Treatment of DVT with Tinzaparin

1
Treatment of DVT with Tinzaparin

• Updated Economic Analysis
• October 9, 2003

2
Background

• An economic model was created for DuPont
• Results published in 2002.
• Costs reported in 1999 US dollars
• Key finding tinzaparin led to better health
  outcomes, and reduced costs
• No comparison with other LMWHs was made.

3
Objectives

• To update the original economic model using most
  recent
• costs
• effectiveness estimates
• To add a comparison with enoxaparin.

4
Methods
5
Model Structure
6
Complications Included

• Major bleeds
• Minor bleeds
• Recurrent DVTs
• PEs
• Thrombocytopenia
• Post-phlebitic complications
• Deaths

7
Clinical Event Rates

• No new trials comparing tinzaparin with UFH
• Event rates for both treatments remain unchanged
  from original study (based on DMP-702-900 trial)
• No head-to-head studies comparing tinzaparin with
  enoxaparin in treatment of DVT
• Indirect comparisons made using rates from
  relevant enoxaparin trials
• Enoxaparin once a day Merli, 2001
• Enoxaparin twice a day pooled results from
  Merli, 2001 Levine 1996
• Relative risks (RR) for key events calculated for
  enoxaparin versus UFH
• RRs then applied to UFH event rates in
  DMP-702-900.
• Where no data, equivalence with tinzaparin
  assumed.

8
Original Model Event Rates
UFH
Tinzaparin
No Complications
Major Bleed - heparin

Major Bleed - long-term warfarin
Minor Bleed - heparin
Minor Bleed - long-term warfarin
Recurrent DVT
Fatal PE (including suspected PEs)
Non Fatal PE
Thrombocytopenia
Other Deaths

9
Enoxaparin Twice per Day
UFH
Tinzaparin
No Complications
78.3
84.5
Major Bleed - heparin

4.1
0.5
Major Bleed - long-term warfarin
0.9
2.3
Minor Bleed - heparin
3.7
3.2
Minor Bleed - long-term warfarin
2.7
2.8
Recurrent DVT
4.1
1.4
Fatal PE (including suspected PEs)
1.8
0.5
Non Fatal PE
1.4
1.4
Thrombocytopenia
0.5
1.4
Other Deaths


7.6
4.4
10
Enoxaparin Once a Day
11
Long Term Outcomes

• Long-Term Complications
• Recurrent venous thromboembolic events
• Mild and severe post-phlebitic syndrome
• Other Long-Term Outcomes
• Survival
• Quality Adjusted Life Years (QALYs)
• Methodology for LT complications and other LT
  outcomes remains unchanged
• Outcomes are over lifetime, and treatment is
  assumed to have no further effect beyond 3
  months.
• Events over first 3 months will influence LT
  outcomes

12
Cost Inputs

• Costing updated to 2003 US dollars.
• Only direct medical costs included.
• Cost of uncomplicated cases (excl. drug and
  associated costs)
• 7,234 (inpatient treatment, 6 day LOS)
• 2,986 (early discharge, 3 day LOS)
• 1,680 (outpatient, including ER visit)
• Cases with complications are significantly more
  expensive.
• Based on event rates used in the model, avg. cost
  per complicated case was between 19,147 and
  20,421.

13
Cost Inputs

• Tinzaparin drug only 52.92 per day (mean weight
  75kg)
• Including associated costs 53.30 to 67.06
  depending on LOC
• 55.64 for inpatient
• Enoxaparin once a day drug only 72.24 per day
• Including associated costs 72.62 to 86.39
• 74.97 for inpatient
• Enoxaparin twice a day drug cost only 96.33 per
  day
• Including associated costs 97.08 to 124.61
• 101.77 for inpatient
• UFH drug only 3.28 (25,000 U/ml)
• Including associated costs 45.05

14
Treatment Location

Principal analyses compare inpatient treatment
for all patients.
Early discharge and outpatient treatment for
those on tinzaparin or enoxaparin only
considered in secondary analyses.
15
Results
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Survival Projections
UFH
100
Tinzaparin
90
of Patients Alive
80
70
60
0
2
4
6
8
10
Year After Initial DVT
17
Survival Projections
UFH
100
Tinzaparin
Enoxaparin 1x
90
Enoxaparin 2x
of Patients Alive
80
70
60
0
2
4
6
8
10
Year After Initial DVT
18
Recurrent VTE
600
500
400
300
Cum. Recurrent VTE Events/ 1,000 Patients
200
100
0
UFH
Tinzaparin
Enox 1x
Enox 2x
19
Short-Term Costs
20
15
?941
cost per patient (,000)
10
5
0
UFH
Tinzaparin
Enox 1x
Enox 2x
20
With Subacute Care
?996
?730
?800
21
Lifetime Costs
?771
Excluding Sub-Acute Costs
22
Cost-Effectiveness
Excluding Sub-Acute Costs
23
DVT Treatment Options
Short-Term Cost Results
15
UFH
Tinzaparin
12
Enox 1x
Enox 2x
9
cost per patient (,000)
6
3
0
Inpatient
3 day LOS
2 day LOS
1 day LOS
Outpatient
Excluding Sub-Acute Costs
24
DVT Treatment Options
Long-Term Cost Results
Excluding Sub-Acute Costs
25
SA Price of Tinzaparin
UFH
1,250
Enox 1x
1,000
Enox 2x
750
500
250
tinzaparin cost per 40,000 IU
net costs per patient
0
80
140
200
260
320
-250
-500
-750
-1,000
-1,250
Excluding Sub-Acute Costs
26
SA Event Rates with Tinzaparin
Excluding Sub-Acute Costs
27
SA All LMWHs Equal
Tinzaparin
20
Enox 1x
Enox 2x
15
cost per patient (,000)
10
5
0
Base Case
All Event Rates Equal
Excluding Sub-Acute Costs
28
SA Non-Rx Treatment Costs
Excluding Sub-Acute Costs
29
SA Discount Rate
Excluding Sub-Acute Costs
30
Conclusion
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Summary

• Tinzaparin is dominant (better health outcomes,
  lower costs) over UFH
• Savings of 800/patient when all treated as
  inpatients
• Over 6,000/patient if tinzaparin on outpatient
  basis
• Tinzaparin also dominates enoxaparin, taken
  either once or twice a day.
• On an inpatient basis, savings of 800 to
  1,000/patient
• Even if enoxaparin assumed to be as effective,
  costs with tinzaparin would be 114 to 273 lower
• Results stable over wide ranges in input estimates

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Submission

• Results against enoxaparin not based on
  head-to-head data
• Even assuming equivalence tinzaparin dominates
• Tinzaparin not indicated for outpatient treatment
• But dominant over UFH even on inpatient
  comparison
• Decisions for submission need to be taken on
• Whether to include a comparison with enoxaparin
• Whether to include outpatient treatment scenarios
• As secondary or sensitivity analyses?
• Manuscripts and abstracts?
• Results against UFH similar to those previously
  published
• Tinzaparin vs. enoxaparin economic analysis would
  be first of its kind
• Submit to ISPOR 2004?

33
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