Off-label Drugs
1. Prevalence Estimates | Vision and Eye Health Surveillance System | Vision Health Initiative (VHI) | CDC. (n.d.). https://www.cdc.gov/visionhealth/vehss/estimates/amd-prevalence.html
2. Treatments for Wet AMD (Advanced Neovascular AMD) | National Eye Institute. (n.d.). https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-related-macular-degeneration/treatments-wet-amd-advanced-neovascular-amd#:~:text=Wet%20AMD%20(also%20called%20advanced,the%20back%20of%20your%20eye.
3. Comparison of Anti-VEGF Treatments for Wet AMD. (2020, February 5). American Academy of Ophthalmology. https://www.aao.org/eye-health/diseases/avastin-eylea-lucentis-difference
4. Office of the Commissioner & Office of the Commissioner. (2018, February 5). Understanding Unapproved Use of Approved Drugs “Off Label.” U.S. Food and Drug Administration. https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/understanding-unapproved-use-approved-drugs-label
5. Off-Label Drugs: What You Need to Know | Agency for Healthcare Research and Quality. (n.d.). https://www.ahrq.gov/patients-consumers/patient-involvement/off-label-drug-usage.html
6. Avastin was initially approved for metastatic colon cancer and has since received subsequent approvals for other cancer indications.
7. Rosenfeld, P. J., Brown, D., Heier, J. S., Boyer, D. S., Kaiser, P. K., Chung, C., & Kim, R. Y. (2006). Ranibizumab for Neovascular Age-Related Macular Degeneration. The New England Journal of Medicine, 355(14), 1419–1431. https://doi.org/10.1056/nejmoa054481
8. Comparative Effectiveness Research, 10 Years After the ACA: Where Do We Go from Here? (2020). Commonwealth Fund. https://doi.org/10.26099/34zd-z807
9. Avastin and Lucentis are equivalent in treating age-related macular. (2015, August 31). National Institutes of Health (NIH). https://www.nih.gov/news-events/news-releases/avastin-lucentis-are-equivalent-treating-age-related-macular-degeneration
10. Davari, M., Khorasani, E., & Tigabu, B. M. (1970). Factors Influencing Prescribing Decisions of Physicians: A Review. Ethiopian Journal of Health Sciences, 28(6). https://doi.org/10.4314/ejhs.v28i6.15
11. Drugs competing with Lucentis: Eylea (Afilbercept), Beovu (brolucizumab-dbll), and Vabysmo (Faricimab-svoa). The three aforementioned drugs are all biologics and were approved in 2011, 2019, and 2022, respectively. Additionally, Lucentis biosimilars Byooviz (2021) and Cimerli (2022) have also been FDA-approved to treat wet AMD in the United States.
12. Jeremias, S. (2022, April 26). Despite Overall Increases, Blockbuster Roche Products Take Hit from Biosimilars. Center for Biosimilars. https://www.centerforbiosimilars.com/view/despite-overall-increases-blockbuster-roche-products-take-hit-from-biosimilars
13. Glasser, D., Parikh, R. B., Lum, F., & Williams, G. (2020). Intravitreal Anti–Vascular Endothelial Growth Factor Cost Savings Achievable with Increased Bevacizumab Reimbursement and Use. Ophthalmology, 127(12), 1688–1692. https://doi.org/10.1016/j.ophtha.2020.06.012
14. Comparison of Anti-VEGF Treatments for Wet AMD. (2020, February 5). American Academy of Ophthalmology. https://www.aao.org/eye-health/diseases/avastin-eylea-lucentis-difference
15. Muhlestein, D., Chopra, A., Lester, C., & Kitterman, K. (2020). ACOs and Age-Related Macular Degeneration (AMD): Practice Patterns Impact Savings. In www.carejourney.com. CareJourney. Retrieved March 22, 2023, from https://carejourney.com/wp-content/uploads/2020/05/ACOs-and-AMD.pdf
16. Glasser, D., Parikh, R. B., Lum, F., & Williams, G. (2020). Intravitreal Anti–Vascular Endothelial Growth Factor Cost Savings Achievable with Increased Bevacizumab Reimbursement and Use. Ophthalmology, 127(12), 1688–1692. https://doi.org/10.1016/j.ophtha.2020.06.012
17. 2023 ASP Drug Pricing Files | CMS. (n.d.). https://www.cms.gov/medicare/medicare-part-b-drug-average-sales-price/2023-asp-drug-pricing-files
Biologics vs. Biosimilars
1. FDA Purple Book. (2023). https://purplebooksearch.fda.gov/results?query=infliximab&title=Remicade
2. Biosimilars in the United States 2023–2027. (2023). In IQVIA. https://www.iqvia.com/-/media/iqvia/pdfs/institute-reports/biosimilars-in-the-united-states-2023-2027/iqvia-institute-biosimilars-in-the-united-states-2023-usl-orb3393.pdf.
3. 42 U.S. Code § 262 - Regulation of biological products. (n.d.-b). LII / Legal Information Institute.
4. Office of the Commissioner & Office of the Commissioner. (2022, August 17). Fact Sheet: FDA at a Glance. U.S. Food And Drug Administration. https://www.fda.gov/about-fda/fda-basics/fact-sheet-fda-glance
5. AmerisourceBergen. (2003). U.S. Biosimilar Report. https://www.amerisourcebergen.com/-/media/assets/amerisourcebergen/biosimilars-page/sgs-biosimilars-usmarketlandscape-020623---copy.pdf
6. Overpatented, Overpriced Curbing patent abuse: Tackling the root of the drug pricing crisis. (2022). In I-MAK. https://www.i-mak.org/wp-content/uploads/2023/01/Overpatented-Overpriced-2023-01-24.pdf
7. Ibid.
8. Dalpoas, S. E., Socal, M. P., Proctor, C. A., & Shermock, K. M. (2020). Barriers to biosimilar utilization in the United States. American Journal of Health-System Pharmacy, 77(23), 2006–2014. https://doi.org/10.1093/ajhp/zxaa297
9. 42 U.S. Code § 262 - Regulation of biological products. (n.d.-b). LII / Legal Information Institute. https://www.law.cornell.edu/uscode/text/42/262#:~:text=(2)%20The%20term%20%E28%9Cbiosimilar,in%20clinically%20inactive%20components%3B%20and9
10. Barriers to biosimilar utilization in the United States. (2020, October 22). American Journal of Health-System Pharmacy. https://academic.oup.com/ajhp/article-abstract/77/23/2006/5935803?redirectedFrom=fulltext
11. Changes to the Purple Book: Progress in Transparency. (2021, August 3). JD Supra. https://www.jdsupra.com/legalnews/changes-to-the-purple-book-progress-in-6749919/
12. Biosimilars in the United States 2023–2027. (2023). In IQVIA. https://www.iqvia.com/-/media/iqvia/pdfs/institute-reports/biosimilars-in-the-united-states-2023-2027/iqvia-institute-biosimilars-in-the-united-states-2023-usl-orb3393.pdf
13. Ibid.
14. Janssen, I. C. W. (2022, December 13). Understanding Unbranded
Biologics. Beckerspayer. https://www.beckerspayer.com/payer/understanding-unbranded-biologics.html
15. Average Sales Price (ASP) is the volume-weighted average of the manufacturers' average sales prices for all National Drug Codes assigned to the drug or biological product. This number is statutorily defined and used as the basis of Medicare reimbursement for pharmaceutical products.
16. Barriers to biosimilar utilization in the United States. (n.d.). https://norc.sharepoint.com/sites/G288-RxSupplyChain836/Shared%20Documents/General/05.%20Playbooks/Biologics_Biosimilars/Reference%20Material/Barriers%20to%20biosimilar%20Utilization_ASHSP%20Article.pdf?CT=1677611633965&OR=ItemsView
17. A Report in Response to the Executive Order on Lowering Prescription Drug Costs for Americans. (n.d.). U.S. Department of Health and Human Services. https://innovation.cms.gov/data-and-reports/2023/eo-rx-drug-cost-response-report
18. Ibid.
19. Pfizer, Johnson & Johnson settle high-profile Remicade biosim lawsuit on undisclosed terms. (2021, July 26). Fierce Pharma. https://www.fiercepharma.com/pharma/pfizer-johnson-johnson-agree-to-a-settlement-terms-undisclosed-biosimilar-lawsuit
20. Ibid.
21. J&J boasted about defending Remicade from biosims. Now it’s under FTC investigation. (2019, July 30). Fierce Pharma. https://www.fiercepharma.com/pharma/j-j-has-boasted-about-its-remicade-defense-and-now-it-s-under-ftc-investigation
22. Dalpoas, S. E., Socal, M. P., Proctor, C. A., & Shermock, K. M. (2020a). Barriers to biosimilar utilization in the United States. American Journal of Health-System Pharmacy, 77(23), 2006–2014. https://doi.org/10.1093/ajhp/zxaa297
23. Z a Seeley, E., & Kesselheim, A. (2019b). Pharmacy Benefit Managers: Practices, Controversies, and What Lies Ahead. https://www.commonwealthfund.org/publications/issue-briefs/2019/mar/pharmacy-benefit-managers-practices-controversies-what-lies-ahead
Cell & Gene Therapy
1. What is Gene Therapy? U.S. Food And Drug Administration. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapy
2. Approved Cellular and Gene Therapy Products. U.S. Food And Drug Administration. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products
3. Spinal Muscular Atrophy. (n.d.). National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/spinal-muscular-atrophy#:~:text=Spinal%20muscular%20atrophy%20(SMA)%20is,to%20muscle%20weakness%20and%20atrophy
4. Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1 - Full Text View - ClinicalTrials.gov. (n.d.). https://clinicaltrials.gov/ct2/show/NCT02122952
5. Clinical studies results. (n.d.). ZOLGENSMA. https://www.zolgensma.com/clinical-studies
6. Novartis data again demonstrate age-appropriate development when Zolgensma is used presymptomatically, and post-hoc data reveal SMA Type 1 patients could speak, swallow and maintain airway protection. (2022, March 14). Novartis. https://www.novartis.com/news/media-releases/novartis-data-again-demonstrate-age-appropriate-development-when-zolgensma-used-presymptomatically-and-post-hoc-data-reveal-sma-type-1-patients-could-speak-swallow-and-maintain-airway-protection
7. Milton, A. (n.d.). “One-and-done” gene therapies. KPMG. https://advisory.kpmg.us/content/dam/advisory/en/pdfs/2021/cell-and-gene-therapies.pdf
8. AveXis Announces Innovative Zolgensma® Gene Therapy Access Programs for US Payers and Families. (n.d.). Novartis. https://www.novartis.com/news/media-releases/avexis-announces-innovative-zolgensma-gene-therapy-access-programs-us-payers-and-families
9. Q3 2022 Results Investor presentation. (n.d.). In Novartis. https://www.novartis.com/sites/novartis_com/files/q3-2022-investor-presentation.pdf
10. Accelerated Approval Program. U.S. Food And Drug Administration. https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program
11. Summary Basis for Regulatory Action. (n.d.). FDA. https://www.fda.gov/media/127961/download
12. Office of the Commissioner & Office of the Commissioner. (2018, March 9). Orphan Drug Act - Relevant Excerpts. U.S. Food And Drug Administration. https://www.fda.gov/industry/designating-orphan-product-drugs-and-biological-products/orphan-drug-act-relevant-excerpts
13. Office of the Commissioner & Office of the Commissioner. (2018a, February 23). The Story Behind the Orphan Drug Act. U.S. Food And Drug Administration. https://www.fda.gov/industry/fdas-rare-disease-day/story-behind-orphan-drug-act
14. Tribble, S. J. (2017, January 17). Drugs For Rare Diseases Have Become Uncommonly Rich
Monopolies. NPR. https://www.npr.org/sections/health-shots/2017/01/17/509506836/drugs-for-rare-diseases-have-become-uncommonly-rich-monopolies
15. Novartis gets FDA nod to begin making Zolgensma in North Carolina. (2022, April 5). Fierce Pharma. https://www.fiercepharma.com/manufacturing/novartis-gets-fda-nod-begin-making-zolgensma-north-carolina
16. Gene therapy coming of age: Opportunities and challenges to getting ahead. (2019, October 2). McKinsey & Company. https://www.mckinsey.com/industries/life-sciences/our-insights/gene-therapy-coming-of-age-opportunities-and-challenges-to-getting-ahead
17. De Luca, M., & Cossu, G. (2023). Cost and availability of novel cell and gene therapies. EMBO Reports, 24(2). https://doi.org/10.15252/embr.202256661
18. Payer perspectives on outcomes tracking for value-based payment arrangements (VBPs). (2021). In MIT
NEWDIGS. https://newdigs.tuftsmedicalcenter.org/wp-content/uploads/2022/06/FoCUS-Research-Brief-Outcomes-Tracking-2021F203v053.pdf
19. Caffrey, M. (2019, June 18). MIT Group Brings Together Stakeholders to Brainstorm How to Pay for Curative Therapies Over Time. AJMC. https://www.ajmc.com/view/mit-group-brings-together-stakeholders-to-brainstorm-how-to-pay-for-curative-therapies-over-time-
20. Ballreich, J., Ezebilo, I., Khalifa, B. a. A., Choe, J. A., & Anderson, G. F. (2022). Coverage of genetic therapies for spinal muscular atrophy across fee-for-service Medicaid programs. Journal of Managed Care & Specialty Pharmacy, 28(1), 39-47. https://doi.org/10.18553/jmcp.2022.28.1.39
HIV Prevention
1. Centers for Disease Control and Prevention. (2022, September 2). HIV Incidence. Retrieved March 21, 2023, from https://www.cdc.gov/hiv/statistics/overview/in-us/incidence.html
2. Smith, D. K., Sullivan, P. F., Cadwell, B. L., Waller, L. A., Siddiqi, A. E. A., Mera-Giler, R., Hu, X., Hoover, K. W., Harris, N., & McCallister, S. (2020). Evidence of an Association of Increases in Pre-exposure Prophylaxis Coverage With Decreases in Human Immunodeficiency Virus Diagnosis Rates in the United States, 2012–2016. Clinical Infectious Diseases, 71(12), 3144–3151. https://doi.org/10.1093/cid/ciz1229
3. US Food & Drug Administration. (2006, January 31). Drug Approval Package: Truvada (Emtricitabine and Tenofovir Disoproxil Fumarate). Retrieved March 21, 2023, from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021752s000_TruvadaTOC.cfm
4. US Food & Drug Administration. (2019, October 3). FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic [Press release]. https://www.fda.gov/news-events/press-announcements/fda-approves-second-drug-prevent-hiv-infection-part-ongoing-efforts-end-hiv-epidemic
5. Generic Truvada Availability. (2023, March 9). Drugs.com. Retrieved March 21, 2023, from https://www.drugs.com/availability/generic-truvada.html#Has%20A%20Generic%20Version%20of%20Truvada%20Been%20approved?
6. Dickson, S., & Killelea, A. (2021). Intentionally Delayed Pharmaceutical Innovation Under Perverse Incentives: Gilead’s HIV Pipeline As A Case Study. Health Affairs Forefront. https://doi.org/10.1377/forefront.20210614.619677
7. Data from SSR Health.
8. FTC Files Amicus Brief Explaining that Pharmaceutical “Product Hopping” Can Violate the Antitrust Laws. (2015, October 1). Federal Trade Commission. https://www.ftc.gov/news-events/news/press-releases/2015/10/ftc-files-amicus-brief-explaining-pharmaceutical-product-hopping-can-violate-antitrust-laws
9. Brill, A. (2020). The Cost of Brand Drug Product Hopping. Matrix Global Advisors. Retrieved June 7, 2023, from https://www.affordableprescriptiondrugs.org/app/uploads/2020/09/CostofProductHoppingSept2020-1.pdf
10. Murphy, T. (2021, October 7). Are Health Centers Needlessly Prescribing Pricey Descovy for PrEP Because They Get a Government Kickback? The Body: The HIV/AIDS Resource. Retrieved March 21, 2023, from https://www.thebody.com/article/needlessly-prescribing-pricey-descovy-for-prep
11. Dickson, S., & Killelea, A. (2021). Intentionally Delayed Pharmaceutical Innovation Under Perverse Incentives: Gilead’s HIV Pipeline As A Case Study. Health Affairs Forefront. https://doi.org/10.1377/forefront.20210614.619677
12. Murphy, T. (2021, October 7). Are Health Centers Needlessly Prescribing Pricey Descovy for PrEP Because They Get a Government Kickback? The Body: The HIV/AIDS Resource. Retrieved March 21, 2023, from https://www.thebody.com/article/needlessly-prescribing-pricey-descovy-for-prep
13. Centers for Disease Control and Prevention. (2022a, June 6). PrEP Effectiveness. Retrieved March 21, 2023, from https://www.cdc.gov/hiv/basics/prep/prep-effectiveness.html
14. AHEAD. (2022, March). The Six EHE Indicators: National Data. Retrieved March 21, 2023, from https://ahead.hiv.gov/data/prep-coverage
15. Data from SSR Health.
16. Clark, B, & Puthiyath, M. S (2022). The Federal 340B Drug Pricing Program: What It Is, and Why It’s Facing Legal Challenges. The Commonwealth Fund. https://doi.org/10.26099/c4z8-pf65
17. Ballreich, J., Levengood, T. W., & Conti, R. M. (2022). Opportunities and Challenges of Generic Pre-Exposure Prophylaxis Drugs for HIV. Journal of Law Medicine & Ethics, 50(S1), 32–39. https://doi.org/10.1017/jme.2022.33
18. Prevention of Human Immunodeficiency Virus (HIV) Infection: Preexposure Prophylaxis. (2019). https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/prevention-of-human-immunodeficiency-virus-hiv-infection-pre-exposure-prophylaxis
19. Coverage of Certain Preventive Services Under the Affordable Care Act. (2015, July 14). Federal Register. https://www.federalregister.gov/documents/2015/07/14/2015-17076/coverage-of-certain-preventive-services-under-the-affordable-care-act
20. Farrow, K. (2022). The Downstream Impacts of High Drug Costs for PrEP Have Hindered the Promise of HIV Prevention. Journal of Law Medicine & Ethics, 50(S1), 47–50. https://doi.org/10.1017/jme.2022.35
Insulin
1. Irving, D. (2021, January 6). The Astronomical Price of Insulin Hurts American Families. RAND Review. https://www.rand.org/blog/rand-review/2021/01/the-astronomical-price-of-insulin-hurts-american-families.html
2. Insulin: Examining the Factors Driving the Rising Cost of a Century Old Drug. (n.d.). United States Senate Finance Committee. https://www.finance.senate.gov/imo/media/doc/Grassley-Wyden%20Insulin%20Report%20(FINAL%201).pdf
3. CDC. (2020). National Diabetes Statistics Report 2020. In CDC. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf
4. National Diabetes Statistics Report | Diabetes | CDC. (n.d.). https://www.cdc.gov/diabetes/data/statistics-report/index.html#print
5. CDC. (2020). National Diabetes Statistics Report 2020. In CDC. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf
6. Gerstein, H. C., & Herman, W. H. (2018). The Cost of Diabetes Care—An Elephant in the Room. Diabetes Care, 41(5), 929–932. https://doi.org/10.2337/dci18-0012
7. Rowley, W., Bezold, C., Arikan, Y., Byrne, E., & Krohe, S. (2017). Diabetes 2030: Insights from Yesterday, Today, and Future Trends. Population Health Management, 20(1), 6–12. https://doi.org/10.1089/pop.2015.0181
8. González, O. (2022, October 18). High insulin prices lead some adults to ration. Axios. https://www.axios.com/2022/10/18/insulin-rationing-prices-study
9. Committee on Oversight and Accountability Democrats. (2021, December 10). Chairwoman Maloney Releases Comprehensive Staff Report Culminating the Committee’s Sweeping Drug Pricing Investigation [Press Release]. https://oversightdemocrats.house.gov/news/press-releases/chairwoman-maloney-releases-comprehensive-staff-report-culminating-the-committee
10. Luo, J., Avorn, J., & Kesselheim, A. S. (2015). Trends in Medicaid Reimbursements for Insulin From 1991 Through 2014. JAMA Internal Medicine, 175(10), 1681. https://doi.org/10.1001/jamainternmed.2015.4338
11. Committee on Oversight and Accountability Democrats. (2021, December 10). Chairwoman Maloney Releases Comprehensive Staff Report Culminating the Committee’s Sweeping Drug Pricing Investigation [Press release]. https://oversightdemocrats.house.gov/news/press-releases/chairwoman-maloney-releases-comprehensive-staff-report-culminating-the-committee
12. Implementation of the Biologics Price Competition and Innovation Act of 2009. U.S. Food And Drug Administration. https://www.fda.gov/drugs/guidance-compliance-regulatory-information/implementation-biologics-price-competition-and-innovation-act-2009
13. Insulin is Now a Biologic—What Does That Mean? | ADA. (2020, March 23). https://diabetes.org/blog/insulin-now-biologic-what-does-mean
14. FDA. (2020, March 23). Insulin Gains New Pathway to Increased Competition [Press release]. https://www.fda.gov/news-events/press-announcements/insulin-gains-new-pathway-increased-competition
15. Mulcahy, A. W. (2022, January 26). Projected US Savings From Biosimilars, 2021–2025. RAND. https://www.rand.org/pubs/external_publications/EP68829.html
16. FDA Approves First Interchangeable Biosimilar Insulin Product for Treatment of Diabetes. (2021, July 28). [Press release]. https://www.fda.gov/news-events/press-announcements/fda-approves-first-interchangeable-biosimilar-insulin-product-treatment-diabetes
17. Knox, R. G. (2020). Insulin insulated: barriers to competition and affordability in the United States insulin market. Journal of Law and the Biosciences, 7(1). https://doi.org/10.1093/jlb/lsaa061
18. Inflation Reduction Act, H.R.5376, 117th Cong. (2022). https://www.congress.gov/bill/117th-congress/house-bill/5376/text
19. Ibid.
20. Lilly Cuts Insulin Prices by 70% and Caps Patient Insulin Out-of-Pocket Costs at $35 Per Month. (2023, March 1). [Press release]. https://investor.lilly.com/news-releases/news-release-details/lilly-cuts-insulin-prices-70-and-caps-patient-insulin-out-pocket
21. Novo Nordisk to lower U.S. prices of several pre-filled insulin pens and vials up to 75% for people living with diabetes in January 2024. (2023, March 14). [Press release]. https://www.novonordisk.com/news-and-media/latest-news/lowering-us-list-prices-of-several-products-.html
22. Press Release: Sanofi cuts U.S. list price of Lantus®, its most-prescribed insulin, by 78% and caps out-of-pocket Lantus costs at $35 for all patients with commercial insurance. (2023, March 16). [Press release]. https://www.sanofi.com/en/media-room/press-releases/2023/2023-03-16-20-06-43-2629188
23. CivicaRx. (2022). Civica to Manufacture and Distribute Affordable Insulin. Civica Rx. https://civicarx.org/civica-to-manufacture-and-distribute-affordable-insulin/
24. Ollove, M. (2023, January 13). More States Are Doing What They Can to Cap Insulin Costs. The Pew Charitable Trusts. https://www.pewtrusts.org/en/research-and-analysis/blogs/stateline/2023/01/12/more-states-are-doing-what-they-can-to-cap-insulin-costs
25. Herman, W. H., Ribero, R., Ryan, M., & Sood, N. (2021). Estimation of the Share of Net Expenditures on Insulin Captured by US Manufacturers, Wholesalers, Pharmacy Benefit Managers, Pharmacies, and Health Plans From 2014 to 2018. JAMA Health Forum, 2(11), e213409. https://doi.org/10.1001/jamahealthforum.2021.3409
26. Ibid.