References

For Derisk Page References

​

Drug Development Statistics and Failure Rates

 Wong, C. H., Siah, K. W., & Lo, A. W. (2019). Estimation of clinical trial success rates and related parameters. Biostatistics, 20(2), 273-286. https://doi.org/10.1093/biostatistics/kxw055

 Slattery, J., Alvarez, Y., & Hidalgo-Simon, A. (2020). Assessment of clinical trials supporting US Food and Drug Administration approval of novel therapeutic agents, 1995-2017. JAMA Network Open, 3(4), e202854. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2764603

 Sertkaya, A., Birkenbach, A., Berlind, A., & Eyraud, J. (2016). Examination of clinical trial costs and barriers for drug development. Office of the Assistant Secretary for Planning and Evaluation, US Department of Health and Human Services. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820566

 Patel, R. (2025). Clinical trial success rates: How many drugs make it to market? Patent PC Blog. https://patentpc.com/blog/clinical-trial-success-rates-how-many-drugs-make-it-to-market-latest-approval-stats

 Prasad, V., & Mailankody, S. (2017). Research and development spending to bring a single cancer drug to market and revenues after approval. JAMA Internal Medicine, 177(11), 1569-1575. https://www.medrxiv.org/content/10.1101/19007047v1

 PhRMA. (2024). Big Pharma's R&D ROI: Merck, Pfizer, J&J, AbbVie strategies. Drug Discovery Trends. https://www.drugdiscoverytrends.com/are-big-pharma-giants-getting-the-right-roi-on-their-rd-investments-a-visual-exploration/

 Georgetown University. (2019). Drug discovery and development - comprehensive drug design and development initiative. Office of the Senior Vice Provost for Research. https://osvpr.georgetown.edu/research-domain/health/drugdiscoveryanddevelopment/

 Darrow, J. J., Avorn, J., & Kesselheim, A. S. (2020). New FDA breakthrough-drug category—implications for patients. New England Journal of Medicine, 383(15), 1433-1435. https://pmc.ncbi.nlm.nih.gov/articles/PMC9115615/

 Deloitte. (2024). Measuring the return from pharmaceutical innovation: 14th annual pharmaceutical innovation report. PR Newswire. https://www.prnewswire.com/news-releases/deloittes-14th-annual-pharmaceutical-innovation-report-pharma-rd-return-on-investment-rebounds-after-record-low-302126552.html

 Nelson, M. R., Tipney, H., Painter, J. L., Shen, J., Nicoletti, P., Shen, Y., ... & Whittaker, J. C. (2019). The support of human genetic evidence for approved drug indications. Nature Reviews Drug Discovery, 18(8), 611-622. https://www.nature.com/articles/s41598-019-54849-w

 Darrow, J. J., Avorn, J., & Kesselheim, A. S. (2020). FDA approval and regulation of pharmaceuticals, 1983-2018. JAMA, 323(2), 164-176. https://pmc.ncbi.nlm.nih.gov/articles/PMC10410475/

 Pharmaceutical Technology. (2024). The top pharmaceutical companies by R&D expenditure. Pharmaceutical Technology. https://www.pharmaceutical-technology.com/features/the-top-pharmaceutical-companies-by-rd-expenditure/

 Ge, X., & Kang, J. (2022). 90% of drugs fail clinical trials. Here's a method for selecting better drug candidates. Medical Xpress. https://medicalxpress.com/news/2022-02-drugs-clinical-trials-method-drug.html

 Schuhmacher, A., Hinder, M., Brief, E., Gassmann, O., & Hartl, D. (2025). Benchmarking R&D success rates of leading pharmaceutical companies: An empirical analysis of FDA approvals (2006-2022). Drug Discovery Today, 30(2), 104291. https://pubmed.ncbi.nlm.nih.gov/39805539/

 Chandra, A., Garthwaite, C., & Stern, A. D. (2024). Characterizing the drug development pipeline for precision medicine. Nature Reviews Drug Discovery, 23(6), 428-440. https://www.rdworldonline.com/how-much-does-the-pharma-industry-spend-on-rd-anyway-probably-more-than-you-thought/

 American Society for Biochemistry and Molecular Biology. (2022). 90% of drugs fail clinical trials. ASBMB Today. https://www.asbmb.org/asbmb-today/opinions/031222/90-of-drugs-fail-clinical-trials

 US Food and Drug Administration. (2022). Drug approvals and databases. FDA. https://www.fda.gov/drugs/development-approval-process-drugs/drug-approvals-and-databases

 Fierce Biotech. (2024). Big Pharma's ROI for drug R&D saw 'welcome' rebound in 2023: Report. Fierce Biotech. https://www.fiercebiotech.com/biotech/big-pharmas-roi-drug-rd-saw-surprise-rebound-2023-report

 Chem Help ASAP. (2020). Clinical failures in drug trials [Video]. YouTube. https://www.youtube.com/watch?v=lqvnF8Jxj0U

 US Food and Drug Administration. (2025). Drug trials snapshots. FDA. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots

Venture Capital Portfolio Diversification

 McClure, D. (2016). 500 Startups' Dave McClure on portfolio diversification. TechCrunch. https://techcrunch.com/2016/08/15/1368972/

 Fierce Healthcare. (2025). Big bets on healthcare AI push digital health funding to $6.4B. Fierce Healthcare. https://www.fiercehealthcare.com/health-tech/healthcare-ai-rakes-nearly-4b-vc-funding-buoying-digital-health-market-2025

 Parker, J. L., & Lopes, G. (2021). Biomarkers dramatically improve success rates of new cancer drugs: Study. University of Toronto Mississauga. https://www.utm.utoronto.ca/main-news/biomarkers-dramatically-improve-success-rates-new-cancer-drugs-study

 Inc42. (2024). Strategies for effective portfolio diversification in venture capital. Inc42. https://inc42.com/resources/mastering-risk-strategies-for-effective-portfolio-diversification-in-venture-capital/

 MedCity News. (2025). Digital health funding in H1 2025: Market stabilizes, AI dominates. MedCity News. https://medcitynews.com/2025/07/digital-health-venture-capital-healthcare-startup/

 Medical Xpress. (2021). Biomarkers dramatically improve success rates of new cancer drugs. Medical Xpress. https://medicalxpress.com/news/2021-02-biomarkers-success-cancer-drugs.html

 McClure, D. (2016). 99 VC problems but a batch ain't one: Why portfolio size matters for returns. Medium. https://500hats.com/99-vc-problems-but-a-batch-ain-t-one-why-portfolio-size-matters-for-returns-16cf556d4af0

 Lee, A. G. (2025). Rise of AI-powered digital health: 2024 review and 2025 looking ahead. LinkedIn. https://www.linkedin.com/posts/alexgeunholee_rise-of-ai-powered-digital-health-2024-review-activity-7285998076652105728-u5XE

 Dhillon, S., Lopes, G., & Parker, J. L. (2014). Biomarkers and receptor targeted therapies reduce clinical trial risk in non-small-cell lung cancer. PubMed. https://pubmed.ncbi.nlm.nih.gov/24419412/

 Fairchild, C. (2018). 500 Startups founder: Venture capitalists are lazy and don't innovate. LinkedIn. https://www.linkedin.com/pulse/500-startups-founder-venture-capitalists-lazy-dont-caroline-fairchild

 eMarketer. (2025). VCs back healthcare AI startups in H1 2025. eMarketer. https://www.emarketer.com/content/ai-no-longer-nice-to-have-digital-health-startups-looking-investment-dollars

 Dhillon, S., Lopes, G., & Parker, J. L. (2023). The effect of biomarkers on clinical trial risk in gastric cancer. PubMed. https://pubmed.ncbi.nlm.nih.gov/36662871/

 Inc42. (2025). How LPs can build a well-diversified VC portfolio. Inc42. https://inc42.com/resources/how-lps-can-build-a-well-diversified-vc-portfolio/

 HIT Consultant. (2025). AI dominates digital health investment in first half of 2025. HIT Consultant. https://hitconsultant.net/2025/07/07/ai-dominates-digital-health-investment-in-first-half-of-2025/

 University of Toronto. (2021). Using predictive biomarkers could improve success rate of new cancer drugs: U of T study. University of Toronto. https://www.utoronto.ca/news/using-predictive-biomarkers-could-improve-success-rate-new-cancer-drugs-u-t-study

 LinkedIn. (2024). A guide to venture capital portfolio strategy: Understanding the breadth of startup investments. LinkedIn. https://www.linkedin.com/pulse/guide-venture-capital-portfolio-strategy-understanding-breadth-ddrie

 American Hospital Association. (2025). Digital health funding surges in Q1, with AI leading the way. AHA. https://www.aha.org/aha-center-health-innovation-market-scan/2025-05-27-digital-health-funding-surges-q1-ai-leading-way

 Mullard, A. (2016). Parsing clinical success rates. Nature Reviews Drug Discovery, 15(7), 447. https://www.nature.com/articles/nrd.2016.136

 LinkedIn. (2023). How can venture capitalists build a diverse portfolio? LinkedIn. https://www.linkedin.com/advice/0/how-can-venture-capitalists-build-diverse-portfolio-xcszf

 CB Insights. (2025). State of digital health Q1'25 report. CB Insights. https://www.cbinsights.com/research/report/state-of-digital-health-q125-report/

Clinical Development and FDA Approval Timelines

 Synerg BioPharma. (2025). How long does FDA approval take after Phase 3? Synerg BioPharma. https://synergbiopharma.com/how-long-does-fda-approval-take-after-phase-three/

 NC State University. (2024). COSO revises its ERM framework. Enterprise Risk Management Initiative. https://erm.ncsu.edu/resource-center/coso-revises-its-erm-framework/

 Viras, S. (2025). Health-AI strategy series: Measuring ROI and value creation in health-AI initiatives. LinkedIn. https://www.linkedin.com/pulse/health-ai-strategy-series-measuring-roi-value-creation-sehul-viras-8mctc

 Kaitin, K. I., & DiMasi, J. A. (2011). Pharmaceutical innovation in the 21st century: New drug approvals in the first decade, 2000-2009. Clinical Pharmacology & Therapeutics, 89(2), 183-188. https://pmc.ncbi.nlm.nih.gov/articles/PMC9869766/

 NC State University. (2020). COSO's ERM framework. Enterprise Risk Management Initiative. https://erm.ncsu.edu/resource-center/cosos-erm-framework/

 Simbo AI. (2025). Evaluating the ROI of AI investments in healthcare: Metrics for success and long-term benefits. Simbo AI Blogs. https://www.simbo.ai/blog/evaluating-the-roi-of-ai-investments-in-healthcare-metrics-for-success-and-long-term-benefits-3400589/

 US Food and Drug Administration. (2018). Step 3: Clinical research. FDA. https://www.fda.gov/patients/drug-development-process/step-3-clinical-research

 World Bank. (2020). Enterprise risk management. Committee on Financial Reporting and Regulatory Reform. https://cfrr.worldbank.org/sites/default/files/2020-02/17.pdf

 Vest, J. R. (2012). Metrics to address quality of care and return on investment. Agency for Healthcare Research and Quality. https://pmc.ncbi.nlm.nih.gov/articles/PMC3392952/

 US Food and Drug Administration. (2022). Development & approval process | Drugs. FDA. https://www.fda.gov/drugs/development-approval-process-drugs

 Mahidol University. (2019). COSO Enterprise Risk Management 2017. Risk Management Center. https://op.mahidol.ac.th/rm/wp-content/uploads/2019/01/Info-COSO-Enterprise-Risk-Management-2017-Jan-2019.pdf

 BHM PC. (2024). Measuring AI's cost and return on investment (ROI). BHM PC. https://bhmpc.com/2024/09/measuring-the-cost-and-return-on-investment-roi-with-ai-implementation/

 Synerg BioPharma. (2024). The FDA NDA review timeline explained: A step-by-step breakdown. Synerg BioPharma. https://synergbiopharma.com/fda-nda-review-timeline/

 IFAC. (2017). Important improvements included in COSO's new enterprise risk management framework. IFAC. https://www.ifac.org/knowledge-gateway/discussion/important-improvements-included-coso-s-new-enterprise-risk-management-framework

 Simbo AI. (2025). Measuring AI ROI: Essential KPIs and tools for healthcare organizations to assess performance and impact. Simbo AI Blogs. https://www.simbo.ai/blog/measuring-ai-roi-essential-kpis-and-tools-for-healthcare-organizations-to-assess-performance-and-impact-3717469/

 Drugs.com. (2024). FDA drug approval process. Drugs.com. https://www.drugs.com/fda-approval-process.html

 Scribd. (2025). COSO ERM Standard - 2017. Scribd. https://www.scribd.com/document/854173331/Coso-Erm-Standard-2017

 AHRQ. (2018). Return on investment tool. Agency for Healthcare Research and Quality. https://www.ahrq.gov/sites/default/files/wysiwyg/professionals/systems/hospital/qitoolkit/combined/f1_combo_returnoninvestment.pdf

 SkillsCommons. (2018). Understanding the drug approval process. SkillsCommons. https://www.skillscommons.org/bitstream/handle/taaccct/5972/Drug%20Approval%20Process.pdf

 SCH Group. (2021). Understanding the foundations of the COSO ERM framework to maximize value. SCH Group. https://www.schgroup.com/insights/blog/risk/understand-coso-erm-framework-maximize-value/

Healthcare Risk Management and Digital Health Funding

 American Society for Healthcare Risk Management. (2016). Enterprise risk management. ASHRM. https://www.ashrm.org/system/files?file=media%2Ffile%2F2019%2F06%2FERM-Tool_final.pdf

 Fierce Healthcare. (2025). Digital health venture funding hit $10.1B in 2024. Fierce Healthcare. https://www.fiercehealthcare.com/digital-health/digital-health-venture-funding-hit-101b-2024-investors-focused-earlier-stage-deals

 Fierce Healthcare. (2025). 2024 a mixed bag for health tech venture capital: HSBC report. Fierce Healthcare. https://www.fiercehealthcare.com/health-tech/2024-mixed-bag-health-tech-venture-capital-hsbc-report

 American Society for Healthcare Risk Management. (2019). Enterprise risk management (ERM) resources. ASHRM. https://www.ashrm.org/resources/erm-resources

 Fierce Healthcare. (2024). Digital health funding hit $5.7B through June, on track to surpass 2019 and 2023, Rock Health reports. Fierce Healthcare. https://www.fiercehealthcare.com/digital-health/digital-health-funding-hit-57b-through-june-track-surpass-2019-and-2023-rock-health

 BioPharma Dive. (2025). Healthcare venture capital investment boosted by AI in 2024: Report. BioPharma Dive. https://www.biopharmadive.com/news/healthcare-venture-captial-funding-ai-boost-2024-silicon-valley-bank/736902/

 American Society for Healthcare Risk Management. (2020). Leading health care risk management. ASHRM. https://www.ashrm.org/leading-health-care-risk-management

 Brock, S. (2025). Rock Health: Digital health funding drops in 2024, investors shift focus. LinkedIn. https://www.linkedin.com/posts/stephenbrockpmd_rock-health-digital-health-funding-drops-activity-7284957459981443072-7RHK

 Healthcare Dive. (2025). Healthcare venture capital investment amplified by AI in 2024: Report. Healthcare Dive. https://www.healthcaredive.com/news/healthcare-venture-captial-funding-ai-boost-2024-silicon-valley-bank/736870/

 American Society for Healthcare Risk Management. (2024). Enterprise risk management for health care, fourth edition. ASHRM. https://www.ashrm.org/enterprise-risk-management-health-care-fourth-edition

 MedCity News. (2025). Rock Health: Digital health funding drops in 2024, investors shift focus to early-stage startups. MedCity News. https://medcitynews.com/2025/01/rock-health-digital-funding-2024/

 Silicon Valley Bank. (2024). Healthcare sector sees steady rise in VC investment and fundraising. SVB. https://www.svb.com/news/company-news/healthcare-sector-sees-steady-rise-in-vc-investment-and-fundraising-silicon-valley-bank-releases-14th-edition-of-mid-year-healthcare-investments-and-exits-report/

 IRMI. (2025). American Society for Healthcare Risk Management (ASHRM). IRMI. https://www.irmi.com/term/insurance-definitions/american-society-for-healthcare-risk-management

 Healthcare Dive. (2025). Digital health funding falls again in 2024: Rock Health. Healthcare Dive. https://www.healthcaredive.com/news/digital-health-funding-declines-2024-rock-health/737476/

 Carta. (2025). How healthcare AI led a 'paradigm shift' in a $23B year for startups. Carta. https://carta.com/data/industry-spotlight-healthcare-2024/

 Origami Risk. (2023). ASHRM 2023. Origami Risk. https://www.origamirisk.com/ashrm-2023

 Healthcare Dive. (2024). Digital health funding shows improvement in 2024: Rock Health. Healthcare Dive. https://www.healthcaredive.com/news/digital-health-funding-first-half-2024-rock-health/720790/

 Carta. (2024). VC funding in healthcare shows resilience. Carta. https://carta.com/data/health-tech-2024/

 American Hospital Association. (2018). ASHRM executive director Matt Hornberger: Leveraging the value of enterprise risk management in a hospital setting. AHA News. https://www.aha.org/news/insights-and-analysis/2018-03-07-ashrm-executive-director-matt-hornberger-leveraging-value

 Rock Health. (2024). Q1 2024 digital health funding: Great (reset) expectations. LinkedIn. https://www.linkedin.com/posts/rock-health_q1-2024-digital-health-funding-great-reset-activity-7183137165197946880-kxO_