Transcript Slide 1

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
Topics to be covered
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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 evidencebased 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
Developed Did not
identical mice Disease
Develop
Disease
Exposed
A
B
Animals
Unexposed
Animals
C
Relative Risk = (A/A+B)/(C/C+D)
D
Randomized Clinical Trial
Random
Allocation
Randomized
trial
(Prospective)
Exposure or
Intervention
Study
Outcome
Occurred
A
No Exposure C
or
Intervention
Did not
Occur
B
D
Relative Risk = (A/A+B)/(C/C+D)
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
Basic
Science
Humans
Clinical
Science
Translational Research
Populations
Epidemiology
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
And back again
Genes
Cells
Animals
Basic
Science
Humans
Clinical
Science
Translational Research
Populations
Epidemiology
The ultimate goal of translational cancer research
is the adoption and wide-spread use of evidencebased 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 Consortium (KCC)
Kentucky Cancer Program (KCP)
Lung Cancer by Area Development District in KY, 2005-2009
High School
Current
Age-
Age-
Education 2006Smokers
Adjusted
Kentucky
Cancer
Registry
(KCR)Adjusted
2010
2001-2005
Incidence
Mortality
Area
Development
District
Kentucky River
Big Sandy
Cumberland Valley
Gateway
Buffalo Trace
Barren River
Lake Cumberland
Fivco
Green River
Pennyrile
Lincoln Trail
Purchase
Northern Kentucky
Kipda
Bluegrass
Percent
Rank
65.6
69.0
67.8
73.7
73.3
78.6
70.9
78.2
83.0
80.1
82.7
83.0
86.4
86.4
84.7
1
3
2
6
5
8
4
7
11
9
10
12
15
14
13
Overall
Rank
Percent Rank Rate Rank Rate Rank
35.7
35.5
35.5
32.0
33.0
31.8
31.1
32.5
30.3
31.3
31.1
28.5
29.0
28.6
28.2
1
2
3
6
4
7
10
5
11
8
9
14
12
13
15
124.7
131.7
117.2
102.1
96.9
105.8
101.2
99.9
105.0
97.2
96.3
97.7
96.2
94.9
92.6
2
1
3
6
11
4
7
8
5
10
12
9
13
14
15
99.8
96.2
86.0
79.9
78.3
78.0
77.7
71.0
76.1
70.1
66.4
69.4
71.4
66.6
68.0
1
2
3
4
5
6
7
10
8
11
15
12
9
14
13
5
8
11
22
25
25
28
30
35
38
46
47
49
55
56
Combining Data from Multiple Sources
Demographic
Characteristics
Contribute to
Risk Factors
Contribute to
Incidence and
Late Stage DX
Contribute to
Cancer
Mortality
Logic Model
What are the common sources of data that
can be used for defining the cancer burden?
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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
U.S.
Kentucky
Barren River
Big Sandy
Bluegrass
Buffalo Trace
Cumberland
Valley
Fivco
Gateway
Green River
Kentucky River
Kipda
Lake
Cumberland
Lincoln Trail
Northern
Kentucky
Pennyrile
Purchase
High
Poverty
School
Rate (%)
Education
2006(%)
2010
2006-2010
Age-Adjusted
Age-Adjusted
Smoking
Incidence
Late Stage
Mortality
Rate (%)
Incidence
2001%
Number Rate
Number Rate
2005
87.6
81.0
78.6
69.0
84.7
73.3
15.1
17.4
19.1
25.2
16.9
22.4
19.96
30.4
31.8
35.5
28.2
33.0
292,495
23077
1569
1155
3449
321
67.0
100.5
105.8
131.7
92.6
96.9
79.7
80.7
83.1
82.9
81.1
80.5
229,103
16701
1148
835
2510
256
52.5
73.2
78.0
96.2
68.0
78.3
67.8
28.7
35.5
1590
117.2
81.6
1153
86.0
78.2
73.7
83.0
65.6
86.4
19.5
25.2
15.5
29.2
14.3
32.5
32.0
30.3
35.7
28.6
866
442
1284
840
4602
99.9
102.1
105.0
124.7
94.9
79.1
79.5
80.2
84.4
77.9
613
342
933
658
3223
71.0
79.9
76.1
99.8
66.6
70.9
24.3
31.1
1295
101.2
80.2
992
77.7
82.7
14.8
31.1
1291
96.3
79.8
873
66.4
86.4
11.4
29.0
1921
96.2
80.8
1413
71.4
80.1
83.0
18.5
16.3
31.3
28.5
1220
1232
97.2
97.7
83.5
81.2
873
879
70.1
69.4
High School Education (2007-2011)
vs Smoking Rate (2001-2005)
37
High School Education vs Smoking
Rate in 2001-2005
Linear (High School Education vs
Smoking Rate in 2001-2005)
35
Percent Smoker
R² = 0.8204
33
31
29
27
65
70
75
80
Percent High School Education
85
90
Smoking (2001-2005) vs Lung
Cancer Incidence (2007-2011)
135
Smoking (2001-2005) vs Lung
Cancer Incidence
Linear (Smoking (2001-2005) vs
Lung Cancer Incidence)
130
Lung Cancer Incidence
125
R² = 0.7015
120
115
110
105
100
95
90
28
29
30
31
32
33
34
Percent Smoker (2001-2005)
35
36
37
Lung Cancer Incidence vs Mortality (2007-2011)
105
Lung Cancer Incidence versus Mortality
Linear (Lung Cancer Incidence versus Mortality)
100
R² = 0.8795
Mortality Rate
95
90
85
80
75
70
65
90
100
110
Lung Cancer Incidence
120
130
Lung Cancer by Area Development District in KY, 2007-2011
Area
Development
District
High School
Education,
2006-2010
Current
Smoker,
2001-2005
AgeAdjusted
Incidence
AgeAdjusted
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
Cumberland
Valley
Gateway
69.0
3
35.5
2
131.7
1
96.2
2
8
67.8
2
35.5
3
117.2
3
86.0
3
11
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
Northern
Kentucky
Kipda
83.0
12
28.5
14
97.7
9
69.4
12
47
86.4
15
29.0
12
96.2
13
71.4
9
49
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%
63.7%
58.6%
60%
50%
40%
30%
63.7%
43.9%
47.2%
34.7%
1999
49th
in the U.S.
2002
2004
2006
2008
2010
20th
in the U.S.
P<.05
Source: http://cancer-rates.info/ky, Accessed January 2014
P<.05
Source: 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!
Questions
Contact Information:
The End
Thomas C. Tucker, PhD, MPH
[email protected]
Markey Cancer Center