Economic assessment of continuous processing for manufacturing of biotherapeutics.

Continuous processing offers a promising approach to revolutionize biotherapeutics manufacturing as reflected in recent years. The current study offers a comparative economic assessment of batch and continuous processing for the production of biotherapeutic products. Granulocyte-colony stimulating factor (GCSF), a protein expressed in E. coli, and an IgG1 monoclonal antibody, were chosen as representatives of microbial and mammalian derived products for this assessment. Economic indicators-cost of goods (COGs), net present value (NPV), and payback time have been estimated for the assessment. For the case of GCSF, conversion from batch to integrated continuous manufacturing induced a $COGs/g reduction of 83% and 73% at clinical and commercial scales, respectively. For the case of mAb therapeutic, a 68% and 35% reduction in $COGs/g on translation from batch to continuous process was projected for clinical and commercial scales, respectively. Upstream mAb titer was also found to have a significant impact on the process economics. With increasing mAb titer, the $COG/g decreases in both operating modes. With titer increasing from 2 to 8 g/L, the $COG/g of batch process was reduced by 53%, and that of the continuous process was reduced by 63%. Cost savings in both the cases were attributed to increased productivity, efficient equipment and facility utilization, smaller facility footprint, and reduction in utilization of consumables like resin media and buffers actualized by the continuous processing platform. The current study quantifies the economic benefits associated with continuous processing and highlights its potential in reducing the manufacturing cost of biotherapeutics.

[Cost-effectiveness of primary prophylaxis with PEG-rhG-CSF in early-stage breast cancer patients receiving chemotherapy in China].

Objective: To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China. Methods: Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio (HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results: Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion: Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

Expression and one step intein-mediated purification of biologically active human G-CSF in Escherichia coli.

Recombinant form of granulocyte colony stimulating factor (G-CSF) was first approved by FDA in 1998 for chemotherapy induced neutropenia. However, despite production of its biosimilars, less expensive production of G-CSF could reduce the overall therapeutic cost. The aim of this study was to evaluate the possibility of producing biologically active recombinant G-CSF via a single step purification procedure mediated by a self-cleavable intein. G-CSF was expressed by E. coli BL21 (DE3) through IPTG induction, followed by its purification using pH optimization on a chitin column. Western blotting, ELISA, size exclusion chromatography, circular diachorism, peptide mapping, and in vitro assays were performed to compare the structural similarity and biological activity of the purified G-CSF with Neupogen™. Protein purification was confirmed by revealing a band of approximately 18.8 kDa on SDS-PAGE. Bioactivity and physicochemical assays based on the US pharmacopeia showed almost identical or acceptable ranges of similarities between recombinant G-CSF and Neopogen™. this study, biologically active soluble recombinant G-CSF was successfully produced with high purity without using chaotropic solvents through a one-step procedure. This shorter and more efficient purification procedure can reduce the cost and time of G-CSF production which makes its industrial production more cost-effective and might be also applicable for production of other biopharmaceuticals.

The long-term social value of granulocyte colony-stimulating factors.

OBJECTIVES: Febrile neutropenia (FN) is a life-threatening complication of chemotherapy that can lead to hospitalizations, chemotherapy dose reductions or delays, and mortality. Granulocyte colony-stimulating factor (G-CSF) prophylaxis reduces the incidence of FN, enabling patients to undergo and remain on myelosuppressive chemotherapy. We estimate the benefits of continuing current G-CSF use patterns and an alternative that aligns prophylactic G-CSF use with guideline recommendations. STUDY DESIGN: Using The Health Economics Medical Innovation Simulation microsimulation, we estimated lifetime social value (SV) of prophylactic G-CSF for a nationally representative US population with breast, lung, and gynecological cancers and non-Hodgkin lymphoma. METHODS: SV estimates included the cost of G-CSF, FN, chemotherapy relative dose intensity (RDI) less than 85% (RDI<85%), medical spending, and deaths for 3 scenarios: current use (current G-CSF use), targeted use (100% G-CSF use among patients with high FN risk), and reduced use (current G-CSF use reduced by 20% across all FN risk categories). RESULTS: Over 10 years, current use, compared with no G-CSF use, would decrease cases of FN by 3.3 million, prevent 354,000 cases of RDI<85%, and generate $96 billion in SV. Compared with current use, targeted use would decrease cases of FN by an additional 3.3 million, prevent 355,000 more cases of RDI<85%, and generate another $119 billion in SV. Reduced use would increase FN and RDI<85%, lowering SV by $18 billion compared with current use. CONCLUSIONS: Current use of G-CSF prophylaxis would provide $96 billion in SV over the next 10 years. Targeting G-CSF prophylaxis to align with guidelines would more than double SV, highlighting the substantial value of appropriate FN risk assessment and targeted G-CSF prophylaxis.

Price competition and reimbursement of biosimilar granulocyte-colony stimulating factor in Hungary.

Objectives: We analyzed the bid approach of the Hungarian National Health Insurance Fund Administration (NHIFA) based on the results of two consecutive bids on colony stimulating factor (CSF).Methods: The Hungarian NHIFA database was used to analyze the changes in the number of patients treated with CSF and reimbursement paid by NHIFA, 12 months preceding and following the bids.Results: 13,974 patients received granulocyte-CSF treatment during 12 months prior to bidding. A 4.5% decrease (13,352) and further 1.3% decrease (13,185) in the total number of patients were observed during the first and second years, respectively. The annual health insurance subsidy paid during 12 months prior to the bids was. 7.49 billion Hungarian Forint (HUF) or 26.8 million Euro (EUR). In the first year following the bid, we found a 3.3 billion HUF (12.4 million EUR) decrease in health insurance subsidy (44% reduction). A further 7.9% reduction was observed during the second year, resulting in an annual health insurance subsidy of 3.59 billion HUF (12.1 million EUR).Conclusion: During the 2 years bid (public procurement procedure), the National Health Insurance Fund Administration managed to reduce the health insurance subsidy paid for the reimbursement of both original and biosimilar G-CSF products.

Outcomes of previously untreated elderly patients with AML: a propensity score-matched comparison of clofarabine vs. FLAG.

The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥ 60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P = 0.045) and OS (7.9 vs. 2.8 months, P = 0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P = 0.002). Finally, we performed a cost analysis that estimated savings to be $30,000-45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.

Comparison of treatment patterns and economic outcomes among metastatic pancreatic cancer patients initiated on nab-paclitaxel plus gemcitabine versus FOLFIRINOX.

BACKGROUND: The economic burden of metastatic pancreatic cancer (mPC) is substantial while treatment options are limited. Little is known about the treatment patterns and healthcare costs among mPC patients who initiated first-line gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-P + G) and FOLFIRINOX. METHODS: The MarketScan® claims databases were used to identify adults with ≥2 claims for pancreatic cancer, 1 claim for a secondary malignancy, completed ≥1 cycle of nab-P + G or FOLFIRINOX during 4/1/2013 and 3/31/2015, and had continuous plan enrollment for ≥6 months pre- and 3 months after the first-line treatment. Duration of therapy, per patient per month (PPPM) costs of total healthcare, mPC-related treatment, and supportive care were measured during first-line therapy. RESULTS: 550 mPC patients met selection criteria (nab-P + G, n = 294; FOLFIRINOX, n = 256). There was no difference in duration of therapy (p = 0.60) between nab-P + G and FOLFIRINOX. Compared with FOLFIRINOX, patients with nab-P + G had higher chemotherapy drug costs but lower treatment administration costs and supportive care costs (all p < 0.01). CONCLUSIONS: Patients treated with nab-P + G (vs FOLFIRINOX) had similar treatment duration but lower costs of outpatient prescriptions, treatment administration and supportive care. Lower supportive care costs in the nab-P + G cohort were mainly driven by lower utilization of pegfilgrastim and anti-emetics.

Management and cost analysis of cancer patients treated with G-CSF: a cohort study based on the French national healthcare insurance database.

OBJECTIVES: To describe the management and costs associated with G-CSF therapy in cancer patients in France. METHODS: This study analyzed a representative random population sample from the French national healthcare insurance database, focusing on 1,612 patients with hematological or solid malignancies who were reimbursed in 2013 or 2014 for at least one G-CSF treatment dispensed in a retail pharmacy. Patient characteristics and treatment costs were analyzed according to the type of cancer. Then the costs and characteristics of patients associated with the use of different G-CSF products were analyzed in the sub-set of breast cancer patients. RESULTS: The most frequent malignancies in the database population were breast cancer (23.3%), hematological malignancies (22.2%), and lung cancer (12.4%). The reimbursed G-CSF was pegfilgrastim in 34.1% of cases, lenograstim in 26.7%, and filgrastim in 17.9%. More than one G-CSF product was reimbursed to 21.3% of patients. The total annual reimbursed health expenses per patient, according to the type of G-CSF, were €27,001, €24,511, and €20,802 for patients treated with filgrastim, lenograstim, and pegfilgrastim, respectively. Ambulatory care accounted for, respectively, 35%, 38%, and 41% of those costs. In patients with breast cancer, ambulatory care cost was €7,915 with filgrastim, €7,750 with lenograstim, and €6,989 with pegfilgrastim, and the respective cost of G-CSF was €1,733, €1,559, and €3,668. CONCLUSION: All available G-CSF products have been shown to be effective in cancer patients, and both daily G-CSFs and pegylated G-CSF are recommended in international guidelines. Nevertheless, this analysis of G-CSF reimbursement indicates that the choice of product can markedly affect the total cost of ambulatory care.

Granulocyte colony-stimulating factors in the prevention of febrile neutropenia: review of cost-effectiveness models.

INTRODUCTION: We reviewed the evolution of the methods used in cost-effectiveness analyses of granulocyte colony-stimulating factors (G-CSFs) in the primary and secondary prevention of febrile neutropenia (FN) in patients receiving myelosuppressive cancer chemotherapy. Areas covered: FN is a side effect of myelosuppressive chemotherapy associated with significant morbidity, mortality, and costs. The risk of FN may depend on the drugs used within a chemotherapy regimen, and an FN event may cause chemotherapy dose reductions or delays in subsequent cycles. Expert commentary: More recent pharmacoeconomic models have reflected these clinical observations by modeling sequential chemotherapy regimens to account for FN risk on a per-cycle basis, and by accounting for chemotherapy dose reductions and consequent survival losses.

Cost-Effectiveness Analysis of Prophylaxis Treatment Strategies to Reduce the Incidence of Febrile Neutropenia in Patients with Early-Stage Breast Cancer or Non-Hodgkin Lymphoma.

OBJECTIVE: The objective of this study was to evaluate the cost effectiveness of no prophylaxis, primary prophylaxis (PP), or secondary prophylaxis (SP) with granulocyte colony-stimulating factors (G-CSFs), i.e., pegfilgrastim, lipegfilgrastim, filgrastim (6- and 11-day), or lenograstim (6- and 11-day), to reduce the incidence of febrile neutropenia (FN) in patients with stage II breast cancer receiving TC (docetaxel, cyclophosphamide) and in patients with non-Hodgkin lymphoma (NHL) receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) over a lifetime horizon from a Belgian payer perspective. METHODS: A Markov cycle tree tracked FN events during chemotherapy (3-week cycles) and long-term survival (1-year cycles). Model inputs, including the efficacy of each strategy, risk of reduced relative dose intensity (RDI), and the impact of RDI on mortality, utilities, and costs (in €; 2014 values) were estimated from public sources and the published literature. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per FN event avoided, life-year (LY) saved, and quality-adjusted LY (QALY) saved. LYs and QALYs saved were discounted at 1.5% annually. Deterministic and probabilistic sensitivity analyses (DSAs and PSAs) were conducted. RESULTS: Base-case ICERs for PP with pegfilgrastim relative to SP with pegfilgrastim were €15,500 per QALY and €14,800 per LY saved for stage II breast cancer and €7800 per QALY and €6900 per LY saved for NHL; other comparators were either more expensive and less effective than PP or SP with pegfilgrastim or had lower costs but higher ICERs (relative to SP with pegfilgrastim) than PP with pegfilgrastim. Results of the DSA for breast cancer and NHL comparing PP and SP with pegfilgrastim indicate that the model results were most sensitive to the cycle 1 risk of FN, the proportion of FN events requiring hospitalization, the relative risk of FN in cycles ≥2 versus cycle 1, no history of FN, and the mortality hazard ratio for RDI (<90% vs ≥90% [for NHL]). In the PSAs for stage II breast cancer and NHL, the probabilities that PP with pegfilgrastim was cost effective or dominant versus all other prophylaxis strategies at a €30,000/QALY willingness-to-pay threshold were 52% (other strategies ≤24%) and 58% (other strategies ≤24%), respectively. CONCLUSION: From a Belgian payer perspective, PP with pegfilgrastim appears cost effective compared to other prophylaxis strategies in patients with stage II breast cancer or NHL at a €30,000/QALY threshold.

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis in chemotherapy-induced febrile neutropenia among breast cancer and Non-Hodgkin's lymphoma patients under Taiwan's national health insurance system.

RATIONALE, AIM AND OBJECTIVE: The beneficial effects of granulocyte colony-stimulating factor (G-CSF) prophylaxis on reducing the risk of chemotherapy-induced febrile neutropenia (CIFN) were well documented throughout the literature. However, existing data regarding its cost-effectiveness were conflicting. We estimated the cost-effectiveness of G-CSF prophylaxis in CIFN under Taiwan's National Health Insurance (NHI) system. METHODS: Data on clinical outcomes and direct medical costs were derived for 5179 newly diagnosed breast cancer and 629 non-Hodgkin's lymphoma (NHL) patients from the NHI claims database. Patients were further categorized into three subgroups as "primary-", "secondary-" and "no -" prophylaxis based on their patterns of G-CSF use. Generalized estimating equations were applied to estimate the impact of G-CSF use on the incidence of CIFN. The incremental cost-effectiveness ratios of primary and secondary prophylactic G-CSF use were calculated and sensitivity analyses were performed. RESULTS: Primary prophylaxis of G-CSF decreased the incidence of CIFN by 27% and 83%, while secondary prophylaxis by 34% and 22% in breast cancer and NHL patients, respectively. Compared with those with no prophylaxis, the incremental cost per CIFN reduced in primary prophylaxis is $931 and $52 among patients with breast cancer and NHL, respectively. In contrast, secondary prophylaxis is dominated by no prophylaxis and primary prophylaxis in both cancer patients. CONCLUSION: Primary but not secondary prophylactic use of G-CSF was cost-effective in CIFN in breast cancer and NHL patients under Taiwan's NHI system.

Cost-effectiveness of febrile neutropenia prevention with primary versus secondary G-CSF prophylaxis for adjuvant chemotherapy in breast cancer: a systematic review.

The adoption of primary (PP) versus secondary prophylaxis (SP) of febrile neutropenia (FN), with granulocyte colony-stimulating factors (G-CSF), for adjuvant chemotherapy (AC) regimens in breast cancer (BC) could be affected by its "value for money". This systematic review examined (i) cost-effectiveness of PP versus SP, (ii) FN threshold at which PP is cost-effective including the guidelines 20 % threshold and (iii) potential impact of G-CSF efficacy assumptions on outcomes. The systematic review identified all cost-effectiveness/cost-utility analyses (CEA/CUA) involving PP versus SP G-CSF for AC in BC that met predefined inclusion/exclusion criteria. Five relevant CEA/CUA were identified. These CEA/CUA examined different AC regimens (TAC = 2; FEC-D = 1; TC = 2) and G-CSF formulations (filgrastim "F" = 4; pegfilgrastim "P" = 4) with varying baseline FN-risk (range 22-32 %), mortality (range 1.4-6.0 %) and utility (range 0.33-0.47). The potential G-CSF benefit, including FN risk reduction with P versus F, varied among models. Overall, relative to SP, PP was not associated with good value for money, as per commonly utilized CE thresholds, at the baseline FN rates examined, including the consensus 20 % FN threshold, in most of these studies. The value for money associated with PP versus SP was primarily dependent on G-CSF benefit assumptions including reduced FN mortality and improved BC survival. PP G-CSF for FN prevention in BC patients undergoing AC may not be a cost-effective strategy at the guidelines 20 % FN threshold.

Competition Between Biosimilars and Patented Biologics: Learning from European and Japanese Experience.

BACKGROUND: The expiry of patents for costly biologics is creating new momentum on the pharmaceutical market for biosimilars (copies of off-patent biologics) and paving the way for their development. However, little is known about the competitiveness of biosimilars versus their originators and other biologics belonging to the same therapeutic class. OBJECTIVE: The main goal of this study was to analyse the type of competition generated by the first biosimilars commercialised on key global biologic markets and to grasp their economic model. The secondary goal was to distinguish the main factors likely to influence the uptake of biosimilars on national markets. METHODS: To be included in this study, countries had to meet three conditions: the regulatory framework for the development of biosimilars closely resembled that in Europe, biosimilars were marketed in 2014, and the value of the biologics market was >US$3 billion. We analysed granulocyte colony-stimulating factors (GCSFs) and erythropoietins (EPOs) over the period 2007-2014 because these are the two main therapeutic classes that have been 'biosimilarised' and thus have many years of experience available. We assessed market sizes, retail/hospital distribution mixes, incentives for using biosimilars and price discounts for originators versus biosimilars. We conducted a linear regression analysis to assess the relationship between uptakes of biosimilars and the market shares of other biologics. RESULTS: The EU-5 (France, Germany, Italy, Spain and the UK) and Japanese GCSF and EPO markets are highly-country-specific. Uptake of biosimilars seems to depend on retail/hospital distribution mixes and on medical practice. Depending on the therapeutic class and the market sector (retail or hospital), biosimilars may compete with first-generation or second-generation products or both. Some incentives implemented to encourage the use of biosimilars had mixed results. Overall, discounts for biosimilars versus originators are not factors that determine global uptake of biosimilars. CONCLUSION: Unlike generics, there appears to be no unique economic model for biosimilars. Moreover, a new phenomenon occurs with biosimilars: sometimes, they are able to take market shares from subsequent generations of biologics.

Administration of G-CSF from day +6 post-allogeneic hematopoietic stem cell transplantation in children and adolescents accelerates neutrophil engraftment but does not appear to have an impact on cost savings.

G-CSF post-allogeneic HSCT accelerates neutrophil engraftment, but evidence that it impacts on cost-related outcomes is lacking. We performed a retrospective child and adolescent single-center cohort study examining G-CSF administration from Day +6 of allogeneic HSCT vs. ad hoc G-CSF use where clinically indicated. Forty consecutive children and adolescents undergoing allogeneic HSCT were included. End-points were as follows: time to engraftment; incidence of acute and chronic GvHD; number of patients alive at Day +100; 180-day TRM; post-transplant days in hospital; and cost of antimicrobials, TPN, and G-CSF usage. Neutrophil engraftment occurred earlier in the group that received G-CSF from Day +6. There was no difference between groups in any of the other end-points with the following exception: the cost of GCSF was significantly higher in the D + 6 G-CSF group. However, median G-CSF cost in this group amounted to only €280. There was a trend towards reduced cost of antimicrobials in the D + 6 G-CSF group, although this did not reach significance (p = 0.13). The median cost per patient of antimicrobial agents between groups differed by €1116. This study demonstrated the administration of G-CSF on Day +6 in pediatric HSCT to be safe. A further study using a larger cohort of patients is warranted to ascertain its true clinico-economic value.

Routine Primary Prophylaxis for Febrile Neutropenia with Biosimilar Granulocyte Colony-Stimulating Factor (Nivestim) or Pegfilgrastim Is Cost Effective in Non-Hodgkin Lymphoma Patients undergoing Curative-Intent R-CHOP Chemotherapy.

OBJECTIVE: This study aims to compare the cost-effectiveness of various strategies of myeloid growth factor prophylaxis for reducing the risk of febrile neutropenia (FN) in patients with non-Hodgkin lymphoma in Singapore who are undergoing R-CHOP chemotherapy with curative intent. METHODS: A Markov model was created to compare seven prophylaxis strategies: 1) primary prophylaxis (PP) with nivestim (biosimilar filgrastim) throughout all cycles of chemotherapy; 2) PP with nivestim during the first two cycles of chemotherapy; 3) secondary prophylaxis (SP) with nivestim; 4) PP with pegfilgrastim throughout all cycles of chemotherapy; 5) PP with pegfilgrastim during the first two cycles of chemotherapy; 6) SP with pegfilgrastim; and 7) no prophylaxis (NP). The perspective of a hospital was taken and cost-effectiveness was expressed as the cost per episode of FN avoided over six cycles of chemotherapy. A probabilistic sensitivity analysis was conducted. RESULTS: Strategies 3, 6, and 7 were dominated in the base case analysis by strategy 5. The costs associated with strategies 2, 5, 1, and 4 were US$3,813, US$4,056, US$4,545, and US$5,331, respectively. The incremental cost-effectiveness ratios for strategy 5 vs. strategy 2, strategy 1 vs. strategy 5, and strategy 4 vs. strategy 1 were US$13,532, US$22,565, and US$30,452, respectively, per episode of FN avoided. Strategy 2 has the highest probability to be cost-effective (ranged from 48% to 60%) when the willingness to pay (WTP) threshold is lower than US$10,000 per FN episode prevented. CONCLUSION: In Singapore, routine PP with granulocyte colony-stimulating factor (nivestim or pegfilgrastim) is cost-effective for reducing the risk of FN in patients receiving R-CHOP.

Granulocyte colony-stimulating factor in secondary prophylaxis for advanced-stage Hodgkin lymphoma treated with ABVD chemotherapy: a cost-effectiveness analysis.

Granulocyte colony-stimulating factor (G-CSF) is commonly administered to patients with Hodgkin lymphoma (HL) with neutropenia. We constructed a decision-analytic model to compare the cost-effectiveness of secondary prophylaxis with G-CSF to a strategy of 'no G-CSF' in response to severe neutropenia for adults with advanced-stage HL treated with ABVD. A Canadian public health payer's perspective was considered and costs were presented in 2013 Canadian dollars. The quality-adjusted life years (QALYs) attained with the G-CSF and 'no G-CSF' strategies were 1.403 and 1.416, respectively. Costs for the strategies with and without G-CSF were $38,971 and $33,982, respectively. In the base case analysis, the 'no G-CSF' strategy was associated with cost savings and improved QALYs; therefore, 'no G-CSF' was the dominant approach. For patients with severe neutropenia during ABVD chemotherapy for advanced-stage HL, a strategy without G-CSF support is associated with improved quality-adjusted outcomes, cost savings, and is the preferred approach.

Annual patient and caregiver burden of oncology clinic visits for granulocyte-colony stimulating factor therapy in the US.

OBJECTIVE: Prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs) is indicated for chemotherapy patients with a significant risk of febrile neutropenia. This study estimates the annual economic burden on patients and caregivers of clinic visits for prophylactic G-CSF injections in the US. METHODS: Annual clinic visits for prophylactic G-CSF injections (all cancers) were estimated from national cancer incidence, chemotherapy treatment and G-CSF utilization data, and G-CSF sales and pricing information. Patient travel times, plus time spent in the clinic, were estimated from patient survey responses collected during a large prospective cohort study (the Prospective Study of the Relationship between Chemotherapy Dose Intensity and Mortality in Early-Stage (I-III) Breast Cancer Patients). Economic models were created to estimate travel costs, patient co-pays and the economic value of time spent by patients and caregivers in G-CSF clinic visits. RESULTS: Estimated total clinic visits for prophylactic G-CSF injections in the US were 1.713 million for 2015. Mean (SD) travel time per visit was 62 (50) min; mean (SD) time in the clinic was 41 (68) min. Total annual time for travel to and from the clinic, plus time at the clinic, is estimated at 4.9 million hours, with patient and caregiver time valued at $91.8 million ($228 per patient). The estimated cumulative annual travel distance for G-CSF visits is 60.2 million miles, with a total transportation cost of $28.9 million ($72 per patient). Estimated patient co-pays were $61.1 million, ∼$36 per visit, $152 per patient. The total yearly economic impact on patients and caregivers is $182 million, ∼$450 per patient. LIMITATIONS: Data to support model parameters were limited. Study estimates are sensitive to the assumptions used. CONCLUSIONS: The burden of clinic visits for G-CSF therapy is a significant addition to the total economic burden borne by cancer patients and their families.

Upfront plerixafor plus G-CSF versus cyclophosphamide plus G-CSF for stem cell mobilization in multiple myeloma: efficacy and cost analysis study.

Cyclophosphamide plus G-CSF (C+G-CSF) is one of the most widely used stem cell (SC) mobilization regimens for patients with multiple myeloma (MM). Plerixafor plus G-CSF (P+G-CSF) has demonstrated superior SC mobilization efficacy when compared with G-CSF alone and has been shown to rescue patients who fail mobilization with G-CSF or C+G-CSF. Despite the proven efficacy of P+G-CSF in upfront SC mobilization, its use has been limited, mostly due to concerns of high price of the drug. However, a comprehensive comparison of the efficacy and cost effectiveness of SC mobilization using C+G-CSF versus P+G-CSF is not available. In this study, we compared 111 patients receiving C+G-CSF to 112 patients receiving P+G-CSF. The use of P+G-CSF was associated with a higher success rate of SC collection defined as ⩾5 × 10(6) CD34+ cells/kg (94 versus 83%, P=0.013) and less toxicities. Thirteen patients in the C+G-CSF arm were hospitalized owing to complications while none in the P+G-CSF group. C+G-CSF was associated with higher financial burden as assessed using institutional-specific costs and charges (P<0.001) as well as using Medicare reimbursement rates (P=0.27). Higher rate of hospitalization, increased need for salvage mobilization, and increased G-CSF use account for these differences.

Estimating the social value of G-CSF therapies in the United States.

OBJECTIVES: To provide a comprehensive estimate of the total social value (TSV) delivered by granulocyte-colony stimulating factor (G-CSF) therapies in the United States in 2014. STUDY DESIGN: Estimation of the TSV of G-CSF, based on a targeted literature review of pivotal studies. METHODS: A literature review was conducted to obtain estimates of the adverse outcomes associated with myelosuppressive chemotherapy-induced febrile neutropenia (FN) and the positive impacts of G-CSFs. We monetized each outcome into a set of mutually exclusive value components that were aggregated to estimate the TSV. To estimate the share of TSV captured by manufacturers, we estimated 2014 profits from G-CSF using measures of industry revenues and operating costs. RESULTS: In 2014, approximately 314,440 patients received G-CSFs. Compared with what they would have experienced without G-CSFs, these patients were less likely to be hospitalized or die from FN, incur reductions in chemotherapy relative dose intensity, receive antibiotics, miss work, or experience reduced health-related quality of life. We estimated the social value from fewer FN hospitalizations to be $770 million; from fewer FN-related deaths, $2.65 billion; from fewer deaths due to higher effective chemotherapy doses, $4.83 billion; from reductions in antibiotics, $2.3 million; from reductions in indirect costs, $230 million; and from improvements in health-related quality of life, $1.9 million. The estimated 2014 US TSV of G-CSFs was $8.5 billion. Industry profits associated with G-CSFs were estimated at $1.3 billion, accounting for approximately 15% of the TSV. CONCLUSIONS: Based on our calculations, the TSV generated by G-CSFs in the United States in 2014 was substantial, with the majority of this value accruing to patients.

Evaluating the use of plerixafor in stem cell mobilisation - an economic analysis of the PHANTASTIC trial.

Plerixafor is an effective haematopoietic stem cell mobilising agent in candidates for autologous transplantation, including patients with myeloma and lymphoma. Here we compare 98 plerixafor recipients in the PHANTASTIC trial with 151 historic controls mobilised by conventional chemotherapy (each with granulocyte colony-stimulating factor, G-CSF). Seventy (71.4%) plerixafor-mobilised patients achieved the composite primary endpoint of ≥4 × 10(6) CD34+ cells kg(-1) in ≤2 aphereses and no clinically significant neutropenia, compared to 48 (31.8%) historic controls (P < 0.001), and this significant advantage was maintained in scenario analyses testing components of this composite endpoint. A patient-level cost analysis was undertaken for 249 patients, which included the cost of remobilising patients where initial mobilisation had failed. Combined mean treatment cost for plerixafor mobilised patients was £12,679 compared with £11,694 for historical controls. However, plerixafor produces an average saving of £3,828 per lymphoma patient but average cost increase by £5,245 per myeloma patient. The present data demonstrate cost-effectiveness for plerixafor as a first line mobilisation agent, certainly for lymphoma patients, where substantial resource savings and achievement of the primary endpoint are likely. J. Clin. Apheresis 31:434-442, 2016. © 2015 Wiley Periodicals, Inc.