Technology Assessment vs. Technology Appraisal-How to Strengthen the Science/Value Dichotomy with EU HTA?

Many countries around the world use health technology assessment (HTA) to inform reimbursement and pricing decisions. HTA is often split into two steps, called assessment and appraisal. While the term HTA itself has been defined by international consortia, there is heterogeneity in the way different stakeholders use the terms assessment and appraisal.

The Role of Medical Societies and the Relevance of Clinical Perspective in the Evolving EU HTA Process: Insights Generated at the 2023 Fall Convention and Survey of the European Access Academy.

Background: This work aimed to determine the role and action points for the involvement of medical societies in the European Health Technology Assessment (EU HTA) Methods: An online pre-convention survey was developed addressing four areas related to the EU HTA: (i) medical societies' role; (ii) role of clinical guidelines; (iii) interface with the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS); and (iv) approaching 'best-available evidence' (BAE). A descriptive analysis of questionnaire outcomes was conducted to inform the European Access Academy (EAA) Fall Convention 2023. Within the working groups (WGs), action points were identified and prioritised.

Navigating the path towards successful implementation of the EU HTA Regulation: key takeaways from the 2023 Spring Convention of the European Access Academy.

Background: The European Regulation on Health Technology Assessment (EU HTA R), effective since January 2022, aims to harmonize and improve the efficiency of common HTA across Member States (MS), with a phased implementation from January 2025. At "midterms" of the preparation phase for the implementation of the Regulation our aim was to identify and prioritize tangible action points to move forward.

Methods: During the 2023 Spring Convention of the European Access Academy (EAA), participants from different nationalities and stakeholder backgrounds discussed readiness and remaining challenges for the Regulation's implementation and identified and prioritized action points.

An Inclusive Civil Society Dialogue for Successful Implementation of the EU HTA Regulation: Call to Action to Ensure Appropriate Involvement of Stakeholders and Collaborators.

Objectives: Stakeholder involvement has long been considered a success factor for a joint European health technology assessment (HTA) process, and its relevance is now anchored in the EU HTA Regulation's (EU HTAR) legislative wording. Therefore, we aimed to explore the roles, challenges, and most important activities to increase the level of involvement per stakeholder group.

Methods: At the 2022 Fall Convention of the European Access Academy (EAA), working groups addressed the involvement of patients, clinicians, regulators, health technology developers (HTD), and national HTA bodies and payers within the EU HTA process.

The role of stakeholder involvement in the evolving EU HTA process: .

Involvement of all relevant stakeholders will be of utmost importance for the success of the developing EU HTA harmonization process. A multi-step procedure was applied to develop a survey across stakeholders/collaborators within the EU HTA framework to assess their current level of involvement, determine their suggested future role, identify challenges to contribution, and highlight efficient ways to fulfilling their role. The 'key' stakeholder groups identified and covered by this research included: patients', clinicians', regulatory, and Health Technology Developer representatives.

How can a joint European health technology assessment provide an 'additional benefit' over the current standard of national assessments? : Insights generated from a multi-stakeholder survey in hematology/oncology.

Objectives: We conducted a multi-stakeholder survey to determine key areas where a joint European health technology assessment (HTA) could provide 'additional benefit' compared to the status quo of many parallel independent national and subnational assessments.

Methods: Leveraging three iterative Delphi cycles, a semiquantitative questionnaire was developed covering evidence challenges and heterogeneity of value drivers within HTAs across Europe with a focus on hematology/oncology. The questionnaire consisted of five sections: i) background information; ii) value drivers in HTA assessments today; iii) evolving evidence challenges; iv) heterogeneity of value drivers across Europe; v) impact of Europe's Beating Cancer Plan (EBCP).

Tissue origin of cytotoxic natural killer cells dictates their differential roles in mouse digit tip regeneration and progenitor cell survival.

Regeneration of amputated digit tips relies on mesenchymal progenitor cells and their differentiation into replacement bone and tissue stroma. Natural killer (NK) cells have well-characterized roles in antigen-independent killing of virally infected, pre-tumorous, or stressed cells; however, the potential for cytotoxic activity against regenerative progenitor cells is unclear. We identified NK cell recruitment to the regenerating digit tip, and NK cytotoxicity was observed against osteoclast and osteoblast progenitors.

Intraindividual Comparisons to Determine Comparative Effectiveness: Their Relevance for G-BA's Health Technology Assessments.

Objectives: Health technology assessments (HTA) rely on head-to-head comparisons. We searched for intraindividual comparisons (IIC) qualifying as head-to-head design to develop comparative evidence.

Methods: Gemeinsamer Bundesausschuss (G-BA) appraisals between January 2011 and April 2020 were reviewed for inclusion of IIC.

Leveraging EUnetHTA's conceptual framework to compare HTA decision drivers in France, Italy, and Germany from a manufacturer's point of view.

Background: Health Technology Assessments (HTA) procedures differ substantially across the various European countries. We reviewed recent appraisals of a pharmaceutical manufacturer in three major European markets (France; Italy; Germany) and identified and categorized related decision drivers.

Methods: New marketing authorisation between January 2011 and August 2017, and Roche being the Marketing Authorization Holder, were included.

"Market withdrawals" of medicines in Germany after AMNOG: a comparison of HTA ratings and clinical guideline recommendations.

Background: According to the AMNOG act, the German Federal Joint Committee (G-BA) determines the additional benefit of new medicines as a basis for subsequent price negotiations. Pharmaceutical companies may withdraw their medications from the market at any time during the process. This analysis aims to compare recommendations in clinical guidelines and HTA appraisals of medicines that were withdrawn from the German market since the introduction of AMNOG in 2011.

Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany.

Background: In oncology clinical trials, crossover is used frequently but may lead to uncertainties regarding treatment effects.

Objective: To investigate the handling of evidence from crossover trials by the European Medicines Agency (EMA) and the German Federal Joint Committee (G-BA).

Methods: For oncology medicines with early benefit assessments before January 2015, presence of crossover, clinical data, EMA requests for additional data, and G-BA benefit ratings/evidence levels were analyzed from manufacturers' dossiers, G-BA appraisals, European Public Assessment Reports, and original publications.

Thulium vapoenucleation of the prostate versus holmium laser enucleation of the prostate for the treatment of large volume prostates: preliminary 6-month safety and efficacy results of a prospective randomized trial.

Purpose: We compared the perioperative and postoperative characteristics of thulium vapoenucleation and holmium laser enucleation of the prostate for the treatment of large volume benign prostatic hyperplasia.

Materials And Methods: A total of 94 patients with benign prostatic hyperplasia and a median prostate size of 80 (IQR 46.75-100) cc were either randomized to thulium vapoenucleation or holmium laser enucleation of the prostate.

Different Weights of the Evidence-Based Medicine Triad in Regulatory, Health Technology Assessment, and Clinical Decision Making.

Evidence-based medicine (EBM) is defined as a systematic approach to clinical problem solving by the integration of best research evidence with real-world clinical expertise and patient values. Since those early days, decision requirements expanded from patient-centric clinical decision making to a population-based view including regulatory health technology assessments (HTAs). Regulatory bodies mainly rely on the totality of research evidence, which includes preclinical and all available clinical data.

Neonatal and Maternal Short-Term Outcome Parameters in Instrument-Assisted Vaginal Delivery Compared to Second Stage Cesarean Section in Labour: A Retrospective 11-Year Analysis.

Background: This study is aimed at comparing the neonatal and maternal short-term outcomes after instrumental-assisted vaginal delivery and cesarean section (CS) in labour.

Methods: This retrospective study over a period of 11 years included singleton pregnancies above 34 + 0 gestational weeks, giving birth either by instrumental-assisted delivery or CS in labour. Maternal and neonatal outcome parameters were analysed using t test or linear regression.

Inconsistent approaches of the G-BA regarding acceptance of primary study endpoints as being relevant to patients - an analysis of three disease areas: oncological, metabolic, and infectious diseases.

Background: Previous evaluations of oncological medicines in the German early benefit assessment (EBA) procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA). Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs) from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas.

Comparison of post-authorisation measures from regulatory authorities with additional evidence requirements from the HTA body in Germany - are additional data requirements by the Federal Joint Committee justified?

Objectives: The aim of this study was to compare post-authorisation measures (PAMs) from the European Medicines Agency (EMA) with data requests in fixed-termed conditional appraisals of early benefit assessments from the German Federal Joint Committee (G-BA).

Methods: Medicinal products with completed benefit assessments during an assessment period of 3.5 years were considered.

Age Dependency of GLI Reference Values Compared with Paediatric Lung Function Data in Two German Studies (GINIplus and LUNOKID).

A hallmark of the newly published GLI (Global Lungs Initiative) spirometric reference values is their "all-age" (3-95yr) predictive power, accomplished by incorporating non-linear age dependencies into modelling parameters. This modelling strategy is especially promising for the age range of puberty; however, the performance of GLI-values for adolescents is currently unknown. We calculated GLI-based z-scores for children/adolescents without apparent respiratory diseases from two different German studies, LUNOKID (N = 1943, 4-19 years) and GINIplus (N = 1042, 15 years) and determined the goodness of fit for specific age groups.

Maternal and pregnancy characteristics affect plasma fibrin monomer complexes and D-dimer reference ranges for venous thromboembolism in pregnancy.

Background: D-dimers have a high negative predictive value for excluding venous thromboembolism outside of pregnancy but the use in pregnancy remains controversial. A higher cut-off value has been proposed in pregnancy due to a continuous increase across gestation. Fibrin monomer complexes have been considered as an alternative diagnostic tool for exclusion of venous thromboembolism in pregnancy due to their different behavior.

Correlation of fetal scalp blood sampling pH with neonatal outcome umbilical artery pH value.

Purpose: Fetal scalp blood sampling is considered as a complimentary tool in addition to cardiotocography to assess fetal well-being. This blood sampling is important as the obstetrician has to judge and make decisions regarding the further management of the delivery based on this pH result. The aim of this study was to analyze the correlation between fetal scalp blood pH and the umbilical artery pH after birth.

Background Knowledge and Attitude of Pregnant Women towards Ultrasound Screening at 20-23 Weeks Gestation.

Background: Prenatal ultrasound screening in the second trimester is widely used in maternal health care. Prenatal diagnosis and prenatal screening is often exposed to several accusation, such as inducing unnecessary anxiety, carrying out a selection and forcing pregnant women into attending ultrasound screening. The aim of this study was to investigate the knowledge and the intention of pregnant women attending the second trimester ultrasound screening.