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The American Journal of Managed Care October 2016
Cost-Effectiveness of a Statewide Falls Prevention Program in Pennsylvania: Healthy Steps for Older Adults
Steven M. Albert, PhD; Jonathan Raviotta, MPH; Chyongchiou J. Lin, PhD; Offer Edelstein, PhD; and Kenneth J. Smith, MD
Economic Value of Pharmacist-Led Medication Reconciliation for Reducing Medication Errors After Hospital Discharge
Mehdi Najafzadeh, PhD; Jeffrey L. Schnipper, MD, MPH; William H. Shrank, MD, MSHS; Steven Kymes, PhD; Troyen A. Brennan, MD, JD, MPH; and Niteesh K. Choudhry, MD, PhD
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Janel Hanmer, MD, PhD; Rachel Hess, MD, MS; Sarah Sullivan, BS; Lan Yu, PhD; Winifred Teuteberg, MD; Jeffrey Teuteberg, MD; and Dio Kavalieratos, PhD
Patients' Success in Negotiating Out-of-Network Bills
Kelly A. Kyanko, MD, MHS, and Susan H. Busch, PhD
Connected Care: Improving Outcomes for Adults With Serious Mental Illness
James M. Schuster, MD, MBA; Suzanne M. Kinsky, MPH, PhD; Jung Y. Kim, MPH; Jane N. Kogan, PhD; Allison Hamblin, MSPH; Cara Nikolajski, MPH; and John Lovelace, MS
A Call for a Statewide Medication Reconciliation Program
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Estimating the Social Value of G-CSF Therapies in the United States
Jacqueline Vanderpuye-Orgle, PhD; Alison Sexton Ward, PhD; Caroline Huber, MPH; Chelsey Kamson, BS; and Anupam B. Jena, MD, PhD
Does Medicare Managed Care Reduce Racial/Ethnic Disparities in Diabetes Preventive Care and Healthcare Expenditures?
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Estimating the Social Value of G-CSF Therapies in the United States

Jacqueline Vanderpuye-Orgle, PhD; Alison Sexton Ward, PhD; Caroline Huber, MPH; Chelsey Kamson, BS; and Anupam B. Jena, MD, PhD
Granulocyte-colony stimulating factors (G-CSFs) reduce the risk of febrile neutropenia in patients with cancer. This study evaluates the clinical and nonclinical value associated with G-CSFs.
To value survival gains associated with avoided chemotherapy dose reductions, we used estimates from Havrilesky et al (2014) who found that an RDI greater than 85% was associated with increased survival for patients with breast and lung cancers.40 Using population weights from Naeim et al (2013), we calculated an average survival gain (SDR) of 17.5 months per G-CSF patient, attributable to chemotherapy dose reductions avoided.32 We then used an estimate of the average cost of CRs ($24,392) calculated from data provided in Naeim et al to account for higher treatment costs associated with this increased dosing (assuming a 15% increase).32 Clinical experts suggested these increased costs should only apply to the roughly 50% of patients receiving chemotherapy from multi-use vials. Applying the value of a cancer-adjusted life-year at $72,000, we used the following equation to estimate the value of lowering the incidence of chemotherapy dose reductions (dose-related mortality [DRM value]) to be $4.8 billion, annually:

DRM Value = [{([IDR – (IDR  × ORDR)] × GCSF Population) × SDR} × VLY] – [(CR × 0.15 ) × ([IDR – (IDR × ORDR)] × GCSF Population)] = $4,827,749,599

DRM Value = {([0.4 – (0.4 × 0.63)] × 314,442) × 1.46} × 100,000 – [($24,392 × 0.15) × [0.4 – (0.4 ×  0.63)] × 314,442] = $4,827,749,599

Antibiotic Use

Myelosuppressive chemotherapy is associated with antibiotic use (AU) to fight infection. According to a randomized controlled trial published by Vogel et al (2005) and a claims analysis by Almenar et al (2009), 10% of patients with breast cancer receive antibiotics.41,42 Our literature review did not provide estimates of the incidence of AU (IAU) for other cancer types; therefore, to derive a proxy estimate, we assumed that other patients with nonmyeloid malignancies receive antibiotics at a similar rate. The estimate would be that 31,444 patients received antibiotics in our 2014 population.

G-CSFs have been estimated to reduce the use of antibiotics substantially. We identified 3 studies that reported relative RRs for AU (RRAU) from randomized controlled trials of 0.64 for patients with small cell lung cancer,39 and 0.80 for patients with breast cancer receiving G-CSFs.41,42 Assuming all tumor types respond similarly, the average of these 2 estimates (0.72) suggests that G-CSFs prevented antibiotic use in roughly 8837 patients in 2014, an incidence rate of 7%. Using the equation below and the cost of AU (CostAU) reported in Elder-Lissai (2008), we estimated G-CSFs generated $2.3 million in value due to fewer patients receiving antibiotics23:

AU Value = [{IAU – (IAU × RRAU)} * GCSF Population] × CostAU = $2,297,596

AU Value = [{0.1 – (0.1 × 0.72)} × 314,442] × $260 = $2,297,596


Total Clinical SV

Table 2 reports the estimated total clinical SV of G-CSFs in 2014. The annual value for each component ranged from $2.3 million for AU to $4.8 billion for reduction in mortality related to chemotherapy dose reductions avoided, summing to a total value of $11 billion.

Nonclinical SV

Indirect costs. Our literature review identified 1 article that analyzed the ICs associated with neutropenia events. Calhoun et al (2001) define total ICs (TICs) as the sum of patient work loss, caregiver work loss, and payments for caregivers.27 Using a sample of patients with ovarian cancer, they estimated the cost of each component was, on average, $4038, $1185, and $1170 per patient per event, respectively, for a TIC of $6393 per patient. We multiplied this by the reduction in FN events due to G-CSFs using the following equation to estimate a total value of $230 million:

IC Value = [{IFN – (IFN × RRFN)} × GCSF Population] × TIC = $230,087,690

IC Value = [{0.22 – (0.22 × 0.48)} × 314,442] × 6393 = $230,087,690

Quality of life. Few studies have measured how FN and G-CSF usage affect patients’ health-related quality of life (HRQoL). Our review identified 1 study that used the difference in Short Form Health Survey 36 (SF-36) scores for a group of patients with neutropenia in the last 7 days and a control group. Fortner et al (2005) found the only significant difference in responses between the groups was for bodily pain.28

To associate this difference in SF-36 scores with a dollar value, we used a published algorithm to calculate the equivalent QALY reduction.43 Using a QALY value of $100,000,25,26 we estimated that neutropenia and FN are associated with an $85 reduction in HRQoL per FN event (HRQoLFN). Multiplying this amount by the reduction in FN events due to G-CSFs, we used the following equation to estimate a total annual value of $1.9 million:

HRQoL Value = [{IFN – (IFN × RRFN)} × GCSF Population] × HRQoLFN = $1,930,031

HRQoL Value = [{0.22 – (0.22 × 0.48)} × 314,442] × $85 = $1,930,031

Nonclinical SV

Although literature on the nonclinical value of G-CSFs was limited, we used all available data to create what can be viewed as a conservative estimate of the nonclinical SV from G-CSF use.27,28 Table 2 shows that the indirect costs avoided account for 99% of our estimates, with an annual savings of $232 million.

Total Social Value

Table 2 presents the estimated TSV of G-CSFs used prophylactically as indicated in 2014. The vast majority of the SV stems from the clinical, rather than nonclinical, benefits of G-CSFs.


Value to Society Versus to Manufacturers

An important question in the debate about G-CSFs, and expensive medical technologies more broadly, is how the value created by these therapies is divided between pharmaceutical manufacturers and patients. For manufacturers, value is represented as profits, and for patients, it is “consumer surplus”—an economic concept that reflects the difference between what individuals are willing to pay for a therapy and what they actually pay. To evaluate this question, we estimated the 2014 profits accruing to G-CSF manufacturers in the United States.

The US G-CSF market is dominated by 2 Amgen products: filgrastim, which maintains around 83% market share despite patent expiration in the United States in 2013; and pegfilgrastim, with patent expiration in October 2015.44 Thus, we based our cost and revenue estimates on Amgen’s 2014 annual report scaled to represent the entire market.45,46 Revenues were reported for their G-CSFs; however, the only cost data available were for all products and included all operating costs. We therefore applied the all-product profit margin to filgrastim and pegfilgrastim revenues to estimate 2014 G-CSF profits of $1.306 billion (see Table 3). Compared with our estimate of $8.5 billion in TSV created by G-CSFs, manufacturer profits account for approximately 15% (Figure 1). This low rate of producer surplus is not surprising when considering the monopolistic form of competition that happens across branded drugs and therapies.

Sensitivity Analysis

When possible, the parameters used in the baseline analysis were based on an average (weighted when appropriate) of estimates from multiple studies. However, 2 stronger assumptions were required to translate the mortality benefits associated with G-CSFs into monetary values. For each FN-related death that G-CSFs prevented, we developed an average number of life-years gained using estimates of life expectancy at diagnosis reported in Liu et al (2013).37

On average, the number of life-years gained in the baseline model assumed FN is a random event among patients with cancer receiving myelosuppressive chemotherapy; however, in practice, older and weaker patients may be more susceptible. These patients likely have below-average life expectancies, which bias our baseline estimate toward longer survival. To test the sensitivity of our results, we recalculated the TSV of G-CSFs assuming the average life-years gained was 50% lower (4.4 instead of 8.8 years). This reduction decreased the TSV estimate by $1.8 billion (Figure 2).

Additionally, the 2 largest drivers of SV in our model are the reduction in FN-related mortality (33%) and the value of avoiding chemotherapy RDI reductions (60%). We performed additional sensitivity analyses using confidence intervals (CIs) presented in the literature for these parameters. For example, Kuderer et al (2007) provided a CI of 0.33 to 0.90 for their estimate of the RR of FN-related mortality with G-CSFs (0.55). The lower end of this interval would add $603 million to the TSV estimate, and the upper end of the interval would reduce the TSV by $945 million. Similarly, Kuderer et al (2007) also provide a CI of 0.30 to 0.65 for their estimate of the incidence of dose reductions (0.4). Our sensitivity analysis suggests that the lower end of the CI would reduce the TSV by almost $1.68 billion, but the upper end of the CI would increase the TSV by almost $4.8 billion.


This study had a number of limitations. First, TSV estimates were limited by the lack of available research, particularly on nonclinical burdens imposed by FN. For example, by reducing the likelihood of chemotherapy dose reductions, G-CSFs may provide patients with less anxiety about complications.

Second, previous research on the value of G-CSFs has been constrained by the limited scope of the study population considered. When possible, we based our SV estimates on results from studies with large sample populations that covered all, or most, of the malignancies for which G-CSFs are typically indicated; however, there were limited data for several SV components. For these value components, our estimates were based on more select samples, and we assumed the outcomes would, on average, be similar across other tumor types. Additionally, prior studies focus almost exclusively on patients for whom G-CSFs are indicated (as previously described), making it impossible to generate estimates of SV for patients for whom G-CSFs are not indicated and for whom TSV would be expected to be lower.

Third, our modeling exercise relied on parameter estimates drawn from the literature. Our findings, therefore, reflect uncertainty stemming from the various study designs on which parameter estimates that populate our model were drawn.


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