EMA. Benefit-risk methodology - development and testing of tools and processes for balancing multiple benefits and risks as an aid to informed regulatory decisions about medicinal products. 2009. https://www.ema.europa.eu/en/about-us/support-research/benefit-risk-methodology. Accessed August 2024.

FDA. Benefit-risk assessment in drug regulatory decision-making, draft PDUFA VI implementation plan (FY 2018–2022). 2018. https://www.fda.gov/files/about%20fda/published/Benefit-Risk-Assessment-in-Drug-Regulatory-Decision-Making.pdf. Accessed August 2024.

Juhaeri J. Benefit-risk evaluation: the past, present and future. Ther Adv Drug Saf. 2019;10:2042098619871180.

Article  PubMed  PubMed Central  Google Scholar 

Sullivan T, Zorenyi G, Feron J, Smith M, Nord M. A structured benefit-risk assessment operating model for investigational medicinal products in the pharmaceutical industry. Ther Innov Regul Sci. 2023;57(4):849–64.

Article  PubMed  PubMed Central  Google Scholar 

FDA. Benefit-risk assessment for new drug and biological products-guidance for industry. 2023. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/benefit-risk-assessment-new-drug-and-biological-products. Accessed August 2024.

CIOMS. Working group XII: Benefit-risk balance for medicinal products. 2023. https://cioms.ch/working-groups/working-group-xii/. Accessed August 2024.

Hughes D, Waddingham E, Mt-Isa S, Goginsky A, Chan E, Downey GF, et al. Recommendations for benefit-risk assessment methodologies and visual representations. Pharmacoepidemiol Drug Saf. 2016;25(3):251–62.

Article  PubMed  Google Scholar 

Ho M, Saha A, McCleary KK, Levitan B, Christopher S, Zandlo K, et al. A framework for incorporating patient preferences regarding benefits and risks into regulatory assessment of medical technologies. Value Health. 2016;19(6):746–50.

Article  PubMed  Google Scholar 

Medical Device Innovation Consortium. Patient centered benefit-risk project report: A framework for incorporating information on patient preferences regarding benefit and risk into regulatory assessments of new medical technology. 2015. https://mdic.org/wp-content/uploads/2015/05/MDIC_PCBR_Framework_Web1.pdf. Accessed August 2024.

Smith MY, Hammad TA, Metcalf M, Levitan B, Noel R, Wolka AM, et al. Patient engagement at a tipping point-the need for cultural change across patient, sponsor, and regulator stakeholders: Insights from the DIA conference, “patient engagement in benefit risk assessment throughout the life cycle of medical products.” Ther Innov Regul Sci. 2016;50(5):546–53.

Article  PubMed  Google Scholar 

Simonetti A, Colilla S, Edwards B, Kubler J, Lackey L, Rodriguez L, et al. Key opinion leaders’ interviews to inform the future of benefit-risk planning in the medical total product life cycle of global pharmaceutical and medical device organizations. Drug Saf. 2024. https://doi.org/10.1007/s40264-024-01442-4.

Article  PubMed  PubMed Central  Google Scholar 

Eek D, Halling K, Flood E, Blowfield M, Meyers O, Venerus M, et al. Patient global impression of benefit-risk (PGI-BR): Incorporating patients’ views of clinical benefit-risk into assessment of new medicines. Drug Saf. 2021;44(10):1059–72.

Article  PubMed  PubMed Central  Google Scholar 

FDA. Public workshop on benefit-risk considerations - meeting transcript. 2017. www.fda.gov/media/109405/download. Accessed August 2024.

Ho MP, Gonzalez JM, Lerner HP, Neuland CY, Whang JM, McMurry-Heath M, et al. Incorporating patient-preference evidence into regulatory decision making. Surg Endosc. 2015;29(10):2984–93.

Article  PubMed  Google Scholar 

FDA. Patient-focused drug development: Collecting comprehensive and representative input. 2020. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-focused-drug-development-collecting-comprehensive-and-representative-input. Accessed August 2024.

Egbrink MO, IJzerman M. The value of quantitative patient preferences in regulatory benefit-risk assessment. J Mark Access Health Policy. 2014;2

Article  Google Scholar 

FDA. Patient-focused drug development glossary. https://www.fda.gov/drugs/development-approval-process-drugs/patient-focused-drug-development-glossary. Accessed January, 2026.

EMA. Patient experience data in EU medicines development and regulatory decision-making. 2022. https://www.ema.europa.eu/en/documents/other/executive-summary-patient-experience-data-eu-medicines-development-and-regulatory-decision-making-workshop_en.pdf. Accessed August 2024.

FDA. Patient preference information - voluntary submission, review in premarket approval applications, humanitarian device exemption applications, and de novo requests, and inclusion in decision summaries and device labeling. 2016. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-preference-information-voluntary-submission-review-premarket-approval-applications. Accessed August 2024.

FDA. Incorporating voluntary patient preference information over the total product life cycle. 2024. https://www.fda.gov/media/181509/download. Accessed August 2024.

FDA. Assessment of the use of patient experience data in regulatory decision-making. 2021. https://www.fda.gov/drugs/development-approval-process-drugs/assessment-use-patient-experience-data-regulatory-decision-making. Accessed August 2024.

FDA. Patient-focused drug development: Incorporating clinical outcome assessments into endpoints for regulatory decision-making. 2023. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-focused-drug-development-incorporating-clinical-outcome-assessments-endpoints-regulatory. Accessed August 2024.

FDA. Patient-focused drug development: Methods to identify what is important to patients. 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-focused-drug-development-methods-identify-what-important-patients. Accessed August 2024.

FDA. Patient-focused drug development: Selecting, developing or modifying fit-for-purpose clinical outcomes assessments. 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-focused-drug-development-selecting-developing-or-modifying-fit-purpose-clinical-outcome. Accessed August 2024.

FDA. Patient engagement in the design and conduct of medical device clinical studies. 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-engagement-design-and-conduct-medical-device-clinical-studies. Accessed August 2024.

EMA. Considerations and learnings from use-cases - EMA multi-stakeholder workshop: Patient experience data in medicines development and regulatory decision-making. 2022. https://www.ema.europa.eu/en/documents/presentation/presentation-considerations-and-learnings-use-cases-m-muller-efpia_en.pdf-0. Accessed August 2024.

EMA. Update on patient experience data: Reflection paper. 2024. https://www.ema.europa.eu/en/documents/presentation/presentation-patient-experience-data-reflection-paper-rosa-gonzalez-quevedo_en.pdf. Accessed August 2024.

EMA. Engagement framework: EMA and patients, consumers and their organisations. 2022. https://www.ema.europa.eu/en/documents/other/engagement-framework-european-medicines-agency-patients-consumers-their-organisations_en.pdf. Accessed August 2024.

Janssens R, Russo S, van Overbeeke E, Whichello C, Harding S, Kübler J, et al. Patient preferences in the medical product life cycle: what do stakeholders think? Semi-structured qualitative interviews in Europe and the USA. Patient. 2019;12(5):513–26.

Article  PubMed  PubMed Central  Google Scholar 

Waschbusch M, Rodriguez L, Brueckner A, Lee KJ, Li X, Mokliatchouk O, et al. Global landscape of benefit–risk considerations for medicinal products: current state and future directions. Pharmaceut Med. 2022;36(4):201–13.

PubMed  Google Scholar 

EMA. Benefit-risk methodology project - work package 2 report: Applicability of current tools and processes for regulatory benefit-risk assessment. 2010. https://www.ema.europa.eu/en/documents/report/benefit-risk-methodology-project_en.pdf. Accessed August 2024.

Hunink M, Glasziou P, Siegel J, Weeks J, Pliskin J, Elstein A. Decision making in health and medicine. Cambridge: Cambridge University Press; 2001.

Google Scholar 

Hammond J, Keeney R, Raiffa H. Smart choices: A practical guide to making better decisions. Boston, MA: Harvard Business School Press; 1999.

Google Scholar 

Coplan PM, Noel RA, Levitan BS, Ferguson J, Mussen F. Development of a framework for enhancing the transparency, reproducibility and communication of the benefit-risk balance of medicines. Clin Pharmacol Ther. 2011;89(2):312–5.

Article  CAS  PubMed  Google Scholar 

The PREFER consortium. PREFER recommendations - why, when and how to assess and use patient preferences in medical product decision-making. 2022. https://doi.org/10.5281/zenodo.6592304. Accessed August 2024.

Reynolds RF, Kurz X, de Groot MC, Schlienger RG, Grimaldi-Bensouda L, Tcherny-Lessenot S, et al. The IMI PROTECT project: Purpose, organizational structure, and procedures. Pharmacoepidemiol Drug Saf. 2016;25(Suppl 1):5–10.

Article  PubMed  Google Scholar 

Gater A, Reaney M, Findley A, Brun-Strang C, Burrows K, Nguyên-Pascal ML, et al. Development and first use of the patient’s qualitative assessment of treatment (PQAT) questionnaire in type 2 diabetes mellitus to explore individualised benefit-harm of drugs received during clinical studies. Drug Saf. 2020;43(2):119–34.

Article  PubMed  PubMed Central  Google Scholar 

Thanarajasingam G, Basch E, Mead-Harvey C, Bennett AV, Mazza GL, Schwab G, et al. An exploratory analysis of the “was it worth it?” questionnaire as a novel metric to capture patient perceptions of cancer treatment. Value Health. 2022;25(7):1081–6.

Article  PubMed  PubMed Central  Google Scholar 

Pleil AM, Coyne KS, Reese PR, Jumadilova Z, Rovner ES, Kelleher CJ. The validation of patient-rated global assessments of treatment benefit, satisfaction, and willingness to continue - the BSW. Value Health. 2005;8(Suppl 1):S25–34.

Article  PubMed  Google Scholar 

Center for Drug Evaluation and Research. Multi-discipline review: Phesgo (pertuzumab and trastuzumab solution for subcutaneous injection. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/761170Orig1s000Approv.pdf. Accessed August 2024.