Do large language models show decision heuristics similar to humans? A case study using GPT-3.5.

A Large Language Model (LLM) is an artificial intelligence system trained on vast amounts of natural language data, enabling it to generate human-like responses to written or spoken language input. Generative Pre-Trained Transformer (GPT)-3.5 is an example of an LLM that supports a conversational agent called ChatGPT. In this work, we used a series of novel prompts to determine whether ChatGPT shows heuristics and other context-sensitive responses. We also tested the same prompts on human participants. Across four studies, we found that ChatGPT was influenced by random anchors in making estimates (anchoring, Study 1); it judged the likelihood of two events occurring together to be higher than the likelihood of either event occurring alone, and it was influenced by anecdotal information (representativeness and availability heuristic, Study 2); it found an item to be more efficacious when its features were presented positively rather than negatively-even though both presentations contained statistically equivalent information (framing effect, Study 3); and it valued an owned item more than a newly found item even though the two items were objectively identical (endowment effect, Study 4). In each study, human participants showed similar effects. Heuristics and context-sensitive responses in humans are thought to be driven by cognitive and affective processes such as loss aversion and effort reduction. The fact that an LLM-which lacks these processes-also shows such responses invites consideration of the possibility that language is sufficiently rich to carry these effects and may play a role in generating these effects in humans. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Real-world outcomes in patients with KRAS G12C-mutated advanced non-small cell lung cancer treated with docetaxel in second-line or beyond.

INTRODUCTION: The KRAS G12C mutation has recently become a druggable target in non-small cell lung cancer (NSCLC). In this observational study, we present real-world clinicopathological characteristics, treatment patterns, and survival outcomes data in patients with KRAS mutation-positive advanced NSCLC (aNSCLC), including those with KRAS G12C and KRAS non-G12C mutations, who received docetaxel as standard-of-care treatment in the second-line and beyond (2L+). METHODS: US-based electronic health record-derived de-identified databases were used to assess clinicopathological characteristics and outcomes in adult aNSCLC patients with KRAS mutations treated with 2L+ docetaxel between January 1, 2011, and March 31, 2021. The primary endpoints were median real-world overall survival OS (rwOS) and median real-world progression-free survival (rwPFS), which were estimated in 2L, third-line, fourth-line, and 2L+ analysis sets among patients who had a 6-month minimum opportunity for follow-up and were not taking a clinical trial drug. RESULTS: Of the 677 patients with KRAS-mutant aNSCLC (KRAS mutant cohort) treated with 2L+ docetaxel, 295 (43.6%) had KRAS G12C mutation (KRAS G12C cohort) and 382 (56.4%) had KRAS non-G12C mutation (KRAS non-G12C cohort). Across all cohorts, approximately 47%, 35%, 14-15%, and 6-9% of patients received 2L, third-line, fourth-line, and fifth- or later-line docetaxel, respectively. In the KRAS G12C cohort, ∼68% of patients were treated with a PD-1/PD-L1 inhibitor prior to 2L+ docetaxel. Most 2L+ docetaxel regimens in the KRAS G12C cohort were combinations (59.5%), primarily with ramucirumab (45.2%). In the KRAS G12C cohort, the median rwOS and median rwPFS after 2L+ docetaxel were 6.0 (95% CI, 4.9-7.1) and 3.4 (95% CI, 2.7-4.2) months, respectively, with similar trends observed in other cohorts and lines of therapy. CONCLUSIONS: Real-world outcomes were poor in patients with KRAS G12C-mutated aNSCLC treated with 2L+ docetaxel. Targeted and more efficacious treatment options in these patients are warranted.

Stereotypes disrupt probabilistic category learning.

Racial stereotypes exert pernicious effects on decision-making and behavior, yet little is known about how stereotypes disrupt people's ability to learn new associations. The current research interrogates a fundamental question about the boundary conditions of probabilistic learning by examining whether and how learning is influenced by preexisting associations. Across three experiments, participants learned the probabilistic outcomes of different card combinations based on feedback in either a social (e.g., forecasting crime) or nonsocial (e.g., forecasting weather) learning context. During learning, participants were presented with either task-irrelevant social (i.e., Black or White faces) or nonsocial (i.e., darker or lighter clouds) stimuli that were stereotypically congruent or incongruent with the learning context. Participants exhibited learning disruptions in the social compared to nonsocial learning context, despite repeated instructions that the stimuli were unrelated to the outcome (Studies 1 and 2). We also found no differences in learning disruptions when participants learned in the presence of negatively (Black and criminal) or positively valenced stereotypes (Black and athletic; Study 3). Finally, we tested whether learning decrements were due to "first-order" stereotype application or inhibition at the trial level, or due to "second-order" cognitive load disruptions that accumulate across trials due to fears of appearing prejudiced (aggregated analysis). We found no evidence of first-order disruptions and instead found evidence for second-order disruptions: participants who were more internally motivated to respond without prejudice, and thus more likely to self-monitor their responses, learned less accurately over time. We discuss the implications of the influence of stereotypes on learning and memory. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The role of attention in status quo bias.

In many decision-making contexts, people often persist with their previous selections. This predisposition to choose to maintain a current (or previous) choice is referred to as the status quo bias (SQB). In this work, we propose that increased attention towards the status quo option-enabled by its visual salience-is a previously underappreciated driver of SQB. We base this hypothesis on three propositions: (1) the status quo bias option is often more visually salient relative to the non-status quo options on offer, (2) greater visual salience of an option biases attention towards that option, and (3) increased attention towards an option leads to that option being selected at greater rates. We examined the attention hypothesis among 6,854 participants in four studies. Studies 1 and 2 showed that increasing the visual salience of a non-status quo option (i.e., the type of visual salience often garnered by the status quo option) increased the selection rate of that option. Study 3 directly tested the hypothesis by lessening the visual salience of the status quo option. Doing so eliminated SQB. Study 4 replicated and extended the findings of Study 3 in a real-world decision context. Collectively, these studies suggest that the selection of the status quo may often be related to its salience relative to other available options.

Megastudies improve the impact of applied behavioural science.

Policy-makers are increasingly turning to behavioural science for insights about how to improve citizens' decisions and outcomes1. Typically, different scientists test different intervention ideas in different samples using different outcomes over different time intervals2. The lack of comparability of such individual investigations limits their potential to inform policy. Here, to address this limitation and accelerate the pace of discovery, we introduce the megastudy-a massive field experiment in which the effects of many different interventions are compared in the same population on the same objectively measured outcome for the same duration. In a megastudy targeting physical exercise among 61,293 members of an American fitness chain, 30 scientists from 15 different US universities worked in small independent teams to design a total of 54 different four-week digital programmes (or interventions) encouraging exercise. We show that 45% of these interventions significantly increased weekly gym visits by 9% to 27%; the top-performing intervention offered microrewards for returning to the gym after a missed workout. Only 8% of interventions induced behaviour change that was significant and measurable after the four-week intervention. Conditioning on the 45% of interventions that increased exercise during the intervention, we detected carry-over effects that were proportionally similar to those measured in previous research3-6. Forecasts by impartial judges failed to predict which interventions would be most effective, underscoring the value of testing many ideas at once and, therefore, the potential for megastudies to improve the evidentiary value of behavioural science.

Managing depression in India: Opportunities for a targeted smartphone app.

BACKGROUND: More than forty million people suffer from depression in India. A lack of awareness, stigma related to mental health issues, and limited accessibility to treatment services magnify the profound personal and societal impact of depression. Given the rise of smartphones in India, mobile technology can help alleviate some of these depression-related challenges. AIMS AND METHOD: The aim of this paper is to investigate the essential features of an India targeted depression smartphone app. We conducted an online survey to profile the needs of individuals with depression in India, which varied based on variables such as socioeconomic background, age, level of awareness toward depression, and the extent of exposure to mental health stigma. We also conducted a systematic evaluation of depression apps currently available to Indian users to investigate the user needs that these apps met and the needs that they failed to meet. Based on our findings, we made a set of recommendations related to the essential features of a future app targeted at managing depression in India. RESULTS: Presently available depression apps fall short in providing some significant features such as local language options, content in audio and video formats, and user location matched resources. These gaps make these apps less than fully relevant to a diverse set of Indian users. CONCLUSIONS: It is essential to provide depression-related information in a targeted manner depending upon each user's particular needs and context. Potential customizations, such as offering content in local languages and flexible formats (e.g. audio, video, and text); and providing user-relevant diagnostic tools and location matched treatment resources can help improve the suitability of the app for diverse users.

The burden of skeletal-related events in four Latin American countries: Argentina, Brazil, Colombia, and Mexico.

AIM: Skeletal-related events (SREs) are major bone complications that frequently occur in patients with solid tumors (ST) and bone metastases, and in patients with multiple myeloma (MM). SREs include pathological fracture, spinal cord compression, radiation to bone, and surgery to bone. Limited data are available regarding the burden of SREs in Latin America. We built an economic model to quantify the current and future economic burden of SREs among adults in four Latin American countries: Argentina, Brazil, Colombia, and Mexico. METHODS: A comprehensive literature review with a systematic search strategy was conducted to parameterize the economic burden of illness (BOI) model. Economic analyses were conducted using a prevalence-based model. Aggregate SRE costs obtained from country-specific sources were used. We also included patient productivity losses. Costs were expressed in 2020 USD for the total annual burden, annual burden per 1,000 at risk, and projected five-year burden. RESULTS: The estimated total number of SREs was 251,503 in 2020, amounting to a total annual cost of USD 1.4 billion. The total projected five-year cost was USD 6.9 billion. Annual costs were highest in Brazil (USD 779.1 million), followed by Mexico (USD 281.8 million), Argentina (USD 174.6 million), and Colombia (USD 120.1 million). The average financial burden per 1,000 at risk was greatest in Brazil (USD 3.6 million), followed by Mexico (USD 3.4 million), Colombia (USD 2.9 million), and Argentina (USD 2.7 million). CONCLUSION: Despite recommendations by medical societies for the use of bone-targeted agents in patients with solid tumors and bone metastasis or with multiple myeloma and bone lesions, a large proportion of patients at risk of experiencing SREs are not treated. Early detection of bone metastases and SREs and the use of the most effective preventative treatments are needed to decrease the clinical and economic burden of SREs in Latin America.

Impacto econômico da adoção de denosumabe em pacientes com metástases ósseas ou mieloma múltiplo sob a perspectiva do sistema de saúde privado brasileiro / Economic impact of denosumab adoption in cancer patients with bone metastases or multiple myeloma from the Brazilian private healthcare system's perspective

Objetivo: Estimar o custo por evento relacionado ao esqueleto (ERE) e o impacto econômico anual da adoção de denosumabe em pacientes com metástases ósseas secundárias ao câncer de mama, próstata e outros tumores sólidos ou mieloma múltiplo sob a perspectiva do sistema de saúde privado brasileiro. Métodos: Um modelo econômico foi desenvolvido para comparar os custos relacionados com denosumabe versus ácido zoledrônico na prevenção de EREs. O modelo incluiu os seguintes custos: medicamento, administração, monitoramento e manejo de ERE. O custo anual foi apresentado em reais (BRL) para 100 pacientes. Os custos do manejo de ERE [fratura vertebral (FV), fratura não vertebral (FNV), radiação óssea (RO), cirurgia óssea (CO) e compressão da medula espinhal (CME)] foram estimados a partir dos recursos e procedimentos coletados da revisão de literatura, bases de dados e painel Delphi. Dados coletados dos estudos clínicos randomizados relacionados com cada tipo de tumor na análise e de um estudo prospectivo observacional foram utilizados para estimar a eficácia clínica de denosumabe versus ácido zoledrônico. Resultados: O custo por cada tipo de ERE variou de BRL 27.246 a BRL 28.035 para FV, BRL 18.023 a BRL 18.811 para FNV, BRL 42.750 a BRL 43.538 para RO, BRL 18.023 a BRL 18.811 para CO e BRL 12.472 a BRL 13.260 para CME. A introdução de denosumabe foi estimada em economia anual por 100 pacientes de até BRL 1.072.043,14 para câncer de mama, BRL 1.212.822,79 para outros tumores sólidos, BRL 1.929.660,67 para câncer de próstata e BRL 77.965,07 para mieloma múltiplo. Conclusão: Esta análise sugere que EREs adicionam custos substanciais no manejo de pacientes com metástases ósseas. Dessa forma, o uso de denosumabe pode prevenir e retardar EREs em pacientes com câncer e pode possivelmente levar à redução do impacto econômico associado aos EREs sob a perspectiva dos pagadores de saúde privada brasileira.

Objective: To estimate the cost per SRE and annual economic impact of denosumab adoption in patients with bone metastases (BM) secondary to breast cancer, prostate cancer, other solid tumors or multiple myeloma from the Brazilian private healthcare system's perspective. Methods: An economic model was developed to compare the cost outcomes associated with denosumab instead of zoledronic acid for SRE prevention. The model included the following costs: drug, administration, monitoring and SRE management. Annual costs per 100 patients were reported in 2019 Brazilian currency (BRL). The SRE management costs (vertebral fracture (VF), non-vertebral fracture (NVF), radiation to bone (RB), surgery to bone (SB) and spinal cord compression (SCC)) were estimated from the resources and procedures collected from literature review, official database, and a Delphi panel. Data collected from randomized clinical trials related to each tumor type in the analysis and from a prospective observational study was used to estimate the clinical efficacy of denosumab vs zoledronic acid. Results: The cost per each type of SREs across all tumors ranged BRL 27,246 ­ BRL 28,035 for VF, BRL 18,023 ­ BRL 18,811 for NVF, BRL 42,750 ­ BRL 43,538 for RB, BRL 18,023 ­ BRL 18,811 for SB and BRL 12,472 ­ BRL 13,260 for SCC. The introduction of denosumab was estimated to result in annual savings per 100 patients of up to BRL 1,072,043.14 for breast cancer, BRL 1,212,822.79 for other solid tumors, BRL 1,929,660.67 for prostate cancer and BRL 77,965.07 for multiple myeloma. Conclusion: This analysis suggests that SREs add substantial costs to the management of patients with bone metastases. In this way, the use of denosumab would prevent and delay SREs in cancer patients and might possibly lead to reduce the economic burden associated with SREs, borne by Brazilian private healthcare payers.

The neural bases of cognitive emotion regulation: The roles of strategy and intensity.

When confronted with unwanted negative emotions, individuals use a variety of cognitive strategies for regulating these emotions. The brain mechanisms underlying these emotion regulation strategies have not been fully characterized, and it is not yet clear whether these mechanisms vary as a function of emotion intensity. To address these issues, 30 community participants (17 females, 13 males, Mage = 24.3 years) completed a picture-viewing emotion regulation task with neutral viewing, reacting to negative stimuli, cognitive reappraisal, attentional deployment, and self-distancing conditions. Brain and behavioral data were simultaneously collected in a 3T GE MRI scanner. Findings indicated that prefrontal regions were engaged by all three regulation strategies, but reappraisal showed the least amount of increase in activity as a function of intensity. Overall, these results suggest that there are both brain and behavioral effects of intensity and that intensity is useful for probing strategy-specific effects and the relationships between the strategies. Furthermore, while these three strategies showed significant overlap, there also were specific strategy-intensity interactions, such as frontoparietal control regions being preferentially activated by reappraisal and self-distancing. Conversely, self-referential and attentional regions were preferentially recruited by self-distancing and distraction as intensity increased. Overall, these findings are consistent with the notion that there is a continuum of cognitive emotion regulation along which all three of these strategies lie.

Value-based decision making: An interactive activation perspective.

Prominent theories of value-based decision making have assumed that choices are made via the maximization of some objective function (e.g., expected value) and that the process of decision making is serial and unfolds across modular subprocesses (e.g., perception, valuation, and action selection). However, the influence of a large number of contextual variables that are not related to expected value in any direct way and the ubiquitous reciprocity among variables thought to belong to different subprocesses suggest that these assumptions may not always hold. Here, we propose an interactive activation framework for value-based decision making that does not assume that objective function maximization is the only consideration affecting choice or that processing is modular or serial. Our framework holds that processing takes place via the interactive propagation of activation in a set of simple, interconnected processing elements. We use our framework to simulate a broad range of well-known empirical phenomena-primarily focusing on decision contexts that feature nonoptimal decision making and/or interactive (i.e., not serial or modular) processing. Our approach is constrained at Marr's (1982) algorithmic and implementational levels rather than focusing strictly on considerations of optimality at the computational theory level. It invites consideration of the possibility that choice is emergent and that its computation is distributed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Emotion regulation choice: a broad examination of external factors.

Emotion regulation choices are known to be profoundly consequential across affective, cognitive, and social domains. Prior studies have identified two important external factors of emotion regulation choice: stimulus intensity and reappraisal affordances. However, whether there are other external factors of emotion regulation choice and how these factors contribute to emotion regulation choice when considered simultaneously is not yet clear. The current studies addressed these gaps by examining the relations between emotion regulation choice (distraction vs. reappraisal) and self-reported stimulus intensity, reappraisal affordances, and several other factors including discrete emotions and distraction affordances. Across three studies using different databases of standardised images to enhance generalizability, our results showed that in the context of our experiments, reappraisal affordances were strongly associated with emotion regulation choice (greater reappraisal affordances predicted higher use of reappraisal). Further, stimulus intensity was independently associated with emotion regulation choice in each study. Our results also demonstrated that the discrete emotion of disgust (but not other discrete emotions) is a previously unidentified external factor of emotion regulation choice. We discuss the implications of the current findings.

The role of reappraisal success in emotional and memory outcomes.

Cognitive reappraisal is an emotion regulation strategy that involves reinterpreting the meaning of an event or its outcome to change its emotional trajectory. In this study, we examined how cognitive reappraisal affects both emotional experience and memory outcomes. We also examined whether these outcomes are modulated by participants' self-reported success at generating reappraisals. To do this, we asked participants to use situation-focused reappraisals to decrease their emotional response to some negative images and to passively view other negative images while facial electromyography (EMG) was recorded. After each trial, participants rated the image's emotional valence and arousal. During reappraisal trials, participants also self-reported their success in generating a reappraisal. One week later, memory was assessed with a surprise free recall test followed by a recognition test. Compared with images that were passively viewed, participants (N = 42) rated the successfully reappraised images as lower in arousal and less negative in valence. Meanwhile, there was an emotional cost associated with failures to generate reappraisals; participants rated these images as higher in arousal and more negative in valence. No similar effects emerged for the EMG ratings. In contrast to these emotional outcomes, a different pattern emerged for the memory outcomes. Instructions to reappraise led to enhanced recall and recognition and to greater memory confidence regardless of whether or not participants successfully generated the reappraisals. Taken together, these results suggest that trying, but failing, to generate a situation-focused cognitive reappraisal may be detrimental. In these situations, people feel worse but remember the situation well. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The regulation of recurrent negative emotion in the aftermath of a lost election.

For some American voters, the news of Mr. Trump's victory in the 2016 presidential election caused recurrent emotions that were negative, persistent, and intense enough to elicit repeated attempts at emotion regulation. This afforded a rare opportunity to analyse the regulation of recurrent emotions in a natural, non-laboratory context. The regulation of recurrent emotion involves additional considerations relative to single-instance emotion, such as representations of past and future encounters with the emotion-eliciting variables, ongoing consequences of each regulatory episode, and a tendency to repeatedly deploy emotion regulation strategies that one is most familiar with in the context of the particular recurrent emotion. Despite the ubiquitous nature of recurrent emotions, its associated regulatory processes have been infrequently examined and are not well-understood. Over eight days (11/10/16-11/18/16), we administered four surveys to 202 participants who voted against Mr. Trump. We examined the determinants and outcomes of regulatory strategies in the context of recurrent emotion. We found that (1) reappraisal (compared to distraction and acceptance) was associated with greater decline in emotion intensity, (2) high-intensity emotions were more likely to be distracted, whereas low-intensity emotions were more likely to be reappraised, and (3) strategy variability was associated with greater affective adaptation.

Cost-effectiveness analysis of ribociclib plus letrozole versus palbociclib plus letrozole in the United Kingdom.

OBJECTIVE: To evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole in post-menopausal women with hormone receptor positive (HR+) and human epidermal growth receptor 2 negative (HER2-) advanced breast cancer from a UK payer perspective. METHODS: A cohort-based partitioned survival model was developed to evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole in post-menopausal women with HR+/HER2- advanced breast cancer over a lifetime horizon. The analysis was carried out from a National Health Services and Personal Social Services perspective, and results are presented in incremental costs per quality adjusted life years. Clinical data from three randomized controlled trials (MONALEESA-2, PALOMA-1 and PALOMA-2 studies) were used, and supplemented with available real world evidence. Costs categories comprised of drug acquisition, medical management, and treatment of adverse events. Healthcare resource utilization data were identified from literature and unit costs sourced from secondary sources. Utility values were derived from MONALEESA-2 study and were supported with values identified from literature. Both deterministic and probabilistic analyses were carried out to assess uncertainty. RESULTS: In the base case, treatment with ribociclib plus letrozole increased mean progression free survival (PFS) by 4.1 months and overall survival by 5.0 months compared to palbociclib plus letrozole. Further, treatment with ribociclib plus letrozole resulted in cost-savings of £8464 and incremental QALYs of 0.261, demonstrating that treatment with ribociclib plus letrozole is dominant to treatment with palbociclib plus letrozole. The probabilistic analysis also yielded mean cost-savings of £7914 and mean QALY gain of 0.273. At willingness-to-pay threshold of £30 000 per QALY, treatment with ribociclib plus letrozole had a 92% probability of being cost-effective compared to palbociclib and letrozole. CONCLUSIONS: The results of the analysis demonstrate that ribociclib plus letrozole treatment is both cost-saving and a cost-effective option amongst the available cyclin dependent kinase 4/6 inhibitors for the treatment of post-menopausal women with advanced breast cancer. The biggest driver of the cost savings were the lower acquisition costs of ribociclib.

To reappraise or not to reappraise? Emotion regulation choice and cognitive energetics.

Research shows that cognitive reappraisal is an effective emotion regulation (ER) strategy that often has clear benefits. Yet, surprisingly, recent findings demonstrate that people use cognitive reappraisal less frequently than might be expected (Suri, Whittaker, & Gross, 2015). We employ cognitive energetics theory (CET) to explain this puzzling behavior. CET posits that the likelihood of launching any cognitive process is a function of two opposing forces: the driving force (i.e., the motivation to launch the process) and the restraining force (i.e., task difficulty). We thus hypothesized that people choose to use cognitive reappraisal relatively rarely because of the difficulty of implementing it. We also postulated that the decision to reappraise (or not) does not simply depend on stimuli emotional intensity because the latter is associated with both the driving and the restraining forces. In support of our hypotheses, we found that when the images' emotional intensity posed difficulty for reappraisal (i.e., highly intense images), reducing this difficulty by asking participants to merely predict others' (Study 1) or their own choices (Study 2) increased reappraisal choice. Finally, in Study 3, we show that a relatively easy to implement reappraisal strategy was chosen more often than the more difficult one for high (but not low) intensity images. These findings illustrate the relevance of a CET-based motivational analysis to emotion regulation choice. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Budget impact of including ribociclib in combination with letrozole on US payer formulary: first-line treatment of post-menopausal women with HR+/HER2- advanced or metastatic breast cancer.

OBJECTIVES: The combination of a cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor with the aromatase inhibitor letrozole is a safe and effective alternative to letrozole monotherapy for first-line hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This study evaluates the budget impact of using the CDK 4/6 inhibitor ribociclib plus letrozole as a first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer, from a United States (US) payer perspective. METHODS: A cohort-based budget impact model was used to calculate the incremental cost of introducing ribociclib plus letrozole over three years for the target population. The analysis compared two scenarios: treatment options excluding or including ribociclib plus letrozole. Market shares were derived from market research and the assumption was the introduction of ribociclib plus letrozole would only displace existing CDK-based therapies. Treatment duration was based on the median time to treatment discontinuation or median progression-free survival for first-line treatment, and on clinical trial data for second- and third-line treatment. Acquisition costs were based on wholesale acquisition costs and considered co-payment. Costs for drug administration and monitoring, subsequent therapy, and relevant adverse events were included. RESULTS: Of 1 million insured members, 263 were eligible for CDK 4/6 inhibitor treatment. Cumulative total savings with ribociclib plus letrozole were $3.01M over three years, corresponding to a cumulative incremental cost saving of $318.11 per member treated per month. CONCLUSIONS: In the US, ribociclib plus letrozole represents a cost-saving first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer.

Cost-Effectiveness of Ribociclib plus Letrozole Versus Palbociclib plus Letrozole and Letrozole Monotherapy in the First-Line Treatment of Postmenopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer: A U.S. Payer Perspective.

BACKGROUND: U.S. regulatory approvals of the cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors ribociclib and palbociclib as add-ons to letrozole greatly enhance the prospects for treating postmenopausal women with hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer. Clinical trials have established that the combination of a CDK 4/6 inhibitor with letrozole can significantly improve progression-free survival (PFS) versus letrozole monotherapy and is safe and well tolerated. Cost-effectiveness studies are required to inform payers and clinical decision makers on the money value of combination treatment in clinical practice. OBJECTIVE: To evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole and versus letrozole monotherapy in the first-line treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer from a U.S. private third-party payer perspective. METHODS: A partitioned survival model including 3 health states (progression free, with either overall response or stable disease; progressed disease; and death) simulated lifetime costs and outcomes over a 40-year lifetime horizon with a 1-month cycle length. Clinical efficacy data (PFS and overall survival [OS]) were derived from a phase III trial of ribociclib plus letrozole (MONALEESA-2; NCT01958021), a phase II trial of palbociclib plus letrozole (PALOMA-1; NCT00721409), and a Bayesian network meta-analysis. Health care costs included drug acquisition and monitoring, disease management, subsequent therapies, and serious drug-related adverse events. Effectiveness was measured in life-years, derived from survival projections, and in quality-adjusted life-years (QALYs), calculated from time spent in each state combined with health-state utility values. A one-way deterministic sensitivity analysis explored the impact of uncertainty in key model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis. RESULTS: Ribociclib plus letrozole was dominant versus palbociclib plus letrozole, with a cost saving of $43,037 and a gain of 0.086 QALYs. Compared with letrozole monotherapy, ribociclib plus letrozole was associated with an incremental cost of $144,915 and an incremental QALY of 0.689, equating to an incremental cost-effectiveness ratio of $210,369 per QALY. Key model drivers included OS HRs for palbociclib plus letrozole versus letrozole and for ribociclib plus letrozole versus letrozole, the PFS HR for palbociclib plus letrozole versus letrozole, PD health-state costs, utility of response, and cost discount rate. The probabilities that ribociclib plus letrozole was cost-effective versus letrozole at thresholds of $50,000, $100,000 and $200,000 per QALY gained were 1.6%, 6.3%, and 50.5%, respectively. CONCLUSIONS: In the United States, ribociclib plus letrozole is a cost-effective alternative to palbociclib plus letrozole for the first-line treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer. Ribociclib plus letrozole is also cost-effective versus letrozole monotherapy at willingness-to-pay thresholds greater than $198,000 per QALY (for probabilistic analysis). DISCLOSURES: Funding for this study was provided by Novartis, which manufactures ribociclib and provided input on the study design and data collection, analysis, and interpretation. Mistry, May, Suri, and Young are employees of PAREXEL. Tang, Mishra, D. Bhattacharyya, and Dalal are employees of Novartis. S. Bhattacharyya was an employee of Novartis during the study period. Tang and Dalal hold stock in Novartis. Brixner, Oderda, and Biskupiak were paid by Millcreek Outcomes Group as consultants for work on this project. Brixner has also consulted for AstraZeneca, UCB, Regeneron, and Abbott.

An investigation into the drivers of avolition in schizophrenia.

Over a century of research has documented that avolition is a core symptom in schizophrenia. However, the drivers of avolition remain unclear. Conceptually, there are at least two potential mutually compatible drivers that could cause avolition in schizophrenia. First, people with schizophrenia might have differences in preferences that result in less goal-directed behavior than non-clinical populations (preference-differences). Second, people with schizophrenia might have difficulty translating their preferences into manifest behavior at rates similar to non-clinical populations (psychological-inertia). In the present work, we modified and validated a well-validated paradigm from the motivation/decision making literature to compare levels of preference-differences and psychological-inertia. To measure preference-differences, people with and without schizophrenia choose between a lower-valenced and higher-valenced image. We measured the rate at which the normatively lower-valenced image was preferred. To measure psychological-inertia, both groups were given the opportunity to volitionally switch from a lower-valenced image and view a higher-valenced image. Contrary to expectations, people with schizophrenia did not differ on either preference-differences or psychological-inertia. Statistical analysis revealed that the possibility of a Type II error for even a weak effect was small. The present data suggest new avenues for research investigating mechanisms underlying avolition and clinical interventions targeting avolition in schizophrenia.

Reducing behavioural risk factors for cancer: An affect regulation perspective.

Nearly half of all cancer deaths are attributable to preventable causes, primarily unhealthy behaviours such as tobacco use, alcohol use and overeating. In this review, we argue that people engage in these behaviours, at least in part, as a means of regulating their affective states. To better understand why people engage in these behaviours and how researchers might design interventions to promote the selection of healthier methods for regulating affect, we propose a conceptual model of affect regulation. We synthesise research from both the stress and coping tradition as well as the emotion and emotion regulation tradition, two literatures that are not typically integrated. In so doing, we indicate where researchers have made headway in understanding these behaviours as affect regulation and note how our model could be used to structure future work in a way that would be particularly advantageous to cancer control efforts.

Emotion regulation choice: the role of environmental affordances.

Which emotion regulation strategy one uses in a given context can have profound affective, cognitive, and social consequences. It is therefore important to understand the determinants of emotion regulation choice. Many prior studies have examined person-specific, internal determinants of emotion regulation choice. Recently, it has become clear that external variables that are properties of the stimulus can also influence emotion regulation choice. In the present research, we consider whether reappraisal affordances, defined as the opportunities for re-interpretation of a stimulus that are inherent in that stimulus, can shape individuals' emotion regulation choices. We show that reappraisal affordances have stability across people and across time (Study 1), and are confounded with emotional intensity for a standardised set of picture stimuli (Study 2). Since emotional intensity has been shown to drive emotion regulation choice, we construct a context in which emotional intensity is separable from reappraisal affordances (Study 3) and use this context to show that reappraisal affordances powerfully influence emotion regulation choice even when emotional intensity and discrete emotions are taken into account (Study 4).