Budget impact analysis of niraparib for first-line maintenance therapy in advanced ovarian cancer from a US payer perspective.

BACKGROUND: Ovarian cancer (OC) is the fifth leading cause of cancer death in women and has the highest mortality rate of gynecological cancers. Niraparib was recently approved by the FDA for the maintenance treatment of adult patients with advanced epithelial OC in complete or partial response to first-line platinum-based chemotherapy (PBC) regardless of biomarker status. OBJECTIVE: To estimate the direct economic impact on US payers of adding niraparib as a first-line maintenance therapy for patients with advanced OC. METHODS: The model considered 2 scenarios: a current scenario in which niraparib does not have regulatory approval for first-line maintenance therapy and a future scenario in which niraparib has regulatory approval for first-line maintenance therapy. The budget impact was calculated as the difference in cost between the 2 scenarios. The budget impact model (BIM) considered 2 different US health care payer perspectives: a commercial health plan and a Medicare plan. Both payer perspectives were assumed to have a hypothetical 1 million affiliates that were covered. Epidemiological data was used to estimate the eligible incident population of patients with OC. Active surveillance, bevacizumab (as a monotherapy), and olaparib (as a monotherapy restricted to patients with the breast cancer gene [BRCA] mutation) were included in the model as alternative maintenance treatment options (maintenance treatment options required 1% market share for inclusion). Cost categories considered in the BIM included diagnostic testing, treatment acquisition and administration, treatment-emergent adverse events, and subsequent therapy. Results were presented as an incremental budget impact to payers over 3 years. RESULTS: For a commercial health plan of 1 million affiliates, the estimated impact of adding niraparib as a first-line maintenance treatment option for advanced epithelial OC was calculated as $87,906, $93,106, and $87,037 for years 1, 2, and 3, respectively. The average budget impact per member per month was $0.007. For a Medicare health plan of 1 million affiliates, the estimated impact was calculated as $206,785, $219,017, and $204,739 for years 1, 2, and 3, respectively. The average budget impact per member per month was $0.018. One-way sensitivity analyses suggested that budget impact was most sensitive to the treatment duration and market share of niraparib, the non-treatment-specific data on overall survival rates, and the treatment duration of bevacizumab. Treatment of drug-specific adverse events had little impact on the budget model. CONCLUSIONS: The model estimated a minimal budget impact to both a commercial or Medicare health plan following the introduction of niraparib as a first-line maintenance therapy for patients with advanced epithelial OC who are in complete or partial response to first-line PBC regardless of biomarker status. DISCLOSURES: This study was financially supported by GlaxoSmithKline. Liu, Hawkes, Maiese, and Hurteau are employees of GlaxoSmithKline. Travers was employed by GlaxoSmithKline at the time of this study. Spalding and Walder are employees of FIECON Ltd., which was contracted by GlaxoSmithKline to develop the budget impact model used in this study.

Real-world adverse events with niraparib 200 mg/day maintenance therapy in ovarian cancer: a retrospective study.

Aim: To assess real-world occurrence of common clinical trial-reported adverse events (AE) among patients with recurrent ovarian cancer initiating niraparib 200 mg/day. Materials & methods: This retrospective observational study used physician-extracted anonymized medical record data of eligible patients initiating niraparib 200 mg/day after platinum-based chemotherapy. Results: Of 153 patients, 57 (37%) experienced ≥1 of the three most common all-grade AEs within 3 months after niraparib initiation: nausea (16%; grade 3/4: 2%), thrombocytopenia (14%; grade 3/4: 3%) and fatigue (24%; grade 3/4: 3%). In the ENGOT-OV16/NOVA trial, these respective AEs occurred in 74, 61 and 59% of patients. Conclusion: Incidence of common clinical trial-reported AEs was lower among patients initiating niraparib 200 mg/day in real-world practice versus patients initiating niraparib 300 mg/day in ENGOT-OV16/NOVA.

Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial.

PURPOSE: This study estimated time without symptoms or toxicity (TWiST) with niraparib compared with routine surveillance (RS) in the maintenance treatment of patients with recurrent ovarian cancer. PATIENTS AND METHODS: Mean progression-free survival (PFS) was estimated for niraparib and RS by fitting parametric survival distributions to Kaplan-Meier data for 553 patients with recurrent ovarian cancer who were enrolled in the phase III ENGOT-OV16/NOVA trial. Patients were categorized according to the presence or absence of a germline BRCA mutation-gBRCAmut and non-gBRCAmut cohorts. Mean time with toxicity was estimated based on the area under the Kaplan-Meier curve for symptomatic grade 2 or greater fatigue, nausea, and vomiting adverse events (AEs). Time with toxicity was the number of days a patient experienced an AE post-random assignment and before disease progression. TWiST was estimated as the difference between mean PFS and time with toxicity. Uncertainty was explored using alternative PFS estimates and considering all symptomatic grade 2 or greater AEs. RESULTS: In the gBRCAmut and non-gBRCAmut cohorts, niraparib treatment resulted in a mean PFS benefit of 3.23 years and 1.44 years, respectively, and a mean time with toxicity of 0.28 years and 0.10 years, respectively, compared with RS. Hence, niraparib treatment resulted in a mean TWiST benefit of 2.95 years and 1.34 years, respectively, compared with RS, which is equivalent to more than four-fold and two-fold increases in mean TWiST between niraparib and RS in the gBRCAmut and non-gBRCAmut cohorts, respectively. This TWiST benefit was consistent across all sensitivity analyses, including modeling PFS over 5-, 10-, and 15-year time horizons. CONCLUSION: Patients who were treated with niraparib compared with RS experienced increased mean TWiST. Thus, patients who were treated with niraparib in the ENGOT-OV16/NOVA trial experienced more time without symptoms or symptomatic toxicities compared with control.

Budget impact of niraparib as maintenance treatment in recurrent ovarian cancer following platinum-based chemotherapy.

Aim: To estimate financial implications of adopting niraparib as maintenance treatment in recurrent ovarian cancer. Materials & methods: A model was developed to estimate the budget impact of treating patients with niraparib compared with alternative maintenance treatment options (olaparib, rucaparib, bevacizumab or 'watch and wait') over 3 years. Results: For a hypothetical plan with 1 million lives representative of US/Medicare-only populations, projected cost savings with niraparib were US$78,721/$293,723, $276,671/$1,009,729 and $353,585/$1,289,712 at years 1, 2 and 3, respectively. Sensitivity analyses showed prices of niraparib, rucaparib and olaparib to have the most significant impact on the budget. Conclusion: Factoring in all treatment-related costs, the use of niraparib could result in significant cost savings compared with other maintenance treatment options.

A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation.

In newly diagnosed multiple myeloma (MM), patients ineligible for front-line autologous stem cell transplantation (ASCT), melphalan and prednisone (MP) with thalidomide (MPT) or bortezomib (VMP) are standard first-line therapeutic options. Despite new treatment regimens incorporating bortezomib or lenalidomide, MM remains incurable. The FIRST study demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS) for the combination of lenalidomide and low-dose dexamethasone (Rd) until progression vs. MPT in transplant-ineligible ndMM patients. However, to date no head-to-head randomized controlled trials (RCTs) have compared Rd or MPT versus VMP. We conducted a network meta-analysis using RCTs identified through a systematic literature review to evaluate the relative efficacy of Rd versus other regimens on survival endpoints in previously untreated MM patients ineligible for ASCT. In this analysis, Rd was associated with a significant PFS and survival advantage versus other first-line treatments (VMP, MPT, MP), challenging the role of alkylators in this setting.

Characteristics and temporal trends in patient registries: focus on the life sciences industry, 1981-2012.

PURPOSE: Patient registries are used to monitor safety, examine real-world effectiveness, and may potentially contribute to comparative effectiveness research. To our knowledge, life sciences industry (LSI)-sponsored registries have not been systematically categorized. This study represents a first step toward understanding such registries over time. METHODS: Studies described as registries were identified in the ClinicalTrials.gov database. Characteristics from these registry records were abstracted and analyzed. RESULTS: Of 1202 registries identified, approximately 47% reported LSI sponsorship. These 562 LSI registries varied in focus: medical devices (n = 193, 34%), specific drugs (n = 173, 31%), procedures (n = 29, 5%), or particular diseases (n = 139, 25%). Thirty-three registries (<6%) evaluated pregnancy outcomes. The most common therapeutic area was cardiovascular (n = 234, 42%); others included endocrinology, immunology, oncology, musculoskeletal disorders, and neurology. The two most often measured outcomes were clinical effectiveness and safety, each of which appeared in 363/562 (65%) of LSI registries. Other outcomes included real-world clinical practice patterns (n = 122, 22%), patient-reported outcomes (n = 106, 19%), disease epidemiology/natural history (n = 69, 12%), and economic outcomes (n = 30, 5%). The number of LSI registries and their geographic diversity has increased over time. CONCLUSIONS: The LSI registries represent a substantial proportion of all patient registries documented in ClinicalTrials.gov. These prospective studies are growing in number and encompass diverse therapeutic areas and geographic regions. Most registries measure multiple outcomes and capture real-world data that may be unavailable through other study designs. This classification of LSI registries documents their use for studying heterogeneity of diseases, examining treatment patterns, measuring patient-reported outcomes, examining economic outcomes, and performing comparative effectiveness research.

The humanistic burden of head and neck cancer: a systematic literature review.

BACKGROUND: Head and neck cancer (HNC) and its treatment can affect communication, nutrition, and physical appearance, and the global impact of this disease on patients' quality of life may be substantial. OBJECTIVE: The aim of this systematic literature review was to describe the impact of HNC and its treatment on the physical, emotional, and social well-being of patients over time, by examining longitudinal studies of patient-reported outcomes (PRO) evaluating these domains. METHODS: Databases (MEDLINE and Embase) were searched to identify studies published in English between January 2004 and January 2014 analyzing the humanistic aspects of HNC in adult patients. Additional relevant publications were identified through manual searches of abstracts from recent conference proceedings. RESULTS: Of 1,566 studies initially identified, 130 met the inclusion criteria and were evaluated in the assessment. Investigations using a variety of PRO instruments in heterogeneous patient populations consistently reported that PRO scores decrease significantly from diagnosis through the treatment period, but generally recover to baseline in the first year post-treatment. This trend was observed for many functional domains, although some side effects, such as xerostomia, persisted well beyond 1 year. In addition, considerable evidence exists that baseline PRO scores can predict clinical endpoints such as overall and progression-free survival. CONCLUSIONS: Many aspects of HNC, both disease and treatment specific, profoundly affect patients' quality of life. Improved knowledge of these effects on PRO may allow for more informed treatment decisions and can help physicians to better prepare patients for changes they may experience during therapy. Furthermore, the predictive value of baseline PRO data may enable healthcare providers to identify at-risk patients in need of more intensive intervention.

Major depressive disorder in Africa and the Middle East: a systematic literature review.

With major depressive disorder (MDD) associated with significant clinical, economic and health-related quality of life impact, we sought to systematically review and synthesize information relevant to the burden of MDD in Africa and the Middle East, from which published evidence is slim. Our literature search identified 54 publications assessing epidemiological (43), humanistic (5), clinical/treatment (7) or economic outcomes (2). General population MDD prevalence and that among chronic disease populations were similar in Africa and the Middle East. No MDD-related economic literature specific to Africa or the Middle East was identified. Five studies of humanistic outcomes were identified; four African studies documented significant reduction of health-related quality of life related to MDD. The frequency of certain risk factors for MDD, such as disease, trauma and associated stress, as well as patterns of MDD treatment, suggest the potential for a higher burden of disease in Africa and the Middle East than in western countries.

Burden and management of chronic kidney disease in Japan: systematic review of the literature.

BACKGROUND: Chronic kidney disease (CKD) is a common disorder with increasing prevalence worldwide. This systematic literature review aims to provide insights specific to Japan regarding the burden and treatment of CKD. METHODS: We reviewed English and Japanese language publications from the last 10 years, reporting economic, clinical, humanistic, and epidemiologic outcomes, as well as treatment patterns and guidelines on CKD in Japan. RESULTS: This review identified 85 relevant articles. The prevalence of CKD was found to have increased in Japan, attributable to multiple factors, including better survival on dialysis therapy and a growing elderly population. Risk factors for disease progression differed depending on CKD stage, with proteinuria, smoking, hypertension, and low levels of high-density lipoprotein commonly associated with progression in patients with stage 1 and 2 disease. Serum albumin levels and hemoglobin were the most sensitive variables to progression in patients with stage 3 and 5 disease, respectively. Economic data were limited. Increased costs were associated with disease progression, and with peritoneal dialysis as compared with either hemodialysis or combination therapy (hemodialysis + peritoneal dialysis) treatment options. Pharmacological treatments were found potentially to improve quality of life and result in cost savings. We found no reports of treatment patterns in patients with early-stage CKD; however, calcium channel blockers were the most commonly prescribed antihypertensive agents in hemodialysis patients. Treatment guidelines focused on anemia management related to dialysis and recommendations for peritoneal dialysis treatment and preventative measures. Few studies focused on humanistic burden in Japanese patients; Japanese patients reported greater disease burden but better physical functioning compared with US and European patients. CONCLUSION: A dearth of evidence regarding the earlier stages of kidney disease presents an incomplete picture of CKD disease burden in Japan. Further research is needed to gain additional insight into CKD in Japan.

Humanistic and economic burden of generalized anxiety disorder in North America and Europe.

BACKGROUND: To review the humanistic and economic burden of generalized anxiety disorder (GAD). METHODS: MEDLINE, EMBASE and the Cochrane Library, limited to articles published in English, between 1987 and 2010, in North America, Europe and Australia. The key focus was humanistic or functional outcomes, cost of illness and economic outcomes. Ninety articles fitting criteria on (a) GAD study population, (b) United States, Europe or Australia, and (c) humanistic burden or economic burden were reviewed. Methods and findings were summarized by two researchers; inconsistencies were resolved by a third reviewer. RESULTS: GAD was associated with increased impairments in psychosocial functioning, role functioning, work productivity and health-related quality of life (HRQL). The HRQL impairments were comparable with those associated with depression or panic disorder. Patients with GAD and co-morbid depression reported significantly greater impairment in HRQL than did those with either disorder alone. GAD patients had significantly higher median medical costs than primary care patients without GAD (US $2375 versus $1448). The mean annual medical cost of GAD was $2138 higher than for other anxiety disorders (mean $6475). Finally, GAD was frequently under-recognized in primary care, and available studies reported that only 20% to 32% of patients were adequately treated. LIMITATIONS: The review was limited to pharmacologic treatments for GAD and to publications in English. CONCLUSIONS: GAD is associated with significant burden on patient functioning and well-being, leading to increased health care utilization and medical costs. Patients with GAD are often suboptimally treated, which adds to the HRQL burden of this disorder.

Integrating Escherichia coli antimicrobial susceptibility data from multiple surveillance programs.

Collaboration between networks presents opportunities to increase analytical power and cross-validate findings. Multivariate analyses of 2 large, international datasets (MYSTIC and SENTRY) from the Global Advisory on Antibiotic Resistance Data program explored temporal, geographic, and demographic trends in Escherichia coli resistance from 1997 to 2001. Elevated rates of nonsusceptibility were seen in Latin America, southern Europe, and the western Pacific, and lower rates were seen in North America. For most antimicrobial drugs considered, nonsusceptibility was higher in isolates from men, older patients, and intensive care unit patients. Nonsusceptibility to ciprofloxacin was higher in younger patients, rose with time, and was not associated with intensive care unit status. In univariate analyses, estimates of nonsusceptibility from MYSTIC were consistently higher than those from SENTRY, but these differences disappeared in multivariate analyses, which supports the epidemiologic relevance of findings from the 2 programs, despite differences in surveillance strategies.

Excess infections due to antimicrobial resistance: the "Attributable Fraction".

Antimicrobial use causes a transient decrease in an individual's resistance to colonization by noncommensal bacteria ("competitive effect") and increases the likelihood of infection upon exposure to a foodborne pathogen. The additional "selective effect" of antimicrobial resistance results in a >3-fold increase in vulnerability to infection by an antimicrobial-resistant pathogen among individuals receiving antimicrobial therapy for unrelated reasons. Combining the increase in vulnerability to infection with the prevalence of taking an antimicrobial agent, it is possible to estimate the attributable fraction, or the number of excess infections that occurred as a result of the unrelated use of an antimicrobial agent to which the pathogen was resistant. Calculations based on estimates of the annual infection rates and attributable fractions of infections with nontyphoidal Salmonella and Campylobacter jejuni suggest that resistance to antimicrobial agents results annually in an additional 29,379 nontyphoidal Salmonella infections, leading to 342 hospitalizations and 12 deaths, and an additional 17,668 C. jejuni infections, leading to 95 hospitalizations.

Morbidity of infections caused by antimicrobial-resistant bacteria.

Antimicrobial resistance can have 2 effects on the outcome of infection: there can be an accompanying change in the virulence of the organism, and there can be a poorer response to treatment because of the empiric choice of an antimicrobial to which the organism is resistant. We have reviewed published studies relating antimicrobial resistance to the outcomes of infection caused by enteric pathogens. The data for Salmonella and Campylobacter infections suggest that antimicrobial-resistant strains are somewhat more virulent than susceptible strains-that is, they cause more prolonged or more severe illness than do antimicrobial-susceptible strains. However, not all studies corrected for possible differences in age and underlying diseases between patients infected by antimicrobial-resistant and -susceptible strains of Salmonella. Two studies of Campylobacter infection suggest that poorer outcomes with antimicrobial-resistant pathogens could be related to the initial choice of an ineffective antimicrobial for treatment. Estimates from various sources indicate that fluoroquinolone resistance, likely acquired from the administration of antimicrobials to food animals, leads to >400,000 excess days of diarrhea in the United States per year compared with the duration that would occur if all of the isolates were susceptible. Antimicrobial resistance also could account for an extra 8677 days of hospitalization for nontyphoidal salmonellosis, mainly arising from food animals.

Review of assessments of the human health risk associated with the use of antimicrobial agents in agriculture.

To our knowledge, no comprehensive risk assessment of agricultural uses of antimicrobial agents has been published. The published risk assessments of antimicrobial use in farm settings are all subject to multiple, serious limitations in scope, including (1) limitation to one species of microorganism; (2) limitation to one or a very few related antimicrobial agents; (3) limitation to a single outcome (death, hospital days, number of illnesses, etc.); (4) limitation to one species of farm animal (e.g., chicken or swine); and (5) limitation to therapeutic use, despite reason for concern about misstated, off-label, or illegal use. In addition, all of the risk assessments reviewed overlooked important issues by accepting 2 further limitations: (6) limiting the scope of the analysis to what has already happened and ignoring the effects of continuing the practices of recent years; and (7) examining only the effects on the species of microorganism that was initially affected and ignoring the cross-species spread of resistance by plasmid transfer. After our review of the risk assessments now available, we propose a comprehensive scheme for organizing existing knowledge and dealing with critical gaps.