Preview

Качественная клиническая практика

Расширенный поиск

Адаптивный дизайн в клинических исследованиях: преимущества и риски

Полный текст:

Аннотация

В последние десятилетия постепенно становится всё более популярным использование методов адаптивного дизайна как средства повышения эффективности ранних и поздних фаз клинических исследований, в частности, путём снижения стоимости, ресурсов и длительности, а также повышения вероятности успеха исследования и получения пациентами более эффективной и безопасной терапии. Проспективно запланированным модификациям могут подвергаться: критерии отбора, размер выборки и/или длительность исследования, параметры рандомизационной процедуры, режимы дозирования, включая число терапевтических групп, сопутствующая терапия, схема оценки состояния пациента, конечные точки, статистические методы. Возможность изменения дизайна в ходе исследования по результатам промежуточного анализа имеет ряд преимуществ перед традиционными исследованиями с фиксированным дизайном. Тем не менее, адаптивные исследования более сложные в исполнении, требуют более тщательного планирования, могут сопровождаться в различной степени статистическими, операционными, логистическими и регуляторными проблемами. Целью этой статьи является обзор основных определений, анализ “за” и “против” применения адаптивного дизайна на разных фазах клинических исследованиях œ статистической и регуляторной точек зрения для лучшего понимания методологии.

Об авторе

И. Б. Бондарева
Федеральное государственное бюджетное учреждение «Федеральный научно-клинический центр физико-химической медицины Федерального медико-биологического агентства»
Россия


Список литературы

1. Chow S.C., Chang M. Adaptive Design Methods in Clinical Trials. Chapman and Hall/CRC Press, Taylor and Francis, New York, NY; 2006.

2. Chow S.C., Chang M. Adaptive design methods in clinical trials - a review. Orphanet Journal of Rare Diseases 2008; 3: 11-24.

3. Kairalla J.A., Coffey C.S., Thomann M.A. and Muller K.E. Adaptive trial designs: a review of barriers and opportunities. Trials 2012;, 13: 145-153

4. Gallo P., Chuang-Stein C., Dragalin V., Gaydos B., Krams M., Pinheiro J. Adaptive design in clinical drug development - an executive summary of the PhRMA Working Group (with discussions). Journal of Biopharmaceutical Statistics 2006; 16 (3): 275-283.

5. Chang M. Adaptive Design Theory and Implementation Using SAS and R. Chapman and Hall/CRC Press, Taylor and Francis, New York, NY; 2007.

6. Chow S.C., Chang M., Pong A. Statistical consideration of adaptive methods in clinical development. Journal of Biopharmaceutical Statistics 2005; 15: 575-591.

7. Ellenberg S.S., Fleming T.R., DeMets D.L. Data Monitoring Committees in Clinical Trials: A Practical Perspective. John Wiley and Sons, New York; 2002.

8. Dragalin V. Adaptive designs: terminology and classification. Drug Inf J 2006; 40: 425-435.

9. Gaydos B., Anderson K.M., Berry D., Burnham N., Chuang-Stein C., Dudinak J., et al. Good practices for adaptive clinical trials in pharmaceutical product development. Drug Information Journal 2009; 43: 539-556.

10. Quinlan J., Krams M. Implementing adaptive designs: logistical and operational considerations. Drug Inf J 2006; 40 (4): 437-44.

11. Lachin J.M. Statistical properties of randomization in clinical trials. Controlled Clinical Trials 1988; 9: 289-311.

12. Rosenberger W.F., Stallard N., Ivanova A., Harper C.N., Ricks M.L. Optimal adaptive designs for binary response trials. Biometrics 2001; 57: 909-913.

13. Hardwick J.P., Stout Q.F. Optimal few-stage designs. Journal of Statistical Planning and Inference 2002; 104: 121-145.

14. Lan K.K.G., DeMets D.L. Group sequential procedures: calendar versus information time. Statistics in Medicine 1987; 8: 1191-1198.

15. Posch M., Bauer P. Adaptive two-stage designs and the conditional error function. Biometrical Journal 1999; 41: 689-696.

16. Lehmacher W., Wassmer G. Adaptive sample size calculations in group sequential trials. Biometrics 1999; 55: 1286-1290.

17. Liu Q., Proschan M.A., Pledger G.W. A unified theory of two-stage adaptive designs. Journal of American Statistical Association 2002; 97: 1034-1041.

18. Jennison C., Turnbull B. W. Group Sequential Methods with Applications to Clinical Trials. Chapman and Hall, New York, NY; 2000.

19. Jennison C., Turnbull B.W. Meta-analysis and adaptive group sequential design in the clinical development process. J Biopharm Stat 2005; 15 (4): 537-558.

20. Cui L., Hung H.M.J., Wang S.J. Modification of sample size in group sequential trials. Biometrics 1999; 55: 853-857.

21. Shih W.J. Group sequential, sample size re-estimation and two-stage adaptive designs in clinical trials: a comparison. Statistics in Medicine 2006; 25: 933-941.

22. Chung-Stein C., Anderson K., Gallo P., Collins S. Sample size reestimation: a review and recommendations. Drug Information Journal 2006; 40: 475-484.

23. Vandemeulebroeke M. Group sequential and adaptive designs-a review of basic concepts and points of discussion. Biometrical J 2008; 50: 541-557.

24. Reflection paper on methodological issues in confirmatory clinical trials planned with an adaptive design (2007). European Medicines Agency. http://www. ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003616.pdf

25. Guidance for Industry (2010) Adaptive Design Clinical Trials for Drugs and Biologicals. Food and Drug Administration. www.fda.gov

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

27. Hay M., Thomas D.W., Craighead J.L., Economides C., Rosenthal J. Clinical development success rates for investigational drugs. Nat. Biotechnol. 2014; 32 (1): 40-51.

28. Sacks L.V., Shamsuddin H.H., Yasinskaya Y.I, Bouri K, LanthierM.L., Sherman R.E. Scientific and Regulatory Reasons for Delay and Denial of FDA Approval of Initial Applications for New Drugs, 2000-2012. JAMA 2014; 311 (4): 378-384.

29. Hay M., Rosenthal J., Thomas D., Craighead J. Bio/BioMedTracker clinical trial success rates study. Presented at: BIO CEO & Investor Conference, 15 February 2011.

30. Bauer P., Bretz F., Dragalin V., Konig F., Wassmer G. Twenty-five years of confirmatory adaptive designs: opportunities and pitfalls. Stat Med 2016; 35: 325-47.

31. Brannath W., Koenig F., Bauer P. Multiplicity and flexibility in clinical trials. Pharm Stat 2007; 6: 205-216.

32. Bauer P., Einfalt J. Application of adaptive designs - a review. Biom J 2006;48 (4): 493-506.

33. Coffey C.S., Kairalla J.A. Adaptive clinical trials. Drugs R&D. 2008; 9 (4): 229-42.

34. Coffey C.S., Levin B., Clark C., Timmerman C., Wittes J., Gilbert P., et al. Overview, hurdles, and future work in adaptive designs: perspectives from a National Institutes of Health-funded workshop. Clin Trials. 2012; 9 (6): 671-80.

35. Retzios A.D. Innovation in Drug Development: Adaptive Designs for Clinical Trial. 2010. Bay Clinical R&D Services.

36. van der Graaf R., Roes K.C., van Delden J.J. Adaptive trials in clinical research: scientific and ethical issues to consider. JAMA 2012; 307: 2379-2380.

37. Bornkamp B., Bretz F., Dmitrienko A., Enas G., Gaydos B., Hsu C., et al. Innovative approaches for designing and analyzing adaptive dose-ranging trials. JBiopharm Stat 2007; 17: 965-995.

38. Freidlin B., Simon R. Evaluation of randomized discontinuation design. J Clin Oncol 2005; 23: 5094-5098.

39. Wang S.J., Hung H.M.J., O’Neill R. T. Adaptive patient enrichment designs in therapeutic trials. Biometrical J 2009; 51: 358-374.

40. Bretz F., Koenig F., Brannath W., Glimm E., Posch M. Adaptive designs for confirmatory clinical trials. Stat Med 2009; 28: 1181-1217.

41. Chuang-Stein C., Beltangady M. FDA draft guidance on adaptive design clinical trials: Pfizer’s perspective. J Biopharm Stat 2010; 20 (6): 1143-9.

42. Cook T., DeMets D.L. Review of draft FDA adaptive design guidance. J Biopharm Stat 2010; 20 (6): 1132-42.

43. Gallo P., Anderson K., Chuang-Stein C., Dragalin V., Gaydos B., Krams M., et al. Viewpoints on the FDA draft adaptive designs guidance from the PhRMA working group. J Biopharm Stat 2010; 20 (6): 1115-24.

44. Brannath W., Burger H.U., Glimm E., Stallard N., Vandemeulebroecke M., et al. Comments on the draft guidance on “adaptive design clinical trials for drugs and biologics” of the U.S. Food and Drug Administration. J Biopharm Stat 2010; 20: 1125-1131.

45. Rong Y. Regulations on Adaptive Design Clinical Trials. Pharmaceut Reg Affairs 2014; 3: 116-123.

46. Jaki T. Uptake of novel statistical methods for early-phase clinical studies in the UK public sector. Clin Trials 2013; 10 (2): 344-6.

47. Dimairo M., Boote J., Julious S.A., Nicholl J.P., Todd S. Missing steps in a staircase: a qualitative study of the perspectives of key stakeholders on the use of adaptive designs in confirmatory trials. Trials. 2015; 16 (1): 430-446.

48. Development TCftSoD. The Adoption and Impact of Adaptive Trial Designs. Boston, MA, USA: TUFTS University. 2013.

49. Hatfield I., Allison A., Flight L, Julious S.A., Dimairo M. Adaptive designs undertaken in clinical research: a review of registered clinical trials. Trials 2016; 17: 150-163.

50. Quinlan J., Gaydos B., Maca J., Krams M. Barriers and opportunities for implementation of adaptive designs in pharmaceutical product development. Clin Trials 2010; 7 (2): 167-73.

51. Elsäßer A., Regnstrom J., Vetter T., Koenig F., Hemmings R.J., Greco M., et al. Adaptive clinical trial designs for European marketing authorization: a survey of scientific advice letters from the European Medicines Agency. Trials 2014; 15 (1): 383-393.

52. Morgan C.C., Huyck S., Jenkins M., Chen L., Bedding A., Coffey C.S., et al. Adaptive design: results of 2012 survey on perception and use. Ther Innov Regul Sci 2014; 48 (4): 473-81.

53. Chow S.C., Corey R. Benefits, challenges and obstacles of adaptive clinical trial designs. Orph J Rare Dis 2011; 6: 79-89.

54. Cheung K., Kaufmann P. Efficiency perspectives on adaptive designs in stroke clinical trials. Stroke 2011; 42: 2990-2994.

55. Coffey C.S. You may worked on more adaptive designs than you think. Stroke 2015; 46 (2): 26-28.

56. Berry D.A. Adaptive clinical trials: the promise and the caution. J Clin Oncol 2011; 29 (6): 606-9.

57. Kaplan R., Maughan T., Crook A., Fisher D., Wilson R., Brown L., et al. Evaluating many treatments and biomarkers in oncology: a new design. J Clin Oncol. 2013; 31 (36): 4562-8.

58. Elman S.A., Ware J.H., Gottlieb A.B., Merola J.F. Adaptive Clinical Trial Design: An Overview and Potential Applications in Dermatology. Journal of Investigative Dermatology 2016; 136: 1325-1329.

59. Hanna N.H., Kaiser R., Sullivan R.N., Aren O.R., Ahn M.J., Tiangco B., et al. Nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with relapsed or refractory, advanced non-small cell lung cancer (LUME-Lung 2): a randomized, double-blind, phase III trial. Lung Cancer 2016; 102: 65-73.

60. Lesaffre E., Edelman M.J., Hanna N.H., Park K., Thatcher N., Willemsen S., et al. Statistical controversies in clinical research: Futility analyses in oncology - lessons on potential pitfalls from a randomized controlled trial. Annals of Oncology 2017; 28 (7): 1419-1426.

61. Jitlal M., Khan I., Lee S.M., Hackshaw A. Stopping clinical trials early for futility: retrospective analysis of several randomised clinical studies. Br J Cancer 2012; 107: 910-917.

62. Hughes S., Cuffe R.L., Lieftucht A., Garrett Nichols W. Informing the selection of futility stopping thresholds: case study from a late-phase clinical trial. Pharm Stat 2009; 8: 25-37.

63. Ravandi F., Ritchie E.K., Sayar H., Lancet J.E, Craig M.D., Vey N., 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 (9): 1025-1036.


Для цитирования:


Бондарева И.Б. Адаптивный дизайн в клинических исследованиях: преимущества и риски. Качественная клиническая практика. 2017;(3):23-34.

For citation:


Bondareva I.B. Adaptive design in clinical trials: benefits and risks. Kachestvennaya klinicheskaya praktika. 2017;(3):23-34. (In Russ.)

Просмотров: 89


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 2588-0519 (Print)
ISSN 2618-8473 (Online)