BCSC as a Platform for Comparative Effectiveness Research

1. BCSC as a Platform for Comparative Effectiveness Research Diana Buist, PhD, MPH for the BCSC

2. Comparative Effectiveness Research definition* Head-to-head comparisons of benefits and harms of different interventions and strategies to prevent, diagnose, treat and monitor health conditions in “real world” settings • To improve health outcomes by developing and disseminating evidence-based information • Which interventions are most effective for which patients under specific circumstances *Health and Human Services definition

3. Where BCSC started… • Were still learning whether mammography was efficacious, much less effective • Did not know much about what influenced screening effectiveness or efficacy • Risk factors • Intervals • Providers • Facilities

4. Why is CER possible in BCSC • Real world settings– community practice screening facilities • Real world women and radiologists – consent (mostly) not required • Geographic and racial distribution • Able to compare important differences in international screening strategies • Ability to conduct ancillary studies off BCSC infrastructure platform

5. International comparisons Examples: -UK vs. US-Norway vs. US (Vermont & North Carolina)

6. Recall is lower at same cancer detection rate in the UK vs. US Smith-Bindman et al JAMA 2003 “UK performs far fewer diagnostic tests and open surgical biopsies to diagnose same number of cancers”

7. Norway vs. US • Hofvind JNCI 2008 • Hofvind et al Med Screen. 2009 • Interval cancer rates significantly higher in Vermont & North Carolina than in Norway • But - diagnosed tumors in US tended to be at an earlier stage

8. Screening intervals

9. Late stage breast cancers are no more likely for women on a 2 year screening intervals vs. 1 year, except for younger women Age at Index Mammogram, y White et al JNCI 2004 “ These findings may be useful for policy decisions about appropriate screening intervals and for use in statistical models that estimate the costs and benefits of mammography by age and screening interval”

10. Mammography does not work as well in younger women because of higher density and faster growing tumors Buist et al. JNCI 2004 • 68% of interval cancers by 12 months in younger women explained by higher mammographic breast density • 31% of interval cancers at 24 months in younger women because of higher mitotic figure count and Ki-67 & 38% because of higher breast density *Used tissue blocks from Group Health in collaboration with Fred Hutchinson Cancer Research Center

11. CER studies to test ways of improving screening • Outreach • Screening strategy • Changing risk factors • New technology

12. JNCI 2000 • Reminding women to schedule a mammogram is as effective as addressing barriers • “Simple intervention groups need to be included as comparison groups in randomized trials so that we better understand more complex intervention effects”

13. CBE had modest incremental benefit to invasive cancer detection over mammography alone, but results in more false-positive results

14. Hormone therapy suspension Randomized trial of short-term hormone therapy suspension does not change mammography recall Buist et al. Annals Intern Med 2009 The Radiological Evaluation and Breast Density (READ) Randomized Trial

15. Specificity 24 month Sensitivity 12 month Sensitivity

16. Local BCSC Research Resources that could be used to expand CER capacity • Biological specimens in well characterized samples • Tissue, blood samples, medical records • Health services data in fee for service and HMO • Treatment, comorbidities • Quality improvement • Technical and clinical quality measures • Radiologists’ interpretation, facility level data • New technologies, including costs • Risk factor data on women for improving risk assessment

17. Conducting CER within BCSC is possible, but worth remembering… • Takes time and funding to engage with facility leaders • Integrating with the clinical flow • Need to be clear on where research ends and clinical care begins • Getting realistic budget estimates and TIME! for interactively working with clinical systems • Clinical priorities are often not aligned with research priorities – particularly true for timelines

18. Some CER citations 1. Buist DS, ML A, Reed SD, Aiello Bowles EJ, Fitzgibbons ED, Gandara JC, Seger D, Newton KM. Short-term hormone therapy suspension and mammography recall: a randomized trial. Ann Intern Med. 2009;150(11):752-65. PMCID: PMC2803099. 2. Buist DS, Porter PL, Lehman C, Taplin SH, White E. Factors contributing to mammography failure in women aged 40-49 years. J Natl Cancer Inst. 2004;96(19):1432-40. 3. Hofvind S, Vacek PM, Skelly J, Weaver DL, Geller BM. Comparing screening mammography for early breast cancer detection in Vermont and Norway. J Natl Cancer Inst. 2008;100(15):1082-91. PMCID: PMC2720695. 4. Hofvind S, Yankaskas BC, Bulliard JL, Klabunde CN, Fracheboud J. Comparing interval breast cancer rates in Norway and North Carolina: results and challenges. J Med Screen. 2009;16(3):131-9. PMCID: journal in process. 5. Jensen A, Geller BM, Gard CC, Miglioretti DL, Yankaskas B, Carney PA, Rosenberg RD, Vejborg I, Lynge E. Performance of diagnostic mammography differs in the United States and Denmark. Int J Cancer. 2010. PMCID: journal in process. 6. Oestreicher N, Lehman CD, Seger DJ, Buist DS, White E. The incremental contribution of clinical breast examination to invasive cancer detection in a mammography screening program. Am J Roentgenol. 2005;184(2):428-32. 7. Smith-Bindman R, Chu PW, Miglioretti DL, Sickles EA, Blanks R, Ballard-Barbash R, Bobo JK, Lee NC, Wallis MG, Patnick J, Kerlikowske K. Comparison of screening mammography in the United States and the United Kingdom. JAMA. 2003;290(16):2129-37. 8. Taplin SH, Barlow WE, Ludman E, MacLehos R, Meyer DM, Seger D, Herta D, Chin C, Curry S. Testing reminder and motivational telephone calls to increase screening mammography: a randomized study. J Natl Cancer Inst. 2000;92(3):233-42. 9. Taplin SH, Rutter CM, Lehman CD. Testing the effect of computer-assisted detection on interpretive performance in screening mammography. AJR Am J Roentgenol. 2006;187(6):1475-82. 10. White E, Miglioretti DL, Yankaskas BC, Geller BM, Rosenberg RD, Kerlikowske K, Saba L, Vacek PM, Carney PA, Buist DS, Oestreicher N, Barlow W, Ballard-Barbash R, Taplin SH. Biennial versus annual mammography and the risk of late-stage breast cancer. J Natl Cancer Inst. 2004;96(24):1832-9.

19. Thank you!