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OBJECTIVES: Reimbursement decisions for new Alzheimer's disease (AD) treatments are informed by economic evaluations. An open-source model with intuitive structure for model cross-validation can support the transparency and credibility of such evaluations. We describe the new IPECAD open-source model framework (version 2) for the health-economic evaluation of early AD treatment and use it for cross-validation and addressing uncertainty. METHODS: A cohort state transition model using a categorized composite domain (cognition and function) was developed by replicating an existing reference model and testing it for internal validity. Then, features of existing "ICER" and "AD-ACE" models assessing lecanemab treatment were implemented for model cross-validation. Additional uncertainty scenarios were performed on choice of efficacy outcome from trial, natural disease progression, treatment effect waning and stopping rules, and other methodological choices. The model is available open-source as R code, spreadsheet and web-based version via https://github.com/ronhandels/IPECAD. RESULTS: In the IPECAD model incremental life years, QALY gains and cost savings were 21-31% smaller compared to the ICER model and 36-56% smaller compared to the AD-ACE model. IPECAD model results were particularly sensitive to assumptions on treatment effect waning and stopping rules and choice of efficacy outcome from trial. CONCLUSIONS: We demonstrated the ability of a new IPECAD opens-source model framework for researchers and decision-makers to cross-validate other (HTA submission) models and perform additional uncertainty analyses, setting an example for open science in AD decision modeling and supporting important reimbursement decisions.
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Which properties of a natural scene affect visual search? We consider the alternative hypotheses that low-level statistics, higher-level statistics, semantics, or layout affect search difficulty in natural scenes. Across three experiments (n = 20 each), we used four different backgrounds that preserve distinct scene properties: (a) natural scenes (all experiments); (b) 1/f noise (pink noise, which preserves only low-level statistics and was used in Experiments 1 and 2); (c) textures that preserve low-level and higher-level statistics but not semantics or layout (Experiments 2 and 3); and (d) inverted (upside-down) scenes that preserve statistics and semantics but not layout (Experiment 2). We included "split scenes" that contained different backgrounds left and right of the midline (Experiment 1, natural/noise; Experiment 3, natural/texture). Participants searched for a Gabor patch that occurred at one of six locations (all experiments). Reaction times were faster for targets on noise and slower on inverted images, compared to natural scenes and textures. The N2pc component of the event-related potential, a marker of attentional selection, had a shorter latency and a higher amplitude for targets in noise than for all other backgrounds. The background contralateral to the target had an effect similar to that on the target side: noise led to faster reactions and shorter N2pc latencies than natural scenes, although we observed no difference in N2pc amplitude. There were no interactions between the target side and the non-target side. Together, this shows that-at least when searching simple targets without own semantic content-natural scenes are more effective distractors than noise and that this results from higher-order statistics rather than from semantics or layout.
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Atenção , Estimulação Luminosa , Tempo de Reação , Semântica , Humanos , Atenção/fisiologia , Masculino , Feminino , Adulto Jovem , Adulto , Tempo de Reação/fisiologia , Estimulação Luminosa/métodos , Reconhecimento Visual de Modelos/fisiologia , Eletroencefalografia/métodos , Potenciais Evocados Visuais/fisiologiaAssuntos
Análise Custo-Benefício , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Avaliação da Tecnologia Biomédica , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/economia , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de VidaAssuntos
Anticorpos Monoclonais Humanizados , Teorema de Bayes , Neoplasias , Avaliação da Tecnologia Biomédica , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Análise Custo-BenefícioRESUMO
Drug repurposing faces various challenges that can impede its success. We developed a framework outlining key challenges in drug repurposing to explore when and how health technology assessment (HTA) methods can address them. We identified 20 drug-repurposing challenges across the categories of data access, research and development, collaboration, business case, regulatory and legal challenges. Early incorporation of HTA methods, including literature review, empirical research, stakeholder consultation, health economic evaluation and uncertainty assessment, can help to address these challenges. HTA methods canassess the value proposition of repurposed drugs, inform further research and ultimately help to bring cost-effective repurposed drugs to patients.
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Reposicionamento de Medicamentos , Avaliação da Tecnologia Biomédica , Reposicionamento de Medicamentos/métodos , Avaliação da Tecnologia Biomédica/métodos , Humanos , Análise Custo-BenefícioRESUMO
It is often assumed that rendering an alert signal more salient yields faster responses to this alert. Yet, there might be a trade-off between attracting attention and distracting from task execution. Here we tested this in four behavioral experiments with eye-tracking using an abstract alert-signal paradigm. Participants performed a visual discrimination task (primary task) while occasional alert signals occurred in the visual periphery accompanied by a congruently lateralized tone. Participants had to respond to the alert before proceeding with the primary task. When visual salience (contrast) or auditory salience (tone intensity) of the alert were increased, participants directed their gaze to the alert more quickly. This confirms that more salient alerts attract attention more efficiently. Increasing auditory salience yielded quicker responses for the alert and primary tasks, apparently confirming faster responses altogether. However, increasing visual salience did not yield similar benefits: instead, it increased the time between fixating the alert and responding, as high-salience alerts interfered with alert-task execution. Such task interference by high-salience alert-signals counteracts their more efficient attentional guidance. The design of alert signals must be adapted to a "sweet spot" that optimizes this stimulus-dependent trade-off between maximally rapid attentional orienting and minimal task interference.
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Atenção , Percepção Visual , Humanos , Tempo de Reação/fisiologia , Atenção/fisiologia , Percepção Visual/fisiologia , Registros , Discriminação PsicológicaRESUMO
Background: Artificial intelligence-derived software technologies have been developed that are intended to facilitate the review of computed tomography brain scans in patients with suspected stroke. Objectives: To evaluate the clinical and cost-effectiveness of using artificial intelligence-derived software to support review of computed tomography brain scans in acute stroke in the National Health Service setting. Methods: Twenty-five databases were searched to July 2021. The review process included measures to minimise error and bias. Results were summarised by research question, artificial intelligence-derived software technology and study type. The health economic analysis focused on the addition of artificial intelligence-derived software-assisted review of computed tomography angiography brain scans for guiding mechanical thrombectomy treatment decisions for people with an ischaemic stroke. The de novo model (developed in R Shiny, R Foundation for Statistical Computing, Vienna, Austria) consisted of a decision tree (short-term) and a state transition model (long-term) to calculate the mean expected costs and quality-adjusted life-years for people with ischaemic stroke and suspected large-vessel occlusion comparing artificial intelligence-derived software-assisted review to usual care. Results: A total of 22 studies (30 publications) were included in the review; 18/22 studies concerned artificial intelligence-derived software for the interpretation of computed tomography angiography to detect large-vessel occlusion. No study evaluated an artificial intelligence-derived software technology used as specified in the inclusion criteria for this assessment. For artificial intelligence-derived software technology alone, sensitivity and specificity estimates for proximal anterior circulation large-vessel occlusion were 95.4% (95% confidence interval 92.7% to 97.1%) and 79.4% (95% confidence interval 75.8% to 82.6%) for Rapid (iSchemaView, Menlo Park, CA, USA) computed tomography angiography, 91.2% (95% confidence interval 77.0% to 97.0%) and 85.0 (95% confidence interval 64.0% to 94.8%) for Viz LVO (Viz.ai, Inc., San Fransisco, VA, USA) large-vessel occlusion, 83.8% (95% confidence interval 77.3% to 88.7%) and 95.7% (95% confidence interval 91.0% to 98.0%) for Brainomix (Brainomix Ltd, Oxford, UK) e-computed tomography angiography and 98.1% (95% confidence interval 94.5% to 99.3%) and 98.2% (95% confidence interval 95.5% to 99.3%) for Avicenna CINA (Avicenna AI, La Ciotat, France) large-vessel occlusion, based on one study each. These studies were not considered appropriate to inform cost-effectiveness modelling but formed the basis by which the accuracy of artificial intelligence plus human reader could be elicited by expert opinion. Probabilistic analyses based on the expert elicitation to inform the sensitivity of the diagnostic pathway indicated that the addition of artificial intelligence to detect large-vessel occlusion is potentially more effective (quality-adjusted life-year gain of 0.003), more costly (increased costs of £8.61) and cost-effective for willingness-to-pay thresholds of £3380 per quality-adjusted life-year and higher. Limitations and conclusions: The available evidence is not suitable to determine the clinical effectiveness of using artificial intelligence-derived software to support the review of computed tomography brain scans in acute stroke. The economic analyses did not provide evidence to prefer the artificial intelligence-derived software strategy over current clinical practice. However, results indicated that if the addition of artificial intelligence-derived software-assisted review for guiding mechanical thrombectomy treatment decisions increased the sensitivity of the diagnostic pathway (i.e. reduced the proportion of undetected large-vessel occlusions), this may be considered cost-effective. Future work: Large, preferably multicentre, studies are needed (for all artificial intelligence-derived software technologies) that evaluate these technologies as they would be implemented in clinical practice. Study registration: This study is registered as PROSPERO CRD42021269609. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR133836) and is published in full in Health Technology Assessment; Vol. 28, No. 11. See the NIHR Funding and Awards website for further award information.
Stroke is a serious life-threatening medical condition caused by a blood clot or haemorrhage in the brain. Quick and effective management, including a brain scan, of the patients with suspected stroke can make a big difference in their outcome. Artificial intelligence-derived computer programmes exist that are intended to help with the interpretation of computed tomography scans of the brain in stroke. We undertook a thorough review of the existing research into the effectiveness and value for money of using these programmes to help doctors and other specialists to interpret computed tomography brain scans. We found very little evidence to tell us how well artificial intelligence-derived computer programmes work in practice. Some studies have looked at artificial intelligence-derived computer programmes on their own (i.e. not taken together with a doctor's judgement, as they were designed to be used). Other studies have looked at what happens to patients who are treated for stroke when artificial intelligence-derived computer programmes are used; these studies provide no information about whether using artificial intelligence-derived computer programmes may have led to patients who could have benefitted from treatment being missed. It is unclear how well artificial intelligence-derived software-assisted review works when added to current clinical practice.
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Inteligência Artificial , Análise Custo-Benefício , Anos de Vida Ajustados por Qualidade de Vida , Acidente Vascular Cerebral , Avaliação da Tecnologia Biomédica , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/economia , Acidente Vascular Cerebral/diagnóstico por imagem , Algoritmos , Software , Encéfalo/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/economia , Análise de Custo-EfetividadeRESUMO
The auditory system has an amazing ability to rapidly encode auditory regularities. Evidence comes from the popular oddball paradigm, in which frequent (standard) sounds are occasionally exchanged for rare deviant sounds, which then elicit signs of prediction error based on their unexpectedness (e.g., MMN and P3a). Here, we examine the widely neglected characteristics of deviants being bearers of predictive information themselves; naive participants listened to sound sequences constructed according to a new, modified version of the oddball paradigm including two types of deviants that followed diametrically opposed rules: one deviant sound occurred mostly in pairs (repetition rule), the other deviant sound occurred mostly in isolation (non-repetition rule). Due to this manipulation, the sound following a first deviant (either the same deviant or a standard) was either predictable or unpredictable based on its conditional probability associated with the preceding deviant sound. Our behavioral results from an active deviant detection task replicate previous findings that deviant repetition rules (based on conditional probability) can be extracted when behaviorally relevant. Our electrophysiological findings obtained in a passive listening setting indicate that conditional probability also translates into differential processing at the P3a level. However, MMN was confined to global deviants and was not sensitive to conditional probability. This suggests that higher-level processing concerned with stimulus selection and/or evaluation (reflected in P3a) but not lower-level sensory processing (reflected in MMN) considers rarely encountered rules.
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Percepção Auditiva , Eletroencefalografia , Potenciais Evocados P300 , Potenciais Evocados Auditivos , Humanos , Feminino , Masculino , Adulto Jovem , Potenciais Evocados P300/fisiologia , Adulto , Percepção Auditiva/fisiologia , Potenciais Evocados Auditivos/fisiologia , Estimulação AcústicaRESUMO
There are sounds that most people perceive as highly unpleasant, for instance, the sound of rubbing pieces of polystyrene together. Previous research showed larger physiological and neural responses for such aversive compared to neutral sounds. Hitherto, it remains unclear whether habituation, i.e., diminished responses to repeated stimulus presentation, which is typically reported for neutral sounds, occurs to the same extent for aversive stimuli. We measured the mismatch negativity (MMN) in response to rare occurrences of aversive or neutral deviant sounds within an auditory oddball sequence in 24 healthy participants, while they performed a demanding visual distractor task. Deviants occurred as single events (i.e., between two standards) or as double deviants (i.e., repeating the identical deviant sound in two consecutive trials). All deviants elicited a clear MMN, and amplitudes were larger for aversive than for neutral deviants (irrespective of their position within a deviant pair). This supports the claim of preattentive emotion evaluation during early auditory processing. In contrast to our expectations, MMN amplitudes did not show habituation, but increased in response to deviant repetition-similarly for aversive and neutral deviants. A more fine-grained analysis of individual MMN amplitudes in relation to individual arousal and valence ratings of each sound item revealed that stimulus-specific MMN amplitudes were best predicted by the interaction of deviant position and perceived arousal, but not by valence. Deviants with perceived higher arousal elicited larger MMN amplitudes only at the first deviant position, indicating that the MMN reflects preattentive processing of the emotional content of sounds.
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Eletroencefalografia , Potenciais Evocados Auditivos , Humanos , Potenciais Evocados Auditivos/fisiologia , Habituação Psicofisiológica , Percepção Auditiva/fisiologia , Som , Estimulação AcústicaRESUMO
Detection of repeating patterns within continuous sound streams is crucial for efficient auditory perception. Previous studies demonstrated a remarkable sensitivity of the human auditory system to periodic repetitions in unfamiliar, meaningless sounds. Automatic repetition detection was reflected in different EEG markers, including sustained activity, neural synchronisation, and event-related responses to pattern occurrences. The current study investigated how listeners' attention and the temporal regularity of a sound modulate repetition perception, and how this influence is reflected in different EEG markers that were previously suggested to subserve dissociable functions. We reanalysed data of a previous study in which listeners were presented with sequences of unfamiliar artificial sounds that either contained repetitions of a certain sound segment or not. Repeating patterns occurred either regularly or with a temporal jitter within the sequences, and participants' attention was directed either towards the pattern repetitions or away from the auditory stimulation. Across both regular and jittered sequences during both attention and in-attention, pattern repetitions led to increased sustained activity throughout the sequence, evoked a characteristic positivity-negativity complex in the event-related potential, and enhanced inter-trial phase coherence of low-frequency oscillatory activity time-locked to repeating pattern onsets. While regularity only had a minor (if any) influence, attention significantly strengthened pattern repetition perception, which was consistently reflected in all three EEG markers. These findings suggest that the detection of pattern repetitions within continuous sounds relies on a flexible mechanism that is robust against in-attention and temporal irregularity, both of which typically occur in naturalistic listening situations. Yet, attention to the auditory input can enhance processing of repeating patterns and improve repetition detection.
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Percepção Auditiva , Som , Humanos , Percepção Auditiva/fisiologia , Estimulação Acústica , Potenciais Evocados , Acústica , Potenciais Evocados Auditivos/fisiologia , EletroencefalografiaRESUMO
The human auditory system is believed to represent regularities inherent in auditory information in internal models. Sounds not matching the standard regularity (deviants) elicit prediction error, alerting the system to information not explainable within currently active models. Here, we examine the widely neglected characteristic of deviants bearing predictive information themselves. In a modified version of the oddball paradigm, using higher-order regularities, we set up different expectations regarding the sound following a deviant. Higher-order regularities were defined by the relation of pitch within tone pairs (rather than absolute pitch of individual tones). In a deviant detection task participants listened to oddball sequences including two deviant types following diametrically opposed rules: one occurred mostly in succession (high repetition probability) and the other mostly in isolation (low repetition probability). Participants in Experiment 1 were not informed (naïve), whereas in Experiment 2 they were made aware of the repetition rules. Response times significantly decreased from first to second deviant when repetition probability was high-albeit more in the presence of explicit rule knowledge. There was no evidence of a facilitation effect when repetition probability was low. Significantly more false alarms occurred in response to standards following high compared with low repetition probability deviants, but only in participants aware of the repetition rules. These findings provide evidence that not only deviants violating lower- but also higher-order regularities can inform predictions about auditory events. More generally, they confirm the utility of this new paradigm to gather further insights into the predictive properties of the human brain.
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Eletroencefalografia , Potenciais Evocados Auditivos , Humanos , Potenciais Evocados Auditivos/fisiologia , Estimulação Acústica , Som , Encéfalo/fisiologiaRESUMO
OBJECTIVE: To demonstrate the value of diagnosing axSpA, by comparing health and costs associated with available diagnostic algorithms and perfect diagnosis. METHODS: Using data from SPACE and other cohorts, a model was developed to estimate health (quality-adjusted life-years, QALYs) and costs (healthcare consumption and work productivity losses) of different diagnostic algorithms for axSpA amongst patients with low back pain referred to a rheumatologist, over a 60-year horizon. The model combined a decision-tree (diagnosis) with a state-transition model (treatment). The three algorithms (Berlin [BER, highest specificity], Modification 1 [M1; less strict inflammatory back pain (IBP) criterion] and Modification 2 [M2; IBP not mandatory as entry criterion, highest sensitivity]) were compared. Changes in sensitivity/specificity were explored and the value of perfect diagnosis was investigated. RESULTS: For each correctly diagnosed axSpA patient, up to 4.7 QALYs and 60,000 could be gained/saved, considering a societal perspective. Algorithm M2 resulted in more health and lower costs per patient (24.23 QALYs; 157,469), compared to BER (23.96 QALYs; 159,423) and M1 (24.15 QALYs; 158,417). Hypothetical improvements in M2 sensitivity resulted in slightly more value compared to improvements in specificity. Perfect diagnosis can cost 7,500 per patient and still provide enough value. CONCLUSION: Correct diagnosis of axSpA results in substantial health and cost benefits for patients and society. Not requiring IBP as mandatory for diagnosis of axSpA (algorithm M2) provides more value and would be preferable. A considerably more expensive diagnostic algorithm with better accuracy than M2 would still be considered good value for money.
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Espondiloartrite Axial , Dor Lombar , Espondilartrite , Humanos , Espondilartrite/diagnóstico , Espondilartrite/complicações , Dor Lombar/diagnóstico , Sensibilidade e Especificidade , AlgoritmosRESUMO
OBJECTIVES: Although the ISPOR Value of Information (VOI) Task Force's reports outline VOI concepts and provide good-practice recommendations, there is no guidance for reporting VOI analyses. VOI analyses are usually performed alongside economic evaluations for which the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 Statement provides reporting guidelines. Thus, we developed the CHEERS-VOI checklist to provide reporting guidance and checklist to support the transparent, reproducible, and high-quality reporting of VOI analyses. METHODS: A comprehensive literature review generated a list of 26 candidate reporting items. These candidate items underwent a Delphi procedure with Delphi participants through 3 survey rounds. Participants rated each item on a 9-point Likert scale to indicate its relevance when reporting the minimal, essential information about VOI methods and provided comments. The Delphi results were reviewed at 2-day consensus meetings and the checklist was finalized using anonymous voting. RESULTS: We had 30, 25, and 24 Delphi respondents in rounds 1, 2, and 3, respectively. After incorporating revisions recommended by the Delphi participants, all 26 candidate items proceeded to the 2-day consensus meetings. The final CHEERS-VOI checklist includes all CHEERS items, but 7 items require elaboration when reporting VOI. Further, 6 new items were added to report information relevant only to VOI (eg, VOI methods applied). CONCLUSIONS: The CHEERS-VOI checklist should be used when a VOI analysis is performed alongside economic evaluations. The CHEERS-VOI checklist will help decision makers, analysts and peer reviewers in the assessment and interpretation of VOI analyses and thereby increase transparency and rigor in decision making.
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Lista de Checagem , Relatório de Pesquisa , Humanos , Análise Custo-Benefício , Padrões de Referência , ConsensoRESUMO
The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Celgene) of oral azacitidine (ONUREG), as part of the Single Technology Appraisal (STA) process, to submit evidence for the clinical effectiveness and cost-effectiveness of oral azacitidine for maintenance treatment of acute myeloid leukaemia (AML) after induction therapy compared with watch-and-wait plus best supportive care (BSC) and midostaurin. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarises the company submission (CS), presents the ERG's critical review on the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations and describes the development of the NICE guidance by the Appraisal Committee. In the QUAZAR AML-001 trial, oral azacitidine significantly improved overall survival (OS) versus placebo: median OS gain of 9.9 months (24.7 months versus 14.8 months; hazard ratio (HR) 0.69 (95% CI 0.55-0.86), p < 0.001). The median time to relapse was also better for oral azacitidine, and the incidences of TEAEs were similar for the two arms. The company excluded two of the comparators listed in the scope, low-dose cytarabine and subcutaneous azacitidine, informed only by clinical expert opinion, leaving only best supportive care (BSC) and midostaurin for the FLT3-ITD and/or FLT3-TKD (FLT3 mutation)-positive subgroup. An ITC comparing oral azacitidine to midostaurin as maintenance therapy in the appropriate subgroup demonstrated that the OS and relapse-free survival (RFS) HRs were favourable for oral azacitidine when compared with midostaurin. However, in the only available trial of midostaurin as maintenance treatment in AML that was used for this ITC, subjects were not randomised at the maintenance phase, but at induction, which posed a substantial risk of bias. The revised and final probabilistic incremental cost-effectiveness ratio (ICER) presented by the company, including a commercial arrangement, was £32,480 per quality-adjusted life year (QALY) gained for oral azacitidine versus watch-and-wait plus BSC. Oral azacitidine was dominant versus midostaurin in the FLT-3 subgroup. The ERG's concerns included the approach of modelling haematopoietic stem cell transplantation (HSCT), the generalisability of the population and the number of cycles of consolidation therapy pre-treatment in the QUAZAR AML-001 trial to UK clinical practice, and uncertainty in the relapse utility. The revised and final ERG base case resulted in a similar probabilistic ICER of £33,830 per QALY gained versus watch-and-wait plus BSC, but with remaining uncertainty. Oral azacitidine remained dominant versus midostaurin in the FLT-3 subgroup. After the second NICE appraisal committee meeting, the NICE Appraisal Committee recommended oral azacitidine (according to the commercial arrangement), within its marketing authorisation, as an option for maintenance treatment for AML in adults who are in complete remission, or complete remission with incomplete blood count recovery, after induction therapy with or without consolidation treatment, and cannot have or do not want HSCT.
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Quimioterapia de Indução , Leucemia Mieloide Aguda , Adulto , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Azacitidina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Análise Custo-Benefício , Avaliação da Tecnologia Biomédica/métodos , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Perceptual learning is a powerful mechanism to enhance perceptual abilities and to form robust memory representations of previously unfamiliar sounds. Memory formation through repeated exposure takes place even for random and complex acoustic patterns devoid of semantic content. The current study sought to scrutinise how perceptual learning of random acoustic patterns is shaped by two potential modulators: temporal regularity of pattern repetition and listeners' attention. To this end, we adapted an established implicit learning paradigm and presented short acoustic sequences that could contain embedded repetitions of a certain sound segment (i.e., pattern) or not. During each experimental block, one repeating pattern recurred across multiple trials, whereas the other patterns were presented in only one trial. During the presentation of sound sequences that contained either temporally regular or jittered within-trial pattern repetitions, participants' attention was directed either towards or away from the auditory stimulation. Overall, we found a memory-related modulation of the event-related potential (ERP) and an increase in inter-trial phase coherence for patterns that recurred across multiple trials (compared to non-recurring patterns), accompanied by a performance increase in a (within-trial) repetition detection task when listeners attended the sounds. Remarkably, we show a memory-related ERP effect even for the first pattern occurrence per sequence when participants attended the sounds, but not when they were engaged in a visual distractor task. These findings suggest that learning of unfamiliar sound patterns is robust against temporal irregularity and inattention, but attention facilitates access to established memory representations upon first occurrence within a sequence.
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Atenção , Aprendizagem , Humanos , Aprendizagem/fisiologia , Atenção/fisiologia , Potenciais Evocados , Acústica , Som , Estimulação Acústica , Percepção Auditiva/fisiologiaRESUMO
Uncertainty assessment is a cornerstone in model-based health economic evaluations (HEEs) that inform reimbursement decisions. No comprehensive overview of available uncertainty assessment methods currently exists. We aimed to review methods for uncertainty assessment for use in model-based HEEs, by conducting a snowballing review. We categorised all methods according to their stage of use relating to uncertainty assessment (identification, analysis, communication). Additionally, we classified identification methods according to sources of uncertainty, and subdivided analysis and communication methods according to their purpose. The review identified a total of 80 uncertainty methods: 30 identification, 28 analysis, and 22 communication methods. Uncertainty identification methods exist to address uncertainty from different sources. Most identification methods were developed with the objective to assess related concepts such as validity, model quality, and relevance. Almost all uncertainty analysis and communication methods required uncertainty to be quantified and inclusion of uncertainties in probabilistic analysis. Our review can help analysts and decision makers in selecting uncertainty assessment methods according to their aim and purpose of the assessment. We noted a need for further clarification of terminology and guidance on the use of (combinations of) methods to identify uncertainty and related concepts such as validity and quality. A key finding is that uncertainty assessment relies heavily on quantification, which may necessitate increased use of expert elicitation and/or the development of methods to assess unquantified uncertainty.