Post on 21-Mar-2020
Cost-Effectiveness Analysis of:
Remote Monitoring of Implantable Cardioverter Defibrillators and Cardiac Resynchronization Therapy Defibrillators
CADTH SymposiumApril 17, 2018
Man Wah Yeung, Vania Costa, Lindsey Falk,
Nancy Sikich, Irfan Dhalla, Vivian Ng
1
All co-authors have no actual or potential conflict of
interest in relation to this topic or presentation.
Disclosure
2
The Provincial Advisor on the Quality of Health Care in Ontario, Canada
3
Clinical Evidenceclinical evidence review
HTA
Health Services
and Medical
Devices
Health Economicseconomic evidence review
economic evaluation
budget impact analysis
Patient Perspectivepublic and patient
engagement
Ontario Health
Technology Advisory
Committee (OHTAC)
in support of HQO
Funding
Recommendations
Ontario Ministry of
Health and Long-
Term Care
Health Technology Assessment at
Health Quality Ontario
http://www.hqontario.ca/Evidence-to-Improve-Care/Health-Technology-Assessment
4
Clinical Evidenceclinical evidence review
HTA
Health Services
and Medical
Devices
Health Economicseconomic evidence review
economic evaluation
budget impact analysis
Patient Perspectivepublic and patient
engagement
Ontario Health
Technology Advisory
Committee (OHTAC)
in support of HQO
Funding
Recommendations
Ontario Ministry of
Health and Long-
Term Care
Health Technology Assessment at
Health Quality Ontario
http://www.hqontario.ca/Evidence-to-Improve-Care/Health-Technology-Assessment
5
Project Team
• Clinical Epidemiologist: Vania Costa
• Health Economist: Man Wah Yeung
• Secondary Health Economist: Lindsey Falk
• Senior Health Economist: Shawn Xie
• Patient Engagement Analyst: Jenny Gilbert and Arshia Ali
• Medical Librarian: Corinne Holubowich
• Business Analyst: Paul Kolodziej
• Project Manager: Claude Soulodre
• Manager, Health Economic Evaluation: Vivian Ng
• Manager, Clinical Reviews: Sarah McDowell
6
Stakeholder Consultations
• CorHealth Ontario (previously Cardiac Care Network)
• Ontario Ministry of Health and Long-Term Care
• Manufacturer representatives
• Clinical experts (nurse, electrophysiologist/ cardiologist)
• Health economic experts from Ontario Health
Technology Advisory Committee, OHTAC
7
Background:Implantable Cardioverter-Defibrillator (ICD)
• Used for primary and secondary prevention of sudden cardiac
death, which is caused by ventricular tachyarrhythmias
• ICD monitors the patient’s heart rhythm, detects irregularities and
corrects them with electrical impulses
• Applies an electrical shock in order to restore normal rhythm when a
life-threatening arrhythmia is detected
Image Source: National Heart, Lung, and Blood Institute; National Institutes of Health; U.S.
Department of Health and Human Services
8
Background:Cardiac Resynchronization Therapy
with Defibrillator (CRT-D)
• Used in patients with advanced heart failure with low ejection
fraction, and at risk for arrhythmias despite optimal medical therapy
• CRT monitors the patient’s heart rhythm, detects irregularities and
corrects them with electrical impulses
• Improves the synchronized contraction of the ventricles
Image Source: National Heart, Lung, and Blood Institute; National Institutes of Health; U.S.
Department of Health and Human Services
9
Usual Care: In-Clinic Visits
• Programmer wand
• Physician reads the data stored in the ICD, CRT-D (e.g.,
arrhythmias, device malfunction)
• Clinical examination, assessment of signs and symptoms,
and medication use
• Usually scheduled every 6 months during maintenance phase
(i.e., 3 months after successful implantation)
• Additional visits may also occur if needed
10
Remote Monitoring of ICD/ CRT-D• Allows transfer of information (data) stored* in the implanted
device to a database that can be accessed by the physician
*Equivalent to information obtained during in-clinic visits
• Data transmitted: Arrhythmias, ICD shocks, device function,
battery depletion
• Data transmission occurs in different ways:
• At scheduled intervals (e.g. daily, weekly, every 3-6 months)
• When triggered by an event, e.g. arrhythmia, ICD shock,
device malfunction = alerts
• In lieu of scheduled, in-clinic visits = remote interrogations
• Does not provide additional therapeutic capabilities to the ICD/
CRT-D
11
Remote Monitoring: Communication
ICD/ CRT-D device
Bedside monitor
Data centre
Internet
(Web application)
Via landline or cellular line
Via MICS (Medical Implant Communication System)
12
Ontario Context
• Between 2010 to 2015, 1,798–2,208 patients implanted
with CRT-Ds and ICDs annually in Ontario
• 5 remote monitoring systems approved by Health
Canada:
– Cardiomessenger® (Biotronik), Carelink® (Medtronic), Latitude®
(Boston Scientific), Merlin-net® (Abbott), Smartview® (Livanova)
• Remote monitoring is not publicly funded, but already
used in Ontario:
– London, Hamilton, Ottawa, Southlake, St Mary’s General
Hospital, Guelph, Kawartha, Kingston, Sudbury, Windsor,
Toronto General, St Michael’s Hospital, among others
• No physician fee code exists for conducting a remote
interrogation in lieu of a scheduled in-clinic visit
13
Clinical ReviewWhat is the effectiveness and safety of remote monitoring
of adult patients implanted with ICDs and CRTs plus in-
clinic visits compared with in-clinic visits?
• 15 open-label RCTs
• Number of patients 151–1,650
• Follow-up: 1–3 years
• Low risk of bias (GRADE approach)
• 8 unpublished RCTs (completed 2012–2017, 1
ongoing)—results could not be included in the review
RCT = randomized controlled trial; GRADE = Grading of
Recommendations Assessment, Development and Evaluation
14
Clinical Review:
Meta-Analysis Results
Compared with in-clinic visits, remote monitoring plus in-
clinic visits:
• Reduced the total number of in-clinic visits, number of
patients with inappropriate ICD shocks, and the time
from medical event onset to both detection by the
physician and clinical action (GRADE: Moderate)
• Showed no difference in adverse events, mortality
(GRADE: Low), stroke (GRADE: Very Low), and
hospitalizations due to heart failure (GRADE: Low)
CRT-D = cardiac resynchronization therapy defibrillator; ICD = implantable cardioverter defibrillator;
GRADE = Grading of Recommendations Assessment, Development and Evaluation
15
Primary Economic Evaluation:
Research Question
Within the context of the Ontario Ministry of Health and
Long-Term Care:
• What is the cost-effectiveness of remote monitoring
(RM) plus in-clinic follow-up in comparison to in-clinic
follow-up alone in adult ICD/CRT-D recipients with heart
failure?
16
Methods
• Analysis type: Cost-utility analysis
• Type of model: Markov model
• Target population: ICD/CRT-D recipients with heart failure
– 65 years, 70% male
– During the maintenance phase (3 months post-
implantation)
• Intervention: Remote monitoring plus in-clinic follow-up, as
per Canadian recommendations1
– 1:1 ratio
– Every 6 months
• Comparator: In-clinic follow-up alone 1 Yee 2013. Can J Cardiology
17
Methods
• Perspective: Public payer (Ontario Ministry of Health
and Long-Term Care)
• Time horizon: 5 years
• Discount rate: 1.5% (CADTH guidelines 4th edition)
• Outcomes:
– Costs (CAD 2017)
– QALYs (quality-adjusted life-year)
– ICER (incremental cost effectiveness ratio)
• Sensitivity & scenario analyses: Structural, parameter,
and methodological uncertainties
18
Markov Model Structure
Events:
• Hospital
admission/
readmission
• Emergency
department visits
• Unscheduled
clinic visits
• Scheduled clinic
visits
CRT-D = cardiac resynchronization therapy defibrillator; ICD = implantable cardioverter defibrillator;
NYHA = New York Heart Association functional class
* Post-hospitalized states: increased
risk of hospital readmission and death
19
Model Assumptions
• Devices from different manufacturers are equivalent
• Single- and dual-chamber devices have the same
effectiveness1,2,3
• There is no crossover between RM and non-RM (i.e.,
patients do not switch between intervention arms)
• Excluded events prior to the maintenance phase and
events that are the same between intervention arms
– Implantation, re-implantation attempts, surgical/ device
complications, lead revisions, device recalls, device upgrades/
downgrades, medications and other therapies
1 Hindricks 2014, 2 Peterson 2013, 3 Toff 2005
20
Key Model Inputs and Sources
Clinical Effectiveness
Source: Meta-analysis
No significant difference in:
• Hospital admissions
• Emergency department visits
• Compliance to scheduled visits
• Mortality
• Health utilities
Statistically significant increase in:
• Unscheduled in-clinic visits
Utilities
Source: Various published
literature
• Health states
• Hospitalization (disutility)
• Age (disutility)
Costs
Source: Schedule of
Benefit, Ontario Case
Costing, Ministry, industry
• Professional fees (physician, nurse)
• Hospital costs
• Emergency department visits
• Remote monitoring system
• SA: Northern Health Travel Grant
• SA: Battery replacement
21
Key Model Inputs and Sources
Clinical Effectiveness
Source: Meta-analysis
No significant difference in:
• Hospital admissions
• Emergency department visits
• Compliance to scheduled visits
• Mortality
• Health utilities
Statistically significant increase in:
• Unscheduled in-clinic visits
Utilities
Source: Various published
literature
• Health states
• Hospitalization (disutility)
• Age (disutility)
Costs
Source: Schedule of
Benefit, Ontario Case
Costing, Ministry, industry
• Professional fees (physician, nurse)
• Hospital costs
• Emergency department visits
• Remote monitoring system
• SA: Northern Health Travel Grant
• SA: Battery replacement
22
Cost Parameters:
Direct Medical Costs
• Remote monitoring (beside transmitter via wireless data
transmission [reference case], bedside transmitter via
landline, accessories only, embedded)
• Hospitalization
• Emergency department visit
• Scheduled and unscheduled in-clinic visit
• Reimbursement for remote interrogation
• Ministry Northern Health Travel Grants [scenario
analysis]
• Battery replacements [scenario analysis]
23
Cost Parameters:Reimbursement for Remote Interrogation
• Currently no physician fee code
• Model assumed fee code created after public funding
– Reference case: Payment for remote visit same as that of an in-
clinic visit
– Scenarios: Reduced payments for remote visit
24
Key Cost Parameters
(2017 CAD)
Variable
Cost, 2017
CAD
SD or
Range Source
In-clinic visit
(Physician, Nursing = 12
mins interrogation)
121 Physician:
61 – 180
Nursing: 0.92
Schedule of Benefits,
Elsner et al. 2006
Remote interrogation*
(Physician, Nursing = 1.2
mins interrogation)
110 Physician:
61 – 180
Nursing: 1.02
Schedule of Benefits,
Elsner et al. 2006
ED visit 17,808 8,780 OCC
Hospital visit 32,247 26,503 OCC
ED = emergency department; OCC = Ontario Case Costing; SD = standard deviation
* Additional administrative costs for remote monitoring (nursing time mean =1.9 mins, SD = 10.6 mins
per month per patient)
25
Sensitivity/ Scenario AnalysesUncertainty Parameter
Structural Time Horizon
Functional status after hospitalization
Parameter:
Natural History
Compliance to scheduled, in-clinic visits
NYHA transition probabilities
Time to battery replacement
Parameter:
Remote Monitoring
Impact on Natural
History
Mortality
All-cause hospitalization
Unscheduled, in-clinic visits
ED visits
Compliance to scheduled, in-clinic visits
Optimistic scenario (↓ mortality, hospitalization, unscheduled in-clinic visits, ED visits, ↑ compliance)
Parameter:
Cost and Resource
Use
Northern Health Travel Grant
Nursing time required for remote interrogation
Physician fee code
Model of payment
Methodological Discount rate
26
Results: Reference Case
Strategy Mean
Costs, $
∆
Costs, $
Mean
QALYs
∆
QALYs
ICER,
$/QALY
In-clinic
only55,138
(15,342; 146,719)
2.38(1.58; 2.97)
Remote
monitoring59,492
(18,124; 154,325) 4,3542.56
(1.69; 3.28) 0.19 23,374
∆ = incremental; CRT-D = cardiac resynchronization therapy defibrillator; ICD = implantable cardioverter
defibrillator; ICER = incremental cost-effectiveness ratio
Note: Results may appear incorrect because of rounding.
27
Reference Case Results: Probabilistic Analysis
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 10000 20000 30000 40000 50000
Pro
babili
ty I
nte
rvention is
Cost-
Effe
ctive
Willingness to Pay Threshold ($/QALY)
Remote monitoring + In-clinic visits
In-clinic visits only
28
Sensitivity and Scenario
Analysis Results
Strategy
Mean
Costs ∆ Cost
Mean
QALYs ∆ QALYs
ICER,
$/QALY
Structural: Time horizon extended to 10 years
In-clinic 99,977 3.57
RM 107,663 7,686 3.89 0.32 23,697
Impact on natural history: Optimistic scenario
RM 44,130 3.20
In-clinic 62,172 -18,042 2.58 0.61 Dominant
Payment model for RM: Accessories only
In-clinic 45,780 2.38
RM 49,251 3,471 2.56 0.19 18,628
Physician fee code: 50% of in-clinic visit reimbursement
In-clinic 55,138 2.38
RM 59,294 4,156 2.56 0.18 23,313
29
Strengths & Limitations
Strengths:
• Effectiveness based on substantial body of RCT
evidence. Estimates based on meta-analyses (GRADE:
mostly moderate quality)
• Patient pathway and costs specific to Canadian/ Ontario
Limitations:
• Only modelled maintenance phase (3 months post-
implantation)
• Did not include downstream costs of battery replacement
(i.e., complications)
30
Primary Economic Evaluation:
Conclusions
• Remote monitoring provides good value for money in
ICD/ CRT-D recipients compared to in-clinic visits alone
– Provides health gains at an additional cost
– Best estimate ICER = $23,374 per QALY
– 71% probability of being cost-effective
31
Clinical Evidenceclinical evidence review
Health Economicseconomic evidence
review
economic evaluation
budget impact analysis
Patient Perspectivepublic and patient
engagement
Decision-Making for Funding
Recommendation
Criteria Sub-Criteria
Overall Clinical
Benefit
Effectiveness
Safety
Burden of Illness
Need
Consistency with
Expected Societal
and Ethical Values
Societal Values
Ethical Values
Value for Money Economic Evaluation
Feasibility of
Adoption
Economic Feasibility
Organizational Feasibility
32
OHTAC Draft Recommendation
• Health Quality Ontario, under the guidance of the Ontario Health
Technology Advisory Committee, recommends publicly funding
remote monitoring for patients with implantable cardioverter-
defibrillators, cardiac resynchronization therapy devices with or
without a defibrillator ….
• Currently open for public comment until April 26th
• Final recommendation pending public comments
Link to Full Report:
http://www.hqontario.ca/Portals/0/Documents/evidence/open-comment/hta-remote-monitoring-of-
implantable-cardioverters-1804.pdf
Link to Submitting Public Comments:
http://www.hqontario.ca/Evidence-to-Improve-Care/Health-Technology-Assessment/Reviews-And-
Recommendations/Remote-Monitoring-of-Implantable-Cardioverter-Defibrillators-Cardiac-
Resynchronization-Therapy-and-Permanent-Pacemakers
33
Questions?
Man Wah Yeung, Health Economist, Health Quality Ontario
manwah.yeung@hqontario.ca
34
Additional Information: Decision Determinants
35
Decision DeterminantsCriteria Sub-Criteria Decision Determinants Considerations
Overall Clinical Benefit Effectiveness Compared to in-clinic visits, remote monitoring plus in-clinic visits reduced the number of in-
clinic visits, the time from medical event onset to both detection by the physician and clinical
action, number of patients with inappropriate ICD shocks (ICDs/CRT-Ds) and the arrhythmia
burden (Pacemakers)
Safety No difference in major adverse events (death, hospitalizations, etc.) between remote
monitoring plus in-clinic visits and in-clinic visits
Burden of
Illness
Burden of illness is expected to be large
Approximately 2,000 patients receive new or replacement ICDs/CRT-Ds and about 6,000
patients receive new or replacement permanent pacemakers each year in Ontario. Unclear
how many are using remote monitoring
Need Remote monitoring may replace some in-clinic visits and may alert the physician’s office of
important medical events and device issues earlier compared to in-clinic visits
Consistency with
Expected Societal and
Ethical Values
Societal Values Patients and their family members reported positive experiences with remote cardiac
monitoring
Participants perceived that these devices provided important medical and safety benefits in
managing their heart condition
Ethical Values Use of the treatments evaluated is expected to be congruent with ethical values
Value for Money Economic
Evaluation
Remote monitoring plus in-clinic visits is good value for money for both ICD/ CRT-D and
pacemaker recipients
Feasibility of Adoption Economic
Feasibility
Remote monitoring plus in-clinic visits may be cost saving over time depending on the current
uptake
Organizational
Feasibility
Remote monitoring is already being used to a certain extent in some hospitals across Ontario
36
Additional Information: Primary Economic Evaluation
Methods
37
Clinical Effectiveness Parameters –
Reference CaseParameter
ICD/CRT-D
(95% CI)
PM
(95% CI)Source
Hospitalizations, RRAll cause: 1.03
(0.97 to 1.09)
All-cause: 0.97
(0.72 to 1.31)
Stroke: 0.82
(0.3 to 2.25)
(i) Meta-analysis
(ii) Meta-analysis
ED visit, IRR 1 (N/A) 1 (N/A)(i) Clinical review
(ii) Assumption
Unscheduled In-
clinic visit, IRR2.8 (2.16 to 3.63) 1 (N/A)
(i) MORE-CARE trial
(ii) Assumption
Compliance, RR 1.06 (0.69 to 1.58) 1 (N/A)(i) MORE-CARE trial
(ii) Assumption
Mortality, RRCardiac: 0.89
(0.75 to 1.06)
All-cause: 1.29
(0.78 to 2.13)
(i) Meta-analysis
(ii) Meta-analysis
Health utilities, MD0.043
(-0.043 to 0.128)
0.12
(-0.04 to 0.27)
(i) EVOLVO trial
(ii) Comoretto 2017
Reported as Mean (95% confidence interval). Measures compare RM versus In-Clinic Only
ED = emergency department; IRR = incidence rate ratio; MD = mean difference; RR = risk ratio
38
Scenario Analysis
CI = confidence interval; ED = emergency department; HR = hazard ratio;
IRR = incidence rate ratio; MD = mean difference; RR = risk ratio; SD = standard deviation
ICD/CRT-D (95% CI) Pacemaker (95% CI)
Reduced
hospitalizations
RR = 0.54 (0.41 to 0.71) RR = 0.60 (0.18 to 2.02)
Reduced ED visits IRR = 0.72 (0.53 to 0.98) Same as ICD/ CRT-D
Reduced scheduled, in-
clinic visits
IRR = 0.65 (0.49 to 0.88) Same as ICD/ CRT-D
Increased compliance RR = 1.26, SD = 0.06 N/A
Reduced mortality HR = 0.36 (0.17 to 0.74) N/A
Improved health utilities N/A MD = 0.12 (-0.04 to 0.27)
• Optimistic scenario (simultaneously modelled alternate
clinical effectiveness parameters in favour of RM)
• Extended 5-year time horizon to 10 years (to include
battery replacement costs)
39
Key Cost Parameters
(2017 CAD)
Variable Cost, $ SD or Range Source
Professional fees (per visit):
Physician 109 61.25 – 179.80 Schedule of
Benefits
Nursing (in-clinic
interrogation = 12 mins)
12 0.92 Elsner et al.
2006
Nursing (remote
interrogation = 1.2 mins)
1 1.02 Elsner et al.
2006
ED visit 17,808 8,780 OCC
Hospital visit 32,247 26,503 OCC
Remote monitoring line item-
wireless transmitter
450 250 – 1400 Manufacturers
Ministry Northern Health
Travel Grants
267 N/A Ministry
ED = emergency department; OCC = Ontario Case Costing; SD = standard deviation
40
Utility ParametersHealth States Mean Utility Source
ICD/ CRT-D:
NYHA class I 0.815 Yao 2007
NYHA class II 0.720
NYHA class III 0.590
NYHA class IV 0.508
Post-hospitalized, Year 1, NYHA I-IV NYHA class – hospital disutility
Pacemaker:
Stable arrhythmia 0.795 Caro 2006
Post-hospitalized, Year 1 Stable arrhythmia – hospital disutility
Post-stroke, Years ≥ 1 0.41 Post 2001
Disutilities
Hospitalization, ICD/ CRT-D
NYHA class I 0.07 Griffiths 2014
NYHA class II 0.03
NYHA class III 0.08
NYHA class IV 0.21
Hospitalization, pacemaker 0.04 Reynolds 2010
Age-related, per year
60 to 69 years 0.004 Berg 2015
≥ 70 years 0.005 Berg 2015
41
Additional Information: Primary Economic Evaluation
Results
42
Results: Probabilistic Analysis
ICD/ CRT-DWillingness-to-pay =
$50,000/ QALY
Cost-effective 71%
Not cost-effective 15%
Inferior 14%
Incremental Effectiveness (QALYs)
Incre
me
nta
l C
ost ($
)
43
Results: One-Way Sensitivity Analysis
ICD/ CRT-D:
EV = expected value; ICER = incremental cost-effectiveness ratio; NHTG = Northern Health Travel Grant;
QALY = quality-adjusted life-year
% using NHTG (0 - 100%):
% reduction in remote interrogation
fee code (100 - 0%)
ICER ($/ QALY)
44
Results: Scenario Analysis
ICD/ CRT-DStrategy Mean
Costs, $
Incremental
Cost, $
Mean
QALYs
Incremental
QALYs
ICER,
$/QALY
Scenario: Optimistic (RM reduced mortality, hospitalizations, and
unscheduled in-clinic and emergency visits; Increased compliance)
Blended RM44130 3.20
RM is
DominantIn-clinic alone 62,173 -18,042 2.58 0.61
Scenario: Ten year time horizon (incl. battery replacement costs)
Blended RM 107,664 3.89
In-clinic alone 99,977 7,686 3.57 0.32 24,019
CRT-D = cardiac resynchronization therapy defibrillator; ICD = implantable cardioverter defibrillator;
RM = remote monitoring
45
Additional Information: Clinical Review
46
ICDs/CRTs: ICD Shocks• 5 RCTs (mean follow-up 12–37 months)
• No statistically significant difference between groups in patients with
total (appropriate + inappropriate) or appropriate ICD shocks
Inappropriate shocks (not due to ventricular tachyarrhythmia)
• Fewer patients in the remote vs. non-remote monitoring group had
inappropriate ICD shocks, 4.4% vs. 8.2%
(Risk difference −0.04 [−0.07 to −0.01]; Risk Ratio 0.53 [0.32–0.89]),
4 RCTs
47
ICDs/CRTs: Time From Event Onset to
Data Review or Clinical Decision
Author, Year
N (RM/no RM)
Follow-up, mean months (SD)
Time From Alert/Onset to Event
Review
Median days (IQR)
Time From Event Onset to Clinical
Decision
Median days (IQR)
Boriani et al, 201732
12 months
N = 148 (76/72)
RM: 3 (1–10)
No RM: 37 (14–71)
P < .001
RM: 2 (1–4)
No RM: 29 (3–51)
P = .004
Landolina et al, 2012
N = 200 (99/101)
Up to 16 months
RM: 1.4 (0.8–7.3)
No RM: 24.8 (9.5–48.8)
P < .001
Not reported
Crossley et al, 201143
N = 1,997 (1,014/983)
15 months
Not reported RM: 4.6
No RM: 22.0
P < .001
Varma et al, 2010
N = 1,339 (908/431)
11.5 (2.6)
RM: 1.0
No RM: 35.5
P < .001
Not reported
• 4 RCTs demonstrated a shorter time from event onset to detection
or to clinical decision of approximately 17–34 days
• Types of events detected: arrhythmias, ICD shocks, device (ICD)
malfunction
48
ICDs/CRTs: In-Clinic Visits
• 10 RCTs (mean follow-up 12–37 months)
• Mean total in-clinic visits (scheduled + unscheduled) per patient-
year was 0.9–3.9 and 1.7–6.3 in the remote and non-remote
monitoring groups, respectively
• 26% to 50% reduction in in-clinic visits with remote vs. non remote
monitoring (rate ratio 0.50–0.74)
3 studies did not report rates of visits and could not be included; their results were consistent with the ones
included in the meta-analysis
49
ICDs/CRTs: Patients with ≥ 1
Hospitalization Due to Heart Failure
• 5 RCTs (mean follow-up 11-33 months)
• No statistically significant difference in the number of patients
with ≥ 1 heart failure hospitalization
• Similar results for all-cause hospitalizations
50
ICDs/CRTs: Emergency Department (ED)
Visits
• 4 RCTs (mean follow-up 15-24 months)
• One study showed a lower rate of ED visits in the remote vs. non-
remote monitoring group
• In another study there was a lower rate of a combination of ED visits
or urgent in-office visits with remote monitoring but not ED visits
alone
• Two studies did not show a statistically significant difference in ED
visits between the two groups
• No statistically significant difference between groups in the % of
patients with an ED visit
51
• No statistically significant difference between the two groups
1 RCT not included as the number of deaths were not provided—the authors reported that the difference between the groups
was not statistically significant
ICDs/CRT-Ds: All-Cause Mortality
52
Summary of Findings: Remote Monitoring
of ICDs/CRT-DsNo. of
Studies
(Design)
Risk of Bias Inconsistency Indirectness Imprecision Publication
Bias
Group 1 Group 2 Effect Estimate
(95% CI)
Quality
Patients with Inappropriate ICD shocks
4 RCTs No serious
limitations
No serious
limitations
No serious
limitations
No serious
limitations
Likely (−1)a 4.4% 8.2% RD: −0.04 (−0.07,
−0.1)
⊕⊕⊕Moderate
Number of In-Clinic Visits
7 RCTs No serious
limitations
No serious
limitations
No serious
limitations
No serious
limitations
Likely (−1)a 0.9–3.9
/p-yr
1.7–3.6
/p-yr
Rate ratio: 0.5–
0.7
⊕⊕⊕Moderate
Time To Event Detection or Clinical Decision
4 RCTs No serious
limitations
No serious
limitations
No serious
limitations
No serious
limitations
Likely (−1)a 1–5
days
9–42
days
Shorter (remote
monitoring)⊕⊕⊕Moderate
Patients with Hospitalizations Due to Heart Failure
5 RCTs No serious
limitations
No serious
limitations
No serious
limitations
Serious
limitations (−1)b
Likely (−1)a 54.8% 53.2% RD: 0.0 (−0.02,
0.03)
⊕⊕ Low
Emergency Department Visits
4 RCTs No serious
limitations
Serious
limitations (−1)c
No serious
limitations
Serious
limitations (−1)d
Likely (−1)a 0.05–
0.24/p-yr
0.08–
0.73/p-y
Inconsistent
results
⊕ Very
Low
CI, confidence interval; p-yr, person-years; RD, risk differenceaWe are aware of seven unpublished completed RCTs and we considered that this could affect the results of our meta-analysis.bAs determined by both the lack of statistically significant results and the fact that the minimal information size was not achieved.cResults were inconsistent across studies.dThree studies did not show a statistically significant difference in the rate of emergency department visits between the two groups.
53
Summary of Findings: Remote Monitoring
of ICDs/CRT-Ds (Cont.)No. of
Studies
(Design)
Risk of Bias Inconsistency Indirectness Imprecision Publication
Bias
Group 1 Group 2 Effect Estimate
(95% CI)
Quality
Stroke
2 RCTs No serious
limitations
No serious
limitations
No serious
limitations
Very serious
limitations (−2)a
Likely (−1)b 0.6% 1.7% RD: −0.01 (−0.02,
0)
⊕ Very
Low
Major Adverse Events (Composite of mortality, cardiovascular, procedural, or device-related adverse events)
3 RCTs No serious
limitations
No serious
limitations
Serious
limitations
(−1)c
No serious
limitationsd
Likely (−1)b No difference, satisfied non-inferiority
hypothesis in two trials
⊕⊕ Low
All-Cause Mortality
CI, confidence interval; RD, risk differenceaThe power to detect a difference between the two groups was very low and the number of events reported in the study was very small.bWe are aware of seven unpublished completed RCTs and we considered that this could affect the results of our meta-analysis.cThe fact that a composite endpoint was used affects the generalizability of the results to clinical practice as it is difficult to separate the contribution of each
individual component and the types of events included may have different implications to the patient.dA statistically significant difference in major adverse events was not observed in any of the 3 studies, however, since two of the three studies were non-
inferiority trials and the non-inferiority hypothesis was satisfied in both, we decided not to downgrade for imprecision.eAs determined by both the lack of statistically significant results and the fact that the minimal information size was not achieved.fTwo studies found a statistically significant difference in quality of life and two studies did not find a difference.gNo statistically significant difference in quality of life was reported in two studies, and in one study, a statistically significant difference was only
demonstrated with one of the quality of life measures but not with the other.
4 RCTs No serious
limitations
Serious
limitations (−1)f
No serious
limitations
Serious
limitations (−1)g
Likely (−1)b Different scales used Inconsistent
results
⊕ Very
Low
13 RCTs No serious
limitations
No serious
limitations
No serious
limitations
Serious
limitations (−1)e
Likely (−1)b 6.8% 8.4% RD: −0.01 (−0.02,
0.01)
⊕⊕ Low
Quality of Life
54
Additional Information: Budget Impact Analysis
55
Research Question
• What is the five-year budget impact (2017–2021) of
implementing remote monitoring for adult patients newly
implanted with cardiac electronic devices from the
perspective of the Ontario Ministry of Health and Long-
term Care?
– Implantable cardioverter defibrillators (ICDs)
– Cardiac resynchronization therapy defibrillators (CRT-Ds)
– Cardiac resynchronization therapy pacemaker (CRT-Ps)
– Pacemakers
56
Target PopulationTotal recipients in Ontario (new devices
and replacements) (CIHI)
N= 10,071
(Year 1)
CRT-D = cardiac resynchronization therapy-defibrillator; CRT-P = cardiac resynchronization therapy-
pacemaker; ICD = implantable cardioverter defibrillator; PM = pacemaker; SA = sensitivity analysis
ICD/ CRT-D/ CRT-P (CIHI) Pacemaker (CIHI)
N= 2,049 N= 5,927
New Devices: 79% of total (Ontario ICD Registry) N= 7,976
Current remote monitoring uptake: 15%
(SA: ICD/ CRT-D/ CRT-P: 50%, PM: 4%) (Expert opinion, manufacturers)
Increase in uptake given funding: 10% per year (SA: 15%)(Expert opinion)
Cap in uptake: 47% (SA: ICD/ CRT-D/ CRT-P: 71%, PM: 22%) (Akar, 2013, Mairesse, 2015)
57
Target Population- Reference Case
Baseline RM Uptake at 15% (all devices)
CRT-D = cardiac resynchronization therapy-defibrillator; CRT-P = cardiac resynchronization therapy-
pacemaker; ICD = implantable cardioverter defibrillator; PM = pacemaker; SA = sensitivity analysis
RM Uptake (%) Year 1 Year 2 Year 3 Year 4 Year 5
Current Scenario: Not Funded
Any device 15 15 15 15 15
New Scenario 1: Funded (10% increase per year, cap at 47%)
Any device 25 35 45 47 47
New Scenario 2: Funded (15% increase per year, cap at 71%)
Any device 30 45 60 71 71
New Scenario 3: Funded (10% increase per year, cap at 71% and
22% for ICD/CRT-D/CRT-P and pacemakers, respectively)
ICD/ CRT-P/ CRT-D 25 35 45 55 65
Pacemakers 22 22 22 22 22
58
Target Population- ScenarioBaseline RM Uptake at 50% (ICD/ CRT-P/ CRT-D)
and 4% (Pacemaker)
RM Uptake (%) Year 1 Year 2 Year 3 Year 4 Year 5
Current Scenario: Not Funded (50% and 4% uptake at baseline for
ICD/CRT-D/CRT-P and pacemakers, respectively)
ICD/ CRT-P/ CRT-D 50 50 50 50 50
Pacemakers 4 4 4 4 4
New Scenario: Funded (10% increase per year, cap at 71%)
ICD/ CRT-P/ CRT-D 60 70 71 71 71
Pacemakers 14 24 34 44 54
CRT-D = cardiac resynchronization therapy-defibrillator; CRT-P = cardiac resynchronization therapy-
pacemaker; ICD = implantable cardioverter defibrillator
59
Resources and CostsPer-Patient Cost to Ministry, CAD 2017
Year 1 Year 2 Year 3 Year 4 Year 5
Remote monitoring:
ICD/ CRT-P/ CRT-D recipients
under public funding16,371 13,613 11,930 10,449 9,163
Pacemaker recipients under
public funding6,921 6,962 6,456 5,845 5,295
ICD/ CRT-P/ CRT-D recipients
without public funding a14,572 12,918 11,219 9,744 8,476
Pacemaker recipients without
public funding a6,684 7,526 7,164 6,684 6,196
In-clinic alone:
ICD/ CRT-P/ CRT-D recipients 15,120 13,524 11,852 10,380 9,101
Pacemaker recipients 6,471 6,874 6,456 5,773 5,295
CRT-D = cardiac resynchronization therapy-defibrillator; CRT-P = cardiac resynchronization therapy-pacemaker; ICD =
implantable cardioverter defibrillator; RM = remote monitoring
a No fee code for remote interrogation, and no payment for RM components
60
Results: Reference Case
Baseline RM Uptake at 15% (all devices)
Total Cost to Ministry, $ million
Total Budget Impact Year 1 Year 2 Year 3 Year 4 Year 5 5 Years
Current Scenario: Not Funded69.45 144.75 216.48 284.04 347.84 1,062.57
New Scenario 1: Funded
(10% increase, cap at 47%) 70.75 144.23 214.03 279.15 340.23 1,048.39
Net Budget Impact 1.29 -0.52 -2.45 -4.90 -7.60 -14.18
61
Results: Reference Case (continued)
Baseline RM Uptake at 15% (all devices)
Total Cost to Ministry, $ million
Net Budget Impact Year 1 Year 2 Year 3 Year 4 Year 5 5 Years
New Scenario 2:
Funded (15%
increase, cap at
71%) 1.55 -0.09 -1.96 -4.30 -7.67 -12.47
New Scenario 3:
Funded (10%
increase, cap at
71% and 22%) 1.25 -0.61 -2.22 -3.43 -4.34 -9.34
62
Net Cost to Ministry, $ million
Year 1 Year 2 Year 3 Year 4 Year 5 5 Years
Total Budget Impact
Current Scenario:
Not Funded 69.41 141.49 210.08 274.29 334.88 1,030.15
New Scenario 4:
Funded (10%
increase, cap at
71%) 72.53 145.41 213.80 277.77 337.77 1,047.28
Net Budget Impact3.12 3.92 3.72 3.48 2.89 17.13
Results- Scenario AnalysisBaseline RM Uptake at 50% (ICD/ CRT-P/ CRT-D)
and 4% (Pacemaker)