On the relationship between subjective decision criteria and paranoid ideations.

Following the conjecture made by (Bliznashki and Hristova in Appetite 167:105645, 2021), we test the hypothesis that liberal subjective decision criteria exhibited during a task involving discrimination between random and systematically correlated patterns should be associated with elevated levels of paranoid ideations. Study 1 establishes the proposed association in the presence of several control measures while also demonstrating that the relationship in question is significantly moderated by subjects' working memory spans and tendencies to be overconfident in their judgments. Study 2 provides further evidence that these effects are indeed specific to tasks involving discrimination between random and systematic patterns and that the observed results are not due to some form of (anti) acquiescence bias or other general trends. Certain specifics of the correlation matrices involving cognitive measures significantly related to the paranoia continuum suggest that our results are consistent with the Entropic Brain Hypothesis. Finally, a simulation study employing a Neural Network demonstrates that increased entropy and liberal decision criteria might be connected to each other with said connection being amenable to an interpretation within the Bayesian paradigm.

Evidence for cortical adjustments to perceptual decision criteria during word recognition in noise.

Extensive increases in cingulo-opercular frontal activity are typically observed during speech recognition in noise tasks. This elevated activity has been linked to a word recognition benefit on the next trial, termed "adaptive control," but how this effect might be implemented has been unclear. The established link between perceptual decision making and cingulo-opercular function may provide an explanation for how those regions benefit subsequent word recognition. In this case, processes that support recognition such as raising or lowering the decision criteria for more accurate or faster recognition may be adjusted to optimize performance on the next trial. The current neuroimaging study tested the hypothesis that pre-stimulus cingulo-opercular activity reflects criterion adjustments that determine how much information to collect for word recognition on subsequent trials. Participants included middle-age and older adults (N = 30; age = 58.3 ± 8.8 years; m ± sd) with normal hearing or mild sensorineural hearing loss. During a sparse fMRI experiment, words were presented in multitalker babble at +3 dB or +10 dB signal-to-noise ratio (SNR), which participants were instructed to repeat aloud. Word recognition was significantly poorer with increasing participant age and lower SNR compared to higher SNR conditions. A perceptual decision-making model was used to characterize processing differences based on task response latency distributions. The model showed that significantly less sensory evidence was collected (i.e., lower criteria) for lower compared to higher SNR trials. Replicating earlier observations, pre-stimulus cingulo-opercular activity was significantly predictive of correct recognition on a subsequent trial. Individual differences showed that participants with higher criteria also benefitted the most from pre-stimulus activity. Moreover, trial-level criteria changes were significantly linked to higher versus lower pre-stimulus activity. These results suggest cingulo-opercular cortex contributes to criteria adjustments to optimize speech recognition task performance.

Statistical Decision Properties of Imprecise Trials Assessing Coronavirus Disease 2019 (COVID-19) Drugs.

OBJECTIVES: Researchers studying treatment of coronavirus disease 2019 (COVID-19) have reported findings of randomized trials comparing standard care with care augmented by experimental drugs. Many trials have small sample sizes, so estimates of treatment effects are imprecise. Hence, clinicians may find it difficult to decide when to treat patients with experimental drugs. A conventional practice when comparing standard care and an innovation is to choose the innovation only if the estimated treatment effect is positive and statistically significant. This practice defers to standard care as the status quo. We study treatment choice from the perspective of statistical decision theory, which considers treatment options symmetrically when assessing trial findings. METHODS: We use the concept of near-optimality to evaluate criteria for treatment choice. This concept jointly considers the probability and magnitude of decision errors. An appealing criterion from this perspective is the empirical success rule, which chooses the treatment with the highest observed average patient outcome in the trial. RESULTS: Considering the design of some COVID-19 trials, we show that the empirical success rule yields treatment choices that are much closer to optimal than those generated by prevailing decision criteria based on hypothesis tests. CONCLUSION: Using trial findings to make near-optimal treatment choices rather than perform hypothesis tests should improve clinical decision making.

The imputation of structure in random patterns as a cognitive factor predicting adult picky eating behavior.

We raise the hypothesis that adult picky eating behavior may be related to subjects' tendency to impute structure in random stimuli. We test said hypothesis in an empirical study which operationalizes subjects' objective abilities and subjective decision criteria in discriminating between correlated and independent signals in terms of the classic Signal Detection Theory. A robust regularized Bayesian multiple regression analysis indicates that liberal subjective decision criteria which indicate a tendency to over-impute structure when trying to discriminate between random and correlated patterns are associated with elevated scores of picky eating while controlling for several other variables. The predictive power of our discriminating procedure appears comparable to that of related eating dispositions. Our results strongly suggest that cognitive factors might indeed have substantial and meaningful relationships with certain eating behaviors.

Optimising the trade-off between type I and II error rates in the Bayesian context.

For any decision-making study, there are two sorts of errors that can be made, declaring a positive result when the truth is negative, and declaring a negative result when the truth is positive. Traditionally, the primary analysis of a study is a two-sided hypothesis test, the type I error rate will be set to 5% and the study is designed to give suitably low type II error - typically 10 or 20% - to detect a given effect size. These values are standard, arbitrary and, other than the choice between 10 and 20%, do not reflect the context of the study, such as the relative costs of making type I and II errors and the prior belief the drug will be placebo-like. Several authors have challenged this paradigm, typically for the scenario where the planned analysis is frequentist. When resource is limited, there will always be a trade-off between the type I and II error rates, and this article explores optimising this trade-off for a study with a planned Bayesian statistical analysis. This work provides a scientific basis for a discussion between stakeholders as to what type I and II error rates may be appropriate and some algebraic results for normally distributed data.

Decision Making Criteria in Oncology.

Decision making is one of the most complex skills required of an oncologist and is affected by a broad range of parameters. For example, the wide variety of treatment options, with various outcomes, side-effects and costs present challenges in selecting the most appropriate treatment. Many treatment choices are affected by limited scientific evidence, availability of therapies or patient-specific factors. In the decision making process, standardized approaches can be useful, but a multitude of criteria are relevant to this process. Thus, the aim of this review is to summarize common types of decision criteria used in oncology by focusing on 3 main categories: criteria associated with the decision maker (both patient and doctor), decision specific criteria, and the often-overlooked contextual factors. Our review aims to highlight the broad range of decision criteria in use, as well as variations in their interpretation.

Emotions as Social Information in Shared Decision-Making in Oncology.

Emotions play an important role in decision-making and they can impact individual as well as shared decisions. With increasing complexity of the decision, the potential for emotions to influence the outcome increases. Emotions are thus an influential factor in oncological decision-making which is a complex and high-stakes situation. As the shared decision-making process is at the center of patient-centric decisions, we model emotions as social information that inform the shared decision-making process. We present and explain a range of emotional concepts, together with a specific clinical example, that can impact the shared decision-making process. Our process model shows that emotions are experienced in various combinations before, during, and after a shared decision is made and how patients' and physicians' emotions interact and spill over during a shared decision situation. Overall, our process model and specific example show how emotions can impact shared decision-making in oncology in a multitude of ways. With this paper, we want to raise awareness of the role of emotions in the shared decision-making process, as emotions are often not explicitly recognized as decision criteria. Increased awareness of emotions may help their optimal utilization and reduce their influence as a bias in shared decision-making.

Choice of first line systemic treatment in pancreatic cancer among national experts.

BACKGROUND: Treatment options for patients with metastatic pancreatic cancer depend on various factors, including performance status, tumor burden and patient preferences. Metastatic pancreatic cancer is incurable and many systemic treatment options have been investigated over the past decades. This analysis of patterns of practice was performed to identify decision criteria and their impact on the choice of first-line management of metastatic pancreatic cancer. MATERIALS AND METHODS: Members of the Swiss Group for Clinical Cancer Research (SAKK) Gastrointestinal Cancer Group were contacted and agreed to participate in this analysis. Decision trees for the first line treatment of metastatic pancreatic cancer from 9 centers in Switzerland were collected and analyzed based on the objective consensus methodology to identify consensus and discrepancies in clinical decision-making. RESULTS: The final treatment algorithms included 3 decision criteria (comorbidities, performance status and age) and 5 treatment options: FOLFIRINOX, FOLFOX, gemcitabine + nab-paclitaxel, gemcitabine mono and best supportive care. CONCLUSION: We identified multiple decision criteria relevant to all participating centers. We found consensus for the treatment of young (age below 65) patients with good performance status with FOLFIRINOX. For patients with increasing age and reducing performance status there was a decreasing trend to use gemcitabine + nab-paclitaxel. Gemcitabine monotherapy was typically offered to patients in the presence of comorbidities. For patients with ECOG 3-4, most of the experts recommended BSC.

When complexity matters: a step-by-step guide to incorporating a complexity perspective in guideline development for public health and health system interventions.

BACKGROUND: Guidelines on public health and health system interventions often involve considerations beyond effectiveness and safety to account for the impact that these interventions have on the wider systems in which they are implemented. This paper describes how a complexity perspective may be adopted in guideline development to facilitate a more nuanced consideration of a range of factors pertinent to decisions regarding public health and health system interventions. These factors include acceptability and feasibility, and societal, economic, and equity and equality implications of interventions. MAIN MESSAGE: A 5-step process describes how to incorporate a complexity perspective in guideline development with examples to illustrate each step. The steps include: (i) guideline scoping, (ii) formulating questions, (iii) retrieving and synthesising evidence, (iv) assessing the evidence, and (v) developing recommendations. Guideline scoping using stakeholder consultations, complexity features, evidence mapping, logic modelling, and explicit decision criteria is emphasised as a key step that informs all subsequent steps. CONCLUSIONS: Through explicit consideration of a range of factors and enhanced understanding of the specific circumstances in which interventions work, a complexity perspective can yield guidelines with better informed recommendations and facilitate local adaptation and implementation. Further work will need to look into the methods of collecting and assessing different types of evidence beyond effectiveness and develop procedural guidance for prioritising across a range of decision criteria.

Generating Robust and Informative Nonclinical In Vitro and In Vivo Bacterial Infection Model Efficacy Data To Support Translation to Humans.

In June 2017, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled "Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens." The aims were to discuss details of various PK/PD models and identify sound practices for deriving and utilizing PK/PD relationships to design optimal dosage regimens for patients. Workshop participants encompassed individuals from academia, industry, and government, including the United States Food and Drug Administration. This and the accompanying review on clinical PK/PD summarize the workshop discussions and recommendations. Nonclinical PK/PD models play a critical role in designing human dosage regimens and are essential tools for drug development. These include in vitro and in vivo efficacy models that provide valuable and complementary information for dose selection and translation from the laboratory to human. It is crucial that studies be designed, conducted, and interpreted appropriately. For antibacterial PK/PD, extensive published data and expertise are available. These have been leveraged to develop recommendations, identify common pitfalls, and describe the applications, strengths, and limitations of various nonclinical infection models and translational approaches. Despite these robust tools and published guidance, characterizing nonclinical PK/PD relationships may not be straightforward, especially for a new drug or new class. Antimicrobial PK/PD is an evolving discipline that needs to adapt to future research and development needs. Open communication between academia, pharmaceutical industry, government, and regulatory bodies is essential to share perspectives and collectively solve future challenges.

The evolution of the cancer formulary review in Canada: Can centralization improve the use of economic evaluation?

Public reimbursement of drugs is a costly proposition for health care systems. Decisions to add drugs to the public formulary are often guided by review processes and committees. The evolution of the formulary review process in Canada's publicly funded health system is characterized by increased centralization and systematization. In the past, the review of evidence and recommendation was conducted at the regional level, but was replaced with the pan-Canadian Oncology Drug Review in 2011. We assess the extent to which centralization and systematization of the review process have responded to past challenges, focusing on the use of economic evaluation in the process. Past challenges with economic evaluation experienced by regionalized review committees were identified from literature and qualitative data collected in the province of Nova Scotia. We categorize these using a typology with a macro-, meso, and micro-level hierarchy, which provides a useful framework for understanding at which level change is required, and who has the authority to influence change. Using grounded theory methods, we identify approaches used by Nova Scotia past committee members to compensate for perceived shortcomings of the process. These include an undue reliance on other committee members, on the multidisciplinarity of the committee, and on past decisions. Using a policy analysis approach, we argue that centralization and systematization of the review process only partially address the shortcomings of the previous regionalized process. Lessons from Canada can inform policy discussions across all health systems, where similar challenges with the formulary review process have been identified. © 2016 The Authors. The International Journal of Health Planning and Management published by John Wiley & Sons Ltd.

A Quadrilateral Geometry Classification Method and Device for Femtocell Positioning Networks.

This article proposes a normalization multi-layer perception (NMLP) geometry classifier to autonomously determine the optimal four femtocell evolved Node Bs (FeNBs), which can use time difference of arrival (TDOA) to measure the location of the macrocell user equipment (MUE) with the lowest GDOP value. The iterative geometry training (IGT) algorithm is designed to obtain the training data for the NMLP geometry classifier. The architecture of the proposed NMLP geometry classifier is realized in the server of the cloud computing platform, to identify the optimal geometry disposition of four FeNBs for positioning the MUE located between two buildings. Six by six neurons are chosen for two hidden layers, in order to shorten the convergent time. The feasibility of the proposed method is demonstrated by means of numerical simulations. In addition, the simulation results also show that the proposed method is particularly suitable for the application of the MUE positioning with a huge number of FeNBs. Finally, three quadrilateral optimum geometry disposition decision criteria are analyzed for the validation of the simulation results.

Agency alters perceptual decisions about action-outcomes.

Humans experience themselves as agents, capable of controlling their actions and the outcomes they generate (i.e., the sense of agency). Inferences of agency are not infallible. Research shows that we often attribute outcomes to our agency even though they are caused by another agent. Moreover, agents report the sensory events they generate to be less intense compared to the events that are generated externally. These effects have been assessed using highly suprathreshold stimuli and subjective measurements. Consequently, it remains unclear whether experiencing oneself as an agent lead to a decision criterion change and/or a sensitivity change. Here, we investigate this issue. Participants were told that their key presses generated an upward dot motion but that on 30 % of the trials the computer would take over and display a downward motion. The upward/downward dot motion was presented at participant's discrimination threshold. Participants were asked to indicate whether they (upward motion) or the computer (downward motion) generated the motion. This group of participants was compared with a 'no-agency' group who performed the same task except that subjects did not execute any actions to generate the dot motion. We observed that the agency group reported seeing more frequently the motion they expected to generate (i.e., upward motion) than the no-agency group. This suggests that agency distorts our experience of (allegedly) caused events by altering perceptual decision processes, so that, in ambiguous contexts, externally generated events are experienced as the outcomes of one's actions.

Decision-making in early clinical drug development.

This paper illustrates an approach to setting the decision framework for a study in early clinical drug development. It shows how the criteria for a go and a stop decision are calculated based on pre-specified target and lower reference values. The framework can lead to a three-outcome approach by including a consider zone; this could enable smaller studies to be performed in early development, with other information either external to or within the study used to reach a go or stop decision. In this way, Phase I/II trials can be geared towards providing actionable decision-making rather than the traditional focus on statistical significance. The example provided illustrates how the decision criteria were calculated for a Phase II study, including an interim analysis, and how the operating characteristics were assessed to ensure the decision criteria were robust. Copyright © 2016 John Wiley & Sons, Ltd.

Algorithms in the First-Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma--Analysis Using Diagnostic Nodes.

BACKGROUND: With the advent of targeted therapies, many treatment options in the first-line setting of metastatic clear cell renal cell carcinoma (mccRCC) have emerged. Guidelines and randomized trial reports usually do not elucidate the decision criteria for the different treatment options. In order to extract the decision criteria for the optimal therapy for patients, we performed an analysis of treatment algorithms from experts in the field. MATERIALS AND METHODS: Treatment algorithms for the treatment of mccRCC from experts of 11 institutions were obtained, and decision trees were deduced. Treatment options were identified and a list of unified decision criteria determined. The final decision trees were analyzed with a methodology based on diagnostic nodes, which allows for an automated cross-comparison of decision trees. The most common treatment recommendations were determined, and areas of discordance were identified. RESULTS: The analysis revealed heterogeneity in most clinical scenarios. The recommendations selected for first-line treatment of mccRCC included sunitinib, pazopanib, temsirolimus, interferon-α combined with bevacizumab, high-dose interleukin-2, sorafenib, axitinib, everolimus, and best supportive care. The criteria relevant for treatment decisions were performance status, Memorial Sloan Kettering Cancer Center risk group, only or mainly lung metastases, cardiac insufficiency, hepatic insufficiency, age, and "zugzwang" (composite of multiple, related criteria). CONCLUSION: In the present study, we used diagnostic nodes to compare treatment algorithms in the first-line treatment of mccRCC. The results illustrate the heterogeneity of the decision criteria and treatment strategies for mccRCC and how available data are interpreted and implemented differently among experts. IMPLICATIONS FOR PRACTICE: The data provided in the present report should not be considered to serve as treatment recommendations for the management of treatment-naïve patients with multiple metastases from metastatic clear cell renal cell carcinoma outside a clinical trial; however, the data highlight the different treatment options and the criteria used to select them. The diversity in decision making and how results from phase III trials can be interpreted and implemented differently in daily practice are demonstrated.

Assessment of three approaches for regulatory decision making on pesticides with endocrine disrupting properties.

Recent EU legislation has introduced endocrine disrupting properties as a hazard-based "cut-off" criterion for the approval of active substances as pesticides and biocides. Currently, no specific science-based approach for the assessment of substances with endocrine disrupting properties has been agreed upon, although this new legislation provides interim criteria based on classification and labelling. Different proposals for decision making on potential endocrine disrupting properties in human health risk assessment have been developed by the German Federal Institute for Risk Assessment (BfR) and other regulatory bodies. All these frameworks, although differing with regard to hazard characterisation, include a toxicological assessment of adversity of the effects, the evaluation of underlying modes/mechanisms of action in animals and considerations concerning the relevance of effects to humans. Three options for regulatory decision making were tested upon 39 pesticides for their applicability and to analyze their potential impact on the regulatory status of active substances that are currently approved for use in Europe: Option 1, based purely on hazard identification (adversity, mode of action, and the plausibility that both are related); Option 2, based on hazard identification and additional elements of hazard characterisation (severity and potency); Option 3, based on the interim criteria laid down in the recent EU pesticides legislation. Additionally, the data analysed in this study were used to address the questions, which parts of the endocrine system were affected, which studies were the most sensitive and whether no observed adverse effect levels were observed for substance with ED properties. The results of this exercise represent preliminary categorisations and must not be used as a basis for definitive regulatory decisions. They demonstrate that a combination of criteria for hazard identification with additional criteria of hazard characterisation allows prioritising and differentiating between substances with regard to their regulatory concern. It is proposed to integrate these elements into a decision matrix to be used within a weight of evidence approach for the toxicological categorisation of relevant endocrine disruptors and to consider all parts of the endocrine system for regulatory decision making on endocrine disruption.

Management of contaminated marine marketable resources after oil and HNS spills in Europe.

Different risk evaluation approaches have been used to face oil and hazardous and noxious substances (HNS) spills all over the world. To minimize health risks and mitigate economic losses due to a long term ban on the sale of sea products after a spill, it is essential to preemptively set risk evaluation criteria and standard methodologies based on previous experience and appropriate scientifically sound criteria. Standard methodologies are analyzed and proposed in order to improve the definition of criteria for reintegrating previously contaminated marine marketable resources into the commercialization chain in Europe. The criteria used in former spills for the closing of and lifting of bans on fisheries and harvesting are analyzed. European legislation was identified regarding food sampling, food chemical analysis and maximum levels of contaminants allowed in seafood, which ought to be incorporated in the standard methodologies for the evaluation of the decision criteria defined for oil and HNS spills in Europe. A decision flowchart is proposed that opens the current decision criteria to new material that may be incorporated in the decision process. Decision criteria are discussed and compared among countries and incidents. An a priori definition of risk criteria and an elaboration of action plans are proposed to speed up actions that will lead to prompt final decisions. These decisions, based on the best available scientific data and conducing to lift or ban economic activity, will tend to be better understood and respected by citizens.

Audiovisual simultaneity windows reflect temporal sensory uncertainty.

The ability to judge the temporal alignment of visual and auditory information is a prerequisite for multisensory integration and segregation. However, each temporal measurement is subject to error. Thus, when judging whether a visual and auditory stimulus were presented simultaneously, observers must rely on a subjective decision boundary to distinguish between measurement error and truly misaligned audiovisual signals. Here, we tested whether these decision boundaries are relaxed with increasing temporal sensory uncertainty, i.e., whether participants make the same type of adjustment an ideal observer would make. Participants judged the simultaneity of audiovisual stimulus pairs with varying temporal offset, while being immersed in different virtual environments. To obtain estimates of participants' temporal sensory uncertainty and simultaneity criteria in each environment, an independent-channels model was fitted to their simultaneity judgments. In two experiments, participants' simultaneity decision boundaries were predicted by their temporal uncertainty, which varied unsystematically with the environment. Hence, observers used a flexibly updated estimate of their own audiovisual temporal uncertainty to establish subjective criteria of simultaneity. This finding implies that, under typical circumstances, audiovisual simultaneity windows reflect an observer's cross-modal temporal uncertainty.

The Use of Evidence to Design an Essential Package of Health Services in Pakistan: A Review and Analysis of Prioritisation Decisions at Different Stages of the Appraisal Process.

BACKGROUND: Pakistan embarked on a process of designing an essential package of health services (EPHS) as a pathway towards universal health coverage (UHC). The EPHS design followed an evidence-informed deliberative process; evidence on 170 interventions was introduced along multiple stages of appraisal engaging different stakeholders tasked with prioritising interventions for inclusion. We report on the composition of the package at different stages, analyse trends of prioritised and deprioritised interventions and reflect on the trade-offs made. METHODS: Quantitative evidence on cost-effectiveness, budget impact, and avoidable burden of disease was presented to stakeholders in stages. We recorded which interventions were prioritised and deprioritised at each stage and carried out three analyses: (1) a review of total number of interventions prioritised at each stage, along with associated costs per capita and disability-adjusted life years (DALYs) averted, to understand changes in affordability and efficiency in the package, (2) an analysis of interventions broken down by decision criteria and intervention characteristics to analyse prioritisation trends across different stages, and (3) a description of the trajectory of interventions broken down by current coverage and cost-effectiveness. RESULTS: Value for money generally increased throughout the process, although not uniformly. Stakeholders largely prioritised interventions with low budget impact and those preventing a high burden of disease. Highly cost-effective interventions were also prioritised, but less consistently throughout the stages of the process. Interventions with high current coverage were overwhelmingly prioritised for inclusion. CONCLUSION: Evidence-informed deliberative processes can produce actionable and affordable health benefit packages. While cost-effective interventions are generally preferred, other factors play a role and limit efficiency.

Needs and feasibility of living systematic reviews (LSRs): Experience from LSRs on COVID-19 vaccine effectiveness.

During 2021 and 2023, a team of researchers at the Robert Koch Institute (RKI) and partnering institutions conducted two living systematic reviews (LSRs) on the effectiveness of COVID-19 vaccines in different age groups to inform recommendations of the Standing Committee on Vaccination in Germany (Ständige Impfkommission, STIKO). Based on our experience from the realization of these LSRs, we developed certain criteria to assess the needs and feasibility of conducting LSRs. Combining these with previously established criteria, we developed the following set to inform future planning of LSRs for STIKO: Needs criterion (N)1: Relevance of the research question, N2: Certainty of evidence (CoE) at baseline; N3: Expected need for Population-Intervention-Comparator-Outcome (PICO) adaptations; N4: Expected new evidence over time; N5: Expected impact of new evidence on CoE; Feasibility criterion (F)1: Availability of sufficient human resources; F2: Feasibility of timely dissemination of the results to inform decision-making. For each criterion we suggest rating options which may support the decision to conduct an LSR or other forms of evidence synthesis when following the provided flowchart. The suggested criteria were developed on the basis of the experiences from exemplary reviews in a specific research field (i.e., COVID-19 vaccination), and did not follow a formal development or validation process. However, these criteria might also be useful to assess whether questions from other research fields can and should be answered using the LSR approach, or assist in determining whether the use of an LSR is sensible and feasible for specific questions in health policy and practice.