Rotterdam School of Management

NTRK gene fusions are rare somatic mutations found across cancer types with promising targeted therapies emerging. Healthcare systems face significant challenges in integrating these treatments, with uncertainty in prevalence and optimal testing methods to identify eligible patients. We performed a systematic review of NTRK fusion prevalence to inform efficient diagnostic screening and scale of therapeutic uptake. We searched Medline, Embase and Cochrane databases on 31/03/2021. Inclusion criteria were studies reporting fusion rates in solid tumours, English language, post-2010 publication and minimum sample size. Critical appraisal was performed using a custom 11-item checklist. Rates were collated by cancer type and pooled if additional synthesis criteria were met. 160 studies were included, with estimates for 15 pan-cancer and 429 specific cancer types (63 paediatric). Adult pan-cancer estimates ranged 0.03–0.70%, with higher rates found in RNA-based assays. In common cancers, rates were consistently below 0.5%. Rare morphological subtypes, colorectal microsatellite instability, and driver mutation exclusion cancers had higher rates. Only 35.6% of extracted estimates used appropriate methods and sample size to identify NTRK fusions. NTRK fusion-positive cancers are rare and widely distributed across solid tumours. Small-scale, heterogeneous data confound prevalence prediction. Further large-scale, standardised genomic data are needed to characterise NTRK fusion epidemiology.

The effects of corporate venture capital (CVC) investments on ventures’ revenues and innovation-related outcomes depend on the characteristics of the investors and on the dynamics of the investment process. Recently, venture financing literature has highlighted the importance of investment timing as a driver for investee ventures development and success. Building on the literatures on complementary assets and relative absorptive capacity, we explore how the timing of CVC investments affects ventures’ revenues and R&D intensity. Using a dataset of Norwegian ventures in knowledge-intensive industries, we find evidence for a differential effect of CVC investments when comparing a venture’s early- and late-stage, showing that investments received in late-stage increase ventures’ revenues, but decrease ventures’ R&D intensity. Further, we find that syndication with multiple CVC investors amplifies this effect. This study contributes to the understanding of the CVC-venture relationship and the impact on venture’s post-CVC outcomes.

Background: Quantitative benefit-risk assessment (qBRA) is a structured process to evaluate the benefit-risk balance of treatment options to support decision-making. The ISPOR qBRA Task Force was recently established to provide recommendations for the design, conduct and reporting of qBRA. Objectives: To present a hypothetical case study illustrating how to apply the Task Force's recommendations towards a qBRA to inform the benefit-risk assessment of brodalumab at the time of initial marketing approval. The qBRA evaluated two dosing regimens of brodalumab (210 mg or 140 mg twice weekly) compared to weight-based dosing of ustekinumab and placebo. Methods: We followed the five steps recommended by the Task Force. Attributes included treatment response (PASI75), suicidal ideation and behavior, and infections. Performance data were drawn from pivotal clinical trials of brodalumab. The qBRA used multi-criteria decision analysis and preference weights from a hypothetical discrete choice experiment. Sensitivity analyses examined the robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, consideration of a subgroup (nail psoriasis), and the maintenance phase of treatment (52 weeks instead of 12). Results: Results from this hypothetical qBRA suggest that brodalumab 210 mg had a more favorable benefit-risk profile compared to ustekinumab and placebo. Ranking of brodalumab compared to ustekinumab was dependent on brodalumab's dose. Sensitivity analyses demonstrated robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, as well as choice of attributes and length of follow-up. Conclusion: This case study demonstrates how to implement the ISPOR Task Force's good practice recommendations on qBRA.

Purpose: Organizational culture plays a major role in prioritizing Diversity, Equity, and Inclusion (DEI) objectives by aligning individual values of employees with organizational values. However, effective strategies to create an inclusive organizational culture, in which these values are aligned, remain unclear. The European Society for Radiotherapy and Oncology (ESTRO) launched a qualitative study, XXX on DEI that highlighted low levels of inclusion and work engagement among radiation oncology (RO) professionals in Europe. The aim of the current study was to gain an understanding of how DEI could be improved within RO departments by creating a more inclusive organizational culture. Materials and methods: A qualitative research study was conducted by enrolling RO professionals from four selected European countries through an open call at the ESTRO platform. Respondents who filled in an online survey and met the inclusion criteria, such as experiencing low DEI levels at work, were invited for an online semi-structured interview. Interview transcripts were analyzed thematically with an abductive approach via concepts in relation to "DEI", "work engagement", "organizational culture" and "professional values". Results: Twenty-six eligible respondents from Great Britain, Italy, Poland, and Switzerland were interviewed. The thematic analysis identified cases in which limited engagement at work emerged when the personal values of RO professionals conflicted with dominant organizational values, hampering DEI. Three conflicts were found between the following personal vs. organizational values: 1) self-development vs. efficiency, 2) togetherness vs. competition, and 3) people-oriented vs. task-oriented cultures. Conclusions: Awareness should be raised on how organizational values can conflict with professionals' values to improve inclusion and engagement in the workplace. Additionally, efforts should be focused on tackling existing power imbalances that hamper effective deliberation on the organizational vs. personal-value conflicts.

Even as research on scaling and High Growth Firms (HFGs) is gaining momentum, the corpus of accumulated research remains largely fragmented and dispersed, with little in the way of a central conceptual foundation or ‘theoretical true north’ to guide empirical development. This Special Issue provides a forum for works that push the theoretical and empirical frontiers of research on scaling and HGFs. We provide a multi‐dimensional conceptualization that recognizes scaling as a dynamic capability entailing routines and processes for expansion, replication, and synchronization. We also present a typology that specifies the multiple types of HGFs. Inspired by the four studies published in the special issue, we finally outline five priorities for future research.

To remain competitive, organizations tend to change their established ways of working, their strategy, the core values, and the organizational structure. Such thorough changes are referred to as transformational change. Unfortunately, transformational change is often unsuccessful because organizational members do not always welcome the change. Although organizations often expect their supervisors to be successful role‐models and change‐agents during the transformational change process, we argue that initiating transformational change could increase supervisors' hindrance stress levels, which may result in abusive behaviors towards employees. More specifically, in a multi‐source survey and an experimental study, we find evidence that transformational change is associated with supervisors' experienced hindrance stress, which subsequently led to more abusive behaviors towards employees.

Background Unprofessional behaviour undermines organizational trust and negatively affects patient safety, the clinical learning environment, and clinician well-being. Improving professionalism in healthcare organizations requires insight into the frequency, types, sources, and targets of unprofessional behaviour in order to refine organizational programs and strategies to prevent and address unprofessional behaviours. Objective To investigate the types and frequency of perceived unprofessional behaviours among health care professionals and to identify the sources and targets of these behaviours. Methods Data was collected from 2017–2019 based on a convenience sample survey administered to all participants at the start of a mandatory professionalism course for health care professionals including attending physicians, residents and advanced practice providers (APPs) working at one academic hospital in the United States. Results Out of the 388 participants in this study, 63% experienced unprofessional behaviour at least once a month, including failing to respond to calls/pages/requests (44.3%), exclusion from decision-making (43.0%) and blaming behaviour (39.9%). Other monthly experienced subtypes ranged from 31.7% for dismissive behaviour to 4.6% for sexual harassment. Residents were more than twice as likely (OR 2.25, p

In countries where systemic inequality is pervasive, purposeful businesses that assume wider societal responsibilities try to counteract its effects by including marginalized social groups in their value creation processes. While current research documents a variety of business approaches for community inclusion, the nature, drivers and effectiveness of these inclusionary practices are not fully understood. We develop and empirically validate a framework of community inclusion that explicates the mechanisms through which purposeful businesses generate civic wealth – or economic and social benefits – to disadvantaged community groups. We differentiate between commercial practices that recast existent firm‐centric processes towards creating value for marginalized groups and collaborative practices that aim to devise novel, participatory processes for engaging marginalized groups. Analysis of primary data from a sample of 430 small businesses in seven African countries confirms that the effect of social purpose on civic wealth is partially mediated by the two inclusionary practices. Businesses are more likely to extend the scope of their inclusion through collaborative practices when they receive favourable external validation and when institutional voids are low. We contribute to the literature by documenting the role of social purpose in motivating the pursuit of community‐level goals and by unpacking the specific inclusionary practices used to achieve them.

Introduction Integrated care can create several advantages, such as better quality of care and better outcomes. These advantages apply especially to clients with multiple problems (CWMPs) who have multiple, interconnected needs that span health and social issues and require different health care (e.g., mental health care or addiction care), social care (e.g., social benefits) and welfare services at the same time. Integrated care is most often studied as a phenomenon taking place at the system, organizational, professional and clinical levels. Therefore, in many studies, clients seem to be implicitly conceptualized as passive recipients of care. Less research has been conducted on how clients and (in)formal caretakers coproduce integrated care. Methods We performed a longitudinal study to investigate how CWPMs and (in)formal caretakers coproduce integrated care. Data were collected among CWMPs and their (in)formal caretakers in Rotterdam, the Netherlands. CWMPs' care trajectories were followed for 1–1.5 years. CWMPs were interviewed three times at an interval of 6 months (T0, T1, T2). Informal caretakers were interviewed three times (T0, T1, T2), and formal caretakers of 16 clients were interviewed twice (T1, T2). Data in the municipal record systems about participating CWMPs were also included. Results Our study shows that the CWMPs' multidimensional needs, which should function as the organizing principle of integrated care, are rarely completely assessed at the start (first 6 weeks) of CWMPs' care trajectories. Important drivers behind this shortcoming are the urgent problems CWMPs enter the support trajectory with, their lack of trust in ‘the government’ and the complexity of their situations. We subsequently found two distinct types of cases. The highest level of integrated care is achieved when formal caretakers initiate an iterative process in which the CWMP's multidimensional needs are constantly further mapped out and interventions are attuned to this new information. Conclusions Our study indicates that integrated care is the joint product of formal caretakers and CWMPs. Integrated care however does not come naturally when CWMPs are ‘put at the center’. Professionals need to play a leading role in engaging CWMPs to coproduce integrated care. Patient Contribution CWMPs and their (in)formal caretakers participated in this study via interviews and contributed with their experiences of the process.

There are more than 7,000 known rare diseases, but pharmaceutical manufacturers developed treatments for only 500 of them. To improve the availability and accessibility of treatments for rare diseases, governments have introduced several programs including subsidies, exogenous pricing, and outcome-based payment schemes in recent years. What kind of subsidy programs and pricing mechanisms can improve patient access? Inspired by various pilot programs, we present a multistage game theoretic model to analyze different subsidy schemes proposed for rare diseases. In addition to the traditional setting in which the manufacturer sets the price, we consider an “exogenous pricing scheme” under which an independent consortium sets the price. We also examine an outcome-based payment scheme, which offers the drug for free if it is not efficacious. We formulate a four-stage Stackelberg game to determine whether it is optimal to subsidize the pharmaceutical manufacturer, the patients, or both. Our results offer several insights. First, we find that government subsidies are crucial to entice new drug development for rare diseases. Also, we find that the pricing scheme matters: The exogenous pricing scheme can improve patient welfare, but it reduces the manufacturer’s expected profit. We find that this result is robust even when an outcome-based payment scheme is used. This paper was accepted by Jayashankar Swaminathan, operations management. Funding: This work was supported by the Dutch Science Foundation [Nederlandse Organisatie voor Wetenschappelijk Onderzoek VENI Talent Scheme]. Supplemental Material: The data files and online appendices are available at https://doi.org/10.1287/mnsc.2022.4634 .

The public debate on voluntary termination of life by elderly people, which has been an intensely controversial subject in the Netherlands for some time, has centered around the issue of “completed life” in recent years. In 2016, an ad hoc governmental advisory committee concluded that the already existing Euthanasia Act provided sufficient scope to resolve most of the problems related to the issue. Most of the older adults who feel they no longer have anything to look forward to in their lives and who have developed a wish to die as a result would be able to invoke this Act. Partly for this reason, the committee considered broadening the legal options relating to assisted suicide undesirable. Analysis of the assessment practice of the regional euthanasia review committees reveals that the room for interpretation offered by the Euthanasia Act is indeed considerable.

Technology transfer from public research institutes (PRIs) to small and medium enterprises (SMEs) facilitated by intermediary agents such as Research Scientists and Engineers (RSEs) has received limited attention. Similarly, the literature on intermediary agents has overlooked the reverse knowledge flow benefits enjoyed by the RSEs who facilitate technology transfer. Motivated by these gaps, we aim to answer the following research question: What characteristics and conditions of technology transfer determine the intangible benefits attained by technology transfer intermediary agents? To do so, we leverage the unique research context of the Technology Upgrading (T-Up) transfer policy in Singapore that commissions PRIs to impart technology capabilities in SMEs, facilitated by RSEs who move between organizations to carry out the transfer. Supported by an in-depth field study and survey data from multiple stakeholders that participated in the technology transfer, we apply fuzzy sets qualitative comparative analysis (fsQCA) to analyze the configuration of factors influencing the reverse knowledge flow benefits attained by the technology transfer intermediary agents. Our findings on the mutually reinforcing nature of intermediary agent-recipient benefits have important implications for research and practice.

Discrete choice experiments (DCEs) are a powerful tool that potentially offer a method to quantify individual and joint care preferences of persons with dementia and their informal caregivers. DCE studies that have included persons with dementia revealed that choice task complexity is a serious challenge to this population, which can lead to heuristic decision making. This feasibility study aims to determine best‐in‐practice dyadic DCE design to enable both persons with dementia and informal caregivers to participate in health care decision‐making. This study included three DCE rounds: (1) persons with dementia alone, (2) informal caregiver only, and (3) persons with dementia and their informal caregivers in dyads. A flexible DCE design was employed, in which choice task complexity was increased systematically to explore individual cognitive limitations in DCE decision making. Choice tasks were presented by illustrations and simplified language to decrease cognitive burden on persons with dementia. A think aloud approach of survey administration was used to provide insights into individual and joint decision‐making processes. The Telephone Interview for Cognitive Status was used for cognitive screening. 15 persons with dementia, 15 informal caregivers, and 14 dyadic discrete choice experiments were conducted. The majority of persons with dementia (53.3%) was able to complete choice tasks including two scenarios characterized by three attributes and completed on average 6.4 (SD 4.1) choice tasks before dropping out. The dyadic DCEs enabled persons with dementia to complete surveys that were somewhat more complex, and on average a higher number of choice tasks (7.9, SD 3.9). In the dyadic DCEs, informal caregivers assisted the person with dementia to understand the choice task, elicited choice motivation, and provided the means to discuss each other’s preferences. Persons with dementia that have a mild to severe cognitive impairment can use discrete choice experiments with low choice task complexity. Dyadic DCEs can enable greater empowerment of the person with dementia while promoting joint decision making. Future work should further explore the mapping of severity of dementia and feasible choice task complexity, to enhance our understanding about designing choice elicitation tasks.

Against the background of regional development, this article analyses the rise and fall of ‘thin identities’, which tend to be utilitarian and deployed to promote regional development. We focus on two constructed regional identities in the Greater Pearl River Delta (GPRD) in China: Pearl River Delta (PRD) and Guangdong‐Hong Kong‐Macau Greater Bay Area (GBA). We analyse the adoption of these identities through news items published in newspapers in both China's Mainland and Hong Kong. The results show that both economic and political events influence the adoption of thin identities, first PRD and then GBA. In the content analysis of news items, we investigate the pathways to their adoption and possible evolution towards thickness (broader social and cultural embeddedness) by distinguishing economic, political, social, and cultural topics. The wish of policymakers to adopt new thin identities, however, does affect the credibility of existing thick ones, a point deserving of serious consideration.

Current mobile systems are capable of efficiently acquiring dense urban point clouds. Still, operational use of such data is hampered by the lack of efficient object extraction methodology. Notably methodology is lacking for automatically extracting objects that do not belong to the road furniture like street signs and light poles but do belong to the street furniture. As an example, object we consider public garbage bins, that are installed and should be maintained in public areas in every city. However, information about types, locations, and condition of these public garbage bins are rarely updated and only obtained through manual measurements. Therefore, an efficient way of collecting information on such public objects is of interest not only for urban management but also when developing digital twins of a city. This study proposes a new method to automatically extract public garbage bins from large urban mobile laser scanning (MLS) point clouds. The proposed method consists of three main steps: (1) cell-, (2) sub-cell-, and (3) surface-based filtering, in which both spatial information of the point clouds and contextual knowledge of the public garbage bins are incorporated to efficiently remove irrelevant 3D points at an early phase and identify and classify different types of public garbage bins. Contextual knowledge includes shape and dimensions, and the relationship between the public garbage bins and the ground surface. A MLS dataset of the city centre of Rotterdam, the Netherlands, consisting of 2.84 billion points organised in 166 tiles of 50 × 75m, and covering an area of about 750 × 750m was used to test the proposed method. Results show that the method can automatically extract ~90 public garbage bins with an overall detection rate of 89.1%. Moreover, the executing time for the entire dataset was only about 163.6 minutes, which is equivalent to 3.46 seconds per one million points. Although the method was tested here one public garbage bins, it can be easily tuned for the detection of other street furniture objects, like benches, post boxes or bollards.

Background: Calcium is a determinant of paravalvular leakage (PVL) after transcatheter aortic valve implantation (TAVI). This is based on a fixed contrast attenuation value while X-ray attenuation is patient-dependent and without considering frame expansion and PVL location. We examined the role of calcium in (site-specific) PVL after TAVI using a patient-specific contrast attenuation coefficient combined with frame expansion. Methods: 57 patients were included with baseline CT, post-TAVI transthoracic echocardiography and rotational angiography (R-angio). Calcium load was assessed using a patient-specific contrast attenuation coefficient. Baseline CT and post-TAVI R-angio were fused to assess frame expansion. PVL was assessed by a core lab. Results: Overall, the highest calcium load was at the non-coronary-cusp-region (NCR, 436 mm3) vs. the right-coronary-cusp-region (RCR, 233 mm3) and the left-coronary-cusp-region (LCR, 244 mm3), p < 0.001. Calcium load was higher in patients with vs. without PVL (1,137 vs. 742 mm3, p = 0.012) and was an independent predictor of PVL (odds ratio, 4.83, p = 0.004). PVL was seen most often in the LCR (39% vs. 21% [RCR] and 19% [NCR]). The degree of frame expansion was 71% at the NCR, 70% at the RCR and 74% at the LCR without difference between patients with or without PVL. Conclusions: Calcium load was higher in patients with PVL and was an independent predictor of PVL. While calcium was predominantly seen at the NCR, PVL was most often at the LCR. These findings indicate that in addition to calcium, specific anatomic features play a role in PVL after TAVI.

Global adoption of electric vehicles (EVs) faces many challenges such as range anxiety, high cost of EVs, and inadequate charging infrastructure. EV-sharing platforms resolve such concerns by setting up an optimal configuration for charging infrastructure and optimizing the charging decisions for depleted EVs. These platforms manage the vehicles’ flow to different charging stations and decide when and to what energy level the depleted vehicles should be recharged. Station-based platforms are one of the mainstream vehicle sharing systems where the customer picks-up and drops-off the vehicle at the designated stations. If a vehicle’s battery energy level falls below a threshold after completing the customer trip, it is charged either partially or fully at the charging station. This study addresses various operational and strategic decisions (such as the number of chargers, vehicle repositioning, and partial charging policy) for a one-way station-based EV-sharing platform using a stylized three-stage analytical framework. We use vehicle dynamics to model the EV powertrain and regenerative braking under different traffic conditions and simulate them using AVL CRUISE™. We model the platform operations using an open queuing network and provide a mixed-integer non-linear optimization program using inputs from the queuing network and vehicle dynamics simulation. We also provide a bound-based heuristic to solve this NP-hard optimization problem. We generate various managerial insights for an efficient implementation of the partial charging policy for EV-sharing platforms. The increase in the partial charging probability (the fraction of depleted vehicles charged partially) reduces the effective charging demand, resulting in fewer chargers and a higher profit. On the other hand, if we increase the target battery energy level for partial charging, the platform’s profit decreases due to higher effective charging demand dominating the benefits of lower charging frequency of vehicles.