{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:40:16Z","timestamp":1792518016346,"version":"4.5.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Sanofi S.A."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ther Innov Regul Sci"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The impact of the Inflation Reduction Act (IRA) upon late-stage developments has assumed to be limited. The Congressional Budget Office\u2019s IRA analysis excluded post-approval innovation, potentially overlooking substantial economic risks to drug developers and declines in the availability of treatments in areas of high unmet medical need such as oncology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 1148 secondary trials from 364 FDA-approved medicines, published from 2018 to 2025, were obtained from Biomedtracker and clinicaltrials.gov. We use fractional logit regression to model the number of studies and use fractional multinomial logit regression to model the share distribution of secondary indication studies across 19 disease groups to identify any change in the share distribution post-IRA .<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We find that, after the IRA\u2019s introduction, small molecule follow-on studies in oncology exhibited a statistically significant 37% decline (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05), lead indication small molecule oncology approvals exhibited a statistically significant 27% decline (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05), and the share of orphan oncology studies exhibited a statistically significant 14% decline (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research Conclusions<\/jats:title>\n                    <jats:p>This study\u2019s results call into question claims that the IRA would have minimal negative effects upon late-stage biopharmaceutical R&amp;D, as the introduction of the IRA is associated with a decline in small molecule oncology studies. We hope this study reinvigorates debate about the law\u2019s possible unintended consequences and encourages thoughtful policy solutions, as the IRA appears to negatively impact patients seeking needed new medicines, particularly those addressing metastatic late-stage cancers with a small molecule modality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s43441-026-01061-4","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:01:47Z","timestamp":1792515707000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Inflation Reduction Act\u2019s Modeled Impacts upon Late-Stage R&amp;D"],"prefix":"10.1007","author":[{"given":"Harry P.","family":"Bowen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwen","family":"O\u2019Loughlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Schleicher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2886-2975","authenticated-orcid":false,"given":"Duane G.","family":"Schulthess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"1061_CR1","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1007\/s43441-025-00773-3","volume":"59","author":"DG Schulthess","year":"2025","unstructured":"Schulthess DG, O\u2019Loughlin G, Askeland M, et al. The Inflation Reduction Act\u2019s impact upon early-stage venture capital investments. Ther Innov Regul Sci. 2025;59:769\u201380. https:\/\/doi.org\/10.1007\/s43441-025-00773-3.","journal-title":"Ther Innov Regul Sci"},{"key":"1061_CR2","unstructured":"https:\/\/www.cbo.gov\/system\/files\/2025-04\/61231-Drug-Development-Model.pdf (accessed 5\/16.26)."},{"key":"1061_CR3","unstructured":"https:\/\/www.ohe.org\/insights\/is-the-revised-congressional-budget-office-model-of-new-drug-development-fit-for-purpose\/ (accessed 5\/15\/26)."},{"key":"1061_CR4","doi-asserted-by":"publisher","unstructured":"\"Biopharma Venture Capital and the Inflation Reduction Act,\"\u00a0Health Affairs Forefront,\u00a0March 5, 2024. https:\/\/doi.org\/10.1377\/forefront.20240229.164848.","DOI":"10.1377\/forefront.20240229.164848"},{"key":"1061_CR5","doi-asserted-by":"publisher","DOI":"10.1377\/forefront.20240229.164848","author":"M Vogel","year":"2024","unstructured":"Vogel M, Conti RM, Chandra A. Biopharma venture capital and the inflation reduction act. Health Aff Forefr. 2024. https:\/\/doi.org\/10.1377\/forefront.20240229.164848.","journal-title":"Health Aff Forefr"},{"key":"1061_CR6","unstructured":"https:\/\/www.keytrudahcp.com\/approved-indications\/ (accessed 5\/15\/26)."},{"key":"1061_CR7","unstructured":"https:\/\/vitaltransformation.com\/wp-content\/uploads\/2022\/11\/AA-Project_FINAL_2022_11_11.pdf Page 21, (accessed 5\/15\/26)."},{"key":"1061_CR8","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1007\/s43441-024-00706-6","volume":"59","author":"JA Patterson","year":"2025","unstructured":"Patterson JA, Motyka J, Salih R, et al. Subsequent indications in oncology drugs: pathways, timelines, and the Inflation Reduction Act. Ther Innov Regul Sci. 2025;59:102\u201311. https:\/\/doi.org\/10.1007\/s43441-024-00706-6.","journal-title":"Ther Innov Regul Sci"},{"key":"1061_CR9","unstructured":"Ibid."},{"issue":"Issue 8","key":"1061_CR10","doi-asserted-by":"publisher","DOI":"10.1093\/haschl\/qxaf152","volume":"Volume 3","author":"H Zheng","year":"2025","unstructured":"Zheng H, Patterson JA, Campbell JD. Early impact of the Inflation Reduction Act on small molecule versus biologic post-approval oncology trials. Health Aff Sch. 2025;Volume 3(Issue 8):qxaf152. https:\/\/doi.org\/10.1093\/haschl\/qxaf152.","journal-title":"Health Aff Sch"},{"key":"1061_CR11","unstructured":"Durbin-Watson tests rejected the presence of AR(1) serial correlation in the share series."},{"key":"1061_CR12","unstructured":"For this analysis, the FMLogit model was estimated using three disease groups: Oncology, Hematology, and all Other groups combined. This aggregation was done after estimating the model for 15 disease groups plus one \u201cother\u201d group that combined the remaining four groups and observing that only the oncology and hematology group equations showed overall significance."},{"key":"1061_CR13","unstructured":"The increases in the proportion of hematology studies is not unexpected since the proportions across disease groups sum to one. Hence, a decline in the proportion of oncology studies would be expected to be accompanied by an increase in the proportion of non-oncology studies."},{"issue":"2","key":"1061_CR14","doi-asserted-by":"publisher","first-page":"8","DOI":"10.21500\/20112084.3951","volume":"12","author":"V Tait","year":"2019","unstructured":"Tait V, Miller HL Jr. Loss aversion as a potential factor in the sunk-cost fallacy. Int J Psychol Res (Medellin). 2019;12(2):8\u201316. https:\/\/doi.org\/10.21500\/20112084.3951.","journal-title":"Int J Psychol Res (Medellin)"},{"key":"1061_CR15","unstructured":"https:\/\/www.congress.gov\/bill\/119th-congress\/house-bill\/946\/all-info (accessed 5\/16\/26)."},{"key":"1061_CR16","unstructured":"Revised Estimate of Changes Under the 2025 Reconciliation Act for Exemptions From Medicare Price Negotiations for Orphan Drugs, October 20, 2025, Cost Estimate CBO responds to questions regarding the orphan drug exemption under Public Law 119\u201325, the 2025 reconciliation act. https:\/\/www.cbo.gov\/publication\/61818 (accessed 5\/16\/26)."},{"key":"1061_CR17","unstructured":"https:\/\/www.forbes.com\/sites\/joshuacohen\/2025\/11\/04\/dems-seek-to-repeal-orphan-only-drugs-exemption-from-medicare-price-negotiations\/ (accessed 5\/16\/26)."},{"key":"1061_CR18","unstructured":"https:\/\/www.congress.gov\/bill\/117th-congress\/house-bill\/5376\/summary\/00 (accessed 5\/19\/26)."},{"key":"1061_CR19","unstructured":"Auble D, Glavin B, Quist P. Open Secrets, \u201cLayers of Lobbying: An examination of 2021 state and federal lobbying from K Street to Main Street,\u201d 2022 June, https:\/\/www.opensecrets.org\/news\/reports\/layers-of-lobbying\/state-and-federal-lobbying (accessed 10\/4\/2026)."},{"key":"1061_CR20","unstructured":"Philipson TJ, et al. The Potentially Larger Than Predicted Impact of the IRA on Small Molecule R&D and Patient Health, University of Chicago Policy Brief, https:\/\/ecchc.economics.uchicago.edu\/files\/2024\/06\/Small-Molecule-Paper-20240625.pd (accessed 5\/19\/26)."},{"issue":"1","key":"1061_CR21","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1080\/13696998.2024.2323903","volume":"27","author":"H Grabowski","year":"2024","unstructured":"Grabowski H, Long G. Post-approval indications and clinical trials for cardiovascular drugs: some implications of the US Inflation Reduction Act. J Med Econ. 2024;27(1):463\u201372.","journal-title":"J Med Econ"}],"container-title":["Therapeutic Innovation &amp; Regulatory Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-026-01061-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-026-01061-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-026-01061-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:01:49Z","timestamp":1792515709000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-026-01061-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":21,"alternative-id":["1061"],"URL":"https:\/\/doi.org\/10.1007\/s43441-026-01061-4","relation":{},"ISSN":["2168-4790","2168-4804"],"issn-type":[{"value":"2168-4790","type":"print"},{"value":"2168-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"assertion":[{"value":"20 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Harry P. Bowen, Gwen O\u2019Loughlin, Claire Schleicher, and Duane Schulthess received compensation as paid consultants to the sponsoring organization of this study.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}