Lead Investigator: Luca Valerio, University Medical Center of the Johannes Gutenberg-University Mainz
Title of Proposal Research: Healthcare resource utilization and economic burden related to pulmonary embolism. An analysis of the PREFER in venous thromboembolism (VTE) study
Vivli Data Request: 6632
Funding Source: Commercial Funding – Funded by Daiichi Sankyo Deutschland GmbH in the setting of proposal DSE-DE-CV-20001, research plan “Filling the gaps of knowledge on healthcare outcomes during long-term anticoagulant treatment of pulmonary embolism”, Approved April 2020, Agreement May 2020; contact persons Mathias Lampartner, Wolfgang Zierhut (Regional) and Sheila Vignali, Martin Meier (Local).
Potential Conflicts of Interest: This project is supported by a grant by the data contributor (Daiichi Sankyo).
The Lead Investigator declares no personal, professional or financial relationship with Daiichi Sankyo that could influence or give the appearance of potentially influencing his work in this project, including personal grants, personal fees, patents/copyrights or non-financial support, either in relation to the present project or outside of it, either currently or in the past.
The grant that supports this project was not bequeathed to the Lead Investigator or any of the investigators of the research team, but only to their institution (University Medical Center of the Johannes Gutenberg-University Mainz).
None of the research projects connected to the grant in question, including the project described here, include any evaluation of products in which the sponsor may have a vested commercial interest, but only represent secondary, observational and purely descriptive post-hoc analyses of clinical and post-clinical course of patients selected based on purely clinical criteria, with no relationship whatsoever to the efficacy/safety of a product or any direct or indirect implication for the quality of a product. In these analyses, no specific direction of any found association would be of higher interest than other directions to either the researchers or the sponsor.
Summary of the Proposed Research:
Survivors of acute pulmonary embolism carry a long-term risk of medical complications related to pulmonary embolism itself, pre-existing conditions or risk factors, and anticoagulation treatment, and their medical follow-up typically includes both planned and unplanned contacts and procedures. In addition, patients recovering from pulmonary embolism suffer from loss of physical performance, need for formal and informal support, and either permanent or temporary loss of work ability, all of which lead to significant personal and societal costs. Detailing this economic burden would support public health resource allocation and help to set priorities in devising and applying clinical prognostic tools to identify patients at high risk of requiring intensive treatment or considerable non-medical support in the long term. However, most data on costs and healthcare resource utilization focus on venous thromboembolism, which encompasses pulmonary embolism and deep vein thrombosis, rather than solely on pulmonary embolism, originate from Northern America and may not be readily applicable to Europe; and, in lack of prospectively collected data, are based on modelling strategies that heavily rely on assumptions rather than observed data.
The completion of large-scale phase IV and prospective registries studies such as the PREFER in venous thromboembolism (VTE) study provide for the first time large and thoroughly monitored real-world populations of patients treated for pulmonary embolism and, with them, the opportunity to thoroughly estimate resource utilization and overall costs during the long-term follow-up of patients with pulmonary embolism in Europe.
Over the past 15 years, no more than 20 studies have been conducted to study the economic burden related to some of the most frequent complications of venous thromboembolism or to venous thromboembolism itself, the vast majority of which have been included in a US and in a EU model for venous thromboembolism costs published by Dr. Mahan and by Dr. Barco in 2011-2012 and in 2014 (see Bibliography). These two studies were able to provide a comprehensive estimate of annualised venous thromboembolism cost for several Western countries: however, they necessarily based their estimates on (i) risks derived from the prior medical literature, (ii) costs and resource utilisations retrieved from national sources or, again, from the medical literature. The advantages of building a new model on the PREFER in venous thromboembolism data would be: (i) profiting from actual risks and utilisations retrieved and collected ad hoc, (ii) extrapolating these figures to the European countries where the study had been conducted.
Taking this into account, one may foresee that this information will be of interest for a population exceeding 200 million and, indirectly, for all stakeholders and investigators acting in the field of venous thromboembolism in Western countries. As a proxy, one should note that the two aforementioned manuscripts have been cited more than 200 times and been cited in international guidelines.
Statistical Analysis Plan:
– Collection of standard costs from previous literature and Eurostat adjusted for inflation and purchase power parity at 2020.
– Count of clinical events directly collected in PREFER in VTE and estimate of the prevalence of rare clinical events not directly collected in PREFER in VTE.
– Costs of non-clinical events as directly collected in PREFER in VTE.
– Distribution of clinical and non-clinical events of interest in patients with pulmonary embolism in PREFER in VTE according to a previously published Markov model for venous thromboembolism (Barco et al., 2016, Thrombosis and haemostasis).
– Estimates of costs for three typical patient profiles:
o Best-case scenario: patient with no clinical events during follow-up;
o Worst-case scenario: patient with number of clinical events above the third quartile;
o Average scenario.
Handling of missing data:
– Patients with missing data will be excluded from analysis, and a sensitivity analysis will be conducted to identify the differences in baseline demographic and clinical features between patients with and without missing follow-up data.
Based on available information from the PREFER in VTE study, particularly concerning the type of clinical outcomes and resource utilization been collected, we will adapt the Markov model used in our prior publications (10.1160/TH11-02-0132, 10.1160/TH15-08-0670). In brief, we will first define a decision tree to model sequelae and treatment associated with incident pulmonary embolism. The decision trees contain probability information on patients’ characteristics and on possible complications of an incident VTE derived from actual entries in PREFER in VTE. These may include: cost of treatment in both inpatient and outpatient settings, readmission and recurrence, minor and major bleeding events, heparin-induced thrombocytopenia (HIT), post-thrombotic syndrome (PTS), and chronic thromboembolic pulmonary hypertension (CTPH). As previously done, estimated costs of a premature death will be considered indirect costs.
Prevention of Thromboembolic Events – European Registry in Venous Thromboembolism (PREFER in VTE)
Data Contributor: Daiichi Sankyo, Inc.
Study ID: DSE-VTE-01-12
Farmakis IT, Barco S, Mavromanoli AC, Agnelli G, Cohen AT, Giannakoulas G, Mahan CE, Konstantinides SV, Valerio L. Cost-of-Illness Analysis of Long-Term Health Care Resource Use and Disease Burden in Patients With Pulmonary Embolism: Insights From the PREFER in VTE Registry. J Am Heart Assoc. 2022 Oct 18;11(20):e027514. doi: 10.1161/JAHA.122.027514