Achieving research impact in medical research through collaboration across organizational boundaries: Insights from a mixed methods study in the Netherlands.

BACKGROUND: In the Netherlands, university medical centres (UMCs) bear primary responsibility for conducting medical research and delivering highly specialized care. The TopCare program was a policy experiment lasting 4 years in which three non-academic hospitals received funding from the Dutch Ministry of Health to also conduct medical research and deliver highly specialized care in specific domains. This study investigates research collaboration outcomes for all Dutch UMCs and non-academic hospitals in general and, more specifically, for the domains in the non-academic hospitals participating in the TopCare program. Additionally, it explores the organizational boundary work employed by these hospitals to foster productive research collaborations. METHODS: A mixed method research design was employed combining quantitative bibliometric analysis of publications and citations across all Dutch UMCs and non-academic hospitals and the TopCare domains with geographical distances, document analysis and ethnographic interviews with actors in the TopCare program. RESULTS: Quantitative analysis shows that, over the period of study, international collaboration increased among all hospitals while national collaboration and single institution research declined slightly. Collaborative efforts correlated with higher impact scores, and international collaboration scored higher than national collaboration. A total of 60% of all non-academic hospitals' publications were produced in collaboration with UMCs, whereas almost 30% of the UMCs' publications were the result of such collaboration. Non-academic hospitals showed a higher rate of collaboration with the UMC that was nearest geographically, whereas TopCare hospitals prioritized expertise over geographical proximity within their specialized domains. Boundary work mechanisms adopted by TopCare hospitals included aligning research activities with organizational mindset (identity), bolstering research infrastructure (competence) and finding and mobilizing strategic partnerships with academic partners (power). These efforts aimed to establish credibility and attractiveness as collaboration partners. CONCLUSIONS: Research collaboration between non-academic hospitals and UMCs, particularly where this also involves international collaboration, pays off in terms of publications and impact. The TopCare hospitals used the program's resources to perform boundary work aimed at becoming an attractive and credible collaboration partner for academia. Local factors such as research history, strategic domain focus, in-house expertise, patient flows, infrastructure and network relationships influenced collaboration dynamics within TopCare hospitals and between them and UMCs.

Health-related quality of life in patients with steroid-refractory acute graft-versus-host disease.

BACKGROUND: Evidence regarding health-related quality of life (HRQoL) in patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD) is lacking. Evaluating HRQoL was a secondary objective of the HOVON 113 MSC trial. Here we describe the outcomes of the EQ-5D-5L, EORTC QLQ-C30, and FACT-BMT for all adult patients who completed these questionnaires at baseline (i.e., before the start of treatment; n = 26). METHODS: Descriptive statistics were used to describe baseline patient and disease characteristics, EQ-5D dimension scores and values, EQ VAS scores, EORTC QLQ-C30 scale/item and summary scores, and FACT-BMT subscale and total scores. RESULTS: The mean EQ-5D value was 0.36. In total, 96% of the patients reported problems with usual activities, 92% with pain/discomfort, 84% with mobility, 80% with self-care, and 72% with anxiety/depression. The mean EORTC QLQ-C30 summary score was 43.50. Mean scale/item scores ranged from 21.79 to 60.00 for functioning scales, from 39.74 to 75.21 for symptom scales, and from 5.33 to 91.67 for single items. The mean FACT-BMT total score was 75.31. Mean subscale scores ranged from 10.09 for physical well-being to 23.94 for social/family well-being. CONCLUSION: Our study showed that HRQoL in patients with SR-aGvHD is poor. Improving HRQoL and symptom management in these patients should be a top priority.

Cost-effectiveness of Anti-CD19 chimeric antigen receptor T-Cell therapy in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia. A societal view.

INTRODUCTION: In several studies, the chimeric antigen receptor T-cell therapy tisagenlecleucel demonstrated encouraging rates of remission and lasting survival benefits in pediatric patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL). We assessed the cost-effectiveness of tisagenlecleucel (list price: 320 000 EUR) among these patients when compared to clofarabine monotherapy (Clo-M), clofarabine combination therapy (Clo-C), and blinatumomab (Blina) from both a healthcare and a societal perspective. We also assessed future medical and future non-medical consumption costs. METHODS: A three-state partitioned survival model was used to simulate a cohort of pediatric patients (12 years of age) through different disease states until the end of life (lifetime horizon). Relevant outcomes were life years, quality-adjusted life years (QALYs), healthcare costs, societal costs, and the incremental cost-effectiveness ratio (ICER). Uncertainty was explored through deterministic and probabilistic sensitivity analyses as well as through several scenario analyzes. RESULTS: Total discounted costs for tisagenlecleucel were 552 679 EUR from a societal perspective, which was much higher than the total discounted costs from a healthcare perspective (ie, 409 563 EUR). Total discounted societal costs for the comparator regimens ranged between 160 803 EUR for Clo-M and 267 259 EUR for Blina. Highest QALYs were estimated for tisagenlecleucel (11.26), followed by Blina (2.25), Clo-C (1.70) and Clo-M (0.74). Discounted societal ICERs of tisagenlecleucel ranged between 31 682 EUR/QALY for Blina and 37 531 EUR/QALY for Clo-C and were considered cost-effective with a willingness-to-pay (WTP) threshold of 80 000 EUR/QALY. None of the scenarios exceeded this threshold, and more than 98% of the iterations in the probabilistic sensitivity analysis were cost-effective. DISCUSSION: At the current price and WTP threshold, tisagenlecleucel is cost-effective from both a healthcare and a societal perspective. Nevertheless, long-term effectiveness data are needed to validate the several assumptions that were necessary for this model.

Which Questionnaire Should Be Used to Measure Quality-of-Life Utilities in Patients with Acute Leukemia? An Evaluation of the Validity and Interpretability of the EQ-5D-5L and Preference-Based Questionnaires Derived from the EORTC QLQ-C30.

OBJECTIVES: The aim of this study was to assess the validity and interpretability of different preference-based questionnaires (generic 5-level EuroQol five-dimensional questionnaire [EQ-5D-5L], cancer-specific Quality of Life Questionnaire Preference-Based Measure, and European Organization of Randomized Controlled Trials 8 Dimension [EORTC-8D]) in patients with acute leukemia. METHODS: Patients who participated in Hemato-Oncologie voor Volwassenen Nederland (HOVON - the Haemato Oncology Foundation for Adults in the Netherlands) clinical trials between 1999 and 2011 at a single hospital were invited to complete the questionnaires. Interpretability was evaluated by the frequency of incomplete data and highest and lowest possible scores. Content validity was evaluated by exploring the health-related quality-of-life domains included in the questionnaires. Construct validity was assessed using correlations with other quality-of-life scales (EQ-visual analogue scale score and global quality-of-life scale of the EORTC Quality of Life Questionnaire) and ability to distinguish between patients with different health statuses. RESULTS: Questionnaires were returned by 89% (111 of 125) of the patients. Six to seven respondents did not return full questionnaires. Perfect health on the EQ-5D-5L was reported by 32 respondents and many of them (N = 17) did report health problems on other questionnaires. All questionnaires were strongly correlated (range 0.61-0.78) with other quality-of-life scales and yielded substantially different utility values for patients with different health statuses. Nevertheless, the disease-specific preference-based questionnaires showed greater discriminatory power. CONCLUSIONS: Although the Quality of Life Questionnaire Preference-Based Measure and the EORTC-8D appear to have better validity, this study does not provide any strong evidence against the use of the EQ-5D-5L for measuring quality-of-life utilities in acute leukemia. However, our findings need to be confirmed in larger longitudinal studies.