{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:36:07Z","timestamp":1787020567156,"version":"build-2736575974"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Health Serv Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Innovative orphan drugs often have an incremental cost-effectiveness ratio (ICER) which is higher than the maximum threshold for reimbursement. Payers have limited budgets and often cannot pay the full price of a new product, but pharmaceutical and biotechnology companies require a minimum price to satisfy their investors. The objective of this study was to present a possible solution to bridge this pricing gap by having early phase price agreements, which reduce the risk for investors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used a Pricing Model, which determines the minimum (break-even) price of an innovative drug from an investor\u2019s perspective. This model is based on economic valuation theory, which uses the expected free cash flows and the required cost of capital. We selected two orphan drugs with a positive clinical assessment and an ICER higsher than the Dutch maximum threshold of \u20ac80,000 per QALY gained to use as examples in the model: Spinraza for spinal muscular atrophy and Orkambi for cystic fibrosis.<\/jats:p>\n                    <jats:p>RESULTS: The results show that early pricing agreements before phase III trials can substantially lower the drug price resulting from a lower cost of capital. The minimum price for orphan drugs can be reduced by 27.4%, when cost of capital decreases from 12 to 9%. An additional adjustment of other critical parameters due to early pricing agreements (lower probabilities of phase III failure and lower research and development (R&amp;D) costs) can further reduce the minimal price by 62.8%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study shows that earlier timing of price negotiations resulting in an agreement on drug price can substantially lower the minimal price of orphan drugs for the investor.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12913-021-06208-7","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T01:03:14Z","timestamp":1615510994000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The impact of early phase price agreements on prices of orphan drugs"],"prefix":"10.1186","volume":"21","author":[{"given":"Mark","family":"Nuijten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Van Wilder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"issue":"6","key":"6208_CR1","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.healthpol.2018.04.001","volume":"122","author":"V Reckers","year":"2018","unstructured":"Reckers V, van Exel NJA, Brouwer WBF. Looking back and moving forward: on the application of proportional shortfall in healthcare priority setting in the Netherlands. Health Policy. 2018;122(6):621\u20139.","journal-title":"Health Policy"},{"issue":"9","key":"6208_CR2","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1038\/s41571-018-0083-2","volume":"15","author":"M Nuijten","year":"2018","unstructured":"Nuijten M, Vis J. Economic comments on proposal for a novel cancer drug pricing model. Nat Rev Clin Oncol. 2018;15(9):587. https:\/\/doi.org\/10.1038\/s41571-018-0083-2.","journal-title":"Nat Rev Clin Oncol"},{"key":"6208_CR3","unstructured":"Herbeoordeling lumacaftor\/ivacaftor (Orkambi). 2016. Reference 2016136882.Zorginstituut Nederland. https:\/\/www.zorginstituutnederland.nl\/publicaties\/adviezen\/2016\/12\/15\/gvs-advies-lumacaftor-ivacaftor-orkambi-bij-cystische-fibrose-cf-bij-patienten-van-12-jaar-en-ouder-die-homozygoot-zijn-voor-de-f508del-mutatie-in-het-cftr-gen-herbeoordeling."},{"key":"6208_CR4","volume-title":"Assessing the financial viability of stratified medicine using decision tree analysis. Working paper","author":"J Sloand","year":"2014","unstructured":"Sloand J. Assessing the financial viability of stratified medicine using decision tree analysis. Working paper. Bethlehem: Lehigh University; 2014."},{"key":"6208_CR5","first-page":"005","volume":"1","author":"M Nuijten","year":"2018","unstructured":"Nuijten M, Fugel HJ, Vis J. Evaluation and valuation of the price of expensive medicinal products: application of the discounted cash flow to orphan drugs. J Rare Dis Disord. 2018;1:005 Volume 1 | Issue 1.","journal-title":"J Rare Dis Disord"},{"key":"6208_CR6","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/s41571-018-0027-x","volume":"15","author":"CA Uyl-de Groot","year":"2018","unstructured":"Uyl-de Groot CA, L\u00f6wenberg B. Sustainability and affordability of cancer drugs: a novel pricing model. Nat Rev Clin Oncol. 2018;15:405\u20136.","journal-title":"Nat Rev Clin Oncol"},{"issue":"1","key":"6208_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.29245\/2572-9411\/2017\/1.1056","volume":"2","author":"MJC Nuijten","year":"2016","unstructured":"Nuijten MJC, Vis J. Evaluation and valuation of innovative medicinal products. J Rare Dis Res Treat. 2016;2(1):1\u201311.","journal-title":"J Rare Dis Res Treat"},{"issue":"1","key":"6208_CR8","doi-asserted-by":"publisher","first-page":"1838191","DOI":"10.1080\/20016689.2020.1838191","volume":"8","author":"M Nuijten","year":"2020","unstructured":"Nuijten M, Capri S. Pricing of orphan drugs in oncology and rare diseases. J Mark Access Health Policy. 2020;8(1):1838191. https:\/\/doi.org\/10.1080\/20016689.2020.1838191 Published 2020 Dec 1.","journal-title":"J Mark Access Health Policy"},{"key":"6208_CR9","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.1512938","volume-title":"Cost of Capital for pharmaceutical, biotechnology, and medical device firms","author":"S Harrington","year":"2009","unstructured":"Harrington S. Cost of Capital for pharmaceutical, biotechnology, and medical device firms. 2009. Prepared for The Handbook of the Economics of the Biopharmaceutical Industry."},{"issue":"6","key":"6208_CR10","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/j.nbt.2016.09.003","volume":"33","author":"HJ Fugel","year":"2016","unstructured":"Fugel HJ, Nuijten M, Postma M. Economic viability of stratified medicine concepts: an investor perspective on drivers and conditions that favour using stratified medicine approaches in a cost-contained healthcare environment. New Biotechnol. 2016;33(6):860\u20137. https:\/\/doi.org\/10.1016\/j.nbt.2016.09.003 Epub 2016 Sep 21. 113. eCollection 2016.","journal-title":"New Biotechnol"},{"key":"6208_CR11","doi-asserted-by":"publisher","unstructured":"Nuijten MJ, Mittendorf T, Persson U. Practical issues in handling data input and uncertainty in a budget impact analysis. 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