Transcript Disease Activity Measure - Brigham and Women`s Hospital

Implementation of TTT in RA
Through a Learning Collaborative:
The TRACTION Trial
Daniel H. Solomon, MD, MPH
Elena Losina, Bing Lu, Agnes Zak, Cassandra
Corrigan, Sara B. Lee, Jenifer Agosti, Asaf Bitton,
Leslie R. Harrold, Ted Pincus, Helga Radner, Zhi Yu,
Josef S. Smolen, Liana Fraenkel, Jeffrey N. Katz
Division of Rheumatology
Division of Pharmacoepidemiology
Brigham and Women’s Hospital
Harvard Medical School
NIH-P60-AR047782
Disclosures
•
•
•
•
•
NIH: NIAMS, NIA, NHLBI
PCORI
A&R Deputy Editor
FDA Arthritis Advisory Committee
Research grants: Amgen, Lilly, Pfizer, BMS,
Genentech, Astra Zeneca, CORRONA
• Pfizer, Executive Committee PRECISION trial (unpaid)
• UpToDate royalties
• No personal financial relationship with any
pharmaceutical company
Acknowledgment
Practice Sites
Team Members
Cedars Sinai (Venturapali)
Venturapali, Gaggi, Uy, Bustos, Vasquez
Loyola
Tehrani, Ostrowski, Briones, Murphy
North Shore
Grober, Malik, Woodrick, Lynn, Sun, Drevlow, Zaacks, Bilbrey, Chavez,
Casey, Gan, Myers
Park Nicollet
Paisansinsup, Shousboe, Glickstein, Steele
University of Kansas
Lindsley, Schmidt, Colbert, Springer, Bhadbhade, Parker, Estephan,
McMillian, Heneghan
University of Kentucky
Lohr, Hanaoka, Lightfoot, Jenkins, Baker, Bisono, Wafford, Wiard, Lenert,
Howard
University of Houston
Scholz, McCray, Barnes, Tan, Homann
University of Vermont
Hynes, Bethina, Kennedy, Lau, Edwards, Libman, Farely
Univeristy of Virginia
Kimpel, Lewis, D’Souza, Potter, Carlson, Mosteanu, Khalique, Khurana,
Swamy
UTMB -- Galveston
Murthy, Musty, Rudrangi, Ganti, Gonzalez, McCullum
Vanderbilt
Annapureddy, Kroop, Hayden
Background
Methods
Results/Conclusions
Background: Treat to Target (TTT)
1.
2.
The primary target for treatment of rheumatoid arthritis should be a state of clinical remission. (III)
Clinical remission is defined as the absence of signs and symptoms of significant inflammatory
disease activity.(IV)
3. While remission should be a clear target, based on available evidence low disease activity may be
an acceptable alternative therapeutic goal, particularly in established long-standing disease.(Ib)
4. Until the desired treatment target is reached, drug therapy should be adjusted at least every
3months.(Ib)
5. Measures of disease activity must be obtained and documented regularly, as frequently as monthly
for patients with high/moderate disease activity or less frequently (such as every 3–6months) for
patients in sustained low disease activity or remission.(IV)
6. The use of validated composite measures of disease activity, which include joint assessments, is
needed in routine clinical practice to guide treatment decisions.(IV)
7. Structural changes and functional impairment should be considered when making clinical decisions,
in addition to assessing composite measures of disease activity.(IV)
8. The desired treatment target should be maintained throughout the remaining course of the
disease.(III)
9. The choice of the (composite) measure of disease activity and the level of the target value may be
influenced by consideration of co-morbidities, patient factors and drug-related risks.(IV)
10. The patient has to be appropriately informed about the treatment target and the strategy planned
to reach this target under the supervision of the rheumatologist.(IV)
1. The primary target for treatment of rheumatoid
arthritis should be a state of clinical remission.
2.Until the desired treatment target is reached, drug
therapy should be adjusted at least every 3months.
3. The use of validated composite measures of disease
activity, which include joint assessments, is needed in
routine clinical practice to guide treatment decisions.
4. The patient has to be appropriately informed about
the treatment target and the strategy planned to reach
this target under the supervision of the
rheumatologist.
Ref: Smolen et al, ARD, 2010 and 2015
Background
Methods
Results/Conclusions
Data Supporting TTT
• At least 10 RCTs have found that TTT produces better
outcomes than usual care in RA, including reduced
pain, improved function, better DAS scores, and less
radiographic progression.
• The treatment algorithm used has varied and the
exact schedule of visits has varied.
• Most trials have occurred in Europe.
Background
Methods
Results/Conclusions
TTT Adherence
• Patients with RA in
Australia with DAS28
• 584 were in MDA or HDA
and had no change in
DMARDs
• Rheumatologists
recorded barriers to
treatment change
Barriers to Treatment Change
%
Irreversible joint damage
20
Patient driven undertreatment
15
MD driven undertreatment
10
Non-inflammatory MSK pain
9
Waiting for DMARD response
9
Safety or contraindications
8
Comorbidities
7
DMARD resistant RA
6
Other*
16
*Logistics, reimbursement, pregnancy
Tymms, AC&R, 2014
Background
Methods
Results/Conclusions
Methods: Design
• Cluster randomized controlled trial
• Wait list control (step wedge design)
Background
Methods
Results/Conclusions
Intervention
• Learning Collaborative (LC)
–
–
–
–
Developed by Institute for Healthcare Improvement
Team learning with frequent measurement
Rapid cycle improvement (PDSA cycles)
Central team coaches with each team contributing to
the collaborative
– Central website for sharing PDSA cycles, results,
questions, resources
– Face-to-face meeting to start with monthly webinars
– Faculty developed a change package which guided LC
Background
Methods
Results/Conclusions
Change Package
Shared decision
making
Disease activity
measurement
Treat to target
Background
Methods
Results/Conclusions
Site Recruitment
• E-mail contact with smaller academic programs plus other practices
• 25 rheumatology practices responded
• Telephone contact to describe program, assess interest, and whether practice
already implemented TTT
• 12 sites expressed interest and were randomized
• 1 site dropped out before start of first phase
Patient Insurance (%)
Treatment Arm
Site location
Intervention
Chicago IL
3
No
No
Total
Patients
Seen in 2014
1800-2000
Houston TX
5
Yes
No
1000
20
20
55
5
Suburban Chicago, IL
10
No
No
920
35
5
59
1
Louisville KY
9
Yes
Yes
1850
23
33
38
3
Burlington VT
5
Yes
Yes
NA
NA
NA
NA
NA
Minneapolis MN
6
No
No
2300
13
12
72
3
Los Angeles CA
2
No
Yes
350
60
1
35
4
Kansas City KS
10
Yes
Yes
500
40
10
45
5
Galveston TX
6
Yes
No
4000
40
15
40
5
UVA Rheumatology
5
No
Yes
550
25
10
50
5
Nashville TN
2
No
No
250
25
5
60
10
Control
Total
Providers
Trainees
MidLevels
Medicare
Medicaid
Commercial
None
31
16
49
4
Background
Methods
Results/Conclusions
Measurement of TTT Adherence
TTT Adherence: 4 components based on visit note
1.
2.
3.
4.
Treatment target
Disease activity measure
Follow TTT paradigm (or if not, document why not)
Shared-decision making if change in Target or change in treatment
Implementation Score
– Ordinal score using above 4 components
– Converted into a percentage
Patient sampling
– Providers participating in at least one learning session
– >40 patients/site with RA with a visit during periods of interest
– Sampled visits in 3-months prior to intervention and last 3-months of
intervention period
Background
Methods
Results/Conclusions
Statistical Analyses
• Compare baseline patient characteristics
• Calculate TTT Implementation Score and
components for each visit
• Aggregate TTT visit Scores by provider,
practice site and treatment assignment
• Estimate change from baseline period to
follow-up period by treatment assignment
• Compare changes by treatment arm after
accounting for clustering (GLM)
Background
Methods
Results/Conclusions
Table 1: Baseline subject characteristics
Control
(n = 321)
Learning
Collaborative
(n = 320)
N (%) unless noted
Age*, years, mean
BMI*, kg/m2, mean
Female sex
RA duration*, years
≤2
2-5
6-10
>10
Serologic status*
Positive
Use of synthetic DMARDs
Use of biologic DMARDs
Comorbidity index, mean ( SD)
Joint erosion
Yes
Total medications
0
1-5
6-10
10+
60
30.1
78
60.
29.4
79
16
29
22
34
26
25
24
25
P-value
0.75
0.24
0.72
0.12
0.15
76
77
41
1.33
82
81
46
1.28
53
60
0.25
0.16
0.24
0.19
0.16
0
13
32
55
0.3
17
37
47
Background
Methods
Results/Conclusions
Figure 1: TTT Implementation
Control sites
70
Intervention sites
p <.0001
60
p =0.004
Percent adherence
50
40
30
20
p = 0.93
10
0
Baseline
Follow-up
Change in
implementation score
Background
Methods
Results/Conclusions
Table 2: TTT Implementation Components
100
100
Target
80
80
60
P = 0.065
40
20
20
0
0
Baseline
Follow-up
Change
Shared Decision Making
80
P < 0.001
40
20
20
0
0
Follow-up
Change
Follow-up
Change
Treatment Decision
60
40
Baseline
Baseline
100
80
60
P = 0.002
60
40
100
Disease Activity Measure
P = 0.064
Baseline
Follow-up
Change
Background
Methods
Results/Conclusions
Percentage of visits fully adherent with TTT
Figure 2: Full Adherence with TTT
100
Control
80
Learning collaborative
60
P = 0.045
40
25.9%
20
P = 0.25
0.0% 0.6%
Baseline
5.6%
Follow-up
Background
Methods
Results/Conclusions
Table 3: Resource use and adverse events
Control
(n = 321)
Learning
Collaborative
(n = 320)
P-value*
Number of tests or adverse events
(mean number per patient)
Monitoring laboratory tests (CBC, CMP)
2614 (8.14)
2591 (8.10)
0.67
CRP or ESR
788 (2.45)
607 (1.90)
0.66
Plain x-ray of musculoskeletal system
308 (0.96)
247 (0.77)
0.96
CT of musculoskeletal system
6 (0.019)
12 (0.038)
0.50
MRI of musculoskeletal system
14 (0.044)
16 (0.050)
0.77
Adverse events (GI, renal, liver, infxn, etc)
138 (0.43)
83 (0.26)
0.04
Background
Methods
Results/Conclusions
Table 4: Supplementary findings
Follow-up measure
Disease activity measure
Control
(n = 69)
Intervention
(n = 284)
N (%)
Remission
18 (26.1%) 115 (40.5%)
Low
19 (27.5%)
73 (25.7%)
Moderate
16 (23.2%)
59 (20.8%)
High
19 (23.2%)
37 (13.0%)
Visits w/ DMARD changes
Control Intervention
(n = 321)
(n = 320)
N (%)
0- 30%
198 (62%)
201 (63%)
>30 – 79%
101 (31%)
64 (20%)
22 (7%)
55 (17%)
80-100%
P-value
0.07
P-value
0.0001
Background
Methods
Results/Conclusions
Strengths/Limitations
• RCT across the US, but relatively small and
participants unblinded to treatment.
• Objective assessment tool to determine TTT
adherence with high reliability, but assessors
unblinded to treatment assignment.
• Complex intervention (Learning Collaborative)
but likely required for behavior change.
Background
Methods
Results/Conclusions
Conclusions
1. Baseline TTT implementation was very low.
– Even in these mostly academic programs.
2. A Learning Collaborative was an effective
intervention to improve implementation of TTT.
– But, few visits (25%) were fully adherent.
3. Explicit treatment target and following paradigm
were most common deficiencies.
4. No excess in resource use or adverse events
observed.
Background
Methods
Results/Conclusions
Implications
• More should be done to enhance adoption of TTT in
the US.
• A Learning Collaborative is a proven intervention to
enhance adoption of TTT, but it requires investment of
time by practices.
– Should professional societies promote TTT Learning
Collaboratives?
– How can practices be incentivized to participate in
Learning Collaboratives or other QI efforts?
• Learning Collaboratives could be developed for other
QI areas in rheumatology, i.e., GIOP, TTT in gout.
Acknowledgment
Practice Sites
Team Members
Cedars Sinai (Venturapali)
Venturapali, Gaggi, Uy, Bustos, Vasquez
Loyola
Tehrani, Ostrowski, Briones, Murphy
North Shore
Grober, Malik, Woodrick, Lynn, Sun, Drevlow, Zaacks, Bilbrey, Chavez,
Casey, Gan, Myers
Park Nicollet
Paisansinsup, Shousboe, Glickstein, Steele
University of Kansas
Lindsley,
Schmidt,
Colbert,
Martinez,,Engelman,
Maz, Springer,
Lindsley, McMillian,
Schmidt, Colbert,
Springer,
Bhadbhade
Parker, Estephan,
Kern,
Parker,
Estephan, Magadan, Crum, Gengelbach, Kunkel
McMillian,
Heneghan
University
University of
of Kentucky
Kentucky
Lohr,
Wiard,
Lohr, Hanaoka,
Hanaoka, Lightfoot,
Lightfoot, Jenkins,
Jenkins, Baker,
Baker, Bisono,
Bisono, Wafford,
Wafford, Beeson
Wiard, Lenert,
Lenert,
HowardHoward
University
University of
of Houston
Houston
University
University of
of Vermont
Vermont
Scholz,
Scholz, McCray,
McCray, Barnes,
Barnes, Tan,
Tan, Homann
Homann
Univeristy
Univeristy of
of Virginia
Virginia
Kimpel,
Kimpel, Lewis,
Lewis, D’Souza,
D’Souza, Potter,
Potter, Carlson,
Carlson, Mosteanu,
Mosteanu, Khalique,
Khalique, Khurana,
Khurana,
Swamy
Swamy
UTMB
UTMB --- Galveston
Galveston
Vanderbilt
Vanderbilt
Murthy,
Murthy, Musty,
Musty, Rudrangi,
Rudrangi, Ganti,
Ganti, Gonzalez,
Gonzalez, McCullum
McCullum
Hynes,
Hynes, Bethina,
Bethina, Kennedy,
Kennedy, Lau,
Lau, Edwards,
Edwards, Libman,
Libman, Farely
Farely
Annapureddy,
Annapureddy, Kroop,
Kroop, Golchha,
Hayden Hayden
Thanks ([email protected])
Disease activity at follow-up
Control
(n = 69)
Disease activity measure
category
Remission
Intervention
(n = 284)
N (%)
18 (26.1%)
115 (40.5%)
Low
19 (27.5%)
73 (25.7%)
Moderate
16 (23.2%)
59 (20.8%)
High
19 (23.2%)
37 (13.0%)
P-value
0.07
Note: These analyses were conducted among the two control sites that routinely
included disease activity measures in their medical record notes as well as all of the
intervention site visits with disease activity measures noted at follow-up. The disease
activity measures included the RAPID-3 and CDAI. P-value from chi-square test.
Back-up slide 1
Month
Activity
Focus/Content
-1
Pre-work
Baseline self-assessment measures
0
Learning Session 1*
Change Package, treat-to-target principles, process improvement methods, PDSAs,
disease activity measures, team building
1
Learning Session 2
Updates on sites’ PDSAs, monthly self-assessment measures
2
Learning Session 3
Updates on sites’ PDSAs, monthly self-assessment measures, disease activity measures
3
Learning Session 4
Updates on sites’ PDSAs, monthly self-assessment measures, documentation
3-4
Coaching Call 1
Individualized team call to summarize progress, discuss challenges, and provide guidance
for future PDSA cycles through written feedback
4
Learning Session 5
Updates on sites’ PDSAs, monthly self-assessment measures, shared decision-making
5
Learning Session 6
Updates on sites’ PDSAs, monthly self-assessment measures, quality improvement
projects
6
Learning Session 7
Updates on sites’ PDSAs, monthly self-assessment measures, sustainability and team
dynamics
7
Learning Session 8
Updates on sites’ PDSAs, monthly self-assessment measures, treat-to-target
7-8
Coaching Call 2
Individualized team call to summarize progress, discuss challenges, and provide guidance
for spread and sustainability through written feedback
8
Learning Session 9
Updates on sites’ PDSAs, monthly self-assessment measures, spread and sustainability
Back-up slide 2
Sample Size Considerations
Intra-cluster
correlation†
Intervention Arm
% Improvement
0.1
20%
30%
40%
20%
30%
40%
20%
30%
40%
0.2
0.3
Control Arm
% Improvement
0%
5%
10%
2
4
26
2
2
3
2
2
2
2
6
NA
2
2
4
2
2
2
2
12
NA
2
2
5
2
2
5
†: Intra-cluster correlation measured at the provider level.
NA: The sample size cannot be estimated with small group difference and large ICC.