• A typology-based decisional framework to support market access and reimbursement decisions for personalised medicines

      Govaerts, Laurenz; Geldof, Tine; Simoens, Steven; Huys, Isabelle (Value in Health. The Journal of the International Society for Pharmacoeconomics and Outcomes Research, 2017)
      New co-development approaches in personalized medicine challenge current decisional frameworks of health-technology access and reimbursement procedures. We aim to conceptualize an efficient typology-based decisional framework which takes into account the development and market access synchronism between therapeutic (Tx) and diagnostic (Dx) components of personalized medicines.
    • A typology-based decisional framework to support market access and reimbursement decisions for personalized medicines

      Govaerts, Laurenz; Geldof, Tine; Simoens, Steven; Huys, Isabelle; Van Dyck, Walter (2017)
    • Barriers and opportunities for implementation of outcome-based spread payments for high-cost, one-shot curative therapies

      Michelsen, Sissel; Nachi, Salma; Van Dyck, Walter; Simoens, Steven; Huys, Isabelle (Frontiers in Pharmacology, 2020)
      Background: The challenging market access of high-cost, one-time curative therapies has inspired the development of alternative reimbursement structures, such as outcome-based spread payments, to mitigate their unaffordability and answer remaining uncertainties. This study aimed to provide a broad overview of barriers and possible opportunities for the practical implementation of outcome-based spread payments for the reimbursement of one-shot therapies in European healthcare systems. Methods: A systematic literature review was performed investigating published literature and publicly available documents to identify barriers and implementation opportunities for both spreading payments and for implementing outcome-based agreements. Data was analyzed via qualitative content analysis by extracting data with a reporting template. Results: A total of 1503 publications were screened and 174 were included. Main identified barriers for the implementation of spread payments are reaching an agreement on financial terms while considering 12-month budget cycles and the possible violation of corresponding (inter)national accounting rules. Furthermore, outcome correction of payments is currently hindered by the need for additional data collection, the lack of clear governance structures and the resulting administrative burden and cost. The use of spread payments adjusted by population- or individual-level data collected within automated registries and overseen by a governance committee and external advisory board may alleviate several barriers and may support the reimbursement of highly innovative therapies. Conclusion: High-cost advanced therapy medicinal products pose a substantial affordability challenge on healthcare systems worldwide. Outcome-based spread payments may mitigate the initial budget impact and alleviate existing uncertainties; however, their effective implementation still faces several barriers and will be facilitated by realizing the required organizational changes.
    • Comparative and combined effectiveness of innovative therapies in cancer: A literature review

      Geldof, Tine; Rawal, Smita; Van Dyck, Walter; Huys, Isabelle (Journal of Comparative Effectiveness Research, 2019)
      To achieve therapeutic innovation in oncology, already expensive novel medicines are often concomitantly combined to potentially enhance effectiveness. While this aggravates the pricing problem, comparing effectiveness of novel yet expensive (concomitant) treatments is much needed for healthcare decision-making to deliver effective but affordable treatments. This study reviewed published clinical trials and real-world studies of targeted and immune therapies. In total, 48 studies compared and/or combined multiple novel products on breast, colorectal, lung and melanoma cancers. To a great extent, products evaluated in each study were owned by one manufacturer. However, cross-manufacturer assessments are also needed. Next to costs and intensive market competition, the absence of a regulatory framework enforcing real-world multiproduct studies prevents these from being conducted. Trusted third parties could facilitate such real-world studies, for which appropriate and efficient data access is needed.
    • Evaluation of precision medicine assessment reports of the Belgian healthcare payer to inform reimbursement decisions

      Govaerts, Laurenz; Waeytens, Anouk; Van Dyck, Walter; Simoens, Steven; Huys, Isabelle (International Journal of Technology Assessment in Health Care, 2020)
      Introduction. Precision medicines rely on companion diagnostics to identify patient subgroups eligible for receiving the pharmaceutical product. Until recently, the Belgian public health payer, RIZIV-INAMI, assessed precision medicines and companion diagnostics separately for reimbursement decisions. As both components are considered co-dependent technologies, their assessment should be conducted jointly from a health technology assessment (HTA) perspective. As of July 2019, a novel procedure was implemented accommodating for this joint assessment practice. The aim of this research was to formulate recommendations to improve the assessment in the novel procedure. Methods. This study evaluated the precision medicine assessment reports of RIZIV-INAMI of the last 5 years under the former assessment procedure. The HTA framework for co-dependent technologies developed by Merlin et al. for the Australian healthcare system was used as a reference standard in this evaluation. Criteria were scored as either present or not present. Results. Thirteen assessment reports were evaluated. Varying scores between reports were obtained for the domain establishing the co-dependent relationship between diagnostic and pharmaceutical. Domains evaluating the clinical utility of the biomarker and the cost-effectiveness performed poorly, whereas the budget impact and the transfer of trial data to the local setting performed well. Recommendations. Based on these results we recommend three amendments for the novel procedure. (i) The implementation of the linked evidence approach when direct evidence of clinical utility is not present, (ii) incorporation of a bias assessment tool, and (iii) further specify guidelines for submission and assessment to decrease the variability of reported evidence between assessment reports.
    • Nearest neighbour propensity score matching and bootstrapping for estimating binary patient response in oncology: A Monte Carlo simulation

      Geldof, Tine; Dusan, Popovic; Van Damme, Nancy; Huys, Isabelle; Van Dyck, Walter (Scientific Reports: A Nature Research Journal, 2020)
      Nearest Neighbour (NN) propensity score (PS) matching methods are commonly used in pharmacoepidemiology to estimate treatment response using observational data. Unfortunately, there is limited evidence on the optimal approach for accurately estimating binary treatment response and, more so, to estimate its variance. Bootstrapping, although commonly used to accurately estimate variance, is rarely used together with PS matching. In this Monte Carlo simulation-based study, we examined the performance of bootstrapping used in conjunction with PS matching, as opposed to diferent NN matching techniques, on a simulated dataset exhibiting varying levels of real world complexity. Thus, an experimental design was set up that independently varied the proportion of patients treated, the proportion of outcomes censored and the amount of PS matches used. Simulation results were externally validated on a real observational dataset obtained from the Belgian Cancer Registry. We found all investigated PS methods to be stable and concordant, with k-NN matching to be optimally dealing with the censoring problem, typically present in chronic cancer-related datasets, whilst being the least computationally expensive. In contrast, bootstrapping used in conjunction with PS matching, being the most computationally expensive, only showed superior results in small patient populations with long-term largely unobserved treatment efects.
    • Patient preferences to assess value in gene therapies: Protocol development for the paving study in Hemophilia

      van Overbeeke, Eline; Hauber, Brett; Michelsen, Sissel; Goldman, Michel; Simoens, Steven; Huys, Isabelle (Frontiers in Medicine, 2021)
      Introduction: Gene therapies are innovative therapies that are increasingly being developed. However, health technology assessment (HTA) and payer decision making on these therapies is impeded by uncertainties, especially regarding long-term outcomes. Through measuring patient preferences regarding gene therapies, the importance of unique elements that go beyond health gain can be quantified and inform value assessments. We designed a study, namely the Patient preferences to Assess Value IN Gene therapies (PAVING) study, that can inform HTA and payers by investigating trade-offs that adult Belgian hemophilia A and B patients are willing to make when asked to choose between a standard of care and gene therapy. Methods and Analysis: An eight-step approach was taken to establish the protocol for this study: (1) stated preference method selection, (2) initial attributes identification, (3) stakeholder (HTA and payer) needs identification, (4) patient relevant attributes and information needs identification, (5) level identification and choice task construction, (6) educational tool design, (7) survey integration, and (8) piloting and pretesting. In the end, a threshold technique survey was designed using the attributes "Annual bleeding rate," "Chance to stop prophylaxis," "Time that side effects have been studied," and "Quality of Life." Ethics and Dissemination: The Medical Ethics Committee of UZ KU Leuven/Research approved the study. Results from the study will be presented to stakeholders and patients at conferences and in peer-reviewed journals. We hope that results from the PAVING study can inform decision makers on the acceptability of uncertainties and the value of gene therapies to patients.
    • Patient-level effectiveness prediction modeling for glioblastoma using classification trees

      Geldof, Tine; Van Damme, Nancy; Huys, Isabelle; Van Dyck, Walter (Frontiers in Pharmacology, 2020)
      Little research has been done in pharmacoepidemiology on the use of machine learning for exploring medicinal treatment effectiveness in oncology. Therefore, the aim of this study was to explore the added value of machine learning methods to investigate individual treatment responses for glioblastoma patients treated with temozolomide.
    • Real-world evidence gathering in oncology: The need for a biomedical big data insight-providing federated network

      Geldof, Tine; Huys, Isabelle; Van Dyck, Walter (Frontiers in Medicine, 2019)
      Moving towards new adaptive pathways for the development and access to innovative medicines implies that real-world data (RWD) collected throughout the medicinal product life cycle is becoming increasingly important. Big data analytics on RWD can obtain new and powerful insights into medicines’ effectiveness. However, the healthcare ecosystem still faces many sector-specific challenges that hamper the use of big data analytics delivering real world evidence (RWE). We distinguish between exploratory (ExTE) and hypotheses-evaluating (HETE) studies testing treatment effectiveness in the real world. From our experience and in the context of the four V’s of data management, we show that to get meaningful results data Variety and Veracity are needed regardless of the type of study conducted. More so, for ExTE studies high data Volume is needed while for HETE studies high Velocity becomes essential. Next, we highlight what are needed within the biomedical big data ecosystem, being: (a) international data reusability; (b) real-time RWD processing information systems; and (c) longitudinal RWD. Finally, in an effort to manage the four V’s whilst respecting patient privacy laws we argue for the development of an underlying federated RWD infrastructure on a common data model, capable of bringing the centrally-conducted big data analysis to the de-centrally kept biomedical data.
    • Shedding light on reimbursement policies of companion diagnostics in European countries

      Govaerts, Laurenz; Simoens, Steven; Van Dyck, Walter; Huys, Isabelle (Value in Health, 2020)
      Ensuring access to precision medicine has been an issue because in some European countries, desynchronized reimbursement decision-making occurs between the medicine and the companion diagnostic (CDx). This has resulted in cases in which precision medicine is reimbursed but not the CDx. In overcoming this issue, an alignment of the decision-making process for reimbursement between the 2 entities should be considered. As pharmaceutical reimbursement procedures are meticulously covered in the literature, we set out to systematically map in vitro diagnostic (IVD) reimbursement procedures and identify policies for aligning these procedures with the pharmaceutical reimbursement procedures.
    • A systematic review of the value assessment frameworks used within health technology assessment of Omics technologies and their actual adoption from HTA agencies

      Hoxhaj, Ilda; Govaerts, Laurenz; Simoens, Steven; Van Dyck, Walter; Huys, Isabelle; Gutiérrez-Ibarluzea, Iñaki; Boccia, Stefania (International Journal of Environmental Research and Public Health, 2020)
      Background: Omics technologies, enabling the measurements of genes (genomics), mRNA (transcriptomics), proteins (proteomics) and metabolites (metabolomics), are valuable tools for personalized decision-making. We aimed to identify the existing value assessment frameworks used by health technology assessment (HTA) doers for the evaluation of omics technologies through a systematic review. Methods: PubMed, Scopus, Embase and Web of Science databases were searched to retrieve potential eligible articles published until 31 May 2020 in English. Additionally, through a desk research in HTA agencies' repositories, we retrieved the published reports on the practical use of these frameworks. Results: Twenty-three articles were included in the systematic review. Twenty-two frameworks, which addressed genetic and/or genomic technologies, were described. Most of them derived from the ACCE framework and evaluated the domains of analytical validity, clinical validity and clinical utility. We retrieved forty-five reports, which mainly addressed the commercial transcriptomic prognostics and next generation sequencing, and evaluated clinical effectiveness, economic aspects, and description and technical characteristics. Conclusions: A value assessment framework for the HTA evaluation of omics technologies is not standardized and accepted, yet. Our work reports that the most evaluated domains are analytical validity, clinical validity and clinical utility and economic aspects.