Implications of comparative effectiveness research for radiation oncology

Practical Radiation Oncology

Volumn 1, Issue 2, 2011, Pages 72-80

  Bekelman, Justin E ^a,b   Shah, Anand ^a   Hahn, Stephen M ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; CANCER RADIOTHERAPY; CLINICAL EFFECTIVENESS; COMPARATIVE EFFECTIVENESS; EXTERNAL VALIDITY; HUMAN; INTERNAL VALIDITY; OBSERVATIONAL STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); STUDY DESIGN;

EID: 79960279119     PISSN: 18798500     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.prro.2011.02.001     Document Type: Article

References (84)

1. American Recovery and Reinvestment Act of 2009. Available at: Accessed January 3, 2011. http://frwebgate.access.gpo.gov/cgi-
2. Federal Coordinating Council Report to the President and the Congress on Comparative Effectiveness Research 2010, Available at:, Accessed December 13, 2010. http://www.hhs.gov/recovery/programs/cer/execsummary.html.
3. Initial National Priorities for Comparative Effectiveness Research 2009, Institute of Medicine of the National Academies, Washington, DC.
4. Patient Protection and Affordable Care Act. 2010. Available at: Accessed January 3, 2011. http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=111_cong_bills&docid=f.
5. Tunis S.R., Benner J., McClellan M. Comparative effectiveness research: policy context, methods development and research infrastructure. Stat Med 2010, 29:1963-1976.
6. Widmark A., Klepp O., Solberg A., et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet 2009, 373:301-308.
7. Fisher B., Anderson S., Bryant J., et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002, 347:1233-1241.
8. Macdonald J.S., Smalley S.R., Benedetti J., et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001, 345:725-730.
9. Miller T.P., Dahlberg S., Cassady J.R., et al. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med 1998, 339:21-26.
10. Thompson I.M., Tangen C.M., Paradelo J., et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 2009, 181:956-962.
11. Clarke M., Collins R., Darby S., et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005, 366:2087-2106.
12. Pignon J.P., Arriagada R., Ihde D.C., et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 1992, 327:1618-1624.
13. Pearson S.D., Bach P.B. How medicare could use comparative effectiveness research in deciding on new coverage and reimbursement. Health Aff (Millwood) 2010, 29:1796-1804.
14. Luce B.R., Drummond M., Jonsson B., et al. EBM, HTA, and CER: clearing the confusion. Milbank Q 2010, 88:256-276.
15. Soares H.P., Kumar A., Daniels S., et al. Evaluation of new treatments in radiation oncology: are they better than standard treatments?. JAMA 2005, 293:970-978.
16. Zwarenstein M., Treweek S., Gagnier J.J., et al. Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ 2008, 337:a2390.
17. Fleurence R.L., Naci H., Jansen J.P. The critical role of observational evidence in comparative effectiveness research. Health Aff (Millwood) 2010, 29:1826-1833.
18. Guyatt G.H., Oxman A.D., Vist G.E., et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008, 336:924-926.
19. Bentzen S.M., Bernier J., Davis J.B., et al. Clinical impact of dosimetry quality assurance programmes assessed by radiobiological modelling of data from the thermoluminescent dosimetry study of the European Organization for Research and Treatment of Cancer. Eur J Cancer 2000, 36:615-620.
20. Poortmans P.M., Venselaar J.L., Struikmans H., et al. The potential impact of treatment variations on the results of radiotherapy of the internal mammary lymph node chain: a quality-assurance report on the dummy run of EORTC Phase III randomized trial 22922/10925 in Stage I-III breast cancer(1). Int J Radiat Oncol Biol Phys 2001, 49:1399-1408.
21. Pettersen M.N., Aird E., Olsen D.R. Quality assurance of dosimetry and the impact on sample size in randomized clinical trials. Radiother Oncol 2008, 86:195-199.
22. Bolla M., de Reijke T.M., Van Tienhoven G., et al. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 2009, 360:2516-2527.
23. Vickers A.J., Bianco F.J., Serio A.M., et al. The surgical learning curve for prostate cancer control after radical prostatectomy. J Natl Cancer Inst 2007, 99:1171-1177.
24. Schwartz D., Lellouch J. Explanatory and pragmatic attitudes in therapeutical trials. J Chronic Dis 1967, 20:637-648.
25. Thorpe K.E., Zwarenstein M., Oxman A.D., et al. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol 2009, 62:464-475.
26. Tunis S.R., Stryer D.B., Clancy C.M. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA 2003, 290:1624-1632.
27. Luce B.R., Kramer J.M., Goodman S.N., et al. Rethinking randomized clinical trials for comparative effectiveness research: the need for transformational change. Ann Intern Med 2009, 151:206-209.
28. Treweek S., Zwarenstein M. Making trials matter: pragmatic and explanatory trials and the problem of applicability. Trials 2009, 10:37.
29. Hemingway H., McCallum A., Shipley M., Manderbacka K., Martikainen P., Keskimaki I. Incidence and prognostic implications of stable angina pectoris among women and men. JAMA 2006, 295:1404-1411.
30. Stein P.D., Yaekoub A.Y., Matta F. Sostman HD. 64-slice CT for diagnosis of coronary artery disease: a systematic review. Am J Med 2008, 121:715-725.
31. Shah B.R., Patel M.R., Peterson E.D., Douglas P.S. Defining optimal research study design for cardiovascular imaging using computed tomography angiography as a model. Am J Cardiol 2008, 102:943-948.
32. Lauer M.S. CT angiography: first things first. Circ Cardiovasc Imaging 2009, 2:1-3.
33. Berenson A., Abelson R. Weighing the Costs of a CT Scan's Look Inside the Heart. New York Times 2008, Available at:, Accessed January 14, 2011. http://www.nytimes.com/2008/06/29/business/29scan.html?_r=1&ref=health.
34. PROMISE trial: clinical coordinating center. 2010. Available at: Accessed December 21, 2010. http://projectreporter.nih.gov/project_info_description.cfm?aid=7940886&icde=5559996.
35. Bellamy S.L., Lin J.Y., Ten Have T.R. An introduction to causal modeling in clinical trials. Clin Trials 2007, 4:58-73.
36. White J.E., Chen T., McCracken J., et al. The influence of radiation therapy quality control on survival, response and sites of relapse in oat cell carcinoma of the lung: preliminary report of a Southwest Oncology Group study. Cancer 1982, 50:1084-1090.
37. Wallner P.E., Lustig R.A., Pajak T.F., et al. Impact of initial quality control review on study outcome in lung and head/neck cancer studies-review of the Radiation Therapy Oncology Group experience. Int J Radiat Oncol Biol Phys 1989, 17:893-900.
38. Chow S.C., Chang M. Adaptive design methods in clinical trials-a review. Orphanet J Rare Dis 2008, 3:11.
39. Berry D.A. Bayesian clinical trials. Nat Rev Drug Discov 2006, 5:27-36.
40. Barker A.D., Sigman C.C., Kelloff G.J., Hylton N.M., Berry D.A., Esserman L.J. I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy. Clin Pharmacol Ther 2009, 86:97-100.
41. Coffey C.S., Kairalla J.A. Adaptive clinical trials: progress and challenges. Drugs R D 2008, 9:229-242.
42. Mahajan R., Gupta K. Adaptive design clinical trials: methodology, challenges and prospect. Indian J Pharmacol 2010, 42:201-207.
43. Quinlan J., Gaydos B., Maca J., Krams M. Barriers and opportunities for implementation of adaptive designs in pharmaceutical product development. Clin Trials 2010, 7:167-173.
44. Chang M., Chow S.C. Analysis strategies for adaptive designs with multiple endpoints. J Biopharm Stat 2007, 17:1189-1200.
45. Hsu J.C. Multiplicity adjustment big and small in clinical studies. Clin Pharmacol Ther 2010, 88:251-254.
46. Proschan M.A., Waclawiw M.A. Practical guidelines for multiplicity adjustment in clinical trials. Control Clin Trials 2000, 21:527-539.
47. Schulz K.F., Grimes D.A. Multiplicity in randomised trials I: endpoints and treatments. Lancet 2005, 365:1591-1595.
48. Research Highlights: IHE-RO. 2011. Available at: Accessed January 16, 2011. http://www.astro.org/Research/ResearchHighlights/IHERO/index.aspx#Whatis.
49. Welcome to the caBIG® Community Website. Available at: Accessed January 16, 2011. https://cabig.nci.nih.gov/.
50. Bill-Axelson A., Holmberg L., Ruutu M., et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2005, 352:1977-1984.
51. Tewari A., Raman J.D., Chang P., Rao S., Divine G., Menon M. Long-term survival probability in men with clinically localized prostate cancer treated either conservatively or with definitive treatment (radiotherapy or radical prostatectomy). Urology 2006, 68:1268-1274.
52. Wong Y.N., Mitra N., Hudes G., et al. Survival associated with treatment vs observation of localized prostate cancer in elderly men. JAMA 2006, 296:2683-2693.
53. Albertsen P.C., Hanley J.A., Penson D.F., Barrows G., Fine J. 13-Year outcomes following treatment for clinically localized prostate cancer in a population based cohort. J Urol 2007, 177:932-936.
54. Cooperberg MR, Carroll PR, Vickers AJ. Reply to comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer [e-pub ahead of print December 14, 2010]. Cancer.
55. Cooperberg M.R., Vickers A.J., Broering J.M., Carroll P.R. Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer. Cancer 2010, 116:5226-5234.
56. Hadley J., Yabroff K.R., Barrett M.J., Penson D.F., Saigal C.S., Potosky A.L. Comparative effectiveness of prostate cancer treatments: evaluating statistical adjustments for confounding in observational data. J Natl Cancer Inst 2010, 102:1780-1793.
57. Litwin M.S., Miller D.C. Treating older men with prostate cancer: survival (or selection) of the fittest?. JAMA 2006, 296:2733-2734.
58. Rubin D.B. Estimating causal effects from large data sets using propensity scores. Ann Intern Med 1997, 127:757-763.
59. Rosenbaum P., Robin D. Reducing bias in observational studies using subclassification on the propensity score. J Am Stat Assoc 1984, 79:516-524.
60. Stukel T.A., Fisher E.S., Wennberg D.E., Alter D.A., Gottlieb D.J., Vermeulen M.J. Analysis of observational studies in the presence of treatment selection bias: effects of invasive cardiac management on AMI survival using propensity score and instrumental variable methods. JAMA 2007, 297:278-285.
61. Rassen J.A., Brookhart M.A., Glynn R.J., Mittleman M.A., Schneeweiss S. Instrumental variables I: instrumental variables exploit natural variation in nonexperimental data to estimate causal relationships. J Clin Epidemiol 2009, 62:1226-1232.
62. Brookhart M.A., Rassen J.A., Schneeweiss S. Instrumental variable methods in comparative safety and effectiveness research. Pharmacoepidemiol Drug Saf 2010, 19:537-554.
63. Mitra N., Heitjan D.F. Sensitivity of the hazard ratio to nonignorable treatment assignment in an observational study. Stat Med 2007, 26:1398-1414.
64. Zeliadt S.B., Potosky A.L., Penson D.F., Etzioni R. Survival benefit associated with adjuvant androgen deprivation therapy combined with radiotherapy for high- and low-risk patients with nonmetastatic prostate cancer. Int J Radiat Oncol Biol Phys 2006, 66:395-402.
65. Lu-Yao G.L., Albertsen P.C., Moore D.F., et al. Survival following primary androgen deprivation therapy among men with localized prostate cancer. JAMA 2008, 300:173-181.
66. Basu A., Heckman J.J., Navarro-Lozano S., Urzua S. Use of instrumental variables in the presence of heterogeneity and self-selection: an application to treatments of breast cancer patients. Health Econ 2007, 16:1133-1157.
67. Brooks J.M., Chrischilles E.A., Scott S.D., Chen-Hardee S.S. Was breast conserving surgery underutilized for early stage breast cancer? Instrumental variables evidence for stage II patients from Iowa. Health Serv Res 2003, 38:1385-1402.
68. Wisnivesky J.P., Halm E., Bonomi M., Powell C., Bagiella E. Effectiveness of radiation therapy for elderly patients with unresected stage I and II non-small cell lung cancer. Am J Respir Crit Care Med 2010, 181:264-269.
69. SEER-Medicare: Medicare enrollment & claims data. Available at: Accessed December 30, 2010. http://healthservices.cancer.gov/seermedicare/medicare/.
70. Warren J.L., Klabunde C.N., Schrag D., Bach P.B., Riley G.F. Overview of the SEER-Medicare data: content, research applications, and generalizability to the United States elderly population. Med Care 2002, 40:IV-3-IV-18.
71. Smith B.D., Smith G.L., Roberts K.B., Buchholz T.A. Baseline utilization of breast radiotherapy before institution of the Medicare practice quality reporting initiative. Int J Radiat Oncol Biol Phys 2009, 74:1506-1512.
72. Surveillance, Epidemiology and End Results (SEER). Available at: Acessed December 31, 2010. http://seer.cancer.gov/.
73. SEER-Medicare linked database. Available at: Accessed December 31, 2010. http://healthservices.cancer.gov/seermedicare/.
74. Bekelman J.E., Zelefsky M.J., Jang T.L., Basch E.M., Schrag D. Variation in adherence to external beam radiotherapy quality measures among elderly men with localized prostate cancer. Int J Radiat Oncol Biol Phys 2007, 69:1456-1466.
75. Abernethy A.P., Ahmad A., Zafar S.Y., Wheeler J.L., Reese J.B., Lyerly H.K. Electronic patient-reported data capture as a foundation of rapid learning cancer care. Med Care 2010, 48:S32-S38.
76. Wu A.W., Snyder C., Clancy C.M., Steinwachs D.M. Adding the patient perspective to comparative effectiveness research. Health Aff (Millwood) 2010, 29:1863-1871.
77. Berger M.L., Mamdani M., Atkins D., Johnson M.L. Good research practices for comparative effectiveness research: defining, reporting and interpreting nonrandomized studies of treatment effects using secondary data sources: the ISPOR Good Research Practices for Retrospective Database Analysis Task Force Report-Part I. Value Health 2009, 12:1044-1052.
78. von Elm E., Altman D.G., Egger M., Pocock S.J., Gotzsche P.C., Vandenbroucke J.P. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007, 147:573-577.
79. Schulz K.F., Altman D.G., Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010, 340:c332.
80. Meltzer D., Basu A., Conti R. The economics of comparative effectiveness studies: societal and private perspectives and their implications for prioritizing public investments in comparative effectiveness research. Pharmacoeconomics 2010, 28:843-853.
81. Garber A.M., Sox H.C. The role of costs in comparative effectiveness research. Health Aff (Millwood) 2010, 29:1805-1811.
82. Wilson J.F. Cancer care: a microcosm of the problems facing all of health care. Ann Intern Med 2009, 150:573-576.
83. Meropol N.J., Schrag D., Smith T.J., et al. American Society of Clinical Oncology guidance statement: the cost of cancer care. J Clin Oncol 2009, 27:3868-3874.
84. Sher D.J. Cost-effectiveness studies in radiation therapy. Expert Rev Pharmacoecon Outcomes Res 2010, 10:567-582.