Response-adaptive clinical trials: case studies in the medical literature

Pharmaceutical Statistics

Volumn 16, Issue 1, 2017, Pages 64-86

  Grieve, Andrew P ^a  

^a Marlow   (United Kingdom)

Author keywords

3+3; Bayesian; biased coin; clinical trials; continual reassessment method; drug development; play the winner; randomised play the winner; response ADs; up and down

Indexed keywords

ADVANCED CANCER; ANALGESIA; ARTICLE; BAYES THEOREM; CLINICAL TRIAL (TOPIC); EXTRACORPOREAL OXYGENATION; FOOD AND DRUG ADMINISTRATION; HEART CATHETERIZATION; HUMAN; LABOR PAIN; LOGISTIC REGRESSION ANALYSIS; MATHEMATICAL MODEL; MAXIMUM TOLERATED DOSE; MEDICAL LITERATURE; MIGRAINE; OUTCOME ASSESSMENT; SOLID TUMOR; TUBERCULOSIS; VENOUS THROMBOEMBOLISM; DRUG DESIGN; DRUG INDUSTRY; METHODOLOGY; PROCEDURES; STATISTICAL ANALYSIS;

CLINICAL TRIALS AS TOPIC; DATA INTERPRETATION, STATISTICAL; DRUG DESIGN; DRUG INDUSTRY; HUMANS; RESEARCH DESIGN;

EID: 84991273589     PISSN: 15391604     EISSN: 15391612     Source Type: Journal    
DOI: 10.1002/pst.1778     Document Type: Article

References (101)

1. Grieve AP. Adaptive Designs: A Fad or the Future of Clinical Research. Presented at the PhRMA Workshop on Adaptive Designs: Opportunities, Challenges and Scope in Drug. Nov 13-14, Washington DC, 2006. Available at: www.innovation.org /index.cfm/NewsCenter/Briefings/Adaptive_Designs_Workshop.
2. Burman-CF, Chuang-Stein C. ADs: A fad or the future of clinical research. Applied Clinical Trials 2009. Available at: http://www.app-liedclinicaltrialsonline.com/adaptive-designs-fad-or-future-clinical-researc.
3. Bretz F, Brannath W. Ten things you need to know about ADs. CRfocus 2008; 19:28–29.
4. Kairalla JA, Coffey CS, Thomann MA, Muller KE. Adaptive trial designs: a review of barriers and opportunities. Trials 2012; 13:145.
5. U.S. Food and drug administration: Draft guidance for industry: AD clinical trials for drugs and biologics. Available at: http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatory{Information}/Guidances/UCM201790.pdf.
6. Fenn J, Raskino M. Mastering the Hype Cycle: How to Choose the Right Innovation at the Right Time. Harvard Business School Press: Cambridge, MA, 2008.
7. Bauer P. Multistage testing with adaptive designs. Biometrie und lnformatik in Medizin und Biologie 1989; 20:130–148.
8. Bauer P, Köhne K. Evaluation of experiments with adaptive interim analyses. Biometrics 1994; 50:1029–1041.
9. ′Quigley J, Pepe M, Fisher L. Continual reassessment method: a practical design for Phase I clinical trials in cancer. Biometric 1990; 46:33–48.
10. Bauer P, Einfalt J. Application of adaptive designs–a review. Biometrical Journal 2006; 48:1–14.
11. Rogatko A, Schoeneck D, Jonas W, Tighiouart M, Khuri FR, Porter A. Translation of innovative designs into phase I trials. Journal of Clinical Oncology 2007; 25:4982–4986.
12. Berry DA, Müller P, Grieve AP, Smith MK, Parke T, Blazek R, Mitchard N, Krams M. Adaptive Bayesian designs for dose-ranging trials. In Case Studies in Bayesian Statistics V, Carlin B, Carriquiry A, Gatsonis C, Gelman A, Kass RE, Verdinelli I, West M (eds). Springer Verlag, 2002; 99–181.
13. Malakoff D. Bayes offers a “new” way to make sense of numbers. Science 1999; 286:1460–1464.
14. Farr-Jones S. Better statistics. BioCentury, The Bernstein Report on BioBusiness 2001; 9. Available at: http://www.biocentury.com/biotech-pharma-news/coverstory/2001-03-12/cover-story-clinical-trials-better-statistics-a1.
15. The Economist. In praise of Bayes. The Economist 2000. Available at: http://www.economist.com/node/382968.
16. Leonhardt D. Adding art to the rigor of statistical science. New York Times 2001. Available at: http://www.nytimes.com/2001/04/28/arts/adding-art-to-the-rigor-of-statistical-science.html?pagewanted=all.
17. Day S. Changing times in pharmaceutical statistics: 2000–2020. Pharmaceutical Statistics 2002; 1:75–82.
18. Thompson W. On the likelihood that an unknown probability exceeds another in view of the evidence of two samples. Biometrika 1933; 25:285–294.
19. Grieve AP. Idle thoughts of a “well-calibrated” Bayesian in clinical drug development. Pharmaceutical Statistics 2016; 15:96–108.
20. Maki RG, Wathen JK, Patel SR, Priebat DA, Okuno SH, Samuels B, Fanucchi M, Harmon DC, X Schuetze SM, Reinke D, Thall PF, Benjamin RS, Baker LH. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: Results of sarcoma alliance for research through collaboration study 002. Journal of Clinical Oncology 2007; 25:2755–2763.
21. Giles FJ, Kantarjian HM, Cortes JE, Garcia-Manero G, Verstovsek S, Faderl S, Thomas DA, Ferrajoli A, O'Brien S, Wathen JK, Xiao LC, Berry DA, Estey EH. Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia. Journal of Clinical Oncology 2003; 21:1722–1727.
22. Grieve AP. Biologische Interpretationen mathematischer Modelle der Quantitativen Risikoabschaetzung. In Biometrie in der chemischpharmazeutischen Industrie III, Vollmar J (ed.).Gustav Fischer Verlag: Stuttgart; 1986; 5–32.
23. Bliss CI. The calculation of the dosage-mortality curve. Annals of Applied Biology 1935; 22:134–167.
24. Dixon WJ, Mood AM. A method for obtaining and analysing sensitivity data. Journal of the American Statistical Association 1948; 43:109–126.
25. Békésy GV. A new audiometer. Acta Oto-Laryngologica 1947; 35:411–422.
26. Roon KI, Olesen J, Diener HC, Ellis P, Hettiarachchi J, Poole PH, Christianssen I, Kleinermans D, Kok JG, Ferrari MD. No acute antimigraine efficacy of CP-122,288, a highly potent inhibitor of neurogenic inflammation: results of two randomized, double-blind, placebo-controlled clinical trials. Annals of Neurology 2000; 47:238–241.
27. Whitehead J, Williamson D. Bayesian decision procedures based on logistic regression models for dose-finding studies. Journal of Biopharmaceutical Statistics 1998; 8:445–467.
28. Camorcia M, Capogna G, Columb MO. Minimum local analgesic doses of ropivacaine, levobupivacaine, and bupivacaine for intrathecal labor analgesia. Anesthesiology 2005; 102:646–650.
29. Ferrari MD, Färkkilä M, Reuter U, Pilgrim A, Davis C, Krauss M, Diener H-C. Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan–a randomised proof-of-concept trial. Cephalalgia 2010; 30:1170–1178.
30. Doufas AG, Komatsu R, Orhan-Sungur M, Sengupta P, Wadhwa A, Mascha E, Shafer SL, Sessler DI. Neuromuscular block differentially affects immobility and cortical activation at near–minimum alveolar concentration anesthesia. Anesthesia & Analgesia 2009; 109:1097–1104.
31. Grieve A, Senn S. Estimating treatment effects in clinical crossover trials. Journal of Biopharmaceutical Statistics 1998; 8:191–233.
32. Cook DR, Stille RL, Weakly JN, Chakravorti S, Brandom BW, Welch RM. In vitro metabolism of mivacurium chloride (BW B1090U) and succinylcholine. Anesthesia & Analgesia 1989; 68:452–456.
33. Robbins H, Monro S. A stochastic approximation method. The Annals of Mathematical Statistics 1951; 22:400–407.
34. Derman C. Non-parametric up-and-down experimentation. The Annals of Mathematical Statistics 1957; 28:795–798.
35. Durham SD, Flournoy N, Rosenberger WF. A random walk rule for phase i clinical trials. Biometrics 1997; 53:745–760.
36. Tran DQH, Dugani S, Dyachenko A, Correa JA, Finlayson RJ. Minimum effective volume of lidocaine for ultrasound-guided infraclavicular block. Regional Anesthesia and Pain Medicine 2011; 36:190–194.
37. Pace NL, Stylianou MP. Advances in and limitations of up-and-down methodology: a precis of clinical use, study design, and dose estimation in anesthesia research. Anesthesiology 2007; 107:144–152.
38. Malkin, Robert A. et al. Estimating the 95% effective defibrillation dose. Biomedical, Engineering, IEEE Transactions on Biomedical Engineering 1993; 40:256–265.
39. Compos AT, Malkin RA, Ideker RE. An up-down Bayesian, defibrillation efficacy estimator. Pacing and Clinical Electrophysiology 1997; 20:1292–1300.
40. Malkin RA, Herre JM, McGowen L, Tenzer MM, Onufer JR, Stamato NJ, Wood M, Bernstein RC. A four-shock Bayesian up-down estimator of the 80% effective defibrillation dose. Journal of Cardiovascular Electrophysiology 1999; 10:973–980.
41. Wald A. Sequential Analysis. Wiley: New York, 1947.
42. Armitage P. Sequential tests in prophylactic and therapeutic trials. Quarterly Journal of Medicine 1954; 23:255–274.
43. Bross I. Sequential medical plans. Biometrics 1952; 8:188–205.
44. Zelen M. Play the winner rule and the controlled clinical trial. Journal of the American Statistical Association 1969; 64:131–146.
45. Robbins H. Some aspects of the sequential design of experiments. Bulletin of the American Mathematics Society 1952; 68:527–535.
46. Wei LJ, Durham S. The randomized play-the-winner rule in medical trials. Journal of the American Statistical Association 1978; 73:838–43.
47. Palmer CR. Ethics, data-dependent designs, and the strategy of clinical trials: time to start learning-as-we-go. Statistical Methods in Medical Research 2002; 11:381–402.
48. Palmer CR, Rosenberger WF. Ethics and practice: alternative designs for phase III randomized clinical trials. Controlled Clinical Trials 1999; 20:172–186.
49. World Medical Association. 52nd Assembly, Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. World Medical Association, Inc.: Edinburgh, 2000.
50. Reiertsen O, Larsen S, Solhaug JH. Development of play-the-winner design: weighting and accumulation of information. Scandinavian Journal of Clinical Laboratory Investigation 1998; 58:241–250.
51. Rout CC, Rocke DA, Levin J, Gouws E, Reddy D. A reevaluation of the role of crystalloid preload in the prevention of hypotension associated with spinal anesthesia for elective cesarean section. Anesthesiology 1993; 79:262–269.
52. Bartlett RH, Roloff DW, Cornell RG, Andrews AF, Dillon PW, Zwischenberger JB. Extracorporeal circulation in neonatal respiratory failure: a prospective randomised trial. Paediatrics 1985; 76:479–487.
53. Grieve AP. How to test hypotheses if you must. Pharmaceutical Statistics 2015; 14:139–150.
54. Dragalin V. Adaptive designs: terminology and classification. Drug Information Journal 2006; 40:425–435.
55. Dragalin V. Sequential methods in multi-arm clinical trials. Sequential Analysis 2010; 29:444–462.
56. Yao Q, Wei LJ. Play the winner for phase II/III clinical trials. Statistics in Medicine 1997; 15:2413–2423.
57. Connor EM, Sperling RS, Gelber R, Kiseley P, Scorr G, O'Sullivan MJ, Vandyke R, Bey M, Shearer W, Jaconson RL, Jimenez E, O'Neill E, Bazin B, Delfraissy J-F, Culnane M, Coomas R, Elkins M, Moye J, Balsley J. Reduction of the maternal-infant transmission of human immunodeficiency virus type I with zidovudine treatment. New England Journal of Medicine 1994; 331:1173–1180.
58. Tamura RN, Faries DE, Andersen JS, Heiligenstein JH. A case study of an adaptive clinical trial in the treatment of out-patients with depressive disorder. Journal of the American Statistical Association 1994; 89:768–776.
59. Altham PME. Exact Bayesian analysis Of a 2 × 2 contingency table, and Fisher's “Exact” significance test. Journal of the Royal Statistical Society Series B 1969; 31:261–269.
60. Heiligenstein JH, Faries DE, Rush AJ, Andersen JS, Pande AC, Roffwarg HP, Dunner D, Gillin JC, James SP, Lahmeyer H, Zajecka J, Tollefson GD, Gardner DM. Latency to rapid eye movement sleep as a predictor treatment response to fluoxetine and placebo in nonpsychotic depressed outpatients. Psychiatry Research 1994; 52:321–339.
61. Grieve AP. The number needed to treat: a useful clinical measure or a case of the emperor's new clothes?. Pharmaceutical Statistics 2003; 2:87–102.
62. Grieve AP. Discussion of the “white paper of the phrma working group on adaptive dose-ranging designs. Journal of Biopharmaceutical Statistics 2007; 17:997–1004.
63. Carter SK. Study design principles for the clinical evaluation of new drugs as developed by the chemotherapy programme of the National Cancer Institute. In Design of Clinical Trials in Cancer Therapy, (Editions Scientifique Européennes), Staquet M (ed.), Proceedings of a clinical pharmacology course held at the Institut Jules Bordet in Brussels from 2 to 5 May, 1972; 1973; pp. 242–289.
64. Storer BE. Design and analysis of phase I clinical trials. Biometrics 1989; 45:925–937.
65. Lin Y, Shih WJ. Statistical properties of the traditional algorithm-based designs for phase I cancer clinical trials. Biostatistics 2001; 2:203–215.
66. Kim TY, Kim DW, Chung JY, Shin SG, Kim SC, Heo DS, Kim NK, Bang YJ. Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clinical Cancer Research 2004; 10:3708–3716.
67. Thall PF. Dysfunctional paradigms in clinical trials: some Bayesian alternatives. Webinar Section on Bayesian Statistical Science, American Statistical Association 2012. Available at:=https://www.amstat.org/sections/sbss/webinarfiles/ThallPresenta-\breaktionSlides6-7-12color.pdf.
68. Lévy V, Zohar S, Bardin C, Vekhoff A, Chaoui, Rio B, Legrand O, Sentenac S, Rousselot P, Raffoux E, Chast F, Chevret S, Marie JP. A phase I dose-finding and pharmacokinetic study of subcutaneous semisynthetic homoharringtonine (ssHHT) in patients with advanced acute myeloid leukaemia. British Journal of Cancer 2006; 95:253–259.
69. Goodman SN, Zahurak ML, Piantadosi S. Some practical improvements in the continual reassessment method for phase I studies. Statistics in Medicine 1995; 14:1149–1161.
70. Korn EL, Midthune D, Chen TT, Rubinstein LV, Christian MC, Simon R. A comparison of two Phase I trials. Statistics in Medicine 1994; 13:1799–1806.
71. Murphy JR, Hall DL. A logistic dose-ranging method for phase I clinical investigations trials. Journal of Biopharmaceutical Statistics 1997; 7:635–647.
72. Babb J, Rogatko A, Zacks S. Cancer phase I clinical trials: efficient dose escalation with overdose control. Statistics in Medicine 1998; 17:1103–1120.
73. Neuenschwander B, Branson M, Gsponer T. Critical aspects of the Bayesian approach to phase I cancer trials. Statistics in Medicine 2008; 27:2420–2439.
74. ′Quigley J. Adaptive dose-finding studies: a review of model-guided phase I clinical trials. Journal of Clinical Oncology 2014; 32:2505–2511.
75. Neuenschwander B, Matano A, Tang Z, Roychoudhury S, Wandel S, Bailey S. A Bayesian industry approach to phase i combination trials in oncology, In Statistical Methods inDrug Combination Studies, Zhao W, Yang H (eds), Vol. 2015. CRC press; 2014, pp. 95–135.
76. Sessa C, Shapiro GI, Bhalla KN, Britten C, Jacks KS, Mita M, Papadimitrakopoulou V, Pluard T, Samuel TA, Akimov M, Quadt C, Fernandez-Ibarra C, Lu H, Bailey S, Chica S, Banerji U. First-in-human phase I dose-escalation study of the HSP90 inhibitor AUY922 in patients with advanced solid tumors. Clinical Cancer Research 2013; 19:3671–3680.
77. Bornkamp B. Functional uniform priors for nonlinear modeling. Biometrics 2012; 68:893–901.
78. Bornkamp B. Practical considerations for using functional uniform prior distributions for dose-response estimation in clinical trials. Biometrical Journal 2014; 56:947–962.
79. Zohar S, Resche-Rigon M, Chevret S. Using the continual reassessment method to estimate the minimum effective dose in phase II dose-finding studies: A case study. Clinical Trials 2013; 10:414–421.
80. Fabre E, Chevret S, Piechaud J-F, Rey E, Vauzelle-Kervroedan F, D'Athis P, Olive G, Pons G. An approach for dose finding in infants: sedation by midazolam studied using the continual reassessment method. British Journal of Clinical Pharmacology 1998; 46:395–401.
81. Zohar S, Chevret S. The continual reassessment method: comparison of Bayesian stopping rules for dose-ranging studies. Statistics in Medicine 2001; 20:2827–2843.
82. Krams M, Lees KR, Hacke W, Grieve AP, Orgogozo JM, Ford GA. Acute stroke therapy by inhibition of neutrophils (ASTIN): an adaptive dose-response study Of UK-279,276 in acute ischaemic stroke. Stroke 2003; 34:2543–2548.
83. Grieve AP, Krams M. ASTIN: a Bayesian adaptive dose–response trial in acute stroke. Clinical Trials 2005; 2:340–351.
84. Berry SM, Spinelli W, Littman GS, Liang JZ, Fardipour P, Berry DA, Lewis RJ, Krams M. A Bayesian dose-finding trial with adaptive dose expansion to flexibly assess efficacy and safety of an investigational drug. Clinical Trials 2010; 7:121–135.
85. Lewis RJ, Viele K, Broglio K, Berry SM, Jones AE. An adaptive, phase II, dose-finding clinical trial design to evaluate L-carnitine in the treatment of septic shock based on efficacy and predictive probability of subsequent phase III success. Critical Care Medicine 2013; 41:1674–1678.
86. Thall PF, Wathen JK. Practical Bayesian adaptive randomisation in clinical trials. European Journal of Cancer 2007; 43:859–866.
87. Cook JD, Nadarajah S. Stochastic inequality probabilities for adaptively randomized clinical trials. Biometrical Journal 2006; 48:356–265.
88. Korn EL, Freidlin B. Outcome-adaptive randomization: is it useful?. Journal of Clinical Oncology 2011; 29:771–776.
89. Berry DA. Adaptive clinical trials: the promise and the caution. Journal of Clinical Oncology 2011; 29:606–609.
90. Thall PF, Fox PS, Wathen JK. Some caveats for outcome adaptive randomization in clinical trials. In Modern Adaptive Randomized Clinical Trials: Statistical, Operational and Regulatory Aspects, Sverdlov O (ed.). CRC Press, 2015, 287–305.
91. Fleischmann R, Nayiager S, Louw I, Rojkovich B, Fu C, Udata C, Fardipour P, Marshall B, Hinz M, Sharma A, Shields K. A Multiple Ascending Dose/Proof of Concept study of ATN-103 (ozoralizumab) in Rheumatoid Arthritis Subjects on a background of Methotrexate [Abstract]. In Arthritis & Rheumatism, Vol. 63; 2011. Suppl 10:Abstract 2630.
92. Braun TM. The bivariate continual reassessment method: extending the CRM to phase I trials of two competing outcomes. Controlled Clinical Trials 2002; 23:240–56.
93. Thall PF, Cook JD. Dose-finding based on efficacy–toxicity trade-offs. Biometrics 2004; 60:684–93.
94. De Lima M, Champlin RE, Thall PF, Wang X, Martin TG, Cook JD, McCormick G, Qazilbash M, Kebriaei P, Couriel D, Shpall EJ. Phase I/II study of gemtuzumab ozogamicin added to fludarabine, melphalan and allogeneic hematopoietic stem cell transplantation for high-risk CD33 positive myeloid leukemias and myelodysplastic syndrome. Leukemia 2008; 22:258–64.
95. Bailey S, Neuenschwander B, Laird G, Branson M. A Bayesian case study in oncology phase I combination dose-finding using logistic regression with covariates. Journal of Biopharmaceutical Statistics 2009; 19:469–84.
96. Demetri GD, Casali PG, Blay JY, von Mehren M, Morgan JA, Bertulli R, Ray-Coquard I, Cassier P, Davey M, Borghaei H, Pink D. A phase I study of single-agent nilotinib or in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors. Clinical Cancer Research 2009; 15:5910–6.
97. Medical research council streptomycin in tuberculosis trials committee. Streptomycin treatment for pulmonary tuberculosis. British Medical Journal 1948; ii:769–82.
98. Hansen AR, Graham DM, Pond GR, Siu LL. Phase 1 trial design: is 3 + 3 the best?. Cancer Control 2014; 21:200–208.
99. Thall PF. SMART design, conduct, and analysis in oncology. In Adaptive treatment strategies in practice: Planning trials and analyzing data for personalized medicine, Kosorok MR, Moodie EM (eds). SIAM: Philadelphia, 2015; pp. 41–54.
100. Clayton DG. Ethically optimised designs. British Journal of Clinical Pharmacology 1982; 13:469–480.
101. Tehranisa JS, Meurer WJ. Can response-adaptive randomization increase participation in acute stroke trials?. Stroke 2014; 45:2131–3.