BACKGROUND:Health technology assessment (HTA) involves a formal review of the clinical, economic, and societal implications of health technologies. Internationally, HTA supports decisions regarding access to novel therapeutics. However, the role of HTA in the decision-making processes of US-based health care payers remains unclear. OBJECTIVE:To assess how frequently US commercial health plans reference HTAs in their specialty drug coverage policies. METHODS:Using the Tufts Medical Center Specialty Drug Evidence and Coverage database, we reviewed the evidence cited in the publicly available specialty drug coverage policies of 17 US commercial health plans. We assessed the frequency of HTA citations and characterized them by (1) country of origin, (2) publishing organization, (3) whether it addressed a treatment's cost-effectiveness, (4) disease category addressed, and (5) whether it assessed orphan or nonorphan treatments. RESULTS:HTAs accounted for 450 of the 14,033 citations in our analysis (3.2%), with the frequency of HTA citations varying across health plans (0.1% to 7.4% of cited evidence). Ex-US HTAs were cited more frequently than US-based HTAs (65.3%). However, a single health plan accounted for the majority of HTA citations (57.1%) and ex-US citations (76.2%). Most cited HTAs included cost-effectiveness assessments (78.7%). The 3 disease categories for which plans most often cited HTAs were neurological disorders (24.8%), musculoskeletal disorders (21.5%), and cancers (14.6%). Health plans cited HTAs for nonorphan drugs more often than for orphan drugs (59.4%). CONCLUSIONS:HTAs represented a small portion of the evidence cited by health plans in specialty drug coverage decisions, with significant variation in citation frequency across plans. Plans cited both US and ex-US HTAs, and most cited HTAs included a cost-effectiveness assessment. These findings suggest that health plans may consider the information provided by HTAs when formulating coverage policies.

The aim of this study was to examine the association between characteristics of novel drugs and incremental health gains relative to standard of care, in terms of quality-adjusted life-years (QALYs). This study’s unit of analysis is the drug–indication pair. For pairs approved by the US FDA from 1999 to 2018, we quantified incremental health gains using QALYs from the published literature and characterized each pair’s novelty in terms of a series of six binary (yes/no) characteristics of novel drugs given special consideration by Health Technology Assessment agencies: Novel mechanism of action, Indicated for a rare disease, Indicated for a pediatric population, Treats a serious condition, Offers meaningful improvement over available therapies, and Potential to address unmet clinical needs. We analyzed measures of bivariate association (Mann-Whitney U and Kolmogorov-Smirnov tests) and multivariable regression, accounting for the influence of multiple novelty characteristics simultaneously. Our sample of 146 drugs represents 21

The Inflation Reduction Act of 2022 requires that Medicare negotiate a Maximum Fair Price for selected small-molecule drugs nine years after their Food and Drug Administration (FDA) approval and thirteen years postapproval for selected biologics. The discrepancy between these time frames raises questions about the relative value of small-molecule drugs versus biologics. We compared the incremental quality-adjusted life-year (QALY) gains, incremental costs, and incremental cost-effectiveness ratios (ICERs) of small-molecule drugs and biologics approved by the FDA during the period 1999-2018. We used the Mann-Whitney U test (to compare medians) and Kolmogorov-Smirnov test (to compare the distributions). We found that small-molecule drugs and biologics offer similar magnitudes of incremental QALY gains (0.08 versus 0.10). Small-molecule drugs tend to be associated with lower additional costs ($4,738 versus $16,020) and more favorable costeffectiveness ($108,314 per QALY versus $228,286 per QALY). Creating parity regarding time to Medicare price negotiation may be appropriate.

BACKGROUND:Health plan coverage is central to patient access to care, especially for rare, chronic diseases. For specialty drugs, coverage varies, resulting in barriers to access. Pulmonary arterial hypertension (PAH) is a rare, progressive, and fatal disease. Guidelines suggest starting or rapidly escalating to combination therapy with drugs of differing classes (phosphodiesterase 5 inhibitors [PDE5is], soluble guanylate cyclase stimulators [sGC stimulators], endothelin receptor antagonists [ERAs], and prostacyclin pathway agents [PPAs]). OBJECTIVE:To assess the variation in commercial health plan coverage for PAH treatments and how coverage has evolved. To examine the frequency of coverage updates and evidence cited in plan policies. METHODS:We used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes publicly available specialty drug coverage policies. Overall, and at the drug and treatment class level, we identified plan-imposed coverage restrictions beyond the drug's US Food and Drug Administration label, including step therapy protocols, clinical restrictions (eg, disease severity), and prescriber specialty requirements. We analyzed variation in coverage restrictiveness and how coverage has changed over time. We determined how often plans update their policies. Finally, we categorized the cited evidence into 6 different types. RESULTS:Results reflected plan coverage policies for 13 PAH drugs active between August 2017 and August 2022 and issued by 17 large US commercial health plans, representing 70% of covered lives. Coverage restrictions varied mainly by step therapy protocols and prescriber restrictions. Seven plans had step therapy protocols for most drugs, 9 for at least one drug, and 1 had none. Ten plans required specialist (cardiologist or pulmonologist) prescribing for at least one drug, and 7 did not. Coverage restrictions increased over time: the proportion of policies with at least 1 restriction increased from 38% to 73%, and the proportion with step therapy protocols increased from 29% to 46%, with generics as the most common step. The proportion of policies with step therapy protocols increased for every therapy class with generic availability: 18% to 59% for ERAs, 33% to 77% for PDE5is, and 33% to 43% for PPAs. The proportion of policies with prescriber requirements increased from 24% to 48%. Plans updated their policies 58% of the time annually and most often cited the 2019 CHEST clinical guidelines, followed by randomized controlled trials. CONCLUSIONS:Plan use of coverage restrictions for PAH therapies increased over time and varied across both drugs and plans. Inconsistency among health plans may complicate patient access and reduce the proportion who can persist on PAH treatments.

Objectives: To examine ultraorphan drugs in terms of incremental health, costs, and costeffectiveness compared with more prevalent disease drugs. Methods: We identified Food and Drug Administration drug approvals from 1999 to 2019. For drugs approved for multiple indications, we considered each drug-indication pair separately. Utilizing Food and Drug Administration's orphan drug designation and US disease prevalence, we categorized drug-indication pairs as: ultraorphan (<10 000 patients), "other" orphan (>= 10 000 and <200 000), and nonorphan (>= 200 000). We searched the PubMed database for costeffectiveness analyses and comparative effectiveness studies. We excluded manufacturer-funded studies. We extracted estimates of incremental health gains in terms of quality-adjusted life- years (QALYs) and incremental costs associated with drug-indication pairs compared with the standard of care at the time of their approval. We compared QALY gains, added costs, and incremental cost-effectiveness ratios (ICERs) using the Kruskal-Wallis, Mann-Whitney U (MWU), and Kolmogorov-Smirnov (KS) tests. Results: Median incremental QALYs, costs, and ICERs differed across nonorphan, "other" orphan, and ultraorphan categories (Kruskal-Wallis P < .01). Compared with nonorphan drugs, ultraorphan drugs had larger QALY gains (0.700 vs 0.050, MWU P < .01, KS P < .01), larger costs ($172 231 vs $3360, MWU P <.01, KS P < .01), and larger ICERs ($1 216 184/QALY vs $114 061/QALY, MWU P < .01, KS P <.01). Compared with "other" orphan drugs, ultraorphan drugs had larger QALY gains (0.700 vs 0.310, MWU P =.65, KS P =.32), larger costs ($172 231 vs $69 308, MWU P = .03, KS P = .03), and larger ICERs ($1 216 184/QALY vs $223 472/QALY, MWU P <.01, KS P <.01). Conclusions: Novel ultraorphan drugs typically offer larger incremental health gains than drugs for more prevalent diseases, but because of their substantial added costs, are typically less costeffective.

BACKGROUND: The Institute for Clinical and Economic Review (ICER) has emerged in a visible role in US health care. However, it is unclear to what extent US commercial health plans use ICER value assessments in their specialty drug coverage decisions.OBJECTIVE: To evaluate the relationship between ICER's reported cost-effectiveness ratios (CERs) and coverage restrictiveness. Also, to examine the frequency with which plans have cited ICER in their coverage policies and to investigate how frequently health plans adjusted their drug coverage criteria in the 12 months after ICER's assessments.METHODS: We analyzed the Tufts Medical Center Specialty Drug Evidence and Coverage Database, which includes specialty drug coverage decisions issued by 17 large US commercial health plans. For ICER-assessed drugs, we recorded ICER's estimated CERs in the form of cost per quality-adjusted life-year (QALY) gained. First, we used multivariate logistic regression to examine the association between ICER's reported CERs and plan coverage restrictiveness, when controlling for other factors that were likely to affect decision-making. Next, we examined how often plans cited ICER's assessments in coverage decisions issued in years 2017-2020. Lastly, we examined whether plans added or removed coverage restrictions (eg, patient subgroup restrictions or step therapy protocols) in the 12 months following ICER's assessment.RESULTS: Plans tended to cover drugs with higher (less favorable) CERs more restrictively than drugs with CERs less than $100,000 per QALY: odds ratio (OR) = 4.48 if $100,000-$175,000 per QALY; OR = 2.00 if $175,000-$500,000 per QALY; and OR = 2.10 if $500,000 or more per QALY (all P < 0.01). Plans cited ICER in 0.8% (5/622) of coverage policies in 2017, 0.6% (5/833) in 2018, 1.7% (19/1,139) in 2019, and 2.4% (33/1,406) in 2020. For drugs with CERs less than $175,000 per QALY, plans adjusted coverage in 37% of cases: added restrictions in 20%, removed restrictions in 15%, and added one restriction but removed another in 2%. For drugs with CERs of $175,000 or more, plans changed coverage criteria in 29% of cases: added restrictions in 21%, removed restrictions in 5%, and added one restriction but removed another in 4%.CONCLUSIONS: We found that when controlling for other factors, health plans' specialty drug coverage decisions were associated with ICER's estimated CERs. Plans infrequently cited ICER value assessments. We did not observe a trend for plans more often narrowing coverage criteria for drugs with CERs $175,000 or more compared with drugs with CERs less than $175,000.

Health plans guide their enrollees’ access to specialty drugs through coverage policies. We examined a set of health plan policies to determine if they have become more or less stringent over time. We did so by comparing the consistency of policies with Food and Drug Administration (FDA) label indications. We considered coverage policies for the same 187 specialty drugs issued by 17 large US commercial health plans from 2017 through 2021. Overall, the proportion of policies that were consistent with the FDA label declined from 57.1% in 2017 to 45.1% in 2021; the proportion of policies that were more restrictive than the FDA label increased from 39.5% to 51.7%. The proportion of policies excluding drug coverage remained approximately constant (3.4% in 2017; 3.2% in 2021). Trends in coverage restrictiveness varied across plans. For 13 plans, the proportion of policies with restrictions increased over time, while for 4 plans it declined.

This cohort study assesses rates at which orphan drugs approved by the US Food and Drug Administration were also approved for supplemental (follow-on) indications.

OBJECTIVES:First, to examine 7 large Medicare Advantage (MA) plans' use of step therapy. Second, to compare step therapy that health plans imposed in their MA and commercial (employer) drug coverage policies.STUDY DESIGN:Database analysis.METHODS:Using data from the Tufts Medical Center Specialty Drug Evidence and Coverage Database, we evaluated 7 large MA plans' use of step therapy in their Part B drug coverage policies. First, we determined the frequency with which different MA plans applied step therapy. Second, we determined the frequency with which plans imposed step therapy protocols across International Classification of Diseases, Tenth Revision, Clinical Modification categories. Third, we compared each step therapy protocol against each drug's corresponding FDA label indication. Fourth, we examined the consistency of step therapy protocols between the same insurer's MA and commercial lines of business.RESULTS:The frequency with which the included MA plans imposed step therapy ranged from 26.1% to 63.7%. Step therapy was most common for dermatology conditions (90.2%) and least common for oncology conditions (28.6%). On average, MA plans' step therapy requirements were consistent with the drug's FDA label indication 29.0% of the time. MA plans' and commercial plans' use of step therapy differed for the same drug-indication pairs 46.1% of the time.CONCLUSIONS:MA plans vary in the frequency with which they impose step therapy protocols in their Part B drug coverage policies. Moreover, insurers often impose different step therapy protocols in their MA plan and commercial plan offerings. Differences in plans' step therapy requirements may result in variability in patients' access to care within MA.

BACKGROUND:Efforts to understand how treatments affect patients and society have broadened the criteria that health technology assessment (HTA) organizations apply to value assessments. We examined whether HTA agencies in eight countries consider treatment novelty in methods and deliberations.METHODS:We defined a novel pharmaceutical product to be one that offers a new approach to treatment (e.g., new mechanism of action), addresses an unmet need (e.g., targets a rare condition without effective treatments), or has a broader impact beyond what is typically measured in an HTA. We reviewed peer-reviewed publications and technical guidance materials from HTA organizations in Australia, Canada, England, France, The Netherlands, Norway, Sweden, and the United States (US). In addition, we explored how HTA organizations integrated novelty considerations into deliberations and recommendations related to two newer therapies-voretigene neparvovec for an inherited retinal disorder and ocrelizumab for multiple sclerosis.RESULTS:None of the HTA organizations acknowledge treatment novelty as an explicit value criterion in their assessments of pharmaceutical products. However, drugs that have novel characteristics are given special consideration, particularly when they address an unmet need. Several organizations document a willingness to expend more resources and accept greater evidence uncertainty for such treatments. Qualitative deliberations about the additional unquantified potential benefits of treatment may also influence HTA recommendations.CONCLUSION:Major HTA organizations do not recognize novelty as an explicit value criterion, although drugs with novel characteristics may receive special consideration. There is an opportunity for organizations to codify their approach to evaluating novelty in value assessment.

To evaluate how a set of large US commercial health plans cover specialty drugs the Institute for Clinical and Economic Review (ICER) determined to be high value (have favorable cost-effectiveness ratios). We examine the relationship between a drug’s cost-effectiveness and the restrictiveness of health plan coverage. We used the Tufts Medical Center Specialty Drug Evidence and Coverage (SPEC) Database, which includes specialty drug coverage policies issued by 17 large US commercial health plans. We identified coverage policies for specialty drugs that ICER determined to be high value (i.e., incremental cost-effectiveness ratio ≤$175,000 per QALY). We grouped drugs into five cost-effectiveness categories: Dominant (more effective and less expensive than study comparator); <$50,000 per QALY; $50,000- $100,000 per QALY; $100,000- $150,000 per QALY; and, $150,000-$175,000 per QALY. Next, we determined whether the health plan imposed any coverage restrictions (e.g., patient subgroup restrictions; step therapy protocols) in their coverage decisions. Data were current as of August 2020. Health plans imposed restrictions in 58% (217/371) of coverage policies for drugs ICER determined to be high value; however, coverage restrictiveness varied by cost-effectiveness category. Health plans tended to more often impose coverage restrictions on drugs with less favorable cost-effectiveness ratios. Plans imposed restrictions in 29% (12/41) of coverage policies for dominant drugs, 39% (29/74) of policies for drugs with ratios less than $50,000 per QALY, 32% (13/41) of policies for drugs with ratios in the range $50,000-$100,000 per QALY, 68% (112/164) of policies for drugs with ratios in the range $100,000-$150,000 per QALY, and 100% (51/51) of policies for drugs with ratios in the range $150,000-$175,000 per QALY. For drugs ICER deemed high value, the included health plans imposed restrictions in the majority of their coverage policies. However, plans less often imposed coverage restrictions on drugs with more favorable cost-effectiveness ratios.

BACKGROUND: Health plans guide enrollees' access to specialty drugs through coverage policies. Practice guidelines recommend that the evidence supporting drug coverage policies should be comprehensive and routinely updated to reflect evidence-based medicine. OBJECTIVE: To examine the frequency with which health plans update their coverage criteria and supporting evidence and to determine the pattern with which plans cited relevant literature in their coverage policies. METHODS: Coverage policies from 17 large US commercial health plans were retrieved from the Tufts Medical Center Specialty Drug Evidence and Coverage database for August 2017 and August 2019. We identified drug-indication pairs (eg, infliximab for rheumatoid arthritis) for which plans had issued coverage policies in August 2017 and August 2019. We examined the frequency with which plans reissued these policies (ie, issued a new coverage document) between these 2 time points and the frequency with which plans altered coverage criteria or updated the cited evidence. A random sample of 20 drug-indication pairs was chosen to determine the comprehensiveness of cited evidence from the Specialty Drug Evidence and Coverage database. For each pair, a systematic literature search was conducted to identify relevant clinical and economic studies. A comparison of the systematic literature search with the evidence cited in each drug-indication pair's coverage policy was conducted to determine the comprehensive nature of each coverage policy's evidence. RESULTS: We identified 4,597 instances of plans issuing a coverage policy for the same drug-indication pair in both August 2017 and August 2019. Of those 4,597 instances, plans reissued an updated coverage document in 4,468 (97%). Fifteen percent of reissued policies revised both their coverage criteria and the evidence cited, 2% only their coverage criteria, 69% only the cited evidence, and 14% made no change. A total of 2,760 literature documents were identified relevant to at least one of the 20 drug-indication pairs, of which at least one plan cited 146 of these documents at least once (5.3%). Plans cited health technology assessments, randomized controlled trials (RCTs), systematic reviews/meta-analyses, and clinical guidelines most comprehensively. CONCLUSIONS: Health plans reissued most of their specialty drug coverage policies over a 2-year period. When plans revised their drug coverage criteria, they also tended to revise the evidence cited in their coverage polices. Of all the evidence found in our systematic review, plans more comprehensively cite health technology assessments, RCTs, and systematic reviews/meta-analyses.

BACKGROUND AND OBJECTIVES:Orphan drugs' high prices raise questions about whether their costs are worth their benefits. We examined the association between an orphan drug's cost-effectiveness and health plan coverage restrictiveness. METHODS:We analyzed a dataset of US commercial health plan coverage decisions (information current as of 2019) for orphan drugs (n = 3298). We used multi-level random-effect logistic regression to examine the association between orphan drug cost-effectiveness and coverage restrictiveness. We identified cost-effectiveness estimates from the Tufts Medical Center Cost-Effectiveness Analysis Registry, and from the Institute for Clinical and Economic Review's value assessments. We included only cost-effectiveness studies not funded by product manufacturers. We included the following independent variables: cancer indication, availability of alternatives, pediatric population, number of years since US Food and Drug Administration (FDA) approval, disease prevalence, annual cost, additional non-orphan indication, safety, and inclusion in a FDA expedited review program. RESULTS:Plans restricted drug coverage in 29.7% (n = 981) of decisions. Plans were more likely to restrict drugs with incremental cost-effectiveness ratios of $50,000-$175,000 per quality-adjusted life-year [QALY] (odds ratio = 1.855, p < 0.05), $175,000-$500,000 per QALY (odds ratio = 1.859, p < 0.05), and >$500,000 per QALY/dominated (odds ratio = 2.032, p < 0.01), compared to drugs with incremental cost-effectiveness ratios <$50,000 per QALY. Plans more often restricted drugs with non-cancer indications, having available alternatives, with more recent approval, in an FDA expedited review program, and for which the FDA additionally issued approval for a non-orphan disease. Plans more often restricted drugs with higher annual costs, and drugs indicated for higher prevalence diseases. All findings p < 0.05. CONCLUSIONS:Among other factors, an orphan drug's cost-effectiveness was associated with health plan drug coverage restrictiveness.

PURPOSE:To examine the RWE U.S. commercial health plans cite in their specialty drug coverage decisions.METHODS:We used the Tufts Medical Center Specialty Drug Evidence and Coverage Database to identify specialty drug coverage decisions (n = 7267) issued by 17 large commercial health plans. We categorized the clinical evidence plans cited in these coverage decisions (n = 5227) as randomized controlled trials (RCTs), RWE studies, and other clinical studies (studies other than RCT or RWE study). We categorized RWE studies with respect to study type, for example, case series, studies based on medical records, and so on. We compared the frequency that plans cited different categories of RWE, cited RWE for different diseases, and cited RWE for drugs on the market for different time periods.RESULTS:RWE comprised 16% of cited clinical studies. Health plans cited RWE with different frequencies (5%-31% of the cited clinical evidence). Overall, plans cited RWE categorized as medical records most often (26% of cited RWE studies). Plans varied in the frequency they cited different RWE categories. Plans most frequently cited RWE for gastroenterological diseases (35% of clinical study citations) and least frequently for respiratory diseases (11% of clinical study citations). Plans cited RWE more for drugs that have long been on the market.CONCLUSIONS:Health plans varied with respect to the number and types of RWE studies they cited in their specialty drug coverage decisions. Plans cited RWE more often for some diseases than others, and cited more RWE for older drugs.