Challenges for novel antiretroviral development in an era of widespread TLD availability.

Over 80% of people living with HIV in low-and-middle-income countries (LMICs) take first-line TDF/XTC/DTG (TLD). Due to hard-fought activism, in >100 LMICs TLD now costs under $45pppy under Voluntary License. With final DTG patents expiring by 2029, generic TLD will soon be available globally. We identify seven critical benchmarks underpinning TLDs success which novel ART should now meet, and an eighth for which novel ART should aim. These are superior efficacy; a high genetic barrier to resistance; safety in hepatitis B coinfection; favourable drug-drug interaction profiles including with antimycobacterials; efficacy in HIV-2; safety in pregnancy, long-acting formulation availability and affordable pricing from the outset. We illustrate when generic TLD will become available worldwide and compare this with trial programmes and approval timelines for two case-study novel ART combinations: islatravir/doravirine and cabotegravir/rilpivirine. We demonstrate that currently these regimens and trial programmes will not meet key benchmarks required to compete with TLD.

Addressing financial toxicity in cancer treatment-An opportunity for the 340B drug pricing program.

Cancer treatment has become increasingly expensive, partially due to the use of specialty drugs. The costs of these drugs are often passed down to patients, who may face the consequences of paying for more than they can afford, leading to financial toxicity. The 340B drug pricing program is a health care policy that may provide an opportunity to mitigate the financial consequences of cancer care. The 340B program requires manufacturers to sell outpatient drugs at a discount to hospitals caring for a significant number of socioeconomically disadvantaged individuals. The program intended for hospitals to use savings from discounted purchases to expand their safety net to vulnerable patients. Some studies have shown that participating hospitals do this by offering more charity and discounted care, whereas others have demonstrated that hospitals fail to sufficiently expand their safety net. A potential flaw of the program is the lack of guidance from governing bodies on how hospitals should use savings from discounted purchases. There has been growing discussion among stakeholders to reform the 340B program given the mixed findings of its effectiveness. With the rising costs of specialty drugs and associated prevalence of financial toxicity in patients with cancer, there is an opportunity to address these issues through reform that improves the program. Directing hospitals to offer specific safety net opportunities, such as passing along discounted drug prices to vulnerable populations, could help the growing number of patients who are financially burdened by medications at the core of the 340B program.

Assessing the Impact of the 340B Drug Pricing Program: A Scoping Review of the Empirical, Peer-Reviewed Literature.

Policy Points The 340B Drug Pricing Program accounts for roughly 1 out of every 100 dollars spent in the $4.3 trillion US health care industry. Decisions affecting the program will have wide-ranging consequences throughout the US safety net. Our scoping review provides a roadmap of the questions being asked about the 340B program and an initial synthesis of the answers. The highest-quality evidence indicates that nonprofit, disproportionate share hospitals may be using the 340B program in margin-motivated ways, with inconsistent evidence for increased safety net engagement; however, this finding is not consistent across other hospital types and public health clinics, which face different incentive structures and reporting requirements. CONTEXT: Despite remarkable growth and relevance of the 340B Drug Pricing Program to current health care practice and policy debate, academic literature examining 340B has lagged. The objectives of this scoping review were to summarize i) common research questions published about 340B, ii) what is empirically known about 340B and its implications, and iii) remaining knowledge gaps, all organized in a way that is informative to practitioners, researchers, and decision makers. METHODS: We conducted a scoping review of the peer-reviewed, empirical 340B literature (database inception to March 2023). We categorized studies by suitability of their design for internal validity, type of covered entity studied, and motivation-by-scope category. FINDINGS: The final yield included 44 peer-reviewed, empirical studies published between 2003 and 2023. We identified 15 frequently asked research questions in the literature, across 6 categories of inquiry-motivation (margin or mission) and scope (external, covered entity, and care delivery interface). Literature with greatest internal validity leaned toward evidence of margin-motivated behavior at the external environment and covered entity levels, with inconsistent findings supporting mission-motivated behavior at these levels; this was particularly the case among participating disproportionate share hospitals (DSHs). However, included case studies were unanimous in demonstrating positive effects of the 340B program for carrying out a provider's safety net mission. CONCLUSIONS: In our scoping review of the 340B program, the highest-quality evidence indicates nonprofit, DSHs may be using the 340B program in margin-motivated ways, with inconsistent evidence for increased safety net engagement; however, this finding is not consistent across other hospital types and public health clinics, which face different incentive structures and reporting requirements. Future studies should examine heterogeneity by covered entity types (i.e., hospitals vs. public health clinics), characteristics, and time period of 340B enrollment. Our findings provide additional context to current health policy discussion regarding the 340B program.

Cost-utility analysis and drug pricing for tirzepatide for type 2 diabetes in the Chinese market compared with semaglutide.

AIM: To investigate the most matchable price of tirzepatide (TIRZ) compared with semaglutide (SEMA) in the treatment of type 2 diabetes in China. METHODS: The patient cohort and clinical efficacy data were derived from the SURPASS-2 trial. Cost-utility analysis and a binary search were performed to identify the most matchable price of TIRZ from a Chinese healthcare provider's perspective. RESULTS: After lifetime simulation, the quality-adjusted life years of TIRZ 5, 10, 15 mg and SEMA 1 mg were 11.17, 11.21, 11.27 and 11.12 years, respectively. Despite an initial assumption that the annual cost of TIRZ equals that of SEMA, our analysis revealed that TIRZ is probably more cost-effective than SEMA. A thorough evaluation of pricing showed that the cost ranges for TIRZ at doses of 5, 10 and 15 mg were $1628.61-$1846.23, $1738.40-$2140.95 and $1800.30-$2430.81, respectively. After adjustment in the univariate sensitivity analysis, the cost ranges for TIRZ 5, 10 and 15 mg were $1542.68-$1757.57, $1573.00-$1967.16 and $1576.54-$2133.96, respectively. These cost intervals were validated through robust probabilistic sensitivity analysis and scenario analysis, except for the cost range for TIRZ 5 mg. CONCLUSIONS: This study shows that, using SEMA as a reference, the annual costs for TIRZ 10 and 15 mg are $1573.00-$1967.16 and $1576.54-$2133.96, respectively, for patients with type 2 diabetes in China.

Cost-utility analysis and drug pricing of once-weekly insulin icodec versus once-daily insulin degludec for type 2 diabetes patients treated with basal insulin in China.

AIM: Insulin icodec is a first once-weekly administration basal insulin analogue for type 2 diabetes. This study aimed to investigate the price range of icodec for type 2 diabetes in the Chinese market, taking insulin degludec as reference. MATERIALS AND METHODS: Long-term health outcomes and costs for icodec and degludec were simulated using the United Kingdom Prospective Diabetes Study Outcomes Model (version 2.1) over 40 years from the Chinese healthcare provider's perspective. The efficacy and safety data were obtained from the ONWARDS 2 trial (Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial). Cost-utility analysis and a binary search were used to investigate the price range of icodec. Sensitivity analyses were performed to verify the robustness of the base-case analysis results. RESULTS: After a 40-year simulation, the quality-adjusted life years (QALY) of icodec and degludec were 10.32 and 10.28 years, respectively. At the initial assumption of the same annual costs of icodec and degludec of $455.40, icodec was the dominant therapy compared with degludec, with higher QALYs and lower total cost. After the binary search, we observed that the annual cost range of icodec was $625.17-$855.25. This cost range was finally adjusted to be $597.66-$736.34 using one-way sensitivity analysis and confirmed using probabilistic sensitivity analysis and scenario analysis. The scenario analysis revealed that the annual cost range of icodec could be $506.70-$736.34 if the price of degludec decreased by 20% in the future. CONCLUSION: Insulin icodec appears to be more cost effective than degludec if the annual cost of icodec ranges from $597.66 to $736.34 for patients with type 2 diabetes in China.

Can Generalized Cost-Effectiveness Analysis Leverage Meaningful Use of Novel Value Elements in Pharmacoeconomics to Inform Medicare Drug Price Negotiation?

OBJECTIVES: Decision makers considering using cost-effectiveness analysis (CEA) to inform health-technology assessment must contend with documented and controversial shortfalls of CEA, including its assumption of disease severity independence and static pricing. ISPOR has recently introduced novel value elements besides direct healthcare cost and effectiveness for the patient, and these should be captured in CEA. Although novel value elements advance our understanding of "what" should be measured (value of hope, severity of disease, health equity, etc), there is limited direction on "how" to measure them in conventional CEA. Furthermore, with Medicare empowered to set drug prices under the Inflation Reduction Act, it is not clear what role CEA might have on where prices are set, given objections to the quality-adjusted life year in conventional approaches. METHODS: We critically reviewed the evidence for expanding conventional CEA methods to a more generalized approach of generalized CEA (GCEA). RESULTS: GCEA accounts for methods that address objections to the quality-adjusted life year and incorporate novel value elements. Although GCEA offers advantages, it also requires further research to develop "off-the-shelf" resources to help inform, for example, maximum fair price in the context of Medicare drug price negotiation. CONCLUSIONS: Should a shift toward GCEA reveal that the societal value of novel medicines exceeds their market-based costs, which will raise the key question of what market failure Medicare negotiation is meant to solve, if any, and therefore what the appropriate role of such negotiation might be to maximize the value society might garner from the development of novel medicines.

Informing the United States Medicare Drug Price Negotiation for Apixaban and Rivaroxaban: Methodological Considerations for Value Assessments Many Years After Launch.

OBJECTIVES: To demonstrate how health technology assessment methods can be used to support Medicare's price negotiations for apixaban and rivaroxaban. METHODS: Following the statutory outline of evidence that will be considered by Medicare, we conducted a systematic literature review, network meta-analyses, and decision analyses to evaluate the health outcomes and costs associated with apixaban and rivaroxaban compared with warfarin and dabigatran for patients with nonvalvular atrial fibrillation. Our methods inform discussions about the therapeutic impact of apixaban and rivaroxaban and suggest price premiums above their therapeutic alternatives over a range of cost-effectiveness thresholds. RESULTS: Network meta-analyses found apixaban resulted in a lower risk of major bleeding compared with warfarin and dabigatran and a lower risk of stroke/systemic embolism compared with warfarin but not compared with dabigatran. Rivaroxaban resulted in a lower risk of stroke/systemic embolism versus warfarin but not dabigatran, and there was no difference in major bleeding. Decision-analytic modeling of apixaban suggested annual price premiums up to $4350 above the price of warfarin and up to $530 above the price for dabigatran at cost-effectiveness thresholds up to $200 000 per equal value of life-years gained. Analyses of rivaroxaban showed an annual price premium of up to $3920 above warfarin and no premium above that paid for dabigatran. CONCLUSIONS: Although health technology assessment is typically performed near the time of regulatory approval, with modifications, we produced comparative clinical and relative cost-effectiveness findings to help guide negotiations on a "fair" price for drugs on the market for over a decade.

Challenges of Incorporating Life Cycle Drug Pricing in Cost-Effectiveness Models: A Review of Methods and Modeling Suggestions.

OBJECTIVES: This study aimed to conduct a review of existing methods used to incorporate life cycle drug pricing (LCDP) in cost-effectiveness analyses (CEAs), identify common methodological challenges, and suggest modeling approaches for prospectively implementing LCDP in CEA. METHODS: Two complementary searches were conducted in PubMed, combined with hand searching and reference mining, to identify English language full-text articles that explored (1) how drug prices change over time and (2) methods used to apply dynamic pricing in cost-effectiveness models (CEMs). Relevant articles were reviewed, and authors discussed the common methodological practices used in the literature and their associated challenges on prospectively implementing LCDP in CEMs. For each key challenge identified, we provide modeling suggestions to address the issue. RESULTS: We screened 1200 studies based on title and abstract; 117 were reviewed for eligibility, and 47 individual studies were included across both searches. Variations in prices over a product's life cycle are complex and multifactorial, and models applying LCDP in CEA varied in their methodology. We identified 4 key challenges to modeling LCDP in CEA, including how to model price trends before and after loss of exclusivity, how to capture the effect of price changes on future patient cohorts, and how to report results. CONCLUSION: Accurately quantifying the impact of LCDP requires careful consideration of multiple aspects pertaining to both the evolution of drug prices and how to reflect these in CEA. Although uncertainties remain, our findings can aid implementation and evaluation of LCDP in economic evaluations.

Commercial markups on pediatric oncology drugs at 340B pediatric hospitals.

Eligible pediatric hospitals can purchase clinician-administered drugs at discounted rates through the 340B Drug Pricing Program and charge payers prices exceeding drug acquisition costs, but the magnitude of these markups is not known. In a study of newly approved oncology drugs at pediatric 340B hospitals, median negotiated prices ranged from 102% (interquartile range [IQR]: 91%-156%) of average sales price (ASP) at Phoenix Children's Hospital to 630% (IQR: 526%-630%) at Driscoll Children's Hospital. Pediatric hospitals participating in the federal 340B Drug Pricing Program can extract steep payments on new drugs from commercial insurers, though with wide variation between and within hospitals.

Institutional design and moral conflict in health care priority-setting.

Priority-setting policy-makers often face moral and political pressure to balance the conflicting motivations of efficiency and rescue/non-abandonment. Using the conflict between these motivations as a case study can enrich the understanding of institutional design in developed democracies. This essay presents a cognitive-psychological account of the conflict between efficiency and rescue/non-abandonment in health care priority-setting. It then describes three sets of institutional arrangements-in Australia, England/Wales, and Germany, respectively-that contend with this conflict in interestingly different ways. The analysis yields at least three implications for institutional design in developed democracies: (1) indeterminacy at the level of moral psychology can increase the probability of indeterminacy at the level of institutional design; (2) situational constraints in effect require priority-setting policy-makers to adopt normative-moral pluralism; and (3) the U.S. health care system may be in an anti-priority-setting equilibrium.

The Zero-Price Conundrum: Exploration of Scenarios Where a Clinically Effective New Drug Might Not Be Cost-Effective at Zero Price.

OBJECTIVES: The zero-price conundrum occurs when a clinically effective drug can justify no greater than a price of zero based on cost-effectiveness criteria from a health system perspective. This is relevant for health systems that require evidence of cost-effectiveness, in addition to safety and efficacy for drug approval and other analyses that may shape drug coverage policies, such as budget impact and comparative effectiveness. This study aimed to clarify and explore the zero-price conundrum to provide a resource in the development of practical and methodological solutions. METHODS: We specified equations representing previously identified zero-price scenarios and used them to elucidate factors contributing to the zero-price conundrum and explore relationships between them. We present real-world considerations and discuss solutions from the literature. RESULTS: The analyses demonstrated that a primary cause of the zero-price problem for a new drug that increases quality-adjusted survival pertains to healthcare costs beyond the influence of the new drug, specifically, disease background costs, costs of existing drugs used in a combination regimen, and costs of future health interventions patients may become eligible to receive. Pragmatic solutions have been to exclude such costs from cost-effectiveness analyses. Proposed modifications to cost-effectiveness analysis include assessing each drug in a combination regimen based on its relative contribution to improved health. CONCLUSIONS: The zero-price dilemma may arise more frequently as the number of drugs in high-cost disease areas continues to grow. As cost-effectiveness methods evolve, there is the opportunity to develop robust solutions that can be applied consistently.

Medicare Drug Price Negotiation in the United States: Implications and Unanswered Questions.

The United States is a relatively free-pricing market for pharmaceutical manufacturers to set list prices at the product launch. Few drug price controls exist, and federal price negotiation as a policy has historically been politically untenable. After decades of debate on whether the federal government, specifically the Medicare program, should more actively manage drug prices, the US Congress passed legislation authorizing Medicare to directly negotiate prices with manufacturers. The purpose of this article is to describe elements and implementation of the price negotiation provisions and then comment on the potential impacts on payers, innovations, and the pharmaceutical industry. While impacting only a few drugs each year in the beginning, price negotiation in the Medicare program will have secondary and long-term effects in the US market and beyond. It is clear that in the United States, the Medicare market for drugs will no longer be a free-pricing environment in the industry.

The Impact on Cost-Effectiveness of Accounting for Generic Drug Pricing: Four Case Studies.

OBJECTIVES: Guidance on the conduct of health technology assessments rarely recommends accounting for anticipated future price declines that can follow loss of marketing exclusivity. This article explores when it is appropriate to account for generic pricing and whether it can influence cost-effectiveness estimates. METHODS: This article presents 4 case studies. Case study 1 considers a hypothetical drug used by a first patient cohort at branded prices and by subsequent, "downstream" cohorts at generic prices. Case study 2 explores whether statin assessments should account for generic prices for downstream cohorts that gain access after the initial cohort. Case study 3 uses a simplified spreadsheet model to assess the impact of accounting for generic pricing for inclisiran, used when statins insufficiently reduce cholesterol. Case study 4 amends this model for a hypothetical, advanced, follow-on treatment displacing inclisiran. RESULTS: Assessments should include generic pricing even if the first cohort using a drug pays branded prices and only downstream cohorts pay generic prices (case study 1). Because eventual generic pricing for statins did not depend on decisions for downstream cohorts, assessing reimbursement for those cohorts could safely omit generic pricing (case study 2). For inclisiran (case study 3), including generic pricing notably improved estimated cost-effectiveness. Displacing inclisiran with an advanced therapy (case study 4) modestly affected estimated cost-effectiveness. CONCLUSIONS: Although this analysis relies on simplified and hypothetical models, it demonstrates that accounting for generic pricing might substantially reduce estimated cost-effectiveness ratios. Doing so when warranted is crucial to improving health technology assessment validity.

The Inflation Reduction Act: How Will Medicare Negotiating Drug Prices Impact Patients with Heart Disease?

PURPOSE OF REVIEW: Cardiovascular medications improve health and prevent early death. However, high drug prices reduce the use of these medications and strain the health system. The Inflation Reduction Act (IRA) of 2022 allows Medicare to negotiate drug prices with manufacturers and reduces out-of-pocket drug costs for Medicare beneficiaries. This article explores the potential impact that the IRA will have on the treatment of cardiovascular disease. RECENT FINDINGS: Cardiovascular disease medications are likely to be selected for price negotiations under the IRA, leading to savings for patients and for Medicare. Recent work suggests that the IRA's reforms to the Medicare Part D drug benefit will meaningfully reduce out-of-pocket costs for important cardiovascular medications. The IRA is expected to impact cardiovascular disease treatments via price negotiations and through the broader access to medications afforded by improvements to Part D coverage design.

Initial and supplementary indication approval of new targeted cancer drugs by the FDA, EMA, Health Canada, and TGA.

BACKGROUND: Previous research focused on the clinical evidence supporting new cancer drugs' initial US Food and Drug Administration (FDA) approval. However, targeted drugs are increasingly approved for supplementary indications of unknown evidence and benefit. OBJECTIVES: To examine the clinical trial evidence supporting new targeted cancer drugs' initial and supplementary indication approval in the US, EU, Canada, and Australia. DATA AND METHODS: 25 cancer drugs across 100 indications were identified with FDA approval between 2009-2019. Data on regulatory approval and clinical trials were extracted from the FDA, European Medicines Agency (EMA), Health Canada (HC), Australian Therapeutic Goods Administration (TGA), and clinicaltrials.gov. Regional variations were compared with χ2-tests. Multivariate logistic regressions compared characteristics of initial and supplementary indication approvals, reporting adjusted odds ratios (AOR) with 95% confidence intervals (CI). RESULTS: Out of 100 considered cancer indications, the FDA approved 96, the EMA 92, HC 86, and the TGA 83 (83%, p < 0.05). The FDA more frequently granted priority review, conditional approval, and orphan designations than other agencies. Initial approvals were more likely to receive conditional / accelerated approval (AOR: 2.69, 95%CI [1.07-6.77], p < 0.05), an orphan designation (AOR: 3.32, 95%CI [1.38-8.00], p < 0.01), be under priority review (AOR: 2.60, 95%CI [1.17-5.78], p < 0.05), and be monotherapies (AOR: 5.91, 95%CI [1.14-30.65], p < 0.05) than supplementary indications. Initial indications' pivotal trials tended to be shorter (AOR per month: 0.96, 95%CI [0.93-0.99], p < 0.05), of lower phase design (AOR per clinical phase: 0.28, 95%CI [0.09-0.85], p < 0.05), and enroll more patients (AOR per 100 patients: 1.19, 95%CI [1.01-1.39], p < 0.05). CONCLUSIONS: Targeted cancer drugs are increasingly approved for multiple indications of varying clinical benefit. Drugs are first approved as monotherapies in rare diseases with a high unmet need. Whilst expedited regulatory review incentivizes this prioritization, indication-specific safety, efficacy, and pricing policies are necessary to reflect each indication's differential clinical and economic value.

Towards sustainability and affordability of expensive cell and gene therapies? Applying a cost-based pricing model to estimate prices for Libmeldy and Zolgensma.

BACKGROUND AIMS: Drug prices are regarded as one of the most influential factors in determining accessibility and affordability to novel therapies. Cell and gene therapies such as OTL-200 (brand name: Libmeldy) and AVXS-101 (brand name: Zolgensma) with (expected) list prices of 3.0 million EUR and 1.9 million EUR per treatment, respectively, spark a global debate on the affordability of such therapies. The aim of this study was to use a recently published cost-based pricing model to calculate prices for cell and gene therapies, with OTL-200 and AVXS-101 as case study examples. METHODS: Using the pricing model proposed by Uyl-de Groot and Löwenberg, we estimated a price for both therapies. We searched the literature and online public sources to estimate (i) research and development (R&D) expenses adjusted for risk of failure and cost of capital, (ii) the eligible patient population and (iii) costs of drug manufacturing to calculate a base-case price for OTL-200 and AVXS-101. All model input parameters were varied in a stepwise, deterministic sensitivity analysis and scenario analyses to assess their impact on the calculated prices. RESULTS: Prices for OTL-200 and AVXS-101 were estimated at 1 048 138 EUR and 380 444 EUR per treatment, respectively. In deterministic sensitivity analyses, varying R&D estimates had the greatest impact on the price for OTL-200, whereas for AVXS-101, changes in the profit margin changed the calculated price substantially. Highest prices in scenario analyses were achieved when assuming the lowest number of patients for OTL-200 and highest R&D expenses for AVXS-101. The lowest R&D expenses scenario resulted in lowest prices for either therapy. CONCLUSIONS: Our results show that, using the proposed model, prices for both OTL-200 and AVXS-101 lie substantially below the currently (proposed) list prices for both therapies. Nevertheless, the uncertainty of the used model input parameters is considerable, which translates in a wide range of estimated prices. This is mainly because of a lack of transparency from pharmaceutical companies regarding R&D expenses and the costs of drug manufacturing. Simultaneously, the disease indications for both therapies remain heavily understudied in terms of their epidemiological profile. Despite the considerable variation in the estimated prices, our results may support the public debate on value-based and cost-based pricing models, and on "fair" drug prices in general.

Do Cost-Effectiveness Analyses Account for Drug Genericization? A Literature Review and Assessment of Implications.

OBJECTIVES: We investigated how health technology assessment (HTA) organizations around the world have handled drug genericization (an allowance for future generic drug entry and subsequent drug price declines) in their guidelines for cost-effectiveness analyses (CEAs). We also analyzed a large sample of published CEAs to examine prevailing practices in the field. METHODS: We reviewed 43 HTA guidelines to determine whether and how they addressed drug genericization in their CEAs. We also selected a sample of 270 US-based CEAs from the Tufts Medical Center's CEA Registry, restricting the sample to studies on pharmaceuticals published from 1991 to 2019 and to analyses taking a lifetime time horizon. We determined whether each CEA examined genericization (and if so, whether in base case or sensitivity analyses), and how inclusion of genericization influenced the estimated incremental cost-effectiveness ratios. RESULTS: Fourteen (33%) of the 43 HTA guidelines mention genericization for CEAs and 4 (9%) recommend that base case analyses include assumptions about future drug price changes due to genericization. Most published CEAs (95%) do not include assumptions about future generic prices for intervention drugs. Only 2% include such assumptions about comparator drugs. Most studies (72%) conduct sensitivity analyses on drug prices unrelated to genericization. CONCLUSIONS: The omission of assumptions about genericization means that CEAs may misrepresent the long run opportunity costs for drugs. The field needs clearer guidance for when CEAs should account for genericization, and for the inclusion of other price dynamics that might influence a drug's cost-effectiveness.

Do Health Technology Assessment organisations consider manufacturers' costs in relation to drug price? A study of reimbursement reports.

INTRODUCTION: Drug reimbursement decisions are often made based on a price set by the manufacturer. In some cases, this price leads to public and scientific debates about whether its level can be justified in relation to its costs, including those related to research and development (R&D) and manufacturing. Such considerations could enter the decision process in collectively financed health care systems. This paper investigates whether manufacturers' costs in relation to drug prices, or profit margins, are explicitly mentioned and considered by health technology assessment (HTA) organisations. METHOD: An analysis of reimbursement reports for cancer drugs was performed. All relevant Dutch HTA-reports, published between 2017 and 2019, were selected and matched with HTA-reports from three other jurisdictions (England, Canada, Australia). Information was extracted. Additionally, reimbursement reports for three cases of expensive non-oncolytic orphan drugs prominent in pricing debates in the Netherlands were investigated in depth to examine consideration of profit margins. RESULTS: A total of 66 HTA-reports concerning 15 cancer drugs were included. None of these reports contained information on manufacturer's costs or profit margins. Some reports contained general considerations of the HTA organisation which related prices to manufacturers' costs: six contained a statement on the lack of price setting transparency, one mentioned recouping R&D costs as a potential argument to justify a high price. For the case studies, 21 HTA-reports were selected. One contained a cost-based price justification provided by the manufacturer. None of the other reports contained information on manufacturer's costs or profit margins. Six reports contained a discussion about lack of transparency. Reports from two jurisdictions contained invitations to justify high prices by demonstrating high costs. CONCLUSION: Despite the attention given to manufacturers' costs in relation to price in public debates and in the literature, this issue does not seem to get explicit systematic consideration in the reimbursement reports of expensive drugs.

Longitudinal study of the impact of three major regulations on the Korean pharmaceutical industry in the last 30 years.

BACKGROUND: The pharmaceutical industry is heavily regulated. Partly for this reason, new drugs generally take over 10 years from the product development stage to market entry. Although regulations affect the pharmaceutical industry over a long period, previous studies investigating the impact of new regulatory policies have usually focused on the short period before and after implementing that policy. Therefore, the purpose of this study is to examine whether and how significantly regulatory policies affect long-term innovation in the pharmaceutical industry in Korea. METHODS: This study focused on three significant regulatory policies: the introduction of the product patent system, changes in the Good Manufacturing Practice (GMP) system, and the Drug Expenditure Rationalization Plan (DERP). The study used interrupted time series (ITS) analysis to investigate the long-term impacts of the policies before and after implementation. RESULTS: Our results show that introducing the product patent system in 1987 significantly increased the number of Korean patent applications. The effect of the revised GMP policies was also statistically significant, both before and after implementation and between pre-emptive companies and non-pre-emptive ones. However, due to the companies' negotiations with the regulatory authorities or the regulatory system that links drug approval and price evaluation, the DERP did not significantly delay new drug registration in Korea. CONCLUSION: This study showed that the policies of the product patent system, GMP policies, and DERP regulations have significantly encouraged pharmaceutical companies to strive to meet regulatory requirements and promote innovation in Korea. The study suggests that it is necessary for companies to pre-emptively respond to systemic changes in development and production strategies to deal with regulatory changes and achieve sustainable growth. Also, our study results indicate that since government policies motivate the innovative system of the pharmaceutical industry, governmental authorities, when formulating pharmaceutical policies, need to consider the impact on the long-term innovation of the industry.

Medicaid and Accelerated Approval: Spending on Drugs with and without Proven Clinical Benefits.

Many state Medicaid officials are concerned about rising prescription drug spending, particularly drugs approved through the Food and Drug Administration's (FDA) accelerated approval pathway. The authors examined how much of Medicaid programs' accelerated approval spending is attributable to products that have demonstrated clinical benefits versus those that have not. Their findings provide support for states' concerns that pharmaceutical companies often fail to complete their required postapproval confirmatory studies within the FDA's requested timeline. But the findings also highlight one issue that policy stakeholders have not yet devoted substantial attention to: the use of surrogate endpoints involved in the postapproval confirmatory studies for most of the products in this study's sample. The granularity of the study's results enabled an analysis of the impact of different policy recommendations on both the accelerated approval pathway and Medicaid programs. These findings inform the current policy debate, suggesting that policy stakeholders might focus attention on products converting their approval on the basis of surrogate outcomes rather than on clinical outcomes.