Retrospective Case Studies of Translational

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Transcript Retrospective Case Studies of Translational

Retrospective Case Studies of
Translational Research
William Trochim, PhD, Director of Evaluation,
Cornell University and Weill Cornell CTSC
Cathleen Kane, Assistant Director of Evaluation,
Cornell University and Weill Cornell CTSC
Weill Cornell Medical College
Translational Process:
Retrospective Case Study
● Goals
 Understand the entire translational process (we don’t have 17
years!)
 Develop a standardized protocol for retrospective translational
case studies
● Approach: mixed methods
 Evolutionary perspective
 Bibliometrics and key marker measurement (e.g., patents)
 Intensive Interviewing
● Case selection criteria
 Had to be a successful translation
 Recent enough to be documented and interviewed
 CTSC partners had to have key involvement
Translational Process:
Retrospective Case Study
May 28, 2001
Translational Case Studies:
Gleevec
Translational Markers by Year
14
Systematic reviews
FDA approval events
Clinical trial publications
Clinical trial starts
Group in Basel, Switzerland discover
Patenting events
Origin Studies
chemical (gleevec or imatinib) that was
12
an ABL (tyrosine kinase) inhibitor
8
molecular cloning of the breakpoint allowed the
molecular definition of the genes; one was the very
well studied Abelson Virus (ABL) a tyrosine kinase
6
Years (1960-2010)
2010
2008
2006
2004
2002
2000
1998
1996
1994
1992
1990
1988
1986
1984
1982
1980
1978
1976
1974
1972
1970
1964
1962
0
1968
chromosomal banding dyes
2
1966
4
first description of the
Philadelphia chromosome
1960
Number of Events)
10
Translational Case Studies:
Gleevec
Translational Markers by Year
Dr. Charles
Sawyer
14
Systematic reviews
4
“it was in 1998 and then the drug was clearly working a year later and we presented the first data in mid-’99
and then late 1999 was when we launched the phase
studies and then the drug was approved in 2001
Years2(1960-2010)
2008
2006
2004
2002
2000
1998
1996
1994
1992
1990
1988
1986
1984
1982
1980
1978
1976
1974
1972
1970
1968
“the FDA…embraced this in all the right ways…A very important component of getting rapid approval was the fact that
another drug that came before called Interferon that was standard of care had used survival as the endpoint…one trial
which was done in the ‘90’s allowed all future trials…to use…the surrogate endpoint for approval so that’s a very
important component of the rapid (FDA) approval time.
1966
0
“…anyway this group of patients self-organized and
created almost the entire CML patient population petition
that went straight to the CEO who…had no idea how
important it was until that and then it was ‘all right we
have a problem because we need to scale this really
fast, we haven’t manufactured enough drug and we don’t
have enough manufacturing capacity right now to just do
it’ so they had to outsource a lot of drug synthesis and so
forth but you know it all worked out.”
2010
6
2
“We told the drug company (CIBA Geigy, now
Novartis)…this drug really works and not only is it working,
it works better than any other drug in this space has ever
worked so you have to do something now…They asked
‘why do we want to treat this disease for which there’s only
5000 new patients a year and this is just totally not a big
pharma project?’”
“I had to start being very careful in my
physician/patient conversations because they
would all be on the web that night when I would get
home. So I see 20 patients in clinic, I could go
home, be exhausted, log on to NewCMLdrug.com
and patients would say “well Dr. Sawyer today told
me blah blah blah” and then they’d say “well Dr.
Druker tell me blah blah blah’”
1964
8
1960
Number of Events)
10
1962
12
“…I was in California in this lab that had cloned
FDAHe
approval
events was in this other lab
the gene.
(Brian Druker)
Clinical
trial
publications
and he’s hearing about the drug and interested
trial starts
in this Clinical
question…he
invited me to be the guest
Patenting
events
speaker…and then
he showed me all this data
Origin
and said
‘youStudies
know do you think we should try to
do a clinical trial?’ ‘Have you ever done a
clinical trial?’ ‘No, have you?’ ‘No’ (chuckle).”
Translational Case Studies:
Gleevec
Translational Markers by Year
14
Systematic reviews
CML patients petition drugmaker
FDA approval events
FDA approval
Clinical trial publications
First clinical trial
Clinical trial starts
Group in Basel, Switzerland discover
Patenting events
Origin Studies
chemical (gleevec or imatinib) that was
12
an ABL (tyrosine kinase) inhibitor
8
molecular cloning of the breakpoint allowed the
molecular definition of the genes; one was the very
well studied Abelson Virus (ABL) a tyrosine kinase
6
Years (1960-2010)
2010
2008
2006
2004
2002
2000
1998
1996
1994
1992
1990
1988
1986
1984
1982
1980
1978
1976
1974
1972
1970
1964
1962
0
1968
chromosomal banding dyes
2
1966
4
first description of the
Philadelphia chromosome
1960
Number of Events)
10
Translational Case Studies:
Gleevec
1975-2009 Age-Adjusted U.S. Mortality Rates, All Ages (Rates are per 100,000 and are age-adjusted to the 2000 US Std Population)
Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. http://seer.cancer.gov/faststats. (Accessed on 4-9-2013)
Systematic reviews
CML patients petition drugmaker
FDA approval events
FDA approval
Clinical trial publications
First clinical trial
Clinical trial starts
Group in Basel, Switzerland discover
Patenting events
Origin Studies
chemical (gleevec or imatinib) that was
12
10
an ABL (tyrosine kinase) inhibitor
8
molecular cloning of the breakpoint allowed the
molecular definition of the genes; one was the very
well studied Abelson Virus (ABL) a tyrosine kinase
6
0.2
Years (1960-2010)
2010
2008
2006
2004
2002
2000
1998
1996
1994
1992
1990
1988
1986
1984
1982
1980
1978
1976
1974
1972
1970
1968
1964
0
1962
0
0.8
0.4
chromosomal banding dyes
2
1966
4
1
0.6
first description of the
Philadelphia chromosome
1960
Number of Events)
1.2
Translational Markers by Year
14
Lessons and Implications
● Lessons





The “start point” and “end point” problems remain key
“Punctuated” activity, not continuous
Interdisciplinary collaboration was key
Patient community self advocacy was key
Methodological development was key
● Implications
 Integrating rich case study data with bibliometrics and
records analysis was essential
 Retrospective case studies can be done and can yield
valuable insights about translation
Postscript
February 1, 2016
Pharmacies across the U.S. will begin receiving shipments of a
generic form of the revolutionary cancer pill Gleevec this week
after the drug lost its patent protection on Monday.
The generic version of drug, known as imatinib, is likely to cost
about 30 percent less than brand-name Gleevec, says Kal
Sundaram, the CEO of Sun Pharmaceuticals, the Mumbai, Indiabased company that will make the first generic.