Abstract
Life Cycle Management of pharmaceutical products consists of many measures aiming to speed up time to and on the market and clinical use while the drug enjoys patent protection.
Among many other factors, LCM decisions ought to consider technology changes that affect diagnostic or clinical pathways in indications covered by the approved pharmaceutical drug.
The current paper discusses an Investigator Sponsored Research (ISR) activity financially supported by the manufacturer of an oral anticoagulant drug. It was a randomized, double-blind siteless clinical trial that successfully established feasibility and effectiveness of a digitally enabled innovative diagnostic pathway. Tools and pathways tested in the trial greatly facilitated detection and subsequent treatment of patients with Atrial Fibrillation which is the main indication of the oral anticoagulant marketed by the pharmaceutical company.
Therefore, the tool and pathway researched in the trial have become a relevant factor in the life cycle management of this prescription drug.
Using this study as an example the paper comprehensively discusses circumstances and conditions needed to successfully leverage external factors like digital technologies for the life cycle management of a classic prescription drug.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Andrade, J., Khairy, P., Dobrev, D., & Nattel, S. (2014). The clinical profile and pathophysiology of atrial fibrillation: Relationships among clinical features, epidemiology, and mechanisms. Circulation Research, 114(9), 1453–1468. https://doi.org/10.1161/CIRCRESAHA.114.303211
BfArM. (2022). ATC Downloads https://www.bfarm.de/DE/Kodiersysteme/Klassifikationen/ATC/Downloads/_node.html. Accessed 31.01.23.
Cervera-Padrell, A. E., Skovby, T., Kiil, S., Gani, R., & Gernaey, K. V. (2012). Active pharmaceutical ingredient (API) production involving continuous processes--a process system engineering (PSE)-assisted design framework. European Journal of Pharmaceutics and Biopharmaceutics, 82(2), 437–456. https://doi.org/10.1016/j.ejpb.2012.07.001
DiMasi, J. A., et al. (2016). Innovation in the pharmaceutical industry: New estimates of R&D costs. Journal of Health Economics, 47(2016), 20–33.
EFPIA. (2022). https://www.efpia.eu/media/637143/the-pharmaceutical-industry-in-figures-2022.pdf. (efpia.eu), Accessed 16.02.22.
Elkind, M. S. (2010). Inflammatory mechanisms of stroke. Stroke, 41(10 Suppl), S3–S8. https://doi.org/10.1161/STROKEAHA.110.594945
EMA. (2002). https://www.ema.europa.eu/en/ich-e6-r2-good-clinical-practice-scientific-guideline#current-version%2D%2Dsection, Accessed 17.02.23.
ESC. (2022). Atrial fibrillation screening using smartphones increases detection and treatment (escardio.org). Accessed 18.02.23.
Ferguson, T., & Frydman, G. (2004). The first generation of e-patients. BMJ, 328(7449), 1148–1149. https://doi.org/10.1136/bmj.328.7449.1148. PMID: 15142894; PMCID: PMC411079.
Freyer, L., von Stülpnagel, L., Spielbichler, P., Sappler, N., Wenner, F., Schreinlechner, M., et al. (2021). Rationale and design of a digital trial using smartphones to detect subclinical atrial fibrillation in a population at risk: The eHealth-based bavarian alternative detection of atrial fibrillation (eBRAVE-AF) trial. American Heart Journal, 241, 26–34. https://doi.org/10.1016/j.ahj.2021.06.008
GKM Gesellschaft für Therapieforschung mbH. (2023). Investigator Initiated Trials (IIT) - CliNFo.EU, accessed 18.03.23.
Guo, Y., Lane, D. A., Wang, L., Zhang, H., Wang, H., Zhang, W., et al. (2020). Mobile health technology to improve Care for Patients with Atrial Fibrillation. Journal of the American College of Cardiology, 75(13), 1523–1534. https://doi.org/10.1016/j.jacc.2020.01.052
Haas, A., et al. (2021). 10 Jahre AMNOG: Eine Erfolgsgeschichte mit angezogener Handbremse. G+S 1/21 DOI: https://doi.org/10.5771/1611-5821-2021-1-8. Accessed 13.08.21.
Haeusler, K. G., Konieczny, M., Endres, M., Villringer, A., & Heuschmann, P. U. (2012). Impact of anticoagulation before stroke on stroke severity and long-term survival. International journal of stroke: official journal of the International Stroke Society, 7(7), 544–550. https://doi.org/10.1111/j.1747-4949.2011.00672.x
Häussler, B., & Höer, A. (2021). Arzneimittelatlas 2021. Medizinisch Wissenschaftliche Verlagsanstalt, MWV.
Herfarth, H. H., Jackson, S., Schliebe, B. G., Martin, C., Ivanova, A., Anton, K., et al. (2017). Investigator-initiated IBD trials in the United States: Facts, obstacles, and answers. Inflammatory Bowel Diseases, 23(1), 14–22. https://doi.org/10.1097/MIB.0000000000000907. PMID: 27598744; PMCID: PMC5177501.
Hering, S., Loretz, B., Friedli, T., Lehr, C. M., & Stieneker, F. (2018). Can lifecycle management safeguard innovation in the pharmaceutical industry? Drug Discovery Today, 23(12), 1962–1973. https://doi.org/10.1016/j.drudis.2018.10.008
Hindricks, G., Potpara, T., Dagres, N., Arbelo, E., Bax, J. J., Blomström-Lundqvist, C., et al. (2021). 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European heart rhythm association (EHRA) of the ESC. European Heart Journal, 42(5), 373–498. https://doi.org/10.1093/eurheartj/ehaa612
Hohnloser, S. H., et al. (2019). Uptake in antithrombotic treatment and its association with stroke incidence in atrial fibrillation: Insights from a large German claims database. Clinical Research in Cardiology, 108(9), 1042–1052. https://doi.org/10.1007/s00392-019-01437-7. Epub 2019 Feb 15. PMID: 30771066.
Jang, J. P., Lin, H. T., Chen, Y. J., Hsieh, M. H., & Huang, Y. C. (2020). Role of remote monitoring in detection of atrial arrhythmia, stroke reduction, and use of anticoagulation therapy - a systematic review and meta-analysis. Circulation Journal: Official Journal of the Japanese Circulation Society, 84(11), 1922–1930. https://doi.org/10.1253/circj.CJ-20-0633
Kornej, J., Benjamin, E. J., & Magnani, J. W. (2021). Atrial fibrillation: global burdens and global opportunities. Heart (British Cardiac Society), heartjnl-2020-318480. Advance online publication. https://doi.org/10.1136/heartjnl-2020-318480
Krijthe, B. P., Kunst, A., Benjamin, E. J., Lip, G. Y., Franco, O. H., Hofman, A., et al. (2013). Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060. European Heart Journal, 34(35), 2746–2751. https://doi.org/10.1093/eurheartj/eht280
Leclercq, C., Witt, H., Hindricks, G., Katra, R. P., Albert, D., Belliger, A., et al. (2022). Wearables, telemedicine, and artificial intelligence in arrhythmias and heart failure: Proceedings of the European Society of Cardiology Cardiovascular Round Table. Europace: European pacing, arrhythmias, and cardiac electrophysiology: journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 24(9), 1372–1383. https://doi.org/10.1093/europace/euac052
Levine, S. A., & Harvey, E. A. (1930). A study of uninfected mural thrombi of the heart. The American Journal of the Medical Sciences, 180, 365–371.
Lip, G. Y., Nieuwlaat, R., Pisters, R., Lane, D. A., & Crijns, H. J. (2010). Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The euro heart survey on atrial fibrillation. Chest, 137(2), 263–272. https://doi.org/10.1378/chest.09-1584
Lubitz, S. A., Faranesh, A. Z., Selvaggi, C., Atlas, S. J., McManus, D. D., Singer, D. E., et al. (2022). Detection of atrial fibrillation in a large population using wearable devices: The Fitbit heart study. Circulation, 146(19), 1415–1424. https://doi.org/10.1161/CIRCULATIONAHA.122.060291
Marini, C., De Santis, F., Sacco, S., Russo, T., Olivieri, L., Totaro, R., et al. (2005). Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: Results from a population-based study. Stroke, 36(6), 1115–1119. https://doi.org/10.1161/01.STR.0000166053.83476.4a
Nihad, A. M. T., et al. (2009). Drug development: From concept to marketing! Nephron Clinical Practice, 113, 125–131.
Ometov, A., Shubina, V., et al. (2021). A survey on wearable technology: History, state-of-the-art and current challenges. Computer Networks, 193, 108074, ISSN 1389-1286. https://doi.org/10.1016/j.comnet.2021.108074
Osterberg, L., & Blaschke, T. (2005). Adherence to medication. The New England Journal of Medicine, 353(5), 487–497. https://doi.org/10.1056/NEJMra050100
Perez, M. V., Mahaffey, K. W., Hedlin, H., Rumsfeld, J. S., Garcia, A., & Ferris, T. (2019). Large-scale assessment of a smartwatch to identify atrial fibrillation. The New England Journal of Medicine, 381(20), 1909–1917. https://doi.org/10.1056/NEJMoa1901183
Rizas, K. D., Freyer, L., Sappler, N., von Stülpnagel, L., Spielbichler, P., & Krasniqi, A. (2022). Smartphone-based screening for atrial fibrillation: A pragmatic randomized clinical trial. Nature Medicine, 28(9), 1823–1830. https://doi.org/10.1038/s41591-022-01979-w
Ruff, C. T., Giugliano, R. P., Braunwald, E., Hoffman, E. B., Deenadayalu, N., & Ezekowitz, M. D. (2014). Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomised trials. Lancet (London, England), 383(9921), 955–962. https://doi.org/10.1016/S0140-6736(13)62343-0
Sposato, L. A., Cipriano, L. E., Saposnik, G., RuÃz Vargas, E., Riccio, P. M., & Hachinski, V. (2015). Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: A systematic review and meta-analysis. The Lancet. Neurology, 14(4), 377–387. https://doi.org/10.1016/S1474-4422(15)70027-X
Statista. (2020). R&D spending share of top pharmaceutical companies 2018and 2024. Online in Internet. https://www.statista.com/statistics/309471/randd-spending-share-of-toppharmaceutical-companies/. Accessed 02.10.23.
Statista. (2022a). Top Pharmaunternehmen - Umsatz und Forschungsausgaben 2021 Statista. Accessed 10.02.23.
Statista. (2022b). AbbVie Humira revenue 2011–2021|Statista. Accessed 13.02.23.
Statista. (2023). Forecast number of mobile users worldwide 2020–2025|Statista. Accessed 17.02.23.
Steinhubl, S. R., Muse, E. D., & Topol, E. J. (2015). The emerging field of mobile health. Science Translational Medicine, 7(283), 283rv3. https://doi.org/10.1126/scitranslmed.aaa3487
Suvarna, V. (2012). Investigator initiated trials (IITs). Perspectives in Clinical Research, 3(4), 119–121. https://doi.org/10.4103/2229-3485.103591
Tamimi, N. A., & Ellis, P. (2009). Drug development: From concept to marketing! Nephron. Clinical Practice, 113(3), c125–c131. https://doi.org/10.1159/000232592
The Economist. (2022). Doctor Google will see you now. The Economist, June 25th 2022.
Turakhia, M. P., Shafrin, J., Bognar, K., Trocio, J., Abdulsattar, Y., Wiederkehr, D., & Goldman, D. P. (2018). Estimated prevalence of undiagnosed atrial fibrillation in the United States. PLoS One, 13(4), e0195088. https://doi.org/10.1371/journal.pone.0195088
Vamathevan, J., Clark, D., Czodrowski, P., Dunham, I., Ferran, E., Lee, G., et al. (2019). Applications of machine learning in drug discovery and development. Nature Reviews. Drug Discovery, 18(6), 463–477. https://doi.org/10.1038/s41573-019-0024-5
VFA. (2022). AMNOG-Einsparungen. https://www.vfa.de/de/wirtschaft-politik/politik/amnog-einsparungen. Accessed 02.10.23
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Mahn, M., Witt, H. (2024). Digitally Enhanced Life Cycle Management for a Blockbuster Prescription Drug. In: Schönbohm, A., von Horsten, H.H., Plugmann, P., von Stosch, M. (eds) Innovation in Life Sciences. Management for Professionals. Springer, Cham. https://doi.org/10.1007/978-3-031-47768-3_3
Download citation
DOI: https://doi.org/10.1007/978-3-031-47768-3_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-47767-6
Online ISBN: 978-3-031-47768-3
eBook Packages: Business and ManagementBusiness and Management (R0)