Ethical considerations in adaptive design clinical trials

Therapeutic Innovation and Regulatory Science

Volumn 51, Issue 2, 2017, Pages 190-199

  Laage, Thomas ^a   Loewy, John W ^b   Menon, Sandeep ^c   Miller, Eva R ^d   Pulkstenis, Erik ^e   Kan Dobrosky, Natalia ^f   Coffey, Christopher ^g  

^a Premier Research   (United States)

^b DataForeThought   (United States)

^c PFIZER INC   (United States)

^d Independent Consultant   (United States)

^e MEDIMMUNE   (United States)

^f Pharmaceutical Product Development   (United States)

^g UNIVERSITY OF IOWA   (United States)

Author keywords

Adaptive design; Belmont Report; Beneficence; Ethics; Justice; Respect for persons

Indexed keywords

BENEFICENCE; CASE STUDY; CLINICAL RESEARCH; CLINICAL TRIAL (TOPIC); EQUIPOISE; ETHICAL DECISION MAKING; MEDICAL ETHICS; METHODOLOGY; OPEN STUDY; PRIORITY JOURNAL; PROFESSIONAL STANDARD; RANDOMIZATION; RESOURCE ALLOCATION; REVIEW; RISK BENEFIT ANALYSIS; SAMPLE SIZE; STUDY DESIGN;

EID: 85018306037     PISSN: 21684790     EISSN: 21684804     Source Type: Journal    
DOI: 10.1177/2168479016667766     Document Type: Review

References (45)

1. Bhatt DL, Mehta C. Adaptive designs for clinical trials. N Engl J Med. 2016;375:65-74.
2. EMA, Committee for Medicinal Products for Human Use. Reflection paper on methodological issues in confirmatory clinical trials planned with an adaptive design. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003616.pdf. Published October 18, 2007. Accessed February 9, 2015.
3. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for industry: adaptive design clinical trials for drugs and biologics. http://www.fda.gov/downloads/Drugs/.../Guidances/UCM201790.pdf. Accessed January 16, 2015.
4. The 21st Century Cures Discussion Document [white paper]. http://energycommerce.house.gov/sites/republicans.energycommerce.house.gov/files/files/114/FINAL%20Cures%20Discussion%20Document%20White%20Paper.pdf. Accessed March 15, 2015.
5. Chow S.-C. Adaptive clinical trial design. Annu Rev Med. 2014; 65:405-415.
6. Office for Human Research Protections, US Department of Health and Human Services. The Belmont Report. HHS.gov. http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html. Published April 18, 1979. Accessed January 16, 2015.
7. Thall PF. Ethical issues in oncology biostatistics. Stat Methods Med Res. 2002;11:429-448.
8. Saxman SB. Ethical considerations for outcome-adaptive trial designs: a clinical researcher’s perspective. Bioethics. 2015;29: 59-65.
9. Hey SP, Kimmelman J. Are outcome-adaptive allocation trials ethical? Clin Trials Lond Engl. 2015;12:102-106.
10. Kirby S, Burke J, Chuang-Stein C, Sin C. Discounting phase 2 results when planning phase 3 clinical trials. Pharm Stat. 2012;11: 373-385.
11. Chuang-Stein C. Sample size and the probability of a successful trial. Pharm Stat. 2006;5:305-309.
12. Léauté-Labrèze C, Hoeger P, Mazereeuw-Hautier J, et al. A randomized, controlled trial of oral propranolol in infantile hemangioma. N Engl J Med. 2015;372:735-746.
13. World Medical Association declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA. 1997;277:925-926.
14. Lo B. Ethical Issues in Clinical Research: A Practical Guide. Philadelphia: Lippincott Williams & Wilkins; 2010.
15. Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, Coates AS, et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005;353:2747-2757.
16. Rimawi M, Hilsenbeck SG. Making sense of clinical trial data: is inverse probability of censoring weighted analysis the answer to crossover bias? J Clin Oncol Off J Am Soc Clin Oncol. 2012;30: 453-458.
17. A Double-masked, Placebo-controlled Study With Open Label Period to Evaluate MEDI-551 in Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders. Clinical- Trials.gov. https://www.clinicaltrials.gov/ct2/show/NCT02200770?id=NCT02200770&rank=1. Accessed November 2, 2015.
18. Cree BA, Bennett JL, Sheehan M, et al. Placebo-controlled study in neuromyelitis optica—ethical and design considerations. Mult Scler Houndmills Basingstoke Engl. December 2015.
19. Henderson GE, Churchill LR, Davis AM, et al. Clinical trials and medical care: defining the therapeutic misconception. PLoS Med. 2007;4:e324.
20. Meurer WJ, Lewis RJ, Berry DA. Adaptive clinical trials: a partial remedy for the therapeutic misconception? JAMA. 2012;307: 2377-2378.
21. Bartlett RH, Roloff DW, Cornell RG, Andrews AF, Dillon PW, Zwischenberger JB. Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study. Pediatrics. 1985;76:479-487.
22. Zelen M. Play the winner rule and the controlled clinical trial. J Am Stat Assoc. 1969;64:131-146.
23. Wei L, Durham S. The randomized play-the-winner rule in medical trials. J Am Stat Assoc. 1978;73:840-843.
24. O’Rourke PP, Crone RK, Vacanti JP, et al. Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospective randomized study. Pediatrics. 1989;84: 957-963.
25. Zelen M. A new design for randomized clinical trials. N Engl J Med. 1979;300:1242-1245.
26. Mike V, Krauss AN, Ross GS. Neonatal extracorporeal membrane oxygenation (ECMO): clinical trials and the ethics of evidence. J Med Ethics. 1993;19:212-218.
27. Torgerson DJ, Roland M. What is Zelen’s design? BMJ. 1998; 316:606.
28. A Study of Trastuzumab Emtansine Versus Taxane in Patients With Advanced Gastric Cancer. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01641939. Accessed May 27, 2015.
29. Safety and Effectiveness of 3 Doses of Crofelemer Compared to Placebo in the Treatment of HIV Associated Diarrhea. Clinical- Trials.gov. https://clinicaltrials.gov/ct2/show/NCT00547898. Accessed May 27, 2015.
30. Macarthur RD, Hawkins TN, Brown SJ, et al. Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT trial): a randomized, double-blind, placebo-controlled, two-stage study. HIV Clin Trials. 2013;14: 261-273.
31. Chowdhury BA, Seymour SM, Michele TM, Durmowicz AG, Liu D, Rosebraugh CJ. The risks and benefits of indacaterol—the FDA’s review. N Engl J Med. 2011;365:2247-2249.
32. Coffey CS, Levin B, Clark C, et al. Overview, hurdles, and future work in adaptive designs: perspectives from a National Institutes of Health-funded workshop. Clin Trials Lond Engl. 2012;9: 671-680.
33. Pritchett YL, Menon S, Marchenko O, et al. Sample size reestimation designs in confirmatory clinical trials—current state, statistical considerations, and practical guidance. Stat Biopharm Res. 2015;7:309-321.
34. Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory Acute Myeloid Leukemia (AML). ClinicalTrials.gov. https://clinicaltrials.gov/ show/NCT01191801. Accessed May 27, 2015.
35. Ravandi F, Ritchie EK, Sayar H, et al. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2015;16:1025-1036.
36. VALOR, an adaptive design, pivotal phase 3 trial of vosaroxin or placebo in combination with cytarabine in first relapsed or refractory acute myeloid leukemia. http://www.sunesis.com/data-pdf/595/sunesis-valor-vosaroxin-201206-ASCO.pdf. Accessed May 27, 2015.
37. Ravandi F, Ritchie E, Sayar H, et al. Improved survival in patients with first relapsed or refractory acute myeloid leukemia (AML) treated with vosaroxin plus cytarabine versus placebo plus cytarabine: results of a phase 3 double-blind randomized controlled multinational study (VALOR) [abstract]. ASH Annual Meeting Abstracts. https://ash.confex.com/ash/2014/webprogram/Paper77078.html. Accessed May 27, 2015.
38. Sunesis Pharmaceuticals, Inc. Investors & Media: News Release. http://ir.sunesis.com/phoenix.zhtml?c=194116&p=irol-newsArticle&ID=1733788. Accessed June 19, 2015.
39. Bauer P, Bretz F, Dragalin V, König F, Wassmer G. Twenty-five years of confirmatory adaptive designs: opportunities and pitfalls. Stat Med. March 2015.
40. Marchenko O, Nolan C. Chapter 11 implementing adaptive designs: operational considerations, putting it all together. In: Weili He, Jose Pinheiro, Olga M. Kuznetsova, eds. In Practical Considerations for Adaptive Trial Design and Implementation. 1st ed. Statistics for Biology and Health. New York, NY: Springer; 2014:203-225.
41. Thall P, Fox P, Wathen J. Statistical controversies in clinical research: scientific and ethical problems with adaptive randomization in comparative clinical trials. Ann Oncol Off J Eur Soc Med Oncol ESMO. May 2015.
42. Berry SM, Connor JT, Lewis RJ. The platform trial: an efficient strategy for evaluating multiple treatments. JAMA. 2015;313: 1619-1620.
43. Mandrekar SJ, Dahlberg SE, Simon R. Improving clinical trial efficiency: thinking outside the box. In: American Society of Clinical Oncology, ed. 2015 Educational Book. ASCO, 2015; 35:e141-e147.
44. Dangi-Garimella S. New oncology clinical trial designs: what works and what doesn’t? Am J Managed Care. http://www.ajmc.com/journals/evidence-based-oncology/2015/the-americansociety-of-clinical-oncology-annual-meeting-2015/new-oncology-clinical-trial-designs-what-works-and-what-doesnt. Published July 10, 2015. Accessed March 17, 2016.
45. Harrington D. Preface. In: Designs of Clinical Trials. New York: Springer-Verlag; 2012:XIV, 206.