Cost comparison of outpatient treatment with granulocyte colony-stimulating factors (G-CSF) in Germany

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1 International Journal of Clinical Pharmacology and Therapeutics, Vol. No. /2012 (1-9) Cost comparison of outpatient treatment with granulocyte colony-stimulating factors (G-CSF) in Germany Original 2012 Dustri-Verlag Dr. K. Feistle ISSN DOI /CP e-pub: Peyman Hadji 1 *, Karel Kostev 2 *, Detlef Schröder-Bernhardi 2 and Volker Ziller 1 1 Philipps-University of Marburg, Marburg, and 2 IMS Health, Frankfurt am Main, Germany Key words biosimilar cancer therapy chemotherapy-induced neutropenia filgrastim granulocyte colony-stimulating factor G-CSF hematopoiesis lenograstim pegfilgrastim therapy cost cost *Both authors contributed equally to the manuscript. Received July 26, 2011; accepted December 1, 2011 Correspondence to Prof. Dr. med. Peyman Hadji Philipps-University of Marburg, Klinik für Gynäkologie, Gynäkologische, Endokrinologie und Onkologie, Baldinger Straße, Marburg, Germany Peyman.Hadji@ t-online.de Abstract. Background: Granulocyte colony-stimulating factors (G-CSF), are available for prevention of neutropenia and reduction of its complications in cytostatic chemotherapy. The purpose of this analysis was to determine the consumption rates for various G-CSF and to compare outpatient medication costs per patient and treatment cycle. Methods: Prescription data of statutory health insurance members in Germany (IMS LRx database) with G-CSF prescriptions between January 2008 and July 2010 were evaluated. A period of observation of at least 6 months prior to and after the G-CSF prescription was required. Results: Prescription data of 8,726 patients treated with original filgrastim, 4,240 with biosimilar filgrastim, 6,456 with lenograstim, and 9,939 with pegfilgrastim were analyzed. The regression model showed statistically significant costreducing effects per cycle for treatment with lenograstim compared with non-lenograstim ( 0.47 vs. original filgrastim; 0.15 vs. biosimilar filgrastim; 1.04 vs. pegfilgrastim; each p < ). This result has been adjusted for patient age, gender, number of injections, and prescribing specialist group. Conclusions: Treatment with the original preparation lenograstim is significantly cheaper compared to the other two original drugs and biosimilar. The costs of G-CSF treatment with the original preparation lenograstim and the filgrastim biosimilars are in a similar range, but with a significantly lower cost for lenograstim. Compared to their reference product the biosimilars thus show a cost advantage. Introduction Indications The probability of the occurrence of neutropenia is high for any patient who must undergo cytostatic chemotherapy for treatment of a malignant hematological disease or a solid tumor. This is considered a complication when fever also occurs, i.e. when the patient has febrile neutropenia. The severity of neutropenia and the probability of febrile neutropenia are determined by the nature of the applied chemotherapy, the underlying malignancy, and patient-specific factors [1, 2, 3]. Any febrile neutropenia may indicate a severe infection. Acute myeloid leukemia patients with neutropenia exhibit an infection rate between 80% and 90% in patients with solid tumors, and neutropenia exhibit an infection rate of 50% [4, 5, 6]. If an infection is suspected, which is the case if a patient with neutropenia suffers from a fever, oncological patients receiving outpatient treatment must be hospitalized and receive antibiotics, which can lead to high follow-up costs [7]. For tumor patients, this results in the need for risk prevention through prophylactic administration of G-CSF to prevent or shorten severe neutropenia or febrile neutropenia following chemotherapy. Treatment recommendations The clinical benefit of treatment with the hematopoietic growth factor granulocyte colony-stimulating factor (G-CSF) for prevention of febrile neutropenia has been described extensively [1]. Prophylaxis with recombinant G-CSF is recommended to prevent febrile neutropenias and associated secondary events such as infections [1, 2, 3]. The individual need for prophylaxis with a G-CSF depends on the type of tumor, the required chemotherapy, the treatment intent, and the presence of patient-specific factors. Higher age of patients (> 65 years), female gender, poor general health, and presence of

2 Hadji, Kostev, Schröder-Bernhardi and Ziller 2 concomitant diseases are high risk factors for infectious complications of neutropenia. Current guidelines recommend prophylactic administration of G-CSF in cases of febrile neutropenia risk of over 20% [1]. If chemotherapy itself is associated with a 20% risk of febrile neutropenia, possible patientspecific risk factors should be considered which could increase the individual risk of the patient to over 20%. The risk assessment should be performed before each cycle since the risk constellation for febrile neutropenia may change during treatment. G-CSF can be administered as primary prophylaxis, i.e. during the first chemotherapy cycle (and hence all subsequent cycles), or as secondary prophylaxis, i.e. upon occurrence of neutropenic complications in one cycle, with administration in all subsequent cycles. At the time of data collection (2008 to 2011), various filgrastim biosimilars were available in Germany, as were three original G-CSF preparations: filgrastim, lenograstim and pegfilgrastim. All G-CSFs effectively reduce the risk of febrile neutropenias after chemotherapy [1, 8]. However, the active ingredients differ in their dosages, durations of use, and available strengths, package sizes, and prices [3, 9]. Pegfilgrastim is administered in a standardized 6 mg dose once per chemotherapy, an active ingredient amount equivalent to 20 consecutive days of individual doses of 30 million units of filgrastim. Lenograstim and filgrastim are dosed as a function of patient-specific body surface and body weight and administered daily until neutrophil counts recover. In outpatient treatment, this goal is achieved after an average of 5 to 6 days. Although the average is 5 to 6 days some patients need longer duration of G-CSF-application up to a maximum of 10 days [10, 11, 12]. Lenograstim is available in strengths of 13 million IU for pediatric patients and 34 million IU for adult patients, and it is approved for patients with a body surface area of up to 1.8 m 2. Filgrastim is available in strengths of 30 million IU (patients up to 60 kg body weight) and 48 million IU (patients up to 96 kg body weight). The daily dose of lenograstim and filgrastim can be rounded to one of the available strengths [3]. The individual dose required and the frequency of G-CSF administration in one chemotherapy cycle are the determining factors in the cost of G-CSF prophylaxis per cycle. The number of individually necessary chemotherapy cycles with G-CSF in the context of the overall tumor treatment determines the total cost incurred per patient. Unlike the cost per cycle, the total cost is dependent upon the underlying disease and the treatment intent, since a primary prophylaxis with curative treatment intent necessarily results in a greater number of G-CSF cycles and a higher total G-CSF cost compared to secondary prophylaxis. Study goals Treatment alternatives The goal of this study was to determine the consumption rates for various G-CSF and to compare outpatient medication costs per patient and treatment cycle. Patients and methods Data sources and resources The IMS LRx database designed and run by IMS Health GmbH & Co. served as data source. It accesses nationwide pharmacy data centers, processing prescription data of all German patients with statutory health insurance for reimbursement purposes. Data entries covered patient specific data over time, such as anonymized identification number, age, gender, insurance company and area of living as well as prescription information including prescribers anonymized identification number, date and medication down to package level. Information on diagnoses and laboratory parameters are not part of the data sets. It is possible to follow the patient`s prescriptions over time even if they change their pharmacies or doctors. The IMS LRx database contained 95% of all prescriptions issued between January 2007 and February 2011 nationwide. To determine G-CSF consumption rates, all prescription data of statutory health insurance members between January 2008 and July 2010 from the IMS LRx database,

3 Cost comparison of outpatient treatment with granulocyte colony-stimulating factors in Germany 3 Table 1. Pharmacy sales prices of G-CSF products. Calculation of costs Molecule Packsize Price ( ) Original filgrastim 30 million IU, 5 syringes Original filgrastim 48 million IU, 5 syringes 1, Filgrastim biosimilars 30 milion IU, 5 syringes Filgrastim biosimilars 48 million IU, 5 syringes 1, Lenograstim 13 million IU, 1 syringe Lenograstim 13 million IU, 5 syringes Lenograstim 34 Mio IU, 1 syringe Lenograstim 34 Mio IU, 5 syringe Pegfilgrastim 6 mg, 1 syringe 1, were analyzed. All patients with at least one G-CSF prescription for which no change of the prescribed G-CSF preparation took place in the entire period and for which complete information about minimum criteria (age, gender, prescribing specialist group, data for a period of at least 6 months before and after the first G-CSF prescription) was available were taken into account. Gynecologists, internal specialists and the so called specialist group of outpatient doctors are three separate groups of doctors. The gynecologists and the internal specialists are both practice based. The outpatient doctors work in an outpatient clinic located at a hospital and are not self employed doctors in comparison to the practice based doctors. These outpatient doctors can be gynecologists, internal specialists or other specialists. G-CSF is prescribed to the majority of patients by these three groups of doctors who also do the chemotherapy treatment. Other oncologists (e.g. urology, head-and-neck and so on) are summarized in others. In addition, G-CSF can also be prescribed by general practitioners. This group of doctors does not deal with chemotherapy but can take care of oncology patients and for this reason prescribe G-CSF. They have therefore been chosen in order to compare them with the oncologists. A preliminary study for the analysis period from October 2005 to January 2007 used the same database to determine the homogeneity of the study cohorts by comparing the proportions of G-CSF treatment changers and patients with only one G-CSF prescription during the investigation period. During this period the filgrastim biosimilars were not yet available, so there is no information about them. Based on the individual prescriptions per patient, the total number of G-CSF treatments per patient was determined and the G-CSF amount per cycle was calculated. A cycle interval of 21 days was assumed, i.e., in case of a G-CSF follow-up prescription within 21 days, the treatment was considered to have fallen within the same cycle, and in case of a G-CSF follow-up prescription after more than 21 days, the G-CSF treatment was considered to have fallen within a new chemotherapy cycle. The influence of different cycle lengths on the total cost was tested for the regression model in a sensitivity analysis (see below). The calculation of G-CSF treatment cost per patient and cycle was carried out on the basis of the prescribed sizes and strengths using the pharmacy sales prices effective in Germany in August 2009 (Table 1). Statistical methods The characteristics of the study cohorts, the G-CSF consumption rates, and the treatment costs were evaluated using descriptive statistical methods. Exploratory pair wise comparisons of the calculated costs and nonparametric tests (Wilcoxon test) were conducted. The influence of various factors on the total cost per cycle and patient was also examined by means of a regression model. Here, the cost effect of the lenograstim treatment compared to non-lenograstim G-CSF treatment (i.e. with pegfilgrastim or filgrastim) was examined. The multiple linear regression model took into account (adjusted for age, gender, and prescribing specialist group) the absolute number of administered injections and the following binary covariates: lenograstim, the specialist groups of outpatient doctors, internal specialists and gynecologists compared with general practitioners as a reference group, the age group of years, the age group of years, and the age group of over 70 years. The full multiple regression model also assumed a cycle length of 21 days. In a sensitivity analysis the model was tested with various cycle intervals ranging from 14 to 28 days. As the distribution of the variables for therapy costs

4 Hadji, Kostev, Schröder-Bernhardi and Ziller 4 Table 2. Selection of study patients. Including criteria Number of patients Lenograstim Pegfilgrastim Original filgrastim Filgrastim biosimilar At least 1 prescription between January 2008 and July ,126 35,944 28,857 13,626 Therapy initiation between January 2008 and July 2010 (index date) 12,835 19,349 17,192 8,020 Patients can be followed up for at least 183 days after index date 9,582 14,890 12,854 5,936 Patients with documented age and sex 6,456 9,939 8,726 4,240 Table 3. Patient demographics. Patient characteristics Number of patients n (%) Lenograstim (n = 6,456) Pegfilgrastim (n = 9,939) Original filgrastim (n = 8,726) Filgrastim biosimilars (n = 4,240) Gender Male 2,230 (34.5) 2,753 (27.7) 3,270 (37.5) 1,440 (34.0) Female 4,226 (65.5) 7,186 (72.3) 5,456 (62.5) 2,800 (66.0) Age group (years) < (7.9) 686 (6.9) 762 (8.7) 232 (5.5) (12.1) 1,505 (15.1) 968 (11.1) 491 (11.6) ,198 (18.6) 2,125 (21.4) 1,696 (19.4) 856 (20.2) ,219 (27.1) 2,594 (26.1) 2,415 (27.7) 1,186 (28.0) > 70 2,219 (34.4) 3,029 (30.5) 2,885 (33.1) 1,475 (34.8) Prescribing physicians General practitioners 476 (7.4) 173 (1.7) 1,015 (11.6) 202 (4.8) Internal specialists 3,650 (55.1) 5,865 (59.0) 4,527 (51.9) 3,135 (73.9) Gynecologists 1,057 (16.4) 2,078 (20.9) 952 (10.9) 679 (16.0) Outpatient doctors 1,364 (21.1) 1,823 (18.3) 2,232 (25.6) 224 (5.3) did not follow a normal distribution, a logarithmical function was used for data analysis. Results Patient cohorts The analysis encompassed the prescriptions of all patients in the database in the evaluation period in the presence of the defined covariates. Prescription data from 8,726 original filgrastim, 4,240 filgrastim biosimilar, 6,456 lenograstim and 9,939 pegfilgrastim were evaluated (Table 2). The age distribution of patients was similar in all three treatment groups: ~ 1/3 of patients in each group ( %) was older than 70 years and % of patients were between 61 and 70 years old. 30.5% of pegfilgrastim patients, 30.7% of filgrastim biosimilar patients, 31.8% of lenograstim patients, and 36.5% of original filgrastim patients were between 41 and 60 years old. Patients younger than 40 years were the smallest age group, with a minimum of 5.5% (lenograstim) to a maximum of 8.7% (pegfilgrastim) (Table 3). The proportion of men across all groups amounts to ~ 1/3 of patients treated with G- CSF. The proportion of women is highest in the pegfilgrastim group (72.3%) compared to the other G-CSF groups ( %). Lenograstim is prescribed at relatively constant rates across specialist groups, ranging from a maximum of 25.8% of all G-CSF prescriptions by general practitioners to a minimum of 20.5% for the collective term others. At 9.4% the proportion of pegfilgrastim prescriptions is considerably lower among general practitioners compared to the other specialist groups. The proportion of pegfilgrastim is highest among gynecologists, with a share of 43.8% of all G-CSF prescriptions. Internal specialists, outpatient doctors, and the collective term other specialties have pegfilgrastim shares of 34.5%, 32.6%, and 31.1%, respectively. The proportion of original filgrastim patients also differs considerably among the specialist groups. Original filgrastim is the

5 Cost comparison of outpatient treatment with granulocyte colony-stimulating factors in Germany 5 Figure 1. Shares of defined G-CSF molecules by general practitioners, internal specialists, gynecologists and outpatient doctors. the strength most often prescribed is that for patients with a body weight of up to 60 kg. Filgrastim is only available in packages with 5 syringes. Lenograstim is available in packs of 1 syringe or 5 syringes. 84.8% of prescribed injections are accounted for by the package size of 5 syringes, 15.2% by the single syringes. 5.7% of lenograstim prescriptions are in the strength of 13 million units and 94.2% as lenograstim 34 million IU, approved for patients with up to 1.8 square meters of body surface area. The average number of injections per patient and the determined number of cycles per patient are shown in the Table 4. Treatment cost Table 4. Average number of injections per patient and of cycles per patient. Molecule Figure 2. Average G-CSF cost per chemotherapy cycle (differences between all treatment groups are highly significant at p < ). Number of injections per patient, mean (SD) Number of cycles per patient, mean (SD) Original filgrastim (11.17) 2.00 (1.62) Filgrastim biosimilars (9.24) 2.25 (1.73) Lenograstim (11.47) 2.39 (1.95) Pegfilgrastim 3.51 (2.27) 3.37 (2.13) most frequently prescribed G-CSF among general practitioners (54.4%) and the least frequently prescribed among gynecologists (20.0%). The specialist group with the highest proportion of biosimilar patients is the internal specialists, with 18.3% of all G-CSF patients. Only 4% of all G-CSF patients by outpatient doctors are biosimilars (Figure 1). Two filgrastim strengths, 30 million IU and 48 million IU, approved for patients with body weights up to 60 kg and 96 kg, respectively, are available. At 70.6% for the original preparation and 80% for the biosimilar, The average cost of a single cycle treatment amounted to 1, for original filgrastim, for filgrastim biosimilar, for lenograstim, and 1, for pegfilgrastim (Figure 2). At p < these differences are highly significant both in the Wilcoxon test and the t-test. Figure 3 shows that there are no relevant differences in the average cost of a single cycle between physician groups prescribing the respective G-CSF. The calculated average cost of a G-CSF treatment per patient amounted to 2, for original filgrastim, 1, for filgrastim biosimilar, 1, for lenograstim, and 5, for pegfilgrastim. If the regression analysis of cost per patient is adjusted for patient age, gender, and the prescribing specialist group, lenograstim is the most cost-saving G-CSF. Pair wise comparisons of the costs per patient and cycle show statistical significance for the differences between all treatment groups (p < for both t- test and Wilcoxon test). Patient gender has no significant effect on cost per cycle or cost per patient. The age of the patient has no significant effect on the cost per cycle but a small effect on the cost per patient. In the age group > 70 years, the cost per patient is slightly less in comparison to the younger patients. The additional cost modeling in the multiple regression model showed a clearly cost-reducing effect only for the variable of lenograstim treatment. The specialty of the prescribing doctor (out-

6 Hadji, Kostev, Schröder-Bernhardi and Ziller 6 Figure 3. Average G-CSF cost per chemotherapy cycle depending on prescribing physicians (mean costs and standard deviation). The cost differences between doctor specialties are not significant (p > 0.05). Table 5. Regression analysis of the cost per cycle adjusted for age, gender, and specialist group. Corrected R 2 = (p < 0.001) Variable Parameter estimator* p value Original filgrastim c 0.47 < Filgrastim biosimilars c 0.16 < Pegfilgrastim c 0.98 < Outpatient doctors a 0.15 < Internal specialists a 0.12 < Gynaecologists a 0.06 < Age group years b Age group years b Age group > 70 years b 0.05 < Number of injections 0.01 < a Reference: general practitioners, b compared to the next younger age group, c Reference: Lenograstim, *p arameter estimator is an adjusted difference of therapy costs per cycle where therapy costs are logarithmical function. patient doctor, gynecologist, or internal specialist) showed a cost-increasing effect per patient and cycle compared with the reference group of general practitioners (Table 5). Patient age, however, had little impact on the total cost per patient and cycle. The sensitivity analysis of the regression model showed little effect of varying cycle lengths of 2 or 4 weeks. Discussion Among G-CSF preparations, lenograstim has the lowest actual treatment cost. The average treatment cost per cycle amounted to for lenograstim, compared to 1, for original filgrastim, for filgrastim biosimilar, and 1, for pegfilgrastim. The identification of lenograstim as the most cost-saving G-CSF by means of the real prescription data from the IMS LRX database is in line with other published cost comparisons [13, 14]. As the adjustment for the number of injections indicated, the significant cost difference between lenograstim and original filgrastim per treatment cycle is not attributable to the different number of days on which G-CSF is administered per cycle. For the first time, the analysis also resulted in data regarding the proportions of prescribed strengths of the G-CSF preparations on the basis of real prescriptions. The strength of lenograstim 34 million IU is approved for a body surface area of up to 1.8 m 2 and, according to this study, is used almost exclusively. A body surface area of 1.8 m 2 is equivalent to that of an average adult, as determined by the 2009 microcensus of the German Federal Statistical Office. The statistics of the Federal Statistical Office also detail the average weight by age-group and gender. Independent of older age and female gender the average body weight is well above 60 kg. In addition it should be mentioned that hematotoxic chemotherapies with G-CSF prophylaxis are generally not applied to cancer patients who are already cachectic. It can therefore be assumed that the body weight of a cancer patient with chemotherapy and G-CSF is in the range of a healthy person [15]. Two filgrastim strengths are available for treatment of adult patients. Filgrastim 30 million IU is approved for a body weight of up to 60 kg; at a weight above that, filgrastim 48 million IU should be used. The calculated costs for the filgrastim preparations result from the proportions of the two different strengths of 30 million IU and 48 million IU. The original preparation with a strength of 30 million IU was used in 70.6% of the patients, that with a strength of 48 million IU in 29.4% of the patients. Although the filgrastim biosimilars have the same strengths and of course the same approved dosages as the reference preparation, the biosimilars with the strength of 30 million IU are used in 80% of the patients, and only 20% receive the strength of 48 million IU. The average body weight as determined by the Federal Statistical Office amounts to 75.6 kg [15]. It can therefore be assumed that the filgrastim preparations, and in particular the

7 Cost comparison of outpatient treatment with granulocyte colony-stimulating factors in Germany 7 Figure 4. Average G-CSF cost per patient (differences between all treatment groups are highly significant at p < ). filgrastim biosimilars, are often used in dosages lower than those approved. Interestingly, the users of biosimilars who presumably want to choose a particularly cost-saving G- CSF treatment also frequently choose a lower strength than the prescribers of the original preparation. The concern here is that the most frequently chosen strength is only approved for patients with body weights of up to 60 kg. This accumulation of dosages that are potentially too low needs to be compared with treatment success in future studies, because so far there are no studies confirming the effectiveness of low strength dosing of this high proportion (80%) of patients. When calculating the cost per cycle, the assumed length of 21 days may have had a distorting effect on the assigned G-CSF prescription quantities. However, a cycle period of 21 days corresponds to the average interval length in everyday treatment practice [7, 8]. Calculations with possible alternative interval durations of 14 and 28 days did not significantly impact the cost effects of the three G-CSF preparations. The cost-reducing effect of lenograstim per cycle and patient compared to the other G-CSF preparations remains unchanged. No bias in the comparative cost representation per cycle due to the selected cycle length is to be expected. The G-CSF pegfilgrastim is administered to every patient once per chemotherapy cycle; individual circumstances are not taken into account. At an assumed cycle interval of 3 weeks, the analysis showed 3.51 injections of pegfilgrastim in 3.37 cycles, corresponding to an average of 1.04 injections per cycle. This analysis confirms the assumed cycle duration of three weeks. For the G-CSF preparations administered daily, an average of injections per cycle was calculated. The average number of ~ 5 6 G-CSF injections corresponds to the published data about the frequency of application [10, 11, 12] The chosen cycle length had no influence on the comparative cost calculation per patient, as this cost calculation is independent of the cycle length. The G-CSF cost comparison per patient also resulted in lower cost for the treatment with lenograstim after adjusting for patient age, gender, number of injections, and specialist group. An analysis by the Gmündner Ersatzkasse also demonstrated the significant cost advantage of lenograstim (1, ) compared to original filgrastim (2, ) and pegfilgrastim (4, ) [13]. Biosimilars were not yet available at the time of this analysis. However, also in this study, the substantial cost difference between lenograstim and original filgrastim suggests that lenograstim is also more cost-saving than filgrastim biosimilars. The number of treatment cycles with G-CSF per patient is decisive for the overall cost per patient. Inhomogeneous treatment groups could thus cause a possible bias in the cost comparison but not in the cost per cycle. The formal characteristics of the samples do not indicate any bias. The

8 Hadji, Kostev, Schröder-Bernhardi and Ziller 8 study groups were also comparable in terms of patient age. The underlying tumor diseases of the patients treated with the G-CSF preparations cannot be determined by means of the database used. For lenograstim and the two filgrastim groups, the average number of cycles per patient was comparable (original filgrastim 2.00 cycles, filgrastim biosimilars 2.25 cycles, lenograstim 2.39 cycles). For pegfilgrastim a higher value of 3.37 cycles per patient was found. This is associated with the higher proportion of female patients in the pegfilgrastim group (72.3%) compared to the lenograstim, original filgrastim, and filgrastim biosimilar groups (65.5%, 62.5%, 66.0%). Until now there has been no invitation to bid for G-CSF from any health insurance. G-CSF are classified as biosimilar medication and not as generics. Only generics can be used to substitute at the pharmacy level if there is a rebate contract. It is not permissable to substitute a doctor s prescription of an original product at the pharmacy with a biosimilar or even a biosimilar with another biosimilar. The specialist group with the highest proportion of pegfilgrastim prescriptions was the gynecologists. This suggests that none of the lenograstim, original filgrastim, or filgrastim biosimilar preparations is used more frequently in primary prophylaxis than the others. When using G-CSF in primary prophylaxis after the first dose of chemotherapy and thus without prior occurrence of neutropenic complications, more cycles of G-CSF are administered per patient than for secondary prophylaxis, when G-CSF is administered only after the occurrence of complications. Gynecologists may use G-CSF more frequently for primary prophylaxis than other specialist groups, and this preference of the gynecologists for pegfilgrastim could explain the slightly higher number of pegfilgrastim cycles per patient. It was shown that general practitioners have a lower prescribing rate for biosimilars, despite the fact that biosimilars are considered as effective as the originator product. The practitioner cannot conduct a patient s chemotherapy treatment by himself. Patients who receive G-CSF from a practitioner are also treated by an oncology specialist. Therefore it can be assumed that a practitioner is not as deeply involved in oncology therapy and will probably stick to the medication he already knows. The relative sample sizes from the population of patients with the appropriate observation period and complete covariate information were similar for all four groups (66.8% pegfilgrastim, 67.4% lenograstim, 67.9% original filgrastim, 71.4% filgrastim biosimilar). A preliminary analysis of all patients treated with G-CSF, based on the same database as the current analysis but without consideration of additional variables such as prescribing specialist group, age, and gender of the patients showed a similar result. Another possible bias due to significantly different rates of G-CSF treatment changers also appears unlikely, as the rate of treatment changers for the period from October 2005 to January 2007 was determined using the same database. In this period the filgrastim biosimilars were not yet available, so no statements can be made about these preparations. The rate of patients who switched from one G-CSF to another G-CSF preparation was similar for all three groups (11.3% for lenograstim, 11.8% for pegfilgrastim, and 8.8% for original filgrastim). The data analysis does not provide information regarding whether the patients who received a daily administered G-CSF after an initial prescription of pegfilgrastim received it in the same chemotherapy cycle or the next cycle of chemotherapy. The analysis of cost factors in the regression model also illustrates a clearly costlowering effect of the lenograstim treatment compared to G-CSF treatment with another preparation. Regarding different factors such as gender, specialty of the prescribing physician, and age, the regression model shows more homogenous conditions across the comparison groups. Apart from the G- CSF preparation used, no other factors with relevant cost-reducing effect on the G-CSF treatment cost were identified in the model. References [1] Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, Lyman GH, Pettengell R, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C; European Organisation for Research and Treatment of Cancer update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult pa-

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