scholarly journals Evaluating the Long-Term Efficacy of COVID-19 Vaccines

2021 ◽  
Author(s):  
Dan-Yu Lin ◽  
Donglin Zeng ◽  
Peter B. Gilbert
Keyword(s):  
Clinical Trials ◽  
Vaccine Efficacy ◽  
Large Scale ◽  
Controlled Clinical Trials ◽  
Crossover Designs ◽  
Term Efficacy ◽  
Timely Access ◽  
Efficacious Vaccine ◽  
Placebo Recipients

AbstractLarge-scale deployment of safe and durably effective vaccines can halt the COVID-19 pandemic.1–3 However, the high vaccine efficacy reported by ongoing phase 3 placebo-controlled clinical trials is based on a median follow-up time of only about two months4–5 and thus does not pertain to long-term efficacy. To evaluate the duration of protection while allowing trial participants timely access to efficacious vaccine, investigators can sequentially cross placebo recipients to the vaccine arm according to priority groups. Here, we show how to estimate potentially time-varying placebo-controlled vaccine efficacy in this type of staggered vaccination of placebo recipients. In addition, we compare the performance of blinded and unblinded crossover designs in estimating long-term vaccine efficacy.SummaryWe show how to estimate potentially waning long-term efficacy of COVID-19 vaccines in randomized, placebo-controlled clinical trials with staggered enrollment of participants and sequential crossover of placebo recipients.

scholarly journals Evaluating the Long-Term Efficacy of COVID-19 Vaccines

2021 ◽  
Author(s):  
Dan-Yu Lin ◽  
Donglin Zeng ◽  
Peter B Gilbert
Keyword(s):  
Large Scale ◽  
Crossover Designs ◽  
Phase 3 ◽  
Term Efficacy ◽  
Timely Access ◽  
Efficacious Vaccine ◽  
Trial Participants ◽  
Ongoing Phase

Abstract Large-scale deployment of safe and durably effective vaccines can curtail the COVID-19 pandemic.1−3 However, the high vaccine efficacy (VE) reported by ongoing phase 3 placebo-controlled clinical trials is based on a median follow-up time of only about two months4−5 and thus does not pertain to long-term efficacy. To evaluate the duration of pro- tection while allowing trial participants timely access to efficacious vaccine, investigators can sequentially cross participants over from the placebo arm to the vaccine arm according to priority groups. Here, we show how to estimate potentially time-varying placebo-controlled VE in this type of staggered vaccination of participants. In addition, we compare the per- formance of blinded and unblinded crossover designs in estimating long-term VE.

scholarly journals Assessing Durability of Vaccine Effect Following Blinded Crossover in COVID-19 Vaccine Efficacy Trials

2020 ◽  
Author(s):  
Dean Follmann ◽  
Jonathan Fintzi ◽  
Michael P. Fay ◽  
Holly E. Janes ◽  
Lindsey Baden ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Clinical Effectiveness ◽  
Late Enhancement ◽  
Open Label ◽  
Term Efficacy ◽  
Efficacy Trials ◽  
Timely Access ◽  
Over Time

ABSTRACTBackgroundSeveral candidate vaccines to prevent COVID-19 disease have entered large-scale phase 3 placebo-controlled randomized clinical trials and some have demonstrated substantial short-term efficacy. Efficacious vaccines should, at some point, be offered to placebo participants, which will occur before long-term efficacy and safety are known.MethodsFollowing vaccination of the placebo group, we show that placebo-controlled vaccine efficacy can be derived by assuming the benefit of vaccination over time has the same profile for the original vaccine recipients and the placebo crossovers. This reconstruction allows estimation of both vaccine durability and potential vaccine-associated enhanced disease.ResultsPost-crossover estimates of vaccine efficacy can provide insights about durability, identify waning efficacy, and identify late enhancement of disease, but are less reliable estimates than those obtained by a standard trial where the placebo cohort is maintained. As vaccine efficacy estimates for post-crossover periods depend on prior vaccine efficacy estimates, longer pre-crossover periods with higher case counts provide better estimates of late vaccine efficacy. Further, open-label crossover may lead to riskier behavior in the immediate crossover period for the unblinded vaccine arm, confounding vaccine efficacy estimates for all post-crossover periods.ConclusionsWe advocate blinded crossover and continued follow-up of trial participants to best assess vaccine durability and potential delayed enhancement of disease. This approach allows placebo recipients timely access to the vaccine when it would no longer be proper to maintain participants on placebo, yet still allows important insights about immunological and clinical effectiveness over time.

scholarly journals Long-term efficacy of psychotherapy in major depression: protocol of a network meta-analysis

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Paula Marinho Vieira ◽  
Carla Cunha
Keyword(s):  
Clinical Trials ◽  
Major Depression ◽  
Meta Analysis ◽  
Long Term Results ◽  
Controlled Clinical Trials ◽  
Face To Face ◽  
Term Efficacy ◽  
Treatment Of Depression

Background: Depression is currently considered the epidemic of the century. In recent decades, research has established that psychotherapy is globally effective for the treatment of depression; however, it remains open which psychotherapeutic treatment is most effective and, particularly, if its efficacy is maintained over the long term. Given the difficulty in performing randomized and controlled clinical trials (RCTs) that simultaneously compare several psychotherapeutic models, meta-analyses aim to provide answers by synthesizing the evidence generated through direct comparisons of treatments.Goals: This protocol describes the meta-analysis study we will perform in order to assess the efficacy and acceptability of long-term results of psychotherapy (i.e., 18-month follow-up or higher) in the treatment of major depression in adults.Methods: Through the use of a recent methodological approach - the network meta-analysis - we will integrate the direct and indirect analysis of evidence from randomized and controlled clinical trials in this domain. We will systematically search seven databases for RCTs of psychotherapy, published since 1994, with evaluation of the efficacy in terms of long-term results for the treatment of depression. All studies with adult participants (18 to 65 years of age) diagnosed with major depression (according to DSM-IV, IV-TR, V or ICD-9, 10) will be eligible and all studies that compare psychotherapy (individual and face-to-face treatment) with a control condition (waiting-list, placebo) will be considered. Data extraction, quality assessment and risk of bias will be carried out independently by three researchers. The primary outcome measure will be the long-term efficacy of treatments (follow-ups of 18 months or above) measured by changes in the overall clinical response and symptoms of depression since post-treatment and follow-ups. The secondary measure will be the acceptability of treatment as measured by the proportion of participants who drop out of follow-up or start another treatment (not psychotherapy). A direct comparison (pairwise meta-analysis) of all studies comparing different psychotherapies will be performed. We will compare relative efficacy and acceptability by indirect comparison, through a bayesian network meta-analysis of random effects to compare different psychological interventions. Further analyses will be conducted if inconsistency and heterogeneity values are found. Discussion: The purpose of this review is to systematize and integrate evidence of long-term maintenance of the results of different psychotherapeutic treatments for major depression, administered individually and face-to-face in RCTs. For this reason, multiple direct and indirect comparisons of treatments (bayesian network) will be made, and the interrelationships between treatments will be estimated in terms of long-term efficacy and acceptability. Even though our scope will be focused on RCTs, we hope that the results obtained can contribute to summarize the present evidence available in terms of long-term results of psychotherapy (i.e., its effectiveness), optimizing the planning of future studies, providing public health guidelines and more informed clinical decisions on the treatment of depression. 

scholarly journals Long-Term Dietary and Physical Activity Interventions in the School Setting and Their Effects on BMI in Children Aged 6–12 Years: Meta-Analysis of Randomized Controlled Clinical Trials

Healthcare ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 396
Author(s):  
Purificación Cerrato-Carretero ◽  
Raúl Roncero-Martín ◽  
Juan D. Pedrera-Zamorano ◽  
Fidel López-Espuela ◽  
Luis M. Puerto-Parejo ◽  
...  
Keyword(s):  
Physical Activity ◽  
Clinical Trials ◽  
Dietary Habits ◽  
Meta Analysis ◽  
Controlled Clinical Trials ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled ◽  
School Based ◽  
School Based Interventions

Preventive actions and potential obesity interventions for children are mainly researched throughout the school period, either as part of the school curricula or after regular school hours, via interventions mostly lasting less than 12 months. We aimed to perform a meta-analysis on randomized controlled clinical trials to evaluate the evidence of the efficacy of long-term school-based interventions in the management of childhood obesity in terms of BMI from a dietary and physical activity-based approach. Eleven randomized controlled clinical trials were examined using the random effects model, and the results showed that there were no significant effects associated with physical activity + nutrition intervention in school children aged 6–12 years, with a pooled standardized mean difference (SMD) (95% CI) of −0.00 (−0.05, 0.04). No effects were observed after subgroup analysis based on the intervention length. The findings from our study indicate that long-term school-based interventions on physical activity and dietary habits received by children aged 6–12 years seem to have no effect on BMI. However, the promotion of such interventions should not be discouraged, as they promote additional positive health outcomes for other domains of children’s health.

scholarly journals Thrombolytic Therapy in the Acute Period of Aortic Thromboembolism in Cats

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Joshua Billy Hannabuss
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Open Access ◽  
Thrombolytic Therapy ◽  
Acute Phase ◽  
Large Scale ◽  
Supportive Therapy ◽  
Controlled Clinical Trials ◽  
Bottom Line ◽  
Adverse Side Effects

<strong>PICO question</strong><br /><p>Of cats that present with aortic thromboembolism, do patients that receive thrombolytic therapy in the acute phase have improved survival as compared to those who do not?</p><strong>Clinical bottom line</strong><br /><p>Based on the current available evidence, the use of thrombolytic therapy in the acute phase of aortic thromboembolism (ATE) does not appear to improve survival when compared to conventional supportive therapy. Frequently reported adverse side effects further questions its merits, and large scale controlled clinical trials would be required to further evaluate any benefit in the use of this therapy.</p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/pr-icon.jpg" alt="Peer Reviewed" />

Large-scale randomized evidence: Trials and meta-analyses of trials

2020 ◽  
pp. 51-66
Author(s):  
Colin Baigent ◽  
Richard Peto ◽  
Richard Gray ◽  
Natalie Staplin ◽  
Sarah Parish ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Large Scale ◽  
Meta Analysis ◽  
False Negative ◽  
Premature Deaths ◽  
Common Causes ◽  
The Common ◽  
Meta Analyses ◽  
Positive Results

Clinical trials generally need to be able to detect or to refute realistically moderate (but still worthwhile) differences between treatments in long-term disease outcome. Large-scale randomized evidence should be able to detect such effects, but medium-sized trials or medium-sized meta-analyses can, and often do, yield false-negative or exaggeratedly positive results. Hundreds of thousands of premature deaths each year could be avoided by seeking appropriately large-scale randomized evidence about various widely practicable treatments for the common causes of death, and by disseminating this evidence appropriately. This chapter takes a look at the use of large-scale randomized evidence—produced from trials and meta-analysis of trials—and how this data should be handled in order to produce accurate result.

Sign in / Sign up

Export Citation Format

Share Document