2. Moving Cancer Research from the Lab to the Population: The Final Step in Translational Research Presented by: Thomas C. Tucker, PhD, MPH Associate Director for Cancer Control Markey Cancer Center University of Kentucky CCAF Meeting San Diego, CA April 15, 2014 Markey Cancer Center

3. Topics to be covered The final step in translational cancer research Why this step is so important The concepts of Internal and External validity How these concepts relate to translational research The Markey Cancer Center Model for moving evidence-based research into the population An example of the potential impact of implementing evidence- based research findings in the population

4. The final step in translational research is the broad based implementation of cancer research findings in the population.

5. Two important concepts Internal validity External validity

6. Animal Studies genetically identical mice Developed Disease Did not Develop Disease Exposed Animals AB Unexposed Animals CD Relative Risk = (A/A+B)/(C/C+D)

7. Randomized Clinical Trial Randomized trial (Prospective) Study Outcome Occurred Did not Occur Exposure or Intervention AB No Exposure or Intervention CD Relative Risk = (A/A+B)/(C/C+D) Random Allocation

8. Internal Validity When differences between the experimental (exposed) group and the control group are completely accounted for, the study is said to have internal validity and causal inferences can be made. In other words, it is possible to determine whether the exposure causes some outcome (disease, etc.). Many have argued that “randomization” was the most important scientific advance of the 20 th century. Why is it that the findings from randomized clinical trials with internal validity almost never have the same effect when they are applied to general populations?

9. External Validity When the findings from a research project or study can be generalized to some defined population, they are said to have external validity. Epidemiology (population science) provides the tools to explore external validity and many argue that moving from studies with strong internal validity to studies with strong external validity is the next step in advancing our scientific understanding. The continuum from research with strong internal validity to studies with strong external validity is also part of “Translational Research”.

10. From the Laboratory to the Population GenesCellsAnimalsHumansPopulations Basic Science Clinical Science Epidemiology Translational Research

11. EXAMPLE Quercitrin, a natural product from apple peel, is tested in an animal model to determine if it prevents UV exposure induced skin cancer Randomized trials in human populations Broad application of the findings to the general population

12. From the Laboratory to the Population GenesCellsAnimalsHumansPopulations Basic Science Clinical Science Epidemiology And back again Translational Research

13. The ultimate goal of translational cancer research is the adoption and wide-spread use of evidence- based research findings that significantly reduce the cancer burden in the population. This includes the wide-spread implementation of evidence-based cancer control interventions.

14. Markey Cancer Center Model for Moving Evidence-based Cancer Research Findings into to the Population Kentucky Cancer Registry (KCR) Kentucky Cancer Program (KCP)Kentucky Cancer Consortium (KCC) Lung Cancer by Area Development District in KY, 2005-2009 Area Development District High School Education 2006- 2010 Current Smokers 2001-2005 Age- Adjusted Incidence Age- Adjusted Mortality Overall Rank PercentRankPercentRankRateRankRateRank Kentucky River65.6135.71124.7299.815 Big Sandy69.0335.52131.7196.228 Cumberland Valley67.8235.53117.2386.0311 Gateway73.7632.06102.1679.9422 Buffalo Trace73.3533.0496.91178.3525 Barren River78.6831.87105.8478.0625 Lake Cumberland70.9431.110101.2777.7728 Fivco78.2732.5599.9871.01030 Green River83.01130.311105.0576.1835 Pennyrile80.1931.3897.21070.11138 Lincoln Trail82.71031.1996.31266.41546 Purchase83.01228.51497.7969.41247 Northern Kentucky86.41529.01296.21371.4949 Kipda86.41428.61394.91466.61455 Bluegrass84.71328.21592.61568.01356

15. Demographic Characteristics Contribute to Risk Factors Contribute to Incidence and Late Stage DX Contribute to Cancer Mortality Combining Data from Multiple Sources Logic Model

16. What are the common sources of data that can be used for defining the cancer burden? Demographic data (Census U.S) Risk factor data (BRFSS) Incidence data (KCR) Mortality data (State Vital Records)

17. Lung Cancer by Area Development District in KY, 2007-2011 Area Development District High School Education (%) 2006-2010 Poverty Rate (%) 2006- 2010 Smoking Rate (%) 2001- 2005 Age-Adjusted Incidence Late Stage Incidence % Age-Adjusted Mortality NumberRateNumberRate U.S. 87.615.1 19.96292,49567.079.7229,10352.5 Kentucky81.017.430.423077100.580.71670173.2 Barren River78.619.131.81569105.883.1114878.0 Big Sandy69.025.235.51155131.782.983596.2 Bluegrass84.716.928.2344992.681.1251068.0 Buffalo Trace73.322.433.032196.980.525678.3 Cumberland Valley 67.828.735.51590117.281.6115386.0 Fivco78.219.532.586699.979.161371.0 Gateway73.725.232.0442102.179.534279.9 Green River83.015.530.31284105.080.293376.1 Kentucky River65.629.235.7840124.784.465899.8 Kipda86.414.328.6460294.977.9322366.6 Lake Cumberland 70.924.331.11295101.280.299277.7 Lincoln Trail82.714.831.1129196.379.887366.4 Northern Kentucky 86.411.429.0192196.280.8141371.4 Pennyrile80.118.531.3122097.283.587370.1 Purchase83.016.328.5123297.781.287969.4

21. Lung Cancer by Area Development District in KY, 2007-2011 Area Development District High School Education, 2006-2010 Current Smoker, 2001-2005 Age- Adjusted Incidence Age- Adjusted Mortality Overall Rank PercentRankPercentRankRateRankRateRank Kentucky River65.6135.71124.7299.815 Big Sandy69.0335.52131.7196.228 Cumberland Valley 67.8235.53117.2386.0311 Gateway73.7632.06102.1679.9422 Buffalo Trace73.3533.0496.91178.3525 Barren River78.6831.87105.8478.0625 Lake Cumberland70.9431.110101.2777.7728 Fivco78.2732.5599.9871.01030 Green River83.01130.311105.0576.1835 Pennyrile80.1931.3897.21070.11138 Lincoln Trail82.71031.1996.31266.41546 Purchase83.01228.51497.7969.41247 Northern Kentucky 86.41529.01296.21371.4949 Kipda86.41428.61394.91466.61455 Bluegrass84.71328.21592.61568.01356

22. An Example In 2001, Kentucky had the highest colorectal cancer incidence rate in the U.S. compared to all of the other states

23. In 2001, it was also noted that Kentucky was ranked 49 th in colorectal cancer screening compared to all other states with the second to the lowest rate (34.7% of the age eligible population).

24. Using the process previously described, data about the burden of colorectal cancer was assembled and presented to each of the 15 District Cancer Councils. Following these presentations, all 15 of the District Cancer Councils implemented evidence based cancer control intervention programs aimed at increasing colorectal cancer screening for age eligible people living in their District. What happened following the implementation of these colorectal cancer screening programs?

25. Colorectal Cancer Screening in Kentucky 70% 60% 50% 40% 30% 200220042006 58.6% 47.2% 43.9% 34.7% 200819992010 63.7% 49 th in the U.S. 20 th in the U.S.

26. P<.05 Source: http://cancer-rates.info/ky, Accessed January 2014http://cancer-rates.info/ky

27. P<.05 Source: http://cancer-rates.info/ky, Accessed January 2014http://cancer-rates.info/ky

28. A 24% reduction in colorectal cancer incidence and a 28% reduction in colorectal cancer mortality is a significant public health success. This provides evidence that the wide spread application of proven cancer research findings (the last step in translational research) can make a real difference in peoples lives.

29. Thank You! Questions The End Contact Information: Thomas C. Tucker, PhD, MPH tct@kcr.uky.edu Markey Cancer Center