Examination of Clinical Trial Costs and Barriers for Drug Development. 6 References


Adams, C., & Brantner, V. (2006). Estimating The Cost Of New Drug Development: Is It Really $802 Million? Health Affairs, 25(2).

Adams, C., & Brantner, V. (2010). Spending on new drug development. Health Economics, 19(2), 130- 141.

Angell, M. (2004). Introduction: Drugs are Different. In M. Angell, The Truth About the Drug Companies (pp. xv-xvi). New York: Random House.

Ashar, B. H., Miller, R. G., Getz, K. J., & Powe, N. R. (2004). Prevalence and Determinants of Physician Participation in Conducting Pharmaceutical-sponsored Clinical Trials and Lectures. Journal of General Internal Medicine, 1140–1145.

Bailey, W., Cruickshank, C., & Sharma, N. (n.d.). Make Your Move: Taking Clinical Trials to the Best Location. Retrieved March 22, 2012, from A.T. Kearney: http://www.atkearney.com/index.php/Publications/make-your-move.html

Bonham, A., Califf, R., Gallin, E., & Lauer, M. (2011). Developing a Robust Clinical Trials Workforce. IOM Forum on Drug Discovery, Development, and Translation. Washington, D.C.: Institute of Medicine of the National Academies.

Brooks, C. (2012). An Independent Perspective on Clinical Trial Timelines: Trending Against Expectations. New York: Citeline.

Buchholzer, F. J. (2011). Implementing the Voluntary Harmonization Procedure for Accelerated Clinical Trial Approval. International Pharmaceutical Industry, 3(2), 68-69.

Califf, R. M., & Muhlbaier, L. H. (2003). Health Insurance Portability and Accountability Act (HIPAA): Must There Be a Trade-Off Between Privacy and Quality of Health Care, or Can We Advance Both? Circulation, 108, 915-918.

Califf, R. M., Filerman, G., Murray, R. K., & Rosenblatt, M. (2011). The Clinical Trials Enterprise in the United States: A Call for Disruptive Innovation. IOM Forum on Drug Discovery, Development, and Translation. Washington, D.C.: Institute of Medicine of the National Academies.

Clinical Trials Facilitation Groups (CTFG). (2010, March). Heads of Medicines Agencies (HMA). Retrieved May 15, 2012, from Guidance document for a Voluntary Harmonisation Procedure (VHP) for the assessment of multinational Clinical Trial Applications: Version 2: http://www.hma.eu/fileadmin/dateien/Human_Medicines/01- About_HMA/Working_Groups/CTFG/2010_03_VHP_Guidance_v2.pdf

Clinical Trials Transformation Initiative (CTTI). (2011). Clinical Trials Transformation Initiative (CTTI) - Identifying Practices that through Broad Adoption will Increase the Quality and Efficiency of Clinical Trials. Retrieved May 25, 2012, from https://www.ctti-clinicaltrials.org/

Collier, R. (2009, February 3). Rapidly rising clinical trial costs worry researchers. Canadian Medical Association Journal, 180(3), 277-278.

Cutting Edge Information. (2011, December 5). Outsourcing of Phase II Drug Development Now Accounts for 63% of R&D Budgets. Retrieved April 2012, 6, from Cutting Edge Information: http://www.cuttingedgeinfo.com/2011/outsourcing-phase-ii-drug-development/

Damodaran, A. (2007). Strategic Risk Taking: A Framework for Risk Management. Upper Saddle River, NJ: Pearson Prentice Hall.

Davis, J. R., Nolan, V. P., Woodcock, J., & Estabrook, R. W. (1999). Assuring Data Quality and Validity in Clinical Trials for Regulatory Decision Making: Workshop Report. Roundtable on Research and Development of Drugs, Biologics, and Medical Devices, Institute of Medicine.

Deloitte. (2009). Secondary Uses of Electronic Health Record (EHR) Data in Life Sciences. Deloitte Development LLC.

Dilts, D. M., & Sandler, A. B. (2006). Invisible Barriers to Clinical Trials: The Impact of Structural, Infrastructural, and Procedural Barriers to Opening Oncology Clinical Trials. Journal of Clinical Oncology, 24(28), 4545-4552.

DiMasi, J. A., Feldman, L., Seckler, A., & Wilson, A. (2010, March). Trends in Risks Associated With New Drug Development: Success Rates for Investigational Drugs. Clinical Pharmacology and Therapeutics, 87(3).

DiMasi, J. A., Grabowski, H. G., & Vernon, J. (2004). R&D Costs and Returns by Therapeutic Category. Drug Information Journal, 38, 211-223.

DiMasi, J. A., Hansen, R. W., & Grabowski, H. G. (2005). Reply: Extraordinary claims require extraordinary evidence. Journal of Health Economics, 1034–1044.

DiMasi, J., Hansen, R., & Grabowski, H. (2003). The price of innovation: new estimates of drug development costs. Journal of Health Economics, 22(2), 151-185.

Downing, N. S., Aminawung, J. A., Shah, N. D., Braunstein, J. B., Krumholz, H. M., & Ross, J. S. (2012, May 16). Regulatory Review of Novel Therapeutics — Comparison of Three Regulatory Agencies. The New England Journal of Medicine.

Eisenberg, P., Kaufmann, P., Sigal, E., & Woodcock, J. (2011). Developing a Clinical Trials Infrastructure. IOM Forum on Drug Discovery, Development, and Translation. Washington, D.C.: Institute of Medicine of the National Academies.

Eisenstein, E. L., Collins, R., Cracknell, B. S., Podesta, O., Reid, E. D., Sandercock, P., . . . Diaz, R. (2008). Sensible approaches for reducing clinical trial costs. Clinical Trials, 75-84.

Eisenstein, E. L., Lemons II, P. W., Tardiff, B. E., Schulman, K. A., Jolly, M. K., & Califf, R. M. (2004). Reducing the costs of phase III cardiovascular clinical trials. American Heart Journal, 149(3), 482-488.

Embi, P. J., Jain, A., Clark, J., Bizjack, S., Hornung, R., & Harris, C. M. (2005). Effect of a Clinical Trial Alert System on Physician Participation in Trial Recruitment. Archives of Internal Medicine, 2272-2277.

English, R., Lebovitz, Y., & Giffin, R. (2010). Transforming Clinical Research in the United States: Challenges and Opportunities: Workshop Summary. Institute of Medicine of the National Academies, Forum on Drug Discovery, Development, and Translation Board on Health Sciences Policy. Washington, D.C.: The National Academies Press.

Getz, K. A. (2006, December 1). Hitching a Ride with the Speed Demons of Drug Development. Retrieved December 15, 2011, from Applied Clinical Trials Online: http://www.actmagazine.com/appliedclinicaltrials/article/articleDetail.j...

Getz, K. A. (2007, September 1). Global Clinical Trials Activity in the Details. Retrieved March 21, 2012, from Applied Clinical Trials Online: http://www.appliedclinicaltrialsonline.com/appliedclinicaltrials/article... 3

Getz, K. A. (2008, May 1). The Heavy Burden of Protocol Design. Retrieved July 23, 2012, from Applied Clinical Trials Online: http://license.icopyright.net/user/viewFreeUse.act?fuid=MTY0NDY1NDE%3D

Getz, K. A. (2010a, November 1). Chasing Veteran U.S. Sites Out of the Enterprise. Retrieved April 19, 2012, from Applied Clinical Trials Online: http://license.icopyright.net/rights/offer.act?inprocess=t&sid=13&tag=3.... 552

Getz, K. A. (2010b, January 1). With Clinical Data, Less is More. Retrieved July 23, 2012, from Applied Clinical Trials Online: http://license.icopyright.net/user/viewFreeUse.act?fuid=MTY0NDU0Njg%3D

Getz, K. A. (2011a, March 1). Low Hanging Fruit in the Fight Against Inefficiency. Retrieved December 14, 2011, from Applied Clinical Trials Online: http://license.icopyright.net/user/viewFreeUse.act?fuid=MTQ4OTUyMDE%3D

Getz, K. A. (2011b, May 1). Protocol Amendments: A Costly Solution. Retrieved December 15, 2011, from Applied Clinical Trials Online: http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/... 719542&sk=9270beba3a37ef7e37f3fa5477eea1cf9%22

Getz, K. A., Wenger, J., Campo, R. A., Sequine, E. S., & Kaitin, K. I. (2008). Assessing the Impact of Protocol Design Changes on Clinical Trial Performance. American Journal of Therapeutics, 450- 457.

Getz, K. A., Zuckerman, R., Cropp, A. B., Hindle, A. L., Krauss, R., & Kaitin, K. I. (2011). Measuring the Incidence, Causes, and Repercussions of Protocol Amendments. Drug Information Journal, 265-275.

Getz, K., & Campo, R. (2013). Drug Development Study Designs have Reached the Danger Zone. Expert Review of Clinical Pharmacology Vol. 6 No. 6, 589–591.

GlaxoSmithKline. (2011, October). Global Public Policy Issues: GlaxoSmithKline’s Position: Clinical Trials in the Developing World. Retrieved May 9, 2012, from GlaxoSmithKline Government Affairs, Public Policy and Patient Advocacy: http://www.gsk.com/policies/GSK-on-clinicaltrials-in-the-developing-worl...

Glickman, S. W., McHutchison, J. G., Peterson, E. D., Cairns, C. B., Harrington, R. A., Califf, R. M., & Schulman, K. A. (2009). Ethical and Scientific Implications of the Globalization of Clinical Research. New England Journal of Medicine, 360(8), 816-823.

Hammons, G. T., Hilman, B. J., Kahan, J. P., & Neu, C. R. (1985). The Decision to Initiate Clinical Trials of Current Medical Practices. RAND Report prepared for the DHHS National Center for Health Services Research and Health Care Technology Assessment.

Harris, G. (2010, September 23). F.D.A. to Restrict Avandia, Citing Heart Risk. The New York Times. Hay, M., Rosenthal, J., Thomas, D., & Craighead, J. (2011, February 15). Presentation: Clinical Trial Success Rates Study (BIO CEO & Investor Conference). Biotechnology Industry Organization (BIO) / BioMedTracker.

Horton, N. J., & Switzer, S. S. (2005). Statistical methods in the journal. New England Journal of Medicine, 1977–1979.

Institute of Medicine Forum on Drug Discovery, Development, and Translation. (Undated). Template for Clinical Trial Agreements. Retrieved March 16, 2012, from http://www.iom.edu/~/media/Files/Activity%20Files/Research/DrugForum/Apr... 28/TemplateCTA%2042209.ashx

International Committee of Medical Journal Editors. (2010, April). Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication. Retrieved March 22, 2012, from International Committee of Medical Journal Editors: http://www.icmje.org/urm_main.html

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). (1996, April). Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance. Retrieved from U.S. Food and Drug Administration: http://www.fda.gov/downloads/Drugs/Guidances/ucm073122.pdf

Jenkins, J. K. (2011, December 8). CDER New Drug Review: 2011 Update - FDA/CMS Summit. Retrieved January 2, 2013, from http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProd... CDER/UCM282984.pdf

Jenkins, V., & Fallowfield, L. (2000). Reasons for accepting or declining to participate in randomized clinical trials for cancer therapy. British Journal of Cancer, 82(11), 1783–1788.

Kass, N. E., Chaisson, L., Taylor, H. A., & Lohse, J. (2011). Length and Complexity of US and International HIV Consent Forms from Federal HIV Network Trials. Journal of General Internal Medicine, 26(11), 1324-1328.

Korieth, K. (2011, February). The High Cost and Questionable Impact of 100% SDV. The CenterWatch Monthly, 18(2).

Krafft, H., Bélorgey, C., & Szalay, G. (2012). Correspondence: Experience and further development with the Voluntary Harmonization Procedure for multinational clinical trials in the European Union. Nature Reviews Drug Discovery.

Kramer, J. M., & Schulman, K. A. (2011). Transforming the Economics of Clinical Trials. IOM Forum on Drug Discovery, Development, and Translation. Washington, D.C.: Institute of Medicine of the National Academies.

Kramer, J. M., Smith, P. B., & Califf, R. M. (2012). Impediments to Clinical Research in the United States. Clinical Pharmacology & Therapeutics, 91(3), 535–541.

Light, D. W., & Warburton, R. N. (2005). Discussion: Extraordinary claims require extraordinary evidence. Journal of Health Economics, 1030-1033.

Lipsky, M. S., & Sharp, L. K. (2001). From Idea to Market: The Drug Approval Process. The Journal of the American Board of Family Practice, 362-367.

Marks, L., & Power, E. (2002). Using technology to address recruitment issues in the clinical trial process. Trends in Biotechnology, 105-109.

Medidata Solutions. (2012, September 5). Press Release: Medidata Solutions Selected to Support U.S. Government Research on Drug Development Costs. Retrieved September 24, 2012, from Medidata Solutions Worldwide, News & Events: http://www.mdsol.com/press/medidatasolutions-selected-to-support-us-gove...

Medidata Solutions. (2012a). CRO Contractor Database (CROCAS®).

Medidata Solutions. (2012b). Grants Manager Database (PICAS®)

Mills, E. J., Seely, D., Rachlis, B., Griffith, L., Wu, P., Wilson, K., . . . Wright, J. R. (2006, February). Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors. The Lancet Oncology, 7(2), 141-148.

Milne, C. (2012, March 2). Defining Conflict of Interest. Retrieved May 22, 2012, from Pharmaceutical Technology: http://license.icopyright.net/user/viewFreeUse.act?fuid=MTYyMjcyMjE%3D

Milne, C. P., & Kaitin, K. I. (2012). FDA Review Divisions: Performance Levels and the Impact on Drug Sponsors. Clinical Pharmacology & Therapeutics, 91(3), 393-404.

Morgan, S., Grootendorst, P., Lexchin, J., Cunningham, C., & Greyson, D. (2011). The cost of drug development: a systematic review. Health Policy, 100(1), 4-17.

Morrison, B. W., Cochran, C. J., White, J. G., Harley, J., Kleppinger, C. F., Liu, A., . . . Neaton, J. D. (2011). Monitoring the quality of conduct of clinical trials: a survey of current practices. Clinical Trials, 342–349.

National Institutes of Health. (2011, August 23). HHS Tightens Financial Conflict of Interest Rules for Researchers. Retrieved March 5, 2013, from National Institutes of Health: http://www.nih.gov/news/health/aug2011/od-23.htm

Neuer, A., Warnock, N., & Slezinger, E. (2010, April 1). The Upfront Cost Hurdle of EDC. Retrieved May 22, 2012, from Applied Clinical Trials Online: http://license.icopyright.net/user/viewFreeUse.act?fuid=MTYyMjgyMzI%3D

Pollack, A. (2012, March 29). Panel Recommends More Testing for Obesity Drugs. The New York Times.

Rai, S. (2005, February 24). Drug Companies Cut Costs With Foreign Clinical Trials. The New York Times.

Ridley, D. B., Grabowski, H. G., & Moe, J. L. (2006). Developing Drugs For Developing Countries. Health Affairs, 25(2), 313-324.

RTI International. (2006, April). Criteria for Distinguishing Effectiveness From Efficacy Trials in Systematic Reviews. Technical Review(12). Agency for Healthcare Research and Quality. Retrieved February 19, 2013, from http://www.ncbi.nlm.nih.gov/books/NBK44029/pdf/TOC.pdf

Schmidt, C. W. (2001). Monitoring research overseas. Modern Drug Discovery, 4(2), 25-26.

Shapiro, M. (2008, September 1). At Home Testing Offers Solution. Retrieved August 20, 2012, from Modern Medicine: http://license.icopyright.net/user/viewFreeUse.act?fuid=MTY1MTY4MTg%3D

Shavers, V. L., Lynch, C. F., & Burmeister, L. F. (2000). Knowledge of the Tuskegee Study and Its Impact on the Willingness to Participate in Medical Research Studies. Journal of the National Medical Association, 92, 563-572.

Sherman, R. B., Woodcock, J., Norden, J., Grandinetti, C., & Temple, R. J. (2011, July 7). New FDA Regulation to Improve Safety Reporting in Clinical Trials. The New England Journal of Medicine, 3-5.

Silverman, E. (2011, June 7). Pf zer And A ‘Cl n cal Tr al In A Bo ’ For Home Use. Retrieved May 31, 2012, from Pharmalot: http://www.pharmalot.com/2011/06/pfizer-and-a-clinical-trial-in-a-boxfor...

Society for Clinical Data Management. (2005). Good Clinical Data Management Practices, Version 4. Society for Clinical Data Management, Inc.

Tantsyura, V., Grimes, I., Mitchel, J., Fendt, K., Sirichenko, S., Waters, J., . . . Tardiff, B. (2010). Riskbased Source Data Verification Approaches: Pros and Cons. Drug Information Journal, 44, 745– 756.

Tufts CSDD. (2011). September/October 2011 Tufts CSDD Impact Report Press Release. Retrieved December 15, 2011, from Tufts Center for the Study of Drug Development: http://csdd.tufts.edu/files/uploads/september-october_impact_report_pres...

Tufts CSDD. (2012). November/December 2012 Tufts CSDD Impact Report Press Release. Retrieved November 7, 2012, from Tufts Center for the Study of Drug Development: http://csdd.tufts.edu/files/uploads/nov-dec_2012_ir_summary.pdf

U.S. Bureau of Labor Statistics. (2012). Consumer Price Index (CPI) Inflation Calculator. Retrieved April 30, 2012, from U.S. Bureau of Labor Statistics: http://data.bls.gov/cgi-bin/cpicalc.pl

U.S. Department of Health & Human Services. (2012, February 17). News Release: HHS Secretary Kathleen Sebelius announces major progress in doctors, hospital use of health information technology. Retrieved November 15, 2012, from U.S. Department of Health & Human Services Newsroom: http://www.hhs.gov/news/press/2012pres/02/20120217a.html

U.S. Food and Drug Administration. (2006a, January). Guidance for Industry, Investigators, and Reviewers: Exploratory IND Studies. Retrieved March 11, 2013, from http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati... m078933.pdf

U.S. Food and Drug Administration. (2006b, March). Guidance for Industry: Using a Centralized IRB Review Process in Multicenter Clinical Trials. Retrieved March 14, 2012, from http://www.fda.gov/RegulatoryInformation/Guidances/ucm127004.htm

U.S. Food and Drug Administration. (2011a, February). Guidance for Industry and FDA Staff: Best Practices for Conducting and Reporting Pharmacoepidemiologic Safety Studies Using Electronic Healthcare Data Sets. Retrieved June 13, 2012, from http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati... CM243537.pdf

U.S. Food and Drug Administration. (2011b, May). Guidance for Clinical Investigators, Industry, and FDA Staff Financial Disclosure by Clinical Investigators: Draft Guidance. Retrieved March 5, 2013, from http://www.fda.gov/downloads/regulatoryinformation/guidances/ucm256525.pdf

U.S. Food and Drug Administration. (2011c, August). Guidance for Industry Oversight of Clinical Investigations — A Risk-Based Approach to Monitoring. Retrieved March 21, 2012, from http://www.fda.gov/downloads/Drugs/.../Guidances/UCM269919.pdf

U.S. Food and Drug Administration. (2012). FY 2011 Performance Report to the President and Congress for the Prescription Drug User Fee Act. Retrieved June 11, 2012, from U.S. Food and Drug Administration: http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/UserFe... rmanceReports/PDUFA/UCM294101.pdf

U.S. Food and Drug Administration. (2012, April 23). Public Hearing. Modernizing the Regulation of Clinical Trials and Approaches to Good Clinical Practice. Silver Spring, Maryland: U.S. Food and Drug Administration, Department of Health and Human Services.

U.S. Food and Drug Administration. (2012a, March 25). Modernizing the Regulation of Clinical Trials and Approaches to Good Clinical Practice Public Hearing. Retrieved May 25, 2012, from U.S. Food and Drug Administration: http://www.fda.gov/Drugs/NewsEvents/ucm284118.htm

U.S. Food and Drug Administration. (2012b, July 24). Notice: Prescription Drug User Fee Rates for Fiscal Year 2013.

U.S. Food and Drug Administration. (2012c). PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2013 Through 2017. Retrieved December 7, 2012, from U.S. Food and Drug Administration: http://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfe...

U.S. Food and Drug Administration. (2013). Impact Innovation Predictability Access: 2012 Novel New Drugs Summary. Silver Spring, MD: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, U.S. Department of Health and Human Services.

Usher, R. W. (2010). PhRMA BioResearch Monitoring Committee Perspective on Acceptable Approaches for Clinical Trial Monitoring. Drug Information Journal, 44, 477–483.

Weisfeld, V., English, R. A., & Claiborne, A. B. (2011). Public Engagement and Clinical Trials: New Models and Disruptive Technologies: Workshop Summary. Institute of Medicine of the National Academies, Forum on Drug Discovery, Development, and Translation. Washington, D.C.: The National Academies Press.

Welton, A. J., Vickers, M. R., Cooper, J. A., Meade, T. W., & Marteau, T. M. (1999). Is recruitment more difficult with a placebo arm in randomised controlled trials? A quasirandomised, interview based study. British Medical Journal (BMJ), 318, 1114–1117.

Windish, D. M., Huot, S. J., & Green, M. L. (2007). Medicine Residents’ Understanding of the Biostatistics and Results in the Medical Literature. JAMA, 298(9), 1010-1022.

World Health Organization. (2006). The World Health Report 2006 - Working Together for Health. Retrieved March 22, 2012, from World Health Organization: http://www.who.int/whr/2006/06_chap4_en.pdf


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