Objective Our objective was to examine perspective and costing approaches used in cost-effectiveness analyses (CEAs) and the distribution of reported incremental cost-effectiveness ratios (ICERs). Methods We analyzed the Tufts Medical Center’s CEA and Global Health CEA registries, containing 6907 cost-per-quality-adjusted-life-year (QALY) and 698 cost-per-disability-adjusted-life-year (DALY) studies published through 2018. We examined how often published CEAs included non-health consequences and their impact on ICERs. We also reviewed 45 country-specific guidelines to examine recommended analytic perspectives. Results Study authors often mis-specified or did not clearly state the perspective used. After re-classification by registry reviewers, a healthcare sector or payer perspective was most prevalent (74%). CEAs rarely included unrelated medical costs and impacts on non-healthcare sectors. The most common non-health consequence included was productivity loss in the cost-per-QALY studies (12%) and patient transportation in the cost-per-DALY studies (21%). Of 19,946 cost-per-QALY ratios, the median ICER was $US26,000/QALY (interquartile range [IQR] 2900–110,000), and 18% were cost saving and QALY increasing. Of 5572 cost-per-DALY ratios, the median ICER was $US430/DALY (IQR 67–3400), and 8% were cost saving and DALY averting. Based on 16 cost-per-QALY studies (2017–2018) reporting 68 ICERs from both the healthcare sector and societal perspectives, the median ICER from a societal perspective ($US22,710/QALY [IQR 11,991–49,603]) was more favorable than from a healthcare sector perspective ($US30,402/QALY [IQR 10,486–77,179]). Most governmental guidelines (67%) recommended either a healthcare sector or a payer perspective. Conclusion Researchers should justify and be transparent about their choice of perspective and costing approaches. The use of the impact inventory and reporting of disaggregate outcomes can reduce inconsistencies and confusion.

BACKGROUND: Orphan drugs offer important therapeutic options to patients suffering from rare conditions, but are typically considerably more expensive than nonorphan drugs, leading to questions about their costeffectiveness. OBJECTIVE: To compare the value of orphan and nonorphan drugs approved by the FDA from 1999 through 2015. DESIGN: We searched the PubMed database to identify estimates of incremental health gains (measured in quality-adjusted life-years, or QALYs) and incremental costs that were associated with orphan and non-orphan drugs compared with preexisting care. We excluded pharmaceutical industry-funded studies from the dataset. When a drug was approved for multiple indications, we considered each drug-indication pair separately. We then compared incremental QALY gains, incremental costs, and incremental cost-effectiveness ratios for orphan and non-orphan drugs using the Mann-Whitney U (MWU) test (to compare median values of the different distributions) and the Kolmogorov-Smirnov (KS) test (to compare the shape of different distributions). RESULTS: We identified estimates for 49 orphan drugindication pairs, and for 169 non-orphan drug-indication pairs. We found that orphan drug-indication pairs offered larger median incremental health gains than non-orphan drug-indication pairs (0.25 vs. 0.05 QALYs; MWU p = 0.0093, KS p = 0.02), but were associated with substantially higher costs

The article Perspective and Costing in Cost-Effectiveness Analysis.

Objectives: Combinations of existing therapies are increasingly being developed and marketed across many indications. Whilst they promise substantial clinical benefits, dual-branded therapies may have substantial financial impacts. Obtaining positive HTA approvals and public reimbursement may be a major challenge, which may be amplified if each monotherapy is marketed by a different company. We evaluated whether combination therapies developed by one manufacturer had faster and/or better outcomes than those where each constituent was developed by a separate manufacturer and whether this varied by different HTA archetypes. Methods: ECapproved combination products, comprising at least one on-patent therapy marketed under a separate brand were identified (01/01/2015-31/12/2018) and the number of manufacturers identified. Corresponding HTA reports were identified from G-BA, HAS, SMC, and NCPE websites and relevant data extracted. Results: 114 HTA assessments across 34 combination products:indications were identified (same manufacturer: 58 assessments, two manufacturers: 56 assessments). For clinicaleffectiveness HTA bodies (G-BA and HAS), the rates of positive recommendations (defined as: any additional benefit or ASMR I-III) was similar for combination therapies developed by one vs. two manufacturers (32% vs. 40%). Whereas, for costeffectiveness HTA bodies (NICE, SMC, and NCPE), combination therapies developed by one manufacturer received numerically higher rates of positive recommendations (defined as: "full or optimized/conditional") than those involving two manufacturers (80% vs. 58%). However, there were no corresponding differences in the median time from EC-approval to positive recommendation (5.5 vs. 5.0 months). Conclusions: HTA bodies assessing cost-effectiveness were more likely to issue positive recommendations for dual-branded treatments if each constituent monotherapy was marketed by one company versus two companies. A single company may have more flexibility in its price setting, facilitating higher HTA recommendation rates. Although time to positive HTA decisions were similar, this may not reflect time to launch in some jurisdictions, due to additional time required for pricing negotiations.

Background: The Institute for Clinical and Economic Review (ICER) has gained prominance through its work conducting health technology assessments of pharmaceuticals in the United States. Objective: To understand the influence of industry comments on pharmaceutical value assessments conducted by ICER. Methods: We reviewed 15 ICER reports issued from 2017 through 2019. We quantified ICER's revisions to its cost-effectiveness analysis (CEA) estimates between release of its draft and revised evidence reports and whether ratios shifted across ICERspecified categories of high, intermediate, or low value. We also reviewed industry-submitted comments recommending revision to ICER's CEAs, noting ICER's response as no change, text revised, assumption(s) revised, or conclusion revised. We evaluated each comment in terms of clarity, whether it offered an alternative to ICER's approach, and whether it characterized the expected impact of revision on ICER's analysis. Results: We identified 53 ICER-reported ratios. Of these, 45 (84.9%) changed between the draft and revised report, but 26 changes (57.8%) were small (,10%). Six ratios shifted across value categories. We identified 256 industry comments recommending that ICER revise its CEA. Of these, 159 (62%) lacked clarity, 145 (57%) offered no alternative, and 243 (95%) did not characterize their impact on ICER's estimated ratio. Ninety-one comments (35.5%) caused ICER to revise its assumptions, but only 5 (2.0%) caused ICER to revise its conclusions. Four of these 5 comments characterized their impact on ICER's findings. Conclusions: Changes in ICER's estimates of cost-effectiveness between its draft and revised evidence reports are generally modest. Greater precision in industry comments could increase the influence of industry critiques, thus enhancing the dialogue around pharmaceutical value.