dr staffan lindblad: clinical development utilizing registers in novel ways in clinical arthritis
TRANSCRIPT
Clinical development Utilizing Registers in novel ways in chronic arthritis
Staffan Lindblad M.D. Medical Management Centrum, Karolinska Institutet and Department of Rheumatology, Karolinska University hospital The C.U.R. project
Crossing the quality chasm
IOM; Crossing the Quality Chasm: A New Health System for the 21st Century, 2001.
Safe
Timely
Effective
Efficient
Equitable
Patient oriented
”The future is bright…” Safe
Timely
Effective
Efficient
Equitable
Patient oriented
I feel secure despite risks of my drugs
I can see when I need a new drug
I can monitor the effect of my drug
I can manage myself much more
I compare my measures with others
I work together with my doctor now
The empowered care provider
Safe
Timely
Effective
Efficient
Equitable
Patient oriented
Side effects can be reported at the visit
Patient needs based clinics
National outcome measures for all
Costs are reduced, results are better
Benchmarking in national quality registers
Patients share the work – task shifting
This is spreading all over Sweden
This is spreading all over Sweden
We use the unique Swedish advantage of national quality registers describing regular clinical practice – what characterizes each patient – which treatments are given – the health outcomes generated
Clinical registers
Rheumatology
Information generator
Clinical trials and studies
Industry bridge
Clinical research
Translational research
Health economy
Care quality improvement
Patient engagement
Law and ethics
Clinical registers
Rheuma
Clinical registers
Rheumatology
Clinical development Utilizing Registers
C.U.R. project
Surveillance drugs
medtech
Swedish Biologics Quality Register
General population controls
Inpatient Register RA
Swedish Rheumatoid Arthritis (RA) Register
Swedish national mandatory registers can be linked to national quality registers analyzing co-morbidity
Register linkages
Increase of tuberculosis inRA patients with TNF blocker
1
General Population
RA, no TNF-antagonist
RA with TNF antagonist
Relative Risk
2
9
1
-
2
9
No increase of lymphoma in RA patients with TNF blocker
Information generator
Clinical trials and studies
Industry bridge
Clinical research
Translational research
Health economy
Care quality improvement
Patient engagement
Law and ethics
Clinical registers
Rheuma
Clinical registers
Rheumatology
The C.U.R. project
Surveillance drugs
medtech
Kliniska register
Surgery
Information generator
Clinical trials and studies
Industry bridge
Clinical research
Translational research
Health economy
Care quality improvement
Patient engagement
Law and ethics
Kliniska register
Primary Care
Kliniska register
Pediatrics
Kliniska register
Neuro
Clinical registers
Rheuma
etc…
Kliniska register
Primary Care
Kliniska register
Surgery
Kliniska register
Pediatrics
Kliniska register
Neurology
Clinical registers
Rheumatology
Surveillance drugs
medtech
Clinical development Utilizing Registers – the CUR platform for care, research and industrial innovation
Information generator
Care quality improvement
Patient engagement
Clinical registers
Rheuma
Clinical registers
Rheumatology
Värdebaserad vård
Project background
• Treatment guidelines of the Swedish Society for Rheumatology are based on evidence from meta-analysis of clinical drug trials
• These guidelines are linked to the rheumatology register’s comprehensive patient overview visualising disease course and effects of treatments prescribed
Improving health in rheumatoid arthritis seen as decreasing inflammation (CRP) over 10 years
0
5
10
15
20
25
30
35
40
45
2000
Ja
nM
arM
aj Jul
Sep
Nov
2001
Ja
nM
arM
aj Jul
Sep
Nov
2002
Ja
nM
arM
aj Jul
Sep
Nov
2003
Ja
nM
arM
aj Jul
Sep
Nov
2004
Ja
nM
arM
aj Jul
Sep
Nov
2005
Ja
nM
arM
aj Jul
Sep
Nov
2006
Ja
nM
arM
aj Jul
Sep
Nov
2007
Ja
nM
arM
aj Jul
Sep
Nov
2008
Ja
nM
arM
aj Jul
Sep
Nov
2009
Ja
nM
arM
aj
Med
elvä
rde
av C
RP
Medel CRP, Falun (N=8 405) Medel CRP, Riket-Falun (N=155 521)
• Treatment guidelines of the Swedish Society for Rheumatology are based on evidence from meta-analysis of clinical drug trials
• These guidelines are linked to the rheumatology register’s comprehensive patient overview visualising disease course and effects of treatments prescribed
• Trial patients and drug protocols are not typical for the every day clinical situation
• Current patient overview in the rheumatology register build on evidence from the single patient only not utilizing the entire medical information available in the register
Project background
Predictive modeling in real time
Aim
• Identification of the optimal treatment for an individual patient directly during the clinical visit
Specific aims
• Development of a predictive model based on the rheumatology registry data (45.000 pats, 300.000 visits)
• Development of an on-line application supporting both a medical provider and a patient during the visit
• A predictive model for treatment decision support has been developed and tested in rheumatoid arthritis
• Variables found to be the most influencing are: doctor‘s global evaluation, disease duration, gender, DAS-28, HAQ, and interactions between DAS-28 & combination-of-drugs as well as disease duration & combination-of-drugs.
Predictive modeling in real time
Predictive modeling in real time
Implementation on the Internet
• Probability that a particular patient will reach a significantly lower or at least unchanged DAS-28 value at the next clinical visit if treated with the proposed combination of drugs
Predictive modeling in real time Tasks to solve – Future potentials
• Improve graphical presentation of the modeling results
• Find better methods to evaluate probabilities despite incomplete data in the voluntary register
• Include effective treatments not yet fully known; a novel drug just approved or one seldom used, which drugs do not appear on the list in the current model
• Future use of two graphs of “combinations of drugs”
– Most frequently used “combinations of drugs”
– Most effective “combinations of drugs”
Success is a journey, not a goal
The 3T:s road map
The ”3T’s” road map to transform US health care, Dougherty D et al, JAMA 2008, 299, 2319
33
Infla
mm
atio
n
40 30 50
Chronic destruction
Unspecific arthritis/arthragia
Autoimmunity
Normal
Diagnosis by patient
Diagnosis by physician
Understanding etiology and pathogenesis of immmune mediated diseases such as rheumatoid arthritis, requires longitudinal studies
60
genes Time
Courtesy of Rikard Holmdahl
34
Infla
mm
atio
n
40 30 50
Chronic destruction
Unspecific arthritis/arthragia
Autoimmunity
Normal
Diagnosis by patient
Diagnosis by physician
Understanding etiology and pathogenesis of immmune mediated diseases such as rheumatoid arthritis, requires longitudinal studies
60
genes
Courtesy of Rikard Holmdahl
Time
35
Initiation of Today´s treatment
Chronic treatment
Results of Today´s treatment
Our patients have improved and have a much better life But prevention and cure is still lacking
Infla
mm
atio
n
40 30 50 60
genes
Chronic destruction Criterion-defined disease
Courtesy of Rikard Holmdahl
Cured
Prevention & cure
The treatments we want
Chronic treatment
Repair
Development of new methods for prevention and treatment is dependent on understanding of etiology and molecular pathogenesis
Infla
mm
atio
n
40 30 50 60
genes
Chronic destruction
Courtesy of Rikard Holmdahl
Disappearance of symtoms, normalized function
Rheumatoid arthritis – a prototype for a complex disease
influenced by genes, immunity and environment