Life Years Gained From the FDA Accelerated Approval Program in Oncology: A Portfolio Model.

BACKGROUND: Although the FDA Accelerated Approval Program (AAP) has come under scrutiny, the population-level health benefit of the program has not been quantified. Therefore, the objective of this study was to estimate the number of life years gained among patients with cancer that can be attributable to the therapies receiving FDA accelerated approvals in oncology between 2006 and 2022 in the United States. METHODS: The data sources used were FDA listings, FDA approval letters and labels, published clinical trial data and other publications including relative effectiveness estimates, and the Ipsos Oncology Uptake Tool for product uptake. Data for 130 oncology treatments approved by the FDA under the AAP were extracted and validated. We developed a decision analytic model to estimate the survival gain for each indication and to accumulate life years gained for consecutive cohorts of patients receiving the therapies. Life year gains were estimated with and without the AAP, and the incremental life years gained were attributed to the program. RESULTS: The analysis estimated that through December 2022 in the United States, the program gained approximately 263,000 life years across 69 products for which overall survival data were available, for approximately 911,000 patients with cancer. CONCLUSIONS: Policy discussions about the evaluation of AAP cannot be complete without assessing its impact on its most important target outcome: patient survival. To date, there has been no estimation of the life year gain delivered by the AAP. Our research shows that substantial number of life years were gained for patients with high unmet need by the cancer therapies approved through the program.

The association between US Food and Drug Administration-expedited review designations and health plan specialty drug coverage.

BACKGROUND: The US Food and Drug Administration (FDA) speeds approval of important clinical advancements through 4 expedited review programs: Priority Review, Accelerated Approval, Fast Track, and Breakthrough Therapy. Whether health plans prioritize coverage of expedited drugs relative to drugs that the FDA determined did not qualify from these programs is unclear. OBJECTIVES: To investigate how fast US commercial health plans issued coverage policies for drugs included in different numbers of FDA-expedited programs. Second, to examine the association between a drug's inclusion in an FDA-expedited program and plan coverage restrictiveness. METHODS: We used a separate dataset for each study objective. For the first objective, we created a dataset of policies issued by 17 large commercial health plans for 2018 FDA-approved drugs. Included policies were active exactly 1 year following each drug's FDA approval. We investigated the relationship between the speed of policy issuance and the number of expedited programs. We controlled for cancer and orphan indication. For the second objective, we analyzed a dataset of commercial health plan specialty drug coverage policies. We categorized drugs with respect to the number of expedited programs (0, 1, or 2+ programs). Coverage policies were categorized as whether plans imposed restrictions beyond a drug's FDA-approved labeling, for example, step therapy requirements. We used regression analysis to examine the association between FDA-expedited review and coverage restrictiveness when controlling for other relevant factors (eg, availability of alternatives). RESULTS: For our first objective, plans issued 62% (742/1,190) of policies within a year of a drug's FDA approval. In unadjusted analysis, policy issuance speed increased with each additional expedited program (hazard ratio=1.15; P<0.01). After controlling for cancer and orphan status, the number of expedited programs was not associated with faster policy issuance (hazard ratio=0.95; P=0.209). For our second objective, plans imposed coverage restrictions in 33% (672/2,027) of policies for drugs the FDA included in at least 1 FDA-expedited program vs 51% (870/1,706) of policies for drugs the FDA excluded from these programs. In multivariable regression, we did not find an association between FDA-expedited review and coverage restrictiveness after controlling for other decision-making factors (including disease prevalence, annual cost, etc). CONCLUSIONS: After controlling for other decision-making factors, we did not find that FDA-expedited approval was associated with faster coverage policy issuance, nor did we find that plans covered drugs the FDA included in expedited review programs less restrictively than drugs excluded from these programs. Our findings raise questions about why plans do not also accelerate access for these clinical advancements. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. Mr Ingham is an employee of Janssen Scientific Affairs, LLC, and is a stockholder of Johnson & Johnson. Dr Chambers reports grants from Janssen Scientific Affairs, LLC, during the conduct of the study.

The impact of non-medical switching among ambulatory patients: an updated systematic literature review.

Background: Non-medical switching (NMS) is defined as switching to a clinically similar but chemically distinct medication for reasons apart from lack of effectiveness, tolerability or adherence. Objective: To update a prior systematic review evaluating the impact of NMS on outcomes. Data sources: An updated search through 10/1/2018 in Medline and Web of Science was performed. Study selection: We included studies evaluating ≥25 patients and measuring the impact of NMS of drugs on ≥1 endpoint. Data extraction: The direction of association between NMS and endpoints was classified as negative, positive or neutral. Data synthesis: Thirty-eight studies contributed 154 endpoints. The direction of association was negative (n = 48; 31.2%) or neutral (n = 91; 59.1%) more often than it was positive (n = 15; 9.7%). Stratified by endpoint type, NMS was associated with a negative impact on clinical, economic, health-care utilization and medication-taking behavior in 26.9%,41.7%,30.3% and 75.0% of cases; with a positive effect seen in 3.0% (resource utilization) to 14.0% (clinical) of endpoints. Of the 92 endpoints from studies performed by the entity dictating the NMS, 88.0%were neutral or positive; whereas, only 40.3%of endpoints from studies conducted separately from the interested entity were neutral or positive. Conclusions: NMS was commonly associated with negative or neutral endpoints and was seldom associated with positive ones.

CMS hospital readmission reduction program and anticoagulants received following a total hip and knee arthroplasty discharge.

OBJECTIVES: To assess association between 30 day readmission rate and treatment received after total hip and knee arthroplasty (THA/TKA) discharge (rivaroxaban vs. warfarin or non-anticoagulant). To subsequently model impact of increasing rivaroxaban use on the Hospital Readmission Reduction Program (HRRP) penalty, which was imposed on hospitals with excess 30 day readmissions after hospitalizations for selected conditions, including THA/TKA. METHODS: The US Truven Health MarketScan Medicare Supplemental database from 1 July 2010 to 30 April 2015 was used. A retrospective claims analysis was conducted to assess the risk of all-cause 30 day readmission among patients receiving either rivaroxaban or warfarin, or no anticoagulation following THA/TKA discharge. Simulations were performed to estimate the impact of post-discharge treatment on the HRRP penalty. RESULTS: The risk-adjusted all-cause 30 day readmission rates were 1.21% (95% confidence interval [95% CI]: 0.94%-1.49%), 1.41% (95% CI: 1.19%-1.58%) and 1.95% (95% CI: 1.81%-2.11%) for rivaroxaban, warfarin and non-anticoagulant cohorts, respectively. Using these rates, simulations illustrated that when switching patients from warfarin or non-anticoagulant to rivaroxaban, annual penalty per hospital would be reduced up to 67% or 88%, respectively. CONCLUSIONS: Rivaroxaban treatment post-THA/TKA discharge reduced the risk of 30 day readmission compared to non-anticoagulants. Simulations illustrated that increasing rivaroxaban use could decrease the HRRP penalty.

Implications of stroke and bleeding risk scores and comorbidities on episode-based bundled payments for patients with nonvalvular atrial fibrillation.

OBJECTIVES: Due to the high cost of nonvalvular atrial fibrillation (NVAF), this condition may be a suitable candidate for condition-specific bundled payments. This paper evaluates the healthcare cost of NVAF and uses common bleeding and stroke risk scores (HAS-BLED and CHA2DS2-VASc) to explore the risk-based healthcare cost differences among NVAF patients. METHODS: MarketScan claims of NVAF patients (ICD-9-CM code 427.31) were analyzed from January 2010 to April 2015. These claims feature more than 196 million covered lives and more than 300 contributing employers and 25 contributing health plans. A retrospective cohort design was used to assess episodes of care costs among patients with NVAF. Previously and newly diagnosed NVAF patients were selected from adult patients with ≥2 diagnoses of NVAF, and without valvular disease. Total all-cause healthcare costs at 1 year were stratified by stroke (CHA2DS2-VASc) and bleeding (HAS-BLED) risk scores. Study data was extracted in the MarketScan Commercial Claims and Encounters Database (Commercial Database) and the MarketScan Medicare Supplemental and Coordination of Benefits Database (Medicare Supplemental Database). RESULTS: Mean all-cause 1 year cost of care based on stroke risk (CHA2DS2-VASc) varied from $15,703 to $59,163 for previously diagnosed and $25,992 to $62,458 for newly diagnosed NVAF. Similarly, mean cost varied base on bleeding risk (HAS-BLED) for previously and newly diagnosed NVAF from $17,950 to $57,029 and $26,356 to $67,104 respectively. CONCLUSION: NVAF patients accrue variable healthcare costs. Stroke and bleeding risk should be taken into account during the creation of NVAF payment bundles.

Adherence to non-vitamin-K-antagonist oral anticoagulant medications based on the Pharmacy Quality Alliance measure.

BACKGROUND: CMS Star Ratings help inform beneficiaries about the performance of health and drug plans. Medication adherence is currently weighted at nearly half of a Part D plan's Star Ratings. Including the adherence to non-vitamin-K-antagonist oral anticoagulants (NOACs) as a measure in the Star Ratings program may increase a plan's incentives to improve patient adherence. OBJECTIVE: To assess the adherence to medication of patients who used the NOACs rivaroxaban, dabigatran, or apixaban in 2014 based on the Pharmacy Quality Alliance (PQA) adherence measure. METHODS: Healthcare claims from the Humana database between July 2013 and December 2014 were analyzed. Adult patients with ≥2 dispensings of NOAC agents in 2014, at least 180 days apart, with >60 days of supply, and ≥180 days of continuous enrollment prior to the index NOAC were identified. The PQA measure was calculated as the percentage of patients who had a proportion of days covered (PDC) ≥0.8. Multivariate logistic regression analyses were also conducted adjusting for baseline confounders. RESULTS: A total of 11,095 rivaroxaban, 6548 dabigatran, and 3532 apixaban users were identified. Based on the PQA adherence measure (PDC ≥0.8), a significantly higher proportion of rivaroxaban users (72.7%) was found to be adherent compared to dabigatran (67.2%: p < 0.001) and apixaban (69.5%: p < 0.001) users. Compared to apixaban users, the adjusted likelihood of being adherent was significantly higher for rivaroxaban users (unadjusted OR [95% CI]: 1.17 [1.08-1.27], p < 0.001; adjusted OR [95% CI]: 1.20 (1.10-1.31), p < 0.001) and significantly lower for dabigatran users (unadjusted OR [95% CI]: 0.90 [0.82-0.98], p = 0.019; adjusted OR [95% CI]: 0.85 [0.77-0.93], p < 0.001). LIMITATIONS: Limitations of the study are potential inaccuracies in claims data, possible change in patterns over time, and the impossibility of knowing whether all supplied tablets were taken. CONCLUSION: Using the PQA's adherence measure, rivaroxaban users were found to have significantly higher adherence compared to apixaban and dabigatran users.

Pharmacy quality alliance measure: adherence to non-warfarin oral anticoagulant medications.

BACKGROUND: The Pharmacy Quality Alliance (PQA) recently endorsed adherence to non-warfarin anticoagulant agents as a new performance measure, but the Medicare Part D Star Ratings program has not yet adopted the measure. The current study aims to assess the real-world adherence to medication of patients who used non-vitamin-K-antagonist oral anticoagulants (NOACs) based on the PQA's adherence measure. METHODS: Healthcare claims from the Humana database during the year of 2013 were analyzed. Patients older than 18 with ≥2 dispensings of NOAC agents, at least 180 days apart between two NOAC dispensings in 2013 (a criterion to include chronic users), with ≥60 days of supply, and ≥180 days of continuous enrollment prior to the index NOAC were identified. The PQA measure on the index therapy was calculated as the percentage of patients who had a proportion of days covered (PDC) ≥0.8 during their follow-up. RESULTS: A total of 9948 NOAC users (rivaroxaban: n = 4194, dabigatran: n = 5489, apixaban: n = 265) were identified. For rivaroxaban users, the proportion of patients with a PDC ≥0.8 (PQA measure) at 75.4% was significantly higher compared to dabigatran users (67.6%; P < 0.001) and higher compared to apixaban users (70.6%; P = 0.076). When allowing switches to other NOAC agents in the PQA measure, rivaroxaban users had a significantly higher PQA measure at 76.9% compared to both dabigatran (72.9%; P < 0.001) and apixaban (71.3%; P = 0.037) users. Multivariate logistic regression analyses corroborated the findings that rivaroxaban had a significantly higher adherence compared to the other NOAC agents. LIMITATIONS: Claims data may have contained inaccuracies, possible change in patterns over time, and the impossibility of knowing whether all supplied tablets were taken. CONCLUSION: Based on the PQA's adherence measure, rivaroxaban users were found to have a higher adherence compared to dabigatran and apixaban users. Healthcare providers may want to consider the impact of anticoagulation selection on their ability to achieve quality metrics.

Economic simulation of canagliflozin and sitagliptin treatment outcomes in patients with type 2 diabetes mellitus with inadequate glycemic control.

OBJECTIVES: This study examines the association between changes in diabetes-related quality measures (QMs) (HbA1c, systolic and diastolic blood pressure [BP], low-density lipoprotein cholesterol [LDL-C], and body weight) and healthcare costs in Type 2 diabetes mellitus (T2DM) patients. It also performs an economic simulation that evaluates the cost implications of the changes in QMs and of the incidence rates (IRs) of adverse events (AEs) associated with canagliflozin (CANA) and sitagliptin (SITA) treatments in a real-world setting. METHODS: Health-insurance claims and electronic medical records from the Reliant Medical Group database (2007-2011) were used to identify adult patients with T2DM receiving metformin and sulfonylurea who did not achieve adequate glycemic control. The association between the changes in QMs and healthcare costs was evaluated using multivariate regression and non-parametric bootstrap methods. AE-related costs were taken from the literature. The cost impact of CANA and SITA outcomes was evaluated using the aforementioned costs and the changes in QMs and the IRs of AEs observed in a recent phase 3 trial comparing CANA and SITA as third oral agent (DIA3015). RESULTS: Eight hundred and fifty-six T2DM patients were identified (mean age = 65.8; female 45.4%). The regression analysis found that increases of 1 percentage point in HbA1C and 1% in systolic and diastolic BP, LDL-C, or weight were associated with a per patient per year (PPPY) cost increase of $4476 (p = 0.028) and $566 (p = 0.006), a decrease of $362 (p = 0.070) and $7 (p = 0.817), and an increase of $241 (p = 0.481), respectively. The economic simulation showed that changes in QMs and IRs of AEs equivalent to those reported in DIA3015 would be associated with a reduction in PPPY healthcare costs of $6061 (p = 0.036) for CANA and $2190 (p = 0.098) for SITA. CONCLUSIONS: This study suggests that integrated approaches that manage to control a combination of quality measures are most successful at reducing downstream healthcare costs.

Cost efficiency of canagliflozin versus sitagliptin for type 2 diabetes mellitus.

OBJECTIVES: To compare 1-year clinical outcomes and cost efficiency of treating adults with type 2 diabetes mellitus (T2DM) with canagliflozin (300 mg/day) or sitagliptin (100 mg/day), both added on a background of metformin and sulfonylurea. STUDY DESIGN: An economic model integrated data from an active-controlled, randomized trial, claims database analyses, and published literature. METHODS: The model adopted a US managed care payer perspective and included the clinical and economic impact of achieving specific clinical quality goals. The model was run separately for 2 single clinical quality metrics, glycated hemoglobin (A1C) < 7% (used as base case) or < 8%, and 4 composite metrics (A1C < 7% or < 8% combined with body mass index < 30 kg/m2 and blood pressure < 140/90 mm Hg or low-density lipoprotein cholesterol < 100 mg/dL). Cost savings of achieving versus not achieving metrics were derived from a claims database analysis. Drug and adverse event costs were included. RESULTS: In the base case, compared with sitagliptin 100 mg, treatment with canagliflozin 300 mg resulted in $215 in annual cost savings and 12.3 absolute percentage points more patients achieving goal. Similar findings were found across all other quality metrics (difference in proportion achieving goal ranging from 6.7% to 19.0% and annual savings ranging from $1 to $669). Canagliflozin remained cost saving versus sitagliptin in sensitivity analyses. CONCLUSIONS: Canagliflozin 300 mg may represent a cost-efficient T2DM treatment option versus sitagliptin 100 mg for patients on metformin plus sulfonylurea due to lower overall costs and better achievement of A1C and quality composite goals.

Attainment of diabetes-related quality measures with canagliflozin versus sitagliptin.

OBJECTIVE: To evaluate attainment of diabetes-related quality measures with canagliflozin, a sodium glucose cotransporter 2 inhibitor, versus sitagliptin in patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: This post hoc analysis included data from a 52-week, randomized, double-blind, phase 3 study comparing canagliflozin 300 mg and sitagliptin 100 mg in patients with T2DM on metformin plus sulfonylurea. METHODS: Individual and composite diabetes-related quality measures based on glycated hemoglobin (A1C), blood pressure (BP), low-density lipoprotein cholesterol (LDL-C) level, body mass index (BMI), and body weight were assessed in the overall population and a subgroup with a baseline BMI of at least 25 kg/m². RESULTS: At baseline, the proportion of patients meeting criteria for quality measures was similar between groups. At week 52, more canagliflozin-treated patients achieved quality measures of an A1C less than 8% or less than 7%, and fewer canagliflozintreated patients had an A1C greater than 9%, compared with sitagliptin. More patients achieved BP measurement less than 140/90 mm Hg, less than 140/80 mm Hg, or less than 130/80 mm Hg with canagliflozin versus sitagliptin. The proportion of patients with an LDL-C level less than 100 mg/dL was similar between groups. More patients had a BMI of at least 25 kg/m² and a greater than 10 lb (4.5 kg) weight loss from baseline, and a BMI less than 30 kg/m² at week 52, with canagliflozin versus sitagliptin. A greater proportion of patients achieved composite end points based on A1C, BP, and LDL-C level with canagliflozin versus sitagliptin. Similar results were observed in the subgroup of patients with a baseline BMI of at least 25 kg/m². CONCLUSION: In this study involving patients with T2DM on metformin plus sulfonylurea, after 52 weeks, patients treated with canagliflozin 300 mg demonstrated better attainment of individual and composite diabetes-related quality measures compared with patients treated with sitagliptin 100 mg.

Quality measure attainment in patients with type 2 diabetes mellitus.

OBJECTIVES: This study examined the demographics, comorbidities, clinical characteristics, and treatments of people with type 2 diabetes mellitus (T2DM) treated with metformin and sulfonylurea as well as an elderly subgroup. Achievement of predefined quality measure goals (glycated hemoglobin [A1C], blood pressure [BP], low-density lipoprotein cholesterol [LDL-C], body mass index [BMI]) and their association with diabetes-related healthcare costs were assessed. STUDY DESIGN: The study applied a retrospective longitudinal cohort design. METHODS: Health insurance claims and electronic medical records from 14,532 adults with T2DM (2007- 2011) were used to identify a sample receiving metformin and sulfonylurea (MET+SU) concomitantly. The index date was the first dispensing of MET+SU after 6 months of eligibility. Clinical characteristics were assessed during baseline. Quality measure attainment (A1C <8%, BP <140/90 mm Hg, LDL-C level <100 mg/dL, BMI <30 kg/m²), was evaluated during the 12 months following the index date. Association between attainment and diabetes-related costs was evaluated using non-parametric bootstrap methods adjusting for imbalance in baseline characteristics between cohorts. RESULTS: Among 2044 patients, including 1283 patients 65 years and older, hyperlipidemia, hypertension, and cardiovascular disease were the most common baseline comorbidities. Quality measure goal attainment was 63.9% for A1C, 33.1% for BP, 68.2% for LDL-C level, and 34.4% for BMI, and was associated with significantly lower diabetes-related costs per patient per year compared with nonattainment (adjusted mean cost differences: -$1445 for A1C; -$1218 for BMI; -$2029 for A1C and BMI; -$2073 for A1C, BMI, and BP; all P <.05). CONCLUSION: This study highlights the high incidence of comorbidities and potential financial implications of attaining T2DM quality outcomes.

Direct medical costs of complications of diabetes in the United States: estimates for event-year and annual state costs (USD 2012).

OBJECTIVE: To estimate the direct medical costs associated with managing complications, hypoglycemia episodes, and infections associated with type 2 diabetes expressed in 2012 United States dollars (USD). METHODS: Direct data analysis and microcosting were used to estimate the costs for an event leading to either a hospital admission or outpatient care, and the post-acute care associated with managing macrovascular and microvascular complications, hypoglycemia episodes, and infections. Data were obtained from many sources, including inpatient and emergency department databases, national physician and laboratory fee schedules, government reports, and literature. Event-year costs reflect the resource use during an acute care episode (initial management in an inpatient or outpatient setting) and any subsequent care provided in the first year. State costs reflect annual resource use required beyond the first year for the ongoing management of complications and other conditions. Costs were assessed from the perspective of a comprehensive US healthcare payer and expressed in 2012 USD. RESULTS: Event-year costs (and state costs) for macrovascular complications were as follows: myocardial infarction $56,445 ($1904); ischemic stroke $42,119 ($15,541); congestive heart failure $23,758 ($1904); ischemic heart disease $21,406 ($1904); and transient ischemic attack $7388 ($179). For two microvascular complications the event-year and state costs were assumed the same: $71,714 for end stage renal disease, and $2862 blindness. The event-year cost was $9041 for lower extremity amputations, and $2147 for diabetic foot ulcers. Costs were also determined for managing hypoglycemic episodes: $176-$16,478 (depending on treatment required), and infections: vulvovaginal candidiasis $111, lower urinary tract infection $105. CONCLUSIONS: This study, which provides up-to-date cost estimates per patient, found that managing macrovascular and microvascular complications results in substantial costs to the healthcare system. This study facilitates conduct of other research studies such as modeling the management of diabetes and estimating the economic burden associated with complications.

Cost-effectiveness of combination therapy with etravirine in treatment-experienced adults with HIV-1 infection.

OBJECTIVE: To assess the cost-effectiveness of etravirine (INTELENCE), a novel nonnucleoside reverse transcriptase inhibitor, used in combination with a background regimen that included darunavir/ritonavir, from a Canadian Provincial Ministry of Health perspective. DESIGN: A Markov model with a 3-month cycle time and six health states based on CD4 cell count ranges was developed to follow a hypothetical cohort of treatment-experienced adults with HIV-1 infection through initial and subsequent treatment regimens. METHODS: Costs (in 2009 Canadian dollars), utilities, and HIV-related mortality data for each health state as well as non-HIV-related mortality data were estimated from Canadian sources and published literature. Transition probabilities between health states and first-year hospitalization and mortality rates were derived from clinical trial data. Incremental 1-year costs per additional adult with viral load less than 50 copies/ml at 48 weeks and incremental lifetime costs per quality-adjusted life-year (QALY) gained were estimated using a 5% discount rate. Sensitivity and variability analyses and model validation were performed. RESULTS: Etravirine was associated with an increased probability of achieving less than 50 copies/ml at 48 weeks of 0.205 and an estimated gain of 0.66 discounted (1.48 undiscounted) QALYs over a lifetime. The incremental 1-year cost per additional person with viral load less than 50 copies/ml was $23,862. The lifetime incremental cost per QALY gained was $49,120. For the uncertainty ranges and variability scenarios tested for the lifetime horizon, the cost-effectiveness ratio was between $28,859 and 66,249. CONCLUSION: When compared with optimized standard of care including darunavir/ritonavir, adding etravirine represents a cost-effective option for treatment-experienced adults in Canada.

The value to patients of reducing lesion severity in plaque psoriasis.

Plaque psoriasis is associated with significant psychosocial, quality-of-life, and economic burden. The objective of this study was to quantify the value to patients of reducing the severity and size of plaque psoriasis lesions. Subjects included individuals with a self-reported diagnosis of plaque psoriasis from a nationally representative US household panel. Subjects completed a web-based conjoint analysis survey and chose between hypothetical treatments in a series of questions. Each alternative was defined by lesion severity, percentage of body surface area (BSA) covered by lesions, type of treatment, injection discomfort or pain (if treatment included injections), risk of serious lung infection, and monthly out-of-pocket cost. 28,200 panelists were invited to participate. 18,330 responded, 503 qualified, and 419 completed the survey. Mean age was 54.5 years and 52% were female. 64% (35%) of patients reported psoriasis severity as mild or mild to moderate (moderate to very severe). Patients were willing to pay $486.73 out-of-pocket per month to eliminate severe lesions covering 25% BSA on the arms and legs and $444.80 out-of-pocket per month to eliminate moderate lesions covering 4% BSA on the face. Individuals with plaque psoriasis are willing to pay substantial amounts to reduce lesion severity and percentage of BSA covered by lesions.

Cost per responder analysis of ustekinumab and etanercept for moderate to severe plaque psoriasis.

OBJECTIVE: To compare the cost per responder of ustekinumab with etanercept based on data from the active comparator ACCEPT trial. METHODS: In ACCEPT, patients received ustekinumab 45 mg (n = 209) or 90 mg (n = 347) at weeks 0 and 4 or etanercept 50 mg (n = 347) twice weekly for 12 weeks. The proportions of patients achieving ≥75% improvement in the Psoriasis Area and Severity Index [PASI 75] were determined at week 12. The cost per PASI 75 responder was determined for week 16, a time coinciding with treatment coverage of both drugs and accounting for the different dosing intervals. Costs for 16 weeks of therapy were based on the Wholesale Acquisition Cost (WAC) in the United States. The analysis used weight-based efficacy results for ustekinumab (45 mg for patients ≤ 100 kg; 90 mg for patients > 100 kg) and overall efficacy for etanercept, consistent with the approved dosages. RESULTS: A total of 28% of patients weighed > 100 kg. The PASI 75 response rates at week 12 were 72.2% for the ustekinumab 45 mg group in patients ≤ 100 kg, 65.0% for the ustekinumab 90 mg group in patients > 100 kg, and 56.8% for the etanercept group. At week 16, the cost per responder was $17,842 for ustekinumab and $20,077 for etanercept. CONCLUSION: The cost per responder was lower for ustekinumab than for etanercept through 16 weeks in psoriasis patients.

Cost effectiveness of darunavir/ritonavir in highly treatment-experienced, HIV-1-infected adults in the USA.

INTRODUCTION: Darunavir is a new protease inhibitor (PI) that is co-administered with low-dose ritonavir and has demonstrated substantial efficacy in clinical trials of highly treatment-experienced patients when combined with an optimized background regimen (with or without enfuvirtide). This study estimates the cost effectiveness of darunavir with ritonavir (DRV/r) in this population over 5-year and lifetime time horizons in the USA. METHODS: A Markov model was used to follow a treatment-experienced HIV-1 cohort through six health states, based on CD4 cell count: greater than 500, 351-500, 201-350, 101-200, 51-100 and 0-50 cells/mm³, and death. The magnitude of the CD4 cell count increase and duration of increasing and stable periods were derived from week 48 DRV/r clinical trial results (POWER 1 and 2). The treatment pathway assumed one regimen switch following treatment failure on the initial regimen. The use of antiretroviral drugs was based on usage in DRV/r clinical trials. US daily wholesale acquisition costs were calculated using the recommended daily doses. For each CD4 cell count range, utility values, HIV-1-related mortality rates and costs for medical resources (other than antiretroviral drug costs) were obtained from published literature. Non-HIV-1-related mortality rates were calculated by applying a relative risk value to the US general population age and gender-specific mortality rates. Costs and outcomes were discounted at 3% per year. One-way and probabilistic sensitivity analyses and variability analysis were performed. RESULTS: In a 5-year analysis, patients receiving DRV/r experienced 3.80 quality-adjusted life-years (QALYs) and incurred total medical costs of US$217,288, while those receiving control PIs experienced 3.60 QALYs and incurred costs of US$218,962. DRV/r was both more effective and less costly than control PIs. For the lifetime analysis, the QALYs and lifetime medical costs with DRV/r were 10.03 and US$565,358, compared with 8.76 and US$527,287 with control PIs. The incremental cost-effectiveness ratio for DRV/r compared with control PIs was US$30,046. One-way sensitivity analyses for both time horizons indicated that the results were most sensitive to changes in the rate of CD4 cell count change during stable and declining periods (lifetime only), duration of stable period (5-year only) and HIV-1-related mortality rates. The results of the variability analysis were most sensitive to the model time horizon. Nevertheless, for all ranges and scenarios tested in these analyses, the incremental cost per QALY gained remained below US$50,000. The probabilistic sensitivity analysis showed that there was a 0.921 and 0.950 probability of a cost-effectiveness ratio below US$50,000 per QALY for the 5-year and lifetime time horizon, respectively. CONCLUSIONS: DRV/r is predicted to be cost effective compared with control PI in highly treatment-experienced patients and is predicted to yield an average of 0.20 additional QALYs per treatment-experienced patient over 5 years and 1.27 additional QALYs over a lifetime in this population.

Pharmacoeconomics of etravirine.

HIV infection, particularly multidrug-resistant HIV, continues to be a major societal and economic challenge worldwide. Etravirine, a new (US FDA approved in 2008) non-nucleoside reverse transcriptase inhibitor, has been shown to be very effective in treating patients who have failed prior antiretroviral therapy. Clinical studies demonstrated that etravirine in combination with other antiretrovirals achieved superior levels of undetectable plasma HIV RNA and CD4 cell count increases that led to reductions in risk of death and development of AIDS-defining illnesses when compared with placebo. Etravirine was also shown to be generally well tolerated, with favorable CNS and psychiatric tolerability profiles. In addition, etravirine in combination with other antiretrovirals has been shown to improve quality of life and quality-adjusted life expectancy. Economic evaluations showed that the addition of etravirine to a regimen was associated with lower costs per person with an undetectable viral load and lower hospital-related costs compared with placebo.

Psychometric evaluation of the functional assessment of HIV Infection (FAHI) questionnaire and its usefulness in clinical trials.

PURPOSE: To evaluate psychometric properties of the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) questionnaire, a 47-item disease-specific instrument evaluating Health-Related Quality of Life (HRQL) in human immunodeficiency virus (HIV)-infected patients. METHODS: Treatment-experienced HIV-infected patients from two clinical programmes (N = 565; N = 1,096) completed the FAHI at Baseline and after 24 weeks of treatment. Psychometric properties of the FAHI were assessed in both trial populations, including minimal important differences (MIDs) calculations. Links between HRQL assessed by FAHI Total score, and biological endpoints were explored by regression analysis and mean score comparisons. RESULTS: Cronbach's alphas ranged from 0.72 to 0.94. Most items met convergent and discriminant validity criteria. Better FAHI scores were seen for patients in earlier HIV stages. Responsiveness was demonstrated with changes in FAHI scores significantly linked to change in EQ-5D score. Depending on methods used, MIDs ranged from 3.2 to 14 for FAHI Total score. Small association was found between FAHI Total score and CD4 count and viral load (r-square < 3%). Mean changes in FAHI scores were not statistically related to viral response. CONCLUSIONS: The FAHI demonstrated acceptable psychometric properties in two independent populations. HRQL assessment enabled detection of changes in patients' health status not revealed by traditional efficacy endpoints.

Effects of etravirine versus placebo on health-related quality of life in treatment-experienced HIV patients as measured by the functional assessment of human immunodeficiency virus infection (FAHI) questionnaire in the DUET trials.

PURPOSE: To study the effects of etravirine versus placebo on the health-related quality of life (HRQL) of HIV-infected patients. METHOD: HRQL of HIV-infected patients was measured using the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) questionnaire in two identically designed phase III clinical trials investigating efficacy and safety of etravirine as part of highly active antiretroviral therapy. Pooled analyses of covariance, adjusted for treatment group, baseline FAHI score, CD4 cell count, viral load, and enfuvirtide use helped investigate changes in FAHI scores between baseline and Week 24 in etravirine-treated (n = 599) and placebo-treated (n = 604) subjects. Responder analyses were also conducted. RESULTS: Significant improvements with etravirine treatment were observed for FAHI physical, functional, emotional, and total scores (P < .001). These improvements were greater and statistically different from those with placebo (.013

Patient-based utilities for bipolar disorder-related health states.

BACKGROUND: Bipolar disorder is a psychiatric disorder which impacts patient functioning and well-being. With increasing interest in cost-effectiveness of treatments, it is necessary to provide estimates of patient's perspectives on treatment outcomes. This study estimated health state utilities for hypothetical bipolar-related health states and patient's current health from bipolar I patients. METHODS: Clinicians completed Young Mania Rating Scale, Montgomery-Asberg Depression Rating Scale, and Global Assessment Score. Patients completed structured standard gamble (SG) utility assessment interviews, and the other patient-based measures. Interviews obtained utilities for hypothetical bipolar-related health states describing symptom severity, functioning and well-being, and treatment-related side effects. RESULTS: Ninety-six patients were recruited from psychiatry outpatient practices. Mean utilities for inpatient states ranged from 0.12 to 0.33; outpatient mania states ranged from 0.29 to 0.64; outpatient stable states ranged from 0.53 to 0.85. Mean utility for current health was 0.80 (S.D.=0.22). Patients preferred monotherapy compared with combination therapy health states. Ordinary least squares regression indicated weight gain was associated with a 0.066 decrease in health state utilities (P=0.013). LIMITATIONS: Study sample consisted of selected stable and educated patients and small sample sizes may limit generalizability for some utilities. CONCLUSIONS: Bipolar disorder patients are capable of participating in utility assessment and providing ratings for hypothetical health states associated with different mood stabilizer treatments.