Preferences for innovations in healthcare delivery models in the Swiss elderly population: a latent class, choice modelling study.

BACKGROUND: With the increasing number of people affected by multiple chronic conditions, it is essential for public-health professionals to promote strategies addressing patient needs for coordinated care. We aim to explore preference heterogeneity for better-coordinated care delivery models in Swiss older adults, and identify profiles of individuals more open to healthcare reforms. METHODS: A DCE (discrete choice experiment) survey was developed online and on paper for the Swiss adults aged 50+, following best practice. To elicit preferences, we estimated a latent class model allowing grouping individuals with similar preferences into distinct classes, and examined what background characteristics contributed to specific class membership. RESULTS: The optimal model identified three classes with different openness to reforms. Class 1 (49%) members were concerned with premium increases and were in favour of integrated care structures with care managed by interprofessional teams. Individuals in class 2 (19%) were younger, open to reforms, and expressed the needs for radical changes within the Swiss healthcare system. Class 3 respondents (32%) were strongly reluctant to changes. CONCLUSIONS: Our study goes beyond average preferences and identifies three distinct population profiles, a majority open to reforms on specific aspects of care delivery, a smallest group in favour radical changes, and a third strongly against changes. Therefore, tailored approaches around healthcare reforms are needed, e.g. explaining the role of interprofessional teams in coordinating care, electronic health records and insurance premium variation.

Expressed Barcoding Enables High-Resolution Tracking of the Evolution of Drug Tolerance.

For a majority of patients with non-small cell lung cancer with EGFR mutations, treatment with EGFR inhibitors (EGFRi) induces a clinical response. Despite this initial reduction in tumor size, residual disease persists that leads to disease relapse. Elucidating the preexisting biological differences between sensitive cells and surviving drug-tolerant persister cells and deciphering how drug-tolerant cells evolve in response to treatment could help identify strategies to improve the efficacy of EGFRi. In this study, we tracked the origins and clonal evolution of drug-tolerant cells at a high resolution by using an expressed barcoding system coupled with single-cell RNA sequencing. This platform enabled longitudinal profiling of gene expression and drug sensitivity in response to EGFRi across a large number of clones. Drug-tolerant cells had higher expression of key survival pathways such as YAP and EMT at baseline and could also differentially adapt their gene expression following EGFRi treatment compared with sensitive cells. In addition, drug combinations targeting common downstream components (MAPK) or orthogonal factors (chemotherapy) showed greater efficacy than EGFRi alone, which is attributable to broader targeting of the heterogeneous EGFRi-tolerance mechanisms present in tumors. Overall, this approach facilitates thorough examination of clonal evolution in response to therapy that could inform the development of improved diagnostic approaches and treatment strategies for targeting drug-tolerant cells. SIGNIFICANCE: The evolution and heterogeneity of EGFR inhibitor tolerance are identified in a large number of clones at enhanced cellular and temporal resolution using an expressed barcode technology coupled with single-cell RNA sequencing.

A systematic literature review on sustainability issues along the value chain in insurance companies and pension funds.

Sustainability is now a priority issue that governments, businesses and society in general must address in the short term. In their role as major global institutional investors and risk managers, insurance companies and pension funds are strategic players in building socio-economic and sustainable development. To gain a comprehensive understanding of the current state of action and research on environmental, social and governance (ESG) factors in the insurance and pension sectors, we conduct a systematic literature review. We rely on the PRISMA protocol and analyze 1 731 academic publications available in the Web of Science database up to the year 2022 and refer to 23 studies outside of scientific research retrieved from the websites of key international and European organizations. To study the corpus of literature, we introduce a classification framework along the insurance value chain including external stakeholders. The main findings reveal that risk, underwriting and investment management are the most researched areas among the nine categories considered in our framework, while claims management and sales tend to be neglected. Regarding ESG factors, climate change, as part of the environmental factor, has received the most attention in the literature. After reviewing the literature, we summarize the main sustainability issues and potential related actions. Given the current nature of the sustainability challenges for the insurance sector, this literature review is relevant to academics and practitioners alike.

Preferences of older adults for healthcare models designed to improve care coordination: Evidence from Western Switzerland.

Implementing innovations in care delivery in Switzerland is challenging due to the fragmented nature of the system and the specificities of the political process (i.e., direct democracy, decentralized decision-making). In this context, it is particularly important to account for population preferences when designing policies. We designed a discrete choice experiment to study population preferences for coordination-improving care models. Specifically, we assessed the relative importance of model characteristics (i.e., insurance premium, presence of care coordinator, access to specialists, use of EMR, cost-sharing for chronic patients, incentives for informal care), and predicted uptake under different policy scenarios. We accounted for heterogeneity in preferences for the status quo option using an error component logit model. Respondents attached the highest importance to the price attribute (i.e. insurance premium) (0.31, CI: 0.27- 0.36) and to the presence of a care coordinator (0.27, CI: 0.23 - 0.31). Policy scenarios showed for instance that gatekeeping would be preferred to free access to specialists if the model includes a GP or an interprofessional team as a care coordinator. Although attachment to the status quo is high in the studied population, there are potential ways to improve acceptance of alternative care models by implementation of positively valued innovations.

On the determinants and the role of the payers in the uptake of genetic testing and data sharing in personalized health.

Background: New health technologies and data offer tailored prevention and spot-on treatments, which can considerably reduce healthcare costs. In healthy individuals, insurers can participate in the creation of health capital through data and preventing the occurrence of a disease. In the onset of a disease, sequencing an individual's genome can provide information leading to the use of more efficient treatments. Both improvements are at the core of the "personalized health" paradigm. As a positive side effect, a reduction in healthcare costs is expected. However, the integration of personalized health in insurance schemes starts with a closer understanding of the demand drivers. Methods: Using novel data from a survey carried out in Switzerland, we determine the factors influencing the uptake and sharing of data from genetic tests. In our regression analyses, we use five sets of socioeconomic, lifestyle, health insurance, sentiment, and political beliefs variables. Furthermore, two framings assess the willingness to undertake a test and the readiness to share results with an insurer when the costs of the test are borne by the insurer or the individual. Results: We find that socioeconomic, lifestyle, or political belief variables have very little influence on the uptake of tests and the sharing of data. On the contrary, our results indicate that sentiment and insurance factors play a strong role. More precisely, if genetic tests are perceived as a mean to perform health prevention, this pushes individuals to take them. Furthermore, using the insurer's smartphone app leads to an increase of the likelihood to undergo a test and doubles the probability to share related data. Regarding insurance plans and deductible levels, there is no strong correlation neither with the willingness to take a test nor to share the data. Finally, individuals with complementary health insurance plans are less likely to share results. From the framings for the payment of genetic tests, our results indicate a positive effect of the insurer as a payer on the willingness to undertake tests as well as on data sharing. Conclusion: Our results lay the ground for a deeper understanding of the role of payers on health decisions and sharing of health-related data. In particular, we find that it is relevant for health insurers to engage with their clients.

Is there a "pandemic effect" on individuals' willingness to take genetic tests?

In this cross-sectional, semi-longitudinal and quasi-experimental study, our goal was to determine the effect of data storage conditions on willingness to take a genetic test. We compared individuals' preferences regarding how they want to store health data collected from genetic tests through two survey experiments fielded in Switzerland in March 2020 and January 2022. We tested for differences whether genetic data are presented as private goods or public goods. Results confirm our initial research expectation: more control over storage increases willingness, so does framing genetic data as private good. However, they also show that the willingness to take a genetic test has noticeably increased between 2020 and 2022. Our results point toward a "pandemic effect" which would have increased willingness take a genetic test, nevertheless, more data are needed to understand this putative effect.

On children's motives to influence parents' long-term care insurance purchase: evidence from Switzerland.

Long-term care (LTC) is not only a concern for elderly individuals but also for their adult children, as the latter often provide financial support and informal care to their elderly dependents. Adult children may therefore have strong incentives to have their parents purchase LTC insurance. Using data from a 2019 Swiss survey, this article first identifies a set of variables, including self-reported interest about LTC insurance, whether elderly parents live with their children and if the latter have provided informal help with personal care, which help predict the interest of adult children in having their parents covered against LTC risk. Second, it investigates the main characteristics of children's motives for influencing their parents to purchase LTC insurance, which are classified as either altruistic, i.e. related to parental well-being, or self-interested, i.e. related to the child's well-being. The results offer valuable insights for both policymakers and insurers when designing public LTC policies and LTC insurance products.

Association between continuity of care (COC), healthcare use and costs: what can we learn from claims data? A rapid review.

OBJECTIVE: To describe how longitudinal continuity of care (COC) is measured using claims-based data and to review its association with healthcare use and costs. RESEARCH DESIGN: Rapid review of the literature. METHODS: We searched Medline (PubMed), EMBASE and Cochrane Central, manually checked the references of included studies, and hand-searched websites for potentially additional eligible studies. RESULTS: We included 46 studies conducted in North America, East Asia and Europe, which used 14 COC indicators. Most reported studies (39/46) showed that higher COC was associated with lower healthcare use and costs. Most studies (37/46) adjusted for possible time bias and discussed causality between the outcomes and COC, or at least acknowledged the lack of it as a limitation. CONCLUSIONS: Whereas a wide range of indicators is used to measure COC in claims-based data, associations between COC and healthcare use and costs were consistent, showing lower healthcare use and costs with higher COC. Results were observed in various population groups from multiple countries and settings. Further research is needed to make stronger causal claims.

How does regulating doctors' admissions affect health expenditures? Evidence from Switzerland.

BACKGROUND: Cost containment is a major issue for health policy, in many countries. Policymakers have used various measures to deal with this problem. In Switzerland, the national parliament and subnational (cantonal) governments have used moratoriums to limit the admission of specialist doctors and general practitioners. METHODS: We analyze the impact of these regulations on the number of doctors billing in free practice and on the health costs created by medical practice based on records from the data pool of Swiss health insurers (SASIS) from 2007 to 2018 using interrupted time series and difference-in-differences models. RESULTS: We demonstrate that the removal of the national moratorium in 2012 increased the number of doctors, but did not augment significantly the direct health costs produced by independent doctors. Furthermore, the reintroduction of regulations at the cantonal level in 2013 and 2014 decreased the number of doctors billing in free practice but, again, did not affect direct health costs. CONCLUSIONS: Our findings suggest that regulating healthcare supply through a moratorium on doctors' admissions does not directly contribute to limiting the increase in health expenditures.

Exploring Patient Multimorbidity and Complexity Using Health Insurance Claims Data: A Cluster Analysis Approach.

BACKGROUND: Although the trend of progressing morbidity is widely recognized, there are numerous challenges when studying multimorbidity and patient complexity. For multimorbid or complex patients, prone to fragmented care and high health care use, novel estimation approaches need to be developed. OBJECTIVE: This study aims to investigate the patient multimorbidity and complexity of Swiss residents aged ≥50 years using clustering methodology in claims data. METHODS: We adopted a clustering methodology based on random forests and used 34 pharmacy-based cost groups as the only input feature for the procedure. To detect clusters, we applied hierarchical density-based spatial clustering of applications with noise. The reasonable hyperparameters were chosen based on various metrics embedded in the algorithms (out-of-bag misclassification error, normalized stress, and cluster persistence) and the clinical relevance of the obtained clusters. RESULTS: Based on cluster analysis output for 18,732 individuals, we identified an outlier group and 7 clusters: individuals without diseases, patients with only hypertension-related diseases, patients with only mental diseases, complex high-cost high-need patients, slightly complex patients with inexpensive low-severity pharmacy-based cost groups, patients with 1 costly disease, and older high-risk patients. CONCLUSIONS: Our study demonstrated that cluster analysis based on pharmacy-based cost group information from claims-based data is feasible and highlights clinically relevant clusters. Such an approach allows expanding the understanding of multimorbidity beyond simple disease counts and can identify the population profiles with increased health care use and costs. This study may foster the development of integrated and coordinated care, which is high on the agenda in policy making, care planning, and delivery.

Continuity of care and multimorbidity in the 50+ Swiss population: An analysis of claims data.

Objective: To assess the relationship between continuity of care (COC) and multimorbidity in the older general population in Switzerland, accounting for relevant determinants of COC, and to apply various expressions of multimorbidity derived from claims data. Methods: We used data on 240'000 insured individuals aged 50+ for the period 2015-2018, received from one of the largest Swiss health insurance company. We calculated Bice-Boxerman index based on all doctor visits (overall COC) and visits to the general practitioners (COC GP). We analyzed the relationship between COC and multimorbidity using generalized linear and probit models. To express multimorbidity, we applied three approaches based on pharmacy-cost groups (PCGs) assigned to an individual. First, we used simple PCG counts. Second, we expressed multimorbidity via clinically relevant disease groups derived from PCGs. Finally, a data-driven approach allowed defining distinct clusters representing different patient complexities. Results: The association between overall COC and multimorbidity expressed in PCG counts was modest: COC among individuals with 3+ PCGs was 2 percentage points higher than COC among individuals with 0 PCGs. The approach of clinically relevant disease groups showed larger variation in COC and its association with multimorbidity. The data-driven approach showed that most complex ("high-cost high-need") individuals tended to have higher overall COC. Additionally, 70% of the sample visited exclusively one general practitioner (COC GP = 1.0). Other important factors associated with COC in the Swiss context were insurance model with gatekeeping, level of deductibles, and region of residence. Conclusions: Multimorbid patients require regular medical attention often involving multiple healthcare providers, which can lead to varying COC, depending on types of doctors seen and specific condition of the patient. Insurance models with gatekeeping may facilitate COC, prompting developments of better-designed models of care. This represents important implications for policymakers, health insurance representatives, medical professionals and hospital managers.

Patient and Public Preferences for Coordinated Care in Switzerland: Development of a Discrete Choice Experiment.

OBJECTIVE: Our objective was to develop and test a discrete choice experiment (DCE) eliciting public and patient preferences for better-coordinated care in Switzerland. METHODS: We applied a multistage mixed-methods procedure using qualitative and quantitative approaches. First, to identify attributes, we performed a review of the DCE literature in healthcare with a focus on chronic care. Next, attribute selection involved stakeholders (N = 7) from various healthcare sectors to select the most relevant and actionable attributes, followed by three organized focus groups involving the general public and patients (N = 21) to verify the selection and the clarity of the DCE tasks and explanations. Finally, we conducted an online pilot in the target population to test the survey and obtain priors for a final six tested attributes to refine the final design of the experiment. RESULTS: After identifying an initial 33 attributes, a final list of six attributes was selected following stakeholder involvement and the three focus groups involving the target population. At the online pilot-testing stage with 301 participants, the majority of respondents found the DCE choice tasks socially relevant for Switzerland but challenging. The quality of the answers was relatively high. Most attributes had signs matching those in the literature and focus group discussions. CONCLUSION: This article will be useful to researchers designing DCEs from a broad health policy perspective. The multistage approach involving a range of stakeholders was essential for the development of a DCE that is relevant for policy makers and well-accepted by the general public and patients.

Continuity of care of Swiss residents aged 50+: a longitudinal study using claims data.

Background: Continuity of care (COC) should be measured for healthcare quality monitoring and evaluation and is a key process indicator for integrated care. Measurement of COC using routinely collected data is widespread, but there is no consensus on which indicator to use and the relevant time horizon to apply. Information about COC is especially warranted in highly fragmented healthcare systems, such as in Switzerland. Our study aimed to compare COC measures in Swiss residents aged 50+ obtained with various indices and time horizons. Methods: Using insurance claims data, we computed and compared several commonly used visit-based Continuity of Care Indices (COCIs): Bice-Boxerman Index, Usual Provider of Care, Herfindahl-Hirschman Index, Modified, Modified Continuity Index and Modified Continuity Index, based on all doctor visits and on primary care (PC) visits only. Indices were computed over short (1 year) and medium (4 years) terms. Results: The mean indices based on all visits varied between 0.51 and 0.77, while PC indices presented less variation with a median of 1.00 for all but one index. Indices focusing on a variety of individual providers decreased with time horizon, while indices focusing on the overall number of visits and providers showed the opposite trend. These findings suggest fundamental differences in the interpretation of COCIs. Conclusions: Broad COC appeared moderately low in Switzerland, although comparable to other countries, and PC COC was close to one. The choice of indices and time horizon influenced their interpretation. Understanding these differences is key to select the appropriate index for the monitoring of COC.

A Phase 1 Study of a CDH6-Targeting Antibody-Drug Conjugate in Patients with Advanced Solid Tumors with Evaluation of Inflammatory and Neurological Adverse Events.

PURPOSE: This first-in-human study (NCT02947152) evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of HKT288, a first-in-class CDH6-targeting antibody-drug conjugate (ADC). EXPERIMENTAL DESIGN: HKT288 was administered intravenously (IV) every 3 weeks until patients experienced unacceptable toxicity or progressive disease (PD). The starting dose of 0.3 mg/kg was determined based on the highest nonseverely toxic dose in monkeys, which was 2 mg/kg IV weekly. Based on preclinical toxicology, skin, eyes, bone marrow, and liver were expected targets of toxicity. RESULTS: Nine patients were enrolled: 5 with renal cell carcinoma and 4 with epithelial ovarian cancer. The best overall response on the 0.3 mg/kg cohort in patients with measurable disease was RECIST v1.1 stable disease in 3 patients and PD in 2 patients. The most frequent adverse events (AEs) regardless of causality were pyrexia (44.4%), constipation (44.4%), fatigue (33.3%), and vomiting (33.3%). Three suspected-related neurologic AEs (Grade 2) were reported on the 0.75 mg/kg cohort: seizure in 1 patient and another patient with aphasia and encephalopathy. Further studies were unable to identify the underlying mechanism of the neurologic AEs, and the study was terminated early. CONCLUSIONS: Preclinical toxicology did not predict the neurotoxicity observed with HKT288, and a comprehensive assessment performed post hoc did not identify the mechanism of toxicity. The development of further CDH6-targeting ADCs should be pursued with caution.

PAX8 lineage-driven T cell engaging antibody for the treatment of high-grade serous ovarian cancer.

High-grade serous ovarian cancers (HGSOC) represent the most common subtype of ovarian malignancies. Due to the frequency of late-stage diagnosis and high rates of recurrence following standard of care treatments, novel therapies are needed to promote durable responses. We investigated the anti-tumor activity of CD3 T cell engaging bispecific antibodies (TCBs) directed against the PAX8 lineage-driven HGSOC tumor antigen LYPD1 and demonstrated that anti-LYPD1 TCBs induce T cell activation and promote in vivo tumor growth inhibition in LYPD1-expressing HGSOC. To selectively target LYPD1-expressing tumor cells with high expression while sparing cells with low expression, we coupled bivalent low-affinity anti-LYPD1 antigen-binding fragments (Fabs) with the anti-CD3 scFv. In contrast to the monovalent anti-LYPD1 high-affinity TCB (VHP354), the bivalent low-affinity anti-LYPD1 TCB (QZC131) demonstrated antigen density-dependent selectivity and showed tolerability in cynomolgus monkeys at the maximum dose tested of 3 mg/kg. Collectively, these data demonstrate that bivalent TCBs directed against LYPD1 have compelling efficacy and safety profiles to support its use as a treatment for high-grade serous ovarian cancers.

Public opinion on health care and public health.

In the health policy literature, scholars and practitioners distinguish broadly between health care and public health interventions. Both types of policies are indispensable to deal with pressing health problems. Nevertheless, we know very little about how individuals support the principle logic behind these two approaches to health policy. In this paper, we analyze empirically whether individuals prefer either a health care-oriented or a public health-oriented approach to health policy. In addition, we explore political and socio-demographic factors explaining individuals' choices. To conduct this analysis, we use multivariate regression analysis based on data ( N = 5 442 ) from the 2018 wave of the Swiss Household Panel Survey. The survey contains high-quality data from a representative sample of the population living in Switzerland. Our results demonstrate that a majority of citizens prefers public health policies rather than policies ensuring access to health care. Especially, individuals with higher out-of-pocket payments in their health insurance plan support a public health over health care policy approach. Furthermore, those who prefer environmental protection over economic growth support public health over health care policy.

Governing Personalized Health: A Scoping Review.

Genetic research is advancing rapidly. One important area for the application of the results from this work is personalized health. These are treatments and preventive interventions tailored to the genetic profile of specific groups or individuals. The inclusion of personalized health in existing health systems is a challenge for policymakers. In this article, we present the results of a thematic scoping review of the literature dealing with governance and policy of personalized health. Our analysis points to four governance challenges that decisionmakers face against the background of personalized health. First, researchers have highlighted the need to further extend and harmonize existing research infrastructures in order to combine different types of genetic data. Second, decisionmakers face the challenge to create trust in personalized health applications, such as genetic tests. Third, scholars have pointed to the importance of the regulation of data production and sharing to avoid discrimination of disadvantaged groups and to facilitate collaboration. Fourth, researchers have discussed the challenge to integrate personalized health into regulatory-, financing-, and service provision structures of existing health systems. Our findings summarize existing research and help to guide further policymaking and research in the field of personalized health governance.

SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms.

SHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered a novel immune modulatory function of SHP2. Targeting this protein with allosteric SHP2 inhibitors promoted anti-tumor immunity, including enhancing T cell cytotoxic function and immune-mediated tumor regression. Knockout of SHP2 using CRISPR/Cas9 gene editing showed that targeting SHP2 in cancer cells contributes to this immune response. Inhibition of SHP2 activity augmented tumor intrinsic IFNγ signaling resulting in enhanced chemoattractant cytokine release and cytotoxic T cell recruitment, as well as increased expression of MHC Class I and PD-L1 on the cancer cell surface. Furthermore, SHP2 inhibition diminished the differentiation and inhibitory function of immune suppressive myeloid cells in the tumor microenvironment. SHP2 inhibition enhanced responses to anti-PD-1 blockade in syngeneic mouse models. Overall, our study reveals novel functions of SHP2 in tumor immunity and proposes that targeting SHP2 is a promising strategy for cancer immunotherapy.

A CRISPR Screen Reveals Resistance Mechanisms to CD3-Bispecific Antibody Therapy.

CD3-bispecific antibodies represent an important therapeutic strategy in oncology. These molecules work by redirecting cytotoxic T cells to antigen-bearing tumor cells. Although CD3-bispecific antibodies have been developed for several clinical indications, cases of cancer-derived resistance are an emerging limitation to the more generalized application of these molecules. Here, we devised whole-genome CRISPR screens to identify cancer resistance mechanisms to CD3-bispecific antibodies across multiple targets and cancer types. By validating the screen hits, we found that deficiency in IFNγ signaling has a prominent role in cancer resistance. IFNγ functioned by stimulating the expression of T-cell killing-related molecules in a cell type-specific manner. By assessing resistance to the clinical CD3-bispecific antibody flotetuzumab, we identified core fucosylation as a critical pathway to regulate flotetuzumab binding to the CD123 antigen. Disruption of this pathway resulted in significant resistance to flotetuzumab treatment. Proper fucosylation of CD123 was required for its normal biological functions. In order to treat the resistance associated with fucosylation loss, flotetuzumab in combination with an alternative targeting CD3-bispecific antibody demonstrated superior efficacy. Together, our study reveals multiple mechanisms that can be targeted to enhance the clinical potential of current and future T-cell-engaging CD3-bispecific antibody therapies.

TGFß-blockade uncovers stromal plasticity in tumors by revealing the existence of a subset of interferon-licensed fibroblasts.

Despite the increasing interest in targeting stromal elements of the tumor microenvironment, we still face tremendous challenges in developing adequate therapeutics to modify the tumor stromal landscape. A major obstacle to this is our poor understanding of the phenotypic and functional heterogeneity of stromal cells in tumors. Herein, we perform an unbiased interrogation of tumor mesenchymal cells, delineating the co-existence of distinct subsets of cancer-associated fibroblasts (CAFs) in the microenvironment of murine carcinomas, each endowed with unique phenotypic features and functions. Furthermore, our study shows that neutralization of TGFß in vivo leads to remodeling of CAF dynamics, greatly reducing the frequency and activity of the myofibroblast subset, while promoting the formation of a fibroblast population characterized by strong response to interferon and heightened immunomodulatory properties. These changes correlate with the development of productive anti-tumor immunity and greater efficacy of PD1 immunotherapy. Along with providing the scientific rationale for the evaluation of TGFß and PD1 co-blockade in the clinical setting, this study also supports the concept of plasticity of the stromal cell landscape in tumors, laying the foundation for future investigations aimed at defining pathways and molecules to program CAF composition for cancer therapy.