scholarly journals Evidence synthesis and decision modelling to support complex decisions: stockpiling neuraminidase inhibitors for pandemic influenza usage

F1000Research ◽  
2017 ◽  
Vol 5 ◽  
pp. 2293
Author(s):  
Samuel I. Watson ◽  
Yen-Fu Chen ◽  
Jonathan S. Nguyen-Van-Tam ◽  
Puja R. Myles ◽  
Sudhir Venkatesan ◽  
...  

Objectives: The stockpiling of neuraminidase inhibitor (NAI) antivirals as a defence against pandemic influenza is a significant public health policy decision that must be made despite a lack of conclusive evidence from randomised controlled trials regarding the effectiveness of NAIs on important clinical end points such as mortality. The objective of this study was to determine whether NAIs should be stockpiled for treatment of pandemic influenza on the basis of current evidence. Methods: A decision model for stockpiling was designed. Data on previous pandemic influenza epidemiology was combined with data on the effectiveness of NAIs in reducing mortality obtained from a recent individual participant meta-analysis using observational data. Evidence synthesis techniques and a bias modelling method for observational data were used to incorporate the evidence into the model. The stockpiling decision was modelled for adults (≥16 years old) and the United Kingdom was used as an example. The main outcome was the expected net benefits of stockpiling in monetary terms. Health benefits were estimated from deaths averted through stockpiling. Results: After adjusting for biases in the estimated effectiveness of NAIs, the expected net benefit of stockpiling in the baseline analysis was £444 million, assuming a willingness to pay of £20,000/QALY ($31,000/QALY). The decision would therefore be to stockpile NAIs. There was a greater probability that the stockpile would not be utilised than utilised. However, the rare but catastrophic losses from a severe pandemic justified the decision to stockpile. Conclusions: Taking into account the available epidemiological data and evidence of effectiveness of NAIs in reducing mortality, including potential biases, a decision maker should stockpile anti-influenza medication in keeping with the postulated decision rule.

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2293
Author(s):  
Samuel I. Watson ◽  
Yen-Fu Chen ◽  
Jonathan S. Nguyen-Van-Tam ◽  
Puja R. Myles ◽  
Sudhir Venkatesan ◽  
...  

Objectives: The stockpiling of neuraminidase inhibitor (NAI) antivirals as a defence against pandemic influenza is a significant public health policy decision that must be made despite a lack of conclusive evidence from randomised controlled trials regarding the effectiveness of NAIs on important clinical end points such as mortality. The objective of this study was to determine whether NAIs should be stockpiled for treatment of pandemic influenza on the basis of current evidence. Methods: A decision model for stockpiling was designed. Data on previous pandemic influenza epidemiology was combined with data on the effectiveness of NAIs in reducing mortality obtained from a recent individual participant meta-analysis using observational data. Evidence synthesis techniques and a bias modelling method for observational data were used to incorporate the evidence into the model. The stockpiling decision was modelled for adults (≥16 years old) and the United Kingdom was used as an example. The main outcome was the expected net benefits of stockpiling in monetary terms. Health benefits were estimated from deaths averted through stockpiling. Results: After adjusting for biases in the estimated effectiveness of NAIs, the expected net benefit of stockpiling in the baseline analysis was £444 million, assuming a willingness to pay of £20,000/QALY ($31,000/QALY). The decision would therefore be to stockpile NAIs. There was a greater probability that the stockpile would not be utilised than utilised. However, the rare but catastrophic losses from a severe pandemic justified the decision to stockpile. Conclusions: Taking into account the available epidemiological data and evidence of effectiveness of NAIs in reducing mortality, including potential biases, a decision maker should stockpile anti-influenza medication in keeping with the postulated decision rule.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lisa Holper

Abstract Background Conditional power of network meta-analysis (NMA) can support the planning of randomized controlled trials (RCTs) assessing medical interventions. Conditional power is the probability that updating existing inconclusive evidence in NMA with additional trial(s) will result in conclusive evidence, given assumptions regarding trial design, anticipated effect sizes, or event probabilities. Methods The present work aimed to estimate conditional power for potential future trials on antidepressant treatments. Existing evidence was based on a published network of 502 RCTs conducted between 1979-2018 assessing acute antidepressant treatment in major depressive disorder (MDD). Primary outcomes were efficacy in terms of the symptom change on the Hamilton Depression Scale (HAMD) and tolerability in terms of the dropout rate due to adverse events. The network compares 21 antidepressants consisting of 231 relative treatment comparisons, 164 (efficacy) and 127 (tolerability) of which are currently assumed to have inconclusive evidence. Results Required sample sizes to achieve new conclusive evidence with at least 80% conditional power were estimated to range between N = 894 - 4190 (efficacy) and N = 521 - 1246 (tolerability). Otherwise, sample sizes ranging between N = 49 - 485 (efficacy) and N = 40 - 320 (tolerability) may require stopping for futility based on a boundary at 20% conditional power. Optimizing trial designs by considering multiple trials that contribute both direct and indirect evidence, anticipating alternative effect sizes or alternative event probabilities, may increase conditional power but required sample sizes remain high. Antidepressants having the greatest conditional power associated with smallest required sample sizes were identified as those on which current evidence is low, i.e., clomipramine, levomilnacipran, milnacipran, nefazodone, and vilazodone, with respect to both outcomes. Conclusions The present results suggest that conditional power to achieve new conclusive evidence in ongoing or future trials on antidepressant treatments is low. Limiting the use of the presented conditional power analysis are primarily due to the estimated large sample sizes which would be required in future trials as well as due to the well-known small effect sizes in antidepressant treatments. These findings may inform researchers and decision-makers regarding the clinical relevance and justification of research in ongoing or future antidepressant RCTs in MDD.


Author(s):  
Ian Leigh Alberts ◽  
Svenja Elizabeth Seide ◽  
Clemens Mingels ◽  
Karl Peter Bohn ◽  
Kuangyu Shi ◽  
...  

Abstract Purpose Many radiotracers are currently available for the detection of recurrent prostate cancer (rPC), yet many have not been compared head-to-head in comparative imaging studies. There is therefore an unmet need for evidence synthesis to guide evidence-based decisions in the selection of radiotracers. The objective of this study was therefore to assess the detection rate of various radiotracers for the rPC. Methods The PUBMED, EMBASE, and the EU and NIH trials databases were searched without date or language restriction for comparative imaging tracers for 13 radiotracers of principal interest. Key search terms included 18F-PSMA-1007, 18F-DCPFyl, 68Ga-PSMA-11, 18F-PSMA-11, 68Ga-PSMA-I&T, 68Ga-THP-PSMA, 64Cu-PSMA-617, 18F-JK-PSMA-7, 18F-Fluciclovine, 18F-FABC, 18F-Choline, 11C-Choline, and 68Ga-RM2. Studies reporting comparative imaging data in humans in rPC were selected. Single armed studies and matched pair analyses were excluded. Twelve studies with eight radiotracers were eligible for inclusion. Two independent reviewers screened all studies (using the PRISMA-NMA statement) for inclusion criteria, extracted data, and assessed risk of bias (using the QUADAS-2 tool). A network meta-analysis was performed using Markov-Chain Monte Carlo Bayesian analysis to obtain estimated detection rate odds ratios for each tracer combination. Results A majority of studies were judged to be at risk of publication bias. With the exception of 18F-PSMA-1007, little difference in terms of detection rate was revealed between the three most commonly used PSMA-radiotracers (68Ga-PSMA-11, 18F-PSMA-1007, 18F-DCFPyl), which in turn showed clear superiority to choline and fluciclovine using the derived network. Conclusion Differences in patient-level detection rates were observed between PSMA- and choline-radiotracers. However, there is currently insufficient evidence to favour one of the four routinely used PSMA-radioligands (PSMA-11, PSMA-1007, PSMA-I&T, and DCFPyl) over another owing to the limited evidence base and risk of publication bias revealed by our systematic review. A further limitation was lack of reporting on diagnostic accuracy, which might favour radiotracers with low specificity in an analysis restricted only to detection rate. The NMA derived can be used to inform the design of future clinical trials and highlight areas where current evidence is weak.


2020 ◽  
Vol 7 (1) ◽  
pp. 5
Author(s):  
Jack Nunn ◽  
Steven Chang

Systematic reviews are a type of review that uses repeatable analytical methods to collect secondary data and analyse it. Systematic reviews are a type of evidence synthesis which formulate research questions that are broad or narrow in scope, and identify and synthesize data that directly relate to the systematic review question. While some people might associate ‘systematic review’ with 'meta-analysis', there are multiple kinds of review which can be defined as ‘systematic’ which do not involve a meta-analysis. Some systematic reviews critically appraise research studies, and synthesize findings qualitatively or quantitatively. Systematic reviews are often designed to provide an exhaustive summary of current evidence relevant to a research question. For example, systematic reviews of randomized controlled trials are an important way of informing evidence-based medicine, and a review of existing studies is often quicker and cheaper than embarking on a new study. While systematic reviews are often applied in the biomedical or healthcare context, they can be used in other areas where an assessment of a precisely defined subject would be helpful. Systematic reviews may examine clinical tests, public health interventions, environmental interventions, social interventions, adverse effects, qualitative evidence syntheses, methodological reviews, policy reviews, and economic evaluations. An understanding of systematic reviews and how to implement them in practice is highly recommended for professionals involved in the delivery of health care, public health and public policy.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Partha Sardar ◽  
Amartya Kundu ◽  
Omosalewa Adenikinju ◽  
Gerald Pekler ◽  
Saurav Chatterjee ◽  
...  

Introduction: Recently few studies evaluated the effects of ACE/ARB in patients with Marfan syndrome. However, as majority of the studies were small and mainly pilot studies, conclusive evidence of benefit with ACE/ARB in this scenario is still pending. The objective of the present meta-analysis was to evaluate the effect of ACE/ARB on the progression of aortic root dilatation in patients with Marfan syndrome. Hypothesis: Treatment with ACE/ARBs is effective for the prevention of aortic-root enlargement in patients with Marfan syndrome. Methods: We searched PubMed, EMBASE, and Cochrane Central Register of Clinical Trials from the inception to April 30, 2013. The main outcome of the present analysis was the change in aortic root diameter with ACE/ABR therapy compared to control. The random effects model of DerSimonian and Laird was used. Results: Four studies were included in the final analysis; three studies were randomized trial and one was observation study. ACE/ARB significantly reduced enlargement of aortic root diameters compared to control; mean difference of -0.97 (95% confidence interval, -1.42 to -0.52; P<0.0001). Consistent benefit of ACE/ARB was observed in all sub-group and sensitivity analyses; against beta blocker, against placebo, in adult patients, with only ARB, analysis with the results from only RCTs. Conclusions: This is the first meta-analysis indicating a beneficial effect of ACE/ARB treatment on aortic root dilatation in patients with Marfan Syndrome. Current evidence supports the use of ARB, specially losartan for this indication.


Healthcare ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 47
Author(s):  
Chun-Yu Chen ◽  
Shih-Chieh Shao ◽  
Yih-Ting Chen ◽  
Cheng-Kai Hsu ◽  
Heng-Jung Hsu ◽  
...  

Hemodialysis (HD) patients are highly susceptible to COVID-19 infection. However, comprehensive assessments of current evidence regarding COVID-19 in HD patients remain incomplete. We systematically searched PUBMED and EMBASE for articles published on incidence or mortality of COVID-19 infection in HD patients until September 2020. Two independent researchers extracted data and study-level risk of bias across studies. We conducted meta-analysis of proportions for incidence and mortality rate. Study heterogeneity and publication bias were assessed. A total of 29 articles with 3261 confirmed COVID-19 cases from a pool of 396,062 HD patients were identified. Incidence of COVID-19 in these HD patients was 7.7% (95% CI: 5.0–10.9%; study heterogeneity: I2 = 99.7%, p < 0.001; risk of publication bias, Egger’s test, p < 0.001). Overall mortality rate was 22.4% (95% CI: 17.9–27.1%; study heterogeneity: I2 = 87.1%, p < 0.001; risk of publication bias, Egger’s test: p = 0.197) in HD patients with COVID-19. Reported estimates were higher in non-Asian than Asian countries. Quality of study may affect the reported incidence but not the mortality among studies. Both incidence and mortality of COVID-19 infection were higher in HD patients. Available data may underestimate the real incidence of infection. International collaboration and standardized reporting of epidemiological data should be needed for further studies.


2020 ◽  
Vol 7 (1) ◽  
pp. 4
Author(s):  
Jack Nunn ◽  
◽  
Steven Chang ◽  

Systematic reviews are a type of review that uses repeatable analytical methods to collect secondary data and analyse it. Systematic reviews are a type of evidence synthesis which formulate research questions that are broad or narrow in scope, and identify and synthesize data that directly relate to the systematic review question.[1] While some people might associate ‘systematic review’ with 'meta-analysis', there are multiple kinds of review which can be defined as ‘systematic’ which do not involve a meta-analysis. Some systematic reviews critically appraise research studies, and synthesize findings qualitatively or quantitatively.[2] Systematic reviews are often designed to provide an exhaustive summary of current evidence relevant to a research question. For example, systematic reviews of randomized controlled trials are an important way of informing evidence-based medicine,[3] and a review of existing studies is often quicker and cheaper than embarking on a new study. While systematic reviews are often applied in the biomedical or healthcare context, they can be used in other areas where an assessment of a precisely defined subject would be helpful.[4] Systematic reviews may examine clinical tests, public health interventions, environmental interventions,[5] social interventions, adverse effects, qualitative evidence syntheses, methodological reviews, policy reviews, and economic evaluations.[6][7] An understanding of systematic reviews and how to implement them in practice is highly recommended for professionals involved in the delivery of health care, public health and public policy.


2019 ◽  
Vol 145 (5) ◽  
pp. 490-507 ◽  
Author(s):  
Laci Watkins ◽  
Katherine Ledbetter-Cho ◽  
Mark O'Reilly ◽  
Lucy Barnard-Brak ◽  
Pau Garcia-Grau

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1087-1095
Author(s):  
Michele Sacco ◽  
Fatima Domenica Elisa De Palma ◽  
Elia Guadagno ◽  
Mariano Cesare Giglio ◽  
Roberto Peltrini ◽  
...  

AbstractIn 2010, serrated polyps (SP) of the colon have been included in the WHO classification of digestive tumors. Since then a large corpus of evidence focusing on these lesions are available in the literature. This review aims to analyze the present data on the epidemiological and molecular aspects of SP. Hyperplastic polyps (HPs) are the most common subtype of SP (70–90%), with a minimal or null risk of malignant transformation, contrarily to sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs), which represent 10–20% and 1% of adenomas, respectively. The malignant transformation, when occurs, is supported by a specific genetic pathway, known as the serrated-neoplasia pathway. The time needed for malignant transformation is not known, but it may occur rapidly in some lesions. Current evidence suggests that a detection rate of SP ≥15% should be expected in a population undergoing screening colonoscopy. There are no differences between primary colonoscopies and those carried out after positive occult fecal blood tests, as this screening test fails to identify SP, which rarely bleed. Genetic similarities between SP and interval cancers suggest that these cancers could arise from missed SP. Hence, the detection rate of serrated-lesions should be evaluated as a quality indicator of colonoscopy. There is a lack of high-quality longitudinal studies analyzing the long-term risk of developing colorectal cancer (CRC), as well as the cancer risk factors and molecular tissue biomarkers. Further studies are needed to define an evidence-based surveillance program after the removal of SP, which is currently suggested based on experts’ opinions.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manit Srisurapanont ◽  
Sirijit Suttajit ◽  
Surinporn Likhitsathian ◽  
Benchalak Maneeton ◽  
Narong Maneeton

AbstractThis study compared weight and cardiometabolic changes after short-term treatment of olanzapine/samidorphan and olanzapine. Eligible criteria for an included trial were ≤ 24 weeks, randomized controlled trials (RCTs) that compared olanzapine/samidorphan and olanzapine treatments in patients/healthy volunteers and reported weight or cardiometabolic outcomes. Three databases were searched on October 31, 2020. Primary outcomes included weight changes and all-cause dropout rates. Standardized mean differences (SMDs) and risk ratios (RRs) were computed and pooled using a random-effect model. This meta-analysis included four RCTs (n = 1195). The heterogeneous data revealed that weight changes were not significantly different between olanzapine/samidorphan and olanzapine groups (4 RCTs, SDM = − 0.19, 95% CI − 0.45 to 0.07, I2 = 75%). The whole-sample, pooled RR of all-cause dropout rates (4 RCTs, RR = 1.02, 95% CI 0.84 to 1.23, I2 = 0%) was not significant different between olanzapine/samidorphan and olanzapine groups. A lower percentage of males and a lower initial body mass index were associated with the greater effect of samidorphan in preventing olanzapine-induced weight gain. Current evidence is insufficient to support the use of samidorphan to prevent olanzapine-induced weight gain and olanzapine-induced cardiometabolic abnormalities. Samidorphan is well accepted by olanzapine-treated patients.


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