Insights into insurance coverage for digital therapeutics: A qualitative study of US payer perspectives.

BACKGROUND: In the last decade there has been an increase in the development and marketing of digital therapeutic (DTx) products aiming to prevent, manage, or treat a medical disorder or disease. Health insurance coverage for these products is not well established, and payers are facing increasing pressure to include these products as a covered benefit. OBJECTIVE: To examine factors and characteristics that could drive health insurance coverage of DTx products from US payers' and coverage decision-makers' perspectives. METHODS: This was a qualitative noninterventional, cross-sectional study conducted from August 2022 to October 2022. Virtual focus group meetings with pharmacy benefit managers/directors or medical directors representing a range of health insurance organizations were held following a semistructured interview guide. Convenience and snowball sampling techniques were used to identify participants. Transcripts were coded and analyzed with Atlas.ti software to identify common themes and subthemes. RESULTS: Five focus group meetings and 1 individual interview were held from August to October 2022. Participants (n = 22) were mostly pharmacists (n = 18, 85%) with more than 15 years of experience (n = 18, 85%). Some participants indicated that DTx products for diabetes (n = 6, 29%), mental/behavioral health (n = 3, 14%), and substance abuse disorders (n = 3, 14%) were already covered by their organizations. The topics generating the most comments grouped by code were issues around the evidence for DTx (67 unique comments) and barriers for coverage (60 unique comments). Participants indicated they want to have evidence of effectiveness that is similar to traditional pharmaceutical products. Barriers for coverage included a need to revise benefit policies, exclusion of nonprescription products, and mechanisms for billing. DTx products with an indication for mental/behavioral health were viewed as most likely to be reimbursed. Coverage of DTx products may occur under either the pharmacy or medical benefit. CONCLUSIONS: Health care payers stated that evidence of effectiveness was a necessary condition for health insurance coverage of DTx products. Given these are relatively new in health care, payers had more questions than answers regarding how these products will be integrated into health benefits.

Real-world evidence for coverage determination of treatments for rare diseases.

Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.

Comparing Preferences for Disease Profiles: A Discrete Choice Experiment from a US Societal Perspective.

OBJECTIVES: There is increasing interest in expanding the elements of value to be considered when making health policy decisions. To help inform value frameworks, this study quantified preferences for disease attributes in a general public sample and examined which combination of attributes (disease profiles) are considered most important for research and treatment. METHODS: A discrete choice experiment (DCE) was conducted in a US general population sample, recruited through online consumer panels. Respondents were asked to select one of a set of health conditions they believed to be most important, characterized by attributes defined by a previous qualitative study: onset age; cause of disease; life expectancy; caregiver requirement; symptom burden (characterized by the Health Utilities Index with varying levels of ambulation independence, dexterity limitations, and degree of pain and discomfort); and disease prevalence. A fractional factorial DCE design was implemented using R, and 60 choice sets were generated (separated into blocks of 10 per participant). Data were analyzed using a mixed-logit regression model, and results used to assess the likelihood of preferring disease profiles. Based on individual attribute preferences, overall preferences for disease profiles, including a profile aligned with Duchenne muscular dystrophy (DMD), were compared. RESULTS: Fifty-two percent of respondents (n = 537) were female, and 70.6% were aged 18-54 years. Attributes considered most important were those related to life expectancy (odds ratio [OR], 95% confidence interval [CI] 1.88 [1.56-2.27] for a 50% reduction in remaining life expectancy vs no impact), and symptom burden (OR [95% CI] 1.84 [1.47-2.31] for severe vs mild burden). Greater importance was also found for pediatric onset, caregiver requirement, and diseases affecting more people. As an example of disease profile preferences, a DMD-like pediatric inherited disease with 50% reduction in life expectancy, extensive caregiver requirement, severe symptom burden, and 1:5000 prevalence had 2.37-fold higher odds of being selected as important versus an equivalent disease with adult onset and no life expectancy reduction. CONCLUSIONS: Of disease attributes included in this DCE, respondents valued higher prevalence of disease, life expectancy and symptom burden as most important for prioritizing research and treatment. Based on expressed attribute preferences, a case study of an inherited pediatric disease involving substantial reductions to length and quality of life and requiring caregiver support has relatively high odds of being identified as important compared to diseases reflecting differing attribute profiles. These findings can help inform expansions of value frameworks by identifying important attributes from the societal perspective.

Risk of bleeding with concomitant use of oral anticoagulants and aspirin: A systematic review and meta-analysis.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Oral anticoagulants (OACs) and aspirin can trigger bleeding events when used alone or in combination. The purpose of this study was to compare the risk of any type of bleeding in individuals exposed to a combination of OAC and aspirin with the risk in those taking an OAC or aspirin alone. METHODS: MEDLINE and Web of Science were queried in January 2021 for eligible articles. Studies were included if they were either randomized controlled trials (RCTs) or observational studies and evaluated the number of any bleeding events in two groups, one with exposure to both OAC and aspirin and one with exposure to OAC alone or aspirin alone. Pooled odds ratios were calculated using a random-effects model. RESULTS: Forty-two studies were included. A significant difference in the risk of bleeding with use of OAC plus aspirin versus OAC alone was observed in an analysis of 15 RCTs (odds ratio [OR], 1.36; 95% CI, 1.15-1.59) and also in an analysis of 19 observational studies (OR, 1.42; 95% CI, 1.09-1.87). When OAC plus aspirin was compared to aspirin alone, a higher rate of bleeding was found in the combination therapy group (OR, 2.36; 95%CI, 1.91-2.92) in the analysis of 15 RCTs, but no significant difference was found among 10 observational studies (OR, 1.93; 95% Cl, 0.99-3.75). CONCLUSION: The risk of any type of bleeding was significantly increased among patients taking aspirin plus OAC compared to those taking OAC alone in both RCTs and observational studies. Evaluation of RCTs comparing OAC plus aspirin to aspirin alone suggests increased bleeding risk as well.

Estimating health state utilities in Duchenne muscular dystrophy using the health utilities index and EQ-5D-5L.

BACKGROUND: The progression of Duchenne muscular dystrophy (DMD) is characterized by loss of ambulation, respiratory insufficiency, cardiomyopathy, and early mortality. DMD profoundly impacts health-related quality-of-life (HRQoL). However, few health state utility data exist; published utilities tend to be derived from small samples for a limited number of health states and are often based on caregiver-reported patient health status. This study estimated utility values for varied clinical and functional health states in DMD, based on patient-reported health status. METHODS: Individuals with DMD in the US aged 12-40 years completed the EQ-5D (5-level) and Health Utilities Index (HUI) preference-based instruments. Based on responses to a clinical questionnaire, participants self-classified into functional health states according to level of lower and upper limb function, use of respiratory support, and presence of cardiomyopathy. Mean [standard deviation (SD)] utility and EQ-5D visual analogue scale (VAS) scores were estimated according to health state; and median (interquartile range) attribute levels calculated to understand which domains of health are most severely affected in DMD. RESULTS: Of 63 males with DMD, mean (SD) age was 19.8 (6.1) years and 11 (17.5%) were ambulatory. Mean (SD) utility values were 0.92 (0.08; HUI2), 0.84 (0.20; HUI3), and 0.84 (0.13; EQ-5D) for ambulatory patients without cardiomyopathy (n = 10). For non-ambulatory patients with moderately impaired upper limb function, night and daytime ventilation without cardiomyopathy, mean (SD) utilities were 0.49 (0.07) for the HUI2, 0.16 (0.15) for the HUI3 and 025 (0.14) for the EQ-5D. Mean (SD) VAS scores for the same health states were 91 (9) and 83 (21), respectively. In addition to impairments in mobility/ambulation, and self-care, attributes like usual activities and pain also showed notable effects of DMD. CONCLUSIONS: In DMD, although a relationship between disease progression and HRQoL is observed, there is large variability in utility within functional health states, and across instruments. Utility values for less severe non-ambulatory health states described by level of upper limb function are novel. These utility values, derived based on direct patient feedback rather than from caregiver report, are relevant to individuals of varying functional statuses and augment scarce DMD-specific utility data.

Sustained Effect of Clinical Decision Support for Heart Failure: A Natural Experiment Using Implementation Science.

OBJECTIVES: In a randomized controlled trial, we found that applying implementation science (IS) methods and best practices in clinical decision support (CDS) design to create a locally customized, "enhanced" CDS significantly improved evidence-based prescribing of ß blockers (BB) for heart failure compared with an unmodified commercially available CDS. At trial conclusion, the enhanced CDS was expanded to all sites. The purpose of this study was to evaluate the real-world sustained effect of the enhanced CDS compared with the commercial CDS. METHODS: In this natural experiment of 28 primary care clinics, we compared clinics exposed to the commercial CDS (preperiod) to clinics exposed to the enhanced CDS (both periods). The primary effectiveness outcome was the proportion of alerts resulting in a BB prescription. Secondary outcomes included patient reach and clinician adoption (dismissals). RESULTS: There were 367 alerts for 183 unique patients and 171 unique clinicians (pre: March 2019-August 2019; post: October 2019-March 2020). The enhanced CDS increased prescribing by 26.1% compared with the commercial (95% confidence interval [CI]: 17.0-35.1%), which is consistent with the 24% increase in the previous study. The odds of adopting the enhanced CDS was 81% compared with 29% with the commercial (odds ratio: 4.17, 95% CI: 1.96-8.85). The enhanced CDS adoption and effectiveness rates were 62 and 14% in the preperiod and 92 and 10% in the postperiod. CONCLUSION: Applying IS methods with CDS best practices was associated with improved and sustained clinician adoption and effectiveness compared with a commercially available CDS tool.

Barriers to Adoption of Tailored Drug-Drug Interaction Clinical Decision Support.

OBJECTIVE: Despite the benefits of the tailored drug-drug interaction (DDI) alerts and the broad dissemination strategy, the uptake of our tailored DDI alert algorithms that are enhanced with patient-specific and context-specific factors has been limited. The goal of the study was to examine barriers and health care system dynamics related to implementing tailored DDI alerts and identify the factors that would drive optimization and improvement of DDI alerts. METHODS: We employed a qualitative research approach, conducting interviews with a participant interview guide framed based on Proctor's taxonomy of implementation outcomes and informed by the Theoretical Domains Framework. Participants included pharmacists with informatics roles within hospitals, chief medical informatics officers, and associate medical informatics directors/officers. Our data analysis was informed by the technique used in grounded theory analysis, and the reporting of open coding results was based on a modified version of the Safety-Related Electronic Health Record Research Reporting Framework. RESULTS: Our analysis generated 15 barriers, and we mapped the interconnections of these barriers, which clustered around three entities (i.e., users, organizations, and technical stakeholders). Our findings revealed that misaligned interests regarding DDI alert performance and misaligned expectations regarding DDI alert optimizations among these entities within health care organizations could result in system inertia in implementing tailored DDI alerts. CONCLUSION: Health care organizations primarily determine the implementation and optimization of DDI alerts, and it is essential to identify and demonstrate value metrics that health care organizations prioritize to enable tailored DDI alert implementation. This could be achieved via a multifaceted approach, such as partnering with health care organizations that have the capacity to adopt tailored DDI alerts and identifying specialists who know users' needs, liaise with organizations and vendors, and facilitate technical stakeholders' work. In the future, researchers can adopt the systematic approach to study tailored DDI implementation problems from other system perspectives (e.g., the vendors' system).

Cost-effectiveness of HLA-B*58:01 testing to prevent Stevens-Johnson syndrome/toxic epidermal necrolysis in Vietnam.

Background: HLA-B*58:01 is strongly associated with allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Vietnam. This study assessed the cost-effectiveness of this testing to prevent SJS/TEN. Methods: A model was developed to compare three strategies: no screening, use allopurinol; HLA-B*58:01 screening; and no screening, use probenecid. A willingness-to-pay of three-times gross domestic product per capita was used. Results: Compared with 'no screening, use allopurinol', 'screening' increased quality-adjusted life-years by 0.0069 with the incremental cost of Vietnam dong (VND) 14,283,633 (US$617), yielding an incremental cost-effectiveness ratio of VND 2,070,459,122 (US$89,398) per quality-adjusted life-year. Therefore, 'screening' was unlikely to be cost-effective under the current willingness-to-pay. Testing's cost-effectiveness may change with targeted high-risk patients, reimbursed febuxostat or lower probenecid prices. Conclusion: The implementation of nationwide HLAB*58:01 testing before the use of allopurinol is not cost-effective, according to this analysis. This may be due to the lack of quality data on the effectiveness of testing and costing data in the Vietnamese population.

Chimeric antigen receptor T-cell immunotherapies adverse events reported to FAERS database: focus on cytopenias.

Chimeric antigen receptor (CAR) T-cell therapy presents a promising treatment for hematologic malignancies, displaying high efficacy but not being exempt from toxicity. In this observational study, we assessed adverse events (AEs) reported to the Food and Drug Adverse Event Reporting System (FAERS) including any of the six approved CAR T-cell therapies. A total of 5249 reports mentioning a CAR T-cell as a suspect product were retrieved from the FAERS database, containing a total of 24333 AEs, of which 3236 (13.3%) were cytopenias. The highest number of AEs mentioned by the report was observed for tisagenlecleucel (mean = 6.7), with the lowest for ciltacabtagene (mean = 1.3). Among all reports, hematopoietic leukopenia was the most frequently reported AEs (n = 1386, 5.7%), with hematopoietic erytropenia the least reported (n = 291, 1.2%). Tisagenlecleucel showed a high reporting odds ratio for hematopoietic erythropenia (27.28, 95%CI 14.04-53.00), leukopenia (4.04, 95%CI 3.52-4.64), and thrombocytopenia (4.01, 95%CI 3.19-5.03). Cytopenias represent one of the most frequently reported AEs in FAERS, a CAR T-cell therapy is indicated, with haematopoetic leukopenia being the most common. When comparing different CAR-T cell therapies, the cytopenias' reporting odds ratio was particularly high for tisagenlecleucel, especially in relation to hematopoietic erythropenia.

Patient Experiences with Clostridioides difficile Infection and Its Treatment: A Systematic Literature Review.

INTRODUCTION: Clostridioides difficile infection (CDI) is a globally recognized cause of morbidity and mortality with devastating effects on health-related quality of life (HRQoL). The objective of this study was to conduct the first systematic literature review (SLR) to assess the humanistic burden of CDI on patient experiences, including HRQoL and related constructs, and attitudes towards treatment alternatives. METHODS: An SLR was conducted to identify peer-reviewed articles that assessed CDI, including recurrent CDI (rCDI), and patient-reported outcomes or HRQoL. PubMed, Embase, and the Cochrane Collaboration abstracting services were used to conduct literature searches from 2010 to 2021 in the English language. This SLR was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. RESULTS: Of 511 identified articles, 21 met study inclusion criteria. The SLR showed CDI has a devastating impact on patients' overall HRQoL that continues well beyond infection clearance. The impact of CDI on physical, emotional, social, and professional well-being rivaled abdominal symptoms of uncontrollable diarrhea, being worse for patients with rCDI. Patients with CDI feel isolated, depressed, lonely, and continue to be frightened of recurrences as well as being contagious to others. Most believe that they will never be free of CDI. CONCLUSION: CDI and rCDI are debilitating conditions affecting physical, psychological, social, and professional functioning of patients' HRQoL, even long after the event has occurred. The results of this SLR suggest that CDI is a devastating condition in need of better prevention strategies, improved psychological support, and treatments that address the microbiome disruption to break the cycle of recurrence. Additional safe and effective therapies are needed to address this unmet medical need.

Clostridioides difficile infection is a gut bacterial infection that can happen after a person has taken antibiotics to treat another infection. C. difficile infection can lead to other medical problems and death. This review of the literature aimed to understand how C. difficile infection (first, previous, and repeat occurrences), the severe diarrhea it causes, and available treatments (both old and new) for C. difficile infection can impact a person's quality of life, daily self-care activities, and attitudes toward treatment. Results from this review of 21 studies showed that C. difficile infection has a negative impact on the quality of life of patients, affecting their physical, mental, and social health. C. difficile infection also disrupted the professional lives of patients and their ability to perform work activities. This negative effect continued over time, long after the infection had cleared because patients feared it would come back again. Treating C. difficile infection improved quality of life. Findings suggest that C. difficile infection is a devastating condition that needs better prevention strategies, improved psychological support, and treatments that stop the cycle of repeated gut infections by restoring good gut flora.

Real-World Persistence, Adherence, Hypoglycemia, and Health Care Resource Utilization in People With Type 2 Diabetes Who Continued With the Second-Generation Basal Insulin Analog Insulin Glargine 300 Units/mL or Switched to a First-Generation Basal Insulin (Insulin Glargine 100 Units/mL or Detemir 100).

People with type 2 diabetes receiving a second-generation basal insulin (BI) analog may be switched to a first-generation formulation for financial reasons or changes in health insurance. However, because second-generation BI analogs have more even pharmacokinetic profiles, longer durations of action (>24 vs. ≤24 hours), and more stable action profiles than first-generation BI analogs, such a change may result in suboptimal treatment persistence and/or adherence. This study compared treatment persistence, treatment adherence, rates of hypoglycemia, and health care resource utilization outcomes in people with type 2 diabetes who either continued treatment with the second-generation BI Gla-300 or switched to a first-generation BI. The study showed that continuing with Gla-300 was associated with a lower risk of discontinuing therapy, fewer emergency department visits, and lower hypoglycemia event rates than switching to a first-generation BI.

A machine learning evaluation of patient characteristics associated with prescribing of guideline-directed medical therapy for heart failure.

Introduction/background: Patients with heart failure and reduced ejection fraction (HFrEF) are consistently underprescribed guideline-directed medications. Although many barriers to prescribing are known, identification of these barriers has relied on traditional a priori hypotheses or qualitative methods. Machine learning can overcome many limitations of traditional methods to capture complex relationships in data and lead to a more comprehensive understanding of the underpinnings driving underprescribing. Here, we used machine learning methods and routinely available electronic health record data to identify predictors of prescribing. Methods: We evaluated the predictive performance of machine learning algorithms to predict prescription of four types of medications for adults with HFrEF: angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACE/ARB), angiotensin receptor-neprilysin inhibitor (ARNI), evidence-based beta blocker (BB), or mineralocorticoid receptor antagonist (MRA). The models with the best predictive performance were used to identify the top 20 characteristics associated with prescribing each medication type. Shapley values were used to provide insight into the importance and direction of the predictor relationships with medication prescribing. Results: For 3,832 patients meeting the inclusion criteria, 70% were prescribed an ACE/ARB, 8% an ARNI, 75% a BB, and 40% an MRA. The best-predicting model for each medication type was a random forest (area under the curve: 0.788-0.821; Brier score: 0.063-0.185). Across all medications, top predictors of prescribing included prescription of other evidence-based medications and younger age. Unique to prescribing an ARNI, the top predictors included lack of diagnoses of chronic kidney disease, chronic obstructive pulmonary disease, or hypotension, as well as being in a relationship, nontobacco use, and alcohol use. Discussion/conclusions: We identified multiple predictors of prescribing for HFrEF medications that are being used to strategically design interventions to address barriers to prescribing and to inform further investigations. The machine learning approach used in this study to identify predictors of suboptimal prescribing can also be used by other health systems to identify and address locally relevant gaps and solutions to prescribing.

Clinician challenges to evidence-based prescribing for heart failure and reduced ejection fraction: A qualitative evaluation.

BACKGROUND: Reasons for suboptimal prescribing for heart failure with reduced ejection fraction (HFrEF) have been identified, but it is unclear if they remain relevant with recent advances in healthcare delivery and technologies. This study aimed to identify and understand current clinician-perceived challenges to prescribing guideline-directed HFrEF medications. METHODS: We conducted content analysis methodology, including interviews and member-checking focus groups with primary care and cardiology clinicians. Interview guides were informed by the Cabana Framework. RESULTS: We conducted interviews with 33 clinicians (13 cardiology specialists, 22 physicians) and member checking with 10 of these. We identified four levels of challenges from the clinician perspective. Clinician level challenges included misconceptions about guideline recommendations, clinician assumptions (e.g., drug cost or affordability), and clinical inertia. Patient-clinician level challenges included misalignment of priorities and insufficient communication. Clinician-clinician level challenges were primarily between generalists and specialists, including lack of role clarity, competing priorities of providing focused versus holistic care, and contrasting confidence regarding safety of newer drugs. Policy and system/organisation level challenges included insufficient access to timely/reliable patient data, and unintended care gaps for medications without financially incentivized metrics. CONCLUSION: This study presents current challenges faced by cardiology and primary care which can be used to strategically design interventions to improve guideline-directed care for HFrEF. The findings support the persistence of many challenges and also sheds light on new challenges. New challenges identified include conflicting perspectives between generalists and specialists, hesitancy to prescribe newer medications due to safety concerns, and unintended consequences related to value-based reimbursement metrics for select medications.

Assessing the value of delandistrogene moxeparvovec (SRP-9001) gene therapy in patients with Duchenne muscular dystrophy in the United States.

Background: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene therapy that may delay progression of Duchenne muscular dystrophy (DMD), a severe, rare neuromuscular disease caused by DMD gene mutations. Early cost-effectiveness analyses are important to help contextualize the value of gene therapies for reimbursement decision making. Objective: To determine the potential value of delandistrogene moxeparvovec using a cost-effectiveness analysis. Study design: A simulation calculated lifetime costs and equal value of life years gained (evLYG). Inputs included extrapolated clinical trial results and published utilities/costs. As a market price for delandistrogene moxeparvovec has not been established, threshold analyses established maximum treatment costs as they align with value, including varying willingness-to-pay up to $500,000, accounting for severity/rarity. Setting: USA, healthcare system perspective Patients: Boys with DMD Intervention: Delandistrogene moxeparvovec plus standard of care (SoC; corticosteroids) versus SoC alone Main outcome measure: Maximum treatment costs at a given willingness-to-pay threshold Results: Delandistrogene moxeparvovec added 10.30 discounted (26.40 undiscounted) evLYs. The maximum treatment cost was approximately $5 M, assuming $500,000/evLYG. Varying the benefit discount rate to account for the single administration increased the estimated value to #$5M, assuming $500,000/evLYG. Conclusion: In this early economic model, delandistrogene moxeparvovec increases evLYs versus SoC and begins to inform its potential value from a healthcare perspective.

Assessing the impact of single or short-term administration on a therapy's cost-effectiveness: a hypothetical disease-agnostic model.

AIMS: Assessing the value of single or short-term therapies (SSTs) within traditional cost-effectiveness analyses (CEAs) has been a topic of discussion as the number of SSTs increases, particularly regarding the effect of discounting on valuation. To quantify the impact of discounting in economic evaluations, a CEA of a hypothetical SST and equivalent chronic therapy was conducted using standard methods. MATERIALS AND METHODS: A lifetime Markov model was developed for a hypothetical chronic, progressive disease that could be treated with an SST, chronic therapy, or no novel treatment, termed standard of care (SoC). Incremental cost-effectiveness ratios (ICERs) with quality-adjusted life years (QALYs) comparing SST vs. SoC and an equivalent chronic therapy vs. SoC were assessed from a payer perspective. Both treatments had equal benefits and undiscounted lifetime costs; 3% discounting was applied to costs/benefits in the base case, and the impact of discounting was assessed. RESULTS: In the base case example, both the SST and equivalent chronic therapy vs. SoC had ICERs of $86,000/QALY without discounting. With 3% discounting, the ICER for the SST increased by 116% ($186,000/QALY) while the ICER for the chronic therapy increased by 10% ($95,000/QALY) despite equal clinical benefit. In scenario analyses, the ICER of the SST was consistently higher than the equivalent chronic therapy across a range of assumptions/inputs. Varying the cost/benefit discount rates had a greater impact on the SST. Differences in the ICERs between the therapies increased with increasing life expectancy/time horizon. LIMITATIONS: The simple model structure may not be reflective of acute or more complex diseases. Also, the scenario of perfect equivalency in efficacy and lifetime costs is hypothetical. CONCLUSIONS: This quantitative assessment showed the extent to which SST CEAs are highly sensitive to discounting, resulting in worse value assessments for SSTs than equivalent chronic therapies.

Recommendations for economic evaluations of cell and gene therapies: a systematic literature review with critical appraisal.

OBJECTIVE: No consensus exists on the ideal methodology to evaluate the economic impact and value of new, potentially curative gene therapies. We aimed to identify and describe published methodologic recommendations for the economic evaluation of gene therapies and assess whether these recommendations have been applied in published evaluations. METHODS: This study was conducted in three stages: a systematic literature review of methodologic recommendations for economic evaluation of gene therapies; an assessment of the appropriateness of recommendations; and a review to assess the degree to which the recommendations were applied in published evaluations. RESULTS: A total of 2,888 references were screened, 83 articles were reviewed to assess eligibility, and 20 papers were included. Fifty recommendations were identified, and 21 reached consensus thresholds. Most evaluations were based on naive treatment comparisons and did not apply consensus recommendations. Innovative payment mechanisms for gene therapies were rarely considered. The only widely applied recommendations related to modeling choices and methods. CONCLUSIONS: Methodological recommendations for economic evaluations of gene therapies are generally not being followed. Assessing the applicability and impact of the recommendations from this study may facilitate the implementation of consensus recommendations in future evaluations.

Cost-effectiveness analysis of five anti-obesity medications from a US payer's perspective.

BACKGROUND AND AIMS: To determine the cost-effectiveness of anti-obesity medications (AOM): tirzepatide, semaglutide, liraglutide, phentermine plus topiramate (PpT), and naltrexone plus bupropion (NpB). METHODS AND RESULTS: From a U.S. perspective we developed a Markov model to simulate weight change over a 40-year time horizon using results from clinical studies. According to the body mass index (BMI), cardiovascular diseases, diabetes and mortality risk were the health states considered in the model, being mutually exclusive. Costs of AOM, adverse events, cardiovascular events, and diabetes were included. We applied a 3% per-year discount rate and calculated the incremental cost-effectiveness ratios (ICERs) of cost per quality-adjusted life-year (QALY) gained. Probabilistic sensitivity analyses incorporated uncertainty in input parameters. A deterministic analysis was conducted to determine the robustness of the model. The model included a cohort of 78.2% females with a mean age of 45 years and BMI of 37.1 (SD 4.9) for females and 36.8 (SD 4.9) for males. NpB and PpT were the least costly medications and, all medications differed no more than 0.5 QALYs. Tirzepatide ICER was $355,616 per QALY. Liraglutide and semaglutide options were dominated by PpT. CONCLUSION: Compared to other AOM, PpT was lowest cost treatment with nearly identical QALYs with other agents.

Drugs That Interact With Colchicine Via Inhibition of Cytochrome P450 3A4 and P-Glycoprotein: A Signal Detection Analysis Using a Database of Spontaneously Reported Adverse Events (FAERS).

BACKGROUND: Colchicine has a narrow therapeutic index. Its toxicity can be increased due to concomitant exposure to drugs inhibiting its metabolic pathway; these are cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). OBJECTIVE: To examine clinical outcomes associated with colchicine drug interactions using the spontaneous reports of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). METHODS: We conducted a disproportionality analysis using FAERS data from January 2004 through June 2020. The reporting odds ratio (ROR) and observed-to-expected ratio (O/E) with shrinkage for adverse events related to colchicine's toxicity (ie, rhabdomyolysis/myopathy, agranulocytosis, hemorrhage, acute renal failure, hepatic failure, arrhythmias, torsade de pointes/QT prolongation, and cardiac failure) were compared between FAERS reports. RESULTS: A total of 787 reports included the combined mention of colchicine, an inhibitor of both CYP3A4 and P-gp drug, and an adverse event of interest. Among reports that indicated the severity, 61% mentioned hospitalization and 24% death. A total of 37 ROR and 34 O/E safety signals involving colchicine and a CYP3A4/P-gp inhibitor were identified. The strongest ROR signal was for colchicine + atazanavir and rhabdomyolysis/myopathy (ROR = 35.4, 95% CI: 12.8-97.6), and the strongest O/E signal was for colchicine + atazanavir and agranulocytosis (O/E = 3.79, 95% credibility interval: 3.44-4.03). CONCLUSION AND RELEVANCE: This study identifies numerous safety signals for colchicine and CYP3A4/P-gp inhibitor drugs. Avoiding the interaction or monitoring for toxicity in patients when co-prescribing colchicine and these agents is highly recommended.

A systematic review of real-world healthcare resource use and costs of Clostridioides difficile infections.

Objective: To conduct a systematic review of published real-world evidence describing the cost and healthcare resource use for Clostridiodes difficile infection (CDI) in the United States. Methods: A systematic literature review was conducted searching for terms for CDI and healthcare costs. Titles of articles and abstracts were reviewed to identify those that met study criteria. Studies were evaluated to examine overall design and comparison groups in terms of healthcare resource use and cost for CDI. Results: In total, 28 articles met the inclusion criteria. Moreover, 20 studies evaluated primary CDI or did not specify, and 8 studies1-8 evaluated both primary CDI and recurrent (rCDI). Data from Medicare were used in 6 studies. Nearly all studies used a comparison group, either controls without CDI (N = 20) or comparison between primary CDI and rCDI (N = 7). Two studies examined costs of rCDI by the number of recurrences. Overall, the burden of CDI is significant, with higher aggregate costs for patients with rCDI. Compared with non-CDI controls, hospital length of stay increased in patients with both primary and rCDI compared to patients without CDI. Patients with primary CDI cost healthcare systems $24,000 more than patients without CDI. Additionally, 2 studies that evaluated the impact of recurrence among those patients with an index case of CDI demonstrated significantly higher direct all-cause medical costs among those with rCDI compared to those without. Conclusion: CDI, and particularly rCDI, is a costly condition with hospitalizations being the main cost driver.