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This paper first reviews the evidence on price levels, price growth, and value for cancer drugs. The available evidence suggests that prices for originator (brand-name) drugs are rising significantly more rapidly than general inflation, but the available data are inadequate for robust comparisons between cancer and other categories of specialty drugs. We then examine the factors contributing to high and rising prices for cancer drugs. This analysis focuses mainly on the USA, which accounts for 46% of global expenditures on cancer drugs. It is the country of first launch for most cancer and other specialty drugs and frequently has the highest prices for drugs.

Differential pricing-manufacturers varying prices for on-patent pharmaceuticals across markets-can, in theory, lead to increased patient access and improved research and development (R&D) incentives compared with charging a uniform price across markets. Theoretical models of price discrimination and Ramsey pricing support differentials based inversely on price elasticities, which are plausibly related to average per capita income. However, these models do not address absolute price levels and dynamic efficiency. Value-based differential pricing theory incorporates insurance coverage and addresses static and dynamic efficiency. Limited empirical evidence indicates a weak positive relationship between prices and gross domestic product (GDP) per capita. External referencing and parallel trade undermine differential pricing. We discuss previously neglected factors that undermine differential pricing in practice. High price growth relative to GDP in the USA leads to widening differentials between the USA and other countries. Concerns over the effects of confidential rebating challenges acceptance of this approach to implementing price differentials. The growth of branded generics in low- and middle-income countries leads to complex markets with product and price differentiation.

Objectives: To analyze how value-based pricing (VBP), which grounds the price paid for pharmaceuticals in their value, can manage "affordability" challenges, defined as drugs that meet cost-effectiveness thresholds but are "unaffordable" within the short-run budget., Methods: Three specific contexts are examined, drawing on recent experience. First, an effective new treatment for a chronic, progressive disease, such as hepatitis C, creates a budget spike that is transitory because initial prevalence is high, relative to current incidence. Second, "cures" that potentially provide lifetime benefits may claim abnormally high VBP prices, with high immediate budget impact potentially/partially offset by deferred cost savings. Third, although orphan drugs in principle target rare diseases, in aggregate they pose affordability concerns because of the growing number of orphan indications and increasingly high prices., Results: For mass diseases, the transitory budget impact of treating the accumulated patient stock can be managed by stratified rollout that delays treatment of stable patients and prioritizes patients at high risk of deterioration. Delay spreads the budget impact and permits potential savings from launch of competing treatments. For cures, installment payments contingent on outcomes could align payment flows and appropriately shift risk to producers. This approach, however, entails high administrative and incentive costs, especially if applied across multiple payers in the United States. For orphan drugs, the available evidence on research and development trends and returns argues against the need for a higher VBP threshold to incentivize research and development in orphan drugs, given existing statutory benefits under orphan drug legislation., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Increased costs in the health sector have put considerable strain on the public budgets allocated to pharmaceutical purchases. Faced with such pressures amplified by financial crises and pandemics, national purchasing authorities are presented with a puzzle: how to procure pharmaceuticals of the highest quality for the lowest price. The literature explored a range of impactful factors using data on producer and reference prices, but largely foregone the use of data on individual purchases by diverse public buyers., Methods: Leveraging the availability of open data in public procurement from official government portals, the article examines the relationship between unit prices and a host of predictors that account for policies that can be amended nationally or locally. The study uses traditional linear regression (OLS) and a machine learning model, random forest, to identify the best models for predicting pharmaceutical unit prices. To explore the association between a wide variety of predictors and unit prices, the study relies on more than 200,000 purchases in more than 800 standardized pharmaceutical product categories from 10 countries and territories., Results: The results show significant price variation of standardized products between and within countries. Although both models present substantial potential for predicting unit prices, the random forest model, which can incorporate non-linear relationships, leads to higher explained variance (R 2  = 0.85) and lower prediction error (RMSE = 0.81)., Conclusions: The results demonstrate the potential of i) tapping into large quantities of purchase-level data in the health care sector and ii) using machine learning models for explaining and predicting pharmaceutical prices. The explanatory models identify data-driven policy interventions for decision-makers seeking to improve value for money., (© 2024. The Author(s).)

This summary section first lists key points from each of the six sections of the report, followed by six key recommendations. The Special Task Force chose to take a health economics approach to the question of whether a health plan should cover and reimburse a specific technology, beginning with the view that the conventional cost-per-quality-adjusted life-year metric has both strengths as a starting point and recognized limitations. This report calls for the development of a more comprehensive economic evaluation that could include novel elements of value (e.g., insurance value and equity) as part of either an "augmented" cost-effectiveness analysis or a multicriteria decision analysis. Given an aggregation of elements to a measure of value, consistent use of a cost-effectiveness threshold can help ensure the maximization of health gain and well-being for a given budget. These decisions can benefit from the use of deliberative processes. The six recommendations are to: 1) be explicit about decision context and perspective in value assessment frameworks; 2) base health plan coverage and reimbursement decisions on an evaluation of the incremental costs and benefits of health care technologies as is provided by cost-effectiveness analysis; 3) develop value thresholds to serve as one important input to help guide coverage and reimbursement decisions; 4) manage budget constraints and affordability on the basis of cost-effectiveness principles; 5) test and consider using structured deliberative processes for health plan coverage and reimbursement decisions; and 6) explore and test novel elements of benefit to improve value measures that reflect the perspectives of both plan members and patients., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

The fourth section of our Special Task Force report focuses on a health plan or payer's technology adoption or reimbursement decision, given the array of technologies, on the basis of their different values and costs. We discuss the role of budgets, thresholds, opportunity costs, and affordability in making decisions. First, we discuss the use of budgets and thresholds in private and public health plans, their interdependence, and connection to opportunity cost. Essentially, each payer should adopt a decision rule about what is good value for money given their budget; consistent use of a cost-per-quality-adjusted life-year threshold will ensure the maximum health gain for the budget. In the United States, different public and private insurance programs could use different thresholds, reflecting the differing generosity of their budgets and implying different levels of access to technologies. In addition, different insurance plans could consider different additional elements to the quality-adjusted life-year metric discussed elsewhere in our Special Task Force report. We then define affordability and discuss approaches to deal with it, including consideration of disinvestment and related adjustment costs, the impact of delaying new technologies, and comparative cost effectiveness of technologies. Over time, the availability of new technologies may increase the amount that populations want to spend on health care. We then discuss potential modifiers to thresholds, including uncertainty about the evidence used in the decision-making process. This article concludes by discussing the application of these concepts in the context of the pluralistic US health care system, as well as the "excess burden" of tax-financed public programs versus private programs., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

The fifth section of our Special Task Force report identifies and discusses two aggregation issues: 1) aggregation of cost and benefit information across individuals to a population level for benefit plan decision making and 2) combining multiple elements of value into a single value metric for individuals. First, we argue that additional elements could be included in measures of value, but such elements have not generally been included in measures of quality-adjusted life-years. For example, we describe a recently developed extended cost-effectiveness analysis (ECEA) that provides a good example of how to use a broader concept of utility. ECEA adds two features-measures of financial risk protection and income distributional consequences. We then discuss a further option for expanding this approach-augmented CEA, which can introduce many value measures. Neither of these approaches, however, provide a comprehensive measure of value. To resolve this issue, we review a technique called multicriteria decision analysis that can provide a comprehensive measure of value. We then discuss budget-setting and prioritization using multicriteria decision analysis, issues not yet fully resolved. Next, we discuss deliberative processes, which represent another important approach for population- or plan-level decisions used by many health technology assessment bodies. These use quantitative information on CEA and other elements, but the group decisions are reached by a deliberative voting process. Finally, we briefly discuss the use of stated preference methods for developing "hedonic" value frameworks, and conclude with some recommendations in this area., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

The third section of our Special Task Force report identifies and defines a series of elements that warrant consideration in value assessments of medical technologies. We aim to broaden the view of what constitutes value in health care and to spur new research on incorporating additional elements of value into cost-effectiveness analysis (CEA). Twelve potential elements of value are considered. Four of them-quality-adjusted life-years, net costs, productivity, and adherence-improving factors-are conventionally included or considered in value assessments. Eight others, which would be more novel in economic assessments, are defined and discussed: reduction in uncertainty, fear of contagion, insurance value, severity of disease, value of hope, real option value, equity, and scientific spillovers. Most of these are theoretically well understood and available for inclusion in value assessments. The two exceptions are equity and scientific spillover effects, which require more theoretical development and consensus. A number of regulatory authorities around the globe have shown interest in some of these novel elements. Augmenting CEA to consider these additional elements would result in a more comprehensive CEA in line with the "impact inventory" of the Second Panel on Cost-Effectiveness in Health and Medicine. Possible approaches for valuation and inclusion of these elements include integrating them as part of a net monetary benefit calculation, including elements as attributes in health state descriptions, or using them as criteria in a multicriteria decision analysis. Further research is needed on how best to measure and include them in decision making., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

This paper presents new evidence on availability, use, and prices of biopharmaceuticals in five major European Union (EU) markets, Canada, Australia, Japan, and Mexico, relative to the United States. Our data set from IMS Health includes all product sales in 2005. Per capita spending on biopharmaceuticals was at least twice as high in the United States as in the other countries. This difference reflects primarily greater availability and use of new, relatively high-price molecules and formulations. Prices for identical formulations are not higher on average in the United States. The broader price indexes, which do not control formulation, are also not higher in the United States, after adjusting for income. [ABSTRACT FROM AUTHOR]

In U.S. vaccine markets, competing producers with high fixed, sunk costs face relatively concentrated demand. This tends to lead to exit of all but one or very few producers per vaccine. Detailed evidence of exits and shortages in the flu vaccine market demonstrates the importance of high fixed costs, demand uncertainty, and dynamic quality competition. A comparison of vaccine suppliers in four industrialized countries compared with the United States shows that smaller foreign markets often have more and different vaccine suppliers. High, country-specific, fixed costs, combined with price and volume uncertainty, plausibly deters these potential suppliers from attempting to enter the U.S. market. [ABSTRACT FROM AUTHOR]

Introduction: The goal of this economic model is to estimate an economically justifiable price (EJP) for using donanemab for the treatment of early symptomatic Alzheimer's disease (AD) in the United States based on clinical data from the phase 3 TRAILBLAZER-ALZ 2 trial (NCT04437511). Methods: We adapted an AD Markov state-transition model developed by the Institute for Clinical and Economic Review to estimate the EJP for donanemab at different willingness-to-pay (WTP) thresholds from the health care system perspective and the societal perspective as co-base cases. Results: Assuming a WTP threshold of $150,000 per quality-adjusted life-year (QALY) gained, the model estimates a 1-year (13-dose) EJP for donanemab of $80,538 from the health care system perspective and $91,126 from the societal perspective; at a WTP threshold of $100,000 per QALY gained, the model estimates a 1-year (13-dose) EJP for donanemab of $44,691 from the health care system perspective and $55,419 from the societal perspective. Mean total treatment costs per patient at the $150,000 per QALY gained EJP derived from the health care system perspective were estimated at $77,812 based on the average number of doses of donanemab patients received in the co-base case analysis. One-way sensitivity analysis (OWSA) indicated that treatment efficacy, disease severity at the time of treatment initiation, and duration of treatment effect were the main drivers of the potential EJP. Conclusions: Results from this modeling simulation informed by the TRAILBLAZER-ALZ 2 study support an EJP for limited-duration treatment with donanemab that exceeds per-dose list prices for currently available amyloid-targeting therapies, implying potentially lower lifetime costs and better value for money. [ABSTRACT FROM AUTHOR]

This paper analyzes determinants of ex-manufacturer prices for originator and generic drugs across countries. We focus on drugs to treat HIV/AIDS, TB, and malaria in middle and low-income countries (MLICs), with robustness checks to other therapeutic categories and the full income range of countries. We examine the effects of per capita income, income dispersion, competition from originator and generic substitutes, and whether the drugs are sold to retail pharmacies versus tendered procurement by non-government organizations. The cross-national income elasticity of prices is 0.27 across the full income range of countries but is 0.0-0.10 between MLICs, implying that drugs are least affordable relative to income in the lowest income countries. Within-country income inequality contributes to relatively high prices in MLICs. Although generics are priced roughly 30% lower than originators on average, the variance is large. Additional generic competitors only weakly affect prices, plausibly because generic quality uncertainty leads to competition on brand rather than price. Tendered procurement that imposes quality standards attracts multinational generic suppliers and significantly reduces prices of originator and generic drugs, compared with their respective prices to retail pharmacies., (© 2013 The Authors Health Economics Published by John Wiley & Sons Ltd.)

Purpose: This study examines the effect of price regulation and competition on launch timing and pricing of new drugs., Methods: Our data cover launch experience in 15 countries from 1992 to 2003 for drugs in 12 major therapeutic classes. We estimate a two-equation model of launch hazard and launch price of new drugs., Findings: We find that launch timing and prices of new drugs are related to a country's average prices of established products in a class. Thus to the extent that price regulation reduces price levels, such regulation directly contributes to launch delay in the regulating country. Regulation by external referencing, whereby high-price countries reference low-price countries, also has indirect or spillover effects, contributing to launch delay and higher launch prices in low-price referenced countries., Implications: Referencing policies adopted in high-price countries indirectly impose welfare loss on low-price countries. These findings have implications for US proposals to constrain pharmaceutical prices through external referencing and drug importation.

Finding better mechanisms to enable differential pricing that reflects different degrees of willingness to pay across countries with different income levels is an important challenge for drug manufacturers and policy makers. Drug prices must be high enough to meet manufacturers' needs--covering costs and ensuring adequate investment in research and development, as well as producing a profit--but low enough to allow consumers access to medicines that they need. Examining drug pricing, we found that in rich countries, insurance coverage can make consumers insensitive to price, which means that manufacturers' prices are largely unrestrained unless payers intervene. In middle- and low-income countries, where most consumers pay for drugs out of pocket, we found that the poorest countries face the highest prices, relative to their mean per capita income. We recommend that countries and payers set their own cost-effectiveness thresholds to reflect how much they are willing to pay for "health gain"--in other words, for a measured improvement in the health of a person or a population. Adopting this approach broadly should lead to appropriate price differences across and within countries, benefiting consumers and manufacturers alike.

The option of legalizing the commercial importation of prescription drugs is of continued policy interest as a way to reduce U.S. drug spending. Using IMS data, we estimate potential savings from commercial drug importation under assumptions about percentage of drugs likely to attract imports; potential supply from foreign countries; and share of savings passed on to payers. Our base case estimate is that $1.7 billion per year, or 0.6 percent of total drug spending, would be saved by payers; sensitivity analyses range from 0.2 to 2.5 percent under plausible assumptions and up to 17.4 percent under unrealistic assumptions about unlimited foreign supply, costless trade, and zero profits for intermediaries. Estimated savings to payers are less than the average price differentials between the United States and foreign countries because proposed legislation exempts certain drugs from importation; foreign markets are small relative to the United States; regulatory and other constraints may limit the volume of exports; trade is costly; and intermediaries will retain some savings. Although savings to U.S. payers/consumers would likely be small and have minimal impact on total U.S. health care spending, costs to other countries could be significant, due to reduced access and possibly higher prices. In the long run, reduced investment in R&D could adversely affect consumers globally.

This paper examines the issue of prices, relative to value, for cancer drugs. The analysis focuses on the effects on manufacturer pricing incentives of insurance coverage, specifically, the effectiveness of patient cost sharing, incentives created by reimbursement rules for physician-dispensed drugs, and payer ability and incentives to negotiate discounts. For pharmacy-dispensed cancer drugs, both Medicare Part D prescription drug plans (PDPs) and private payers' pharmacy benefit managers are increasingly placing these drugs on specialty tiers that offer no leverage for negotiating discounts and imply often unaffordable cost sharing for patients who lack catastrophic coverage. Simulation analysis of financial risks faced by PDPs confirms their incentives to place costly drugs on specialty tiers if more preferred formulary placement would increase use, possibly because of adverse selection risk. Faced with largely price-insensitive consumers and payers, manufacturers would rationally charge high prices. This situation is exacerbated for physician-dispensed cancer drugs, where Medicare's average selling price plus 6% reimbursement rule favors high-priced drugs. Because U.S. payers do not require evidence on prices relative to value, U.S. data are unavailable to test whether prices are higher, relative to value, for cancer drugs than for other drugs. Evidence from the Canadian Common Drug Review on cost-utility values suggests that cancer drugs are relatively high priced, although conclusions are tentative because of very small samples and non-U.S. data. Making such outcomes-adjusted prices available in the U.S. would be helpful to physicians, payers, and patients and indirectly constrain pricing to align with value.

This paper compares pharmaceutical spending, availability, use, and prices in twelve countries in 2005. Drug spending per capita was higher in the United States than in other countries. The United States had relatively high use of new drugs and high-strength formulations; other countries used more of older drugs and weaker formulations. Thus, whether U.S. overall volume of use is lower or higher depends on the measure of volume and type of product. Comprehensive price indexes show foreign prices to be 20-40 percent lower than U.S. manufacturer prices, but only 10-30 percent lower than U.S. public prices. Generics are cheaper in the United States than in other countries.

Background: Germany was the first country worldwide to offer mobile digital health applications (mHealth apps, "DiGA") on prescription with full cost coverage by statutory health insurances. Especially statutory health insurances criticize the current pricing and payment regulations in Germany due to "free and non-transparent" pricing in the first year and lack of cost use evidence. The study consists of two parts: The first part evaluates interests of digital health application providers and statutory health insurances in Germany to identify overlaps and divergences of interests. The second part includes the development of a comprehensive pricing and payment taxonomy for reimbursable mHealth apps in general. Methods: Both parts of the study used the input from 16 expert interviews with representatives of digital health application providers and statutory health insurances in Germany. In part one the authors conducted a qualitative content analysis and in part two they followed the taxonomy development process according to Nickerson et al. (2013). Results: A value based care model is expected to bring the greatest benefit for patients while statutory health insurances welcome the idea of usage based pricing. The final pricing and payment taxonomy consists of four design and negotiation steps (price finding, payment prerequisites, payment modalities, composition of negotiation board). Conclusions: As healthcare resources are scarce and thus need to be optimally allocated, it is important to implement pricing and payment terms for reimbursable mHealth apps that result in the greatest benefit for patients. To the best of the authors' knowledge, there has been no structured study yet that examines alternative pricing strategies for reimbursable mHealth apps.The developed pricing and payment taxonomy for reimbursable mHealth apps serves as planning and decision basis for developers, health policy makers and payers internationally. [ABSTRACT FROM AUTHOR]

We examine the short-term market impact of the beginning of the military conflict between Russia and Ukraine (24 February 2022) on the world's largest insurance firms. Using an event study for the 100 largest listed insurers globally, we observe that the unexpected loss effect seems to prevail over the long-term growth effect, leading to a decrease of insurance firm's equity market values. Furthermore, our results show a higher negative stock market reaction for foreign insurers with a high exposure to Russian/Ukrainian markets. These results also confirm the existence of a 'proximity penalty' for firms in the vicinity of the war zone. Finally, our results provide insight into which insurer-specific characteristics emerge as value drivers. Larger, well-capitalised, profitable and life or diversified insurance firms with less institutional ownership have superior stock market returns and are more able to handle the losses resulting from the war. [ABSTRACT FROM AUTHOR]

Background: Cost-effectiveness analysis (CEA) has become a crucial technique in appraising the efficiency of healthcare interventions and resource allocation decisions. Cost-effectiveness analysis is now widely used to evaluate whether the effect of a healthcare intervention justifies additional expenditure. Method: We used PubMed database with search descriptors: "Cost effectiveness" [Title / Abstract] OR "Cost effectiveness analysis" [Title / Abstract] AND "Healthcare" [Title / Abstract]. The common bibliometric indicators were applied. Results: We retrieved a total of 7,561 articles within 2013 and 2023. The growth pattern showed a progressive pattern. Articles with 5 authors signature had the highest number in publication. The most productive authors in cost effectiveness research in healthcare were Liew Danny and Ademi Zanfina. The most utilized journals for the publications were BMJ Open, PLoS One and Journal of Medical Economics. The most productive institutions were resident in United Kingdom with the University of York and University of Oxford at the helm. Conclusion: Scientific production in Cost effectiveness in healthcare research was found to be progressive. This study provides a reference for health policy makers, funders, policy decision makers, academics, and hospital economics researchers. [ABSTRACT FROM AUTHOR]

Objective: The engagement of patients and family caregivers in value assessment is pivotal since they provide valuable contributions to assessment acceptability and relevance. The proposed study aims to use patient-centered techniques and multicriteria decision analysis (MCDA) to evaluate the values of disease-modifying therapies (DMTs) for multiple sclerosis (MS) from the perspectives of patients and family caregivers living in three 'Deep South' States of the US—Alabama, Louisiana, and Mississippi. Methods: This study will follow guidance from the Patient-Centered Outcomes Research Institute (PCORI) for patient engagement and two best practice reports for MCDA from the Professional Society for Health Economics and Outcomes Research (ISPOR) to complete value assessment. Throughout the study, we will engage multiple stakeholders, including patients, family caregivers, healthcare providers, and payers. Forty patients with MS and their family caregivers from Alabama, Louisiana, and Mississippi will be invited to participate in this study. We will intensively train them for value assessment knowledge and MCDA before we engage them in MCDA to determine the value of DMTs for MS. Discussions: Our approach differs from common MCDA since we incorporated a patient-centered framework in this study. Unlike previous studies only briefly inform or prepare participants before the MCDA process, in this study, we will provide basic value assessment trainings for patients and family caregivers to ensure they can effectively engage throughout the patient-centered MCDA process. We expect this study will demonstrate that the patient-centered MCDA approach is feasible and likely leads to improved patients' and family caregivers' engagement in value assessment. [ABSTRACT FROM AUTHOR]

The role of essential medicines is to smoothen life and overall improvement of health in the society. However, increased demand for medications and the role of patent rights are forcing a lack of access to essential medicines. Innovations in crucial times helped solve many population issues. Despite the availability of medication technology, there is a shortage or non-availability of essential medicines in various parts of the world. This is indirectly attributed to the existing patent laws and intellectual property rights. This paper argues in favour of and against the pharmaceutical sector’s patent laws in the context of access to medicines. Further, access to medicine is discussed in the context of the non-availability of medications among the vulnerable population in India and the world. The Indian setup helps in acquiring world technologies in various business negotiations. There is also a need for support in terms of resources and ecosystems in India for further development. Given that multi-national companies are interested in the Indian market, many things can be done quickly. However, the gain in the patent rights may not help solve the issues of access to essential medicines. Public financing for research can be much more useful for access to medicine. Overall, patent rights must not be a hurdle for addressing public health issues in the process of increasing access to medicines. [ABSTRACT FROM AUTHOR]

An important issue in economic evaluations is determining whether all relevant impacts are considered, given the perspective chosen for the analysis. Acknowledging that patients are not isolated individuals has important implications in this context. Increasingly, the term "spillovers" is used to label consequences of health interventions on others. However, a clear definition of spillovers is lacking, and as a result, the scope of the concept remains unclear. In this study, we aim to clarify the concept of spillovers by proposing a definition applicable in health economic evaluations. To illustrate the implications of this definition, we highlight the diversity of potential spillovers through an expanded impact inventory and conduct a mapping review that outlines the evidence base for the different types of spillovers. In the context of economic evaluations of health interventions, we define spillovers as all impacts from an intervention on all parties or entities other than the users of the intervention under evaluation. This definition encompasses a broader range of potential costs and effects, beyond informal caregivers and family members. The expanded impact inventory enables a systematic approach to identifying broader impacts of health interventions. The mapping review shows that the relevance of different types of spillovers is context-specific. Some spillovers are regularly included in economic evaluations, although not always recognised as such, while others are not. A consistent use of the term "spillovers", improved measurement of these costs and effects, and increased transparency in reporting them are still necessary. To that end, we propose a research agenda. [ABSTRACT FROM AUTHOR]

Using data on over 900 firms for the period 1988-2000, we estimate the effect on phase-specific biotech and pharmaceutical R&D success rates of a firm's overall experience, its experience in the relevant therapeutic category, the diversification of its experience across categories, the industry's experience in the category, and alliances with large and small firms. We find that success probabilities vary substantially across therapeutic categories and are negatively correlated with mean sales by category, which is consistent with a model of dynamic, competitive entry. Returns to experience are statistically significant but economically small for the relatively straightforward phase 1 trials. We find evidence of large, positive and diminishing returns to a firm's overall experience (across all therapeutic categories) for the larger and more complex late-stage trials that focus on a drug's efficacy. There is some evidence that a drug is more likely to complete phase 3 if developed by firms whose experience is focused rather than broad (diseconomies of scope). There is evidence of positive knowledge spillovers across firms for phase 1. However, for phase 2 and phase 3 the estimated effects of industry-wide experience are negative, which may reflect either higher Food and Drug Administration (FDA) approval standards in crowded therapeutic categories or that firms in such categories must pursue more difficult targets. Products developed in an alliance tend to have a higher probability of success, at least for the more complex phase 2 and phase 3 trials, and particularly if the licensee is a large firm.

Reimbursement options for pharmaceuticals reimbursed under Medicare Part B (physician-dispensed drugs) are changing and the new comprehensive Part D Medicare outpatient drug benefit brings further changes. The Medicare Prescription Drug, Improvement and Modernization Act of 2003 (MMA) replaces traditional policy, of reimbursing Part B drugs at 95% of average wholesale price (AWP, a list price), with a percentage markup over the manufacturer's average selling price; in 2005 an indirect competitive procurement option will be introduced. In our view, although AWP-based reimbursement has been fraught with problems in the past, these could be fixed by constraining growth in AWP and periodically adjusting the discount off AWP. With these revisions, an AWP-based rule would preserve incentives for competitive discounting and deliver savings to Medicare. By contrast, basing Medicare reimbursement on a manufacturer's average selling price undermines incentives for discounting and, like any cost-based reimbursement rule, may result in higher prices to both public and private purchasers. Indirect competitive procurement for drugs alone, using specialty pharmacies, pharmacy benefit managers, or prescription drug plans, is unlikely to constrain costs to acceptable levels unless contractors retain flexibility to use standard benefit management tools. Folding Part B and Part D into comprehensive contracting with health plans for full health services is likely to offer the most efficient approach to managing the drug benefit.

We analyze the effect of price regulation on delays in launch of new drugs. Because a low price in one market may 'spill-over' to other markets, through parallel trade and external referencing, manufacturers may rationally prefer longer delay or non-launch to accepting a relatively low price. We analyze the launch in 25 major markets, including 14 EU countries, of 85 new chemical entities (NCEs) launched between 1994 and 1998. Each NCE's expected price and market size in a country are estimated using lagged average price and market size of other drugs in the same (or related) therapeutic class. We estimate a Cox proportional hazard model of launch in each country, relative to first global launch. Only 55% of the potential launches occur. The US leads with 73 launches, followed by Germany (66) and the UK (64). Only 13 NCEs are launched in Japan, 26 in Portugal and 28 in New Zealand. The results indicate that countries with lower expected prices or smaller expected market size have fewer launches and longer launch delays, controlling for per capita income and other country and firm characteristics. Controlling for expected price and volume, country effects for the likely parallel export countries are significantly negative.

The price differentials reported by Gerard Anderson and colleagues are not fully representative and are probably biased upward. If Congress does seek to reduce drug prices, there are no simple, effective, and efficient strategies. The most likely is drug importation, which would be ineffective at lowering U.S. drug costs and would pose sizable safety risks, yet it would reduce research and development (R&D) costs and access for foreign consumers. Careful cost-effectiveness analysis would be more appropriate than trying to import other countries' price controls. Income-related subsidies are a better strategy for dealing with excessive cost sharing for low-income seniors.

This paper describes three prototypical systems of therapeutic reference pricing (RP) for pharmaceuticals--Germany, the Netherlands, and New Zealand--and examines their effects on the availability of new drugs, reimbursement levels, manufacturer prices, and out-of-pocket surcharges to patients. RP for pharmaceuticals is not simply analogous to a defined contribution approach to subsidizing insurance coverage. Although a major purpose of RP is to stimulate competition, theory suggests that the achievement of this goal is unlikely, and this is confirmed by the empirical evidence. Other effects of RP differ across countries in predictable ways, reflecting each country's system design and other cost-control policies. New Zealand's RP system has reduced reimbursement and limited the availability of new drugs, particularly more expensive drugs. Compared to these three countries, if RP were applied in the United States, it would likely have a more negative effect on prices of onpatent products because of the more competitive U.S. generic market, and on research and development (R&D) and the future supply of new drugs, because of the much larger U.S. share of global pharmaceutical sales.

This paper reviews the economic case for patents and the potential for differential pricing to increase affordability of on-patent drugs in developing countries while preserving incentives for innovation. Differential pricing, based on Ramsey pricing principles, is the second best efficient way of paying for the global joint costs of pharmaceutical R&D. Assuming demand elasticities are related to income, it would also be consistent with standard norms of equity. To achieve appropriate and sustainable price differences will require either that higher-income countries forego trying to "import" low drug prices from low-income countries, through parallel trade and external referencing, or that such practices become less feasible. The most promising approach that would prevent both parallel trade and external referencing is for payers/purchasers on behalf of developing countries to negotiate contracts with companies that include confidential rebates. With confidential rebates, final transactions prices to purchasers can differ across markets while manufacturers sell to distributors at uniform prices, thus eliminating opportunities for parallel trade and external referencing. The option of compulsory licensing of patented products to generic manufacturers may be important if they truly have lower production costs or originators charge prices above marginal cost, despite market separation. However, given the risks inherent in compulsory licensing, it seems best to first try the approach of strengthening market separation, to enable originator firms to maintain differential pricing. With assured market separation, originators may offer prices comparable to the prices that a local generic firm would charge, which eliminates the need for compulsory licensing. Differential pricing could go a long way to improve LDC access to drugs that have a high income market. However, other subsidy mechanisms will be needed to promote R&D for drugs that have no high income market.

This study compares average price levels for pharmaceuticals in eight countries--Canada, Chile, France, Germany, Italy, Japan, Mexico, and the United Kingdom--relative to the United States. Our most comprehensive indexes, adjusted for U.S. manufacturer discounts, show Japan's prices to be higher than U.S. prices, and other countries' prices ranging from 6 percent to 33 percent lower than U.S. prices. The decline of the Canadian dollar and rise of the U.K. pound contribute to the finding of lower Canadian prices and higher U.K. prices in 1999 than in 1992. Our findings suggest that U.S.-foreign price differentials are roughly in line with income and smaller for drugs than for other medical services.

Background and Objective: Health plans are increasingly using more open drug formularies that offer differential prescription copayments as an incentive to enrollees to use brands that plans prefer. How much this financial incentive affects use of preferred brands has not been widely reported. The aim of this study was to estimate the effect of tiered copayments on the choice between preferred and nonpreferred brand medications., Materials and Methods: Longitudinal logistic regression analyses of pharmacy claims from 1998 and 1999 comparing concurrent groups that were or were not exposed to tiered copayments., Subjects: Enrollees in four independent physician practice association model health plans who had pharmacy claims for angiotensin converting enzyme inhibitors (ACEI), proton pump inhibitors (PPI), or hydroxymethylglutaryl coenzyme A reductase inhibitors (STATINS)., Outcome Measure: Change in the percentage of prescription claims that were for preferred brands., Main Results: Regression adjusted estimates of the average net increase in the percentage use of preferred brands of ACEI, PPI and STATIN from first quarter 1998 to third quarter 1999 attributed to tiered prescription copayments were 13.3 (P = 0.001), 8.9 (P = 0.03), and 6.0 (P <0.001) percentage points, respectively., Conclusions: Tiered prescription copayments were associated with a significant shift from nonpreferred to preferred brand medications. This type of financial incentive can help purchasers providing open access drug benefits by steering use of medications toward lower cost brands. The clinical effects of changes in medication use brought about differential copayments warrant further investigation.

Most studies on the indirect costs of an illness and the cost effectiveness of a medical intervention or employer-sponsored wellness program assume that the value of reducing the number of days employees miss from work due to illness is the wage rate. This paper presents a general model to examine the magnitude and incidence of costs associated with absenteeism under alternative assumptions regarding the size of the firm, the production function, the nature of the firm's product, and the competitiveness of the labor market. We conclude that the cost of lost work time can be substantially higher than the wage when perfect substitutes are not available to replace absent workers and there is team production or a penalty associated with not meeting an output target. In the long run, workers are likely to bear much of the incidence of the costs associated with absenteeism, and therefore be the likely beneficiaries of any reduction in absenteeism., (Copyright 2001 John Wiley & Sons, Ltd.)

As policymakers consider whether and how to add prescription drug coverage to Medicare, they need to understand the relationship between insurance coverage and the adoption of new medical technologies, including drugs. Even the direction of these relationships is not always so clear. In this Issue Brief, Drs. Danzon and Pauly examine the shift from inpatient to outpatient care in the last 20 years,and ask two broad questions: to what extent was this shift encouraged by changes in insurance, and to what extent was insurance coverage influenced by this shift?

This paper traces the relationship between insurance coverage and the technology-induced shift of the locus of medical care and medical spending from the inpatient to the outpatient setting. This shift was accompanied by an increase in the extent of private insurance coverage for outpatient treatments; technological change both caused the increase in coverage (for more costly treatments) and was affected by it (as lower user prices increased the demand for new types of care). Changes in insurance administration technology also facilitated the transformation. Some aspects of the change may have been inefficient, because of the presence of tax subsidy and legal requirements to cover costly new technologies of low effectiveness, but the transformation appears thus far to have worked better for private insurance than for Medicare.

Bilateral drug price and quantity indexes, based on comprehensive data for seven countries (US, Canada, France, Germany, Italy, Japan and the UK), refute the conventional wisdom that US drug prices are much higher than elsewhere, for Laspeyres (US-weighted) indexes. Previous drug-price comparisons are biased by unrepresentative samples and unweighted indexes. Quasi-hedonic regression shows that cross-national price differences reflect differences in product characteristics and in their implicit prices, which reflect the regulatory regime. Strict price regulation systematically lowers prices for older molecules and globally diffused molecules. Generic competition lowers prices in less-regulated regimes, which also have more price-elastic demand.

The potential for parallel trade in the European Union (EU) has grown with the accession of low price countries and the harmonisation of registration requirements. Parallel trade implies a conflict between the principle of autonomy of member states to set their own pharmaceutical prices, the principle of free trade and the industrial policy goal of promoting innovative research and development (R&D). Parallel trade in pharmaceuticals does not yield the normal efficiency gains from trade because countries achieve low pharmaceutical prices by aggressive regulation, not through superior efficiency. In fact, parallel trade reduces economic welfare by undermining price differentials between markets. Pharmaceutical R&D is a global joint cost of serving all consumers worldwide; it accounts for roughly 30% of total costs. Optimal (welfare maximising) pricing to cover joint costs (Ramsey pricing) requires setting different prices in different markets, based on inverse demand elasticities. By contrast, parallel trade and regulation based on international price comparisons tend to force price convergence across markets. In response, manufacturers attempt to set a uniform 'euro' price. The primary losers from 'euro' pricing will be consumers in low income countries who will face higher prices or loss of access to new drugs. In the long run, even higher income countries are likely to be worse off with uniform prices, because fewer drugs will be developed. One policy option to preserve price differentials is to exempt on-patent products from parallel trade. An alternative is confidential contracting between individual manufacturers and governments to provide country-specific ex post discounts from the single 'euro' wholesale price, similar to rebates used by managed care in the US. This would preserve differentials in transactions prices even if parallel trade forces convergence of wholesale prices.

Cross-national price comparisons for pharmaceuticals are commonly used for two purposes. Comparisons based on a sample of products are used to draw conclusions about differences in average price levels. Cross-national comparisons applied to individual products are also used by governments to set domestic prices. This paper examines the major methodological issues raised by international price comparisons, focusing on measurement of differences in average price levels and the validity of policy conclusions drawn from such price comparison studies. It argues that valid measures of average price levels can only be obtained from comparisons based on a comprehensive or representative sample of products, appropriately weighted, following standard index number methods. Comparisons of individual product prices should take into account the manufacturer's entire product portfolio over time rather than focus narrowly on a single product at a point in time. Because of the great variation across countries in both the range of drug compounds available and the dosage forms, strengths and pack sizes for each compound, obtaining a broadly comprehensive or representative sample is problematical. If products are required to match on all dimensions, including molecule, manufacturer, strength and pack, as is common in most international price comparisons, then only a very small and unrepresentative sample of the drugs available in each country can be included in the analysis. A trade-off between the desire to compare only identical products and the need to compare a truly representative sample of a country's pharmaceutical market is therefore necessary. A valid comparison of average drug prices should include generics and over-the-counter products that are good substitutes for branded prescription drugs, with all forms, strengths and packs. To achieve this broad representation, however, the requirements of same manufacturer, same brand, dosage form, strength and pack size must be dropped. When such an approach is taken to the comparison of international drug prices, quite different results from those obtained from less comprehensive comparisons may be obtained. Indeed, a major conclusion of this analysis is that international drug price comparisons are extremely sensitive to choices made about certain key methodological issues, such as sample selection, unit of measurement for price and volume, the relative weight given to consumption patterns in the countries being compared, and the use of exchange rates or purchasing power parities for currency conversion. In particular, the results of this analysis indicate that recent reports suggesting that manufacturer prices in the US are 32% higher than in Canada and 60% higher than in the UK are in fact overstatements which arise from limitations of the sample and methods used to calculate these price differentials.

Rising expenditures on health care in the U.S. have been facilitated by the fundamental problems of asymmetric information and insurance-induced moral hazard. If managed care is to succeed, it must take both into account through strategies such as information-based consumer education and provider risk-sharing. Because larger networks offer significant advantages in implementing such strategies, hospital mergers, physician-hospital alliances, and economies of scale are major trends in the evolution of managed care.