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Objective: Little guidance exists on the conduct of randomised clinical trials (RCT) that seek to randomise patients away from standard of care. We sought to test the technique of network meta‐analysis (NMA) to ascertain best available evidence for the purposes of informing the ethical evaluation of RCTs under these circumstances. We used the example of RCTs for patients with symptomatic, moderate to severe carotid stenosis that seek to compare surgical intervention plus medical therapy (standard of care) versus medical therapy (less than standard of care). Study Design and Setting: Network meta‐analysis of RCTs of adults with symptomatic carotid artery stenosis of 50%–99% who were treated with carotid endarterectomy (CEA), carotid artery stenting (CAS), or medical therapy (MT). The primary outcome was any stroke or death until end of follow‐up, and secondary outcome was 30‐day risk of ipsilateral stroke/death. Results: We analysed eight studies, with 7187 subjects with symptomatic moderate/severe stenosis (50%–99%). CEA was more efficacious than MT (HR = 0.82, 95% credible intervals [95% CrI] = 0.73–0.92) and CAS (HR 0.73, 95% CrI = 0.62–0.85) for the prevention of any stroke/death. At 30 days, the odds of experiencing an ipsilateral stroke/death were significantly lower in the CEA group compared to both MT (OR = 0.58, 95% CrI = 0.47–0.72) and CAS (OR = 0.68, 95% CrI = 0.55–0.83). Conclusion: Our results support the feasibility of using NMA to assess best available evidence to inform the ethical evaluation of RCTs seeking to randomise patients away from standard of care. Our results suggest that a strong argument is required to ethically justify the conduct of RCTs that seek to randomise patients away from standard of care in the setting of symptomatic moderate to severe carotid stenosis. [ABSTRACT FROM AUTHOR]

Rationale: The coherence theory of truth, the epistemology of evidence-based medicine, mathematical statistics, and axiomatic mathematics., Aims and Objectives: To explore mathematical misconceptions inhering in randomised controlled trial designs, suggest improvements, encourage meta-methodological discussions and call for further interdisciplinary studies., Method: Mathematical-statistical analyses and science-philosophical considerations., Results: Randomisation does not (necessarily) generate equal samples, ergo, outcomes of usual RCTs are not as reliable as they claim. Moreover, ignoring initial sample discrepancies may cause inaccuracies similar to type I and type II errors. Insufficient awareness of these flaws harms final RCT statements about significance and evidence levels, hence their loss of trustworthiness. Statistical parameters such as the standard error of the mean may help to estimate the expected distinction between random samples., Conclusion: Researchers in EBM should be aware of systemic misconceptions in RCT standards. Pre-measurement can reduce shortcomings, e.g. through calculation how sample differences impact on usual RCT processing, or randomisation is given up in favour of mathematical minimisation of sample differences, i.e. optimising statistical sample equality. Moreover, the promising future of dynamic simulation models is highlighted., (© 2024 John Wiley & Sons Ltd.)

This study introduces a blazingly fast, no‐loss expert system for tic‐tac‐toe using decision trees called T3DT, which tries to emulate human gameplay as closely as possible. It does not make use of any brute force, minimax, or evolutionary techniques, but is still always unbeatable. To make the gameplay more human‐like, randomisation is prioritised and T3DT randomly chooses one of the multiple optimal moves at each step. Since it does not need to analyse the complete game tree at any point, T3DT is exceptionally faster than any brute force or minimax algorithm, this has been shown theoretically as well as empirically from clock‐time analyses in this study. T3DT also does not need the data sets or the time to train an evolutionary model, making it a practical no‐loss approach to play tic‐tac‐toe. [ABSTRACT FROM AUTHOR]

Biddick & Burns (2021) proposed a null/neutral model that reproduces the island rule as a product of random drift. We agree that it is unnecessary to assume adaptive processes driving island dwarfing or gigantism, but several flaws make their approach unrealistic and thus unsuitable as a stochastic model for evolutionary size changes. [ABSTRACT FROM AUTHOR]

Summary: Neighbour balance and evenness of distribution designs help to address user concerns in the two‐dimensional layout of agricultural field trials. This is done by minimising the occurrence of pairwise treatment plot neighbours and ensuring that the replications of treatments are spread out across rows and columns of a trial. Such considerations result in a restriction on the normal randomisation process for a row‐column design which can lead to error variance bias. In this paper, uniformity trial data is used to assess the degree of this bias for both resolvable and non‐resolvable designs. Comparisons are made with a similar investigation using Linear Variance spatial designs. This article assesses the degree of error variance bias associated with neighbour balance and evenness of distribution designs. [ABSTRACT FROM AUTHOR]

Summary: Covariate information is often available in randomised clinical trials for each subject prior to treatment assignment and is commonly utilised to make covariate adjustment for baseline characteristics predictive of the outcome in order to increase precision and improve power in the detection of a treatment effect. Motivated by a nonparametric covariance analysis, we study a projection approach to making objective covariate adjustment in randomised clinical trials on the basis of two unbiased estimating functions that decouple the outcome and covariate data. The proposed projection approach extends a weighted least‐squares procedure by projecting one of the estimating functions onto the linear subspace spanned by the other estimating function that is E‐ancillary for the average treatment effect. Compared with the weighted least‐squares method, the projection method allows for objective inference on the average treatment effect by exploiting the treatment specific covariate–outcome associations. The resulting projection‐based estimator of the average treatment effect is asymptotically efficient when the treatment‐specific working regression models are correctly specified and is asymptotically more efficient than other existing competitors when the treatment‐specific working regression models are misspecified. The proposed projection method is illustrated by an analysis of data from an HIV clinical trial. In a simulation study, we show that the proposed projection method compares favourably with its competitors in finite samples. [ABSTRACT FROM AUTHOR]

Abstract: Tax experiments have been gaining momentum in recent years, although this literature dates back several decades. With new developments in methods and data availability, tax experiments have gradually moved away from lab settings and towards the field. This movement from the lab to the field has happened against the background of the ‘credibility revolution’ in applied economics, which has seen more rigorous methods applied to policy relevant questions, and of the availability to researchers of administrative data from tax returns. These developments have allowed significant advances in the experimental literature on tax compliance. This paper reviews this literature, giving particular attention to field experiments using administrative data, but putting them in the broader context of the compliance literature. A particular effort is made to take a global perspective, in a literature that is only recently seeing the emergence of evidence from Africa, Latin America and Asia. [ABSTRACT FROM AUTHOR]

Interconnected sensor nodes can be used for a long term monitoring of widely spread ecosystems. Individual nodes can be unavailable during the runtime due to a lack of energy, disruption of communication channels, or physical damages of nodes. In this study, a new approach to transfer messages from nodes to gateways (and optional to flood gate nodes) in such dynamically disturbed networks is presented. The focus is the routing in branched line‐structures, for example, flood barriers. The usage of gradient structures in each node allow tree routing, tree propagation, energy‐efficient exploring broadcast, exploitation of line‐structures, and collection of position information. In addition, a generic preference evaluation and decision making concept allows energy or signal quality evaluation, routing decision, structure setup decision, position estimation, synchronisation adaption, and randomisation of security approaches. It can be extended by further rules. [ABSTRACT FROM AUTHOR]

The problems of observing, controlling and stabilizing wave processes arise in many different contexts ranging from structural mechanics to seismic waves. In a suitable functional setting, they are closely interconnected and sometimes completely equivalent. In a series of previous articles we have addressed the problem of the optimal design of sensors for purely conservative wave models. We analyzed a relaxed version of the optimal observation problem, considering the expectation of solutions under a randomisation procedure, rather than that where all possible solutions are considered in a purely deterministic setting. From an analytical point of view, this randomisation procedure had the advantage of leading to a spectral diagonalisation of the observations. In this way, using fine asymptotic spectral properties of the Laplacian, we disclosed the links between the geometric properties of the domain where waves propagate and the existence of optimal locations for the sensors or, by the contrary, the emergence of relaxation phenomena. Here we show that spectral randomised observability is equivalent to the property of spectral controllability by means of a discrete set of lumped controls acting everywhere on the domain, and distributed according to the shape of the eigenfunctions. Our results on optimal observation then find natural equivalents on the problem of optimal spectral control. We also give an interpretation of these results in terms of a feedback stabilization property, ensuring the exponential decay of the energy of solutions as time tends to infinity. [ABSTRACT FROM AUTHOR]

We compared test sensitivity (in terms of prevented cancers) and overdiagnosis (in terms of non-progressive pre-invasive lesions) between the human papillomavirus test (HPV test, Hybrid Capture 2) and the traditional Pap test in routine screening for cervical cancer. The design was a randomised (1:1) health services study in Finland with intake between 2003 and 2007. We estimated sensitivity by the incidence method within one screening round. Overdiagnosis was based on the rate of cervical intraepithelial Grade 3 (CIN3) lesions diagnosed at screen and during the following interval. Out of 203,788 randomised women 132,298 attended (65% in both study arms) and 600,753 person-years accumulated among attenders up to the end of 2010. In all attenders, 34 invasive cervical cancers and 288 CIN3 lesions were diagnosed at screen or during the following interval. The interval cancer incidence was 2.5/105 person-years (sensitivity 0.87) and 1.4 (sensitivity 0.93) in the HPV arm and Pap test arm, respectively. The rate of CIN3 lesions was 57.1 and 38.8, respectively. In conclusion, sensitivity of HPV testing was similar to that of Pap testing but caused more overdiagnosis. Therefore, implementation of HPV testing needs to be reconsidered especially in countries with well organised programmes. [ABSTRACT FROM AUTHOR]

I consider seven misunderstandings that may be encountered about the nature, purpose and properties of randomisation in clinical trials. Some concern the practical realities of clinical research on patients. Others are to do with the value and purpose of balance. Still others are to do with a confusion about the role of conditioning in valid statistical inference. I consider a simple game of chance involving two dice to illustrate some points about inference and then consider the seven misunderstandings in turn. I conclude that although one should not make a fetish of randomisation, when proposing alternatives to randomisation in clinical trials, one should be very careful to be precise about the exact nature of the alternative being considered if one is to avoid the danger of underestimating the advantages that randomisation can offer. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The paper assesses biased-coin designs for sequential treatment allocation in clinical trials. Comparisons emphasise the importance of considering randomness, as well as treatment balance, which are calculated as bias and loss. In the numerical examples, the responses are assumed normally distributed, perhaps after transformation, and balance is required over a set of covariates. The effect of covariate distribution on the properties of five allocation rules is investigated, with an emphasis on methods of comparison, which also apply to other forms of response. The concept of admissibility shows that the widely used minimisation rule is outperformed by Atkinson's rule derived from the theory of optimum experimental design. We present a simplified form of this rule. For this rule, the ability to guess the next treatment allocation decreases with study size. For the other rules, it is constant. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Issues. The aim of this study is to examine the extent to which drug-dependent patients are ineligible for or unwilling to participate in randomised clinical trials. This is important because unrepresentative sample selection is a potentially important problem for randomised trials in the drug dependence field and little is known about the magnitude of the problem. Approach. A total of 98 clinical trials were drawn for analysis from a systematic review of the drug dependence treatment literature. Key Findings. The trials reviewed excluded an average of 29% of potential subjects as ineligible; a further 29% of the eligible subjects were unwilling to participate. Trials comparing widely different treatments had a higher proportion of ineligible and unwilling subjects than did studies comparing more similar treatments. Experiments with large samples enrolled a smaller proportion of patients from their sampling pool than did experiments with small samples. Implications. Drug-dependent trial subjects are a minority of all drug patients seen in real-world clinical practice. It is necessary to improve the reporting of these potential problems in randomised trials. Systematic reviews of the literature ought to use this information to distinguish reliable from less reliable findings. Conclusion. Unrepresentative sample selection is a serious problem for randomised trials in the drug dependence field.[Melberg HO, Humphreys K. Ineligibility and refusal to participate in randomised trials of treatments for drug dependence. Drug Alcohol Rev 2009] [ABSTRACT FROM AUTHOR]

Chemical and enzymatic interesterification are used to create spreadable fats. However, a comparison between the two processes in terms of their acute metabolic effects has not yet been investigated. A randomised crossover study in obese (plasma TAG > 1.69 mmol/L, and BMI > 30 (BMI = kg/m2) or waist circumference > 102 cm, n = 11, age = 59.3 ± 1.8 years) and non-obese (plasma triacylglycerol (TAG) < 1.69 mmol/L, and BMI < 30 or waist circumference < 102 cm, n = 10, age = 55.8 ± 2.2 years) men was undertaken to compare the effects of chemical versus enzymatic interesterification on postprandial risk factors for type 2 diabetes (T2D) and cardiovascular disease (CVD). TAG, cholesterol, glucose, insulin and free fatty acid concentrations were measured for 6 h following consumption of 1 g fat/kg body mass of non-interesterified (NIE), chemically interesterified (CIE), enzymatically interesterified (EIE) stearic acid-rich fat spread or no fat, each with 50 g available carbohydrate from white bread. Interesterification did not affect postprandial glucose, insulin, free fatty acids or cholesterol ( P > 0.05). Following ingestion of NIE, increases in serum oleic acid were observed, whereas both oleic and stearic acids were increased with CIE and EIE ( P < 0.05). While postprandial TAG concentrations in non-obese subjects were not affected by fat treatment ( P > 0.05), obese subjects had an 85% increase in TAGs with CIE versus NIE ( P < 0.05). The differences in TAG response between non-obese and obese subjects suggest that interesterification may affect healthy individuals differently compared to those already at risk for T2D and/or CVD. [ABSTRACT FROM AUTHOR]

1. Comparisons of biodiversity estimates among sites or through time are hampered by a focus on using mean and variance estimates for diversity measures. These estimators depend on both sampling effort and on the abundances of organisms in communities, which makes comparison of communities possible only through the use of rarefaction curves that reduce all samples to the lowest sample size. However, comparing species richness among communities does not demand absolute estimates of species richness and statistical tests of similarity among communities are potentially more straightforward. 2. This paper presents a program that uses randomisation methods to robustly test for differences in species richness among samples. Simulated data are used to show that the analysis has acceptable type I error rates and sufficient power to detect violations of the null hypothesis. An analysis of published bee data collected in 4 years shows how both sample size and hierarchical structure in sample type are incorporated into the analysis. 3. The randomisation program is shown to be very robust to the presence of a dominant species, many rare species, and decreased sample size, giving quantitatively similar conclusions under all conditions. This method of testing for differences in biodiversity provides an important tool for researchers working on questions in community ecology and conservation biology. [ABSTRACT FROM AUTHOR]