# TB Drugs

Part
01
of three
Part
01

## Tuberculosis Drug Costs: Brazil

To provide an estimate of the costs of prescription medications used to treat Tuberculosis (TB) in Brazil, we found the standard treatment regimen for TB and pricing for each medication. Below, I will explain the standard treatment regimen for non-drug-resistant TB and the calculations performed to estimate average cost. All the prices are Brazilian reals.

### TB Treatment in Brazil

Prior to 2010, Brazil used to use a combination of three drugs in two phases to treat TB. This treatment, called 2RHZ/4RH, included an intensive two-month phase in which a patient took rifampin, isoniazid, and pyrazinamide daily, followed by a four-month phase in which a patient took rifampin and isoniazid daily. After seeing drug resistances increase over a decade, the Brazilian National Tuberculosis Control Program decided to include another drug in the intensive phase — ethambutol. The new treatment, called 2RHZE/4RH, had a two-month intensive phase of rifampin, isoniazid, pyrazinamide, and ethambutol daily, followed by a four-month phase of rifampin and isoniazid.

Fixed-dose treatment is a treatment that combines fixed doses of each medication into one pill for a patient to take daily. Without information on pricing of these kinds of medications, we provided pricing for each medication separately, which is still a common form of treatment.

### Calculations

The following approach was taken to calculate the costs of drug treatment.

1. The number of pills needed for each medication was calculated using 30 days as a substitute for one month. Each pill is taken daily, meaning one day is equal to one pill.

Six (two intensive + four non-intensive) months of rifampin - 180 pills
Six (two intensive + four non-intensive) months of isoniazid - 180 pills
Two (two intensive) months of pyrazinamide - 60 pills
Two (two intensive) months of ethambutol - 60 pills

2. The Brazilian Chamber of Market Regulation of Medications (CMED) was used to find prices for each medication. CMED lists each drug by active ingredient and includes the factory price (PF) and the maximum consumer price (PMC) for each drug divided into several tax levels. Taxes on drugs differ by state, so I have listed the prices at the lowest and highest tax rates. The PF is the price that pharmacies and drugstores pay for drugs, and the PMC is the maximum price that pharmacies and drugstores can charge for each drug.

Not every drug was allowed to be sold to consumers, so I have broken the costs into PMC and PF pricings for more accuracy. Additionally, as these are the absolute highest prices that are allowed, if multiple generics exist I have chosen the lowest priced drug to avoid overestimation.

### Factory price (pf)

Rifampin (also known as rifampicin) costs R\$10.53 - R\$13.16 per 6 pills. TB treatment requires 180 rifampin pills, so the total cost would be between R\$315.90 and R\$394.80.

Isoniazid costs R\$31.2 - R\$39 per 10 pills. Treatment requires 180 pills, so the total cost would be between R\$561.6 and R\$702.

Pyrazinamide costs \$R111.08 for 10 pills. Treatment requires 60 pills, so the total cost would be R\$666.48.

Ethambutol costs R\$162.99 for 5 pills. Treatment requires 60 pills, so the total cost would be R\$1,955.88.

Based on the above, the total cost for TB treatment drugs purchased by a factory to treat one person is between R\$3,499.86 and R\$3,719.16.

### Maximum Consumer price (PMC)

For this calculation, I had to present prices for a drug other than ethambutol, is it is not available for purchase by consumers. A recent study showed that moxifloxacin can be a good substitute for ethambutol when treating TB, so I have included the PMC pricing for moxifloxacin in this estimate. Moxifloxacin is considerably cheaper than ethambutol, but without PMC pricing for it, ethambutol cannot be included in this estimation.

Rifampin (also known as rifampicin) costs R\$14.56 - R\$18.19 per 6 pills. TB treatment requires 180 rifampin pills, so the total cost would be between R\$436.8 and R\$545.7.

Isoniazid costs R\$43.13 - R\$53.92 per 10 pills. Treatment requires 180 pills, so the total cost would be between R\$776.34 and R\$970.56.

Pyrazinamide costs \$R153.6 for 10 pills. Treatment requires 60 pills, so the total cost would be R\$921.36.

Moxifloxacin costs R\$80.72 -R\$100.9 for 5 pills. Treatment requires 60 pills, so the total cost would be between R\$968.64 and R\$1,210.8.

Based on the figures provided above, the total cost for TB treatment drugs purchased by a consumer to treat one person ranges between R\$3,103.14 and R\$3,648.42.

### Note on pricing and purchasing

Drug pricing for consumers is a bit of a nebulous way to calculate the cost of prescription medications because essential medicines that treat the most common diseases (like TB) are distributed free of charge to Brazilian citizens, which means some people pay nothing for their TB treatment. However, the availability of these free medications is not always enough to satisfy need, so the Brazilian government launched a “popular pharmacy” program that sells medications at low prices. Even though medication is supposed to be free to citizens, Brazilians spend about 2% of all household income on medications. About a quarter of families in Brazil pay for private health insurance, which does not cover all medications. Due to the inaccessibility of free medicines and the use of private insurance, medication still has consumer pricing.

### Conclusion

The factory price for the drugs needed to treat TB in one person in Brazil ranges between R\$3,499.86 and R\$3,719.16. The consumer price for this treatment is R\$3,103.14 and R\$3,648.42, with ethambutol substituted with commercially available moxifloxacin. If the medications are available, some people in Brazil may not even pay for their TB treatment as the government may provide essential medicines free of charge.
Part
02
of three
Part
02

## Tuberculosis Drug Costs: China

Different studies identify different ranges of costs for full tuberculosis treatement in China. An academic study identifies the average out-of-pocket costs of \$2,262 for Zhangjiagang (CNY 14,304.4) and \$891.5 for Tunxi (CNY 5,639.2). An economic study that focused on four provinces in China identified the range of costs as CNY 1,240 (\$196.08) in Xinjiang to CNY 2,600 (\$411.14) in Liaoning for a tuberculosis patient's complete diagnosis and treatement. BMC Public Health research found out that low income patients pay between \$149 and \$724 for medical costs for one treatment course. When expressed as a percentage of annual household income, this amounts to between 42% and 119%. The Global Fund in China research lists the patient costs that range from \$4,797 during RV to \$6,274 during NCE.

### METHODOLOGY

In this research, we were able to identify the full cost of treatement (from diagnosis to cure) for tuberculosis patients. We identified a range of costs, as well as an average across different counties in China, as costs vary across the country. We specified all costs in USD\$, and if they haven't been indicated as such, we used a converter to provide all the amounts in dollars.

We weren't able to find the costs of drug treatment for both drug-sensitive and drug-resistant strains of Tuberculosis, as these two types of costs weren't differentiated in sources we were able to find.
The first source is an academic research from 2015, which is older than the standard Wonder source age of up to 24 months. However, we included it as we find it valuable because it provides a range of costs across two different counties in China and lists the costs for the full treatment. After looking for the recent repeat of this research, we identified that this was the only such research conducted so far.

While this source is older than 24 months, it provides a great overview of difference in costs in different parts of China. Such study hasn't been conducted since, which is the main reason we are including it in this research. This study was published in 2015, and it is an academic study between two counties in China listing the average (median, interquartile range) total cost of CNY 18,793.33 for patients in Zhangjiagang county, which was significantly higher than for patients in Tunxi (CNY 6,598.33). After excluding expenses covered by health insurance, the average out-of-pocket costs were CNY 14,304.4 in Zhangjiagang and CNY 5,639.2 in Tunxi.

According to this converter, 1 USD = 6.32311 CNY. This leads to the total cost for the Zhangjiagang county of \$2,972.2 (CNY 18,793.33), and \$1,043.5 for Tunxi county (CNY 6,598.33). After excluding expenses, this amounts to the average out-of-pocket costs of \$2,262 for Zhangjiagang (CNY 14,304.4) and \$891.5 for Tunxi (CNY 5,639.2).

Based on the multivariable linear regression analysis, factors that were related to the total out-of-pocket costs were "study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs".

### Global fund in china findings

The Global Fund in China research lists the patient costs that range from \$4,797 during RV to \$6,274 during NCE. In each Global Fund round, the cost per patient were different in composition of expenditures and also when it comes to the total cost. Hospitalization fees accounted for much of these differences, with \$500 (10.4%) under RV, \$1,000 (18.2%) under RVII, and \$1,700 (28.4%) under both SSF and NCE.

During RV, just 20% of patients were hospitalized, with increased hospitalization provisions set up in order to have more adequate coverage of patient expenses.

Second-line drugs were the main source of costs and accounted for more than 50% of overall costs during all four phases: "Under RV, standardized second-line treatment cost \$3,153, increasing to \$3,250 under RVII due to the addition of levofloxacin (Lfx) in 2009. Under SSF, cycloserine (Cs), moxifloxacin (Mfx), clarithromycin (Clr), and amoxicillin plus clavulanate (Amx/Clv) were added in 2012, with total treatment cost of \$3,432. In 2013 under NCE, cost increased to \$3,727 in order to regulate the amikacin (Am): capreomycin (Cm) ratio from 8:2 to 6:4. Under SSF, the Chinese Ministry of Civil Affairs took over responsibility for providing subsidies for poor patients".

### ECONOMIC STUDY of FOUR PROVINCES

An economic study was conducted in four provinces of China where researchers interviewed 889 tuberculosis patients and 2560 community residents as well as conducted in-depth interviews with key informants. Costs ranged from CNY 1,240 (\$196.08) in Xinjiang to CNY 2,600 (\$411.14) in Liaoning for a tuberculosis patient's complete diagnosis and treatment.

### BMC Public Health research

BMC Public Health research found out that low income patients pay between \$149 and \$724 for medical costs for one treatment course. When expressed as a percentage of annual household income, this amounts to between 42% and 119%. This leads to the conclusion that "despite a policy of free drug treatment for TB in China, health services charge all income groups, and costs are high".

### Conclusion

The full cost of treatment (from diagnosis to cure) for tuberculosis in China varies across the country. It ranges from \$149 to \$6,274. When expressed as a percentage of annual household income, this amounts to between 42% and 119%.
Part
03
of three
Part
03

## Tuberculosis Drug Costs: Russia

Research from 2002 indicates the average cost per patient (outpatient) of drug therapy over several months was \$50. If drug costs and dollar exchange ratio remains the same rate, today's cost for the same several months of chemotherapy would be \$27 in US dollars.

Assuming that the ratio of drug costs and dollar exchange rate is the same:
Estimated cost per normal TB patient is \$81 (for 9 months); Estimated cost per MDR-TB patient is \$216 (for 24 months); Estimated cost per MDR-TB patient is \$216 (for 24 months).
Estimated cost of treatment of Normal TB patients = \$4,565,808 to \$4,715,496 for 9 months of treatment;
Estimated cost of treatment of MDR- TB patients = \$5,388,984 to \$5,788,368 for around 24 months of treatment
Estimated cost of treatment of XDR- TB patients = \$199,584 for around 24 months of treatment.

I was unable to find data on what Russia is paying for TB drugs today. From my research, I understand that Russia is trying to source most of the drugs domestically. I am almost certain that using American pricing of TB drugs would skew incorrectly for the Russian market. Therefore, I have referred to the exchange rates and made a ratio comparison.

### Findings

According to WHO, the estimated TB incidence (new and relapse) in Russia in 2016 is 92,407 people. The countries national TB treatment budget for 2016 was \$1.175 billion (\$1,175,000,000) in US dollars. Tuberculosis diagnosis, medical treatment and care are, by law, free to patients in Russia since 2001.

Of the total number of TB cases in Russia, the incidence of MDR-TB (multidrug-resistant TB) is estimated at 27-29% and the incidence of XDR-TB (extensively multidrug-resistant TB) is estimated at 10% .

### Treatment of MDR-TB and XDR-TB

Treatment of MDR-TB and XDR-TB require additional stepped drug therapy using five groups of medications including higher doses of:
1. Isoniazid, pyrazinamide, and ethambutol
2. Fluoroquinolones,
3. Injectable antibiotics from the aminoglycoside class
4. Second-line drugs (for cases resistant to drugs from groups one through three)
5. A group of antibiotic drugs whose efficacy in resistant TB cases is not certain.

### ESTIMATED COST OF PRESCRIPTION MEDICATIONS IN RUSSIA

In a 3-year study (1999–2002) conducted in the Samara Oblast region of the Russian Federation, the average cost an outpatient-based course of chemotherapy was about US\$50, spread over
several months. Unfortunately, this is the most recent information available with exact costs for TB drugs.

The exchange rate for US dollars to Russian Rubles on
January 30, 2002, was 0.033 USD per 1 ruble.
January 30, 2018, is 0.018 USD per 1 ruble.

Note: The following currency amounts are in US dollars.

### Calculations

Assumption made: The ratio of drug costs and dollar exchange rate is the same, which is most likely not the case.

0.018/0.033=0.54 x \$50 (USD)= \$27 for several months of therapy.

According to Centers for Disease Control and Prevention, TB therapy takes 6 to 9 months.

Assuming that several months means three months, the drug cost for 6 to 9 months treatment would be:
3 months (\$91.50) x2= \$54 (for 6 months) to 3 months (\$91.50) x 3 = \$81 (for 9 months).
MDR-TB therapy takes around 24 months:
\$27 x (24/3) =\$216
XDR-TB therapy also requires at least 24 months of therapy:
\$27 x (24/3) =\$216
The estimated total TB incidence in Russia (new and relapse) is 92407 people
Normal TB is estimated to constitute 61% to 63% of the TB treatment population —
[56,368 to 58,216 people] x \$81 =\$4,565,808 to \$4,715,496 in TB drug costs for 9 months.
Estimated MDR- TB population under treatment — 27% to29%= [24,949 to 26798] x 216 = \$5,388,984 — \$5,788,368

Estimated XDR-TB population — 10% of total TB population= 924 X \$216 = \$199,584

### CONCLUSION

Assuming that the ratio of drug costs and dollar exchange rate is the same, which is most likely not the case.
Estimated cost per normal TB patient is \$81 (for 9 months).
Estimated cost per MDR-TB patient is \$216 (for 24 months).
Estimated cost per MDR-TB patient is \$216 (for 24 months).

Estimated cost of treatment of Normal TB patients = \$4,565,808 to \$4,715,496 for 9 months of treatment.

Estimated cost of treatment of MDR- TB patients =\$5,388,984 to \$5,788,368 for around 24 months of treatment.

Estimated cost of treatment of XDR- TB patients =\$199,584 for around 24 months of treatment.
Sources
Sources