Associations between commonly used patient-reported outcome tools in postpartum depression clinical practice and the Hamilton Rating Scale for Depression.

The objective of this study is to explore the associations between the patient-reported Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire (PHQ)-9 and clinician-reported 17-item Hamilton Depression Rating Scale (HAMD-17) in order to facilitate clinical decision-making. An integrated efficacy dataset of three randomized placebo-controlled trials (NCT02614547, NCT02942004, and NCT02942017) evaluating brexanolone injection, a neuroactive steroid chemically identical to allopregnanolone, in women with postpartum depression was used for this post hoc analysis. Data were pooled across treatment arms. Associations were assessed at day 30 (end-of-trial follow-up). Pearson correlation assessed the relationship between EPDS and PHQ-9 item and total scores and HAMD-17 total score. Cohen's kappa assessed agreement of EPDS remission (score < 10) and PHQ-9 remission (score < 5) with HAMD-17 remission (score ≤ 7). Ordinary least squares (OLS) regression models were used to develop equations estimating HAMD-17 total scores from EPDS and PHQ-9 scores, respectively. The total scores showed large correlations (HAMD-17/EPDS: r = 0.71, p < 0.001; HAMD-17/PHQ-9: r = 0.75, p < 0.001). Individual EPDS and PHQ-9 items significantly correlated (r= 0.35 to 0.67, all p < 0.001) with HAMD-17 total score. EPDS had 79% sensitivity and 67% specificity to detect HAMD-17 remission; corresponding estimates for PHQ-9 were 76% and 78%. OLS models yielded the following equations: HAMD-17 total = 2.66 + (EPDS total × 0.87) and HAMD-17 total = 3.99 + (PHQ-9 total × 0.97). There were large and statistically significant associations between patient-reported outcomes (EPDS, PHQ-9) and clinician-reported outcomes (HAMD-17) as clinical improvements were associated with patient-reported symptom improvement. These results provide tools to help translate clinical trial data to clinical practice, thus aiding shared decision-making for this critical population.

Cost-Effectiveness of Brexanolone Versus Selective Serotonin Reuptake Inhibitors for the Treatment of Postpartum Depression in the United States.

BACKGROUND: Brexanolone injection (BRX) was approved by the FDA in 2019 for the treatment of adult patients with postpartum depression (PPD), but its cost-effectiveness has not yet been evaluated. OBJECTIVE: To estimate the cost-effectiveness of BRX compared with treatment with selective serotonin reuptake inhibitors (SSRIs) for PPD. METHODS: We projected costs (2018 U.S. dollars) and health (quality-adjusted life-years [QALYs]) for mothers treated with BRX or SSRIs and their children. A health state transition model projected clinical and economic outcomes for mothers based on the Edinburgh Postnatal Depression Scale, from a U.S. payer perspective. The modeled population consisted of adult patients with moderate to severe PPD, similar to BRX clinical trial patients. Short-term efficacy for BRX and SSRIs came from an indirect treatment comparison. Long-term efficacy outcomes over 4 weeks, 11 years (base case), and 18 years were based on results from an 18-year longitudinal study. Maternal health utility values came from analysis of trial-based short-form 6D responses. Other inputs were derived from the literature. RESULTS: The incremental cost-effectiveness ratio for BRX versus SSRIs was $106,662 per QALY gained over an 11-year time horizon. Drug and administration costs for BRX averaged $38,501, compared with $25 for SSRIs over the studied time horizon. Maternal total direct medical costs averaged $65,908 in the BRX arm, compared with $73,653 in the SSRI arm. BRX-treated women averaged 6.230 QALYs compared with 5.979 QALYs for the SSRI arm. Adding partner costs and utilities in a sensitivity analysis further favored BRX. Results were sensitive to the severity of PPD at baseline and the model time horizon. Probabilistic sensitivity analyses indicated that BRX was cost-effective at the $150,000-per-QALY threshold with 58% probability. CONCLUSIONS: Analysis using a state transition model showed BRX to be a cost-effective therapy compared with SSRIs for treating women with PPD. DISCLOSURES: This study was funded by Sage Therapeutics, Cambridge, MA. Eldar-Lissai, Gerbasi, and Hodgkins are employees of Sage Therapeutics and own stock or stock options in the company. Gerbasi also reports previous employment with Policy Analysis Inc. Cohen contributed to this work as an independent consultant. Meltzer-Brody has a sponsored clinical research agreement with Sage Therapeutics to the University of North Carolina, as well as a sponsored research agreement from Janssen to the University of North Carolina, unrelated to this work. Meltzer-Brody has also received personal consulting fees from Cala Health and MedScape, unrelated to this work. Johnson, Chertavian, and Bond are employees of Medicus Economics, which was paid fees by Sage to conduct the research for this study. Study findings do not necessarily represent the views of CEVR or Tufts Medical Center.

When is cancer care cost-effective? A systematic overview of cost-utility analyses in oncology.

New cancer treatments pose a substantial financial burden on health-care systems, insurers, patients, and society. Cost-utility analyses (CUAs) of cancer-related interventions have received increased attention in the medical literature and are being used to inform reimbursement decisions in many health-care systems. We identified and reviewed 242 cancer-related CUAs published through 2007 and included in the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org). Leading cancer types studied were breast (36% of studies), colorectal (12%), and hematologic cancers (10%). Studies have examined interventions for tertiary prevention (73% of studies), secondary prevention (19%), and primary prevention (8%). We present league tables by disease categories that consist of a description of the intervention, its comparator, the target population, and the incremental cost-effectiveness ratio. The median reported incremental cost-effectiveness ratios (in 2008 US $) were $27,000 for breast cancer, $22,000 for colorectal cancer, $34,500 for prostate cancer, $32,000 for lung cancer, and $48,000 for hematologic cancers. The results highlight the many opportunities for efficient investment in cancer care across different cancer types and interventions and the many investments that are inefficient. Because we found only modest improvement in the quality of studies, we suggest that journals provide specific guidance for reporting CUA and assure that authors adhere to guidelines for conducting and reporting economic evaluations.

Economic analysis of prophylactic pegfilgrastim in adult cancer patients receiving chemotherapy.

OBJECTIVES: Neutropenia and its complications, including febrile neutropenia (FN), are a common side effect of cancer chemotherapy. Results of clinical trials showed that prophylactic use of granulocyte colony-stimulating factors (G-CSF) is effective in preventing FN. In this study, the cost effectiveness (measured as cost per quality-adjusted time [days]) of three treatment alternatives were evaluated: no G-CSF, filgrastim administered daily for 7-12 days after chemotherapy, and a pegylated form of G-CSF pegfilgrastim, administered once per cycle. METHODS: A cost-utility model based on standard clinical practice of treating FN with immediate hospitalization or with ambulatory treatment, from a societal perspective was developed. Direct medical cost estimates for hospitalization were derived from claims data reported by 115 US academic medical centers. Indirect medical costs, productivity costs, probabilities, and utilities are based on published literature. Results were subjected to sensitivity analyses and 95% confidence intervals are based on a Monte Carlo simulation. RESULTS: Mean estimated costs/day of hospitalization were $1984 (SD $1040, N = 24,687) for surviving patients and $3139 (SD $2014, N = 1437) for dying patients. Under baseline conditions, pegfilgrastim dominated both filgrastim and no G-CSF, with expected costs and effectiveness of $4203 and 12.361 quality adjusted life-days (QALDs) for no G-CSF, $3058 and 12.967 QALDs for pegfilgrastim, and $5264 and 12.698 QALDs for filgrastim. CONCLUSIONS: This cost-utility analysis provides strong evidence that pegfilgrastim is not only cost-effective but also cost-saving in most common clinical and economic settings. There appear to be both clinical and economic benefits from prophylactic administration of pegfilgrastim.

Therapeutic use of granulocyte colony-stimulating factors for established febrile neutropenia: effect on costs from a hospital perspective.

BACKGROUND: The prophylactic use of granulocyte colony-stimulating factors (G-CSFs) reduces the severity and duration of neutropenia and reduces the incidence of febrile neutropenia after cancer chemotherapy. However, the use of G-CSFs, particularly filgrastim, to treat established neutropenia remains controversial. A recent meta-analysis of randomised controlled trials (RCTs) evaluating G-CSF treatment for established febrile neutropenia demonstrated a reduction in prolonged hospitalisations. Because more than one-third of patients in the analysis were hospitalised for at least 10 days, this finding has broad pharmacoeconomic and clinical significance. This analysis presents the potential cost implications of G-CSF treatment for established neutropenia among hospitalised patients. METHODS: Direct medical costs ($US, year 2003 values) related to hospitalisation for established neutropenia were modelled using a hospital perspective and according to two treatment options: (i) no use of G-CSF during the neutropenic episode (control); and (ii) addition of daily G-CSF until neutrophil recovery. Within each option, we modelled the probability of a long stay (>or=10 days) and patient survival. The model used three data sets: discharge data from a consortium of academic medical institutions, drug cost data (filgrastim) from Federal payers, and estimates of G-CSF efficacy derived from a meta-analysis of RCTs of treatment in patients with established febrile neutropenia. The lowest expected total cost was predicted for both treatment options; sensitivity analyses and Monte Carlo simulations were used to evaluate the robustness of the model. RESULTS: The G-CSF arm produced the lowest expected cost, and predicted net estimated savings of $US1046 per neutropenic episode compared with the control strategy. G-CSF was less expensive than the control for most reasonable estimates of cost per day and all lengths of stay (LOS) >or=10 days. G-CSF was the least costly strategy for 73.5% of 10,000 Monte Carlo iterations, while the no-G-CSF control strategy predicted savings in 26.5% of iterations. CONCLUSIONS: This pharmacoeconomic model suggests that therapeutic use of G-CSF should be considered for patients with established neutropenia in order to reduce overall hospital cost. G-CSF treatment may offer substantial potential savings for hospitalised patients with established neutropenia over a wide range of model assumptions. Therapeutic G-CSF use among patients hospitalised for established neutropenia may complement the recommended prophylactic use of these agents for the prevention of neutropenic episodes.