Implementing Outcomes-Based Managed Entry Agreements for Rare Disease Treatments: Nusinersen and Tisagenlecleucel.

Background And Objective: Enthusiasm for the use of outcomes-based managed entry agreements (OBMEAs) to manage uncertainties apparent at the time of appraisal/pricing and reimbursement of new medicines has waned over the past decade, as challenges in establishment, implementation and re-appraisal have been identified. With the recent advent of innovative treatments for rare diseases that have uncertainties in the clinical evidence base, but which could meet a high unmet need, there has been renewed interest in the potential of OBMEAs. The objective of this research was to review the implementation of OBMEAs for two case studies across countries in the European Union, Australia and Canada, to identify good practices that could inform development of tools to support implementation of OBMEAs.

Precision cancer medicine: What has translated into clinical use in Belgium?

Rationale: In 2016, Belgium launched the Next Generation Sequencing (NGS) Roadbook, consisting in 10 Actions, across the health care system, to facilitate the uptake of NGS in routine clinical practice. We compiled feedback on deployment of the NGS Roadbook from governmental stakeholders and beneficiaries: health policy makers, insurance providers, pathologists, geneticists, and oncologists.

Main Findings: The Roadbook ensured the establishment of a Commission on Personalized Medicine and NGS testing guidelines.

Bratislava Statement: consensus recommendations for improving pancreatic cancer care.

Pancreatic cancer is one of the most lethal tumours, and it is the fourth cause of cancer death in Europe. Despite its important public health impact, no effective treatments exist, nor are there high-visibility research efforts to improve care. This alarming situation is emblematic of a larger group of cancer diseases, known as neglected cancers.

Evaluation of precision medicine assessment reports of the Belgian healthcare payer to inform reimbursement decisions.

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.

Real-world evidence to support Payer/HTA decisions about highly innovative technologies in the EU-actions for stakeholders.

Objectives: There are divergent views on the potential of real-world data (RWD) to inform decisions made by regulators, health technology assessment (HTA) bodies, payers, clinicians, and patients. This RWE4Decisions initiative explored the particularly challenging setting of highly innovative technologies, which require Payers/HTAs to make decisions on a small evidence base with major uncertainties. The aim was to go beyond strategic intent to consider actions that each stakeholder could take to improve use of RWD in this setting.

Psychosocial determinants predicting long-term sickness absence: a register-based cohort study.

Background: This study assessed the psychosocial determinants as explanatory variables for the length of the work disability period. The aim was to estimate the predictive value of a selected set of psychosocial determinants from the Quickscan questionnaire for the length of the sick leave period. A comparison was also made with the most common biomedical determinant: diagnosis.

Regulatory and health technology assessment advice on postlicensing and postlaunch evidence generation is a foundation for lifecycle data collection for medicines.

The understanding of the benefit risk profile, and relative effectiveness of a new medicinal product, are initially established in a circumscribed patient population through clinical trials. There may be uncertainties associated with the new medicinal product that cannot be, or do not need to be resolved before launch. Postlicensing or postlaunch evidence generation (PLEG) is a term for evidence generated after the licensure or launch of a medicinal product to address these remaining uncertainties.

Influence of reimbursement policies on phlebological surgical practice in Belgium between 2007 and 2017.

Background: To date, it is unclear how treatment of patients with chronic venous disease (CVD) is influenced by national reimbursement systems. In Belgium, catheters or fibers used for endovenous thermal ablation (EVTA) are reimbursed only once in a lifetime. The potential impact of the Belgian public health insurance reimbursement policy on surgical practice in phlebology needs to be investigated.

The financial impact of SBRT for oligometastatic disease: A population-level analysis in Belgium.

Introduction: There is a steady rise in Stereotactic Body RadioTherapy (SBRT) utilization in oligometastatic disease (OMD). This may generate important financial consequences for radiotherapy budgets. The National Institute for Health and Disability Insurance of Belgium (NIHDI) initiated a coverage with evidence development (CED) project for innovative radiotherapy, including SBRT, in 2011.

Multiple Criteria Decision Analysis for HTA across four EU Member States: Piloting the Advance Value Framework.

Multiple Criteria Decision Analysis (MCDA) has emerged as a methodology for Health Technology Assessment (HTA). However, limited empirical evidence is available on its use by decision-makers; where available, it only comes from single-setting exercises, while cross-country comparative studies are unavailable. This study applies the Advance Value Framework (AVF), an MCDA methodology for HTA based on multi-attribute value theory, through a series of case studies with decision-makers in four countries, to explore its feasibility and compare decision-makers' value preferences and results.

Real-life effectiveness of omalizumab in difficult-to-treat severe asthma: a national cohort study in Belgium.

Background: Guidelines recommend omalizumab in patients with uncontrolled severe allergic asthma. We investigated real-life use of omalizumab, the proportion of patients fulfilling eligibility criteria, its costs and its effectiveness.

Method: In a cohort of asthma patients initiating treatment with omalizumab in Belgium between 2010 and 2016, we investigated fulfilment of eligibility criteria (chronic use of high-dose inhaled corticosteroids (ICSs) plus long-acting β-agonists (LABAs) and ≥2 severe asthma exacerbations in previous year), and compared hospitalisations and systemic corticosteroid consumption in the year before and after omalizumab initiation.

Map-Assisted Generation of Procedure and Intervention Encoding (Magpie): An Innovative Approach for ICD-10-PCS Coding.

ICD-10-PCS coding is challenging because of the large number of codes, non-intuitive terms and paucity of the ICD-10-PCS index. We previously repurposed the richer ICD-9-CM procedure index for ICD-10-PCS coding. We have developed the MAGPIE tool based on the repurposed ICD-9-CM index with other lexical and mapping resources.

Re-purposing the ICD-9-CM Procedures Index for Coding in ICD-10-PCS and SNOMED CT.

Compared to the ICD-10-PCS index, the ICD-9-CM Procedure (ICD9V3) Index is richer and contains more clinician-friendly terms including abbreviations and eponyms. We re-purposed the ICD9V3 index by mapping the index terms to SNOMED CT and the ICD-9-CM codes to ICD-10-PCS codes through the General Equivalent Mappings. The re-purposed index outperformed the ICD-10-PCS index in the retrieval of ICD-10-PCS codes using a list of commonly used procedure names, with significantly higher recall, precision and F-score.

Quickscan assesses risk factors of long-term sickness absence: A cross-sectional (factorial) construct validation study.

Objectives: The number of sick-listed employees has increased dramatically worldwide. Therefore, many countries aim to stimulate early and sustainable return to work opportunities to obtain better health outcomes and lower costs for disability pensions. To effectively orientate resources to patients with a high risk of not resuming work spontaneously, it is necessary to screen patients early in their sickness absence process.

High uptake of pre-exposure prophylaxis (PrEP) during early roll-out in Belgium: results from surveillance reports.

Unlabelled: Background Since 1 June 2017, oral pre-exposure prophylaxis (PrEP) could be prescribed and reimbursed in Belgium as prophylactic medication for people who are at increased risk of HIV acquisition. The aim of this study was to determine the uptake of daily and event-driven PrEP in Belgium during the first 9 months of roll-out.

Methods: Routine aggregated data on the number of reimbursement requests and the number of boxes of Truvada (Gilead Sciences, Cambridge, UK) delivered for PrEP through the Belgian pharmacies were obtained from the National Institute for Health and Disability Insurance.

The European challenges of funding orphan medicinal products.

Background: Funding of orphan medicinal products (OMPs) is an increasing challenge in the European Union (EU).

Objectives: To identify the different methods for public funding of OMPs in order to map the availability for rare disease patients, as well as to compare the public expenditures on OMPs in 8 EU member states.

Methods: Information on the reimbursement status of 83 OMPs was collected in 8 countries by distinguishing standard and special reimbursements.

Roadbook for the implementation of next-generation sequencing in clinical practice in oncology and hemato-oncology in Belgium.

In the field of oncology research, next-generation sequencing has contributed significantly to the discovery of DNA mutations associated with diagnosis and prognosis. It also aids in the development of targeted therapies to specific mutations and the rise of personalized medicine. As part of molecular diagnostics in cancer patients, analysis by next-generation sequencing is becoming part of routine clinical practice.

A multi-criteria decision approach for ranking unmet needs in healthcare.

Early temporary reimbursement (ETR) schemes for new interventions targeting high unmet needs are increasingly applied in pharmaceutical policy. Crucial for these schemes is the assessment of unmet healthcare needs of patients and society. This study develops and tests a multi-criteria decision approach (MCDA) for assessing therapeutic and societal needs.

Achieving Logical Equivalence between SNOMED CT and ICD-10-PCS Surgical Procedures.

Surgical procedures are coded in SNOMED CT in the electronic health record and in ICD-10-PCS in administrative systems. We compared the logical definitions of SNOMED CT concepts to the ICD-10-PCS axial components to identify overlap and gaps. The biggest discrepancy was in the surgical approach which was specified in all ICD-10-PCS codes but only in 8.

The impact of parallel regulatory-health technology assessment scientific advice on clinical development. Assessing the uptake of regulatory and health technology assessment recommendations.

Aims: The parallel regulatory-health technology assessment scientific advice (PSA) procedure allows manufacturers to receive simultaneous feedback from both EU regulators and health technology assessment (HTA) bodies on development plans for new medicines. The primary objective of the present study is to investigate whether PSA is integrated in the clinical development programmes for which advice was sought.

Methods: Contents of PSA provided by regulators and HTA bodies for each procedure between 2010 and 2015 were analysed.

Perspectives on the integration of Immuno-Oncology Biomarkers and drugs in a Health Care setting.

Immunotherapies, specifically checkpoint inhibitors, are becoming an important component in cancer care with the most application now in melanoma and lung cancer patients. Some drawbacks that converge with this new evolution are the rather low response rates to these drugs and their high cost with a significant economic impact on the health care system. These major challenges can likely be circumvented by implementing a "personalized immuno-oncology" approach to accomplish a selection of optimal responders based on biomarkers.

Payers' Views of the Changes Arising through the Possible Adoption of Adaptive Pathways.

Payers are a major stakeholder in any considerations and initiatives concerning adaptive licensing of new medicinal products, also referred to as Medicines Adaptive Pathways to patients (MAPPs). Firstly, the scope and necessity of MAPPs need further scrutiny, especially with regard to the definition of unmet need. Conditional approval pathways already exist for new medicines for seriously debilitating or life-threatening diseases and only a limited number of new medicines are innovative.

The heart and pulmonary arterial hypertension in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs (gastrointestinal tract, heart, kidneys and lungs). Although the prevalence is low, SSc is a disease with high morbidity and mortality. Since pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) and clinically evident cardiac involvement is associated with increased mortality, the cardiac complications and PAH in SSc are reviewed.