Indirect comparison of pembrolizumab monotherapy versus nivolumab + ipilimumab in first-line metastatic lung cancer.

Aim: This study indirectly compared the effectiveness of pembrolizumab monotherapy versus nivolumab + ipilimumab in metastatic non-small-cell lung cancer. Materials and methods: A matching-adjusted indirect comparison was conducted using pooled individual patient data from KEYNOTE-024 and KEYNOTE-042 and published aggregate data from CheckMate 227 Part 1A, with platinum doublet chemotherapy as the anchor. Results: After matching, estimated hazard ratios (95% CI) of pembrolizumab monotherapy versus nivolumab + ipilimumab for overall survival and progression-free survival were 1.07 (0.82, 1.39) and 1.16 (0.93, 1.45), respectively. For objective response rate, the estimated risk ratio (95% CI) was 0.93 (0.71, 1.22) and the risk difference (95% CI) was -2.86%(-11.38, 5.67). Conclusion: Matching-adjusted indirect comparison results demonstrated comparable effectiveness between pembrolizumab monotherapy and nivolumab + ipilimumab as first-line therapies for metastatic non-small-cell lung cancer with PD-L1 tumor-proportion score ≥1%.

Cost-Minimization Analysis of Pembrolizumab Monotherapy Versus Nivolumab in Combination with Ipilimumab as First-Line Treatment for Metastatic PD-L1-Positive Non-small Cell Lung Cancer: A US Payer Perspective.

BACKGROUND: Pembrolizumab monotherapy and nivolumab in combination with ipilimumab are US FDA-approved first-line (1L) regimens for patients with metastatic non-small cell lung cancer (NSCLC) without epidermal growth factor receptor or anaplastic lymphoma kinase genomic aberrations and with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥ 1%. A published matching-adjusted indirect comparison found the two regimens yield comparable overall and progression-free survival outcomes. OBJECTIVE: The aim of this study was to compare direct medical costs of pembrolizumab and nivolumab plus ipilimumab for PD-L1-positive metastatic NSCLC treatment within the first 3 years following treatment initiation from a US payer perspective. METHODS: A cost-minimization model was built to estimate and compare treatment, disease management, and adverse event costs based on KEYNOTE-024 and -042, and CheckMate 227 Part 1a trial survival and adverse event data. RESULTS: 1L pembrolizumab generates $54,343, $75,744, and $76,259 per patient cost savings compared with 1L nivolumab plus ipilimumab for patients with NSCLC with PD-L1 TPS ≥ 1% within 1, 2, and 3 years of treatment initiation, respectively. CONCLUSION: Pembrolizumab is cost saving as 1L treatment for PD-L1-positive metastatic NSCLC in comparison with nivolumab plus ipilimumab, at least for the short term.

Cost-effectiveness of pembrolizumab + chemotherapy versus chemotherapy and pembrolizumab monotherapy in first line treatment of NSCLC in the US - updated analyses with additional trial follow-up.

OBJECTIVE: Pembrolizumab + chemotherapy substantially extends life expectancy for metastatic non-small cell lung cancer (NSCLC) patients. Its cost-effectiveness (CE) was previously evaluated based on interim trial analyses (follow-up ∼1 year). The present analysis describes CE incorporating additional follow-up based on protocol-specified final trial analyses (1-1.5 years additional follow-up), from a US healthcare payer perspective. METHODS: A partitioned survival model is used to compare pembrolizumab + chemotherapy vs chemotherapy using data from the KN189 (non-squamous patients) and KN407 (squamous patients) clinical trials. An indirect treatment comparison vs pembrolizumab monotherapy is made for patient subgroups with PD-L1 TPS ≥50% and 1-49% based on data from the KN024 and KN042 trials. Efficacy, treatment utilization, health utility, and safety data are derived from trials and projected over 20 years. Costs for drugs, non-drug disease management, and adverse events are also incorporated. RESULTS: Overall, versus chemotherapy alone, pembrolizumab + chemotherapy is projected to increase life expectancy by 1.12 years (3.35 vs 2.23) and 0.67 years (3.17 vs 2.50) in non-squamous and squamous patients, respectively. Resultant ICERs ($158,030/QALY and $178,387/QALY) are below a US 3-times GDP per capita threshold ($195,000/QALY). ICERs vs chemotherapy also generally fall below the threshold within PD-L1 sub-groups (except in squamous PD-L1 < 1%, which may have differed due to small sample size) while ICERs vs pembrolizumab monotherapy in PD-L1 ≥ 50% and 1-49% sub-groups generally exceed it (except in squamous PD-L1 1-49%); largely a result of the higher drug acquisition cost of pembrolizumab + chemotherapy relative to differences in life expectancy. CONCLUSIONS: Taken together, with longer-term trial follow-up and in the context of prior literature, in the US, one of the two options for pembrolizumab use (either pembrolizumab + chemotherapy or pembrolizumab monotherapy), represents a cost-effective treatment in virtually all non-squamous and squamous metastatic NSCLC patient populations and PD-L1 sub-groups evaluated.

A Review of Cost-Effectiveness Studies of Pembrolizumab Regimens for the Treatment of Advanced Non-small Cell Lung Cancer.

Pembrolizumab monotherapy or combination therapy is an approved treatment for various advanced non-small cell lung cancer (NSCLC) indications. We review published cost-effectiveness analyses (CEAs) of pembrolizumab as treatment for NSCLC and provide in-depth assessment of their methodologies. Fourteen studies were selected through searches of the PubMed database. Modeling approaches, survival and cost estimation, and utility analyses were compared and evaluated. These publications covered regulatory-approved pembrolizumab NSCLC indications based on the following randomized clinical trials: KEYNOTE-010 (one publication), KEYNOTE-024 (six), KEYNOTE-042 (four), KEYNOTE-189 (two), and KEYNOTE-407 (one). Differences were observed in health states (progression free, progressed disease, and death vs stable disease, progressed disease, death, and treatment discontinuation), modeling approaches (partitioned survival vs Markov), survival extrapolation/transition probability estimation, inclusion of additional costs to drug, disease management and adverse event costs (e.g., programmed death-ligand 1 [PD-L1] testing, subsequent treatment, terminal care), treatment duration approaches (trial-based time on treatment vs treat to progression), utility sources (trial data vs literature), and utility analyses (time to death vs progression status). Certain aspects of variability across models were problematic, including deviation from observed treatment utilization within trials and predicted long-term mortality risks for pembrolizumab higher than historical real-world NSCLC mortality data prior to the availability of pembrolizumab. Consequently, results differed even among studies examining the same population and comparator within similar time intervals. Differences in methodology across CEAs may lead to distinct results and conclusions. Payers and policy makers should carefully examine study designs and assumptions and choose CEAs with greater validity and accuracy for evidence-based decision-making.

A Matching-Adjusted Indirect Comparison of Pembrolizumab + Chemotherapy vs. Nivolumab + Ipilimumab as First-Line Therapies in Patients with PD-L1 TPS ≥1% Metastatic NSCLC.

BACKGROUND: In the absence of head-to-head trials, this study indirectly compared the effectiveness of pembrolizumab + chemotherapy vs nivolumab + ipilimumab for the first-line treatment of metastatic stage IV NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1%. METHODS: An anchored matching-adjusted indirect comparison (MAIC) was conducted using pooled individual patient data (IPD) from the ITT population in KEYNOTE-021G, KEYNOTE-189 and KEYNOTE-407 (n = 816) and published aggregate data of nivolumab + ipilimumab from CheckMate 227 Part 1A (n = 793). To adjust for cross-trial differences in baseline characteristics, data from KEYNOTE-021G/KEYNOTE-189/KEYNOTE-407 were re-weighted to match the baseline characteristics of CheckMate 227 Part 1A. Outcomes included OS, PFS and ORR. Base case analyses were restricted to patients with PD-L1 TPS ≥1%, with sub-group analyses in PD-L1 TPS ≥50% and 1-49%. RESULTS: The estimated HR (95% CI) of pembrolizumab + chemotherapy vs nivolumab + ipilimumab was 0.80 (0.59,1.09) and 0.53 (0.41,0.68) for OS and PFS, respectively. For ORR, the estimated risk ratio was 1.8 (1.3,2.4) for pembrolizumab + chemotherapy vs nivolumab + ipilimumab and the risk difference was 25.5% (15.0,36.0). PD-L1 TPS ≥50% and 1-49% sub-groups showed an OS HR of 0.89 (0.58,1.36) and 0.68 (0.46,1.01), respectively. CONCLUSION: These MAIC results suggest that pembrolizumab + chemotherapy leads to a greater clinical benefit vs nivolumab + ipilimumab in patients with PD-L1 TPS ≥1% across multiple endpoints.

Cost Effectiveness of PD-L1-Based Test-and-Treat Strategy with Pembrolizumab as the First-Line Treatment for Metastatic NSCLC in Hong Kong.

BACKGROUND: Pembrolizumab, a monoclonal antibody against programmed death ligand 1 (PD-L1), is approved by several regulatory agencies for first-line treatment of metastatic non-small-cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥ 50% and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase genomic tumor aberrations. This study was conducted from the perspective of the Hospital Authority in Hong Kong and aimed to evaluate the cost effectiveness of a biomarker (PD-L1) test-and-treat strategy (BTS), in which patients with a TPS ≥ 50% received pembrolizumab and other patients received platinum doublet chemotherapy versus all patients receiving platinum doublet chemotherapy. METHODS: The model used a partitioned survival approach to estimate the incremental cost-effectiveness ratio (ICER) expressed as the cost per quality-adjusted life-year (QALY) gained. The clinical efficacy, utility and safety data were derived from the KN024 trial. Costs and health outcomes were projected over a 10-year time horizon and discounted at 3% per year. Costs for drug acquisition, PD-L1 testing, drug administration and disease management were used. Sensitivity analyses were conducted to evaluate the robustness of results. RESULTS: The BTS approach led to an increase of 0.29 QALYs at an additional cost of Hong Kong dollars (HK$) 249,077 (US$31,933) compared with platinum doublet chemotherapy, resulting in an ICER of HK$865,189 (US$110,922) per QALY gained. This is lower than the World Health Organization cost-effectiveness threshold of three times the 2016 gross domestic product (GDP) per capita for Hong Kong of HK$1017,819 (US$130,490). Probabilistic sensitivity analyses showed a 59.4% chance that the ICER would be below this threshold. CONCLUSION: First-line treatment with pembrolizumab in a BTS to identify patients with NSCLC with PD-L1 TPS ≥ 50% can be considered cost effective in Hong Kong compared with platinum doublet chemotherapy based on a three-times GDP per capita threshold. However, local data on clinical efficacy and safety were not available to estimate overall survival (OS) and progression-free survival (PFS) specific to patients with NSCLC in Hong Kong. Further, uncertainty is inherent in the survival projections/extrapolation of PFS and OS beyond the trial period, and future research may help to further inform these parameters.

Cost effectiveness of pembrolizumab vs chemotherapy as first-line treatment for metastatic NSCLC that expresses high levels of PD-L1 in Switzerland.

AIM: The study aim was to evaluate the cost effectiveness of pembrolizumab monotherapy compared with chemotherapy as a first-line treatment for previously untreated metastatic non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50%, from a Swiss payer perspective. Cost effectiveness of pembrolizumab for this indication has not previously been evaluated in Switzerland. METHODS: We conducted an analysis using a partitioned survival model with a cycle length of one week, base-case time horizon of 20 years and discount rate of 3% for cost and health outcomes. KEYNOTE-024 randomised controlled trial data for pembrolizumab monotherapy compared with chemotherapy was used as a basis for projecting time-on-treatment, progression-free survival and overall survival, over a 20-year period. For overall survival and progression-free survival, we used Kaplan-Meier probabilities for a brief initial period of the model, followed by parametric curves that had the best fit with subsequent trial data. Quality-adjusted life years (QALYs) were calculated based on the EuroQol 5-dimensional 3-level (EQ-5D-3L) questionnaire administered to trial patients. Costs (in CHF, year 2018) of drug acquisition/administration, adverse events and disease management were included. RESULTS: For the base-case, pembrolizumab monotherapy resulted in mean incremental costs of CHF 77,060 (pembrolizumab CHF 223,324, chemotherapy CHF 146,264) and mean incremental QALYs of 1.34 (pembrolizumab 3.05, chemotherapy 1.71), leading to an incremental cost-effectiveness ratio of CHF 57,402 per QALY gained. Cost-effectiveness results were most sensitive to overall survival and relatively insensitive to other parameters varied. In probabilistic sensitivity analysis, the probability of cost effectiveness of pembrolizumab, with an assumption of a willingness-to-pay threshold of CHF 100,000 per QALY gained, was 88%. CONCLUSION: Pembrolizumab is likely to be cost effective for treating Swiss patients with previously untreated metastatic NSCLC expressing PD-L1 TPS ≥50%. (This economic evaluation was based on the KEYNOTE-024 trial. The trial identifier is NCT02142738.).

Cost-effectiveness of pembrolizumab versus chemotherapy as first-line treatment in PD-L1-positive advanced non-small-cell lung cancer in the USA.

Aim: This analysis aimed to evaluate the cost-effectiveness of pembrolizumab monotherapy as first-line treatment in advanced non-small-cell lung cancer patients with a programmed death ligand 1 (PD-L1) tumor proportion score ≥1% from a US payer perspective. Materials & methods: A partitioned survival model was developed using efficacy and safety data from the KEYNOTE-042 trial and projected over 20 years. Costs accounted for treatment, toxicity and disease management. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were reported. Results: Pembrolizumab resulted in an expected gain of 0.60 life years and 0.49 QALYs compared with platinum-based chemotherapy. The incremental cost-effectiveness ratio was US$130,155/QALY. Conclusion: Pembrolizumab is projected to be cost-effective compared with platinum-based chemotherapy as first-line treatment for advanced non-small-cell lung cancer with PD-L1 tumor proportion score ≥1%.

Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis.

AIM: A systematic review and network meta-analysis were conducted to evaluate the efficacy of pembrolizumab + pemetrexed + platinum relative to other regimens in metastatic nonsquamous non-small-cell lung cancer (NSq-NSCLC). PATIENTS & METHODS: Eligible studies evaluated first-line regimens in NSq-NSCLC patients without known targetable mutations. Relative treatment effects were synthesized with random effects proportional hazards Bayesian network meta-analyses. RESULTS: The hazard ratio (HR) for overall survival (OS) for pembrolizumab + pemetrexed + platinum was statistically significant over all platinum-doublet (HR range: 0.42-0.61), platinum-doublet + bevacizumab (HR range: 0.44-0.53) and platinum-doublet + atezolizumab regimens (HR range: 0.56-0.62). Additionally, pembrolizumab + pemetrexed + platinum numerically improved OS over atezolizumab + paclitaxel + carboplatin + bevacizumab (HR: 0.65; 95% credible interval: 0.43, 1.01). Pembrolizumab + pemetrexed + platinum had 95.6% probability of being the best treatment regimen for OS. CONCLUSION: Pembrolizumab + pemetrexed + platinum is likely the most efficacious first-line regimen for metastatic NSq-NSCLC.

Cost-effectiveness of pembrolizumab in combination with chemotherapy versus chemotherapy and pembrolizumab monotherapy in the first-line treatment of squamous non-small-cell lung cancer in the US.

Objective: To describe the cost-effectiveness of pembrolizumab plus chemotherapy (carboplatin and paclitaxel or nab-paclitaxel; P + C) in metastatic, squamous, non-small-cell lung cancer (NSCLC) patients in the US. Methods: A model comparing P + C versus C alone is developed utilizing partitioned survival analysis. Primary clinical efficacy, treatment utilization, health utility and safety data are derived from the KEYNOTE-407 trial and projected over 20 years. Costs for drugs and non-drug disease management are also incorporated. Additionally, the cost-effectiveness of P + C vs. pembrolizumab monotherapy (P) is evaluated via an indirect treatment comparison, for patient subgroups with PD-L1 Tumor Proportion Score (TPS) ≥ 50% and 1-49%. Results: Overall, P + C is projected to increase life expectancy by 1.95 years vs. C (3.86 versus 1.91). The resultant ICER is $86,293/QALY. In patients with PD-L1 ≥ 50%, 1-49% and <1 the corresponding incremental cost-effectiveness ratios (ICERs) are $99,777/QALY, $85,986/QALY and $87,507/QALY, respectively. Versus P, in the PD-L1 ≥ 50% subgroup, P + C appears cost saving; however, this result should be interpreted with caution as there is considerable uncertainty in the relative efficacy of these comparators. Conclusions: Across all eligible patients, the addition of pembrolizumab to chemotherapy is projected to approximately double life expectancy, yielding an extension to a point not previously seen in metastatic squamous NSCLC. Overall, and within all relevant PD-L1 subgroups, use of P + C yields an ICER below $100,000/QALY, and can be a cost-effective first-line treatment for eligible metastatic squamous NSCLC patients for whom chemotherapy is currently administered. In the PD-L1 ≥ 50% subgroup, additional follow-up within trials of pembrolizumab plus chemotherapy and pembrolizumab monotherapy are needed to better define cost-effectiveness between these comparators.

Cost-effectiveness of pembrolizumab in combination with chemotherapy in the 1st line treatment of non-squamous NSCLC in the US.

AIMS: To describe cost-effectiveness of pembrolizumab plus platinum and pemetrexed chemotherapy in metastatic, non-squamous, NSCLC patients in the US. MATERIALS AND METHODS: A model is developed utilizing partitioned survival analysis to estimate the cost-effectiveness of KEYNOTE-189 trial comparators pembrolizumab + chemotherapy (carboplatin/cisplatin + pemetrexed) vs chemotherapy alone. Clinical efficacy, treatment utilization, health utility, and safety data are derived from the trial and projected over 20 years. For extrapolating survival beyond the trial, a novel SEER population-data approach is applied (primary analysis), with separate estimation via traditional parametric extrapolation methods. Costs for drugs and non-drug disease management are also incorporated. Based on an indirect treatment comparison, cost-effectiveness of pembrolizumab + chemotherapy vs pembrolizumab monotherapy is evaluated for patients with programmed death-ligand 1 (PD-L1) ≥ 50%. RESULTS: In the full non-squamous population, pembrolizumab + chemotherapy is projected to increase life expectancy by 2.04 years vs chemotherapy (3.96 vs 1.92), for an approximate doubling of life years. Resultant incremental cost-effectiveness ratios (ICERs) are $104,823/QALY and $87,242/life year. In patients with PD-L1 ≥ 50% and 1-49%, life expectancy is more than doubled (4.53 vs 1.88 years) and (4.87 vs 2.01 years), with a 32% (2.60 vs 1.97 years) increase in PD-L1 < 1% patients. Corresponding incremental costs/quality-adjusted life year (QALY) are $103,402, $66,837, and $183,529 for PD-L1 ≥ 50%, 1-49%, and <1% groups, respectively. Versus pembrolizumab monotherapy in PD-L1 ≥ 50% patients, representing current standard of care, pembrolizumab + chemotherapy increases life expectancy by 65% (4.53 vs 2.74 years) at an ICER of $147,365/QALY. LIMITATIONS AND CONCLUSIONS: The addition of pembrolizumab to chemotherapy is projected to extend life expectancy to a point not previously seen in previously untreated metastatic non-squamous NSCLC. Although ICERs vary by sub-group and comparator, results suggest pembrolizumab + chemotherapy yields ICERs near, or in most cases, well below a 3-times US per capita GDP threshold of $180,000/QALY, and may be a cost-effective first-line treatment for metastatic non-squamous NSCLC patients.

Cost-effectiveness Analysis of Golimumab in the Treatment of Non-Radiographic Axial Spondyloarthritis in Scotland.

INTRODUCTION: The aim of this study is to assess the cost-effectiveness of golimumab for the treatment of non-radiographic axial spondyloarthritis (nr-axSpA) vs. conventional therapy and other tumor necrosis factor inhibitors from the Scottish payer perspective. METHODS: A model comprising a short-term decision tree and a long-term Markov model was developed to compare cost-effectiveness (incremental costs per quality-adjusted life-year [QALY]) for patients in Scotland with nr-axSpA treated by conventional therapy, adalimumab, certolizumab pegol, etanercept, or golimumab for a lifetime period. A network meta-analysis (NMA) was conducted to identify clinical and safety data for treatments and synthesize the available evidence into relative treatment effects between comparators. The probability of patients achieving an Assessment of SpondyloArthritis International Society 20/40% response criteria (ASAS20/ASAS40) or a 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index score (BASDAI50) at week 12 was obtained from the NMA for each of the comparators. Baseline health state utilities were based on the EQ-5D questionnaire collected in the golimumab GO-AHEAD study. The cost of treatment was calculated based on drug acquisition, drug administration, and initiation/monitoring costs. RESULTS: Golimumab resulted in an increase of 2.06 QALYs and additional cost of £39,770 compared with conventional therapy. Incremental cost per QALY gained was £19,280 for golimumab, which was lower than adalimumab (£19,737), etanercept (£20,089), and higher than certolizumab pegol (£18,710). Golimumab remained cost-effective throughout a range of sensitivity analyses where key assumptions were tested. CONCLUSIONS: From a Scottish perspective, golimumab was a cost-effective treatment for nr-axSpA compared with conventional therapy at a willingness-to-pay threshold of £30,000 per QALY. FUNDING: Merck & Co., Inc.

A discrete event simulation model of clinical and operating room efficiency outcomes of sugammadex versus neostigmine for neuromuscular block reversal in Canada.

BACKGROUND: The objective of this analysis is to explore potential impact on operating room (OR) efficiency and incidence of residual neuromuscular blockade (RNMB) with use of sugammadex (Bridion™, Merck & Co., Inc., Kenilworth, NJ USA) versus neostigmine for neuromuscular block reversal in Canada. METHODS: A discrete event simulation (DES) model was developed to compare ORs using either neostigmine or sugammadex for NMB reversal over one month. Selected inputs included OR procedure and turnover times, hospital policies for paid staff overtime and procedural cancellations due to OR time over-run, and reductions in RNMB and associated complications with sugammadex use. Trials show sugammadex's impact on OR time and RNMB varies by whether full neuromuscular recovery (train-of-four ratio ≥0.9) is verified prior to extubation in the OR. Scenarios were therefore evaluated reflecting varied assumptions for neuromuscular reversal practices. RESULTS: With use of moderate neuromuscular block, when full neuromuscular recovery is verified prior to extubation (93 procedures performed with sugammadex, 91 with neostigmine), use of sugammadex versus neostigmine avoided 2.4 procedural cancellations due to OR time over-run and 33.5 h of paid staff overtime, while saving an average of 62 min per OR day. No difference was observed between comparators for these endpoints in the scenario when full neuromuscular recovery was not verified prior to extubation, however, per procedure risk of RNMB at extubation was reduced from 60% to 4% (reflecting 51 cases prevented), with associated reductions in risks of hypoxemia (12 cases avoided) and upper airway obstruction (23 cases avoided). Sugammadex impact in reversing deep neuromuscular block was evaluated in an exploratory analysis. When it was hypothetically assumed that 30 min of OR time were saved per procedure, the number of paid hours of staff over-time dropped from 84.1 to 32.0, with a 93% reduction in the per patient risk of residual blockade. CONCLUSIONS: In clinical practice within Canada, for the majority of patients currently managed with moderate neuromuscular block, the principal impact of substituting sugammadex for neostigmine is likely to be a reduction in the risk of residual blockade and associated complications. For patients maintained at a deep level of block to the end of the procedure, sugammadex is likely to both enhance OR efficiency and reduce residual block complications.

EQ-5D™-derived utility values for different levels of migraine severity from a UK sample of migraineurs.

BACKGROUND: To estimate utility values for different levels of migraine pain severity from a United Kingdom (UK) sample of migraineurs. METHODS: One hundred and six migraineurs completed the EQ-5D to evaluate their health status for mild, moderate and severe levels of migraine pain severity for a recent migraine attack, and for current health defined as health status within seven days post-migraine attack. Statistical tests were used to evaluate differences in mean utility scores by migraine severity. RESULTS: Utility scores for each health state were significantly different from 1.0 (no problems on any EQ-5D dimension) (p < 0.0001) and one another (p < 0.0001). The lowest mean utility, - 0.20 (95% confidence interval [CI]: -0.27 - -0.13), was for severe migraine pain. The smallest difference in mean utility was between mild and moderate migraine pain (0.13) and the largest difference in mean utility was between current health (without migraine) and severe migraine pain (1.07). CONCLUSIONS: Results indicate that all levels of migraine pain are associated with significantly reduced utility values. As severity worsened, utility decreased and severe migraine pain was considered a health state worse than death. Results can be used in cost-utility models examining the relative economic value of therapeutic strategies for migraine in the UK.

Costs associated with outpatient, emergency room and inpatient care for migraine in the USA.

BACKGROUND: Data on the average US costs of an outpatient visit, emergency room (ER) visit or hospitalization for migraine are scant, with the most recent available values based on healthcare charges reported from 1994 data. METHODS: We estimated healthcare costs associated with outpatient and ER visits and inpatient hospitalizations related to migraine retrospectively obtained from the 2007 Medstat MarketScan Commercial Claims & Encounters database. Tabulated costs reflected payments from insurers, patients and other sources. All costs were adjusted to 2010 US dollars. RESULTS: The estimated mean cost (95% CI) for migraine-related care per outpatient visit (N = 680,946) was $139.88 ($139.35-140.41); per ER visit (N = 88,128) was $775.09 ($768.10-782.09); and per inpatient hospitalization (N = 5516) was $7317.07 ($7134.96-7499.17). The most frequently coded procedures at outpatient and ER visits were subcutaneous or intra-muscular injection, and for hospitalizations was computed tomography. Estimated annual US healthcare costs in 2010 for migraine associated with: outpatient visits were $3.2 billion, ER visits were $700 million, and inpatient hospitalizations were $375 million. CONCLUSIONS: Direct healthcare costs associated with patient visits and hospitalizations for migraine headaches have increased since previously published estimates. Further research is needed to understand the current overall healthcare cost burden per patient and within the US population.

Distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia and invasive cervical cancer in Canada.

Infection with high-risk human papillomavirus (HPV) causes cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC). The distribution of HPV types in cervical diseases has been previously described in small studies for Canadian women. The prevalence of 36 HPV genotypes in 873 women with CIN and 252 women with ICC was assessed on cervical exfoliated cells analyzed with the Linear Array (Roche Molecular System). HPV16 was the most common genotype in CIN and ICC. The seven most frequent genotypes in order of decreasing frequency were HPV16, 51, 52, 31, 39, 18, and 56 in women with CIN1, HPV16, 52, 31, 18, 51, 39, and 33 in women with CIN2, HPV16, 31, 18, 52, 39, 33, and 58 in women with CIN3, and HPV16, 18, 45, 33, 31, 39, and 53 in women with ICC. HPV18 was detected more frequently in adenocarcinoma than squamous cell carcinoma (P = 0.013). Adjustment for multiple type infections resulted in a lower percentage attribution in CIN of HPV types other than 16 or 18. The proportion of samples containing at least one oncogenic type was greater in CIN2 (98.4%) or CIN3 (100%) than in CIN1 (80.1%; P < 0.001 for each comparison). Multiple type infections were demonstrated in 51 (20.2%) of 252 ICC in contrast to 146 (61.3%) of 238 women with CIN3 (P < 0.001). Adjusting for multiple HPV types, HPV16 accounted for 52.1% and HPV18 for 18.1% of ICCs, for a total of 70.2%. Current HPV vaccines should protect against HPV types responsible for 70% of ICCs in Canadian women.

Incident cervical HPV infections in young women: transition probabilities for CIN and infection clearance.

BACKGROUND: We describe transition probabilities for incident human papillomavirus (HPV) 16/18/31/33/35/45/52/58/59 infections and cervical intraepithelial neoplasia (CIN) 1 lesions. METHODS: Women ages 16 to 23 years underwent cytology and cervical swab PCR testing for HPV at approximately 6-month intervals for up to 4 years in the placebo arm of an HPV vaccine trial. The cumulative proportion of incident HPV infections with diagnosed CIN, clearing (infection undetectable), or persisting without CIN, were estimated. RESULTS: Most incident infections cleared, without detection of CIN, ranging at 36 months from 66.9% for HPV31 to 91.1% for HPV59. There was little variation in the 36-month proportion of incident HPV16, 18, and 31 infections followed by a CIN1 lesion positive for the relevant HPV type (range 16.7%-18.6%), with lower risks for HPV59 (6.4%) and HPV33 (2.9%). Thirty-six-month transition probabilities for CIN2 ranged across types from 2.2% to 9.1%; however, the number of events was generally too small for statistically significant differences to be seen across types for this endpoint, or CIN3. CONCLUSIONS: Some incident HPV types appear more likely to result in diagnosed CIN1 than others. The relative predominance of HPV16, vis-à-vis some other high-risk HPV types (e.g., HPV33) in prevalent CIN2/3, appears more directly associated with relatively greater frequency of incident HPV16 infections within the population, than a higher risk of infection progression to CIN2/3. IMPACT: Nearly all incident HPV infections either manifest as detectable CIN or become undetectable within 36 months. Some HPV types (e.g., 16 and 33) appear to have similar risk of CIN2/3 despite widely varied incidence.

EuroQol (EQ-5D) health utility scores for patients with migraine.

PURPOSE: Previous studies have reported health utilities for migraine patients as generally measured between migraine attacks, but health utility data for within a migraine attack are unavailable. We evaluated within-attack health utilities among acute migraine patients experiencing different grades of headache severity. METHODS: We examined data for 330 20-65-year-old adults, in good physical health, who had 1-6 moderate/severe migraine attacks per month in the 2 months prior to the screening visit. Data were collected from a multicenter, double-blind study of a treatment for acute migraine in the United States. The EQ-5D system was used to measure generic health status at baseline and 24 h post-treatment within an acute migraine attack, and patients were also asked to rate their pain level at these time points (no, mild, moderate, or severe pain). The D1 time-trade-off scoring algorithm for the U.S. population was applied. Confidence intervals were estimated by bootstrap methods. RESULTS: The study population was 88% women and 78% white ethnicity, with 60% of subjects over age 40. The disutility of mild migraine pain was estimated to be 0.140 (95% CI: 0.0848, 0.1940), with a disutility for moderate migraine pain of 0.186 (95% CI: 0.1645, 0.2053) and for severe migraine pain of 0.493 (95% CI: 0.4100, 0.5654). CONCLUSIONS: Within-attack disutilities estimated for migraine in this study are much greater than those reported for migraine when evaluated as a chronic health condition (e.g., valuations collected at random time points). These data can be of value in adapting results from clinical trials of migraine interventions to cost-utility policy analyses.

Incidence, duration, and reappearance of type-specific cervical human papillomavirus infections in young women.

BACKGROUND: We describe the incidence and duration of cervical human papillomavirus (HPV) infection episodes along with the risk of infection reappearance following a period of nondetection. METHODS: Women (1,788) ages 16 to 23 years underwent cytologic testing and PCR-based testing of cervical swab samples for HPV DNA (HPV-16/18/31/33/35/45/52/58/59) at approximately 6-month intervals for up to 4 years in the context of a phase 3 clinical trial (placebo arm). HPV type-specific incidence rates were estimated per 100 person-years. Duration of type-specific cervical infection episodes and risk of reappearance following a period of nondetection were estimated using Kaplan-Meier methods. RESULTS: HPV-16 exhibited the highest (5.9), and HPV-35 and HPV-33 exhibited the lowest (1.0) incidence rates per 100 person-years. Mean cervical infection durations ranged from 13 months for HPV-59 to 20 months for HPV-16 and 58 (with ongoing infections censored at the time of treatment, if done). The risk of cervical infection reappearance within approximately 3 years following a period of nondetection ranged from 0% to 16% across HPV types, with a mean of 8%. Limited evidence was found for a role of false-positive HPV tests, missed infections that were above the threshold for detection, or new acquisition of infection in accounting for patterns of infection reappearance. CONCLUSIONS: Incidence of high-risk cervical infection was observed to vary considerably more across HPV types than infection duration. A nontrivial proportion of women exhibited infection reappearance following a period of nondetection, with a potential explanation for many such events observed within this analysis being a return to detectable levels of a previously acquired infection. IMPACT: The risk of HPV infection reappearance following a period of nondetection has not been previously reported for individual HPV types, and this study finds that a nontrivial proportion of infected women exhibit reappearances. Future studies could ascertain subject-level factors that potentially modify the risk of infection reappearance.