{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:11:06Z","timestamp":1785413466074,"version":"3.56.0"},"reference-count":70,"publisher":"National Academy of Sciences","issue":"28","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,7,14]]},"abstract":"<jats:p>The US Food and Drug Administration (FDA) makes and communicates decisions that directly affect the health choices and well-being of the US public. Behavioral and decision scientists have long supported FDA\u2019s pharmaceutical (medical drug) regulatory and public health mission, working alongside clinical and pharmaceutical scientists. This Perspective describes four interrelated cases illustrating these collaborations: a) creating the Benefit\u2013Risk Framework to guide regulatory decisions regarding new drug approvals; b) launching an internal decision support service to facilitate specific regulatory decisions; c) implementing the Patient-Focused Drug Development initiative to strengthen the use of patient input to inform regulatory decision making; and d) developing FDA SOURCE, a dynamic systems simulation model to assess potential strategies to address the US opioid overdose crisis. Key to the success of these efforts has been their behavioral and decision science foundations, strategically implemented by an expert team dedicated to fostering trusted collaborations with internal and external partners. These cases offer a model for other agencies facing complex decisions of public impact.<\/jats:p>","DOI":"10.1073\/pnas.2525995123","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T19:09:56Z","timestamp":1783364996000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Applied behavioral and decision sciences in support of US FDA\u2019s drug regulatory mission"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5928-1174","authenticated-orcid":false,"given":"Sara L.","family":"Eggers","sequence":"first","affiliation":[{"name":"Independent Scholar","place":["Takoma Park"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3416-2230","authenticated-orcid":false,"given":"Tamar","family":"Krishnamurti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of General Internal Medicine, University of Pittsburgh School of Medicine","place":["Pittsburgh"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3030-6874","authenticated-orcid":false,"given":"Baruch","family":"Fischhoff","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05x2bcf33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Engineering and Public Policy and Carnegie Mellon Institute for Strategy and Technology, Carnegie Mellon University","place":["Pittsburgh"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"e_1_3_4_1_2","unstructured":"U.S. Food and Drug Administration About FDA. https:\/\/www.fda.gov\/about-fda. Accessed 29 September 2025."},{"key":"e_1_3_4_2_2","unstructured":"U.S. Food and Drug Administration New drug therapy approvals 2024. https:\/\/www.fda.gov\/files\/drugs\/published\/new-drug-therapy-2025-annual-report.pdf. Accessed 30 September 2025."},{"key":"e_1_3_4_3_2","unstructured":"U.S. Food and Drug Administration 2024 new drug application and biologic license application efficacy supplement calendar year approvals. https:\/\/www.fda.gov\/media\/185465\/download?attachment. Accessed 30 September 2025."},{"key":"e_1_3_4_4_2","unstructured":"U.S. Food and Drug Administration Drug safety-related labeling changes. https:\/\/www.accessdata.fda.gov\/scripts\/cder\/safetylabelingchanges\/index.cfm. Accessed 30 September 2025."},{"key":"e_1_3_4_5_2","unstructured":"U.S. Food and Drug Administration Approved risk evaluation and mitigation strategy (REMS). https:\/\/www.accessdata.fda.gov\/scripts\/cder\/rems\/index.cfm. Accessed 30 September 2025."},{"key":"e_1_3_4_6_2","unstructured":"U.S. Food and Drug Administration BeSafeRx: Your source for online pharmacy information. https:\/\/www.fda.gov\/drugs\/buying-using-medicine-safely\/besaferx-your-source-online-pharmacy-information. Accessed 29 September 2025."},{"key":"e_1_3_4_7_2","unstructured":"U.S. Food and Drug Administration Drug safety communications. https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/drug-safety-communications#current. Accessed 29 September 2025."},{"key":"e_1_3_4_8_2","unstructured":"U.S. Food and Drug Administration Drug approvals and databases. https:\/\/www.fda.gov\/drugs\/development-approval-process-drugs\/drug-approvals-and-databases. Accessed 29 September 2025."},{"key":"e_1_3_4_9_2","unstructured":"U.S. Food and Drug Administration Benefit-risk assessment for new drug and biologic products\u2014Guidance for industry (2023). https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/benefit-risk-assessment-new-drug-and-biological-products. Accessed 29 September 2025."},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1037\/a0040438"},{"key":"e_1_3_4_11_2","unstructured":"U.S. Food and Drug Administration Strategic plan for regulatory science (2011). https:\/\/www.fda.gov\/science-research\/advancing-regulatory-science\/strategic-plan-regulatory-science. Accessed 29 September 2025."},{"key":"e_1_3_4_12_2","volume-title":"The Future of Drug Safety: Promoting and Protecting the Health of the Public","author":"Institute of Medicine","year":"2006","unstructured":"Institute of Medicine, The Future of Drug Safety: Promoting and Protecting the Health of the Public (National Academies Press, Washington, DC, 2006)."},{"key":"e_1_3_4_13_2","unstructured":"U.S. Food and Drug Administration Structured approach to benefit-risk assessment in drug regulatory decision-making: Draft PDUFA V implementation plan (2013). https:\/\/www.fda.gov\/files\/about%20fda\/published\/PDUFA-V-Implementation-Plan--Structured-Approach-to-Benefit-Risk-Assessment-in-Drug-Regulatory-Decision-Making-%28Draft%29.pdf. Accessed 24 February 2026."},{"key":"e_1_3_4_14_2","unstructured":"U.S. Food and Drug Administration PDUFA reauthorization performance goals and procedures fiscal years 2013 through 2017. (2012). https:\/\/www.fda.gov\/media\/81306\/download. Accessed 30 September 2025."},{"key":"e_1_3_4_15_2","unstructured":"U.S. Food and Drug Administration Benefit\u2013risk assessment in drug regulatory decision-making: Draft PDUFA VI implementation plan. (2018). https:\/\/www.fda.gov\/media\/112570\/download."},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9781139174084"},{"key":"e_1_3_4_17_2","unstructured":"U.S. Food and Drug Administration Center for Drug Evaluation and Research 208712Orig1s000 integrated review (2021). https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2022\/208712Orig1s000IntegratedR.pdf. Accessed 29 September 2025."},{"key":"e_1_3_4_18_2","unstructured":"U.S. Food and Drug Administration Center for Drug Evaluation and Research 215498Orig1s000 integrated review (2021). https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2021\/215498Orig1s000IntegratedR.pdf. Accessed 29 September 2025."},{"key":"e_1_3_4_19_2","unstructured":"U.S. Food and Drug Administration FDA briefing document for NDA 214511 (pegulicianine). Medical Imaging Drug Advisory Committee. (2024) https:\/\/www.fda.gov\/media\/176708\/download. Accessed 30 September 2025."},{"key":"e_1_3_4_20_2","first-page":"1146","article-title":"FDA\u2019s benefit\u2013risk framework for human drugs and biologics: Role in benefit\u2013risk assessment and analysis of use for drug approvals","volume":"54","author":"Lackey L. G.","year":"2020","unstructured":"L. G. Lackey, G. W. Thompson, S. L. Eggers, FDA\u2019s benefit\u2013risk framework for human drugs and biologics: Role in benefit\u2013risk assessment and analysis of use for drug approvals. Ther. Innov. Regul. Sci. 54, 1146\u20131153 (2020).","journal-title":"Ther. Innov. Regul. Sci."},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.56759\/gwfz1791"},{"key":"e_1_3_4_22_2","unstructured":"U.S. Food and Drug Administration Draft guidance for industry: REMS logic model: A framework to link program design with assessment (2024). https:\/\/www.fda.gov\/media\/178291\/download. Accessed 22 December 2025."},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-025-01542-9"},{"key":"e_1_3_4_24_2","unstructured":"U.S. Food and Drug Administration Staff manual guide 1270.21 (2020). https:\/\/www.fda.gov\/media\/85616\/download. Accessed 29 September 2025."},{"key":"e_1_3_4_25_2","volume-title":"Facilitator\u2019s Guide to Participatory Decision-Making","author":"Kaner S.","year":"2014","unstructured":"S. Kaner, L. Lind, C. Toldi, S. Fisk, D. Berger, Facilitator\u2019s Guide to Participatory Decision-Making (Jossey-Bass, San Francisco, CA, ed. 3, 2014).","edition":"3"},{"key":"e_1_3_4_26_2","volume-title":"Smart Choices: A Practical Guide to Making Better Decisions","author":"Hammond J. S.","year":"2015","unstructured":"J. S. Hammond, R. L. Keeney, H. Raiffa, Smart Choices: A Practical Guide to Making Better Decisions (Harvard Business Review Press, Boston, MA, 2015)."},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2021.02.057"},{"key":"e_1_3_4_28_2","unstructured":"U.S. Food and Drug Administration Guidance for industry: Warning and precautions contraindications and boxed warning sections of labeling for human prescription drugs and biological products. (2010). https:\/\/www.fda.gov\/media\/71866\/download. Accessed 29 September 2025."},{"key":"e_1_3_4_29_2","unstructured":"K. Clarridge FDA Drug Topics: Safety Labeling Changes for Leukotriene Receptor Antagonists and Decisions Behind a Boxed Warning (Food and Drug Administration 2021). https:\/\/fda.report\/media\/148762\/Montelukast_Webinar_cleared.pdf. Accessed 24 February 2026."},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3636"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2022.12.006"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.053294"},{"key":"e_1_3_4_33_2","unstructured":"U.S. Food and Drug Administration Excellence in social and behavioral science group award (2022). https:\/\/www.fda.gov\/science-research\/about-science-research-fda\/excellence-social-and-behavioral-science-group-award. Accessed 22 December 2025."},{"key":"e_1_3_4_34_2","unstructured":"U.S. Food and Drug Administration FDA decision memo: New drug application 17031 supplement 41 application for full prescription-to-nonprescription switch of Norgestrel tablets 0.075 mg (2023). https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2023\/017031Orig1s041SumR.pdf. Accessed 29 September 2025."},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1177\/17407745221084127"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40900-018-0093-3"},{"key":"e_1_3_4_37_2","unstructured":"U.S. Food and Drug Administration CDER patient-focused drug development. https:\/\/www.fda.gov\/drugs\/development-approval-process-drugs\/cder-patient-focused-drug-development. Accessed 29 September 2025."},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1416123"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511814679"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.publhealth.19.1.173"},{"key":"e_1_3_4_41_2","unstructured":"U.S. Food and Drug Administration Prescription drug user fee act patient-focused drug development: Public meeting and request for comments. Docket No. FDA-2012-N-0967 (2012). https:\/\/www.federalregister.gov\/documents\/2012\/09\/24\/2012-23454\/prescription-drug-user-fee-act-patient-focused-drug-development-public-meeting-and-request-for. Accessed 29 September 2025."},{"key":"e_1_3_4_42_2","unstructured":"U.S. Food and Drug Administration Chronic fatigue syndrome\/myalgic encephalomyelitis: Developing drug products for treatment: Draft guidance for industry (2014). https:\/\/www.fda.gov\/media\/87875\/download. Accessed 29 September 2025."},{"key":"e_1_3_4_43_2","volume-title":"Beyond Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: Redefining an Illness","author":"Institute of Medicine","year":"2015","unstructured":"Institute of Medicine, Beyond Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: Redefining an Illness (National Academies Press, Washington, DC, 2015)."},{"key":"e_1_3_4_44_2","unstructured":"U.S. Food and Drug Administration Condition-specific meeting reports and other information related to patients\u2019 experience. https:\/\/www.fda.gov\/industry\/prescription-drug-user-fee-amendments\/condition-specific-meeting-reports-and-other-information-related-patients-experience. Accessed 29 September 2025."},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40271-023-00648-5"},{"key":"e_1_3_4_46_2","unstructured":"U.S. Food and Drug Administration Guidance for industry\u2014Opioid analgesic drugs: Considerations for benefit-risk assessment framework guidance for industry (2019). https:\/\/www.fda.gov\/media\/128150\/download. Accessed 22 December 2025."},{"key":"e_1_3_4_47_2","unstructured":"U.S. Food and Drug Administration Food and drug administration overdose prevention framework. https:\/\/www.fda.gov\/media\/160381\/download. Accessed 29 September 2025."},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1257\/pol.20170082"},{"key":"e_1_3_4_49_2","volume-title":"Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use","author":"National Academies of Sciences, Engineering, and Medicine","year":"2017","unstructured":"National Academies of Sciences, Engineering, and Medicine, Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use (National Academies Press, Washington, DC, 2017)."},{"key":"e_1_3_4_50_2","unstructured":"U.S. Food and Drug Administration Introduction to FDA\u2019s opioid systems model (2021). https:\/\/www.fda.gov\/media\/146916\/download. Accessed 29 September 2025."},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2115714119"},{"key":"e_1_3_4_52_2","unstructured":"U.S. Centers for Disease Control Provisional drug overdose death counts. https:\/\/www.cdc.gov\/nchs\/nvss\/vsrr\/drug-overdose-data.htm. Accessed 29 September 2025."},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm8147"},{"key":"e_1_3_4_54_2","unstructured":"U.S. Food and Drug Administration Safety and effectiveness of certain naloxone hydrochloride drug products for nonprescription use; Request for comments. Fed. Reg. 87 68702\u201368713. Docket No. FDA-2022-N-2673 (2022). https:\/\/www.federalregister.gov\/d\/2022-24874. Accessed 30 September 2025."},{"key":"e_1_3_4_55_2","unstructured":"U.S. Food and Drug Administration A systems approach to considering the impacts of OxyContin Abuse Deterrent Formulation. Joint meeting of the Drug Safety and Risk Management and Anesthetic and Analgesic Drug Products Advisory Committees (2020) https:\/\/web.archive.org\/web\/20210306201006\/https:\/www.fda.gov\/media\/141973\/download. Accessed 29 September 2025."},{"key":"e_1_3_4_56_2","unstructured":"U.S. Food and Drug Administration A framework for assessing the impacts of strategies to manage risks of higher dose and higher dosage strength opioid analgesic products. Joint meeting of the joint meeting of the Drug Safety and Risk Management and Anesthetic and Analgesic Drug Products Advisory Committees (2019). https:\/\/web.archive.org\/web\/20191214114201\/https:\/www.fda.gov\/media\/128863\/download. Accessed 29 September 2025."},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1080\/16066359.2024.2420087"},{"key":"e_1_3_4_58_2","unstructured":"U.S. Food and Drug Administration Excellence in data and computational science (2023) https:\/\/www.fda.gov\/science-research\/about-science-research-fda\/excellence-data-and-computational-science-0. Accessed 22 December 2025."},{"key":"e_1_3_4_59_2","unstructured":"System Dynamics Society 2025 award winners at the International System Dynamics Conference (2025). https:\/\/systemdynamics.org\/2025-award-winners-at-the-international-system-dynamics-conference\/. Accessed 22 December 2025."},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvsv.2013.04.005"},{"key":"e_1_3_4_61_2","unstructured":"U.S. Food and Drug Administration Office of prescription drug promotion (OPDP) research (2025). https:\/\/www.fda.gov\/about-fda\/center-drug-evaluation-and-research-cder\/office-prescription-drug-promotion-opdp-research. Accessed 30 September 2025."},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1177\/21501327211004735"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-024-01488-4"},{"key":"e_1_3_4_64_2","unstructured":"U.S. Food and Drug Administration Communicating risks and benefits: An evidence-based user\u2019s guide (2011). https:\/\/www.fda.gov\/media\/81597\/download. Accessed 29 September 2025."},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1214646110"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.60236"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2021.8075"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02328-1"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2015.5355"},{"key":"e_1_3_4_70_2","volume-title":"Presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Annual Meeting","author":"Eggers S. L.","year":"2012","unstructured":"S. L. Eggers, \u201cCDER\u2019s benefit-risk assessment framework: Lessons learned on the road to primetime\u201d in Presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Annual Meeting (Washington, DC, 2012)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2525995123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T19:17:16Z","timestamp":1783365436000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2525995123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,6]]},"references-count":70,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2026,7,14]]}},"alternative-id":["10.1073\/pnas.2525995123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2525995123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,6]]},"assertion":[{"value":"2026-07-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2525995123"}}