(s):  
Neil Thivalapill ◽  
Shahin Lockman ◽  
Kathleen Powis ◽  
Rebecca Zash ◽  
Jean Leidner ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Observational Study ◽  
External Validity ◽  
Lower Risk ◽  
Proportional Hazards ◽  
Standard Of Care ◽  
Randomized Controlled ◽  
Study Setting ◽  
Trial Setting ◽  
The U.S

Abstract Background: The external validity of the randomized controlled trial (RCT) refers to the extent to which the results of the RCT apply to the non-trial population. External validity of RCTs is impacted by the representativeness of the population enrolled and differences in the standard of care between the trial and non-trial setting. In spite of these concerns that have been historically acknowledged, external validity of RCTs is difficult to study empirically given confounding due to time and population under study. Here, we compared the outcomes of mortality and hospitalization between an RCT and an observational study that concurrently enrolled HIV-exposed uninfected (HEU) newborns in Botswana. Methods: The Mpepu Study was a clinical trial that enrolled HEU newborns in Botswana to determine whether co-trimoxazole provided survival benefit. The Maikaelelo study was an observational study that enrolled HEU newborns in Botswana with telephone follow-up and no in-person visits. Mortality and morbidity were compared using survival analysis and treatment effects approaches. Cox-proportional hazards model were fit with time to death or time to first hospitalization and where the proportional hazards assumption was determined to be violated, interaction terms were generated between the study setting and time. The causal effect of study setting was obtained through the inverse probability weighted estimator. Results: In total, 4,010 infants were included; 1,306 were enrolled into Maikaelelo and 2,704 were enrolled into Mpepu. No significant differences in mortality were observed between the two settings (HR: 1.28, 95% CI: 0.76, 2.13), but RCT participants had a lower risk of hospitalization (HR: 0.72, 95% CI: 0.58, 0.89) that decreased with age. However, RCT participants had a higher risk of hospitalization within the first six months of life. The causal risk difference in hospitalizations attributable to the trial setting was -0.03 (95% CI: -0.05, -0.01). Conclusions: Children in an RCT with rigorous application of national standard of care guidelines experienced a significantly lower risk of hospitalization than children participating in an observational study that did not alter clinical care. Future research is needed to further investigate outcome disparities when real-world results fail to mirror those achieved in a clinical trial. Trial Registration: : The Mpepu Trial was funded by the U.S. National Institutes of Health (No. NCT01229761) and the Maikaelelo Study was funded primarily by the U.S. Centers for Disease Control and Prevention (32AI007433-21).

scholarly journals Pivoting during a pandemic: lessons learned from transitioning a multisite randomized controlled trial to a remote protocol in response to COVID-19

2021 ◽  
Author(s):  
Hailey Inverso ◽  
Fayo Abadula ◽  
Troy Morrow ◽  
Lauren LeStourgeon ◽  
Angelee Parmar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Research ◽  
Controlled Trial ◽  
Clinical Care ◽  
Lessons Learned ◽  
Diabetes Distress ◽  
Randomized Controlled ◽  
Testing Strategies ◽  
Glycemic Outcomes

Abstract THR1VE! is an ongoing multisite randomized clinical trial of a positive psychology intervention designed to treat diabetes distress and improve glycemic outcomes in teens with type 1 diabetes. Due to the COVID-19 pandemic restrictions on clinical research and changes in diabetes clinical care, THR1VE! was adapted from an in-person enrollment protocol to a remote protocol through a series of development and testing strategies. We discuss the process of transitioning the protocol and the demonstrated feasibility of ongoing recruitment, enrollment, and retention outcomes. These findings offer support for a remotely transitioned protocol that has larger applications for ongoing and future clinical research.

scholarly journals Association of social distancing and masking with risk of COVID-19

2020 ◽  
Author(s):  
Sohee Kwon ◽  
Amit D. Joshi ◽  
Chun-Han Lo ◽  
David A. Drew ◽  
Long H. Nguyen ◽  
...  
Keyword(s):  
Decision Making ◽  
Cohort Study ◽  
Severe Acute Respiratory Syndrome ◽  
Lower Risk ◽  
Unmet Need ◽  
Risk Of Infection ◽  
Social Distancing ◽  
Inform Decision Making ◽  
The U.S ◽  
Reduced Risk

AbstractGiven the continued burden of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) disease (COVID-19) across the U.S., there is a high unmet need for data to inform decision-making regarding social distancing and universal masking. We examined the association of community-level social distancing measures and individual masking with risk of predicted COVID-19 in a large prospective U.S. cohort study of 198,077 participants. Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported masking was associated with a 63% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing. These findings provide support for the efficacy of mask-wearing even in settings of poor social distancing in reducing COVID-19 transmission. In the current environment of relaxed social distancing mandates and practices, universal masking may be particularly important in mitigating risk of infection.

Comparision of two fluoride varnishes for controlling white spot lesions. Randomized clinical trial

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Jesús Alberto Luengo - Fereira
Keyword(s):  
Clinical Trial ◽  
Randomized Clinical Trial ◽  
White Spot ◽  
Controlled Clinical Trial ◽  
White Spot Lesions ◽  
Randomized Controlled Clinical Trial ◽  
Chi Square ◽  
Randomized Controlled ◽  
Anterior Teeth ◽  
The Mean

Objective: To compare two fluorinated varnishes for the control of white spot lesions.Material and Methods: A randomized controlled clinical trial was conducted. A total of 103 active whitespot lesions on permanent upper anterior teeth from 24 patients, aged 7 to 9 years were randomly assigned totwo groups, G1: Duraphat® (n=52) and G2: DuraShield® (n=51). Weekly applications were perform for fourconsecutive weeks. Fifth week the dimension, regression and activity of the lesions were evaluated. Student’sT test, Wilcoxon Ranks and Chi square were used at 5% significance. Results: At the end of the study, the lesion reduction was observed in 69.7%, finding significant differences(p<0.05) in the mean of the initial and final dimensions in general (2.74 mm to 1.91 mm) and in each group, G1(2.84 mm to 2.03 mm), G2 (2.64 mm to 1.78 mm). In the activity of the lesions, it was found in the G1, 12 active and6 inactive lesions; while in G2, there were 14 active and 29 inactive; these differences were significant (p<0.05). Conclusions: The two evaluated products showed similar clinical efficacy in the remineralization of activewhite spot lesions after 4 weeks of therapy.

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