Eligibility for vericiguat in a real-world heart failure population according to trial, guideline and label criteria:Data from the Swedish Heart Failure Registry

Aim: We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. Methods and results: From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration ≥6 months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. Conclusion: In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality.</p

Adherence Barriers to Antimicrobial Treatment Guidelines in Teaching Hospital, the Netherlands

To optimize appropriate antimicrobial use in a university hospital and identify barriers hampering implementation strategies, physicians were interviewed regarding their opinions on antimicrobial policies. Results indicated that effective strategies should include regular updates of guidelines that incorporate the views of relevant departments and focus on addressing senior staff and residents because residents do not make independent decisions in a teaching-hospital setting

Perspectives on a Way Forward to Implementation of Precision Medicine in Patients With Diabetic Kidney Disease; Results of a Stakeholder Consensus-Building Meeting

Aim: This study aimed to identify from different stakeholders the benefits and obstacles of implementing precision medicine in diabetic kidney disease (DKD) and to build consensus about a way forward in order to treat, prevent, or even reverse this disease. Methods: As part of an ongoing effort of moving implementation of precision medicine in DKD forward, a two-day consensus-building meeting was organized with different stakeholders involved in drug development and patient care in DKD, including patients, patient representatives, pharmaceutical industry, regulatory agencies representatives, health technology assessors, healthcare professionals, basic scientists, and clinical academic researchers. The meeting consisted of plenary presentations and discussions, and small group break-out sessions. Discussion topics were based on a symposium, focus groups and literature search. Benefits, obstacles and potential solutions toward implementing precision medicine were discussed. Results from the break-out sessions were presented in plenary and formed the basis of a broad consensus discussion to reach final conclusions. Throughout the meeting, participants answered several statement and open-ended questions on their mobile device, using a real-time online survey tool. Answers to the statement questions were analyzed descriptively. Results of the open-ended survey questions, the break-out sessions and the consensus discussion were analyzed qualitatively. Results and conclusion: Seventy-one participants from 26 countries attended the consensus-building meeting in Amsterdam, April 2019. During the opening plenary on the first day, the participants agreed with the statement that precision medicine is the way forward in DKD (n = 57, median 90, IQR [75–100]). Lack of efficient tools for implementation in practice and generating robust data were identified as significant obstacles. The identified benefits, e.g., improvement of the benefit-risk ratio of treatment, offer substantive incentives to find solutions for the identified obstacles. Earlier and increased multi-stakeholder collaboration and specific training may provide solutions to alter clinical and regulatory guidelines that lie at the basis of both obstacles and solutions. At the end of the second day, the opinion of the participants toward precision medicine in DKD was somewhat more nuanced (n = 45, median 83, IQR [70–92]) and they concluded that precision medicine is an important way forward in improving the treatment of patients with DKD

The role of stakeholder involvement in the evolving EU HTA process:Insights generated through the European Access Academy’s multi-stakeholder pre-convention questionnaire

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. The survey was circulated to a wide expert audience including all relevant stakeholder groups in order to determine self-perception by the ‘key’ stakeholders regarding involvement in the HTA process (self-rating), and in a second, slightly modified version of the questionnaire, to determine the perception of ‘key’ stakeholder involvement by HTA bodies, payers, and policymakers (external rating). Predefined analyses were conducted on the submitted responses. Fifty-four responses were received (patients 9; clinicians: 8; regulators: 4; HTDs 14; HTA bodies: 7; Payers: 5; policymakers 3; others 4). The mean self-perceived involvement score was consistently lower for each of the ‘key’ stakeholder groups than the respective external ratings. Based on the qualitative insights generated in the survey, a RACI Chart (Responsible/Accountable/Consulted/Informed) was developed for each of the stakeholder groups to determine their roles and involvement in the current EU HTA process. Our findings suggest extensive effort and a distinct research agenda are required to ensure adequate involvement of the key stakeholder groups in the evolving EU HTA process.</p

A full-document analysis of the semantic relation between European Public Assessment Reports and EMA guidelines using a BERT language model

In the European Union, the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) develop guidelines to guide drug development, supporting development of efficacious and safe medicines. A European Public Assessment Report (EPAR) is published for every medicine application that has been granted or refused marketing authorisation within the EU. In this work, we study the use of text embeddings and similarity metrics to investigate the semantic similarity between EPARs and EMA guidelines. All 1024 EPARs for initial marketing authorisations from 2008 to 2022 was compared to the 669 current EMA scientific guidelines. Documents were converted to plain text and split into overlapping chunks, generating 265,757 EPAR and 27,649 guideline text chunks. Using a Sentence BERT language model, the chunks were transformed into embeddings and fed into an in-house piecewise matching algorithm to estimate the full-document semantic distance. In an analysis of the document distance scores and product characteristics using a linear regression model, EPARs of anti-virals for systemic use (ATC code J05) and antihemorrhagic medicines (B02) present with statistically significant lower overall semantic distance to guidelines compared to other therapeutic areas, also when adjusting for product age and EPAR length. In conclusion, we believe our approach provides meaningful insight into the interplay between EMA scientific guidelines and the assessment made during regulatory review, and could potentially be used to answer more specific questions such as which therapeutic areas could benefit from additional regulatory guidance.</p