Figure 1
Structure of the microsimulation model.
The above microsimulation model was used with a cycle time of one month to estimate costs and DALYs in two hypothetical cohort of 10,000 individuals (males and females respectively) with ages 40-69yr at the start of the simulation. Multiple scenarios with combinations of coverage and adherence were simulated, and the incremental cost per DALY averted was calculated in reference to the status quo of 17% coverage and 30% adherence. The blue square indicates the choice between various intervention scenarios, and the orange circle indicates the chosen intervention. The health states (indicated by green pentagon) comprises of (1) well (no past CVD event), (2) occurrence of a CVD event, (3) surviving post a myocardial infarction (postMI), (4) surviving post a stroke (postStroke), and (5) deceased state. The blue-colored branches from each heath state lead to another heath state based on the probability of the intermediate event (indicated by the green circle). The (2) CVD event is a transitionary markov state and comprises of either an occurrence of MI or stroke.
CVD = Cardiovascular disease, MI = Myocardial infarction, DALYs = Disability adjusted life year.
Table 1
Select input parameters for the microsimulation model.
| Input Parameter | Value | Source(s) |
|---|---|---|
| Population characteristics | ||
| Individual profiles consisting of Age, Sex, Systolic blood pressure, BMI and Smoking habit | WHO SAGE [24] | |
| Baseline status-awareness ratio | 40.8% | PURE Study [34] |
| Baseline treatment initiation ratio | 77.7% | PURE Study [34] |
| Baseline treatment persistence ratio | 61% | Van Wijk et al. 2005 [35] |
| Baseline medication compliance ratio | 50.3% | Dennis et al. 2011 [36] |
| Blood pressure increase with increase in age of an individual | Age and initial SBP-specific | Simulated based on model developed by Bellows et al. 2019 [37] |
| Mortality and risk of cardiovascular diseases | ||
| Non-CVD death rate | 0.005–0.176 (Age- and sex- specific)# | Calculated from WHO lifetables and GBD 2017 [3, 27] |
| Probability of first-time cardiovascular disease (CVD) event | Individual risk characteristic specific | Obtained from the Globorisk Office Calculator standardized for India [25] |
| Acute CVD Events | ||
| Myocardial Infarction (MI) | ||
| Probability of MI if CVD event occurs | 37.6– 66.7% (Age- and sex- specific)# | Calculated based on GBD 2017 [3] |
| 30-day fatality | 0.01–0.13 (Age- and sex– specific)# | Calibrated based on findings of Huffman et al. 2018 [29] |
| Reinfarction (in 30 days) | 0.0120 (0.0099–0.0141)ψ | ACS QUIK Study by Huffman et al. 2018 [29] |
| Acute Stroke (in 30 days) | 0.0060 (0.0045–0.0075)ψ | ACS QUIK Study by Huffman et al. 2018 [29] |
| Stroke | ||
| Probability of Stroke if CVD event occurs | 33.2–62.3% (Age- and sex- specific)# | Calculated based on GBD 2017 [3] |
| 30-day fatality | 0.12, 0.13 (Sex-specific)# | Calibrated based on a multi-site study by Pandian and Sudhan 2013 [30] |
| Repeat Stroke (in 30 days) | 0.15 (0.1–0.2)ψ | Petty et al. 1998 [32] |
| Chronic CVD Events | ||
| Ischemic Heart Disease (IHD) | ||
| Monthly risk of mortality | 0.001–0.019 (Age- and sex- specific)# | Calibrated based on GBD 2017 [3] |
| Reinfarction | 0.079 (0.073–0.085)ψ | Based on Steg et al. 2007 [31] and derived by Lin et al. 2019 [33] |
| Acute Stroke | 0.014 (0.012–0.016)ψ | Based on Steg et al. 2007 [31], and derived by Lin et al. 2019 [33] |
| Stroke | ||
| Monthly risk of mortality | 0.001–0.013 (Age- and sex- specific)# | Calibrated based on GBD 2017 [3] |
| Acute MI | 0.043 (0.038–0.048)ψ | Based on Steg et al. 2007 [31], and derived by Lin et al. 2019 [33] |
| Acute Stroke | 0.037 (0.033–0.041)ψ | Based on Steg et al. 2007 [31], and derived by Lin et al. 2019 [33] |
| Relative risk of fatality for an individual with two or more CVD events | 1.5 | Smolina et al. 2012 [38] |
| Effect of antihypertensive medication | ||
| Medication protocol for an individual | Initial SBP-specific# | Based on India Hypertension Control Initiative (IHCI) implemented in Punjab [39, 40] |
| IHD relative risk due to medication | 0.32–0.89 (Age- and initial SBP-specific)# | Based on findings by Law et al. 2009 [28] |
| Stroke relative risk due to medication | 0.20–0.89 (Age- and initial SBP-specific)# | Based on findings by Law et al. 2009 [28] |
| IHD relative risk if partially adherent | 0.66–0.95 (Age- and initial SBP-specific) | Calculated based on a linear relationship between adherence and efficacy as considered by Cherry et al. 2009 [41] |
| Stroke relative risk if partially adherent | 0.60–0.95 (Age- and initial SBP-specific) | Calculated based on a linear relationship between adherence and efficacy as considered by Cherry et al. 2009 [41] |
| Costs | ||
| Programmatic Cost of Intervention | $0.13 per individual per annum# | Calculated from resource costs of India Hypertension Control Initiative |
| Antihypertensive treatment | ||
| Antihypertensive medication (per individual per annum) in public sector | $0.88–17.90 (Drug and dosage specific)§ | Drug costs based on government rate contracts [42], and the type and dosage drug dispensed is based on the treatment protocol |
| Antihypertensive medication (per individual per annum) in private sector | $5.42–$125.14 (Drug and dosage specific)§ | Average cost from Indian online drug retailer 1mg.com [43], and the type and dosage drug dispensed is based on the treatment protocol |
| Out-patient consultations (per visit) | $1.94 ($1.36–$2.47)§ | Based on Indian public healthcare sector study by Prinja et al. 2020 [44] |
| One-time diagnostic tests | $2.27 | Government rate contracts [45] |
| Acute CVD care | ||
| In-patient costs for MI | $1040 | WHO Choice [46] inflated to 2019–20 |
| In-patient costs for Stroke | $940 | WHO Choice [46] inflated to 2019–20 |
| Chronic CVD care | ||
| Secondary care medication in public sector (per individual per annum) | $92, $184 (Dosage-specific)§ | International Drug Price Indicator inflated to 2019–20 [47] |
| Secondary care medication in private sector (per individual per annum) | $227, $454 (Dosage-specific)§ | Mean cost from Indian online drug retailer 1mg.com [43] |
| Outpatient cost for IHD (per annum) | $45 | WHO Choice [46] inflated to 2019–20 |
| Outpatient cost for Stroke (per annum) | $67 | WHO Choice [46] inflated to 2019–20 |
| Disability Weights | ||
| Disutility due to daily medication | 0.049 (0.031–0.072)ψ | GBD disability weights [48] |
| Acute Events | ||
| Myocardial Infarction | 0.432 (0.288–0.579)ψ | GBD disability weights [48] |
| Stroke | 0.570 (0.377–0.707)ψ | GBD disability weights [48] |
| Occurrence of second or later CVD event | 0.985 (0.992–0.989)ψ | GBD disability weights and Lin et al. 2019 [33] |
| Chronic States | ||
| Ischemic Heart Disease | 0.08 (0.02–0.24)ψ | GBD disability weights [48] |
| Stroke | 0.135 (0.01–0.437)ψ | GBD disability weights [48] |
| Alive post 2+ CVD Events | 0.242 (0.11–0.437)ψ | GBD disability weights [48] |
[i] The ranges marked with # are further expanded in the Appendix Table S2–5 since the specific value for an individual is based on an individual’s age, sex, and/or SBP. The cost ranges marked with § are based on the specific drug and dosage administered to an individual and has been further expanded in the Appendix Table S6–9. The ranges with the superscript of ψ are 95% confidence intervals with the values sampled based on a β distribution in the simulation runs.
Table 2
Costs and health outcomes associated with 70% coverage and adherence in a hypertension control intervention for individuals between 40–69 yrs from 2020–40
| ICER ($/DALY averted, 95% UI) | DALYs Averted (percent, 95% UI) | CVD Events Averted (percent, 95% UI) | Per-capita incremental costs over 20 years^ | Annual net expenditure^,ψ (in ‘000 US $) | Proba-bility of Cost Saving# | ||||
|---|---|---|---|---|---|---|---|---|---|
| Female | Male | Female | Male | Female | Male | Antihypertensive Treatment ($, 95% UI) | CVD Treatment ($, 95% UI) | ||
| Cost-saving | Cost-Saving | 2.17 (2.15 to 2.19) | 1.30 (1.29 to 1.32) | 5.85 (5.82 to 5.89) | 3.78 (3.75 to 3.81) | 18.04 (17.95 to 18.13) | –19.43 (–19.55 to –19.3) | –$26,740 | 0.721 |
[i] The results are based on 1000 simulation runs with a time horizon of 20 years in two hypothetical cohorts of 10,000 individuals (males and females respectively) with ages 40–69 yrs at the start of the simulation. The status quo is based on 17% coverage, 30% adherence, and the NPCDCS medication guideline.
^ Negative values indicate cost-saving, i.e., lower expenditure compared to status quo, and the values are calculated based on the estimated Indian population of age 40–69 yrs in 2020.
ψ The estimated population of age 40–69 yrs in 2020 was used to calculate the annual expenditure for the population.
# The probability of cost-saving was calculated based on the number of simulations runs which saved overall costs among the 1000 simulation runs.
Figure 2
Increasing coverage vis-à-vis adherence.
We assessed multiple scenarios of coverage and adherence to antihypertensive treatment compared to the status quo (coverage = 17%, adherence = 30%), and present the cost-effectiveness (panel A), incremental cost (panel B) and DALYs averted (panel C). Each column provides information for a coverage scenario with varying adherence, and each row provides information for a adherence scenario with varying treatment coverage. In panel A, the cells in blue indicate a cost-saving scenario, and cells in purple and yellow indicate a highly cost-effective scenario. The gradient of cell color is indicative of the changing cost-effectiveness. In panel B and C, the incremental cost and DALYs averted is presented with different scenarios of coverage and adherence compared to status quo. In general, moving from yellow to blue is advantageous. The results are based on 1000 simulation runs with a time horizon of 20 years in two hypothetical cohort of 10,000 individuals (males and females respectively) with ages of 40–69 yrs at the start of the simulation.
ICER = Incremental Cost Effectiveness Ratio, DALY = Disability Adjusted Life Year, CS = Cost Saving.
Figure 3
Incremental costs and DALYs averted under changes in sensitivity parameters.
We assessed the robustness of our model through changes in select input parameters in a one-way sensitivity analysis. The x-axis and y-axis represent the DALYs averted and incremental cost compared to the status quo, and the error bars are based on the 95% confidence intervals. The text in the parenthesis along with the scenario name is the ICER ($/DALYs averted), with CS representing cost-saving scenario. The base case analysis) was cost-saving. If the medication cost was increased, the scenarios were no longer cost-saving, but the ICERs were below $110 and thus highly cost-effective. When the programmatic cost was quadrupled, the scenario did not save overall costs, but remained highly cost-effective. Under the assumption that the Globorisk calculator overestimates CVD risk, we ran the simulation with a 20% reduction in baseline risk and found the scenario no longer saved costs. If the treatment protocol was changed to the current NPCDCS guideline the cost savings increased. If the simulations were run with a reduced time horizon of 10 years, the scenario was highly cost-effective. When the simulations were run for a longer time-horizon of 40 years, the cost-savings increased. The values in the green band indicate cost savings, whereas the values in blue band indicate high cost-effectiveness. The results are based on 1000 simulation runs in two hypothetical cohort of 10,000 individuals (males and females respectively) with ages of 40–69 yrs at the start of simulation, with a high cost-effectiveness threshold of 0.5* GDP ($1169).
ICER = Incremental Cost Effectiveness Ratio, GDP = Gross Domestic Product.