The impact of tinnitus on Dutch general practices: A retrospective study using routine healthcare data.

Purpose: Global prevalence of tinnitus (15%) is rising, indicating an increase in patients seeking help for this common symptom and potentially affecting the accessibility of care. The aim of this retrospective study is twofold; describing the morbidity trends and healthcare utilization among patients with recorded tinnitus at Dutch general practices (GP), and comparing overall healthcare utilization before and after tinnitus to similar patients without recorded tinnitus.

Patients And Methods: Routine electronic health records data from general practices participating in Nivel Primary Care Database were used to describe trends in age- and sex-specific incidence, contact prevalence and healthcare utilization (contacts, prescriptions, and referrals to secondary care) for tinnitus from 2012 to 2021.

Outcomes of community-acquired pneumonia using the Pneumonia Severity Index the CURB-65 in routine practice of emergency departments.

Background: The Pneumonia Severity Index (PSI) and the CURB-65 score assess disease severity in patients with community-acquired pneumonia (CAP). We compared the clinical performance of both prognostic scores according to clinical outcomes and admission rates.

Methods: A nationwide retrospective cohort study was conducted using claims data from adult CAP patients presenting to the emergency department (ED) in 2018 and 2019.

Childhood cancer and hematological disorders negatively affect spermatogonial quantity at diagnosis: a retrospective study of a male fertility preservation cohort.

Study Question: What is the impact of cancer or hematological disorders on germ cells in pediatric male patients?

Summary Answer: Spermatogonial quantity is reduced in testes of prepubertal boys diagnosed with cancer or severe hematological disorder compared to healthy controls and this reduction is disease and age dependent: patients with central nervous system cancer (CNS tumors) and hematological disorders, as well as boys <7 years are the most affected.

What Is Known Already: Fertility preservation in pediatric male patients is considered based on the gonadotoxicity of selected treatments. Although treatment effects on germ cells have been extensively investigated, limited data are available on the effect of the disease on the prepubertal male gonad.

HARmonized Protocol Template to Enhance Reproducibility of Hypothesis Evaluating Real-World Evidence Studies on Treatment Effects: A Good Practices Report of a Joint ISPE/ISPOR Task Force.

Objectives: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias.

HARmonized Protocol Template to Enhance Reproducibility of hypothesis evaluating real-world evidence studies on treatment effects: A good practices report of a joint ISPE/ISPOR task force.

Problem: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias.

EUnetHTA relative effectiveness assessments: efforts to increase usability, transparency and inclusiveness.

Objectives: The objective of the European Network for Health Technology Assessment (EUnetHTA) Joint Action 3 (JA3) was to develop a sustainable European model for future collaboration on HTA, by reducing duplication in HTA production and increasing patient access to health technologies. Compared to the previous JA2, several procedural changes were made aiming to increase usability, transparency, and inclusiveness of relative effectiveness assessments (REAs). This article presents and highlights these changes, explains their rationale as well as their influence on HTA production.

Addressing uncertainty in relative effectiveness assessments by HTA organizations.

This study outlines the ways in which different health technology assessment (HTA) organizations deal with uncertainty in relative effectiveness assessments (REAs), using the GRADE framework as a common reference. Guidelines regarding REA and uncertainty assessment methods and three most recent HTA reports (as of April 2020) of seven HTA organizations in Germany, England and Wales, France, the Netherlands, Europe (EUnetHTA), the USA, and Canada were included. First, it was analyzed how each organization addressed uncertainty on the following levels of evidence: (i) individual studies, (ii) body of evidence for one outcome, (iii) body of evidence across all outcomes, and (iv) added net benefit.

Early Cost-Effectiveness of Onasemnogene Abeparvovec-xioi (Zolgensma) and Nusinersen (Spinraza) Treatment for Spinal Muscular Atrophy I in The Netherlands With Relapse Scenarios.

Objectives: Onasemnogene Abeparvovec-xioi (AVXS-101) is a gene therapy intended for curative treatment of spinal muscular atrophy (SMA) with an expected price of around €2 000 000. The goal of this study is to perform a cost-effectiveness analysis of treatment of SMA I patients with AVXS-101 in The Netherlands including relapse scenarios.

Methods: An individual-based state-transition model was used to model treatment effect and survival of SMA I patients treated with AVXS-101, nusinersen and best supportive care (BSC).

Patient involvement in relative effectiveness assessments in the European Network for Health Technology Assessment.

Patient involvement in the process of producing health technology assessments has become increasingly important. In the European Network for Health Technology Assessment (EUnetHTA), several approaches to patient involvement were explored. The outcome was a document on "Patient Input in Relative Effectiveness Assessments" that is available for access and was published in 2019.

The Application and Implications of Novel Deterministic Sensitivity Analysis Methods.

Deterministic sensitivity analyses (DSA) remain important to interpret the effect of uncertainties in individual parameters on results of cost-effectiveness analyses. Classic DSA methodologies may lead to wrong conclusions due to a lack of or misleading information regarding marginal effects, non-linearity, likelihood and correlations. In addition, tornado diagrams are misleading in some situations.

Increasing the information provided by probabilistic sensitivity analysis: The relative density plot.

Background: Results of probabilistic sensitivity analyses (PSA) are frequently visualized as a scatterplot, which is limited through overdrawing and a lack of insight in relative density. To overcome these limitations, we have developed the Relative Density plot (PSA-ReD).

Methods: The PSA-ReD combines a density plot and a contour plot to visualize and quantify PSA results.

The Role of Regulator-Imposed Post-Approval Studies in Health Technology Assessments for Conditionally Approved Drugs.

Background: The European Medicines Agency (EMA) aims to resolve uncertainties associated with conditionally approved drugs by imposing post-approval studies. Results from these studies may be relevant for health technology assessment (HTA) organizations. This study investigated the role of regulator-imposed post-approval studies within HTA.

Assessment of significant benefit for orphan medicinal products by European regulators may support subsequent relative effectiveness assessments by health technology assessment organizations.

To maintain orphan drug status at the time of market authorization, orphan medicinal products (OMPs) need to be assessed for all criteria, including significant benefit, by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA). Subsequently, health technology assessment (HTA) organizations evaluate the same OMPs in their relative effectiveness assessments (REAs). This review investigates the similarities and differences between the two frameworks for six HTA organizations, including the European Network for HTA.

Efficacy gap between phase II and subsequent phase III studies in oncology.

Aims: There is a trend for more flexibility in timing of evidence generation in relation to marketing authorization, including the option to complete phase III trials after authorization or not at all. This paper investigated the relation between phase II and III clinical trial efficacy in oncology.

Methods: All oncology drugs approved by the European Medicines Agency (2007-2016) were included.

Lower versus Traditional Treatment Threshold for Neonatal Hypoglycemia.

Background: Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment.

Methods: In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia.

Phase I/II Clinical Trial-Based Early Economic Evaluation of Acalabrutinib for Relapsed Chronic Lymphocytic Leukaemia.

Objectives: The objective of this study was to construct an early economic evaluation for acalabrutinib for relapsed chronic lymphocytic leukaemia (CLL) to assist early reimbursement decision making. Scenarios were assessed to find the relative impact of critical parameters on incremental costs and quality-adjusted life-years (QALYs).

Methods: A partitioned survival model was constructed comparing acalabrutinib and ibrutinib from a UK national health service perspective.

Graphical Depiction of Longitudinal Study Designs in Health Care Databases.

Pharmacoepidemiologic and pharmacoeconomic analysis of health care databases has become a vital source of evidence to support health care decision making and efficient management of health care organizations. However, decision makers often consider studies done in nonrandomized health care databases more difficult to review than randomized trials because many design choices need to be considered. This is perceived as an important barrier to decision making about the effectiveness and safety of medical products.

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.

Is there a conflict between general practitioners applying guidelines for antibiotic prescribing and including their patients' preferences?

Objectives: One perceived barrier to guideline adherence is the existence of conflicting patient preferences. We examined whether patient preferences influence the prescription of antibiotics in general practice, and how this affects guideline adherence. We hypothesized that preferences play a larger role in prescribing antibiotics if the guideline allows for preferences to be taken into account, ie, if prescribing antibiotics is an option which can be considered rather than a clear recommendation to prescribe or not.

Comparing the hta core model with a national health technology assessment report.

Objectives: The HTA Core Model is a framework for producing health technology assessments (HTAs) in a structured format. The Model splits the content of a HTA into assessment elements. The objective is to explore the adaptability of these assessment elements in national report production in a pilot case study comparing a national HTA report and the HTA Core Model.

Why patients may not exercise their choice when referred for hospital care. An exploratory study based on interviews with patients.

Background: Various north-western European health-care systems encourage patients to make an active choice of health-care provider. This study explores, qualitatively, patients' hospital selection processes and provides insight into the reasons why patients do or do not make active choices.

Methods: Semi-structured individual interviews were conducted with 142 patients in two departments of three Dutch hospitals.