Moving Cancer Research from the Lab to the Population: The Final Step in Translational Research

Presented by:

Thomas C. Tucker, PhD, MPHAssociate Director for Cancer ControlMarkey Cancer CenterUniversity of Kentucky

CCAF MeetingSan Diego, CAApril 15, 2014

Markey Cancer Center

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

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

Two important concepts

• Internal validity•External validity

Animal Studies

genetically identical mice

Developed Disease

Did not Develop Disease

Exposed Animals

A B

Unexposed Animals

C D

Relative Risk = (A/A+B)/(C/C+D)

Randomized Clinical Trial

Randomized trial (Prospective)

Study Outcome Occurred

Did not Occur

Exposure or Intervention

A B

No Exposure or Intervention

C D

Relative Risk = (A/A+B)/(C/C+D)

Random Allocation

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 20th 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?

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”.

From the Laboratory to the Population

Genes Cells Animals Humans Populations

Basic Science

ClinicalScience

Epidemiology

Translational Research

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

From the Laboratory to the Population

Genes Cells Animals Humans Populations

Basic Science

ClinicalScience

Epidemiology

And back again

Translational Research

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.

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 Smokers2001-2005

Age-Adjusted Incidence

Age-Adjusted Mortality

Overall Rank

Percent Rank Percent Rank Rate Rank Rate Rank

Kentucky River 65.6 1 35.7 1 124.7 2 99.8 1 5Big Sandy 69.0 3 35.5 2 131.7 1 96.2 2 8

Cumberland Valley 67.8 2 35.5 3 117.2 3 86.0 3 11Gateway 73.7 6 32.0 6 102.1 6 79.9 4 22

Buffalo Trace 73.3 5 33.0 4 96.9 11 78.3 5 25Barren River 78.6 8 31.8 7 105.8 4 78.0 6 25

Lake Cumberland 70.9 4 31.1 10 101.2 7 77.7 7 28Fivco 78.2 7 32.5 5 99.9 8 71.0 10 30

Green River 83.0 11 30.3 11 105.0 5 76.1 8 35Pennyrile 80.1 9 31.3 8 97.2 10 70.1 11 38

Lincoln Trail 82.7 10 31.1 9 96.3 12 66.4 15 46Purchase 83.0 12 28.5 14 97.7 9 69.4 12 47

Northern Kentucky 86.4 15 29.0 12 96.2 13 71.4 9 49Kipda 86.4 14 28.6 13 94.9 14 66.6 14 55

Bluegrass 84.7 13 28.2 15 92.6 15 68.0 13 56

Demographic Characteristics Contribute to

Risk Factors Contribute to

Incidence and Late Stage DX Contribute to

Cancer Mortality

Combining Data from Multiple Sources

Logic Model

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)

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

Number Rate Number Rate

U.S. 87.6 15.1 19.96 292,495 67.0 79.7 229,103 52.5Kentucky 81.0 17.4 30.4 23077 100.5 80.7 16701 73.2

Barren River 78.6 19.1 31.8 1569 105.8 83.1 1148 78.0Big Sandy 69.0 25.2 35.5 1155 131.7 82.9 835 96.2Bluegrass 84.7 16.9 28.2 3449 92.6 81.1 2510 68.0

Buffalo Trace 73.3 22.4 33.0 321 96.9 80.5 256 78.3Cumberland

Valley67.8 28.7 35.5 1590 117.2 81.6 1153 86.0

Fivco 78.2 19.5 32.5 866 99.9 79.1 613 71.0Gateway 73.7 25.2 32.0 442 102.1 79.5 342 79.9

Green River 83.0 15.5 30.3 1284 105.0 80.2 933 76.1Kentucky River 65.6 29.2 35.7 840 124.7 84.4 658 99.8

Kipda 86.4 14.3 28.6 4602 94.9 77.9 3223 66.6Lake

Cumberland70.9 24.3 31.1 1295 101.2 80.2 992 77.7

Lincoln Trail 82.7 14.8 31.1 1291 96.3 79.8 873 66.4Northern Kentucky

86.4 11.4 29.0 1921 96.2 80.8 1413 71.4

Pennyrile 80.1 18.5 31.3 1220 97.2 83.5 873 70.1Purchase 83.0 16.3 28.5 1232 97.7 81.2 879 69.4

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

Percent Rank Percent Rank Rate Rank Rate Rank

Kentucky River 65.6 1 35.7 1 124.7 2 99.8 1 5

Big Sandy 69.0 3 35.5 2 131.7 1 96.2 2 8Cumberland

Valley67.8 2 35.5 3 117.2 3 86.0 3 11

Gateway 73.7 6 32.0 6 102.1 6 79.9 4 22

Buffalo Trace 73.3 5 33.0 4 96.9 11 78.3 5 25

Barren River 78.6 8 31.8 7 105.8 4 78.0 6 25

Lake Cumberland 70.9 4 31.1 10 101.2 7 77.7 7 28

Fivco 78.2 7 32.5 5 99.9 8 71.0 10 30

Green River 83.0 11 30.3 11 105.0 5 76.1 8 35

Pennyrile 80.1 9 31.3 8 97.2 10 70.1 11 38

Lincoln Trail 82.7 10 31.1 9 96.3 12 66.4 15 46

Purchase 83.0 12 28.5 14 97.7 9 69.4 12 47Northern Kentucky

86.4 15 29.0 12 96.2 13 71.4 9 49

Kipda 86.4 14 28.6 13 94.9 14 66.6 14 55

Bluegrass 84.7 13 28.2 15 92.6 15 68.0 13 56

An Example

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

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

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?

Colorectal Cancer Screening in Kentucky

70%

60%

50%

40%

30%2002 2004 2006

58.6%

47.2%43.9%

34.7%

20081999 2010

63.7%63.7%

49th in the U.S.

20th in the U.S.

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

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

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.

Thank You!

QuestionsThe EndContact Information:

Thomas C. Tucker, PhD, MPHtct@kcr.uky.edu

Markey Cancer Center