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 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 Implementing a standard-of-care clinic for stroke prevention in children with sickle cell disease in Nigeria: a feasible strategy outside a clinical trial setting

2017 ◽  
Vol 1 (Suppl) ◽  
pp. 23-25
Author(s):  
Najibah A. Galadanci ◽  
Shehu U. Abdullahi ◽  
Leah D. Vance ◽  
Musa A. Tabari ◽  
Shehi Abubakar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Stroke Prevention ◽  
Standard Of Care ◽  
Cell Disease ◽  
Care Clinic ◽  
Clinical Trial Setting ◽  
Trial Setting

scholarly journals Efficacy of intravenous infusions of UC-derived MSCs for the treatment of COVID-19: A structured summary of a phase II double blinded, randomized controlled clinical trial

2020 ◽  
Author(s):  
Muhammad Ali ◽  
Azra Mehmood ◽  
Moazzam Nazeer Tarar ◽  
John D Gottsch ◽  
Zafar Nawaz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Inflammatory Responses ◽  
Standard Of Care ◽  
Convincing Evidence ◽  
Controlled Clinical Trial ◽  
Immune Reactivity ◽  
Randomized Controlled Clinical Trial ◽  
Beneficial Effects ◽  
Randomized Controlled ◽  
Double Blinded

Abstract In this clinical research project, we will conduct a highly rigorous clinical trial where we randomize the patients between umbilical cord (UC)-derived mesenchymal stem cell (MSC) and standard of care (SOC). This study will ask the question whether the allogenic MSCs are effective in reducing death and/or progression of COVID-19 disease when administered to patients with moderate to severe symptoms. MSCs are unique group of cells with minimal immune reactivity and produce multiple beneficial effects, which include reduction of severe inflammatory reaction. There is convincing evidence from human studies that intravenous (IV) delivery of MSCs can directly impact the hyper-inflammatory responses of COVID-19 induced injury of the heart and lungs. Our study will evaluate the safety and efficacy of allogenic UC-derived MSCs administered intravenously to COVID-19 patients with moderate to severe symptom in a randomized, controlled clinical trial. In addition, we will determine whether : (i) UC-derived MSCs are effective in reducing 30-day all-cause mortality (primary endpoint) and (ii) UC-derived MSCs are effective in preventing progression to mechanical ventilation, and/or reducing an inflammatory response, and/or improving overall patient condition (secondary endpoints).

scholarly journals Unnecessary Overtreatment Index: a useful tool in family practice

2015 ◽  
Vol 10 (35) ◽  
pp. 1-2
Author(s):  
Mohammad Zakaria Pezeshki ◽  
Sina Pezeshki
Keyword(s):  
Clinical Trial ◽  
Family Practice ◽  
External Validity ◽  
Controlled Clinical Trial ◽  
Randomized Controlled Clinical Trial ◽  
Randomized Controlled ◽  
Double Blinded ◽  
Quaternary Prevention

One of the most important aspects of quaternary prevention is avoiding the exposure of the patients to unnecessary overtreatment.  In this commentary we explain how a valid and reliable double blinded randomized controlled clinical trial (RCT) with a good external validity may help a physician to estimate the magnitude of unnecessary overtreatment.

DOES CLINICAL TRIAL SUBJECT SELECTION RESTRICT THE ABILITY TO GENERALIZE USE AND COST OF HEALTH SERVICES TO “REAL LIFE” SUBJECTS?

2003 ◽  
Vol 19 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Wendy A. Kennedy ◽  
Claudine Laurier ◽  
Jean-Luc Malo ◽  
Heberto Ghezzo ◽  
Jocelyne L'archevêque ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Health Services ◽  
External Validity ◽  
Inhaled Corticosteroids ◽  
Controlled Trial ◽  
Real Life ◽  
Randomized Controlled ◽  
Subject Selection ◽  
Trial Subject ◽  
Subject Differences

Objectives: To explore one aspect of the external validity of the randomized controlled trial (RCT), specifically how being selected for inclusion in a trial and having participated has influenced the use and cost of asthma-related health services.Methods: Services used by asthmatic users of inhaled corticosteroids (iCSTs) having previously participated in an RCT (TS, n = 46) were compared with individuals who had never participated (NS, n = 51).Results: TS were more likely to use higher (≥400 μg) daily doses of iCSTs than NS (OR, 3.3; 95% CI, 1.1–8.3) but less likely to visit emergency departments (OR, 0.3; 95% CI, 0.1–0.7). Total asthma-related costs did not differ significantly.Conclusions: Subject differences may impede generalizing from RCTs to real life.

scholarly journals Predictive Monitoring: IMPact in Acute Care Cardiology Trial (PM-IMPACCT) - A Randomized Clinical Trial Protocol (Preprint)

2021 ◽  
Author(s):  
Jess Keim-Malpass ◽  
Sarah J Ratcliffe ◽  
Liza P Moorman ◽  
Matthew T Clark ◽  
Katy N Krahn ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Acute Care ◽  
Predictive Analytics ◽  
Healthcare Providers ◽  
Standard Of Care ◽  
Clinical Deterioration ◽  
Controlled Clinical Trial ◽  
Randomized Controlled ◽  
Icu Transfer ◽  
The Impact

BACKGROUND Patients on acute care wards who deteriorate and are emergently transferred to intensive care units have poor outcomes. Early identification of decompensating patients might allow for earlier clinical intervention and reduced morbidity and mortality. Advances in bedside continuous predictive analytics monitoring (i.e., artificial intelligence (AI)-based risk prediction) make complex data easily available to healthcare providers, and can provide early warning of potentially catastrophic clinical events. We present a dynamic, visual predictive analytics monitoring tool that integrates real-time bedside telemetric physiologic data into robust clinical models to estimate and communicate risk of imminent events. This tool, CoMET (Continuous Monitoring of Event Trajectories), has been shown in retrospective observational studies to predict clinical decompensation on the acute care ward. There is a need to more definitively study this advanced predictive analytics or AI monitoring system in a prospective, randomized controlled clinical trial. OBJECTIVE The goal of this trial is to determine the impact of an AI-based visual risk analytic, CoMET, on: (1) improving patient outcomes related to clinical deterioration, (2) response time to proactive clinical action, and (3) costs to the healthcare system. METHODS We propose a cluster randomized controlled trial (NCT04359641) to test the impact of displaying CoMET on an acute care cardiology and cardiothoracic surgery hospital floor. The number of admissions to a room undergoing cluster-randomization is estimated to be 10,424 over the 20-month study period. Cluster randomization based on bed number occurs every 2 months. The intervention cluster will have the CoMET score displayed (along with standard of care), while the usual care group receives standard of care only. RESULTS The primary outcome will be hours free from events of clinical deterioration. Hours of acute clinical events are defined as time when one or more of the following occur: emergent ICU transfer, emergent surgery prior to ICU transfer, cardiac arrest prior to ICU transfer, emergent intubation, or death. The clinical trial began randomization in January 2021. CONCLUSIONS Very few AI-based health analytics are translated from algorithm to real-world use. This study will use robust prospective, randomized controlled clinical trial methodology to assess the effectiveness of an advanced AI predictive analytics monitoring system incorporating real-time telemetric data for identifying clinical deterioration on acute care wards. This analysis will strengthen the ability of healthcare organizations to evolve as learning health systems, which apply bioinformatics data to improve patient outcomes by incorporating AI into knowledge tools that are successfully integrated into clinical practice by healthcare providers. CLINICALTRIAL Clinical trials identifier: NCT04359641

scholarly journals Effect of Convalescent Plasma in Critically Ill Patients With COVID-19: An Observational Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Pedro Kurtz ◽  
Cassia Righy ◽  
Monica Gadelha ◽  
Fernando A. Bozza ◽  
Patricia T. Bozza ◽  
...  
Keyword(s):  
Observational Study ◽  
Clinical Improvement ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Proportional Hazards ◽  
Therapeutic Option ◽  
Standard Of Care ◽  
Cox Proportional Hazards ◽  
Clinical Trial Registration ◽  
Kaplan Meier

Background: Convalescent plasma is a potential therapeutic option for critically ill patients with coronavirus disease 19 (COVID-19), yet its efficacy remains to be determined. The aim was to investigate the effects of convalescent plasma (CP) in critically ill patients with COVID-19.Methods: This was a single-center prospective observational study conducted in Rio de Janeiro, Brazil, from March 17th to May 30th, with final follow-up on June 30th. We included 113 laboratory-confirmed COVID-19 patients with respiratory failure. Primary outcomes were time to clinical improvement and survival within 28 days. Secondary outcomes included behavior of biomarkers and viral loads. Kaplan–Meier analyses and Cox proportional-hazards regression using propensity score with inverse-probability weighing were performed.Results: 41 patients received CP and 72 received standard of care (SOC). Median age was 61 years (IQR 48–68), disease duration was 10 days (IQR 6–13), and 86% were mechanically ventilated. At least 29 out of 41CP-recipients had baseline IgG titers ≥ 1:1,080. Clinical improvement within 28 days occurred in 19 (46%) CP-treated patients, as compared to 23 (32%) in the SOC group [adjusted hazard ratio (aHR) 0.91 (0.49–1.69)]. There was no significant change in 28-day mortality (CP 49% vs. SOC 56%; aHR 0.90 [0.52–1.57]). Biomarker assessment revealed reduced inflammatory activity and increased lymphocyte count after CP.Conclusions: In this study, CP was not associated with clinical improvement or increase in 28-day survival. However, our study may have been underpowered and included patients with high IgG titers and life-threatening disease.Clinical Trial Registration: The study protocol was retrospectively registered at the Brazilian Registry of Clinical Trials (ReBEC) with the identification RBR-4vm3yy (http://www.ensaiosclinicos.gov.br).

scholarly journals Effectiveness and Safety of Niclosamaide as Add-on Therapy to the Standard of Care Measures in COVID-19 Management: Randomized controlled clinical trial

2021 ◽  
Author(s):  
Ahmed S. Abdulamir ◽  
Faiq I. Gorial ◽  
Sattar J Saaedi ◽  
Mohammed Fauzi Maulood ◽  
Hashim Ali Hashim ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Survival Rate ◽  
Viral Infections ◽  
Standard Of Care ◽  
Antiviral Effect ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Open Label ◽  
Randomized Controlled ◽  
Experimental Group

Background: COVID-19 pandemic has ignited the urge for repurposing old drugs as candidate antiviral medicines to treat novel challenges of viral infections. Niclosamide (NCS) is an anti-parasitic drug of known antiviral potential. Therefore, this study attempts to investigate the antiviral effect and safety of NCS on SARS-CoV-2 caused COVID-19 patients. Methods: Randomized controlled open label clinical trial encompassed 75 COVID-19 patients treated with standard of care plus NCS were included as experimental group and 75 COVID-19 patients treated with only standard of care therapy as control group. Each group was composed of 25 mild, 25 moderate and 25 severe patients. Survival rate, time to recovery, and side effects were the main endpoints for the assessment of the therapeutic effect and safety of NCS. Results: NCS did not enhance survival rate as three of severe COVID-19 patients in NCS and in control groups died (P>0.05). However, NCS, compared to control group, reduced the time to recovery in moderate and severe COVID-19 patients about 5 and 3 days, respectively but not in mild patients (P≤0.05). Most interestingly, NCS lowered time to recovery up to five days in patients with co-morbidities (P≤0.05) whereas only one day lowered in patients without co-morbidities (P>0.05). Conclusion: It is concluded that NCS accelerates time to recovery about 3 to 5 days in moderate to severe COVID-19 patients especially those with co-morbidities; hence, NCS is of clinical benefit for freeing hospital beds for more patients in pandemic crisis.

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