Resources and Costs Associated with the Treatment of Advanced and Metastatic Gastric Cancer in the Mexican Public Sector: A Patient Chart Review

Resources and Costs Associated with the Treatment of Advanced and Metastatic Gastric Cancer in... PharmacoEconomics Open (2018) 2:191–201 https://doi.org/10.1007/s41669-017-0043-2 ORIGINAL RESEARCH ARTICLE Resources and Costs Associated with the Treatment of Advanced and Metastatic Gastric Cancer in the Mexican Public Sector: A Patient Chart Review 1 1 2 3 4 • • • • • Miguel Quintana Jose ´ A. Toriz Diego Novick Kyla Jones Brenda S. Botello Juan Alejandro Silva Published online: 31 July 2017 The Author(s) 2017. This article is an open access publication Abstract (IMSS) tariffs, the average total cost per patient-month in Background Little evidence is available on the manage- first- and second-line therapy was US$1230 [95% confi- ment and cost of treating patients with advanced or meta- dence interval (CI) 1034–1425] and US$1192 (95% CI static gastric cancer (GC). This study evaluates patient 913–1471), respectively. Administration and acquisition of characteristics, treatment patterns, and resource utilization chemotherapy comprised the majority of costs. for these patients in Mexico. Conclusions This study shows considerable variation in Methods Data were collected from three centers of inves- first- and second-line chemotherapy regimens of patients tigation (tertiary level). Patients were C18 years of age, with advanced or metastatic GC. Understanding GC treat- diagnosed between 1 January 2009 and 1 January 2015, ment patterns in Mexico will help address unmet needs. had advanced or metastatic GC, received first-line fluo- ropyrimidine/platinum, and had C3 months follow-up after discontinuing first-line treatment. Data were summarized Key Points for Decision Makers using descriptive statistics. Results The study sample totaled 180. Patients’ mean age A considerable variety of chemotherapy regimens in was 57.2 years (±12.4) and 57.0% were male; 151 (83.9%) first- and second-line therapy of patients with patients received second-line chemotherapy. A total of 16 advanced or metastatic GC was observed; however, and 19 regimens were identified in first- and second-line conformity was seen in the most frequently selected therapy. Of the sample, 51 (28.3%) received third-line regimens. therapy, and\10% received more than three lines of active Administration and acquisition of chemotherapy chemotherapy. Supportive care received in first- and sec- comprised the majority of costs; the frequent use of ond-line chemotherapy, included pain interventions (12.2 and 7.9%), nutritional support (3.3 and 1.3%), radiotherapy regimens including capecitabine may reflect a conscious move of doctors towards cost-saving (6.1 and 16.6%), and transfusions (13.3 and 10.6%), measures. respectively. Using Mexican Institute of Social Security & Diego Novick 1 Introduction novick_diego@lilly.com Department of Medical Oncology, Hospital de Oncologı´a, Over the last 50 years, the reduction in incidence and Centro Me´dico Siglo XXI, Instituto Mexicano del Seguro mortality due to gastric cancer (GC) worldwide has been Social, Mexico City, Mexico significant [1]. However, despite this, GC remains highly Eli Lilly and Company, Surrey, UK ranked in both incidence and mortality due to cancer; in ´ ´ Tecnologıa e Informacion para la Salud, Mexico City, 2012 the World Health Organization (WHO) ranked it as Mexico the fifth most common malignancy and the third most Eli Lilly and Company, Mexico City, Mexico 192 M. Quintana et al. common cause of cancer death worldwide [2]. In particu- This study was developed to better understand the cur- lar, GC has a high burden of disease in developing coun- rent treatment patterns of patients diagnosed with GC in tries, where approximately 60% of all cases are detected Mexico in order to support public policy regarding GC [3], and where stomach cancer is ranked among the most treatment programs. The primary objectives of the study frequent type of cancer in terms of incidence and mortality were to (1) describe the demographic and clinical charac- [4]. teristics of the target patient population in Mexico, and (2) The high mortality rate associated with GC is in part due identify and describe treatment patterns used in standard to its lack of distinct symptoms, which allow GC to go practice. Secondary objectives were to estimate direct costs unnoticed until advanced stages, where treatment options associated with the treatment of these patients. This study are limited [5]. While surgery is considered standard focuses on second-line therapy. treatment for early-stage GC, the chemotherapy recom- mended for advanced stages remains relatively nonstan- dardized in terms of regimen selection. International 2 Methods guidelines recommend a two-drug combination of fluo- ropyrimidine and platinum in first-line treatment, without A retrospective, observational study was designed to col- recommending specific regimens or specific product lect data regarding patient characteristics and institutional endorsements [6–8]. In second-line chemotherapy, ramu- resource use from medical records in the Mexican public cirumab, paclitaxel, docetaxel and irinotecan are labeled as system. The target population was patients diagnosed with the preferred treatment options by the National Compre- metastatic/unresectable GC (including gastroesophageal hensive Cancer Network (NCCN; 2014), however only junction) between 1 January 2009 and 1 January 2015, and ramucirumab has formal approval in the indication. treated in tertiary-level centers of investigation. We defined Nonetheless, in terms of real-world experience, little evi- the index date as the date recorded for diagnosis of dence is reported on GC management practices that iden- advanced or metastatic GC. tify the most frequently implemented strategies from the A sample size of 200 was set as a target. Ethics approval wide range of options available. was obtained, and data capture respected international This lack of data is surprising as, according to the few patient privacy regulations. published studies available, the economic burden of GCs is Inclusion criteria were: relatively high and data regarding treatment patterns could • Patients completed first-line chemotherapy that potentially identify areas of cost saving. Presented as an included a platinum analog and a fluoropyrimidine, abstract of a retrospective study, in 2011 Knopf et al. with or without another medication, and continued with collected monthly resource utilization data on patients with either second-line treatment or palliative therapy; GC versus a nondiagnosed control, for the period • Patients were[18 years of age at the time of diagnosis; 2007–2009. The mean monthly costs for patients with GC • Medical records were required to have a follow-up of was US$10,653, versus US$571 for the control group [9]. C3 months following the last administration of first- Knopf et al. posited that while GC has a low prevalence in line treatment, except those recording a documented the US, the cost per patient has an overproportionate death: impact in the cost of care when compared with other cancers. In a study by the US National Cancer Institute, the • This criterion was applied due to a pilot analysis of cost of GC was estimated to be US$1.82 billion in 2010 data collected within the first 3 days which showed that the number of patients with either (1) less than [10]. In a third study in the US by Yabroff et al., it was observed that the cost of GC, in terms of initial care, was 3 months of follow-up, or (2) documented death approximately US$5348, while for the last year of patient within 3 months, exceeded one-third of the col- care the cost rose to US$7435 [11]. lected sample. Mexico is currently considered a medium-risk area of The prespecified criterion regarding minimum follow-up GC, as defined by incidence rate; in 2012, the WHO esti- was included in order to allow for analysis on types of mated a rate of 7.9 per 100,000 inhabitants [2]. Never- agents used in second-line treatment in a situation where a theless, national resources rank GC as the second cause of large percentage of patients was being lost to follow-up. death associated with cancer, and the first cause of mor- This loss of follow-up was experienced in a similar study tality in the country due to digestive tract neoplasms [12]. conducted by the sponsor in Brazil, where a high per- However, similar to international literature, there is little centage of patients left third-level facilities once receiving published evidence on patient management, resource uti- best supportive care (BSC) [14]. As such, the sponsor lization and economic burden, and none on the economic recommended the inclusion of this criterion in order to impact of the disease [13]. Advanced and metastatic gastric cancer: resources and costs in the Mexican public sector 193 prioritize the capture of resource utilization of patients who was calculated using the number of cycles multiplied by remain in tertiary-level hospitals over the calculation of the total milligrams per cycle, based on reported posology. percentage of patients who are treated in second-line with Costs per milligram were used. Costs of administration, an active chemotherapy and the resource utilization of radiotherapy, and supportive care units were calculated by BSC. the reported number of sessions or units. The number of Exclusion criteria consisted of patients who had partic- grade 3 and 4 adverse events was collected, and the cost of ipated, or were currently participating, in any controlled treatment was calculated by adding reported treatment and clinical study, and patients with a second malignant disease procedures. Hospitalization for adverse events was inclu- diagnosed before or after the diagnosis of metastatic/ ded in costs for inpatient hospitalization; inpatient hospi- unresectable GC. talization days were calculated according to reported admission and discharge dates only. Outpatient costs were 2.1 Data Collection calculated according to the reported type of visit, specifi- cally emergency room (ER) visits, pain clinic, or oncology Data were captured using a paper Data Report File (DRF) clinic/consultation. Supportive care resources included that had been validated by the principal investigator against tests and procedures not captured in adverse events, but did the Mexican Institute of Social Security (IMSS) patient not include medication as posology data were not captured files. DRFs were monitored for completeness and precise- for supportive care. Treatment prior to diagnosis of ness by a third-party monitor and transferred to an elec- advanced or metastatic GC was not included in the tronic database. Variables collected included patient analysis. demographics and clinical characteristics, treatment This study estimated direct medical costs from a payer received, adverse events, hospitalization and outpatient perspective, from the index date to the recorded data point visits, and resource utilization. or to the end of data collection (8 August 2015). Cost estimates were calculated using resource utilization data 2.2 Outcomes and their corresponding unitary costs. Unit costs were taken from the IMSS unitary costs list for procedures The primary outcomes of the analysis were defined as the (2015) [15], while the acquisition cost of medication was demographic and clinical characteristics of the patient taken from the IMSS public tenders (2015) [16]. A limited population in Mexico, the proportion of patients treated number of supportive-care costs not published by the IMSS with each chemotherapy regimen per treatment line, and were taken from the National Institute of Cancer (INCAN) resource utilization, while secondary outcomes were 2015 unitary costs list [17](n = 16 variables); however, due to the number and general low cost of the affected defined as cost per patient-month and the distribution of cost per patient-month by category. variables, this had little impact on results. All estimated Start and end dates, as well as duration, were calculated costs were in 2015 Mexican pesos (MXN$) and then using dates reported in the patient files. The number of converted to 2015 US dollars (US$). The exchange rate days from diagnosis to treatment was calculated using the was 0.06317, calculated as the average exchange rate of index date of diagnosis to the day of the first chemotherapy 2015 from the database of the Bank of Mexico (1 January treatment in first-line. In order to include all resources used to 31 December). in each line of therapy, lines of treatment were calculated from the first day of treatment to the day before the fol- 2.3 Statistical Methods lowing line of chemotherapy; for the first-line of treatment, this was defined as the first date of hospitalization, radio- Statistical analysis was descriptive due to the observational therapy or chemotherapy following a diagnosis of nature of the study, and was performed for all main vari- advanced or metastatic GC. End of treatment was calcu- ables collected. The mean, median, mode and standard lated by the last date registered before loss of follow-up, deviation was calculated for continuous variables, and death, or the cut-off date of data capture. frequency and proportion were calculated for categorical Healthcare utilization rates were categorized by the type variables. All measures were assessed using complete case of medical resource service; specifically, acquisition of analysis, with missing values being omitted in the final chemotherapy and premedication products, administration, analysis of each variable. Descriptive analyses were com- adverse events, radiotherapy, inpatient hospitalization, pleted in Excel 2010 (Microsoft Corporation, Redmond, outpatient visits, use of supportive care procedures and WA, USA), and cost analysis was completed in STATA tests. Medicine use, both chemotherapy and premedication, v11 (StataCorp LLC, College Station, TX, USA). 194 M. Quintana et al. metastatic location are shown in Fig. 2. Patients had an 3 Results average waiting time of 30.5 days [95% confidence interval 3.1 Demographic and Clinical Characteristics (CI) 19.4–41.7] from diagnosis to first-line treatment. The final sample size of the study was 180, collected from 3.2 Treatment Patterns three tertiary-level centers of investigation. Due to the low incidence, all patients meeting the inclusion criteria in the A total of 16 and 19 unique treatment regimens were identified for first- and second-line active treatment, participating institutes were included. In the IMSS hospital, Centro Me´dico Nacional (CMN) Siglo XXI, patient files respectively. Each of the five most used regimens in first- line therapy represented C10% of the total population, are organized according to consulting office; all patients summing to 93.9% of all selected therapies. Selection of who met the inclusion criteria of the two consulting offices second-line treatment showed each of the three most fre- were included. quently used regimens representing C10% of the overall The majority of patients were treated in IMSS CMN Siglo XXI (n = 167; 92.8%), followed by the Secretary of population, and 64.9% of all regimens. Of the sample, 29 patients went on to receive BSC after first-line treatment, the Navy (SEMAR) (n = 7; 3.9%), and patients found through the investigation center IBiomed (n = 6; 3.3%). however, due to the small sample and lack of data on resource use, results for these patients are not presented. The patient selection process is outlined in Fig. 1. The demographic and clinical characteristics of patients are No obvious tendency of cycle length per regimens could be observed, however due to the small sample size of each summarized in Table 1. regimen, statistical differences were not tested for. Details The maximum level of education reported was generally for treatment characteristics and frequently used regimens low (n = 137): no schooling, 7.3%; primary school (age are included in Tables 2 and 3. 6–12 years), 29.2%; secondary school (age 12–14 years), 27.0%; high-school, 21.9%; and completing university or 3.3 Resource Utilization postgraduate studies, 14.6%. The majority of patients (57.1%) reported no comorbidities, 14.9% reported dia- The majority of hospitalization in first- and second-line betes, and 9.1% reported idiopathic hypertension; five patients had missing values. All other comorbidities treatment was associated with surgery. In second-line treatment, inpatient care was also linked to treatment of impacted\5% of the sample. Smoking was associated with 52.0 and 3.5%, actively and formerly, respectively, of the toxicity and adverse events. Supportive care was most associated with pain treatment (pain clinic and narcotics) 173 patients who reported on the variable. and the use of endoscopies (see Table 4 for details). Almost all patients included in the study were diagnosed Of the sample, 151 (84%) patients received two lines of with adenocarcinoma, totaling 98.9% of the 179 patients chemotherapy, 51 (28.3%) received three lines, and\10% reporting data on the variable. Of the 173 patients with data, 96.1% were diagnosed with metastasis: approximately one- received more than three lines of active chemotherapy. The maximum lines of therapy received by a patient was seven. third of patients (28.9%) in two or more locations, 8.9% in three or more sites, and only 2.2% in four sites. Tumor Estimated average costs per patient-month are presented in Table 5. characteristics of both the primary location and the Fig. 1 Selection of patients Total no. of paents entered into study database: entered in the study n = 225 Paents included in the review Paents excluded from the review (cause) n = 45 n = 180 st n = 22 (ineligible 1 –line treatment) n = 22 (follow-up duraon <3 months) st n = 1 (not treated in 1 line in instute: no data) Paents included in the analysis Complete count analysis was conducted, only paents with data were included in each calculaon Advanced and metastatic gastric cancer: resources and costs in the Mexican public sector 195 Table 1 Characteristics of the a Variable (n) Mean (SD) 95% CI Min Max patient population Age at diagnosis, years (180) 57.2 (12.4) 55.4–59.0 24.1 82.1 Height, cm (180) 160.4 (9.4) 159.0–161.8 120.0 191.0 Weight, kg (180) 62.7 (11.6) 61.0–64.4 40.0 101.0 BMI, kg/m (180) 24.4 23.7–25.0 13.4 47.9 Variable (n) Category (n) n (%) Sex (179) Male 102 (57.0) Helicobacter pylori infection Tested (180) 61 (33.9) Positive (61) 23 (37.7) Family history of gastric cancer (160) Positive 18 (11.3) Tumor stage at diagnosis of gastric cancer (180) IA 2 (1.1) IB 1 (0.6) IIA 2 (1.1) IIB 4 (2.2) IIIA 23 (12.8) IIIB 58 (32.2) IV 79 (43.9) IIIA/IIIB 11 (6.1) SD standard deviation, CI confidence interval, Min minimum, Max maximum, BMI body mass index, AJCC American Joint Committee on Cancer Sample size of the variable Tumor stage was defined using the AJCC TNM staging system 7th edition,n = 169; 6th edition, n = 3; unknown, n = 9 Fig. 2 Tumor characteristics. a Primary gastric tumor location of the sample (n = 180), b metastatic tumor sites of the sample (n = 173) The patient population of Mexico follows international 4 Discussion tendencies for late- or advanced-stage diagnosis, with the majority of patients being diagnosed with stage III and IV Given the limited information that currently exists on patients diagnosed with advanced or metastatic GC in GC. Of the study population, approximately 80% of patients started first-line treatment in Eastern Cooperative Mexico, this study was designed to better understand patient characteristics, real-world treatment patterns, and Oncology Group (ECOG) 1. While this number decreased to 56.6% in second-line treatment, this reflects patients healthcare resource use. Additionally, this study estimated who had C3 months of follow-up, and likely represents the average cost per patient-month. 196 M. Quintana et al. Table 2 Treatment First-line therapy Second-line therapy characteristics Patients [n (%)] 180 (100.0) 151 (100.0) ECOG score [n (%)] 176 (100.0) 145 (100.0) 1. Symptomatic but completely ambulatory 141 (80.1) 82 (56.6) 2. Symptomatic, \50% in bed during the day 31 (17.6) 50 (34.5) 3. Symptomatic, [50% in bed but not bed-bound 4 (2.3) 13 (9.0) Duration of treatment period Cycles [mean (95% CI)] 4.6 (3.6–5.5) 4.2 (3.6–4.8) Duration of line of treatment Months [mean (95% CI)] 5.5 (4.8–6.2) 4.5 (3.4–5.6) Reason for ending treatment [n (%)] According to treatment protocol 49 (27.2) 36 (23.8) Toxicity/intolerance 49 (27.2) 19 (12.6) Tumor progression 30 (16.7) 31 (20.5) c d Others 52 (28.9) 65 (43.0) ECOG Eastern Cooperative Oncology Group, CI confidence interval Duration of treatment was defined as time on active treatment; data available for n = 179 in the first-line therapy group, and n = 131 in the second-line therapy group Duration of line of treatment was defined as time from the first day of chemotherapy until the day before the next line of chemotherapy; data available for n = 179 in the first-line therapy group, and n = 131 in the second-line therapy group Including deterioration of patient health, improvement in tolerance for oral therapy, stable disease, partial response, programmed surgery Including deterioration of patient health, stable disease, treatment still underway patients who had a more positive response to treatment. viability of oral treatment was improved by first-line Nonetheless, the data further suggest that few patients are intravenous regimens. treated once reaching ECOG 3. Oral chemotherapy may also be a demonstration of The findings of this study show a wide variety of regi- cost-constraining policies being implemented in the main mens used in both first- and second-line treatment, with a hospital of the study, i.e. IMSS, as an attempt by doctors total of 16 and 19 unique treatment regimens, respectively. to reduce hospital visits. Administration of chemotherapy Variability in treatment patterns has been demonstrated to was identified as the main cost driver of this analysis, and be an internationally consistent trait, as demonstrated in a reduction of visits for this purpose would have an similar studies conducted in the US, Taiwan, and South important impact on overall costs. Additionally, the study Korea [18–20]. The variation in Mexico remains compar- estimated that, on average, patients wait 30.5 days from atively high, which may reflect the lack of hospital-specific diagnosis of metastatic GC to treatment. This may be guidelines for the institutions included in the analysis. another cost-constraining effort as the IMSS manages a However, the fact that the most frequently used regimens global budget and a delay in treatment may increase in first- and second-line therapy represent 93.9 and 64.9% cashflow flexibility for administrators. However, it is of patients, respectively, suggests a level of conformity in important to note that this may be institute-specific as the selection process. When the investigating physicians wait times for elective services are reported as highly were consulted on the results, it was submitted that regi- variable across and within institutes [21]. Finally, the men selection is influenced primarily by the availability of study saw a lack of follow-up in tertiary-level care specific chemotherapies in the hospital pharmacy at the institutes for patients receiving BSC as the demand for time of prescription, and their form of administration. resources by the high-volume IMSS hospital requires that The preference towards prescribing orally administered these patients move to primary care units for follow-up products may be a reflection of this latter variable; care. specifically, capecitabine was administrated to 58.3 and In terms of overall cost estimates, the administration 60.3% of patients in first- and second-line treatment, schedule of the selected regimen had the largest impact on respectively. Patients were purposefully switched to cape- the average cost per patient, representing 35–48% of total citabine from first- to second-line therapy when the costs in first- and second-lines of treatments. This, Advanced and metastatic gastric cancer: resources and costs in the Mexican public sector 197 Table 3 Frequently used Regimen Percent of population Agent Mean cycles 95% CI treatment regimens in first- and second-line therapy First-line therapy EOX 32.2 Epirubicin 5.7 2.9–8.5 Oxaliplatin Capecitabine XELOX 23.3 Capecitabine 4.4 3.6–5.1 Oxaliplatin ECF 14.4 Epirubicin 2.4 1.8–3.0 Cisplatin 5-FU FLOX 13.9 5-FU 5.2 3.8–6.6 Folinic acid Oxaliplatin FUP 10.0 5-FU 3.3 2.2–4.5 Cisplatin Other Second-line therapy CAP 34.4 Capecitabine 4.3 3.3–5.3 DOC 16.6 Docetaxel 3.9 2.7–5.0 XELOX 13.9 Capecitabine 4.4 2.1–6.7 Oxaliplatin Other 5-FU 5-fluorouracil, CI confidence interval, CAP capecitabine, DOC docetaxel, EOX (epirubicin/oxali- platin/capecitabine), ECF (epirubicin/cisplatin/5-FU), FLOX (5-FU/folinic acid/oxaliplatin), FUP (5-FU/ cisplatin), XELOX (capecitabine/oxaliplatin) Cisplatin/5-FU/paclitaxel; DCF (doxetaxel/cisplatin/5-FU); EOF (epirubicin/oxaliplatin/5-FU); DOX (docetaxel/oxaliplatin/capecitabine); carboplatin/5-FU; carboplatin/5-FU/paclitaxel; DCX (doxetaxel/cis- platin/capecitabine); oxaliplatin/capecitabine/trastuzumab/doxorubicin; DCX/trastuzumab; capac- itabine/cisplatin; DOF (doxetaxel/oxaliplatin/5-FU) Paclitaxel/carboplatin; EOX; FLOX; paclitaxel; FUP; ECX (epirubicin/cisplatin/capecitabine); ECF; carboplatin; DOX (doxetaxel/oxaliplatin/capecitabine); EOF; capecitabine/cisplatin; capecitabine/cis- platin/docetaxel/trastuzumab; irinotecan; FOLFIRI (5-FU/leucovorin/irinotecan); FLOT (5-FU/leucovorin/ oxaliplatin/docetaxel); radiotherapy compared with the 14–21% for the cost of drug acquisition, MXN$154,018 and MXN$199,274, respectively, equiva- highlights the generic status of the products used. Inpatient lent to US$9729 and US$12,587, respectively, using the hospitalization and supportive care used a comparable previously stated 2015 average exchange rate [22]. While proportion of resources as medication. Supportive care firm conclusions are hard to make given the different time medication and outpatient care were minimal and were horizons of the analysis, if considering the short overall primarily associated with analgesics and narcotics (mor- survival of GC patients it may be expected that the overall phine, buprenorphine, and tramadol), as well as nutritional spending on advanced GC in Mexico is similar to that of support. breast cancer. The total average cost per patient-month of first- and This is the first Health Resource Utilization study second-line care were very similar, at US$1230 and completed in Mexico focusing on the standard care of US$1192, which is significantly lower than the US$10,653 treatment of patients diagnosed with advanced and meta- per patient-month published by Knopf et al. for patients static GC, and can be seen as a step towards providing diagnosed with GC in the US [9]. In comparison, Yabroff information regarding treatment patterns and estimating the et al. estimated that the last year of patient care for a patient overall costs of these patients. This is of particular with GC in the US was US$7435 [11]. This may be importance in a field where the majority of treatment comparable with the results of a recently published paper in options remain generic and the recent and future develop- Mexico that estimated the cost per patient-year of late- ment of innovative products will increase overall treatment stage breast cancer in the IMSS for stages III and IV of costs for public providers. 198 M. Quintana et al. Table 4 Patient supportive care and hospitalization by phase of therapy [17] First-line therapy (n = 180) Second-line therapy (n = 151) Supportive care [n (%)] Analgesics 135 (75) 109 (72.2) Diuretics 4 (2.2) 2 (1.3) Antidepressants 1 (0.6) 0 (0) Granulocyte colony-stimulating factors 9 (5) 6 (4.0) Pain interventions 22 (12.2) 12 (7.9) Erythropoiesis-stimulating agents 1 (0.6) 1 (0.7) Granulocyte/macrophage colony-stimulating factor 1 (0.6) 2 (1.3) Blood transfusion 24 (13.3) 16 (10.6) Endoscopy 161 (89.4) 78 (51.7) Radiotherapy 11 (6.1) 25 (16.6) Nutritional support, patients with information available [n (%)] Nutritional support clinic 2 (1.1) 0 (0) Total parenteral nutrition ? nonspecified nutritional support 6 (3.3) 2 (1.3) Inpatient hospitalization Hospitalization per patient (n) 0.27 0.18 At least one inpatient stay [n (%)] 40 (22.2) 22 (14.6) Length of stay/hospitalization (days) [n (95% CI)] 7.0 (4.9–9.1) 7.1 (4.6–9.6) Main reasons for visit [n (%)] 49 28 Disease symptom management 7 (14.3) 5 (17.9) Gastric cancer-related surgery 31 (63.3) 11 (39.3) Adverse events/toxicity 3 (6.1) 8 (28.6) Others 8 (16.3) 4 (14.3) Outpatient care, patients with information available Mean visits/all patients (n) 0.25 0.27 Patients with at least one visit [n (%)] 26 (14.4) 14 (9.3) Mean visits/patient requiring outpatient care (n) 1.7 2.9 CI confidence interval Pain interventions include use of the pain clinic and use of narcotics, including morphine, buprenorphine and tramadol The radiotherapy data presented in this paper differ from the poster presented on the same study (Jones et al. [23]); differences were found between the reporting of posology, necessary for the cost calculations included in this paper, and general resource use included in the poster. This paper decided to report resource use using posology data due to the greater level of detail presented and in order to maintain consistency of data between resource use and costs. Differences are potentially due to capture error (transfer from paper Data Report File to electronic database) and patients who received radiotherapy but did not have posology details on file Healthcare in Mexico is provided by multiple public Institute of Social Security and Services of Employees of institutes that deliver full or subsidized care depending on the State (ISSSTE) and Mexican Petroleums (PEMEX), employment status. However, provision of care between and MXN$1262.42/US$80 for the Seguro Popular [24]. institutes is not equal; each institute makes its own decision These differences in spending are accounted for by the on the benefits and products to be provided, given the social/economic difference of the contributing population. available resources. The results presented in this study are While the study provides an important starting point for primarily a reflection of treatment practices and costs in the data collection in GC in Mexico, it is important to note IMSS, the largest public healthcare provider in Mexico, certain limitations. In particular, the small sample size which covers private sector employees and their depen- combined with the range of regimens identified in both dents. The IMSS provides free care at the point of access, first- and second-line therapy limited the ability to estimate spending an estimated MXN$2909/US$184 per patient, on costs per regimen and to compare results across regimens. average (data from 2013); this in comparison to Furthermore, the generalization of these results to all MXN$3326/US$210 and MXN$16,772/US$1059 for public institutes is limited. While the IMSS is the largest Advanced and metastatic gastric cancer: resources and costs in the Mexican public sector 199 Table 5 Average cost per patient-month and distribution of costs of patients treated for metastatic gastric cancer First-line therapy Second-line therapy Total Total cost per 1230 (1034–1425) 1192 (913–1471) 1292 (1044–1541) patient-month (95% CI) Resources n Mean % 95% 95% n Mean % 95% 95% n Mean % 95% 95% cost CI CI cost CI CI cost CI CI (low) (high) (low) (high) (low) (high) Drug aquisition 171 174 14.1 131 218 128 244 20.5 171 316 120 250 19.3 173 327 Administration 179 586 47.6 478 695 131 421 35.3 270 5720 180 627 48.5 466 789 Adverse events 179 5 0.4 2 8 131 2 0.2 1 3 180 10 0.8 0 19 Radiotherapy 179 9 0.7 2 15 131 139 11.7 75 202 180 55 4.3 38 73 Hospitalization 179 185 15.0 80 289 131 247 20.7 92 403 180 227 17.6 95 360 (inpatient) Outpatient visits 179 51 4.1 -5 106 131 14 1.2 -3 30 180 26 2.0 13 39 Supportive care 179 200 16.3 154 245 131 152 12.8 110 194 180 279 21.6 174 384 CI confidence interval To calculate the cost per patient-month per line of treatment, patients who had missing values in any of the variables were eliminated: first-line therapy, n = 171; second-line therapy, n = 128; all lines, n = 120; first-line therapy costs start at the first input of chemotherapy, radiation, or hospitalization The sample size between the drug aquisition cost and the remaining costs is different due to the missing values in the number of cycles received or the dose, which made it impossible to estimate the total milligrams received, and to therefore calculate a cost. Given that the number of cycles and the dose are clinical patient-dependent variables, it was considered that no statistical method exists to appropriately reflect the missing values Outpatient care: emergency room visits, rehabilitation and auxiliary units visits Supportive care includes tests and procedures, but does not include medications as posology data were not captured for supportive care public institute in Mexico (insuring approximately 32% of was not possible to calculate the proportion of patients the population [25]), as can be inferred by the different treated with active care in second-line versus BSC. levels of expenditure between institutes, treatment patterns Finally, future investigations should look to expand the may vary across institutes. The treatment patterns pre- objective patient population to all patients, increase the sented here illustrate the IMSS as an institute rather than study size, and include additional public institutes of the national tendencies. Similarly, the unitary costs are interest in order to calculate more universally applicable representative of the IMSS, and care should be taken when results. applying to other institutes with different cost structures. A direct comparison between the price lists of the IMSS and the Secretariat of Health shows that the costs published for 5 Conclusion INCAN and the National Institute of Medical Science and Nutrition Salvador Zubiran (INCMNSZ) are approximately To our knowledge, this is the first study to look at patient 5 and 12% of the cost of the IMSS. This difference has the management and resource use for patients with advanced potential to change both the total costs and the distribution or metastatic GC in Mexico, with results showing consid- of costs, even while resource use remains constant across erable variation in first- and second-line chemotherapy institutes. regimens. Understanding GC treatment patterns in Mexico Importantly, the protocol planned for the possible loss of will help measure the impact of new innovations in treat- patients to the system and included a criterion of a mini- ment practice and create opportunities to harmonize treat- mum of 3 months of follow-up in cases where more than ment options. one-third of all patients were lost before 3 months. This Acknowledgements The authors would like to thank Barbara Mon- prioritized the capture of resource utilization of patients roy Cruz for assistance with the statistical analysis conducted in the treated in tertiary care hospitals over the calculation of the study, although any errors are our own. percentage of patients treated in second-line with an active chemotherapy, and proved an important bias as patients are Author Contributions MQ: Substantial contributions to conception and design of the study; acquisition, analysis, and interpretation of frequently sent to local health units to receive BSC. As a data; critically revising the manuscript for important intellectual result, these patients were not captured in the study and it 200 M. Quintana et al. content; provided final approval of the version to be published. JAT: 2. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers Substantial contributions to conception and design of the study; C, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality acquisition, analysis, and interpretation of data; drafting and critically worldwide: IARC CancerBase No. 11. Lyon: International revising the manuscript for important intellectual content; provided Agency for Research on Cancer; 2013. http://globocan.iarc.fr. final approval of the version to be published. DN: Substantial con- Accessed 3 Dec 2015. tributions to conception and design of the study; acquisition, analysis, 3. Stewart BW, Kleihues P, editors. World cancer report. Lyon: and interpretation of data; critically revising the manuscript for IARC Press; 2003. important intellectual content; provided final approval of the version 4. Kanavos P. The rising burden of cancer in the developing world. to be published. KJ: Substantial contributions to conception and Ann Oncol. 2006;17(Suppl 8):viii15–23. design of the study; acquisition, analysis, and interpretation of data; 5. Torpy JM, Cassio L, Glass RM. Stomach cancer. JAMA. drafting the manuscript; provided final approval of the version to be 2010;303(17):1771. published. BSB: Substantial contributions to conception and design of 6. National Comprehensive Cancer Network (NCCN). NCCN the study; acquisition, analysis and interpretation of data; critically clinical practice guidelines in oncology: gastric cancer version revising the manuscript for important intellectual content; provided 1.2014. NCCN; 2014. final approval of the version to be published. JAS: Substantial con- 7. Waddel T, Verheij M, Allum W, Cunningham D, Cervantes A, tributions to conception and design of the study; acquisition of data; Arnold D. Gastric cancer: ESMO–ESSO–ESTRO clinical prac- critically revising the manuscript for important intellectual content; tice guidelines for diagnosis, treatment and follow-up. Ann provided final approval of the version to be published. Oncol. 2013;24(Suppl 6):vi57–63. 8. Association Japanese Gastric Cancer. Japanese gastric cancer Compliance with Ethical Standards treatment guidelines 2010 (ver. 3). Gastric Cancer. 2011;14:113–23. 9. Knopf KB, Smith DB, Doan JF, Munakata J. Estimating the Data availability statement The data are not made available at this economic burden of gastric cancer in the United States (abstract time as they are currently being analyzed for further publications. no. e16589). J Clin Oncol. 2011;29(15 Suppl). doi:10.1200/jco. 2011.29.15_suppl.e16589. Ethical statement Ethics approval was obtained from each of the 10. Mariotto AB, Yabroff R, Shao Y, Feuer EJ, Brown ML. Pro- participating institutes. Approval letters are available for review in ´ ´ ´ jections of the cost of cancer care in the United States: PDF format. (1) IMSS: Comision Nacional de Investigacion Cientı- 2010–2020. J Natl Cancer Inst. 2011;103:117–28. fica: # de Registro: 2014-785- 083. (2) iBiomed Aguascalientes: ´ ´ ´ ´ 11. Yabroff KR, Davis WW, Lamont EB, Fahey A, Topor M, Brown Comite de Etica en Investigacion de Investigacion Biomedica para el ´ ML, et al. Patient time costs associated with cancer care. J Natl Desarrollo de Farmacos (12 June 2015; oficio: 0000004). (3) iBiomed ´ Cancer Inst. 2007;99(1):14–23. ´ ´ ´ Queretero: Comite de Etica en Investigacion de Investigacion Bio- 12. On˜ate-Ocan˜a LF. Gastric cancer in Mexico. Gastric Cancer. ´ ´ medica para el Desarrollo de Farmacos (12 June 2015; oficio: 2001;4:162–4. 0000003). (4) SEMAR: Comite´ de Bioe´tica e Investigacio´n (24 July 13. Sampieri CL, Mora M. Gastric cancer research in Mexico: a 2015). Patient consent was not required as the study was a retro- public health priority. World J Gastroenterol. spective, observational, patient chart review. 2014;10(16):4491–502. 14. Vieira FMAC, Victorin APOS, Cubero DIG, Beato CAM, Min- Consent for publication Data capture respected international patient owa E, Julian GS, et al. Real world treatment patterns in meta- privacy regulations. Data that allowed for patient identification were static and/or unresectable gastric cancer patients in Brazil not collected. (abstract no. PCN308). ISPOR 19th annual European conference, Vienna. 29 Oct–2 Nov 2016. Funding Funding for this study was provided by Eli Lilly and 15. Tabla que contiene los Costos Unitarios por Nivel de Atencio´n Company. Me´dica actualizados al 2015. DOF: 11/02/2015 ACUERDO ACDO.AS3.HCT.280115/7.P.DF. Insituto Mexicano del Seguro Conflict of interest Miguel Quintana has received professional fees as Social; 2015. http://www.dof.gob.mx/nota_detalle.php?codigo= a speaker on issues of GC for Eli Lilly and Company in Mexico. Diego 5381602&fecha=11/02/2015. Accessed 8 Jul 2015. Novick declares he is an employee of and owns stock in Eli Lilly and 16. Bu´squeda Productos. Portal de Compras del IMSS. http:// Company. Kyla Jones has received professional fees to conduct both the compras.imss.gob.mx/?P=search_alt. Accessed Jul 2015. current study and additional studies for Eli Lilly and Company. Brenda 17. Instituto Nacional de Cancerologıa Tabulador Autorizado de S. Botello is an ex-employee of Eli Lilly and Company who was ´ ´ Cuotas de Recuperacion. Oficio No. 349-B-032. Subsecretarıade employed during data acquisition, analysis and development of the Ingresos: Unidad de Politica de Ingresos no Tributarios. Mexico manuscript. She has no current competing interests. D.F., 30 Jan 2015. 18. Karve S, Lorenzo M, Liepa AM, Hess L, Kaye J, Calingaert B. Open Access This article is distributed under the terms of the Treatment patterns, costs, and survival among medicare-enrolled Creative Commons Attribution-NonCommercial 4.0 International elderly patients diagnosed with advanced stage gastric cancer: License (http://creativecommons.org/licenses/by-nc/4.0/), which per- analysis of a linked population-based cancer registry and mits any noncommercial use, distribution, and reproduction in any administrative claims database. J Gastric Cancer. medium, provided you give appropriate credit to the original 2015;15(2):87–104. author(s) and the source, provide a link to the Creative Commons 19. Cuyun Carter G, Kaltenboeck A, Ivanova J, Liepa AM, San license, and indicate if changes were made. Roman A, Koh M, et al. Treatment patterns in patients with advanced gastric cancer in Taiwan. Asia Pac J Clin Oncol. 2017;13(3):185–94. References 20. Cuyun Carter G, Kaltenboeck A, Ivanova J, Liepa AM, San Roman A, Koh M, et al. Real-world treatment patterns among patients with advanced gastric cancer in South Korea. Cancer Res 1. Roder D. The epidemiology of gastric cancer. Gastric Cancer. 2002;5(Suppl 1):5–11. Treat. 2017;49(3):578–87. doi:10.4143/crt.2016.001. Advanced and metastatic gastric cancer: resources and costs in the Mexican public sector 201 ´ ´ 21. Contreras-Loya D, Gomez-Dantes O, Puentes E, Garrido-Latorre adenocarcinoma (GC) in Mexico (abstract no. 143). J Clin Oncol. F, Castro-Tinoco M, Fajardo-Dolci G. Waiting times for surgical 2016;34(Suppl):4S. and diagnostic procedures in public hospitals in Mexico. Salud 24. Estado actual de la Seguridad Social en Mexico. 2013. Centro de ´ ´ ´ ´ Publica Mex. 2015;57:29–37. Investigacion Economica y Presupuestaria; 6 Nov 2016. Centro 22. Knaul FM, Arreola-Ornelas H, Vela´zquez E, Dorantes J, Me´ndez de Investigacio´n Econo´mica y Presupuestaria. http://ciep.mx/ O, Avila-Burgos L. El costo de la atencio´nme´dica del ca´ncer estado-actual-de-la-seguridad-social-en-mexico-2013. Accessed mamario: el caso del Instituto Mexicano del Seguro Social. Salud 17 Sept 2016. Publica Mex. 2009;5(Suppl 2):S286–95. 25. Gutie´rrez JP, Herna´ndez-Avila M. Cobertura de proteccio´nen 23. Jones K, Silva JA, Novick D, Botello BS, Monroy Cruz B, salud y perfil de la poblacio´n sin proteccio´nenMe´xico, Iglesia-Chiesa J, et al. Real world treatment patterns of previ- 2000-2012. Salud Publica Mex. 2013;55(Suppl 2):S83–90. ously treated advanced gastric and gastroesophageal junction http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png PharmacoEconomics - Open Springer Journals

Resources and Costs Associated with the Treatment of Advanced and Metastatic Gastric Cancer in the Mexican Public Sector: A Patient Chart Review

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PharmacoEconomics Open (2018) 2:191–201 https://doi.org/10.1007/s41669-017-0043-2 ORIGINAL RESEARCH ARTICLE Resources and Costs Associated with the Treatment of Advanced and Metastatic Gastric Cancer in the Mexican Public Sector: A Patient Chart Review 1 1 2 3 4 • • • • • Miguel Quintana Jose ´ A. Toriz Diego Novick Kyla Jones Brenda S. Botello Juan Alejandro Silva Published online: 31 July 2017 The Author(s) 2017. This article is an open access publication Abstract (IMSS) tariffs, the average total cost per patient-month in Background Little evidence is available on the manage- first- and second-line therapy was US$1230 [95% confi- ment and cost of treating patients with advanced or meta- dence interval (CI) 1034–1425] and US$1192 (95% CI static gastric cancer (GC). This study evaluates patient 913–1471), respectively. Administration and acquisition of characteristics, treatment patterns, and resource utilization chemotherapy comprised the majority of costs. for these patients in Mexico. Conclusions This study shows considerable variation in Methods Data were collected from three centers of inves- first- and second-line chemotherapy regimens of patients tigation (tertiary level). Patients were C18 years of age, with advanced or metastatic GC. Understanding GC treat- diagnosed between 1 January 2009 and 1 January 2015, ment patterns in Mexico will help address unmet needs. had advanced or metastatic GC, received first-line fluo- ropyrimidine/platinum, and had C3 months follow-up after discontinuing first-line treatment. Data were summarized Key Points for Decision Makers using descriptive statistics. Results The study sample totaled 180. Patients’ mean age A considerable variety of chemotherapy regimens in was 57.2 years (±12.4) and 57.0% were male; 151 (83.9%) first- and second-line therapy of patients with patients received second-line chemotherapy. A total of 16 advanced or metastatic GC was observed; however, and 19 regimens were identified in first- and second-line conformity was seen in the most frequently selected therapy. Of the sample, 51 (28.3%) received third-line regimens. therapy, and\10% received more than three lines of active Administration and acquisition of chemotherapy chemotherapy. Supportive care received in first- and sec- comprised the majority of costs; the frequent use of ond-line chemotherapy, included pain interventions (12.2 and 7.9%), nutritional support (3.3 and 1.3%), radiotherapy regimens including capecitabine may reflect a conscious move of doctors towards cost-saving (6.1 and 16.6%), and transfusions (13.3 and 10.6%), measures. respectively. Using Mexican Institute of Social Security & Diego Novick 1 Introduction novick_diego@lilly.com Department of Medical Oncology, Hospital de Oncologı´a, Over the last 50 years, the reduction in incidence and Centro Me´dico Siglo XXI, Instituto Mexicano del Seguro mortality due to gastric cancer (GC) worldwide has been Social, Mexico City, Mexico significant [1]. However, despite this, GC remains highly Eli Lilly and Company, Surrey, UK ranked in both incidence and mortality due to cancer; in ´ ´ Tecnologıa e Informacion para la Salud, Mexico City, 2012 the World Health Organization (WHO) ranked it as Mexico the fifth most common malignancy and the third most Eli Lilly and Company, Mexico City, Mexico 192 M. Quintana et al. common cause of cancer death worldwide [2]. In particu- This study was developed to better understand the cur- lar, GC has a high burden of disease in developing coun- rent treatment patterns of patients diagnosed with GC in tries, where approximately 60% of all cases are detected Mexico in order to support public policy regarding GC [3], and where stomach cancer is ranked among the most treatment programs. The primary objectives of the study frequent type of cancer in terms of incidence and mortality were to (1) describe the demographic and clinical charac- [4]. teristics of the target patient population in Mexico, and (2) The high mortality rate associated with GC is in part due identify and describe treatment patterns used in standard to its lack of distinct symptoms, which allow GC to go practice. Secondary objectives were to estimate direct costs unnoticed until advanced stages, where treatment options associated with the treatment of these patients. This study are limited [5]. While surgery is considered standard focuses on second-line therapy. treatment for early-stage GC, the chemotherapy recom- mended for advanced stages remains relatively nonstan- dardized in terms of regimen selection. International 2 Methods guidelines recommend a two-drug combination of fluo- ropyrimidine and platinum in first-line treatment, without A retrospective, observational study was designed to col- recommending specific regimens or specific product lect data regarding patient characteristics and institutional endorsements [6–8]. In second-line chemotherapy, ramu- resource use from medical records in the Mexican public cirumab, paclitaxel, docetaxel and irinotecan are labeled as system. The target population was patients diagnosed with the preferred treatment options by the National Compre- metastatic/unresectable GC (including gastroesophageal hensive Cancer Network (NCCN; 2014), however only junction) between 1 January 2009 and 1 January 2015, and ramucirumab has formal approval in the indication. treated in tertiary-level centers of investigation. We defined Nonetheless, in terms of real-world experience, little evi- the index date as the date recorded for diagnosis of dence is reported on GC management practices that iden- advanced or metastatic GC. tify the most frequently implemented strategies from the A sample size of 200 was set as a target. Ethics approval wide range of options available. was obtained, and data capture respected international This lack of data is surprising as, according to the few patient privacy regulations. published studies available, the economic burden of GCs is Inclusion criteria were: relatively high and data regarding treatment patterns could • Patients completed first-line chemotherapy that potentially identify areas of cost saving. Presented as an included a platinum analog and a fluoropyrimidine, abstract of a retrospective study, in 2011 Knopf et al. with or without another medication, and continued with collected monthly resource utilization data on patients with either second-line treatment or palliative therapy; GC versus a nondiagnosed control, for the period • Patients were[18 years of age at the time of diagnosis; 2007–2009. The mean monthly costs for patients with GC • Medical records were required to have a follow-up of was US$10,653, versus US$571 for the control group [9]. C3 months following the last administration of first- Knopf et al. posited that while GC has a low prevalence in line treatment, except those recording a documented the US, the cost per patient has an overproportionate death: impact in the cost of care when compared with other cancers. In a study by the US National Cancer Institute, the • This criterion was applied due to a pilot analysis of cost of GC was estimated to be US$1.82 billion in 2010 data collected within the first 3 days which showed that the number of patients with either (1) less than [10]. In a third study in the US by Yabroff et al., it was observed that the cost of GC, in terms of initial care, was 3 months of follow-up, or (2) documented death approximately US$5348, while for the last year of patient within 3 months, exceeded one-third of the col- care the cost rose to US$7435 [11]. lected sample. Mexico is currently considered a medium-risk area of The prespecified criterion regarding minimum follow-up GC, as defined by incidence rate; in 2012, the WHO esti- was included in order to allow for analysis on types of mated a rate of 7.9 per 100,000 inhabitants [2]. Never- agents used in second-line treatment in a situation where a theless, national resources rank GC as the second cause of large percentage of patients was being lost to follow-up. death associated with cancer, and the first cause of mor- This loss of follow-up was experienced in a similar study tality in the country due to digestive tract neoplasms [12]. conducted by the sponsor in Brazil, where a high per- However, similar to international literature, there is little centage of patients left third-level facilities once receiving published evidence on patient management, resource uti- best supportive care (BSC) [14]. As such, the sponsor lization and economic burden, and none on the economic recommended the inclusion of this criterion in order to impact of the disease [13]. Advanced and metastatic gastric cancer: resources and costs in the Mexican public sector 193 prioritize the capture of resource utilization of patients who was calculated using the number of cycles multiplied by remain in tertiary-level hospitals over the calculation of the total milligrams per cycle, based on reported posology. percentage of patients who are treated in second-line with Costs per milligram were used. Costs of administration, an active chemotherapy and the resource utilization of radiotherapy, and supportive care units were calculated by BSC. the reported number of sessions or units. The number of Exclusion criteria consisted of patients who had partic- grade 3 and 4 adverse events was collected, and the cost of ipated, or were currently participating, in any controlled treatment was calculated by adding reported treatment and clinical study, and patients with a second malignant disease procedures. Hospitalization for adverse events was inclu- diagnosed before or after the diagnosis of metastatic/ ded in costs for inpatient hospitalization; inpatient hospi- unresectable GC. talization days were calculated according to reported admission and discharge dates only. Outpatient costs were 2.1 Data Collection calculated according to the reported type of visit, specifi- cally emergency room (ER) visits, pain clinic, or oncology Data were captured using a paper Data Report File (DRF) clinic/consultation. Supportive care resources included that had been validated by the principal investigator against tests and procedures not captured in adverse events, but did the Mexican Institute of Social Security (IMSS) patient not include medication as posology data were not captured files. DRFs were monitored for completeness and precise- for supportive care. Treatment prior to diagnosis of ness by a third-party monitor and transferred to an elec- advanced or metastatic GC was not included in the tronic database. Variables collected included patient analysis. demographics and clinical characteristics, treatment This study estimated direct medical costs from a payer received, adverse events, hospitalization and outpatient perspective, from the index date to the recorded data point visits, and resource utilization. or to the end of data collection (8 August 2015). Cost estimates were calculated using resource utilization data 2.2 Outcomes and their corresponding unitary costs. Unit costs were taken from the IMSS unitary costs list for procedures The primary outcomes of the analysis were defined as the (2015) [15], while the acquisition cost of medication was demographic and clinical characteristics of the patient taken from the IMSS public tenders (2015) [16]. A limited population in Mexico, the proportion of patients treated number of supportive-care costs not published by the IMSS with each chemotherapy regimen per treatment line, and were taken from the National Institute of Cancer (INCAN) resource utilization, while secondary outcomes were 2015 unitary costs list [17](n = 16 variables); however, due to the number and general low cost of the affected defined as cost per patient-month and the distribution of cost per patient-month by category. variables, this had little impact on results. All estimated Start and end dates, as well as duration, were calculated costs were in 2015 Mexican pesos (MXN$) and then using dates reported in the patient files. The number of converted to 2015 US dollars (US$). The exchange rate days from diagnosis to treatment was calculated using the was 0.06317, calculated as the average exchange rate of index date of diagnosis to the day of the first chemotherapy 2015 from the database of the Bank of Mexico (1 January treatment in first-line. In order to include all resources used to 31 December). in each line of therapy, lines of treatment were calculated from the first day of treatment to the day before the fol- 2.3 Statistical Methods lowing line of chemotherapy; for the first-line of treatment, this was defined as the first date of hospitalization, radio- Statistical analysis was descriptive due to the observational therapy or chemotherapy following a diagnosis of nature of the study, and was performed for all main vari- advanced or metastatic GC. End of treatment was calcu- ables collected. The mean, median, mode and standard lated by the last date registered before loss of follow-up, deviation was calculated for continuous variables, and death, or the cut-off date of data capture. frequency and proportion were calculated for categorical Healthcare utilization rates were categorized by the type variables. All measures were assessed using complete case of medical resource service; specifically, acquisition of analysis, with missing values being omitted in the final chemotherapy and premedication products, administration, analysis of each variable. Descriptive analyses were com- adverse events, radiotherapy, inpatient hospitalization, pleted in Excel 2010 (Microsoft Corporation, Redmond, outpatient visits, use of supportive care procedures and WA, USA), and cost analysis was completed in STATA tests. Medicine use, both chemotherapy and premedication, v11 (StataCorp LLC, College Station, TX, USA). 194 M. Quintana et al. metastatic location are shown in Fig. 2. Patients had an 3 Results average waiting time of 30.5 days [95% confidence interval 3.1 Demographic and Clinical Characteristics (CI) 19.4–41.7] from diagnosis to first-line treatment. The final sample size of the study was 180, collected from 3.2 Treatment Patterns three tertiary-level centers of investigation. Due to the low incidence, all patients meeting the inclusion criteria in the A total of 16 and 19 unique treatment regimens were identified for first- and second-line active treatment, participating institutes were included. In the IMSS hospital, Centro Me´dico Nacional (CMN) Siglo XXI, patient files respectively. Each of the five most used regimens in first- line therapy represented C10% of the total population, are organized according to consulting office; all patients summing to 93.9% of all selected therapies. Selection of who met the inclusion criteria of the two consulting offices second-line treatment showed each of the three most fre- were included. quently used regimens representing C10% of the overall The majority of patients were treated in IMSS CMN Siglo XXI (n = 167; 92.8%), followed by the Secretary of population, and 64.9% of all regimens. Of the sample, 29 patients went on to receive BSC after first-line treatment, the Navy (SEMAR) (n = 7; 3.9%), and patients found through the investigation center IBiomed (n = 6; 3.3%). however, due to the small sample and lack of data on resource use, results for these patients are not presented. The patient selection process is outlined in Fig. 1. The demographic and clinical characteristics of patients are No obvious tendency of cycle length per regimens could be observed, however due to the small sample size of each summarized in Table 1. regimen, statistical differences were not tested for. Details The maximum level of education reported was generally for treatment characteristics and frequently used regimens low (n = 137): no schooling, 7.3%; primary school (age are included in Tables 2 and 3. 6–12 years), 29.2%; secondary school (age 12–14 years), 27.0%; high-school, 21.9%; and completing university or 3.3 Resource Utilization postgraduate studies, 14.6%. The majority of patients (57.1%) reported no comorbidities, 14.9% reported dia- The majority of hospitalization in first- and second-line betes, and 9.1% reported idiopathic hypertension; five patients had missing values. All other comorbidities treatment was associated with surgery. In second-line treatment, inpatient care was also linked to treatment of impacted\5% of the sample. Smoking was associated with 52.0 and 3.5%, actively and formerly, respectively, of the toxicity and adverse events. Supportive care was most associated with pain treatment (pain clinic and narcotics) 173 patients who reported on the variable. and the use of endoscopies (see Table 4 for details). Almost all patients included in the study were diagnosed Of the sample, 151 (84%) patients received two lines of with adenocarcinoma, totaling 98.9% of the 179 patients chemotherapy, 51 (28.3%) received three lines, and\10% reporting data on the variable. Of the 173 patients with data, 96.1% were diagnosed with metastasis: approximately one- received more than three lines of active chemotherapy. The maximum lines of therapy received by a patient was seven. third of patients (28.9%) in two or more locations, 8.9% in three or more sites, and only 2.2% in four sites. Tumor Estimated average costs per patient-month are presented in Table 5. characteristics of both the primary location and the Fig. 1 Selection of patients Total no. of paents entered into study database: entered in the study n = 225 Paents included in the review Paents excluded from the review (cause) n = 45 n = 180 st n = 22 (ineligible 1 –line treatment) n = 22 (follow-up duraon <3 months) st n = 1 (not treated in 1 line in instute: no data) Paents included in the analysis Complete count analysis was conducted, only paents with data were included in each calculaon Advanced and metastatic gastric cancer: resources and costs in the Mexican public sector 195 Table 1 Characteristics of the a Variable (n) Mean (SD) 95% CI Min Max patient population Age at diagnosis, years (180) 57.2 (12.4) 55.4–59.0 24.1 82.1 Height, cm (180) 160.4 (9.4) 159.0–161.8 120.0 191.0 Weight, kg (180) 62.7 (11.6) 61.0–64.4 40.0 101.0 BMI, kg/m (180) 24.4 23.7–25.0 13.4 47.9 Variable (n) Category (n) n (%) Sex (179) Male 102 (57.0) Helicobacter pylori infection Tested (180) 61 (33.9) Positive (61) 23 (37.7) Family history of gastric cancer (160) Positive 18 (11.3) Tumor stage at diagnosis of gastric cancer (180) IA 2 (1.1) IB 1 (0.6) IIA 2 (1.1) IIB 4 (2.2) IIIA 23 (12.8) IIIB 58 (32.2) IV 79 (43.9) IIIA/IIIB 11 (6.1) SD standard deviation, CI confidence interval, Min minimum, Max maximum, BMI body mass index, AJCC American Joint Committee on Cancer Sample size of the variable Tumor stage was defined using the AJCC TNM staging system 7th edition,n = 169; 6th edition, n = 3; unknown, n = 9 Fig. 2 Tumor characteristics. a Primary gastric tumor location of the sample (n = 180), b metastatic tumor sites of the sample (n = 173) The patient population of Mexico follows international 4 Discussion tendencies for late- or advanced-stage diagnosis, with the majority of patients being diagnosed with stage III and IV Given the limited information that currently exists on patients diagnosed with advanced or metastatic GC in GC. Of the study population, approximately 80% of patients started first-line treatment in Eastern Cooperative Mexico, this study was designed to better understand patient characteristics, real-world treatment patterns, and Oncology Group (ECOG) 1. While this number decreased to 56.6% in second-line treatment, this reflects patients healthcare resource use. Additionally, this study estimated who had C3 months of follow-up, and likely represents the average cost per patient-month. 196 M. Quintana et al. Table 2 Treatment First-line therapy Second-line therapy characteristics Patients [n (%)] 180 (100.0) 151 (100.0) ECOG score [n (%)] 176 (100.0) 145 (100.0) 1. Symptomatic but completely ambulatory 141 (80.1) 82 (56.6) 2. Symptomatic, \50% in bed during the day 31 (17.6) 50 (34.5) 3. Symptomatic, [50% in bed but not bed-bound 4 (2.3) 13 (9.0) Duration of treatment period Cycles [mean (95% CI)] 4.6 (3.6–5.5) 4.2 (3.6–4.8) Duration of line of treatment Months [mean (95% CI)] 5.5 (4.8–6.2) 4.5 (3.4–5.6) Reason for ending treatment [n (%)] According to treatment protocol 49 (27.2) 36 (23.8) Toxicity/intolerance 49 (27.2) 19 (12.6) Tumor progression 30 (16.7) 31 (20.5) c d Others 52 (28.9) 65 (43.0) ECOG Eastern Cooperative Oncology Group, CI confidence interval Duration of treatment was defined as time on active treatment; data available for n = 179 in the first-line therapy group, and n = 131 in the second-line therapy group Duration of line of treatment was defined as time from the first day of chemotherapy until the day before the next line of chemotherapy; data available for n = 179 in the first-line therapy group, and n = 131 in the second-line therapy group Including deterioration of patient health, improvement in tolerance for oral therapy, stable disease, partial response, programmed surgery Including deterioration of patient health, stable disease, treatment still underway patients who had a more positive response to treatment. viability of oral treatment was improved by first-line Nonetheless, the data further suggest that few patients are intravenous regimens. treated once reaching ECOG 3. Oral chemotherapy may also be a demonstration of The findings of this study show a wide variety of regi- cost-constraining policies being implemented in the main mens used in both first- and second-line treatment, with a hospital of the study, i.e. IMSS, as an attempt by doctors total of 16 and 19 unique treatment regimens, respectively. to reduce hospital visits. Administration of chemotherapy Variability in treatment patterns has been demonstrated to was identified as the main cost driver of this analysis, and be an internationally consistent trait, as demonstrated in a reduction of visits for this purpose would have an similar studies conducted in the US, Taiwan, and South important impact on overall costs. Additionally, the study Korea [18–20]. The variation in Mexico remains compar- estimated that, on average, patients wait 30.5 days from atively high, which may reflect the lack of hospital-specific diagnosis of metastatic GC to treatment. This may be guidelines for the institutions included in the analysis. another cost-constraining effort as the IMSS manages a However, the fact that the most frequently used regimens global budget and a delay in treatment may increase in first- and second-line therapy represent 93.9 and 64.9% cashflow flexibility for administrators. However, it is of patients, respectively, suggests a level of conformity in important to note that this may be institute-specific as the selection process. When the investigating physicians wait times for elective services are reported as highly were consulted on the results, it was submitted that regi- variable across and within institutes [21]. Finally, the men selection is influenced primarily by the availability of study saw a lack of follow-up in tertiary-level care specific chemotherapies in the hospital pharmacy at the institutes for patients receiving BSC as the demand for time of prescription, and their form of administration. resources by the high-volume IMSS hospital requires that The preference towards prescribing orally administered these patients move to primary care units for follow-up products may be a reflection of this latter variable; care. specifically, capecitabine was administrated to 58.3 and In terms of overall cost estimates, the administration 60.3% of patients in first- and second-line treatment, schedule of the selected regimen had the largest impact on respectively. Patients were purposefully switched to cape- the average cost per patient, representing 35–48% of total citabine from first- to second-line therapy when the costs in first- and second-lines of treatments. This, Advanced and metastatic gastric cancer: resources and costs in the Mexican public sector 197 Table 3 Frequently used Regimen Percent of population Agent Mean cycles 95% CI treatment regimens in first- and second-line therapy First-line therapy EOX 32.2 Epirubicin 5.7 2.9–8.5 Oxaliplatin Capecitabine XELOX 23.3 Capecitabine 4.4 3.6–5.1 Oxaliplatin ECF 14.4 Epirubicin 2.4 1.8–3.0 Cisplatin 5-FU FLOX 13.9 5-FU 5.2 3.8–6.6 Folinic acid Oxaliplatin FUP 10.0 5-FU 3.3 2.2–4.5 Cisplatin Other Second-line therapy CAP 34.4 Capecitabine 4.3 3.3–5.3 DOC 16.6 Docetaxel 3.9 2.7–5.0 XELOX 13.9 Capecitabine 4.4 2.1–6.7 Oxaliplatin Other 5-FU 5-fluorouracil, CI confidence interval, CAP capecitabine, DOC docetaxel, EOX (epirubicin/oxali- platin/capecitabine), ECF (epirubicin/cisplatin/5-FU), FLOX (5-FU/folinic acid/oxaliplatin), FUP (5-FU/ cisplatin), XELOX (capecitabine/oxaliplatin) Cisplatin/5-FU/paclitaxel; DCF (doxetaxel/cisplatin/5-FU); EOF (epirubicin/oxaliplatin/5-FU); DOX (docetaxel/oxaliplatin/capecitabine); carboplatin/5-FU; carboplatin/5-FU/paclitaxel; DCX (doxetaxel/cis- platin/capecitabine); oxaliplatin/capecitabine/trastuzumab/doxorubicin; DCX/trastuzumab; capac- itabine/cisplatin; DOF (doxetaxel/oxaliplatin/5-FU) Paclitaxel/carboplatin; EOX; FLOX; paclitaxel; FUP; ECX (epirubicin/cisplatin/capecitabine); ECF; carboplatin; DOX (doxetaxel/oxaliplatin/capecitabine); EOF; capecitabine/cisplatin; capecitabine/cis- platin/docetaxel/trastuzumab; irinotecan; FOLFIRI (5-FU/leucovorin/irinotecan); FLOT (5-FU/leucovorin/ oxaliplatin/docetaxel); radiotherapy compared with the 14–21% for the cost of drug acquisition, MXN$154,018 and MXN$199,274, respectively, equiva- highlights the generic status of the products used. Inpatient lent to US$9729 and US$12,587, respectively, using the hospitalization and supportive care used a comparable previously stated 2015 average exchange rate [22]. While proportion of resources as medication. Supportive care firm conclusions are hard to make given the different time medication and outpatient care were minimal and were horizons of the analysis, if considering the short overall primarily associated with analgesics and narcotics (mor- survival of GC patients it may be expected that the overall phine, buprenorphine, and tramadol), as well as nutritional spending on advanced GC in Mexico is similar to that of support. breast cancer. The total average cost per patient-month of first- and This is the first Health Resource Utilization study second-line care were very similar, at US$1230 and completed in Mexico focusing on the standard care of US$1192, which is significantly lower than the US$10,653 treatment of patients diagnosed with advanced and meta- per patient-month published by Knopf et al. for patients static GC, and can be seen as a step towards providing diagnosed with GC in the US [9]. In comparison, Yabroff information regarding treatment patterns and estimating the et al. estimated that the last year of patient care for a patient overall costs of these patients. This is of particular with GC in the US was US$7435 [11]. This may be importance in a field where the majority of treatment comparable with the results of a recently published paper in options remain generic and the recent and future develop- Mexico that estimated the cost per patient-year of late- ment of innovative products will increase overall treatment stage breast cancer in the IMSS for stages III and IV of costs for public providers. 198 M. Quintana et al. Table 4 Patient supportive care and hospitalization by phase of therapy [17] First-line therapy (n = 180) Second-line therapy (n = 151) Supportive care [n (%)] Analgesics 135 (75) 109 (72.2) Diuretics 4 (2.2) 2 (1.3) Antidepressants 1 (0.6) 0 (0) Granulocyte colony-stimulating factors 9 (5) 6 (4.0) Pain interventions 22 (12.2) 12 (7.9) Erythropoiesis-stimulating agents 1 (0.6) 1 (0.7) Granulocyte/macrophage colony-stimulating factor 1 (0.6) 2 (1.3) Blood transfusion 24 (13.3) 16 (10.6) Endoscopy 161 (89.4) 78 (51.7) Radiotherapy 11 (6.1) 25 (16.6) Nutritional support, patients with information available [n (%)] Nutritional support clinic 2 (1.1) 0 (0) Total parenteral nutrition ? nonspecified nutritional support 6 (3.3) 2 (1.3) Inpatient hospitalization Hospitalization per patient (n) 0.27 0.18 At least one inpatient stay [n (%)] 40 (22.2) 22 (14.6) Length of stay/hospitalization (days) [n (95% CI)] 7.0 (4.9–9.1) 7.1 (4.6–9.6) Main reasons for visit [n (%)] 49 28 Disease symptom management 7 (14.3) 5 (17.9) Gastric cancer-related surgery 31 (63.3) 11 (39.3) Adverse events/toxicity 3 (6.1) 8 (28.6) Others 8 (16.3) 4 (14.3) Outpatient care, patients with information available Mean visits/all patients (n) 0.25 0.27 Patients with at least one visit [n (%)] 26 (14.4) 14 (9.3) Mean visits/patient requiring outpatient care (n) 1.7 2.9 CI confidence interval Pain interventions include use of the pain clinic and use of narcotics, including morphine, buprenorphine and tramadol The radiotherapy data presented in this paper differ from the poster presented on the same study (Jones et al. [23]); differences were found between the reporting of posology, necessary for the cost calculations included in this paper, and general resource use included in the poster. This paper decided to report resource use using posology data due to the greater level of detail presented and in order to maintain consistency of data between resource use and costs. Differences are potentially due to capture error (transfer from paper Data Report File to electronic database) and patients who received radiotherapy but did not have posology details on file Healthcare in Mexico is provided by multiple public Institute of Social Security and Services of Employees of institutes that deliver full or subsidized care depending on the State (ISSSTE) and Mexican Petroleums (PEMEX), employment status. However, provision of care between and MXN$1262.42/US$80 for the Seguro Popular [24]. institutes is not equal; each institute makes its own decision These differences in spending are accounted for by the on the benefits and products to be provided, given the social/economic difference of the contributing population. available resources. The results presented in this study are While the study provides an important starting point for primarily a reflection of treatment practices and costs in the data collection in GC in Mexico, it is important to note IMSS, the largest public healthcare provider in Mexico, certain limitations. In particular, the small sample size which covers private sector employees and their depen- combined with the range of regimens identified in both dents. The IMSS provides free care at the point of access, first- and second-line therapy limited the ability to estimate spending an estimated MXN$2909/US$184 per patient, on costs per regimen and to compare results across regimens. average (data from 2013); this in comparison to Furthermore, the generalization of these results to all MXN$3326/US$210 and MXN$16,772/US$1059 for public institutes is limited. While the IMSS is the largest Advanced and metastatic gastric cancer: resources and costs in the Mexican public sector 199 Table 5 Average cost per patient-month and distribution of costs of patients treated for metastatic gastric cancer First-line therapy Second-line therapy Total Total cost per 1230 (1034–1425) 1192 (913–1471) 1292 (1044–1541) patient-month (95% CI) Resources n Mean % 95% 95% n Mean % 95% 95% n Mean % 95% 95% cost CI CI cost CI CI cost CI CI (low) (high) (low) (high) (low) (high) Drug aquisition 171 174 14.1 131 218 128 244 20.5 171 316 120 250 19.3 173 327 Administration 179 586 47.6 478 695 131 421 35.3 270 5720 180 627 48.5 466 789 Adverse events 179 5 0.4 2 8 131 2 0.2 1 3 180 10 0.8 0 19 Radiotherapy 179 9 0.7 2 15 131 139 11.7 75 202 180 55 4.3 38 73 Hospitalization 179 185 15.0 80 289 131 247 20.7 92 403 180 227 17.6 95 360 (inpatient) Outpatient visits 179 51 4.1 -5 106 131 14 1.2 -3 30 180 26 2.0 13 39 Supportive care 179 200 16.3 154 245 131 152 12.8 110 194 180 279 21.6 174 384 CI confidence interval To calculate the cost per patient-month per line of treatment, patients who had missing values in any of the variables were eliminated: first-line therapy, n = 171; second-line therapy, n = 128; all lines, n = 120; first-line therapy costs start at the first input of chemotherapy, radiation, or hospitalization The sample size between the drug aquisition cost and the remaining costs is different due to the missing values in the number of cycles received or the dose, which made it impossible to estimate the total milligrams received, and to therefore calculate a cost. Given that the number of cycles and the dose are clinical patient-dependent variables, it was considered that no statistical method exists to appropriately reflect the missing values Outpatient care: emergency room visits, rehabilitation and auxiliary units visits Supportive care includes tests and procedures, but does not include medications as posology data were not captured for supportive care public institute in Mexico (insuring approximately 32% of was not possible to calculate the proportion of patients the population [25]), as can be inferred by the different treated with active care in second-line versus BSC. levels of expenditure between institutes, treatment patterns Finally, future investigations should look to expand the may vary across institutes. The treatment patterns pre- objective patient population to all patients, increase the sented here illustrate the IMSS as an institute rather than study size, and include additional public institutes of the national tendencies. Similarly, the unitary costs are interest in order to calculate more universally applicable representative of the IMSS, and care should be taken when results. applying to other institutes with different cost structures. A direct comparison between the price lists of the IMSS and the Secretariat of Health shows that the costs published for 5 Conclusion INCAN and the National Institute of Medical Science and Nutrition Salvador Zubiran (INCMNSZ) are approximately To our knowledge, this is the first study to look at patient 5 and 12% of the cost of the IMSS. This difference has the management and resource use for patients with advanced potential to change both the total costs and the distribution or metastatic GC in Mexico, with results showing consid- of costs, even while resource use remains constant across erable variation in first- and second-line chemotherapy institutes. regimens. Understanding GC treatment patterns in Mexico Importantly, the protocol planned for the possible loss of will help measure the impact of new innovations in treat- patients to the system and included a criterion of a mini- ment practice and create opportunities to harmonize treat- mum of 3 months of follow-up in cases where more than ment options. one-third of all patients were lost before 3 months. This Acknowledgements The authors would like to thank Barbara Mon- prioritized the capture of resource utilization of patients roy Cruz for assistance with the statistical analysis conducted in the treated in tertiary care hospitals over the calculation of the study, although any errors are our own. percentage of patients treated in second-line with an active chemotherapy, and proved an important bias as patients are Author Contributions MQ: Substantial contributions to conception and design of the study; acquisition, analysis, and interpretation of frequently sent to local health units to receive BSC. As a data; critically revising the manuscript for important intellectual result, these patients were not captured in the study and it 200 M. Quintana et al. content; provided final approval of the version to be published. JAT: 2. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers Substantial contributions to conception and design of the study; C, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality acquisition, analysis, and interpretation of data; drafting and critically worldwide: IARC CancerBase No. 11. Lyon: International revising the manuscript for important intellectual content; provided Agency for Research on Cancer; 2013. http://globocan.iarc.fr. final approval of the version to be published. DN: Substantial con- Accessed 3 Dec 2015. tributions to conception and design of the study; acquisition, analysis, 3. Stewart BW, Kleihues P, editors. World cancer report. Lyon: and interpretation of data; critically revising the manuscript for IARC Press; 2003. important intellectual content; provided final approval of the version 4. Kanavos P. The rising burden of cancer in the developing world. to be published. KJ: Substantial contributions to conception and Ann Oncol. 2006;17(Suppl 8):viii15–23. design of the study; acquisition, analysis, and interpretation of data; 5. Torpy JM, Cassio L, Glass RM. Stomach cancer. JAMA. drafting the manuscript; provided final approval of the version to be 2010;303(17):1771. published. BSB: Substantial contributions to conception and design of 6. National Comprehensive Cancer Network (NCCN). NCCN the study; acquisition, analysis and interpretation of data; critically clinical practice guidelines in oncology: gastric cancer version revising the manuscript for important intellectual content; provided 1.2014. NCCN; 2014. final approval of the version to be published. JAS: Substantial con- 7. Waddel T, Verheij M, Allum W, Cunningham D, Cervantes A, tributions to conception and design of the study; acquisition of data; Arnold D. Gastric cancer: ESMO–ESSO–ESTRO clinical prac- critically revising the manuscript for important intellectual content; tice guidelines for diagnosis, treatment and follow-up. Ann provided final approval of the version to be published. Oncol. 2013;24(Suppl 6):vi57–63. 8. Association Japanese Gastric Cancer. Japanese gastric cancer Compliance with Ethical Standards treatment guidelines 2010 (ver. 3). Gastric Cancer. 2011;14:113–23. 9. Knopf KB, Smith DB, Doan JF, Munakata J. Estimating the Data availability statement The data are not made available at this economic burden of gastric cancer in the United States (abstract time as they are currently being analyzed for further publications. no. e16589). J Clin Oncol. 2011;29(15 Suppl). doi:10.1200/jco. 2011.29.15_suppl.e16589. Ethical statement Ethics approval was obtained from each of the 10. Mariotto AB, Yabroff R, Shao Y, Feuer EJ, Brown ML. Pro- participating institutes. Approval letters are available for review in ´ ´ ´ jections of the cost of cancer care in the United States: PDF format. (1) IMSS: Comision Nacional de Investigacion Cientı- 2010–2020. J Natl Cancer Inst. 2011;103:117–28. fica: # de Registro: 2014-785- 083. (2) iBiomed Aguascalientes: ´ ´ ´ ´ 11. Yabroff KR, Davis WW, Lamont EB, Fahey A, Topor M, Brown Comite de Etica en Investigacion de Investigacion Biomedica para el ´ ML, et al. Patient time costs associated with cancer care. J Natl Desarrollo de Farmacos (12 June 2015; oficio: 0000004). (3) iBiomed ´ Cancer Inst. 2007;99(1):14–23. ´ ´ ´ Queretero: Comite de Etica en Investigacion de Investigacion Bio- 12. On˜ate-Ocan˜a LF. Gastric cancer in Mexico. Gastric Cancer. ´ ´ medica para el Desarrollo de Farmacos (12 June 2015; oficio: 2001;4:162–4. 0000003). (4) SEMAR: Comite´ de Bioe´tica e Investigacio´n (24 July 13. Sampieri CL, Mora M. Gastric cancer research in Mexico: a 2015). Patient consent was not required as the study was a retro- public health priority. World J Gastroenterol. spective, observational, patient chart review. 2014;10(16):4491–502. 14. Vieira FMAC, Victorin APOS, Cubero DIG, Beato CAM, Min- Consent for publication Data capture respected international patient owa E, Julian GS, et al. Real world treatment patterns in meta- privacy regulations. Data that allowed for patient identification were static and/or unresectable gastric cancer patients in Brazil not collected. (abstract no. PCN308). ISPOR 19th annual European conference, Vienna. 29 Oct–2 Nov 2016. Funding Funding for this study was provided by Eli Lilly and 15. Tabla que contiene los Costos Unitarios por Nivel de Atencio´n Company. Me´dica actualizados al 2015. DOF: 11/02/2015 ACUERDO ACDO.AS3.HCT.280115/7.P.DF. Insituto Mexicano del Seguro Conflict of interest Miguel Quintana has received professional fees as Social; 2015. http://www.dof.gob.mx/nota_detalle.php?codigo= a speaker on issues of GC for Eli Lilly and Company in Mexico. Diego 5381602&fecha=11/02/2015. Accessed 8 Jul 2015. Novick declares he is an employee of and owns stock in Eli Lilly and 16. Bu´squeda Productos. Portal de Compras del IMSS. http:// Company. Kyla Jones has received professional fees to conduct both the compras.imss.gob.mx/?P=search_alt. Accessed Jul 2015. current study and additional studies for Eli Lilly and Company. Brenda 17. Instituto Nacional de Cancerologıa Tabulador Autorizado de S. Botello is an ex-employee of Eli Lilly and Company who was ´ ´ Cuotas de Recuperacion. Oficio No. 349-B-032. Subsecretarıade employed during data acquisition, analysis and development of the Ingresos: Unidad de Politica de Ingresos no Tributarios. Mexico manuscript. She has no current competing interests. D.F., 30 Jan 2015. 18. Karve S, Lorenzo M, Liepa AM, Hess L, Kaye J, Calingaert B. 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