Bridging the Causeway:

Transcription

1 Bridging the Causeway: A Center for Healthcare Policy and Research Symposium In cooperation with: The Clinical and Translational Science Center The Center for Reducing Health Disparities Cancer Breakout Group University of California, Davis Memorial Union March 25, 2008

2 Therapeutic Resistance in Her2(+) Breast Cancer Colleen Sweeney, Ph.D. Associate Professor Biochemistry & Molecular Medicine UC Davis School of Medicine

3 Therapeutic Resistance in Her2(+) Breast Cancer Her2 is amplified in ~ 25% of human breast cancers & predicts reduced disease free and overall survival. Herceptin is a humanized monoclonal antibody used in combination with chemotherapy for the management of Her2 (+) breast cancer. Primary & acquired resistance to Herceptin combination therapy is a vexing clinical problem: 20 50% of patients display primary resistance; most patients show evidence of disease progression within one year.

4 Her2 signaling in tumor cell growth

5 Proposed Mechanisms of Action of Herceptin

6 Resistance Mechanisms Sawyers CL Nature 449,

7 Met in Her2 (+) breast cancer IB: Her2 IB: Met IB: Actin 200 HGF Met Receptor % expression therapy responsive non-responsive

8 Inhibition of Met improves response to Herceptin Percent Inhibition BT474 Con SU IB: pmet IB: Met IB: Actin 0 SU11274 Trastuzumab Trastuzumab + SU11274 Percent Inhibition SKBR3 Con SU IB: pmet IB: Met IB: Actin 5 0 SU11274 Trastuzumab Trastuzumab + SU11274

9 Multiple RTKs are activated in Her2 (+) Breast Cancer Tumor #1 Tumor #2 Phospho-RTK array analysis of Her2 (+) breast tumors

10 Therapeutic Resistance in Her2(+) Breast Cancer Oncogene addiction predicts that single molecule targeting should be effective. Kinase switching allows tumors to escape growth inhibition by targeted agents such as Herceptin. Simultaneous inhibition of multiple RTK pathways holds the promise of a more complete approach to anti-cancer therapy Targeted agents Personalized therapy Inadequate access to patient specimens limits translation of results from bench to bedside; partnering with physicians will address this problem.

11 Tailored Interactive Multimedia to Improve Colorectal Cancer Screening in Primary Care Anthony Jerant, MD Department of Family & Community Medicine UC Davis School of Medicine Peter Franks, MD; Richard Kravitz, MD, MSPH; Matthew Kreuter, PhD, MPH; Mairin Rooney; Scott Amerson Funded by UC Davis Health System and UC Davis Department of Family & Community Medicine Research Grants

12 Goals Discuss the initial results and follow-up plans from a study of a new approach to increasing colorectal cancer (CRC) screening uptake Provide an example of fundable, cross-disciplinary T2 translational research

13 CRC Screening Uptake is Low Uptake: Proportion of those eligible for screening in a population invited for and completing screening in a given time period 2004 BRFSS data: Uptake of 57 % in adults aged > 50 years, much lower than for other evidence-based cancer screening tests!

14 Personally Tailored (PT) Interventions Individualized education and feedback, provided in direct response to a patient s answers to questions Growing body of research: may more powerfully influence health behaviors than traditional patient education approaches Most successful when tailoring is to mediators of health behavior Interactive multimedia computer programs (IMCPs) attractive potential method of delivery

15 Personally Tailored (PT) Interventions Research question: Can a PT IMCP be successfully deployed in primary care offices, linked with doctor visits, to increase colorectal cancer screening uptake? Jerant AF et al. Patient Education & Counseling 2006; 66:67-74

16 Hypotheses Compared with a non-tailored IMCP (attention control), the PT IMCP will result in: Significantly more favorable CRC screening readiness and selfefficacy, significantly fewer perceived barriers to screening core variables from the Transtheoretical Model (TTM) of behavior Trend toward greater CRC screening uptake

17 Subjects and Recruitment English speaking patients aged > 50 in the UC Davis Primary Care Network lacking up to date CRC screening per USPSTF recommendations Asked to arrive 60 minutes before appointment to do informed consent, use study software in primary care office on a laptop we provided Random assignment by computer program to experiment or attention control ( electronic leaflet ) at each patient s log in Patient answered series of questions Demographics, health status CRC screening knowledge CRC screening preferences, prior experiences CRC screening determinants from the TTM

18 Tailored Information First feedback message: tailored CRC screening recommendation (22 message variants) Generated by an algorithm that considered (in priority order) subject s responses to the following questions: CRC screening preference Readiness Self-efficacy Perceived barriers Prior experiences No specific method recommendation for controls

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20 Tailored Information Subsequent feedback messages: tailored to enhance self-efficacy and readiness for and reduce perceived barriers to screening Up beat, can do, gently persuasive framing Tap into prior preventive habits or successes Vicarious experiences (testimonials) Direct ties to patient s answers to key tailoring variable questions (microtailoring) Control subjects: non-tailored information

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23 Results 54 subjects enrolled Data for 5 excluded - software glitches 49 subjects with analyzable data 25 control, 24 experimental

24 Results Versus control, the tailored intervention group had: A significant increase in CRC screening self-efficacy. Adjusted improvement of 0.23 on a 5-point scale, 95% CI (0.00, 0.46), p = Effect size = 0.51, compares favorably with those observed in prior studies of personalized behavioral interventions that improved outcomes A significantly greater likelihood of moving to higher stage of readiness for screening. Adjusted OR = 5.01, 95% CI (1.13, 23.23), p = 0.034

25 Results At 1 year, CRC screening uptake was: Higher in experimental vs. control subjects: 48% vs. 39% Higher among experimental vs. control group Hispanics: 50% vs. 25% Sample was small, effects not statistically significant

26 Results Subjects required an average of 55 minutes to use the software Study RA provided assistance to about 1/3 of subjects 1/3 of intervention subjects had to finish the pre-visit part of the program post-visit No difference in satisfaction with software, good in both groups

27 Summary Personally tailored interactive multimedia computer program (PT IMCP) was more effective in bolstering several key determinants of CRC screening than a non-tailored attention control IMCP The PT IMCP was successfully deployed prior to doctor visits in busy primary care offices

28 Limitations Small study sample size Powered only to look at screening determinants, not actual screening outcomes Beta software - further iterations must: Require less time to complete (reduce content) Have a simpler user interface (touch screen) Be more reliable (1000s of lines of code to debug!)

29 Future Translational Research Follow-up NCI R01 proposal - Tailored Interactive Multimedia to Reduce Colorectal Cancer Screening Disparities Powered to examine CRC screening uptake and explore ability of PT IMCP to lessen or eliminate the glaring Hispanic/non-Hispanic White CRC screening disparity Develop similar personally tailored IMCPs to influence other health behaviors and outcomes Kravitz RL et al NIMH R01 - Depression care seeking and initial treatment adherence

30 Cross-Disciplinary Collaboration Such work requires a talented team with expertise in many areas: Health education Models and mediators of health behavior Tailoring - algorithm development, implementation Computer programming and interface design Cross-cultural issues in health care Health disparities Development and evaluation of health care interventions

31 Digital vs. Film Mammography: Does Evidence Drive Technology Transfer? Neal D. Kohatsu, MD, MPH Kirsten Knutson, MPH California Department of Public Health

32 Digital vs. Film Mammography: Overview Radiation dose is comparable In general, digital is as accurate as film for screening Digital is more accurate than film in: Pre- and peri-menopausal women Women under 50 Women with dense breast tissue Interpretation more important than technology for quality

33 Digital vs. Film Mammography: Advantages Electronic image acquisition, transmission, and storage Image can be seen just after capturing Contrast, brightness and magnification can be changed Easy to send or retrieve No lost images Potential for lower radiation dose than film Potential to integrate with facility s existing technology Improved workflow Side-by-side exam comparison Less training for radiologists Long-term cost savings

34 Digital vs. Film Mammography: Greater cost Disadvantages Expense of technology and equipment Cost of integrating with facility s existing technology Initial loss in efficiency Not cost-effective (except for one subgroup of women) Potential for quality breakdowns Lack of radiologist experience in using technology Lack of compatibility of digital technology across systems and over time Lack of compatibility of digital technology with facility s other technology Mortality benefit not proven

35 Prevalence of Digital Mammography Mammography is one of last radiology tests to be digitized Many facilities are replacing film with digital Mammography Facilities Providing Digital Mammography Number % U.S. Digital (March 2008) 2, California (Nov 2007) Digital Only Film and Digital 37 5 Film Only

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37 Why are Providers Adopting Digital Mammography? Scientific evidence that digital is at least as accurate as film Marketing Patient demand Concern for market competitiveness Possibility for increased profit for facilities Film obsolescence; digital future Liability fears

38 Research Implications Can (should) research address adoption of new medical technology? How can economic analyses be better integrated with outcomes research? How can research optimize population benefit in a PH mammography program?

39 Bridging the Causeway: A Center for Healthcare Policy and Research Symposium In cooperation with: The Clinical and Translational Science Center The Center for Reducing Health Disparities Cancer Breakout Group University of California, Davis Memorial Union March 25, 2008