Figure 6

Causal loop diagram of creat access to new medicine

Figure 7

Causual loop diagram of supply consumption of medicine

Figure 8

Causual loop diagram of health consequences

Figure 9

Results of defrazirox and deferoxamine simulations in thalassemia. A. Birth rate simulation pattern, B. Thalassemia incidence simulation pattern, C. Thalassemia outbreak behavior simulation pattern, D. Simulated pattern of patients' treatment demand Thalassemia, E. Simulation pattern of deferoxamine use, F. Simulated pattern of use of Deferasirox and exjade, G. Simulated pattern of deferasirox production, H. Simulated pattern of production of Deferoxamine, I. Simulated pattern of import of Exjade, J. Simulated behavior of burden of thalassemia, K. Simulated cost behavior of thalassemia patients, L. Simulated model of health system cost in thalassemia patients

Equation:

Prevalence = INTEG (Incidence-finished patients)

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Incidence = ((Incidence rate Children*Birth) + (Incidence rate Children*Children Population) + (Incidence rate middle*Middle Population) + (Incidence rate old*Population old) + (Incidence rate young*Young Population))*(congeniality*Contiguous multiplier*Gender Multiplier*Diagnose Multiplier*Incidence Multiplier)

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Finished patients = (Prevalence*survival) + Death Rate*Prevalence

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Demand: Treatment-Monthly Unit = INTEG MIN (5e + 007, MAX (0, Primary demands-The Alternative consumption-No Medication Need-The Medicine Consumption))

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Primary demands = Prevalence*(1 + Induced Demand)*"X1 coif."*Treatment rate by the Alternative.

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No Medication Need = IF THEN ELSE ("Demand: Treatment-Monthly Unit" < 1, 0, Controlled with ought medication*"Demand: Treatment-Monthly Unit”)

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Consumption: The new Medicine = INTEG (The Medicine Consumption)

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The New Medicine Consumption = IF THEN ELSE ("Demand: Treatment-Monthly Unit" < 1, 0, MAX (0, ((1-"Consumption rate Alt/Med")*"Demand: Treatment-Monthly Unit"*"the Medicine DDD/mo."*Adherence to the New Medicine*the New Medicine Purchase Rate*Treatment Duration for the Medicine/120)))

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The New Medicine Purchase Rate = SMOOTH ((The New Medicine vailability^0.2)*(The New Medicine Affordability + WTP for The New Medicine)/2, 4)

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Adherence to the New Medicine = (efficacy of New Medicine + Quality of New Medicine + Patients preferences for New Medicine + Safety of The New Medicine + Usage Interval for New Medicine—Treatment Duration of The New Medicine—Death Rate of New Medicine-ADR for New Medicine)/9

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Consumption: The Current Alternative = INTG (The Alternative consumption)

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The Alternative consumption = IF THEN ELSE ("Demand: Treatment-Monthly Unit" < 1, 0,"Consumption rate Alt/Med"*"Demand: Treatment-Monthly Unit"*"The Alternative DDD/Mo"*Adherence to the Alternative*The Alternative Purchase Rate*Alternative Treatment Duration/120)

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Adherence to the Alternative = (Alternative Medicine Efficacy + Quality of Alternative Medicine + Alternative Patients preferences + Alternative Product Safety + Alternative Usage Interval-Alternative Treatment Duration-Death rate of Alternative-ADR for Alternative)/9

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Consumption rate Alt/Med = ("Initial rate Alt/Med" + MIN (1,"Consumption: The Current alternative"/"Consumption: The new Medicine"))/2

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The Alternative Purchase Rate = SMOOTH ((Availability of alternative^0.2) * (The Alternative Affordability + WTP for Alternative Medicine)/2, 4)

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The Alternative stock = INTEG "Alt. Domestic Production “ + Importation of Alternative-Current Alternative Consumer Purchase-"Stock Reducer Alt."

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Importation of Alternative = MAX (Need to Supply of Alternative*(1-"Alt Dom/Imp"), 0)

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Alt. Domestic Production = MAX (Need to Supply of Alternative*"Alt Dom/Imp"*"Alt. Profit of Producer", 0)

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Alt Dom/Imp = "Alt. Dom. Prim Ratio"*(1 + Investment)

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Current Alternative Consumer Purchase = IF THEN ELSE (The Alternative stock > 0, MIN (The Alternative stock, The Alternative consumption), 0)

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Stock Reducer Alt = The Alternative stock*Alt Reducer Coe/100

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Alt. Profit of Producer = SMOOTH ((Alternative product price-"Alt. Production cost")/Alternative product price, 4)

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Need to Supply of Alternative = IF THEN ELSE (The Alternative stock < 4*The Alternative consumption: OR: The Alternative stock < "Demand: Treatment-Monthly Unit", The Alternative consumption *1.1, The Alternative consumption*0.01)

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The new Medicines stock = INTEG (NM Domestic Production + Importation + Single Prescription suppliers-Current Consumer Purchase-Stock Reducer N med)

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NM Importation = Need to Supply the Medicine*(1-"Product (Domestic ratio)")

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NM Domestic Production = Need to Supply the Medicine*"Product (Domestic ratio)" + 0*"NM. Profit of Producer"

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Product (Domestic ratio) = NM Prim Dom*(1 + Investment)

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Single Prescription suppliers = IF THEN ELSE (“product (in IDL, out IDL)" = 1, 0, 0.01)

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NM. Profit of Producer = SMOOTH ((product price-"NM. Production Costs")/product price, 4)

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Current Consumer Purchase = IF THEN ELSE (The new Medicines stock > 0, MIN (The new Medicines stock, The New Medicine Consumption), 0)

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Stock Reducer N med = The Med Reducer Coe*the new Medicines stock/100

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Need to Supply the New Medicine = IF THEN ELSE (The new Medicines stock < 4*The New Medicine Consupmtion: OR: The new Medicines stock < "Demand: Treatment-Monthly Unit", The New Medicine Consumption*1.1, 0.05)

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The New Medicine Availability = MIN (1, the new Medicines stock/ ("Demand: Treatment-Monthly Unit" + 1))

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Availability of alternative = MIN (1, The Alternative stock/ (1 + "Demand: Treatment-Monthly Unit"))

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Total patients cost = INTEG (total costs-Income)

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Total costs = household cost + OOP of the New Medicine + Indirect non-medical Costs + indirect cost

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Income = Initial Income*(1 + Income Increase) ^Time

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Catastrophic expenditure = OOP of the New Medicine/income-household cost

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Impoverished Costs = total health cost/Catastrophic expenditure

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Household cost = Household Initial*(1 + Inflation Rate) ^Time

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Saving = (Income-household cost)

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Equity = ABS (MIN (0, (Insurances Coverage of New Medicine*(OOP of the New Medicine + Catastrofic expenditure + 1))))*0.0001

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Insurances Coverage of Alternative = IF THEN ELSE ("Alternative product basic insurance coverage (positive, negative)" = 1, IF THEN ELSE ("Product place of use (In-patients, out-patients)" = 1, 0.9, 0.7), 0

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Insurances Coverage of New Medicine = IF THEN ELSE ("product basic insurance coverage (positive, negative)" = 1, IF THEN ELSE ("Product place of use (In-patients, out-patients)" = 1, 0.9, 0.7), 0)

**********************************************************************

OOP of the Alternative Medicine = IF THEN ELSE (Alternative product in PHC, 0, "Alt. medication costs"*(1-Insurances Coverage of Alternative))

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OOP of the New Medicine = IF THEN ELSE (product in PHC, 0, the medication costs*(1-Insurances Coverage of New Medicine)) + Illegal supply Counterfeit

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Alt. medication costs = (Alternative product price-Alternative product subsidy)*"The Alternative DDD/Mo"*((1 + Inflation Rate) ^Time)

********************************************************************

The Alternative Affordability = IF THEN ELSE (OOP of the Alternative Medicine < Saving, 1, Saving / OOP of the Alternative Medicine)

**********************************************************************

Patient Life Time of Alternative = IF THEN ELSE ("Consumption: The Current Alternative" > 1, Adherence to the Alternative, 0)

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Quality of Life of Alternative Medicine = IF THEN ELSE ("Consumption: The Current Alternative" > 1, Adherence to the Alternative, 0)

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The Alternative Stop rate = 1/ (Adherence to the Alternative + 1)

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Efficacy of New Medicine: "Consumption: The new Medicine"/ ("Demand: Treatment-Monthly Unit “ + ”Consumption: The new Medicine" + 1)

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Burden of Diseases = (Patient with Disability + Patient with dying prematurely)-("Patient with life time (Alt)" + "Patient with life time (NM)" + "Patient with QOL (MN)" + "Patient with QOL (Alt)")

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Quality of Life of New medicine: (0.6*Adherence to the New Medicine*0.4*"Consumption: The new Medicine"*efficacy of New Medicine*1e-005)

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Patient Life Time of New Medicine = 0.8*Adherence to the New Medicine*0.6*efficacy of New Medicine*"Consumption: The new Medicine"*5e-006

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Impact (Health level) = (Burden of Diseases + Equity + Life Expectancy + Patient Life Time of New Medicine + Patinet Life Time of Alternative + Quality of Life of New medicine + Qulaity of Life of Alternative Medicine)/7

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Access = (The New Medicine Affordability + the New Medicine Availability + efficacy of New Medicine + Safety of The New Medicine + GDP)/5

**********************************************************************

Induced Demand = Product Promotion

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Illegal supply Counterfeit = INTEG IF THEN ELSE (The new Medicines stock < The New Medicine Consumption, 1, 0)

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The New Medicine Affordability = IF THEN ELSE (OOP of the New Medicine < Saving, 1, Saving / OOP of the New Medicine)

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The New medication costs = (product price-product subsidy)*"the Medicine DDD/mo."*((1 + Inflation Rate) ^Time)

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GDP = INTEG (GDP Growth-GDP outflow)

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GDP Growth = ("Alt. Domestic Production"*"Alt. Profit of Producer “ + NM Domestic Production*"NM. Profit of Producer “ + Complexity Index*GDP/10 + "Impact (Health level)"*GDP/20 + "Res. & Eddo"*GDP/20 + Tech Transfer*GDP/50)/10000

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GDP outflow = GDP*"gdp red."

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Children Population = INTEG (Birth-Becoming Young-death children)

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Birth = Birth Rate for youth*Young Population + Birth Rate for Middle*Middle Population

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Death children = Death Rate Children*Children Population

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Becoming Young = Children Population/Child Age

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Young Population = INTEG (Becoming Young-Becoming Middle-Death Young)

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Becoming Middle = Young Population/Young Age

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Death Young = Death Rate Young*Young Population

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Becoming Middle = Young Population/Young Age

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Middle Population = INTEG (Becoming Middle-Becoming Old-Death Middle)

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Death Middle = Middle Population*Death Rate Middle

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Becoming Old = Middle Population/Middle Age

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Old Population = INTEG (Becoming Old-Death Old)

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Death Old = Population old/Old age

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Population total = Young Population + Population old + Children Population + Middle Population

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Death Rate = death total/population total

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Death total = Death Young + Death Old + death children + Death Middle