Estimation of the Incremental Cumulative Cost of HIV Compared with a Non-HIV Population.

OBJECTIVE: There are limited real-world data comparing cumulative incremental healthcare costs in people living with HIV (PLWH) and those without HIV. This study evaluated all-cause cumulative and incremental costs in PLWH in the US using a matched-cohort design. MATERIALS AND METHODS: This retrospective, multi-year, cross-sectional analysis evaluated annual costs from 2013 to 2017, and projected cumulative costs of HIV from age 25 to 69 years. IQVIA's commercial adjudicated claims database was used to identify patients with HIV and match them with patients without HIV (controls). Cumulative all-cause costs were derived from the health plan-allowed costs incurred from ages 25-69 years. Undiscounted, discounted, and incremental costs between PLWH and non-HIV populations were reported in 2017 US dollars (US$), and annual all-cause costs were estimated for each year by 10-year age bands. RESULTS: A total of 25,261, 24,134, 31,654, 35,374, and 29,039 PLWH and 75,783, 72,402, 94,962, 106,122, and 87,117 matched controls were identified in the years 2013 through 2017, respectively. The mean undiscounted cumulative costs were $1,840,554 for PLWH and $285,065 for controls, an incremental cost difference of $1,555,489, while the mean discounted cumulative cost for PLWH was $983,897 compared with $133,340 for controls, an incremental cost difference of $850,557. Mean all-cause annual and cumulative costs were up to seven times higher for PLWH compared with controls. There was a trend for costs to increase each year with increasing age. LIMITATIONS AND CONCLUSIONS: While cumulative all-cause cost estimates only approximate total cost burden for any given patient, and the results of this study may not be generalizable to all population subgroups, this is one of the first US studies to examine annual and cumulative costs in a real-world cohort of commercially insured PLWH compared with a population without HIV. In this large, representative sample of commercially insured US adults with HIV, PLWH had substantially higher all-cause cumulative costs than individuals without HIV.

Treatment Adherence And Persistence Among HIV-1 Patients Newly Starting Treatment.

OBJECTIVE: To assess adherence and persistence with first-line single-tablet regimen (STR) and multi-tablet regimen (MTR) antiretroviral therapy (ART) in newly treated HIV-1 patients. METHODS: Retrospective analysis of longitudinal pharmacy claims among US patients initiating ART between 1/1/2016 and 5/31/2016 (index date was defined by first ART claim for STRs, and fill date for the last therapy in the regimen for MTRs). Adherence was assessed over a 12-month period and reported as the proportion of adherent or non-adherent (defined as ≤5-day and > a 5-day gap between successive fills, respectively) patients. Sensitivity analysis using ≤7-day and ≤14-day gap thresholds to define adherence was performed. Persistence was assessed as the number of days on therapy from index until treatment discontinuation (>90 day gap in therapy). Kaplan-Meier curves and Cox Proportional Hazard models were generated to evaluate discontinuation rates. Assessments were performed on STRs vs MTRs overall and by regimen. RESULTS: Patients initiating ART (STR: n=10,623; MTR: n=2504) had a mean age of 42.8 years; 76.0% were male. STR patients were >2 times more likely to be adherent over 12 months than MTR patients (24.9% vs 11.7%, respectively). Patients using EVG/COBI/FTC/TAF had greater adherence than those using other STRs. Among MTRs, patients were more adherent with FTC/TDF+DTG (15.1%) than other MTRs. Persistence was also greater with STRs, with MTR patients being 61% more likely to discontinue therapy. Persistence was best for FTC/TAF-based regimens. Predictors of treatment discontinuation included younger age, female gender, and Medicare or Medicaid insurance type. CONCLUSION: Patients receiving STRs were significantly less likely to discontinue therapy and were more adherent with their regimens, providing further evidence of greater adherence and persistence with STRs versus MTRs. However, there was a large proportion of patients who interrupted or discontinued treatment. Further research examining treatment patterns beyond first line is warranted.

Challenges Involved in the Development and Delivery of Abuse-deterrent Formulations of Opioid Analgesics.

PURPOSE: This commentary examines the development, regulatory, and reimbursement challenges facing abuse-deterrent formulation (ADF) products. METHODS: In January 2017, the Tufts Center for the Study of Drug Development convened a roundtable to explore clinical development, regulatory, and reimbursement challenges with respect to ADFs of opioid analgesics. Roundtable participants, who included a range of pharmaceutical industry and other experts, discussed multiple challenges. FINDINGS: First, several key clinical development challenges were identified and discussed. These challenges pertain to prodrug development and development of deterrents against oral abuse. Second, experts suggested that more clarity is needed from regulatory authorities regarding standards for proving ADF labeling claims and for being rewarded with 3-year data exclusivity. Similarly, given the substantial burdens associated with the development of postapproval evidence generation, experts raised the need for a consistent regulatory policy related to postapproval evidence generation for all ADFs (branded and generic). Third, despite the public health benefits of certain ADF products, current coverage and access policies impede patient access. Payer justification for restrictive policies appears to be based more on budget impact considerations than cost-effectiveness. Fourth, there remains a need to further expand the evidence base regarding clinical and cost-effectiveness as well as abuse deterrence in a real-world setting for all ADF products. IMPLICATIONS: Clinical development challenges need to be overcome with respect to novel ADF technologies, such as prodrugs and deterrents against oral abuse. More clarity is needed from regulatory authorities on labeling claims and data exclusivity eligibility with respect to ADFs. Ensuring prescriber training and awareness of various options for treating pain, including ADF products, is an important step, as is educating payers about the public health benefits of ADFs in appropriate subpopulations of pain patients. In addition, physicians may need to incorporate appropriate risk stratification methods. Finally, it is important to establish a level playing field between coverage of ADF and non-ADF products so that non-ADF products are not given preferred formulary placement.

Rising Drug Costs Drives the Growth of Pharmacy Benefit Managers Exclusion Lists: Are Exclusion Decisions Value-Based?

OBJECTIVE: We examine whether drugs' excluded versus recommended status on pharmacy benefit manager exclusion lists corresponds to evidence from cost-effectiveness analyses, lack of evidence, or rebates. DATA SOURCES: To find cost-effectiveness data for drugs on 2016 exclusion lists of CVS Caremark and Express Scripts, we searched the Tufts Cost-Effectiveness Analysis Registry and the peer-reviewed literature. STUDY DESIGN: For each excluded and recommended drug, we compared the mean cost-per-QALY, and we calculated the difference between the numbers of excluded and recommended drugs for which we could find no cost-effectiveness evidence. DATA COLLECTION: As keywords in our searches, we used the brand and generic drug name and "cost-effectiveness" and "cost-per-quality-adjusted life-year." Of 240 retrieved studies, 110 were selected for analysis. PRINCIPAL FINDINGS: The mean cost-per-QALY for excluded drugs was higher ($51,611) than the cost-per-QALY for recommended drugs ($49,474), but not statistically significant. We could find no cost-effectiveness evidence in the Registry or peer-reviewed literature for 23 of the excluded drugs, and no evidence for 5 of the recommended drugs. CONCLUSIONS: Cost-effectiveness does not correlate with a drug's excluded or recommended status. Lack of cost-effectiveness evidence favors a drug's excluded status.

Progress Report on Neglected Tropical Disease Drug Donation Programs.

PURPOSE: Neglected tropical diseases (NTDs) impose a significant burden on public health, particularly in developing nations. Many can be treated cost-effectively with drugs donated or offered at or below marginal cost. In 2012, the World Health Organization published an NTD roadmap that outlined a strategy for the prevention, control, and eradication of 17 NTDs by 2020. Inspired by this roadmap, executives from 13 pharmaceutical companies, government agencies, and other interested parties signed the London Declaration on Neglected Tropical Diseases in January 2012. In this paper, we will assess progress in meeting commitments on drug donations laid out in the London Declaration. METHODS: We conducted Medline and LexisNexis searches of peer-reviewed publications and trade journals, as well as product development partnership and government reports. Subsequently, we designed a survey instrument and surveyed 10 company signatories (companies with drug donation programs) to the London Declaration to determine current donations and pledges. FINDINGS: Nine of 10 companies with donation programs responded to the survey. The respondents reported substantial progress in meeting the goals laid out in the London Declaration. Survey respondents maintained 17 drug donation programs across 10 disease categories. In 2014, companies donated >1 billion treatments, with a dollar value of nearly $1.5 billion. However, not all donated products were distributed to patients in need. In addition, 4 of the 17 programs were slated to end before 2020, three of the 17 programs did not report explicit program objectives, and 7 of 17 did not measure the impact of programs in terms of numbers of patients treated. None of our survey respondents reported on whether the programs were leading to a reduction in disease prevalence. IMPLICATIONS: Donations are a necessary but insufficient condition for patient access to neglected disease drugs. Additional resources must be allocated to ensure delivery of donated products to patients. In addition, drug donation programs should provide explicit descriptions of program objectives, measurements of the impacts of their programs, and extension of all donation commitments through 2020. To achieve this, multiple stakeholders with a vested interest in reducing the burden of neglected diseases must collaborate in a multipronged approach toward NTD elimination.

Impact of Postapproval Evidence Generation on the Biopharmaceutical Industry.

PURPOSE: Meeting marketplace demands for proving the value of new products requires more data than the industry has routinely produced. These data include evidence from comparative effectiveness research (CER), including randomized, controlled trials; pragmatic clinical trials; observational studies; and meta-analyses. METHODS: We designed and conducted a survey to examine the industry's perceptions on new data requirements regarding CER evidence, the acceptability of postapproval study types, payer-specific issues related to CER, communication of data being generated postapproval, and methods used for facilitating postapproval evidence generation. FINDINGS: CER is being used by payers for most types of postapproval decisions. Randomized, controlled trials were indicated as the most acceptable form of evidence. At the same time, there was support for the utility of other types of studies, such as pragmatic clinical trials and observational studies. Respondents indicated the use of multiple formats for communicating postapproval data with many different stakeholders including regulators, payers, providers, and patients. Risk-sharing agreements with payers were unanimously supported by respondents with regard to certain products with unclear clinical and economic outcomes at launch. In these instances, conditional reimbursement through coverage with evidence development was considered a constructive option. The Food and Drug Administration's initiative called Regulatory Science was considered by the respondents as having the most impact on streamlining the generation of postapproval research-related evidence. IMPLICATIONS: The biopharmaceutical industry is faced with a broad and complex set of challenges related to evidence generation for postapproval decisions by a variety of health care system stakeholders. Uncertainty remains as to how the industry and payers use postapproval studies to guide decision making with regard to pricing and reimbursement status. Correspondingly, there is uncertainty regarding whether the industry's investment in CER will have a positive return on investment in terms of reimbursement and market access.

Can genomic medicine improve financial sustainability of health systems?

Recent years have seen increased use of genomic technologies in a variety of research and clinical settings. Genomic medicine is not a cost-containment measure per se, but is viewed as having the potential to bend the healthcare cost curve. Currently, it is unknown how systematic adoption of genomic medicine in clinical practice will impact healthcare costs. This article discusses the potential economic impact of genomic medicine and the challenges that lie ahead.

Measuring progress in neglected disease drug development.

BACKGROUND: Since the late 1990s, funding for development of neglected disease drugs has increased with an influx of resources from product development partnerships (PDPs). Previous research showed modest gains in drug approvals and products in Phase III of clinical development in the period 2000-2008. OBJECTIVE: We assessed the 2009-2013 period in terms of numbers of products in Phase III development and numbers of approvals. Subsequently, we calculated the PDP share in terms of sponsorship of new approvals. We also identified the numbers of 2000-2013 approvals included in the World Health Organization's Essential Drug List (EDL). METHODS: We identified new approvals and Phase III products targeting neglected diseases in the period 2009-2013 by searching ClinicalTrials.gov, IMS R&D Focus, and Investigational Drugs Database, as well as drug regulatory agency websites. Subsequently, we determined which products approved between 2000 and 2013 have been included in the most recent version of the EDL. RESULTS: We found 20 new approvals targeting neglected diseases in the period 2009-2013. PDPs were the primary sponsor of 57% of new approvals in this time frame. Approvals included 1 new molecular entity, 5 vaccines, 2 new indications, 9 fixed-dose combinations, and 3 new formulations. HIV/AIDS (pediatric indications) and malaria accounted for 60% of approvals in 2009-2013. The average number of new approvals per year for neglected diseases rose from 2.6 in 2000-2008 to 4.9 in 2009-2013. The World Health Organization included 44% of 2000-2013 approved products on the EDL. We found 18 products currently in Phase III of clinical development. Products in Phase III testing included 3 new molecular entities, 6 vaccines, 2 fixed-dose combinations, 5 new indications, and 2 new formulations. CONCLUSIONS: Increased funding through PDPs for neglected disease drug development seems to be producing results. Approvals and products in Phase III testing have shown a steady increase since 2000, with nearly a doubling of products in 2009-2013, compared with 2000-2008, in terms of the annual average yield. However, only 3 new molecular entities have been approved in 14 years. In addition, malaria and HIV (pediatric indications) seem to have benefited most from increased funding, whereas less success has occurred with other diseases. Inclusion of newly approved products on the EDL has been slow and limited, with only 44% of new approvals added to the list. Uneven progress suggests funding could be better targeted. In addition, PDPs could do more to facilitate access, in particular by working closely with the World Health Organization to assess the clinical effectiveness and cost-effectiveness of new approvals.

Complying with state and federal regulations on essential drug benefits: implementing the Affordable Care Act.

OBJECTIVES: To examine health plan compliance with essential drug benefit regulations in California and Massachusetts and at the federal level. STUDY DESIGN: Health plan formulary review and analysis. METHODS: We analyzed formularies from the 3 largest small group plans in California and Massachusetts, including each state's benchmark plan. With respect to both federal and state regulations, for each health plan, we examined whether the drug was covered, the designated patient cost sharing tier of the drug, and which conditions of reimbursement were applied to the drug. RESULTS: Most drugs included in state and federal mandates are covered by both benchmark and non-benchmark plans. However, health plans are not fully compliant with state and federal regulations. Significant differences among plans relate more to cost sharing and conditions of reimbursement, such as prior authorization, step edits, and quantity limits, than to drug coverage. CONCLUSIONS/POLICY IMPLICATIONS: Because health plans in California and Massachusetts are not fully compliant with state and federal mandates, they will have to adjust their formularies to meet minimum requirements. State policy makers need to balance competing aims of comprehensiveness of coverage and drug affordability. They must consider: (1) choice of benchmark plan -choice of a more generous benchmark plan implies less leverage for negotiating lower prices; and (2) breadth of state mandates which, if they exceed federal mandates, must be paid for by the states.

Personalized Medicine's Bottleneck: Diagnostic Test Evidence and Reimbursement.

BACKGROUND: Personalized medicine is gradually emerging as a transformative field. Thus far, seven co-developed drug-diagnostic combinations have been approved and several dozen post-hoc drug-diagnostic combinations (diagnostic approved after the drug). However, barriers remain, particularly with respect to reimbursement. Purpose, methods: This study analyzes barriers facing uptake of drug-diagnostic combinations. We examine Medicare reimbursement in the U.S. of 10 drug-diagnostic combinations on the basis of a formulary review and a survey. FINDINGS: We found that payers reimburse all 10 drugs, but with variable and relatively high patient co-insurance, as well as imposition of formulary restrictions. Payer reimbursement of companion diagnostics is limited and highly variable. In addition, we found that the body of evidence on the clinical- and cost-effectiveness of therapeutics is thin and even less robust for diagnostics. Conclusions, discussion: The high cost of personalized therapeutics and dearth of evidence concerning the comparative clinical effectiveness of drug-diagnostic combinations appear to contribute to high patient cost sharing, imposition of formulary restrictions, and limited and variable reimbursement of companion diagnostics. Our findings point to the need to increase the evidence base supportive of establishing linkage between diagnostic testing and positive health outcomes.

Are payers treating orphan drugs differently?

BACKGROUND: Some orphan drugs can cost hundreds of thousands of dollars annually per patient. As a result, payer sensitivity to the cost of orphan drugs is rising, particularly in light of increased numbers of new launches in recent years. In this article, we examine payer coverage in the United States, England and Wales, and the Netherlands of outpatient orphan drugs approved between 1983 and 2012, as well as the 11 most expensive orphan drugs. METHODS: We collected data from drug regulatory agencies as well as payers and drug evaluation authorities. RESULTS: We found that orphan drugs have more coverage restrictions than non-orphan drugs in all three jurisdictions. From an economic perspective, the fact that a drug is an orphan product or has a high per-unit price per se should not imply a special kind of evaluation by payers, or necessarily the imposition of more coverage restrictions. CONCLUSION: Payers should consider the same set of decision criteria that they do with respect to non-orphan drugs: disease severity, availability of treatment alternatives, level of unmet medical need, and cost-effectiveness, criteria that justifiably may be taken into account and traded off against one another in prescribing and reimbursement decisions for orphan drugs.

Comparative-effectiveness research: does it matter?

BACKGROUND: For several years there has been a vigorous policy debate on comparative effectiveness research (CER). This debate has focused on whether more evidence should be gathered, and who should be doing the funding and developing of evidence. There has been less emphasis on implementation of CER findings, and examining whether CER has or will have an impact on prescribing patterns, reimbursement, health outcomes, and health care spending. OBJECTIVE: This paper addresses both empirical and normative aspects of CER in terms of its impact on prescribing, reimbursement, cost-containment, and health outcomes. RESULTS: A significant gap persists between the best available evidence on therapeutic effectiveness and tolerability and typical patterns of prescribing care, as well as patient choices. Consequently, there is room for building a more systematic evidence base in the United States, so that policymakers are better equipped to understand variation in clinical outcomes while promoting appropriate prescribing and reimbursement patterns. METHODS: The author carried out a non-systematic literature review of both empirical and normative aspects pertaining to CER and its policy implications. Keywords for the Medline search were "comparative effectiveness research" and "policy implications." CONCLUSION: CER has a modest impact on prescribing, reimbursement, cost-containment, and health outcomes. This impact will likely intensify as funding increases and novel models to steer prescribing and reimbursement choices incorporate comparative-effectiveness evidence.

Evaluating the impact of Medicare Part D on quality metrics.

Subsidized access to medical and pharmacy benefits is not a goal in and of itself; it is a means toward an end (improved health outcomes). Accordingly, the addition of an outpatient prescription drug benefit (Part D) to Medicare in 2006 will be deemed a success if it provides better, more affordable access to outpatient prescription drugs for Medicare beneficiaries and, more importantly, improves drug adherence and health outcomes, together with reducing or at least bending the cost curve by offsetting certain healthcare costs such as hospitalizations and emergency room visits. Priest and colleagues examine these claims and find suboptimal outcomes despite improved access.

Overcoming regulatory and economic challenges facing pharmacogenomics.

The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist. From a regulatory perspective, therapeutics and companion diagnostics are ideally developed simultaneously, with the clinical significance of the diagnostic established using data from the clinical development program of the corresponding therapeutic. Nevertheless, this is not (yet) happening. Most personalized medicines are personalized post hoc, that is, a companion diagnostic is developed separately and approved after the therapeutic. This is due in part to a separate and more complex regulatory process for diagnostics coupled with a lack of clear regulatory guidance. More importantly, payers have placed restrictions on reimbursement of personalized medicines and their companion diagnostics, given the lack of evidence on the clinical utility of many tests. To achieve increased clinical adoption of diagnostics and targeted therapies through more favorable reimbursement and incorporation in clinical practice guidelines, regulators will need to provide unambiguous guidance and manufacturers will need to bring more and better clinical evidence to the market place.