Use of Efficiency Frontiers to Align Prices and Clinical Benefits of Biologic Therapies for Plaque Psoriasis.

Importance: The US lacks a systematic approach for aligning drug prices with clinical benefit, and traditional cost-effectiveness analysis (CEA) faces political obstacles. The efficiency frontier (EF) method offers policymakers an alternative approach. Objective: To assess how the EF approach could align prices and clinical benefits of biologic medications for plaque psoriasis and estimate price reductions in the US vs 4 peer countries: Australia, Canada, France, and Germany. Design and Setting: This health economic evaluation used the EF approach to compare the prices and clinical benefits of 11 biologics and 2 biosimilars for plaque psoriasis in the US, Australia, Canada, France, and Germany. Data were collected from February to March 2023 and analyzed from March to June 2023. Main Outcome Measures: EFs were constructed based on each biologic's efficacy, measured using the Psoriasis Area and Severity Index (PASI) 90 response rate, and annual treatment cost as of January 2023; US costs were net of estimated manufacturer rebates. Prices based on the EF were compared with traditional CEA-based prices calculated by the Institute for Clinical and Economic Review at a threshold of $150 000 per quality-adjusted life-year gained. Results: Among 13 biologics, PASI 90 response rates ranged from 17.9% (etanercept) to 71.6% (risankizumab); US net annual treatment costs ranged from $1664 (infliximab-dyyb) to $79 277 (risankizumab). The median (IQR) net annual treatment cost was higher in the US ($34 965 [$20 493-$48 942]) than prerebate costs in Australia ($9179 [$6691-$12 688]), Canada ($15 556 [$13 017-$16 112]), France ($9478 [$6637-$11 678]), and Germany ($13 829 [$13 231-$15 837]). The US EF included infliximab-dyyb (PASI 90: 57.4%; annual cost: $1664), ixekizumab (PASI 90: 70.8%; annual cost: $33 004), and risankizumab (PASI 90: 71.6%; annual cost: $79 277). US prices for psoriasis biologics would need to be reduced by a median (IQR) of 71% (31%-95%) to align with those estimated using the EF; the same approach would yield smaller price reductions in Canada (41% [6%-57%]), Australia (36% [0%-65%]), France (19% [0%-67%]), and Germany (11% [8%-26%]). Except for risankizumab, the EF-based prices were lower than the prices based on traditional CEA. Conclusions and Relevance: This economic evaluation showed that for plaque psoriasis biologics, using an EF approach to negotiate prices could lead to substantial price reductions and better align prices with clinical benefits. US policymakers might consider using EFs to achieve prices commensurate with comparative clinical benefits, particularly for drug classes with multiple therapeutic alternatives for which differences can be adequately summarized by a single outcome measurement.

Mandatory disclaimers on dietary supplements do not reliably communicate the intended issues.

Some efforts by the government to regulate the promotional statements of pharmaceutical manufacturers have recently been found unconstitutional under the First Amendment, which has been interpreted to protect commercial as well as personal speech. As an alternative means of protecting patients from unreliable marketing claims, courts have proposed that the Food and Drug Administration could add disclaimers to promotional messages that discuss off-label, or unapproved, uses. We conducted a systematic review of studies of the disclaimers currently required for dietary supplements, to assess how well disclaimers inform consumers' health choices. A few small studies reported a modest impact of disclaimers on consumers' attitudes about dietary supplements, but larger and more rigorous studies generally revealed that many consumers were unaware of a disclaimer or reported that it did not affect their perceptions of a product. The available evidence indicates that replacing government restrictions on pharmaceutical marketing with potentially ineffective disclaimers will be an inadequate way of informing patients about the efficacy and safety of drugs, and it risks returning the United States to a previous era when inappropriate marketing claims about prescription drugs proliferated and contributed to the inappropriate use of those products.

Patterns of initiation of oral anticoagulants in patients with atrial fibrillation- quality and cost implications.

BACKGROUND: Dabigatran, rivaroxaban, and apixaban have been approved for use in patients with atrial fibrillation based upon randomized trials demonstrating their comparable or superior efficacy and safety relative to warfarin. Little is known about their adoption into clinical practice, whether utilization is consistent with the controlled trials on which their approval was based, and how their use has affected health spending for patients and insurers. METHODS: We used medical and prescription claims data from a large insurer to identify patients with nonvalvular atrial fibrillation who were prescribed an oral anticoagulant in 2010-2013. We plotted trends in medication initiation over time, assessed corresponding insurer and patient out-of-pocket spending, and evaluated the cumulative number and cost of anticoagulants. We identified predictors of novel anticoagulant initiation using multivariable logistic models. Finally, we estimated the difference in total drug expenditures over 6 months for patients initiating warfarin versus a novel anticoagulant. RESULTS: There were 6893 patients with atrial fibrillation that initiated an oral anticoagulant during the study period. By the end of the study period, novel anticoagulants accounted for 62% of new prescriptions and 98% of anticoagulant-related drug costs. Female sex, lower household income, and higher CHADS2, CHA2DS2-VASC, and HAS-BLED scores were significantly associated with lower odds of receiving a novel anticoagulant (P <.001 for each). Average combined patient and insurer anticoagulant spending in the first 6 months after initiation was more than $900 greater for patients initiating a novel anticoagulant. CONCLUSIONS: This study demonstrates rapid adoption of novel anticoagulants into clinical practice, particularly among patients with lower CHADS2 and HAS-BLED scores, and high health care cost consequences. These findings provide important directions for future comparative and cost-effectiveness research.

Cost-effectiveness of oral anticoagulants for treatment of atrial fibrillation.

BACKGROUND: New anticoagulants may improve health outcomes in patients with atrial fibrillation, but it is unclear whether their use is cost-effective. METHODS AND RESULTS: A Markov state transition was created to compare 4 therapies: dabigatran 150 mg BID, apixaban 5 mg BID, rivaroxaban 20 mg QD, and warfarin therapy. The population included those with newly diagnosed atrial fibrillation who were eligible for treatment with warfarin. Compared with warfarin, apixaban, rivaroxaban, and dabigatran, costs were $93 063, $111 465, and $140 557 per additional quality-adjusted life year gained, respectively. At a threshold of $100 000 per quality-adjusted life year, apixaban provided the greatest absolute benefit while still being cost-effective, although warfarin would be superior if apixaban was 2% less effective than expected. Although apixaban was the optimal strategy in our base case, in probabilistic sensitivity analysis, warfarin was optimal in an equal number of iterations at a cost-effectiveness threshold of $100 000 per quality-adjusted life year. CONCLUSIONS: While at a standard cost-effectiveness threshold of $100 000 per quality-adjusted life year, apixaban seems to be the optimal anticoagulation strategy; this finding is sensitive to assumptions about its efficacy and cost. In sensitivity analysis, warfarin seems to be the optimal choice in an equal number of simulations. As a result, although all the novel oral anticoagulants produce greater quality-adjusted life expectancy than warfarin, they may not represent good value for money.

Comparative efficacy and safety of new oral anticoagulants in patients with atrial fibrillation.

BACKGROUND: Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons. METHODS AND RESULTS: We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score ≥3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban. CONCLUSIONS: An indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score ≥3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.

Impact of drug cost sharing on service use and adverse clinical outcomes in elderly receiving antidepressants.

BACKGROUND: Depression imposes enormous burdens on the elderly. Despite this, rates of initiation of and adherence to recommended pharmacotherapy are frequently low in this population. Although initiatives such as the Medicare Modernization Act (MMA) have improved seniors' access to antidepressants, there are concerns that the patient cost-sharing incorporated in the MMA may have unintended consequences if it reduces essential drug use. Age-related pharmacokinetic and pharmacodynamic changes could make seniors particularly vulnerable to antidepressant regimens used inappropriately to save costs, increasing their risks of morbidity, hospitalizations, and nursing home placements. Two sequential large-scale "natural experiments'' in British Columbia provide a unique opportunity to evaluate the effect of cost sharing on outcomes and mental health service use among seniors. In January 2002 the province introduced a CAD 25 copay (CAD10 for low-income seniors). In May 2003 this copay policy was replaced by a second policy consisting of an income-based deductible, 25% coinsurance once the deductible was met, and full coverage once an out-of-pocket ceiling was met. The transition between the two policies is analogous to what many U.S. seniors experience when they transition from private insurance requiring copays to Medicare Part D requiring deductibles and coinsurance. AIMS: To evaluate whether declines in antidepressant initiation after the introduction of two drug cost-sharing policies in British Columbia were associated with increased use of physician services, hospitalizations, and nursing home admissions among all British Columbia residents aged 65+. METHODS: Records of physician service use, inpatient hospitalizations, and residential care admissions were obtained from administrative databases. Population-level patterns over time were plotted, and effects of implementing the cost-sharing policies examined in segmented linear regression models. RESULTS: Neither policy affected the rates of visits to physicians or psychiatrists for depression, hospitalizations with a depression diagnosis, or long-term care admissions. DISCUSSION: The cost-sharing policies studied may have contained non-essential antidepressant use without substantially increasing mental health service utilization. However, it is possible that the policies had effects that we were unable to detect, such as increasing rates of visits to social workers or psychologists or forcing patients to reduce other spending. Further, the sequential implementation of the policy changes, makes it difficult to estimate the effect of a direct change from full coverage to a coinsurance/income-based deductible policy. IMPLICATIONS FOR HEALTH POLICIES: It may be possible to design policies to contain non-essential antidepressant use without substantially increasing other service utilization or adverse events. However, because undertreatment remains a serious problem among depressed elderly, well-designed prescription drug policies should be coupled with interventions to address under-treatment.

Pharmacological management of osteoporosis in nursing home populations: a systematic review.

Nursing home (NH) residents fall 11 times as frequently as their age-matched community-dwelling counterparts. The benefits of fall prevention strategies and hip protectors in terms of fracture risk in this setting are unclear. Moreover, there is no consensus on the efficacy of osteoporosis medication in NH residents. A systematic review was conducted to evaluate the efficacy of medications for osteoporosis in this population and to examine utilization studies in the NH setting to define prescribing practices. Electronic searches of MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials were supplemented with a hand search of bibliographies. All English-language studies published between January 1, 1974, and December 31, 2006, that studied osteoporosis pharmacotherapy in the NH environment were obtained, and studies of medication benefits and utilization patterns were identified. No restrictions were placed on study method. Studies required inclusion of NH patients and extractable data with bone mineral density (BMD) or fracture outcomes. Forty full-text articles were retrieved, of which 15 studies met selection criteria. In the nine studies examining medication effects, calcium (1,200 mg) and vitamin D (800 IU) supplementation were shown to reduce fracture risk and improve BMD. One study supported the role of alendronate, but none documented the utility of raloxifene, calcitonin, or teriparatide in NH residents. All six medication utilization studies reported infrequent use of osteoporosis medications (9-25%). Prescribing for elderly NH patients is difficult, considering the risk:benefit ratio and issues of longevity, but these medications may be underused in the NH environment.

Nononcologic use of human recombinant erythropoietin therapy in hospitalized patients.

BACKGROUND: Human recombinant erythropoietin (rHuEPO) is widely used to stimulate red blood cell production in patients with anemia due to cancer, renal disease, and other medical conditions, but concern has grown about its overuse and potential for harm. Little is known about the nature of rHuEPO use in hospitalized patients who receive rHuEPO therapy for nononcologic indications. METHODS: We reviewed the drug utilization data from a large academic medical center for all patients admitted during 3 years to identify all patients without cancer who received at least 1 dose of rHuEPO, including their age and sex; diagnoses; hematocrit and hemoglobin and iron levels; and use of supplemental iron. We also compared the rates of laboratory testing and iron supplementation in patients with and without chronic kidney disease (CKD). RESULTS: A total of 1360 distinct patients with 3094 hospitalizations received at least 1 dose of rHuEPO. In 2959 admissions for which hematocrit was determined within 14 days before rHuEPO use, mean values were less than 33% in 1792 (61%) and greater than 36% in 553 (19%). Patients with CKD were more likely than patients without CKD to receive rHuEPO with hematocrit greater than 36% (22% vs 8%; P<.001). Monitoring of iron status was more common in patients with CKD than in those without CKD (64% vs 45%; P <.001). Almost one fourth (23%) of rHuEPO recipients in whom iron levels were measured had absolute iron deficiency (serum ferritin concentration <100 ng/mL). In patients with CKD, only about half (54%) had adequate iron stores at the time of rHuEPO administration; this rate was even lower in patients without CKD (33%; P<.001). Only 66% of patients with documented iron deficiency who were receiving rHuEPO also received concomitant iron supplementation; this rate did not differ between patients with or without CKD. CONCLUSIONS: There is significant variability in the degree of anemia, completeness of iron measurement, and use of iron supplementation in hospitalized patients without cancer who are prescribed rHuEPO. Our results identify potential targets for quality improvement in patients both with and without CKD.

Internet marketing of herbal products.

CONTEXT: Passage of the Dietary Supplement Health and Education Act in 1994 restricted the Food and Drug Administration's control over dietary supplements, leading to enormous growth in their promotion. The Internet is often used by consumers as a source of information on such therapies. OBJECTIVE: To assess the information presented and indications claimed on the Internet for the 8 best-selling herbal products. DATA SOURCES: We searched the Internet using the 5 most commonly used search engines. For each, we entered the names of the 8 most widely used herbal supplements (ginkgo biloba, St John's wort, echinacea, ginseng, garlic, saw palmetto, kava kava, and valerian root). We analyzed the health content of all Web sites listed on the first page of the search results. STUDY SELECTION: We analyzed all accessible, English-language Web sites that pertained to oral herbal supplements. A total of 522 Web sites were identified; of these, 443 sites met inclusion criteria for the analysis. DATA EXTRACTION: The nature of the Web site (retail or nonretail), whether it was a sponsored link, and all references, indications, claims, and disclaimers were recorded. Two reviewers independently categorized medical claims as disease or nondisease according to Food and Drug Administration criteria. DATA SYNTHESIS: Among 443 Web sites, 338 (76%) were retail sites either selling product or directly linked to a vendor. A total of 273 (81%) of the 338 retail Web sites made 1 or more health claims; of these, 149 (55%) claimed to treat, prevent, diagnose, or cure specific diseases. More than half (153/292; 52%) of sites with a health claim omitted the standard federal disclaimer. Nonretail sites were more likely than retail sites to include literature references, although only 52 (12%) of the 443 Web sites provided referenced information without a link to a distributor or vendor. CONCLUSIONS: Consumers may be misled by vendors' claims that herbal products can treat, prevent, diagnose, or cure specific diseases, despite regulations prohibiting such statements. Physicians should be aware of this widespread and easily accessible information. More effective regulation is required to put this class of therapeutics on the same evidence-based footing as other medicinal products.

The nephrologist's role in the management of calcium-phosphorus metabolism in patients with chronic kidney disease.

BACKGROUND: In patients with chronic kidney disease (CKD), timely referral to a nephrologist has been shown to improve outcomes, but the specific care measures mediating these superior outcomes have not been sufficiently described. METHODS: In a cohort of 3014 patients with CKD, we evaluated whether they had any indicators of calcium-phosphorus metabolism management prior to renal replacement therapy (RRT). These included measurement of parathyroid hormone (PTH) or vitamin D metabolites, or receipt of calcitriol or calcium-containing phosphate binders (CCPB) prior to RRT. Control patients without such care were selected by risk-set matching. We used multivariate conditional logistic regression analysis to test whether use of these interventions was associated with prior nephrologist consultation. We then used Cox proportional hazards models to assess whether implementation of such care was associated with differences in 1-year mortality once RRT was instituted. RESULTS: Only 3.4% of CKD patients had their PTH assessed prior to RRT, and 0.3% had vitamin D status measured. Use of calcitriol (12.2%) and CCPBs (16%) was slightly more prevalent. Seeing a nephrologist was highly associated with use of the tests and drugs studied (odds ratio, 1.28 to 6.46; all P values <0.001), but care by generalists or other specialists was not. Management of calcium-phosphorus metabolism was independently associated with a 35% decreased likelihood of death (hazards ratio=0.65; 95%CI, 0.51 to 0.84) in the first year of RRT. CONCLUSION: Improvements in management of calcium-phosphorus metabolism in patients with CKD are attributable to nephrologist care and appear to mediate the survival benefit seen in patients who see a nephrologist relatively early in the course of their CKD.