The Agile Approach to Adaptive Research: Optimizing Efficiency in Clinical Development

The Agile Approach to Adaptive Research: Optimizing Efficiency in Clinical Development

Volumn , Issue , 2010, Pages

  Rosenberg, Michael J ^a  

^a NONE

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[No Author keywords available]

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EID: 84891583716     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470599686     Document Type: Book

References (196)

1. Go A, Lee W, Yang J, Lo J, Gurwitz J. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA 2006;296:2105-11.
2. Department of Health and Human Services (US), Food and Drug Administration. Consumer update: celebrating the successes of the Orphan Drug Act. Washington (DC): 2008 Feb 8 [cited Aug 3, 2008]; [about two screens]. Available from: http://www.fda.gov/ consumer/updates/oda020808.html.
3. Diabetes. World Health Organization. Geneva: Sept 2006 (Fact Sheet No. 312). Available from: http://www.who.int/mediacentre/factsheets/fs312/en/.
4. Susman E, Analysis: HIV life expectancy now normal. United Press International. Toronto: Aug 25, 2006. Available from: http://www.terradaily.com/reports/HIV_Life_Ex-pectancy_Now_Normal_999.html.
5. Bates S, Weitz J. New anticoagulants: beyond heparin, low-molecular-weight heparin and warfarin. Br J Pharmacol 2005;144:1017-28.
6. Pfizer Inc. annual reports 2001-2007 New York; available from: http://www.pfizer.com/ investors/financial_reports/financial_reports.jsp.
7. Morrow D. Warner-Lambert recovers from $7 billion scare. New York Times. Apr 15, 1998. Available from: http://query.nytimes.com/gst/fullpage.html?res=940CE0DF163CF 936A25757C0A96E958260&sec=&spon=&pagewanted=2.
8. Pharmaceutical industry profile 2008. Washington (DC): Pharmaceutical Research and Manufacturers of America; Mar 2008. p. ii.
9. Pharma 2020: the vision; which path will you take? New York: PricewaterhouseCoopers LLP. 2007, p. 6. Available from: http://www.pwc.com/extweb/pwcpublications.nsf/doci d/91BF330647FFA402852572F2005ECC22.
10. Pharmaceutical Industry Profile 2008. Washington (DC): Pharmaceutical Research and Manufacturers of America; Mar 2008; Pharmaceutical Industry Profile 2006. Washington (DC): Mar 2006; Food and Drug Administration Center for Drug Evaluation and Research. Available from: http://www.fda.gov/AboutFDA/WhatWeDo/History/ProductReg-ulation/SummaryofNDAAprovalsReceiptsl938tothepresent/ucm2006085.htm, accessed October 31, 2009.
11. Rx R&D myths: the case against the drug industry's R&D scare card. Washington (DC): Public Citizen; Jul 23, 2001. Available from: http://www.citizen.org/documents/rd-myths.pdf
12. The economics of TB drug development. New York: Global Alliance for TB Drug Development; Oct 2001. Available from: http://www.tballiance.org/newscenter/publications.php.
13. DiMasi J, Hansen R, Grabowski H. Assessing claims about the cost of new drug development: a critique of the Public Citizen and TB Alliance reports. Tufts Center for the Study of Drug Development. Boston: Nov 1, 2004. Available from: http://csdd.tufts. edu/_documents/www/Doc_231_45_735.pdf.
14. DiMasi J, Hansen R, Grabowski H. The price of innovation: new estimates of drug development costs. J Health Econ. 2003;22:151-85.
15. CNNMoney [Internet] Slud M. Pfizer shareholders OK deal. Apr 27, 2000 [cited Aug 3, 2008]. Available from: http://money.cnn.com/2000/04/27/companies/pfizer/.
16. Berenson A. End of drug trial is a big loss for Pfizer. New York Times. Dec 4, 2006. Available from: http://www.nytimes.com/2006/12/04/health/04pfizer.html.
17. Krauskopf L, Hirschler B. Pfizer shares plunge after cholesterol drug fails. Reuters News Service, New York/London: Dec 4, 2006.
18. Saul S. Release of generic Lipitor is delayed. New York Times. June 19, 2008.
19. Sorkin AR, Wilson D. Pfizer agrees to pay $68 billion for rival drug maker Wyeth. New York Times. Jan 25, 2009.
20. Tansey B. When clinical trial results just say 'no.' San Francisco Chronicle. Mar 11, 2007. Available from: http://www.sfgate.info/cgi-bin/article.cgi?f=/c/a/2007/03/ll/BUGC20HQJ21.DTL&type=chart.
21. Pear R. Spending rise for health care and prescription drugs slows. New York Times. Jan 5, 2009.
22. Fingertip Formulary Insights [Internet]. Glen Rock, NJ: Sept 2007 [cited Aug 3, 2008]; pp. 1-5. Available from: http://www.fingertipformulary.com/newsletter/2007-09/pdf/ Insights_Sept07.pdf.
23. Norman P. Generic competition 2007 to 2011 - the impact of patent expiries on sales of major drugs. Summary. Urch Publishing, London: Feb 2007 [cited Aug 3, 2008]. Available from: http://www.urchpublishing.com/publications/general/generic_competi-tion_2011_00.html.
24. Goodman M. Market Watch: Pharma industry performance metrics: 2007-2012E. Nat Rev Drug Discov. 2008;7:795.
25. Simons J. Pfizer's puzzle. The Fortune 500; Pfizer No. 31. Fortune. Apr 17, 2006. pp. 152-53.
26. Gamier J-P. Rebuilding the R&D engine in big pharma. Harvard Business Review. 2008;86:68-76.
27. IMS Health [Internet], Global pharmaceutical sales, 2000-2007. Mar 28, 2008 [cited Aug 3, 2008]; Norwalk (CT). Available from: http://www.imshealth.com/portal/site/im-Shealth/menuitem.a46c6d4df3db4b3d88f611019418c22a/?vgnextoid=67a89df4609e911 0VgnVCMl0000071812ca2RCRD&cpsextcurrchannel=l.
28. Loftus, P. US drug market faces down year. Wall Street Journal. Apr 23, 2009.
29. Adams C, Brantner V. Estimating the cost of new drug development: is it really S802 million? Health Aff. 2006;25:420-28.
30. Tollman P, Guy P, Altshuler J, Flanagan A, Steiner M. A revolution in R&D: how genomics and genetics are transforming the biopharmaceutical industry. Boston (MA): Boston Consulting Group. Nov 2001. 60 p. Available from: http://www.bcg.com/publications/ files/eng_genomicsgenetics_rep_l l_01.pdf [cited Aug 3, 2008].
31. Gilbert J, Henske P, Singh A. Rebuilding big pharma's business model. Windhover Information Inc. In Vivo, the Business and Medicine Report 2003;21:73-80.
32. DiMasi J, Grabowski H. The cost of pharmaceutical R&D: is biotech different? Managerial Decis Econ. 2007;28:469-79.
33. Tufts Center for the Study of Drug Development. Boston (MA): Citing Boston Consulting Group, 1993; Peck, Food and Drug Law J, 1997; Parexel, 2002.
34. Growing protocol design complexity stresses investigators, volunteers. Tufts CSDD Impact Report. Tufts Center for the Study of Drug Development. Boston (MA): 2008;10. Summary available from: http://csdd.tufts.edu/_documents/www/Doc_309_65_893.pdf.
35. Getz K. Protocol design trends and their effect on clinical trial performance. Regul Affairs J - Pharma. 2008;19:315-6.
36. Prescription drug trends. Kaiser Family Foundation. Menlo Park (CA). May 2007. (Fact Sheet No.: 3057-06.) Available from: http://www.kff.org/rxdrugs/upload/3057_06.pdf.
37. Prescription drug trends. Kaiser Family Foundation. Menlo Park (CA). Oct 2004. (Fact Sheet No.: 3057-03.) Available from: http://www.kff.org/rxdrugs/upload/Prescription-Drug-Trends-October-2004-UPDATE.pdf.
38. Bazell R. Strange medicine: why are the new cancer drugs so expensive? [Internet] Slate. Jun 23, 2004. Available from: http://www.slate.com/id/2102844/.
39. Mayer R. Two steps forward in the treatment of colorectal cancer. NEJM 2004;350:2406-2508.
40. Kolata G, Pollack A. The evidence gap: costly cancer drug offers hope, but also a dilemma. New York Times. July 6, 2008. Available from: http://www.nytimes. com/2008/07/06/health/06avastin.html?_r=l&oref=slogin.
41. Martinez B, Johnson A. Drug makers, hospitals raise prices. Wall Street Journal. Apr 15, 2009.
42. Department of Labor (US), Bureau of Labor Statistics. Consumer price index summary. Washington (DC). Apr 15, 2009. Available from: http://www.bls.gov/news.release/cpi. nr0.htm.
43. Views on prescription drugs and the pharmaceutical industry. Kaiser Health Poll Report. Kaiser Family Foundation, Menlo Park (CA). Jan/Feb 2005. Available from: http:// www.kff.org/healthpollreport/feb_2005/index.cfm.
44. Views on prescription drugs and the pharmaceutical industry. Kaiser Public Opinion Spotlight. Kaiser Family Foundation. Menlo Park (CA). Updated Apr 2008. Available from: http://www.kff.org/spotlight/rxdrugs/upload/Rx_Drugs.pdf.
45. Trusheim M, Berndt E, Douglas F. Impact of genetic diagnostics on drug development strategy. Nat Rev Drug Discov. 2007;6:287-93.
46. 2006 Report: Medicines in development, biotechnology. Pharmaceutical Research and Manufacturers of America. Washington (DC): July 2006. Available from: http://www. phrma.org/files/Biotech%202006.pdf.
47. Danzon P, McCulloch J, Nicholson S. Biotech-pharma alliances as a signal of asset and firm quality. J Bus. 2002;78:1433-64.
48. Cyranoski D. Pharmaceutical future: Made in China? Nature. 2008;455:1168.
49. The changing dynamics of pharma outsourcing in Asia: Are you readjusting your sights? PricewatershouseCoopers. 2008.
50. Dolan K. The drug research war. Forbes.com. May 4, 2008. Available from: http://www. forbes.com/2004/05/28/cz_kd_0528outsourcing.html.
51. White paper on Indian pharma industry quest for global leadership. Cygnus Business Consulting & Research. Hyderabad, India: Nov 14, 2006. [cited Aug 3, 2008] Available from: http://www.cygnusindia.com/white_papers.asp.
52. Fishman T. China Inc. New York: Scribner; 2005. p. 223.
53. Fishman 2005. p. 118. Quoted from: Lucier G. China as an emerging regional and technology power: implications for US economic and security interests. Testimony before the US-China Economic and Security Review Commission. Washington (DC): Feb 12-13, 2004. [Cited Aug 3, 2008] Available from: http://www.uscc.gov/ hearings/2004hearings/written_testimonies/04_02_12wrts/lucier.htm.
54. Drugs & pharmaceutical research. Scientific programmes. Technology development. Department of Science & Technology (India). New Delhi, [cited Aug 3, 2008] Available from: http://dst.gov.in/scientific-programme/td-drugs.htm.
55. Palnitkar U. The Indian pharmaceutical industry: promises and perils. Pharma Focus Asia. 2007;3(4). Pharmafocusasia.com [Internet].Ochre Media Pvt. Ltd. Hyderabad, India. Available from: http://www.pharmafocusasia.com/strategy/indian_pharma_promises.htm.
56. Jayaraman KS. Firms discovering reality of clinical research in India. Nat Rev Drug Discov. 2006;5:6.
57. Reymond E. China lives up to outsourcing hype. Outsourcing-pharma.com. Jan 16, 2007. [cited Aug 3, 2008]; [about 2 screens]. Available from: http://www.outsourcing-pharma.com/Clinical-Development/China-lives-up-to-outsourcing-hype.
58. Behera D, Shindikar A. Clinical trials: Growing opportunities for India. Pharmainfo.net. [Cited Aug 3, 2008] Available from: http://www.pharmainfo.net/reviews/clinical-trials-growing-opportunities-india.
59. Rahul Das D, Sharma A. Destination: India. Drug Discovery & Development. Aug 1, 2007. [cited Aug 3, 2008] Available from: http://www.dddmag.com/destination-india. aspx
60. Finkelstein S, Temin P. Reasonable Rx: Solving the drug price crisis. Upper Saddle River, NJ: FT Press; 2008.
61. DiMasi J. The value of improving the productivity of the drug development process: faster times and better decisions. Pharmacoeconomics. 2002;20 Suppl 3:1-10.
62. Keyhani S, Diener-West M, Powe N; Academy Health. Meeting (2005: Boston). Abstr AcademyHealth Meet. 2005; 22: abstract no. 3676. Available from: http://gateway.nlm. nih.gov/MeetingAbstracts/ma?f=103623139.html.
63. Prescription drug development time has decreased over 10 years, study finds. Medical News Today. Mar 10, 2006. Available from: http://www.medicalnewstoday.com/ articles/39161.php.
64. Outlook 2009. Tufts Center for the Study of Drug Development. Boston: Jan 2009. Available from: http://csdd.tufts.edu/InfoServices/OutlookReports.asp.
65. Oxman MN, Levin MJ, Johnson GR, A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. NEJM. 2005;352(22):2271-84; also, supplementary appendix. Available from: http://content.nejm.Org/cgi/data/352/22/2271/DCl/l.
66. Department of Veterans Affairs (US). Trial of varicella zoster vaccine for the prevention of herpes zoster and its complications. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Dec 29, 2000. [Cited Aug 12, 2008]. Available from: http://clinicaltrials.gov/ct2/show/NCT00007501.
67. Womack J, Jones D. Lean thinking. 1st Free Press Edition. New York: Simon & Schuster; 2003.
68. Taylor F. The principles of scientific management. New York: Harper & Brothers; 1911.
69. Drucker P. The practice of management. New York: Harper & Row; 1954.
70. Drucker P. Landmarks of tomorrow: a report on the new 'post-modern' world. New York: Harper & Brothers; 1959.
71. Drucker P. The essential Drucker: The best of sixty years of Peter Drucker's essential writings on management. New York: HarperCollins; 2001. pp. 120-21.
72. CenterWatch Staff. An industry in evolution. Third Edition. Boston: Thomson CenterWatch; 2001. p. 204.
73. Surowiecki J. The wisdom of crowds. New York: Random House; 2005.
74. Surowiecki J. The open secret of success. The New Yorker. May 12, 2008.
75. Ohno T. Toyota seisan hoshiki (The Toyota production system). Tokyo: Daiyamondo-sha; 1978.
76. Womack J, Jones D. The machine that changed the world. 1st Harper Perennial edition. New York: HarperCollins; 1990.
77. Fachet R. Open telematic platforms. In Proceedings of Automotive Electronics, 2006; The 2nd IEE Conference on Automotive Electronics. Mar 20-21, 2006;21-46.
78. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Washington (DC). Innovation or stagnation: Critical path opportunities report. Mar 2006. p. 12.
79. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health. Guidance for the use of Bayesian statistics in medical device clinical trials-Draft guidance for industry and FDA staff. Washington (DC). May 2006. Available from: http://www.fda.gov/cdrh/osb/guidance/1601.html.
80. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Washington (DC). Guidance for industry end-of-phase 2A meetings. Sept 2008. Available from: http://www.fda.gov/cder/Guidance/8297dft.htm.
81. European Medicines Agency, Committee for Medicinal Products for Human Use. Reflection paper on methodological issues in confirmatory clinical trials with flexible design and analysis plan. London. Mar 2006. Available from: www.emea.europa.eu/pdfs/hu-man/ewp/245902en.pdf.
82. Gallo P, Chuang-Stein C, Dragalin V, Gaydos B, Krams M, Pinheiro J. Adaptive designs in clinical drug development-an executive summary of the PhRMA Working Group. J Biopharm Stat. 2006;16:275-83.
83. Pong A, Luo Z, editors. Adaptive design in clinical research. J Biopharm Stat. 2005;15:535-752.
84. Wald A. Sequential analysis. New York: John Wiley & Son; 1948.
85. Armitage P. Sequential medical trials. Oxford: Blackwell Scientific Publications; 1961.
86. Pocock S. Group-sequential methods in the design and analysis of clinical trials. Bi-ometrika. 1977;64:191-200.
87. Wei LJ, Durham SD. The randomized play-the-winner rule in medical trials. J Am Stat Assoc. 1978;73:840-43.
88. Zelen M. A new design for randomized clinical trials. NEJM. 1979;300:1242-45.
89. Bauer P, Kohne K. Evaluation of experiments with adaptive interim analyses. Biometrics. 1994;50:1029-41.
90. Berry DA, Miiller P, Grieve AP, Smith M, Parke T, Blazek R, Mitchard N, Krams M. Adaptive Bayesian designs for dose-ranging drug trials. In: Gatsonis C, Kass RE, Carlin B, Carriquiry A, Gelman A, Verdinelli I, West M, editors. Case studies in Bayesian statistics V. New York: Springer-Verlag; 2001. pp. 99-181.
91. Jennison C, Turnbull BW. Efficient group-sequential designs when there are several effect sizes under consideration. Stat Med. 2006;25:917-32.
92. Ivanova A. Dose finding in oncology-nonparametric methods. Conventional or 3+3 design. In: Dose finding in drug development. Ting N, editor. New York: Springer Science + Business Media, Inc.; 2006. Chapter 4; p. 50.
93. Whitehead J, Patterson S, Webber D, Francis S. Easy-to-implement Bayesian methods for dose-escalation studies in healthy volunteers. Biostatistics. 2001;2:47-61.
94. Garret-Mayer E. Taking new agents to the clinic: phase I study design. Presented at: Neuroscience Institute, Medical University of South Carolina, c 2008 [cited Aug 12, 2008]. Available from: http://people.musc.edu/~elg26/talks/PhaseI.YukoClass2.pdf.
95. O'Quigley JO, Pepe M, Fisher L. Continual reassessment method: a practical design for phase I clinical trials in cancer. Biometrics. 1990;46:33-48.
96. Garrett-Mayer E. Understanding the continual reassessment method for dose finding studies: an overview for non-statisticians. Johns Hopkins University, Dept. of Biostatistics Working Papers. Working Paper 74. Berkeley Electronic Press [Internet], Mar 2005 [cited Aug 12, 2008]. Available from: http://www.bepress.com/jhubiostat/paper74.
97. Garrett-Mayer E. The continual reassessment method for dose-finding studies: a tutorial. Clin Trials. 2006;3:57-71.
98. Goodman S, Zahurak M, Piantadosi S. Some practical improvements in the continual reassessment method for phase I studies. Stat Med. 1995;14:1149-61.
99. Piantadosi S, Liu G. Improved designs for phase I studies using pharmacokinetic measurements. Stat Med. Aug 15, 1996;15:1605-18.
100. Quigley J. Another look at two phase I clinical trial designs. Stat Med. 1999;18:2683-90; discussion 2691-2.
101. Loeb D, Garret-Mayer E, Sgouros G, Wharam M, Scott T, Schwartz C. A dose finding study of 153SM-EDTMP in patients with high risk of osteosarcoma. Poster at 12th Annual Meeting of Connective Tissue Oncology Society, Venice, Italy. Nov 2-4, 2006.
102. Pollack, I, et al. Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: A Pediatric Brain Tumor Consortium report. Neuro Oncol 2007;9:145-60.
103. Tighiouart M, Rogatko A. Dose-escalation with overdose control. In: Chevret S, editor. Statistical methods for dose-finding experiments. New York: John Wiley & Sons; 2006. Chapter 8, pp. 173-88.
104. Krams M, Lees KR, Berry DA. The past is the future: innovative designs in acute stroke therapy trials. Stroke. 2005;36:1341-7.
105. Whelan H, Cook J, Amlie-Lefond C, Hovinga C, Chan A, Ichord R, deVeber G, Thall P. Practical model-based dose-finding in early phase clinical trials: optimizing tPA dose for treatment of ischemic stroke in children. University of Texas MD Anderson Cancer Center Year 2008 Working Paper 1. Collection of Biostatistics Research Archive, Berkeley Electronic Press [Internet]. Jan 2008 [cited Aug 12, 2008]. Available from: http:// www.bepress.com/cgi/viewcontent.cgi?article=1040&context=mdandersonbiostat.
106. Lawrence D. Phase II/III adaptive design with treatment selection: a case study. Presented at: Seminar on Adaptive Designs in Drug Development. Basel Biometric Section, European Federation of Statisticians in the Pharmaceutical Industry. Jun 15, 2007. Basel. Available from: http://www.efspi.org/PDF/activities/international/ adaptive_design_Basel_2007/7_Adaptive_Designs_Case_Study_3_DL.pdf.
107. Smith M, Jones I, Morris M, Grieve A, Tan K. Implementation of a Bayesian adaptive design in a proof-of-concept study. Pharm Stat. 2006;5:39-50.
108. Smith MK, Morris M, Jones I, Grieve A, Tan K. An adaptive design for dose-response using the normal dynamic linear model. Oral presentation at the thirteenth meeting of the Population Approach Group in Europe. June 17-18, 2004. Uppsala, Sweden. Available from: www.page-meeting.org/page/page2004/oral.pdf.
109. Chuang-Stein C, Anderson K, Gallo P, Collins S. Sample size reestimation: a review and recommendations. Druglnf J. 2006;40:475-84.
110. Lan KKG, DeMets DL. Discrete sequential boundaries for clinical trials. Biometrika. 1983;70:659-63.
111. Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989;10:1-10.
112. Thomas P. The adaptive design: issues in current research and implementation. Presentation at fourth national congress of the Societa Italiana di Statistica Medica ed Epidemiologia Clinica. Feb 2, 2007. Milan, Italy.
113. Anderson K. Adaptive designs: sample size reestimation: a review and recommendations. Presentation to PhRMA Adaptive Designs Workshop. Nov 13, 2006. Bethesda, MD. Available from: http://www.innovation.org/documents/File/Adaptive_Designs_Pre-sentations/13_Anderson_Sample_Size_reestimation_A_review_and_recommendation. pdf.
114. Mehta CR. Design and interim monitoring of flexible clinical trials. Presentation to Eleventh Annual Biopharmaceutical Applied Statistics Symposium. Nov 3-4, 2004. Savannah, GA. Available from: http://www.cytel.com/Papers/bass_ll_04.pdf.
115. Taylor AL, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. NEJM. 2004;351:2049-57.
116. MacDonald TM, et al. Effect on blood pressure of lumiracoxib versus ibuprofen in patients with osteoarthritis and controlled hypertension: a randomized trial. J Hypertension 2008;26:1695-1702.
117. O'Connor CM, et al. Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial. JAMA. 2003;290:1459-66.
118. Agnieszka M, et al. Phase I/II study to investigate the use of gemcitabine in combination with raltitrexed in locally advanced or metastatic pancreatic adenocarcinoma. Internet J Oncol [Internet]. 2006 [cited Aug 12, 2008];3(2). Available from: http://www.ispub.com/ ostia/index.php?xmlFilePath=journals/ijo/vol3n2/gemcitabine.xml.
119. Bretz F, Schmidli H, Konig F, Racine A, Maurer W. Confirmatory seamless phase 11/ III clinical trials with hypotheses selection at interim: general concepts. Biom J. 2006;48:623-34.
120. Wang L, Cui L. Seamless Phase II/III combination study through response adaptive randomization. J Biopharm Stat. 2007;17:1177-87.
121. Chow Shein-Chung, Chang M. Adaptive design methods in clinical trials. Boca Raton, FL: Chapman & Hall/CRC; 2007.
122. Krams M, et al. Acute stroke therapy by inhibition of neutrophils (ASTIN): an adaptive dose-response study of UK-279,276 in acute ischemic stroke. Stroke. 2003;34:2543-8. Available from: http://stroke.ahajournals.org/cgi/content/full/34/ll/2543.
123. Berry DA, et al. Adaptive Bayesian designs for dose-ranging drug trials. In: Gatsonis C, et al., editors. Case studies in Bayesian statistics V. New York: Springer-Verlag; 2001. pp. 99-181.
124. Miiller P, et al. A Bayesian decision-theoretic dose-finding trial. Decision Anal. 2006;3:197-207.
125. A randomised, double-blind, placebo controlled, multicentre prospective dose-finding phase II/III study with atacicept given subcutaneously to subjects having recently experienced a flare of systemic lupus erythematosus (SLE). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Feb 15, 2008. [Cited Aug 12, 2008]. Available from: http://clinicaltrials.gov/ct2/show/NCT00624338.
126. Hu F, Rosenberger W. The theory of response-adaptive randomization in clinical trials. Hoboken, NJ: John Wiley & Sons, 2006.
127. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31:103-15.
128. Wexler L, et al., for the Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial Investigators. Non-Q-wave myocardial infarction following thrombolytic therapy: a comparison of outcomes in patients randomized to invasive or conservative post-infarct assessment strategies in the Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial. J Am Coll Cardiol. 2001;37:19-25.
129. Wei LJ, Lachin J. Properties of the urn randomization in clinical trials. Control Clin Trials. 1988;9:345-64. [Erratum, Control Clin Trials Mar 1989;10(l):following 126.]
130. Giles F, et al. Adaptive randomized study of idarubicin and cytarabine versus trox-acitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia. J Clin Oncol. 2003;21:1722-27.
131. Hommel G, Kropf S. Clinical trials with an adaptive choice of hypotheses. Drug Inf J. 2001;35:1423-9.
132. Zuber E, et al. Adaptive seamless designs for subpopulation based on time to event. Presented at the 5th International Conference on Multiple Comparison Procedures, Vienna, 2007. Available from: http://www.mcp-conference.org/2007/presenta-tions/Zuber_Emmanuel.pdf.
133. Streamlining clinical trials. Durham, NC: Cutting Edge Information; 2008.
134. CenterWatch Surveys of U.S. (2009, n=950), Asian (2006, n=156), Latin American (2005, n=317), European and Canadian (2006, n=356) investigative sites.
135. Galbreath AD, Smith B, Wood P, Forkner E, Peters JI. Cumulative recruitment experience in two large single-center, randomized controlled clinical trials. Contemp Clin Trials. 2008;29:335-42.
136. Sweet S, Legro RS, Coney P. A comparison of methods and results in recruiting white and black women into reproductive studies: the MMC-PSIIU cooperating center on reproduction experience. Contemp Clin Trials. 2008;29:478-81.
137. Monaghan H, et al. A randomised trial of the effects of an additional communication strategy on recruitment into a large, multi-centre trial. Contemp Clin Trials. 2007;28(1):1-5.
138. Malakoff D. Spiraling costs threaten gridlock. Science. 2008;322:210-3.
139. Borfitz D. Decisions, decisions: Michael Rosenberg on adaptive research. Bio-ITWorld's eCliniqua newsletter. Sept 6, 2007. Available from: http://www.bio-itworld.com/ newsitems/2007/sept/09-06-07-rosenberg.
140. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Washington. Guidance for Industry. Part 11, Electronic Records; Electronic Signatures - Scope and Application. Aug 2003. Available from: http://www.fda.gov/cder/guidance/5667fnl.htm.
141. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Washington. Guidance for industry end-of-phase 2A meetings. Sept 2008. Available from: http://www.fda.gov/cder/ Guidance/8297dft.htm.
142. Stanksi DR. Model-based drug development: a Critical Path opportunity. Feb 25, 2004. Available from: http://www.fda.gov/oc/initiatives/criticalpath/stanski/stanski.html.
143. O'Neill RT. FDA's Critical Path Initiative: a perspective on contributions of biostatistics. Biom J. 2006;48(4):559-64.
144. Salsburg D. The lady tasting tea. First Owl Books Edition. New York: Henry Holt and Company; 2002. pp. 111-2.
145. Neyman J, Pearson E. On the problem of the most efficient tests of statistical hypotheses. Philos Trans R Soc Ser A. 1933;231:289-337.
146. Dickens C. David Copperfield. 2000 Modern Library Paperback Edition. New York: Random House; 2000. p. 166.
147. Bayes T. An essay towards solving a problem in the doctrine of chances. (A Letter from the Late Reverend Mr. Thomas Bayes, F. R. S. to John Canton, M. A. and F. R. S.) Philos Trans R Soc. 1763;53:370-418.
148. Savage LJ. The foundations of statistics. Second revised edition. New York: Dover Publications, 1972.
149. Good IJ. A. M. Turing's statistical work in World War II. Biometrika. 1979;66:393-6.
150. Mosteller F, Wallace D. Applied Bayesian and classical inference: the case of the Federalist Papers. New York: Springer Verlag; 1984.
151. Fienberg S. When did Bayesian inference become "Bayesian"? Bayesian Anal. 2006;1:1-40.
152. Zdziarski J. Ending spam: Bayesian content filtering and the art of statistical language classification. San Francisco: No Starch Press; 2005.
153. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health. Guidance for the use of Bayesian statistics in medical device clinical trials-Draft guidance for industry and FDA staff. Washington [DC). May 2006. Available from: http://www.fda.gov/cdrh/osb/guidance/1601.html.
154. U.S. Department of Health and Human Services, Food and Drug Administration, Johns Hopkins University. Can Bayesian approaches to studying new treatments improve regulatory decision making. Bethesda (MD). May 20-21, 2004. Presentations available from: http://www.cfsan.fda.gov/~frf/bayesdl.html.
155. European Medicines Agency, Committee for Medicinal Products for Human Use. Guideline on clinical trials in small populations. London. July 2006. Available from: http:// www.emea.europa.eu/pdfs/human/ewp/8356105en.pdf.
156. Bayarri MJ, Berger JO. The interplay of Bayesian and frequentist analysis. Statist Sci. 2004;19:58-80.
157. Little RJA. Calibrated Bayes: A Bayes/frequentist roadmap. Am Stat. 2006;60:213-23.
158. Austin PC, Brunner LJ, Hux JE. Bayeswatch: an overview of Bayesian statistics. J Eval ClinPract. 2002;8:277-86.
159. Berry DA. Statistics: A Bayesian perspective. Pacific Grove, CA: Duxbury Press; 1995.
160. Spiegelhalter DJ, Abrams KR, Myles JP. Bayesian approaches to clinical trials and health-care evaluation. Chichester: John Wiley & Sons; 2004.
161. Berry DA. Bayesian statistics and the efficiency and ethics of clinical trials. Stat Sci. 2004;19:175-87.
162. Malakoff D. Bayes offers a 'new' way to make sense of numbers. Science. 1999;286:1460-4.
163. Berry D, Stangl D. Eds. Bayesian biostatistics. New York: Marcel Dekker; 1996.
164. Spiegelhalter DJ, Freedman SL, Parmar BKM. Bayesian approaches to randomized trials. J R Stat Soc (A). 1994;157:357-416.
165. Chow S, Chang M. Adaptive design methods in clinical trials. Boca Raton (FL): Chapman & Hall/CRC; 2007.
166. Schmier JK, Kane DW, Halpern MT. Practical applications of usability theory to electronic data collection for clinical trials. Contemp Clin Trials. 2005;26:376-85.
167. Boldt R, Raasch J. Analysis of current technologies and devices for mobile data capture: A qualitative usability-study for comparison of data capture via keyboard, tablet PC, personal digital assistant, and digital pen and paper. Usability lab of the department of computer science at the Hochschule fur Angewandte Wissenschaften. Oct 2, 2008.
168. Cole E, Pisano ED, Clary GJ, Zeng D, Koomen M, Kuzmiak CM, Seo BK, Lee Y, Pavic D. A comparative study of mobile electronic data entry systems for clinical trials data collection. Int J Med Inform. 2006;75:722-9.
169. Marks RG. Validating electronic source data in clinical trials. Controlled Clin Trials. 2004;25:437-46.
170. Connor C. U.S. electronic data capture 2006-2011: Spending forecast and analysis. Health Industry Insights. Apr 30, 2007.
171. Senior M. Making clinical trials more efficient. In Vivo: The Business and Medicine Report. 2005;23:1-6.
172. Parke T. Adaptive clinical trials in the real world. Presentation to the Massachusetts Biotechnology Council. Apr 23, 2008. Slide 29, EDC lite. Available from: www.massbio.org/writable/committees/presentations/mbc act_in_the_real_world.ppt; cited Dec, 11 2008.
173. Abu-Hasaballah K, James A, Aseltine RH Jr. Lessons and pitfalls of interactive voice response in medical research. Contemp Clin Trials. 2007;28:593-602.
174. Froderberg U. Pen power. Int Clin Trials. 2008;3:32-8.
175. Borfitz D. Actelion opts for digital pen and paper over EDC. Bio IT World eCliniqua. Oct 1, 2007. Available from: http://www.bio-itworld.com/newsitems/2007/oct/01-digital-pen-and-paper/; cited Dec 11, 2008.
176. Estellat C, Tubach F, Costa Y, Hoffmann I, Mantz J, Ravaud P. Data capture by digital pen in clinical trials: A qualitative and quantitative study. Contemp Clin Trials. 2008;29:314-23.
177. Missinou MA, et al. Short report: Piloting paperless data entry for clinical research in Africa. Am J Trop Med Hyg. 2005;72:301-3.
178. Lane SJ, Heddle NM, Arnold E, Walker I. A review of randomized controlled trials comparing the effectiveness of hand held computers with paper methods for data collection. BMC Medical Informatics and Decision Making. 2006;6:23.
179. Shelby-James T, Abernethy A, McAlindon A, Currow DC. Handheld computers for data entry: high tech has its problems too. Trials. 2007;8:5.
180. Matthew AG, et al. Personal digital assistant data capture: The future of quality of life measurement in prostate cancer treatment. J Oncol Pract. 2007;3:115-20.
181. Pollack P. Aerospace gets Japan's message; without military largess, industry takes the lean path. New York Times. Mar 9, 1999.
182. Martinez B, Johnson A. Drug makers, hospitals raise prices. Wall Street J. Apr 15, 2009.
183. Loftus, P. US drug market faces down year. Wall Street J. Apr 23, 2009.
184. Goldstein J. Sanofi-Aventis CEO looks to cut research spending. Wall Street J Health Blog. Mar 6, 2009. Available from: http://blogs.wsj.com/health/2009/03/06/sanofi-aventis-ceo-looks-to-cut-research-spending/.
185. Pisano GP. Science Business. Boston: Harvard Business School Press; 2006.
186. Womack J, Jones D. Lean thinking. 1st Free Press Edition. New York: Simon & Schuster; 2003. p. 69.
187. Kaitin KI, editor. CRO contribution to drug development is substantial and growing globally. Tufts Center for the Study of Drug Development Impact Report 2006 Jan/ Feb;8(1).
188. Anderson B. How we fail to use CROs effectively. Applied Clin Trials. 2008;8:42-8.
189. Christel M. Long-term investment. R&D Directions. 2008;14:20-7.
190. Weiner LM. Focus on research: cancer immunotherapy: the endgame begins. N Engl J Med. 2008;358:2664-5.
191. Womack J, Jones D, Roos D. The machine that changed the world. First HarperPeren-nial Edition. New York: HarperCollins; 1991. pp. 109-10.
192. Winslow R. After Pfizer blockbuster's failure, what's next for the heart? Wall Street J. Dec 5, 2006.
193. DiMasi J. The value of improving the productivity of the drug development process. Pharmacoeconomics. 2002;20:Suppl 3:1-10.
194. DiMasi J, Hansen R, Grabowski H. The price of innovation: new estimates of drug development costs. J Health Econ. 2003;22:151-85.
195. Scanlon J, Berwick D. Curing the healthcare system. How Dr. Donald Berwick and the Institute for Healthcare Improvement apply business best practices-from lean manufacturing to innovation. Business Week. Nov 17, 2008. Available from: http://www. businessweek.com/innovate/content/nov2008/id20081117_820750_page_2.htm.
196. Improvement tip: find muda and root it out. Institute for Healthcare Improvement. Cambridge MA. Oct 2005;53. Accessed Dec 27, 2008. Available from: http://www.ihi. org/IHI/Topics/Improvement/ImprovementMethods/ImprovementStories/Improvement-TipFindMudaandRootitOut.htm.