Public procurement of antineoplastic agents used for treating breast cancer in Brazil between 2013 and 2019.

BACKGROUND: Breast cancer is the most common cancer among women in Brazil and the country's public health care system is the main care provider. Timely treatment can increase the chance of cure, prevent metastasis and improve quality of life. Effective public procurement of antineoplastic agents can therefore improve access to drug therapy. This study investigates patterns in the procurement of selected antineoplastic agents used for treating breast cancer by public bodies and avoidable expenditure on these drugs between January 2013 and December 2019.
METHODS: We selected antineoplastic agents used for adjuvant or preoperative chemotherapy listed in the 2018 Breast Cancer Diagnosis and Treatment Guidelines and included in category L of the WHO Anatomical Therapeutic Chemical classification system. We analyzed regular purchases of antineoplastic agents registered in the Integrated General Services Administration System (SIASG), considering purchased quantity, unit price, date of purchase and procuring entity. Prices were inflation-adjusted to July 2019 based on the National Consumer Price Index.
RESULTS: A total of 10 antineoplastic agents were selected. Trastuzumab and tamoxifen accounted for the largest share of total spending and largest volume of purchases, respectively. The Ministry of Education was the largest purchaser in volume terms of all the drugs studied, except trastuzumab 440 mg, where the category "Other Institutions" accounted for most purchases, and vinorelbine 20 mg, where the Ministry of Health made most purchases. The category "Other Institutions" accounted for the largest share of total spending. Total avoidable expenditure was R$99,130,645. Prices paid for medicines and avoidable expenditure were highest in the Ministry of Defense.
CONCLUSIONS: The differences observed in the performance of different categories of buyers as to amounts purchased and prices practiced for antineoplastic agents could be reduced by employing strategies to expand the centralization of purchases, resulting in expanded access to breast cancer medicines in the public sector.

Background

Cancer is a major public health problem in both developing and developed countries. Globally, the disease is the second leading cause of death and was responsible for around 9.6 million deaths in 2018. One in five deaths is due to cancer and approximately 70% of cancer deaths occur in low and middle-income countries [1]. In Brazil, neoplasms are considered a public health problem due to their significant disease burden, high care costs and complex health care needs, which include surgery, chemotherapy, radiotherapy and complementary tests. Data from the country’s mortality information system (SIM, acronym in Portuguese) reveal that there were 235,301 cancer deaths in 2019, with the largest number of deaths occurring in the Southeast region [2].

Breast cancer has the highest mortality rate among malignant neoplasms in Brazil and worldwide. The World Health Organization (WHO) estimates that there are more than one million new cases of this type of cancer worldwide each year, making it the most common cancer among women [3]. The population-adjusted breast cancer mortality rate is increasing and breast cancer is currently the leading cause of cancer deaths among women in Brazil, resulting in 13.68 deaths/100,000 population in 2015 [4]. Figures from the National Cancer Institute (INCA, acronym in Portuguese) show that there was an annual average of 66,280 new breast cancer cases in Brazil between 2020 and 2022, confirming that it is the most common cancer among women [5].

Breast cancer treatments include chemotherapy, which is used in between 60 and 70% of patients [6]. The steady rise in the cost of treatment using antineoplastic agents is worrying, especially considering that this class of medicines has a major impact on spending by the country’s national health service – Sistema Único de Saúde (SUS) or Unified Health System – accounting for 46% of total expenditure on medicines in 2012 [7, 8]. Spending on cancer treatment has risen dramatically in recent years, from R$470 million in 1999 to R$3.3 billion in 2015. Around two-thirds of this expenditure was related to chemotherapy [9]. In view of the high incidence and prevalence of breast cancer in the country and the import role the public health system plays in cancer treatment, the analysis of government procurement of medicines can provide essential information for understanding the availability of and access to antineoplastic agents.

The aim of this study was to analyze patterns in the procurement of selected antineoplastic agents used for treating breast cancer by public bodies between 2013 and 2019, focusing on purchase quantities, prices paid, and avoidable expenditure on these drugs.

Methods

Study Design

We conducted a quantitative cross-sectional study of public procurement of antineoplastic agents used for treating breast cancer between January 2013 and December 2019.

Selection of antineoplastic drugs

The selection of antineoplastic drugs was based on those used for adjuvant (prophylactic) or preoperative (neoadjuvant/cytoreductive) chemotherapy listed in the 2018 Breast Cancer Diagnosis and Treatment Guidelines [10] and included in category L of the WHO Anatomical Therapeutic Chemical (ATC) classification system [11]. Only medicines purchased by the Ministry of Health in at least five of the seven years of the study period were included. Most of the drugs are only employed in breast cancer, while others have broader indications.

Substances used in combination therapy regimens were excluded (CEF – cyclophosphamide, epirubicin, 5-fluorouracil; CAF – cyclophosphamide, doxorubicin, 5-fluorouracil; AC - doxorubicin (adriamycin), cyclophosphamide; CMF – cyclophosphamide, methotrexate, 5-fluorouracil; and DC – docetaxel, cyclophosphamide).

The final sample included: anastrozole (1 mg); docetaxel (40 mg); exemestane (25 mg); letrozole (2.5 mg); paclitaxel (6 mg); tamoxifen (20 mg); trastuzumab (440 mg); and vinorelbine (10, 20 and 30 mg).1

Data extraction

Data on purchase quantities and prices paid for the selected medicines were obtained from the Integrated General Services Administration System (SIASG). Run by the Ministry of Planning, Budgeting and Management, the data produced by this public procurement and contracting tool are publicly accessible [12]. All purchases made by the Ministry of Health’s Department of Health Logistics and by Ministry of Health hospitals and outpatient facilities, as well those made by university hospitals linked to the Ministry of Education, must be recorded in this system. Ministry of Defense medical services and state and municipal health services register purchases on their own systems and transfer the data to the SIASG [13]. Under Brazilian legislation, quality is assessed as part of the bidding procedures and for the purposes of this study, only active purchases made using competitive bidding procedures were included.

Analysis

The following purchase characteristics were analyzed: medicine specification; unit/dosage form (tablet, capsule, ampoule); purchase date; purchase status (active or inactive); procurement entity; number of units purchased; unit price; and type of procurement (competitive bidding/normal; waiver of competitive bidding; or bidding not required). Furthermore, purchaser categories were assigned: Ministry of Health, Ministry of Education, Ministry of Defense, and “Other Institutions” (other government bodies and subnational organizations, including state and municipal health authorities).

As docetaxel, paclitaxel, trastuzumab and vinorelbine do not have a listed defined daily dose (DDD), for the purposes of this study purchase volume was standardized to mg to allow comparison between medicines. Volume was calculated by multiplying the total number of purchased dosage forms by the dose (mg) of each form.

The annual weighted average price per mg (WAP/mg) paid by each purchaser category for each medicine was calculated by multiplying the volume of each individual drug purchase by the unit price paid and dividing overall expenditure by the total number of mg purchased. We also calculated corrected WAP/mg to allow comparisons over time. Prices were inflation-adjusted to July 2019 based on annual variations in the National Consumer Price Index (IPCA), obtained using the Central Bank citizen’s calculator, available at https://www3.bcb.gov.br/CALCIDADAO. This method was used because the law regulating the pharmaceutical industry (Law 10,742/2003) applies an inflation-based cap to drug prices based on this index [14].

For each year, total spending on each medicine by each purchaser category was divided by the lowest WAP/mg for the medicine in the respective year and multiplied by the WAP/mg actually paid by the procuring entity to calculate how much would have been spent if the medicine had been purchased at the lower price. The resulting amount was then subtracted from actual expenditure to calculate “avoidable expenditure”.

Avoidable expenditure was then divided by the lowest WAP/mg for the medicine in the respective year to calculate the additional quantity of drugs that could have been purchased by applying the principle of economy. The purchase data were organized by year in separate spreadsheets, tabulated and analyzed in dynamic tables using Microsoft Excel® version 2205. The datasets generated during the current study are available in the Arca Dados repository, 10.35078/PPYTKP [15].

Results

Purchases volumes

The Ministry of Education was the largest purchaser in volume terms of all the drugs studied, except trastuzumab 440 mg, where the category “Other Institutions” represented 41.29% of purchases, and vinorelbine 20 mg, where the Ministry of Health accounted for 41.24% of purchases. The Ministry of Health was the second largest purchaser of all drugs, except exemestane 25 mg and letrozole 2.5 mg. The Ministry of Defense was the second largest purchaser of the latter drugs, accounting for 18.96 and 28.86% of purchases, respectively. Tamoxifen 20 mg accounted for the largest volume of purchases across all purchaser categories (Table 1).

Table 1

Public procurement of antineoplastic agents used for treating breast cancer - purchase quantities in mg by purchaser category. Brazil, 2013–2019

Medicine	Ministry of Education		Ministry of Health		Ministry of Defense		Other Institutions		Total (mg)
	N	%	N	%	N	%	N	%
Anastrozole 1 mga	10,838,515	41.25	8,803,262	33.50	2,913,665	11.09	3,722,340	14.17	26,277,782
Docetaxel 40 mgb	12,097,460	45.50	8,352,420	31.41	1,834,800	6.90	4,304,760	16.19	26,589,440
Exemestane 25 mgc	21,923,725	48.42	7,926,800	17.51	8,587,175	18.96	6,842,850	15.11	45,280,550
Letrozole 2.5 mga	2,109,253	58.52	196,850	5.46	1,040,350	28.86	257,963	7.16	3,604,415
Paclitaxel 6 mgb	60,776,655	63.34	18,113,116	18.88	5,987,234	6.24	11,082,205	11.55	95,959,210
Tamoxifen 20 mga	394,563,360	54.89	205,193,800	28.55	26,791,300	3.73	92,260,920	12.84	718,809,382
Trastuzumab 440 mgb	3,030,720	10.25	7,537,200	25.49	6,787,880	22.96	12,208,240	41.29	29,564,040
Vinorelbine 10 mgd	2,058,470	57.79	854,040	23.98	233,700	6.56	415,870	11.67	3,562,080
Vinorelbine 20 mgd	1,047,080	40.60	1,063,520	41.24	428,380	16.61	40,000	1.55	2,578,980
Vinorelbine 30 mgd	3,007,350	56.41	1,512,930	28.38	750,600	14.08	60,000	1.13	5,330,880

Dosage forms: atablet; bampoule; ccapsule; dampoule and capsule.

Source: Integrated General Services Administration System (SIASG)

Expenditures

Total spending over the period was R$1,012,271,080 reais. The category “Other Institutions” accounted for the largest share of total spending (31.76%), followed by the Ministry of Health (26.24%) (Table 2).

Table 2

Public procurement of antineoplastic agents used for treating breast cancer - total spending (R$) by purchaser category. Brazil, 2013–2019

Medicine	Ministry of Education		Ministry of Health		Ministry of Defense		Other Institutions		Total (R$)
	R$	%	R$	%	R$	%	R$	%
Anastrozole 1 mga	13,196,020	39.67	9,337,267	28.07	5,263,653	15.83	5,464,512	16.43	33,261,452
Docetaxel 40 mgb	22,886,244	38.63	19,535,557	32.97	6,095,049	10.29	10,729,355	18.11	59,246,205
Exemestane 25 mgc	16,301,476	50.07	4,857,270	14.92	6,449,958	19.81	4,948,653	15.20	32,557,358
Letrozole 2.5 mga	6,683,805	56.11	573,524	4.81	3,549,046	29.79	1,105,916	9.28	11,912,291
Paclitaxel 6 mgb	26,010,194	57.78	8,515,488	18.92	4,896,219	10.88	5,591,795	12.42	45,013,696
Tamoxifen 20 mga	19,865,277	54.79	9,197,183	25.37	1,604,663	4.43	5,589,036	15.42	36,256,160
Trastuzumab 440 mgb	79,911,241	10.86	195,836,172	26.62	174,182,648	23.68	285,744,659	38.84	735,674,721
Vinorelbine 10 mgd	6,305,699	57.00	2,153,148	19.46	814,825	7.37	1,788,105	16.16	11,061,777
Vinorelbine 20 mgd	6,338,358	40.90	6,429,645	41.49	2,498,773	16.13	228,920	1.48	15,495,696
Vinorelbine 30 mgd	17,960,731	56.49	9,193,434	28.92	4,351,541	13.69	286,020	0.90	31,791,725
Total	215,459,045	21.28	265,628,688	26.24	209,706,375	20.72	321,476,971	31.76	1,012,271,080

Dosage forms: atablet; bampoule; ccapsule; dampoule and capsule.

Source: Integrated General Services Administration System (SIASG)

The findings show that procurement patterns differ across purchaser categories, with the Ministry of Education showing a considerably different profile to the rest of the categories (Fig. 1). Trastuzumab 440 mg represented the largest share of total spending (72.68%) (Table 2). Spending on trastuzumab as a percentage of overall spending was highest in the categories “Other Institutions” and Ministry of Defense and lowest in the category Ministry of Education. There was a reduction in spending on trastuzumab 440 mg as a percentage of total spending in 2016 across all purchaser categories, with the Ministry of Health not making any purchases of this drug in this year. In contrast, spending on tamoxifen 20 mg as a percentage of total spending increased across all categories. This increase was more pronounced in the category Ministry of Health. The Ministry of Defense was the purchaser category with the most even pattern of spending on these medicines over the study period (Fig. 1).

Fig. 1

Spending per medicine as a percentage of total spending on antineoplastic agents used for treating breast cancer by purchaser category. Brazil, 2013–2019. Source: Integrated General Services Administration System (SIASG)

Purchasing patterns

There are two main purchasing patterns: an expected or market pattern, where volume of purchases and WAP/mg are inversely proportional; and a pattern characterized by inelasticity, where volume of purchases does not appear to influence WAP/mg. The WAP/mg of trastuzumab 440 mg is apparently inelastic across all purchaser categories throughout the study period, while the WAP/mg of exemestane 25 mg is inelastic in the first three years of the study period across all categories. Other medicines with inelastic WAP/mg include vinorelbine (10, 20 and 30 mg), anastrozole 1 mg and docetaxel 40 mg, which show small variations in price in relation volume purchased by the ministries of health and education. Tamoxifen 20 mg shows a similar pattern across all categories, with prices tending to be higher in 2015 and 2016. It is important to highlight that the scales used for each medicine differ. The findings show price fluctuations over time and differing WAP/mg patterns between medicines and across categories (Fig. 2).

Fig. 2

Patterns of weighted average pricea per mg (R$) and total purchase quantities of antineoplastic agents used for treating breast cancer by purchaser category. Brazil, 2013–2019. ª Inflation-adjusted annual weighted average prices, compared to December 2019 values. ME: Ministry of Education; MH: Ministry of Health; MD: Ministry of Defense; OI: Other Institutions. Source: Integrated General Services Administration System (SIASG)

The WAP/mg of paclitaxel 6 mg rose in 2019. This rise was more pronounced in the category “Other Institutions”, probably due to the lower volume of purchases made by this category. In previous years, the WAP/mg of paclitaxel 6 mg was not influenced by volume of purchases across all purchaser categories. Vinorelbine 10 mg, docetaxel 40 mg and anastrozole 1 mg showed different price patterns across different purchaser categories (Fig. 2).

Avoidable expenditures

Total avoidable expenditure over the study period was R$99,130,645. Avoidable expenditure was highest in the Ministry of Defense and lowest in the category “Other Institutions” (R$32,109,286 and R$13,168,716, respectively). Trastuzumab 440 mg was the medicine with the highest amount of avoidable expenditure in all categories (R$55,428,008). Avoidable expenditure on this drug was highest in the Ministry of Defense (R$21,197,898). Docetaxel 40 mg was the medicine with the second highest amount of avoidable expenditure in the Ministry of Health (R$3,665,684), Ministry of Defense (R$2,925,025), and “Other Institutions” (R$3,034,617). The medicine with the second highest amount of avoidable expenditure in the Ministry of Education was paclitaxel 6 mg (R$3,899,524). The findings show that an additional 23,358,891 units could have been purchased at the lowest WAP/mg, including 11,694,264 units of tamoxifen 20 mg, 5,892,583 units of anastrozole 1 mg, and 4,789,924 units of paclitaxel 6 mg. The number of additional units that could have been purchased was highest in the Ministry of Education (10,440,753) (Table 3).

Table 3

Total avoidable expenditure (R$) and additional quantities that could have been purchased at the lowest weighted average pricea by medicine (units) and purchaser category. Brazil, 2013–2019

MINISTRY OF EDUCATION

Medicine&

2013

2014

2015

2016

2017

2018

2019

Total

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

Anastrozole 1 mg1

310,500s

235,227

350,880s

265,818

58,597s

48,030

268,443s

221,854

83,946s

68,249

NA

NA

387,309o

1,046,781

1,459,675

1,885,959

Docetaxel 40 mg2

390,477o

4067

NA

NA

768,635o

12,397

NA

NA

552,559s

7467

391,184s

5927

10,923d

155

2,113,778

30,014

Exemestane 25 mg3

260,230s

15,536

NA

NA

241,621s

13,240

117,260o

6013

27,111o

1276

101,956s

5826

126,217s

28,048

874,396

69,939

Letrozole 2.5 mg1

NA

NA

NA

NA

80,412s

12,092

539,006o

56,001

NA

NA

340,783s

54,525

NA

NA

960,201

122,618

Paclitaxel 6 mg2

301,885s

173,497

NA

NA

1,672,640s

1,161,556

712,742d

329,973

NA

NA

NA

NA

1,212,257s

396,162

3,899,524

2,061,188

Tamoxifen 20 mg1

271,405s

678,513

NA

NA

2,451,137s

4,085,228

NA

NA

1,158,080s

1,447,600

NA

NA

NA

NA

3,880,623

6,211,342

Trastuzumab 440 mg2

3,131,527o

295

920,266o

90

1,304,827o

131

328,739o

32

1,506,941o

144

3,185,909s

315

843,025d

100

11,221,235

1107

Vinorelbine 10 mg4

97,010s

3789

188,306s

8559

153,513s

6823

48,856s

1816

230,746s

8125

506,126s

20,574

49,657s

2104

1,274,214

51,791

Vinorelbine 20 mg4

41,334d

304

14,394d

114

27,455s

242

20,011d

170

61,538d

531

21,901s

185

51,889d

504

238,522

2050

Vinorelbine 30 mg4

107,430d

567

41,584d

219

63,109s

370

92,181s

539

148,594d

869

48,123d

271

273,096o

1908

774,117

4744

MINISTRY OF HEALTH

Medicine&

2013

2014

2015

2016

2017

2018

2019

Total

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

Anastrozole 1 mg1

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

82,660e

99,591

99,310o

268,405

181,970

367,995

Docetaxel 40 mg2

3,247,794o

33,831

147,224e

2217

206,006o

3323

64,661e

913

NA

NA

NA

NA

NA

NA

3,665,685

40,284

Exemestane 25 mg3

NA

NA

NA

NA

NA

NA

96,606o

4954

96,196o

4527

NA

NA

NA

NA

192,801

9481

Letrozole 2.5 mg1

1362e

164

NA

NA

NA

NA

NA

NA

230e

25

NA

NA

16,162e

5213

17,753

5402

Paclitaxel 6 mg2

NA

NA

5711e

2884

NA

NA

61,613d

28,525

171,549e

58,350

1,068,095e

468,463

NA

NA

1,306,968

558,222

Tamoxifen 20 mg1

NA

NA

NA

NA

NA

NA

1,285,271e

918,051

NA

NA

NA

NA

NA

NA

1,285,271

918,051

Trastuzumab 440 mg2

8,496,516o

801

4,553,299o

447

2,594,719o

260

NA

NA

3,746,929o

358

NA

NA

570,309d

67

19,961,772

1934

Vinorelbine 10 mg4

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

Vinorelbine 20 mg4

31,586d

232

NA

NA

NA

NA

10,337d

88

36,843d

318

NA

NA

48,881d

475

127,648

1113

Vinorelbine 30 mg4

240,228d

1267

NA

NA

NA

NA

NA

NA

62,664d

366

1021d

6

112,578o

787

416,490

2426

MINISTRY OF DEFENSE

Medicine&

2013

2014

2015

2016

2017

2018

2019

Total

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

Anastrozole 1 mg1

175,371s

132,857

301,078s

228,090

364,487s

298,759

71,568s

59,147

1,160,270s

943,309

229,449e

276,445

185,286o

500,773

2,487,509

2,439,380

Docetaxel 40 mg2

28,038o

292

159,722e

2405

945,109o

15,244

81,561e

1152

592,045s

8001

1,118,551s

16,948

NA

NA

2,925,026

44,042

Exemestane 25 mg3

219,671s

13,115

13,113e

656

96,936s

5312

65,326o

3350

156,005o

7341

121,042s

6917

572,184s

127,152

1,244,278

163,842

Letrozole 2.5 mg1

4687e

563

40,085e

5257

82,559s

12,415

26,446o

2748

83,644e

8946

244,233s

39,077

318,416e

102,715

800,071

171,721

Paclitaxel 6 mg2

193,477s

111,194

1,335,805e

674,649

249,584s

173,322

NA

NA

79,445e

27,022

325,684e

142,844

337,189s

110,193

2,521,184

1,239,223

Tamoxifen 20 mg1

72,358s

180,896

31,192s

51,986

295,977s

493,295

22,452e

16,037

97,743s

122,179

76,082s

95,103

NA

NA

595,805

959,496

Trastuzumab 440 mg2

3,269,234o

308

4,268,039o

419

4,736,421o

475

639,984o

62

6,876,263o

657

1,407,957s

139

NA

NA

21,197,898

2060

Vinorelbine 10 mg4

9412s

368

65,409s

2973

36,320s

1614

8213s

305

30,110s

1060

33,388s

1357

57,289s

2427

240,141

10,105

Vinorelbine 20 mg4

NA

NA

NA

NA

33,911s

299

NA

NA

NA

NA

323s

3

NA

NA

34,234

301

Vinorelbine 30 mg4

NA

NA

NA

NA

19,258s

113

2632s

15

NA

NA

NA

NA

41,251o

288

63,141

417

OTHER INSTITUTIONS

Medicine&

2013

2014

2015

2016

2017

2018

2019

Total

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

AE (R$)

Units

Anastrozole 1 mg1

273,649s

207,310

148,643s

112,608

215,818s

176,900

456,011s

376,868

76,409s

62,121

218,657e

263,442

NA

NA

1,389,186

1,199,249

Docetaxel 40 mg2

NA

NA

213,948e

3222

NA

NA

2,007,159e

28,350

322,482s

4358

491,028s

7440

NA

NA

3,034,617

43,369

Exemestane 25 mg3

15,042s

898

28,088e

1404

36,445s

1997

NA

NA

NA

NA

280,207s

16,012

610,704s

135,712

970,486

156,023

Letrozole 2.5 mg1

49,663e

5966

1082e

142

3500s

526

NA

NA

108,797e

11,636

4065s

650

5913e

1907

173,020

20,827

Paclitaxel 6 mg2

411,748s

236,637

245,363e

123,921

362,000s

251,389

39,448d

18,263

263,379e

89,585

404,387e

177,363

104,450s

34,134

1,830,775

931,291

Tamoxifen 20 mg1

568,902s

1,422,254

918,086s

1,530,144

213,870s

356,450

168,534e

120,382

NA

NA

140,916s

176,146

NA

NA

2,010,309

3,605,375

Trastuzumab 440 mg2

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

1,050,590s

104

1,996,514d

236

3,047,104

340

Vinorelbine 10 mg4

3422s

134

34,022s

1546

7198s

320

28,195s

1048

428,934s

15,103

114,889s

4670

73,749s

3125

690,408

25,947

Vinorelbine 20 mg4

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

22,812d

221

22,812

221

Vinorelbine 30 mg4

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

Legend: AE avoidable expenditure. Units – number of units. NA not applicable. e Ministry of Education, s Ministry of Health, d Ministry of Defense, o Other Institutions

ª Inflation-adjusted annual weighted average prices, compared to December 2019 values

Dosage forms: 1tablet; 2ampoule; 3capsule; 4ampoule and capsule

Source: Integrated General Services Administration System (SIASG)

Discussion

The findings show that the Ministry of Education accounted for the largest volume of antineoplastic agent purchases during the study period. This can be explained by the large number of purchases made by complex-care university hospitals, which play an important role in cancer care, education and research in the country [16, 17]. Total spending on antineoplastic drugs during the study period was more than R$1 billion. According to the literature, the rising cost of antineoplastic drugs may be caused by a number of different factors, including: increased access and utilization [18, 19] (due to growing incidence of different types of cancer and wider access to diagnosis and, consequently, treatment); an increase in prices [20, 21] of both newly-approved technologies and medicines already firmly established on the market; and changes in drug utilization profiles [22, 23], including an increase in purchases of higher-cost medicines fuelled by the rising number of patients needing treatment for advanced cancer. However, despite the sharp rise in spending on antineoplastic agents, the availability of these medicines remains low in many countries, including Brazil [24-26].

The largest component of breast cancer patient costs is systemic therapy, which includes chemotherapy and hormone therapy [27, 28]. Anticancer therapy has a high cost for the SUS. A study conducted by Lana [29] showed that the SUS spent R$14.9 billion on cancer care between 2001 and 2014, with the treatment of breast cancer accounting for the largest share of expenditure (R$6.4 billion or 43% of spending on the cancers investigated by the study). In addition, chemotherapy represented the largest share of direct costs associated with all types of cancer analyzed by the study (R$9538.7 million, equivalent to 64% of total cancer care costs). Data show that total direct expenditure on admissions, chemotherapy and social security benefits for people with breast cancer rose by 110% between 2008 and 2015, from approximately R$302 million to R$633 million, with chemotherapy accounting for 68% of total spending [30]. In 2018, antineoplastic agents and immunomodulators led sales (16.4% of overall drug purchases), amounting to more than R$12.4 billion [31].

The purchaser category that spent most on antineoplastic agents over the study period was “Other Institutions”, followed by the Ministry of Health. It is important to highlight that state and municipal health authorities represent a significant share of the procuring entities in the category “Other Institutions”. In a public interest civil action brought by the public prosecutor’s office in the Federal District, it was found that certain companies charged a state health authority different prices than those already agreed in contracts to supply medicines awarded by the Ministry of Health [32]. This may be explained by the law of supply and demand, bearing in mind that state and municipal health authorities tend make considerably smaller purchases than the Ministry of Health.

The findings show that the purchasing patterns observed in the Ministry of Education differ from those of the other purchaser categories. This may be explained by a number of factors, including: the variety of possible treatments for the same type of tumor; adoption of different protocols (due to the lack of clinical protocols and the flexibility of DDTs, meaning that service providers can choose what treatment to use) [33]; use of medicines in research and clinical trials [17]; different approaches to hospital management15; and non-centralized purchases [34]. There was a notable change in the distribution of expenditure in 2016. Spending on trastuzumab 440 mg as a percentage of overall spending decreased across all purchaser categories, with the Ministry of Health not making any purchases of this drug in this year. For want of an explanation in the literature, it is assumed that this reduction is associated with a number of factors, including stockpiling, supply problems, and purchasing difficulties and/or budget shortfalls. However, the fall in spending on trastuzumab as a percentage of overall spending does not appear to be related to a reduction in utilization. In this regard, a study by Ferraris [35] analyzing the utilization of trastuzumab for the treatment of breast cancer in the state of Rio de Janeiro observed that services surpassed the number of expected procedures in 2016.

Our findings also show that the response of WAP/mg to quantity procured differs according to drug and purchaser category. WAP/mg and demand were shown to be both elastic and inelastic. The literature shows that medicines, especially antineoplastic agents, have peculiar market characteristics – such as lack of supply chain transparency, limited competition due to market segmentation and monopolies over medicines, and imbalances between supply, consumption and demand – which can contribute to price variations across regions and countries [36, 37].

Trastuzumab accounted for the largest share of total spending across all purchaser categories. The category “Other Institutions” led purchases of this drug, representing around 40% of total spending, corroborating the findings of Moraes et al. [34], who investigated the potential implications of global trastuzumab price policies in seven countries in Latina America. The study shows that the medicine was considered unprofitable in 2015, meaning that it was necessary to cut prices by between 70 and 95% to make it cost effective [38]. In this regard, it is known that high drug prices and high general treatment costs in poorly structured health systems are barriers to access [18, 39].

While trastuzumab was the country’s top-selling active ingredient in terms of revenue in 2018 [31], access to high-cost medicines on the SUS is restricted and generally well behind developed countries when it comes to newly-approved medicines [19, 25]. Trastuzumab is also notable for its price inelasticity of demand across all purchaser categories. This may be explained by the complexity and structure of the market for antineoplastic drugs and other factors that make medicine prices less predictable [1]. The drug that accounted for the largest volume of purchases was tamoxifen. This may be explained by the fact that tamoxifen is the most commonly used medicine in hormonal therapy (indicated for the treatment of early and advanced-stage breast cancer in pre and post-menopausal women), being standard treatment by consensus and according to clinical guidelines and associated with gains in disease-free and overall survival [40, 41].

From a cost-effectiveness perspective, the findings show that total avoidable expenditure was approximately R$100 million. It is known that underfunding and irregular cash flow have always been inherent problems in Brazil’s public health system [42]. In this regard, this study reveals that procurement problems extend beyond budget deficits to include poor management and high WAP/mg. The data show that the potential savings made by purchasing at the lowest WAP/mg could have been used to purchase a significant quantity of medicines, expanding availability and consequently enabling wider access to antineoplastic drugs on the SUS. This is particularly relevant given that the SUS has limited facilities to absorb breast cancer patient demand and provided adequate treatment [43], including deficiencies in screening and diagnosis, consequently leading to delays in various stages of treatment and contributing to negative prognoses [44].

The Ministry of Defense was the poorest performing purchaser category when it comes to WAP/mg and consequently responsible for the highest amount of avoidable expenditure during the study period. A study by Moraes et al. [34] analyzing federal government procurement of the antineoplastic drugs imatinib mesylate, trastuzumab and L-asparaginase also reported that the procuring entity that paid the highest mean prices was the Ministry of Defense. The medicine that accounted for the largest share of avoidable expenditure was trastuzumab, followed by docetaxel, except in the Ministry of Education, where paclitaxel represented the second largest share. The findings show that by purchasing at the lowest WAP/mg it would have been possible to acquire an additional 11,694,264 units of tamoxifen 20 mg, 5,892,583 units of anastrozole 1 mg and 4,789,924 units of paclitaxel 6 mg. This shows the importance of analyzing avoidable expenditure, especially given the effects of cancer patient treatment costs on society, the government and health systems [45]. The importance of assessing avoidable expenditure is reinforced when we look at the number of additional units that could have been purchased as a percentage of the total quantities of each medicine purchased over the study period: tamoxifen (32.54%), paclitaxel 6 mg (30%), vinorelbine 10 mg (24.66%) and docetaxel (23.73%). These additional units could have played an important role in reducing iniquity in access to chemotherapy drugs provided by the SUS.

The present study analyzed public procurement using competitive bidding procedures, excluding drug purchases by court order. However, given the increased judicialization of purchases as an alternative means to expand access to antineoplastic agents through the SUS, it is important to highlight that the cost of bringing such lawsuits is high, constituting another factor that contributes to the growing economic burden of cancer [46, 47]. Effective procurement would avoid unnecessary expense and help increase the availability of medicines on the SUS, consequently minimizing spending on health litigation.

This study has some limitations. First, the exclusion of medicines that were not purchased by the Ministry of Health in at least five of the seven years of the study period meant that a complete overview of adjuvant and neoadjuvant therapy for breast cancer was unobtainable. Second, some of the antineoplastic agents investigated by this study are used for treating diseases other than breast cancer which may overrepresent consumption for breast cancer. However, this limitation is partially overcome because in the Brazilian public system prescribing of these medicines is restricted to cancer treatments. While this may broaden actual use to other cancer indications, all would profit from elimination of avoidable expenditures. Finally, SIASG is a national aggregated database of drug purchases by procuring entities and does not include individually prescribed/dispensed medicines, meaning it is not possible to identify therapeutic indication.

Conclusions

The Brazilian Ministry of Education was the largest purchaser of antineoplastic agents in terms of volume, showing considerably different spending patterns to the rest of the purchaser categories. State and municipal health authorities spent most on antineoplastic agents, mainly with trastuzumab. Tamoxifen and trastuzumab accounted for the largest volume of purchases and largest share of total spending, respectively. Tamoxifen is considered the gold standard for breast cancer treatment while trastuzumab was characterized by price inelasticity of demand. Total avoidable expenditure was approximately R$100 million and overspending was highest in the Ministry of Defense.

Breast cancer is the most common cancer in women in Brazil and studying public procurement of antineoplastic agents used for the treatment of this disease is of utmost importance. The findings also suggest that the SUS is facing a shortage of medicines in high-complexity health care facilities and high-complexity cancer care centers. The effective management of public procurement of antineoplastic agents can help expand access to these medicines and promote the financial sustainability of the SUS.