Remote Monitoring of Implantable Cardioverter Defibrillators and Cardiac Resynchronization Therapy Defibrillators

Transcription

1 Cost-Effectiveness Analysis of: Remote Monitoring of Implantable Cardioverter Defibrillators and Cardiac Resynchronization Therapy Defibrillators CADTH Symposium April 17, 2018 Man Wah Yeung, Vania Costa, Lindsey Falk, Nancy Sikich, Irfan Dhalla, Vivian Ng

2 Disclosure All co-authors have no actual or potential conflict of interest in relation to this topic or presentation. 1

3 The Provincial Advisor on the Quality of Health Care in Ontario, Canada 2

4 Health Technology Assessment at Health Quality Ontario HTA Health Services and Medical Devices Clinical Evidence clinical evidence review Health Economics economic evidence review economic evaluation budget impact analysis Ontario Health Technology Advisory Committee (OHTAC) in support of HQO Funding Recommendations Patient Perspective public and patient engagement Ontario Ministry of Health and Long- Term Care 3

5 Health Technology Assessment at Health Quality Ontario HTA Health Services and Medical Devices Clinical Evidence clinical evidence review Health Economics economic evidence review economic evaluation budget impact analysis Ontario Health Technology Advisory Committee (OHTAC) in support of HQO Funding Recommendations Patient Perspective public and patient engagement Ontario Ministry of Health and Long- Term Care 4

6 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 5

7 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 6

8 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 7

9 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 8

10 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 9

11 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 10

12 Remote Monitoring: Communication ICD/ CRT-D device Via MICS (Medical Implant Communication System) Bedside monitor Via landline or cellular line Data centre Internet (Web application) 11

13 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 12

14 Clinical Review What is the effectiveness and safety of remote monitoring of adult patients implanted with ICDs and CRTs plus inclinic 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 , 1 ongoing) results could not be included in the review RCT = randomized controlled trial; GRADE = Grading of Recommendations Assessment, Development and Evaluation 13

15 Clinical Review: Meta-Analysis Results Compared with in-clinic visits, remote monitoring plus inclinic 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 14

16 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? 15

17 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 postimplantation) Intervention: Remote monitoring plus in-clinic follow-up, as per Canadian recommendations 1 1:1 ratio Every 6 months Comparator: In-clinic follow-up alone 1 Yee Can J Cardiology 16

18 Methods Perspective: Public payer (Ontario Ministry of Health and Long-Term Care) Time horizon: 5 years Discount rate: 1.5% (CADTH guidelines 4 th edition) Outcomes: Costs (CAD 2017) QALYs (quality-adjusted life-year) ICER (incremental cost effectiveness ratio) Sensitivity & scenario analyses: Structural, parameter, and methodological uncertainties 17

19 Markov Model Structure Events: Hospital admission/ readmission Emergency department visits Unscheduled clinic visits Scheduled clinic visits * Post-hospitalized states: increased risk of hospital readmission and death CRT-D = cardiac resynchronization therapy defibrillator; ICD = implantable cardioverter defibrillator; NYHA = New York Heart Association functional class 18

20 Model Assumptions Devices from different manufacturers are equivalent Single- and dual-chamber devices have the same effectiveness 1,2,3 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 19 1 Hindricks 2014, 2 Peterson 2013, 3 Toff 2005

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 Utilities Source: Various published literature Costs Source: Schedule of Benefit, Ontario Case Costing, Ministry, industry Statistically significant increase in: Unscheduled in-clinic visits Health states Hospitalization (disutility) Age (disutility) Professional fees (physician, nurse) Hospital costs Emergency department visits Remote monitoring system SA: Northern Health Travel Grant SA: Battery replacement 20

22 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 Utilities Source: Various published literature Costs Source: Schedule of Benefit, Ontario Case Costing, Ministry, industry Statistically significant increase in: Unscheduled in-clinic visits Health states Hospitalization (disutility) Age (disutility) Professional fees (physician, nurse) Hospital costs Emergency department visits Remote monitoring system SA: Northern Health Travel Grant SA: Battery replacement 21

23 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] 22

24 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 inclinic visit Scenarios: Reduced payments for remote visit 23

25 Key Cost Parameters (2017 CAD) Variable In-clinic visit (Physician, Nursing = 12 mins interrogation) Remote interrogation* Cost, 2017 CAD SD or Range 121 Physician: Nursing: 0.92 Source Schedule of Benefits, Elsner et al Physician: Schedule of Benefits, (Physician, Nursing = 1.2 Elsner et al Nursing: 1.02 mins interrogation) ED visit 17,808 8,780 OCC Hospital visit 32,247 26,503 OCC * Additional administrative costs for remote monitoring (nursing time mean =1.9 mins, SD = 10.6 mins per month per patient) ED = emergency department; OCC = Ontario Case Costing; SD = standard deviation 24

26 Sensitivity/ Scenario Analyses Uncertainty Structural Parameter: Natural History Parameter: Remote Monitoring Impact on Natural History Parameter: Cost and Resource Use Methodological Parameter Time Horizon Functional status after hospitalization Compliance to scheduled, in-clinic visits NYHA transition probabilities Time to battery replacement 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) Northern Health Travel Grant Nursing time required for remote interrogation Physician fee code Model of payment Discount rate 25

27 Results: Reference Case Strategy Mean Costs, $ Costs, $ Mean QALYs QALYs ICER, $/QALY In-clinic only Remote monitoring 55,138 (15,342; 146,719) 59,492 (18,124; 154,325) 4, (1.58; 2.97) 2.56 (1.69; 3.28) ,374 Note: Results may appear incorrect because of rounding. = incremental; CRT-D = cardiac resynchronization therapy defibrillator; ICD = implantable cardioverter defibrillator; ICER = incremental cost-effectiveness ratio 26

28 Probability Intervention is Cost-Effective Reference Case Results: Probabilistic Analysis Remote monitoring + In-clinic visits In-clinic visits only Willingness to Pay Threshold ($/QALY) 27

29 Sensitivity and Scenario Analysis Results Strategy Mean Costs Cost Mean QALYs QALYs ICER, $/QALY Structural: Time horizon extended to 10 years In-clinic 99, RM 107,663 7, ,697 Impact on natural history: Optimistic scenario RM 44, In-clinic 62,172-18, Dominant Payment model for RM: Accessories only In-clinic 45, RM 49,251 3, ,628 Physician fee code: 50% of in-clinic visit reimbursement In-clinic 55, RM 59,294 4, ,313 28

30 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 postimplantation) Did not include downstream costs of battery replacement (i.e., complications) 29

31 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 30

32 Decision-Making for Funding Recommendation Clinical Evidence clinical evidence review Health Economics economic evidence review economic evaluation budget impact analysis Patient Perspective public and patient engagement Criteria Overall Clinical Benefit Consistency with Expected Societal and Ethical Values Value for Money Feasibility of Adoption Sub-Criteria Effectiveness Safety Burden of Illness Need Societal Values Ethical Values Economic Evaluation Economic Feasibility Organizational Feasibility 31

33 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 cardioverterdefibrillators, cardiac resynchronization therapy devices with or without a defibrillator. Currently open for public comment until April 26 th Final recommendation pending public comments Link to Full Report: Link to Submitting Public Comments: Recommendations/Remote-Monitoring-of-Implantable-Cardioverter-Defibrillators-Cardiac- Resynchronization-Therapy-and-Permanent-Pacemakers 32

34 Questions? Man Wah Yeung, Health Economist, Health Quality Ontario 33

35 Additional Information: Decision Determinants 34

36 Decision Determinants Criteria Sub-Criteria Decision Determinants Considerations Overall Clinical Benefit Effectiveness Compared to in-clinic visits, remote monitoring plus in-clinic visits reduced the number of inclinic 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) Consistency with Expected Societal and Ethical Values Safety Burden of Illness Need Societal Values Ethical Values No difference in major adverse events (death, hospitalizations, etc.) between remote monitoring plus in-clinic visits and in-clinic visits 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 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 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 Use of the treatments evaluated is expected to be congruent with ethical values Value for Money Feasibility of Adoption Economic Evaluation Economic Feasibility Organizational Feasibility Remote monitoring plus in-clinic visits is good value for money for both ICD/ CRT-D and pacemaker recipients Remote monitoring plus in-clinic visits may be cost saving over time depending on the current uptake Remote monitoring is already being used to a certain extent in some hospitals across Ontario 35

37 Additional Information: Primary Economic Evaluation Methods 36

38 Clinical Effectiveness Parameters Reference Case Parameter Hospitalizations, RR ICD/CRT-D (95% CI) All cause: 1.03 (0.97 to 1.09) PM (95% CI) All-cause: 0.97 (0.72 to 1.31) Stroke: 0.82 (0.3 to 2.25) ED visit, IRR 1 (N/A) 1 (N/A) Unscheduled Inclinic visit, IRR 2.8 (2.16 to 3.63) 1 (N/A) Compliance, RR 1.06 (0.69 to 1.58) 1 (N/A) Mortality, RR Health utilities, MD Cardiac: 0.89 (0.75 to 1.06) ( to 0.128) All-cause: 1.29 (0.78 to 2.13) 0.12 (-0.04 to 0.27) Source (i) (ii) Meta-analysis Meta-analysis (i) Clinical review (ii) Assumption (i) MORE-CARE trial (ii) Assumption (i) MORE-CARE trial (ii) Assumption (i) Meta-analysis (ii) Meta-analysis (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 37

39 Scenario Analysis Optimistic scenario (simultaneously modelled alternate clinical effectiveness parameters in favour of RM) Reduced hospitalizations ICD/CRT-D (95% CI) Pacemaker (95% CI) 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, inclinic visits IRR = 0.65 (0.49 to 0.88) Increased compliance RR = 1.26, SD = 0.06 N/A Reduced mortality HR = 0.36 (0.17 to 0.74) N/A Same as ICD/ CRT-D Improved health utilities N/A MD = 0.12 (-0.04 to 0.27) Extended 5-year time horizon to 10 years (to include battery replacement costs) CI = confidence interval; ED = emergency department; HR = hazard 38ratio; IRR = incidence rate ratio; MD = mean difference; RR = risk ratio; SD = standard deviation

40 Key Cost Parameters (2017 CAD) Variable Cost, $ SD or Range Source Professional fees (per visit): Physician Schedule of Benefits Nursing (in-clinic interrogation = 12 mins) Elsner et al Nursing (remote interrogation = 1.2 mins) Elsner et al ED visit 17,808 8,780 OCC Hospital visit 32,247 26,503 OCC Remote monitoring line itemwireless transmitter Manufacturers Ministry Northern Health Travel Grants 267 N/A Ministry ED = emergency department; OCC = Ontario Case Costing; SD = standard deviation 39

41 Utility Parameters Health States Mean Utility Source ICD/ CRT-D: NYHA class I Yao 2007 NYHA class II NYHA class III NYHA class IV Post-hospitalized, Year 1, NYHA I-IV NYHA class hospital disutility Pacemaker: Stable arrhythmia Caro 2006 Post-hospitalized, Year 1 Stable arrhythmia hospital disutility Post-stroke, Years 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 Berg years Berg

42 Additional Information: Primary Economic Evaluation Results 41

43 Incremental Cost ($) Results: Probabilistic Analysis ICD/ CRT-D Willingness-to-pay = $50,000/ QALY Not cost-effective 15% Cost-effective 71% Inferior 14% Incremental Effectiveness (QALYs) 42

44 Results: One-Way Sensitivity Analysis ICD/ CRT-D: % using NHTG (0-100%): % reduction in remote interrogation fee code (100-0%) ICER ($/ QALY) EV = expected value; ICER = incremental cost-effectiveness ratio; NHTG = Northern Health Travel Grant; QALY = quality-adjusted life-year 43

45 Results: Scenario Analysis ICD/ CRT-D Strategy 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 RM In-clinic alone 62,173-18, RM is Dominant Scenario: Ten year time horizon (incl. battery replacement costs) Blended RM 107, In-clinic alone 99,977 7, ,019 CRT-D = cardiac resynchronization therapy defibrillator; ICD = implantable cardioverter defibrillator; RM = remote monitoring 44

46 Additional Information: Clinical Review 45

47 ICDs/CRTs: ICD Shocks 5 RCTs (mean follow-up 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 [ ]), 4 RCTs 46

48 ICDs/CRTs: Time From Event Onset to Data Review or Clinical Decision 4 RCTs demonstrated a shorter time from event onset to detection or to clinical decision of approximately days Types of events detected: arrhythmias, ICD shocks, device (ICD) malfunction Author, Year N (RM/no RM) Follow-up, mean months (SD) Boriani et al, months N = 148 (76/72) Landolina et al, 2012 N = 200 (99/101) Up to 16 months Crossley et al, N = 1,997 (1,014/983) 15 months Varma et al, 2010 N = 1,339 (908/431) 11.5 (2.6) Time From Alert/Onset to Event Review Median days (IQR) RM: 3 (1 10) No RM: 37 (14 71) P <.001 RM: 1.4 ( ) No RM: 24.8 ( ) P <.001 Time From Event Onset to Clinical Decision Median days (IQR) RM: 2 (1 4) No RM: 29 (3 51) P =.004 Not reported Not reported RM: 4.6 RM: 1.0 No RM: 35.5 P <.001 No RM: 22.0 P <.001 Not reported 47

49 ICDs/CRTs: In-Clinic Visits 10 RCTs (mean follow-up months) Mean total in-clinic visits (scheduled + unscheduled) per patientyear was and 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 ) 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 48

50 ICDs/CRTs: Patients with 1 Hospitalization Due to Heart Failure 5 RCTs (mean follow-up months) No statistically significant difference in the number of patients with 1 heart failure hospitalization Similar results for all-cause hospitalizations 49

51 ICDs/CRTs: Emergency Department (ED) Visits 4 RCTs (mean follow-up months) One study showed a lower rate of ED visits in the remote vs. nonremote 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 50

52 ICDs/CRT-Ds: All-Cause Mortality 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 51

53 No. of Studies (Design) Summary of Findings: Remote Monitoring of ICDs/CRT-Ds Risk of Bias Inconsistency Indirectness Imprecision Publication Bias Patients with Inappropriate ICD shocks Group 1 Group 2 Effect Estimate (95% CI) Quality 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 /p-yr /p-yr Rate ratio: 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 Likely ( 1) a 54.8% 53.2% RD: 0.0 ( 0.02, limitations ( 1) b 0.03) Low Emergency Department Visits 4 RCTs No serious limitations Serious limitations ( 1) c No serious limitations Serious Likely ( 1) a 0.05 limitations ( 1) d 0.24/p-yr /p-y Inconsistent results Very Low CI, confidence interval; p-yr, person-years; RD, risk difference a We are aware of seven unpublished completed RCTs and we considered that this could affect the results of our meta-analysis. b As determined by both the lack of statistically significant results and the fact that the minimal information size was not achieved. c Results were inconsistent across studies. d Three studies did not show a statistically significant difference in the rate of emergency department visits between the two groups. 52

54 No. of Studies (Design) Stroke Summary of Findings: Remote Monitoring of ICDs/CRT-Ds (Cont.) Risk of Bias Inconsistency Indirectness Imprecision Publication Bias Group 1 Group 2 Effect Estimate (95% CI) Quality 2 RCTs No serious limitations No serious limitations No serious limitations Very serious Likely ( 1) b 0.6% 1.7% RD: 0.01 ( 0.02, limitations ( 2) a 0) Major Adverse Events (Composite of mortality, cardiovascular, procedural, or device-related adverse events) Very Low 3 RCTs No serious limitations No serious limitations Serious limitations ( 1) c No serious Likely ( 1) b No difference, satisfied non-inferiority limitations d hypothesis in two trials Low All-Cause Mortality 13 RCTs No serious limitations No serious limitations No serious limitations Serious Likely ( 1) b 6.8% 8.4% RD: 0.01 ( 0.02, limitations ( 1) e 0.01) Low Quality of Life 4 RCTs No serious limitations Serious limitations ( 1) f No serious limitations Serious Likely ( 1) b Different scales used Inconsistent limitations ( 1) g results Very Low CI, confidence interval; RD, risk difference a The power to detect a difference between the two groups was very low and the number of events reported in the study was very small. b We are aware of seven unpublished completed RCTs and we considered that this could affect the results of our meta-analysis. c The 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. d A statistically significant difference in major adverse events was not observed in any of the 3 studies, however, since two of the three studies were noninferiority trials and the non-inferiority hypothesis was satisfied in both, we decided not to downgrade for imprecision. e As determined by both the lack of statistically significant results and the fact that the minimal information size was not achieved. f Two studies found a statistically significant difference in quality of life and two studies did not find a difference. g No statistically significant difference in quality of life was reported in two studies, and in one study, a statistically significant difference was only 53 demonstrated with one of the quality of life measures but not with the other.

55 Additional Information: Budget Impact Analysis 54

56 Research Question What is the five-year budget impact ( ) of implementing remote monitoring for adult patients newly implanted with cardiac electronic devices from the perspective of the Ontario Ministry of Health and Longterm Care? Implantable cardioverter defibrillators (ICDs) Cardiac resynchronization therapy defibrillators (CRT-Ds) Cardiac resynchronization therapy pacemaker (CRT-Ps) Pacemakers 55

57 Target Population Total recipients in Ontario (new devices and replacements) (CIHI) N= 10,071 (Year 1) New Devices: 79% of total (Ontario ICD Registry) N= 7,976 ICD/ CRT-D/ CRT-P (CIHI) Pacemaker (CIHI) N= 2,049 N= 5,927 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) CRT-D = cardiac resynchronization therapy-defibrillator; CRT-P = cardiac resynchronization therapypacemaker; ICD = implantable cardioverter defibrillator; PM = pacemaker; SA = sensitivity analysis 56

58 Target Population- Reference Case Baseline RM Uptake at 15% (all devices) RM Uptake (%) Year 1 Year 2 Year 3 Year 4 Year 5 Current Scenario: Not Funded Any device New Scenario 1: Funded (10% increase per year, cap at 47%) Any device New Scenario 2: Funded (15% increase per year, cap at 71%) Any device 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 Pacemakers CRT-D = cardiac resynchronization therapy-defibrillator; CRT-P = cardiac resynchronization therapypacemaker; ICD = implantable cardioverter defibrillator; PM = pacemaker; SA = sensitivity analysis 57

59 Target Population- Scenario Baseline 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 Pacemakers New Scenario: Funded (10% increase per year, cap at 71%) ICD/ CRT-P/ CRT-D Pacemakers CRT-D = cardiac resynchronization therapy-defibrillator; CRT-P = cardiac resynchronization therapypacemaker; ICD = implantable cardioverter defibrillator 58

60 Resources and Costs Remote monitoring: Per-Patient Cost to Ministry, CAD 2017 Year 1 Year 2 Year 3 Year 4 Year 5 ICD/ CRT-P/ CRT-D recipients under public funding Pacemaker recipients under public funding 16,371 13,613 11,930 10,449 9,163 6,921 6,962 6,456 5,845 5,295 ICD/ CRT-P/ CRT-D recipients without public funding a 14,572 12,918 11,219 9,744 8,476 Pacemaker recipients without public funding a 6,684 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 a No fee code for remote interrogation, and no payment for RM components CRT-D = cardiac resynchronization therapy-defibrillator; CRT-P = cardiac resynchronization therapy-pacemaker; ICD = implantable cardioverter defibrillator; RM = remote monitoring 59

61 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 Funded , New Scenario 1: Funded (10% increase, cap at 47%) , Net Budget Impact

62 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%) New Scenario 3: Funded (10% increase, cap at 71% and 22%)

63 Results- Scenario Analysis Baseline RM Uptake at 50% (ICD/ CRT-P/ CRT-D) and 4% (Pacemaker) Total Budget Impact Current Scenario: Net Cost to Ministry, $ million Year 1 Year 2 Year 3 Year 4 Year 5 5 Years Not Funded , New Scenario 4: Funded (10% increase, cap at 71%) , Net Budget Impact