Bayesian Hierarchical Models Combining Different Study Types and Adjusting for Covariate Imbalances: A Simulation Study to Assess Model Performance

BACKGROUND: Bayesian hierarchical models have been proposed to combine evidence from different types of study designs. However, when combining evidence from randomised and non-randomised controlled studies, imbalances in patient characteristics between study arms may bias the results. The objective of this study was to assess the performance of a proposed Bayesian approach to adjust for imbalances in patient level covariates when combining evidence from both types of study designs. METHODOLOGY/PRINCIPAL FINDINGS: Simulation techniques, in which the truth is known, were used to generate sets of data for randomised and non-randomised studies. Covariate imbalances between study arms were introduced in the non-randomised studies. The performance of the Bayesian hierarchical model adjusted for imbalances was assessed in terms of bias. The data were also modelled using three other Bayesian approaches for synthesising evidence from randomised and non-randomised studies. The simulations considered six scenarios aimed at assessing the sensitivity of the results to changes in the impact of the imbalances and the relative number and size of studies of each type. For all six scenarios considered, the Bayesian hierarchical model adjusted for differences within studies gave results that were unbiased and closest to the true value compared to the other models. CONCLUSIONS/SIGNIFICANCE: Where informed health care decision making requires the synthesis of evidence from randomised and non-randomised study designs, the proposed hierarchical Bayesian method adjusted for differences in patient characteristics between study arms may facilitate the optimal use of all available evidence leading to unbiased results compared to unadjusted analyses

The importance of adjusting for potential confounders in Bayesian hierarchical models synthesising evidence from randomised and non-randomised studies: an application comparing treatments for abdominal aortic aneurysms

<p>Abstract</p> <p>Background</p> <p>Informing health care decision making may necessitate the synthesis of evidence from different study designs (e.g., randomised controlled trials, non-randomised/observational studies). Methods for synthesising different types of studies have been proposed, but their routine use requires development of approaches to adjust for potential biases, especially among non-randomised studies. The objective of this study was to extend a published Bayesian hierarchical model to adjust for bias due to confounding in synthesising evidence from studies with different designs.</p> <p>Methods</p> <p>In this new methodological approach, study estimates were adjusted for potential confounders using differences in patient characteristics (e.g., age) between study arms. The new model was applied to synthesise evidence from randomised and non-randomised studies from a published review comparing treatments for abdominal aortic aneurysms. We compared the results of the Bayesian hierarchical model adjusted for differences in study arms with: 1) unadjusted results, 2) results adjusted using aggregate study values and 3) two methods for downweighting the potentially biased non-randomised studies. Sensitivity of the results to alternative prior distributions and the inclusion of additional covariates were also assessed.</p> <p>Results</p> <p>In the base case analysis, the estimated odds ratio was 0.32 (0.13,0.76) for the randomised studies alone and 0.57 (0.41,0.82) for the non-randomised studies alone. The unadjusted result for the two types combined was 0.49 (0.21,0.98). Adjusted for differences between study arms, the estimated odds ratio was 0.37 (0.17,0.77), representing a shift towards the estimate for the randomised studies alone. Adjustment for aggregate values resulted in an estimate of 0.60 (0.28,1.20). The two methods used for downweighting gave odd ratios of 0.43 (0.18,0.89) and 0.35 (0.16,0.76), respectively. Point estimates were robust but credible intervals were wider when using vaguer priors.</p> <p>Conclusions</p> <p>Covariate adjustment using aggregate study values does not account for covariate imbalances between treatment arms and downweighting may not eliminate bias. Adjustment using differences in patient characteristics between arms provides a systematic way of adjusting for bias due to confounding. Within the context of a Bayesian hierarchical model, such an approach could facilitate the use of all available evidence to inform health policy decisions.</p

Apolipoprotein E Genotype and Cardiovascular Diseases in the Elderly

The apolipoprotein E (APOE) genotype is a genetic risk factor for dementia, Alzheimer’s disease, and cardiovascular disease (CVD). It includes three alleles (e2, e3, e4) that are located on chromosome 19q3.2. The e3 allele is the most common and is more common in people of Northern European ancestry and less common in those of Asian ancestry. Those with at least one e4 allele are at increased risk for CVD outcomes. It is well established that the presence of an e4 allele is linked to higher low-density lipoprotein cholesterol levels, even at young ages. Even though most CVD occurs in older people, there are few studies of the effects of APOE on CVD in older people. This review addresses recent research on the links between APOE, CVD, and vascular mechanisms by which APOE may affect CVD in the elderly

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population

Influence of biotic and abiotic factors on prymnesin profiles in three strains of<i> Prymnesium parvum</i>

Harmful algal blooms of Prymnesium parvum have resulted in significant fish kill events globally. These haptophytes produce the ichthyotoxic prymnesins, large polyethers categorized into A-, B- and C-types based on their carbon backbones with several analogs varying by the degree of glycosylation, chlorination, and double bonds. However, the influence of various biotic or abiotic factors on prymnesin profiles remains unknown. We investigated the influence of growth phase, nitrogen availability, light intensity, and salinity on prymnesin profiles of three P. parvum strains (UTEX 2797, K-0374 and PPSR01). Strains were selected based on their chemotypic expression of the three prymnesin backbones. Results demonstrated that different growth conditions led to strain-specific changes in prymnesin profiles. In the stationary phase, increased glycosylation was observed compared to the exponential growth phase for all strains. Additionally, at early stationary phase the tri-chlorinated analogs represented &gt;90 % of all prymnesins of P. parvum strains UTEX-2797 and PPSR01 when cultured at salinity of 10 psu. By gaining an understanding of the effects of biotic and abiotic factors, culture conditions could be modified to promote specific prymnesin profiles to support the development of analytical reference materials. Furthermore, evaluating prymnesin profiles in combination with toxicity assays will provide insights into prymnesin biosynthesis, mode of action and toxicity

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease