Online Supplement

Appendix # 1: Medications cost (methodology)

Medications data were obtained for the following drug classes: anticoagulants, antiplatelet inhibitors, blood pressure lowering drugs, cholesterol lowering drugs, NSAIDs (non-steroidal anti-inflammatory drugs), glucose lowering drugs, vitamin supplements, other medications and study drug i.e. Red Heart Pill (RHP 1c and RHP 2c). Since the UMPIRE trial recorded detailed information of medications prescribed to the study participants (drug class, trade name, generic name, strength, dose frequency, start and stop dates, and reason for stopping the drug), we used Pharmatrac drug database [https://aiocdawacs.com/ProductDetail.aspx] for January 2012 to derive the MRP (maximum retail price) of each drug prescribed to the patient (using the given trade name and dose). We calculated the total number of days a patient took a particular drug and multiplied the dose frequency with the unit cost of the medication (MRP taken from the Pharmatrac drug database), to estimate the total medication cost per patient. A template of the medications cost calculation sheet is outlined below.

Example calculation sheet for medications cost within trial

Patient id

Treatment group

Drug class

Trade name

Dose (units)

Unit cost

Dose freq.

Start date

End date

Total no. of days

Total cost per patient

001

Control

Antiplatelet inhibitor

Aspirin

75 mg

0.25

OD

26/08/2010

26/04/2012

609

152.25

001

Control

BP lowering

Losartan

50 mg

5.9

BD

31/08/2010

12/05/2012

620

7316

002

Polypill

FDC

RHP 1c

1 Cap

3.3

OD

27/08/2010

11/02/2011

168

554.4

003

Control

Lipid lowering

Atorva

10 mg

14.8

OD

26/08/2010

08/05/2012

621

9190.8

*BP: blood pressure, FDC: fixed dose combination, RHP: Red Heart Pill, OD: once daily, BD: twice a day, Cap – capsule, mg – milligram, freq. - frequency

Appendix 2: Unit cost of resource utilization data including clinic visits, hospitalizations, and procedures [US$, 2012]

No.

Item

Average cost ($)

Minimum cost ($)

Maximum cost ($)

1

OPD visit

7.5

6.2

18.7

2

ED visit

6.6

5.6

93.6

3

Other consultant visit

11.2

5.6

18.7

4

Other healthcare provider visit

5.6

4.7

11.2

5

Specialist visit

9.4

5.6

37.5

6

Sudden cardiac death in hospital

1578.4

1020.6

2528.1

7

Non-fatal stroke

1732.9

936.3

2809.0

8

ORH (Hypoglycaemia)

183.5

93.6

224.7

9

ORH (Abdominal discomfort)

116.1

93.6

187.3

10

PTCA

2294.0

1404.5

5618.0

11

ORH (Erosions in pyloric antrum, duodenal helminthiasis)

224.7

93.6

561.8

12

CABG

4152.6

3089.9

5337.1

13

ORH (Chronic Kidney Disease)

368.9

187.3

842.7

14

Hospitalization due to cardiac reason (Bradycardia)

3456.5

561.8

4119.9

15

ORH (Upper GI pain + Uncontrolled blood sugar)

305.2

99.3

470.0

16

Unstable Angina

1578.4

1020.6

2340.8

17

ORH (UTI)

224.7

93.6

280.9

18

ORH (Pervaginal bleeding)

198.5

93.6

468.2

19

Non-fatal Stroke + UTI + Sepsis

3690.5

1005.4

3932.6

20

ORH (Chronic Pancreatitis)

412.0

151.7

561.8

21

PVD

1901.5

936.3

2434.5

22

ORH (lower respiratory infection)

224.7

93.6

468.2

23

ORH (acute diarrheal disease leading to renal failure)

468.2

374.5

2340.8

*ORH: other related hospitalizations, PVD: Peripheral Vascular Disease, UTI - Urinary Tract Infection, PTCA: Percutaneous Transluminal Coronary Angiography, CABG: Coronary Artery Bypass graft surgery, GI: Gastro intestinal, OPD: outpatient department, ED: emergency department

Online Figures:

Figure 1: Cost-effectiveness planes for different polypill pricing scenarios [A-E]

Scenario # A: representing polypill price as $0.062 (INR. 3.3) per day. ICER point estimates falls in southeast quadrant meaning that polypill is a cost-saving option at this low price for adherence, SBP, and LDLc outcomes.

Scenario # B: representing polypill price as $0.22 (INR. 11.55) per day. Almost all ICER point estimates falls in southeast quadrant i.e. polypill is a cost-saving option at a price equivalent to aggregate sum cost of polypill constituents.

Scenario # C: polypill price as $0.29 (INR. 15.4) per day. ICER point estimates mostly falls in southeast quadrant indicating that polypill is a cost-saving option at a price equivalent to market price of other FDCs available in India.

Scenario # D: polypill price $0.47 (INR. 25) per day. ICER points falls in northeast and southeast quadrants meaning that there is some uncertainty in cost-saving of polypill.

Scenario # E: representing polypill price as $0.94 (INR. 50) per day. ICER point estimates falls mostly in northeast quadrant suggesting that there is greater clinical benefit at higher cost with the polypill strategy versus usual care.

Figure 2: Cost-effectiveness acceptability curves (CEAC) for different polypill pricing scenarios A-E

Scenario # A: representing polypill price as INR. 3.3 ($0.062) per day. CEAC clearly indicates that polypill is 100% time cost-effective at any willingness to pay (value of ceiling ratio, $) as it costs less than usual care treatment.

Scenario # B: representing polypill price as INR. 11.55 ($0.22) per day. CEAC clearly indicates that polypill is 100% time cost-effective at any willingness to pay (value of ceiling ratio, $) as it costs less than usual care treatment

.

Scenario # C: representing polypill price as INR. 15.4 ($0.29) per day. CEAC clearly indicates that polypill is 100% time cost-effective at any willingness to pay (value of ceiling ratio, $) as it costs less than usual care treatment.

Scenario # D: representing polypill price as INR. 25 ($0.47) per day. CEAC clearly indicates that as willingness to pay (value of ceiling ratio, $) increases so is the cost-effectiveness probability for polypill strategy.

Scenario # E: representing polypill price as INR. 50 ($0.94) per day. CEAC clearly indicates that as willingness to pay (value of ceiling ratio, $) increases so is the cost-effectiveness probability for polypill strategy.

Online Table 1: Sensitivity analysis results (in US $, 2012)

Input Parameter

Values

Incremental cost per 10% increase in adherence ($)

Incremental cost per unit reduction in LDLc ($)

Incremental cost per unit reduction in SBP ($)

One-way sensitivity analysis

 

 

 

 

1. Assessing parametric uncertainty

 

 

 

 

1.a. Effectiveness of Polypill (adherence)

25.3

na

na

na

 

10.0

 

 

 

1.b. Effectiveness of Polypill (LDLc)

2.9

na

na

na

 

8.5

na

na

na

1.c. Effectiveness of Polypill (SBP)

6.5

na

na

na

 

21.1

na

na

na

1.d. Cost of Polypill

$0.06/day

na

na

na

 

$0.29/day

na

na

na

 

$0.48/day

na

na

na

 

$0.94/day

209.8

21.0

64.7

1.e. Cost of Healthcare visits

Minimum

na

na

na

Maximum

na

na

na

1.f. Cost of Events & Hospitalization

Minimum

na

na

na

Maximum

na

na

na

Multivariable sensitivity analysis

 

 

 

2. Scenario Analysis

ᴪ Worst case

373

504

202

 

¶ Best case

na

na

na

ᴪ Worst case: low effectiveness values of polypill, maximum cost of polypill, maximum cost of healthcare visits and hospitalizations

¶ Best case: higher effectiveness of polypill, minimum cost of polypill and minimum cost of healthcare visits and hospitalizations

na: polypill strategy was dominant (negative ICER)

*LDLc – low density lipoprotein cholesterol, SBP – systolic blood pressure, $ - united states dollar

Online Table 2: Mean within trial costs for subgroups analysed in the UMPIRE trial (Overall costs) (in US $, 2012)

 

Polypill group

Usual care group

Cost difference

(n=501)

(n=499)

 

No. of patients

Costs (mean)

No. of patients

Costs (mean)

(Polypill – Usual care)

Age

<55 years

180

214.8

205

410.7

-195.9

≥ 55 years

321

315.2

294

532.4

-217.2

Sex

Male

390

278.3

393

484.4

-206.1

Female

111

281.9

106

475.0

-193.1

Established CVD

No

39

243.8

41

551.7

-307.9

Yes

462

282.1

458

476.2

-194.1

Diabetes

No

339

151.8

329

313.7

-161.9

Yes

162

545.4

170

808.8

-263.4

Adherence rates

High or Moderate (≥4days)

478

265.8

209

376.6

-110.8

Low (<4 days)

23

554.7

290

558.6

-211.8

Healthcare setting

Private

342

283.7

342

472.1

-188.4

Public

159

269.2

157

505.0

-235.8

Education

Up to secondary school

413

276.5

398

451.7

-175.1

Graduation and above

88

291.2

101

603.6

-312.4

Income levels, INR, (in $)

<20,000 (<$374.5)

345

269.0

336

441.8

-172.8

≥20,000 (≥$374.5)

77

294.4

96

532.6

-238.2

Employment

Full-time

142

249.6

140

466.9

-217.3

Part-time

46

325.1

47

374.0

-48.8

Retired/unemployed

313

285.7

312

505.7

-220.0

*CVD – cardiovascular disease, $: United States dollar