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An analysis of expenditures on primary care prescription drugs in the United States versus ten comparable countries
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An analysis of expenditures on primary care prescription drugs in the United States versus ten comparable countries Steven G. Morgan a,∗ , Chester B. Good b , Christine Leopold c , Anna Kaltenboeck d , Peter B. Bach d , Anita Wagner c a
School of Population and Public Health, University of British Columbia, #267 – 2206 East Mall, Vancouver, BC, V6T 1Z3, Canada UPMC Center for Value-Based Pharmacy Initiatives, and University of Pittsburgh, School of Pharmacy and School of Medicine, Pittsburgh, PA, USA c Drug Policy Research Group, Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, USA d Center for Health Policy and Outcomes, Memorial Sloan Kettering Cancer Center, New York, USA b
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Article history: Received 13 March 2017 Received in revised form 5 July 2018 Accepted 6 July 2018 Keywords: Pharmaceuticals Expenditures Cost-drivers Prices International comparisons Prescription drugs
a b s t r a c t Objective: We sought to estimate size and sources of differences in per capita expenditures on primary care medications in the US versus ten comparable countries combined: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom. Methods: Using market research data on year 2015 volumes and sales of medicines, we measure total per capita expenditures on six categories of primary care prescription drugs: hypertension treatments, pain medications, lipid lowing medicines, non-insulin diabetes treatments, gastrointestinal preparations, and antidepressants. We quantified the contributions of five drivers of the observed differences in per capita expenditures. Results: We estimated that the US spent 187% more per capita on primary care pharmaceuticals than did the ten comparable countries. Despite the difference in spending levels, on average, Americans actually purchased 14% fewer days of related therapies than residents of the comparator countries. Most of the observed difference in expenditures was due to higher transaction prices of medicines and the use of a more expensive mix of medicines in the US. Conclusions: If utilization patterns and pharmaceutical prices in the US were similar to those in the 10 comparator countries combined, total spending on primary care pharmaceuticals would fall by 30% or more. Such evidence on the level and drivers of US pharmaceutical expenditures should inform policies in this sector. © 2018 Published by Elsevier B.V.
1. Introduction Concern about the cost of prescriptionmedications in the United States (US) is growing, in large part due to recent increases in the prices of new drugs and older ones. [1,2] Prudent management of pharmaceutical expenditures is important so that health systems can ensure universal and affordable access to available medicines [3], and so that the pricing system provides appropriate incentives for valued innovation. While most recent attention has focused on the rising cost of specialty pharmaceuticals, health systems must also manage the cost of more commonly used primary care prescription medicines. Because of the large volume of use, primary care pharmaceuti-
∗ Corresponding author. E-mail address: [email protected] (S.G. Morgan).
cals are expected to account for the majority of pharmaceutical expenditures in the US and comparable health systems for the foreseeable future [4]. Further, competition within primary care drug categories with many off-patent medicines can create savings to expand coverage of medicines still on patent, including specialty medicines. In this study, we quantify the level and drivers of US expenditures on primary care pharmaceuticals relative to ten comparator countries. We do so using economic price and quantity indexes developed to compute cost-drivers in the pharmaceutical sector. Our focus on primary care categories of medicine illustrates differences in these high-volume therapeutic categories. This focus also facilitated the selection of categories wherein drugs are typically sold in oral solid dosage forms (as compared to drug classes where medicines frequently come in varied dosage forms), and are predominantly purchased from community pharmacies (as opposed to institutional settings such as hospitals or cancer clinics). Both
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of those characteristics of the drugs classes under study increase the reliability and comparability of market research data across countries.
2. Design and methods This is a comparative economic analysis of 2015 prescription drug sales and volume for the US and ten comparator countries: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom. These countries were chosen because their combined population in 2015 was similar to the US population of (318 million versus 321 million) and they are all high-income countries (average GDP per capita of US$45,018 in 2015) whose health care systems are used for comparison to the USA in the annual Commonwealth Fund’s International Health Policy surveys [5]. Residents of all of the comparator countries except Canada were eligible for universal health coverage that included universal coverage of outpatient prescription drugs. Residents in Canada were eligible for universal public health insurance for medical and hospital care (including inpatient prescription drugs) but may or may not have access to either public or private coverage for prescriptions used in the community setting depending on their age, occupation, income, and province of residence [6]. The systems of drug coverage in Australia, New Zealand, Norway, Sweden, and the United Kingdom can be described as universal public systems. In these countries, prescription medicines are financed predominantly by government and either government or an arms-length public body manages the selection and the price setting of medicines to be covered by the universal system of public financing. Prescription drugs in France, Germany, the Netherlands, and Switzerland are financed through multiple-payer, social insurance systems with various statutory policies governing minimum coverage and pricing for originators and generics.
3. Data sources The local currency value and volume of sales of medicines in the US and comparator countries were obtained from the IMS MIDAS sales database, which captures more than 95 percent of the value of the global pharmaceutical market [7]. These data reflect transaction prices that exclude rebates received from manufacturers of branded products by institutional purchasers in the US and other countries. Foreign sales were converted to US$ by applying a constant exchange rate (Q1 2016). A sensitivity analysis found that the alternative use of purchasing power parities PPPs did not alter findings because ratios of exchange rates to PPPs varied across the comparator countries. The database tracks sales volumes in terms of standard units of a medicine and kilograms of the primary active ingredient. IMS converted these figures into standardized days of therapy using average daily doses for each medicine as computed from IMS Prescribing Insights, which draws on information from a panel of office-based physicians in each country. Although differences are small, estimated average daily doses of some medicines vary by country, reflecting local prescribing behaviors. Sensitivity analyses based showed that differences in average daily doses by country altered overall findings of price versus volume effects by five percent. As rebates paid to institutional purchasers are typically confidential, we were unable to measure them directly. Instead, we estimated spending given ranges of relative price rebates for the US in sensitivity analyses.
4. Drug categories included in the analysis We study the use of and expenditure on six therapeutic categories of primary care prescription drugs based on primary indication. In order of their frequency of use in the United States, these categories were as follows: hypertension treatments; lipid lowing medicines; antidepressants; gastrointestinal preparations (primarily drugs for ulcers and heartburn); non-insulin diabetes treatments; and pain medicines, including nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. Details concerning the drugs within each category are provided in Appendix A. We selected these primary care categories of medicines because they are widely used, typically sold in oral solid dosage forms, and predominantly sold through community pharmacies (as opposed to inpatient settings). All of these factors increase the reliability and comparability of market research data across countries. We focus on medicines with prescription-only status in the United States, which excludes pharmaceuticals commonly sold over-the-counter (e.g., plain acetaminophen for pain) and herbal therapies (e.g., caraway for digestive problems). A total of 1035 different products were included in the study, identified by active ingredient(s) and whether they were branded or generic. These products were assigned into hierarchical, mutually exclusive groupings using the World Health Organization’s Anatomical Therapeutic Chemical (ATC) classification system. In total, the dataset contained 614 different drugs (merging brand and generic versions of the same active ingredients together) that fell into 81 pharmacological classes within the 6 broad therapeutic categories. Collectively, these therapeutics categories account for approximately 25% of prescription drug expenditures in the US.
5. Drivers of variation in expenditure For each therapeutic category, we quantify mutually exclusive sources of the difference in prescription drug expenditures between the US and the combined comparator countries using economic indexes that were developed to compute cost-drivers in the pharmaceutical sector [8–10]. We estimated the effects of five sources of difference in expenditures that fall into three broad categories: volume, choice, and price effects (Fig. 1). Volume reflects the average amounts of prescription drug therapy received by a population. It depicts how much of the difference in expenditures per capita between the US and comparator countries is the result of differences in the average number of days of therapy purchased per capita. The remaining cost-drivers estimate the sources of differences in costs per day of therapy. Choices describe the differences in average daily cost of treatment that stem from differences in the average mix of medicines selected from within therapeutic categories, holding the relative prices of treatment options constant. Other things being equal, prescribing higher cost therapeutic options will result in higher overall spending. The “broad mix” cost-driver reflects the cost impact of the pharmacologic classes selected from within each broad therapeutic category. This includes such choices as whether or not to use diuretics or ACE inhibitors for hypertension treatment. The “narrow mix” cost-driver reflects the cost impact of the selection of specific active ingredients within a particular pharmacologic class. This includes such choices as whether or not to use enalapril or ramipril within the class of ACE-inhibitors; it is, in effect, a choice between a narrower range of therapeutic options than is captured by the broad mix cost-driver.
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6. Statistical and sensitivity analyses This analysis relies on non-stochastic measures; standard tests of statistical significance therefore do not apply. In advance of analysis, we decided that differences of less than 5% in absolute value would not be considered significant. To test for sensitivity of results to the measure of daily doses, analyses were conducted separately for three different measures of quantity: physical units of medicines purchased, kilograms of active ingredient, and days of therapy. To test for sensitivity of results to the exclusion of US rebates, we performed analyses on hypothetical US sales figures under two rebated scenarios based on estimated rebate levels for major purchasers in the US: one scenario in which average rebates for branded products in the US represented 30% of all branded product sales in the US, and one in which US rebates for branded products were assumed to equal 50% of all sales [11,12]. In both cases, we assumed there were no rebates in the comparator countries, which biases results toward understating US prices relative to comparator countries given that confidential rebates are now common and sizable in the comparator countries studied here [13–15].
7. Findings
Fig. 1. Framework for determining the drivers of differences in spending on six primary care medication categories.
Price effects are factors that influence the average unit cost of treatments without altering the quantity or type of active ingredient used. These cost-drivers include “generic use”, which captures the average difference in unit costs of particular types of drug that stem from differences in the rate of generic use of those types of drug, when multi-source products are prescribed. Price effects also include simple differences in “prices”, as measured by a salesweighted average of differences in the unit prices of branded or generic versions of a product. These cost-drivers are computed based on a series of Fisher’s ideal economic price and quantity indexes that have the desirable property of “adding up” in the sense that they explain the total difference in spending between jurisdictions without residuals. The methods are described in detail elsewhere [8,9]. For ease of interpretation, we used logarithms to convert the multiplicative results of the analysis into additive percent changes for each component. The individual cost-drivers will add up exactly to the three respective main cost-driver sub-totals, and those sub-totals will add up to the total differences observed.
As shown in Table 1, total per capita expenditures on the six therapeutic categories of primary care medicines included in this study were $217.1 in the US, compared to $71.6 among the combined comparator countries. In total, expenditures per capita were 203% higher in the US than the comparators. The US spent more per capita on each of the six therapeutic categories, with the greatest differences observed for non-insulin diabetes treatments (436% difference), lipid lowering medicines (290%), and gastrointestinal preparations (223%). Differences in the volume of therapy purchased in US and comparator countries did not explain the differences in expenditures per capita. In total, per capita use of the primary care therapies studied was 12% lower in the US than in the comparator countries (223.2 days of therapy compared to 253.8). Antidepressants were the only therapeutic category studied from which Americans purchased more days of therapy on average than did residents of comparator countries (31.9 days versus 25.9, respectively, a 23% difference). Results were similar in order and magnitude when quantities were measured using standardized units or kilograms of primary active ingredient. The average cost per day of primary care prescription drug therapy in the US was 245% higher than in comparator countries. This was partially due to the selection of higher cost therapeutic options, which increased costs per capita in the US by approximately 44% relative to comparators. However, the biggest driver of higher primary care pharmaceutical expenditure per capita in the US was the higher average prices paid for the products selected. This was primarily due to higher prices of products in these therapeutic categories, rather than differences in generic substitution rates for multi-source drugs. Total estimated expenditures in the US were $69.8 billion in 2015 at transaction prices. This total would be $54.9 billion if branded product sales are rebated at an overall average of 30% in the US, and $44.9 billion if branded products are rebated at an average of 50%. As shown in Table 2, Americans would have spent an estimated total of $23.0 billion on these medicines if the US had per capita expenditure levels equal to that of the comparator countries combined. (The comparator figure is unaffected by assumptions about US branded product price rebates.) The total value of the difference in expenditures in the US under different assumptions about domestic price rebates ranges from $21.9 billion higher to $46.8 billion higher than it would be under
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Table 1 Level and drivers of differences in estimated 2015 spending per capita in the US versus all comparator countries combined. All six therapeutic categories
Non-insulin diabetes treatments
Pain medi- Lipid lowering cations medications
Hypertension medications
Gastrointestinal preparations
Antidepressants
Domestic spending in US per capita Comparator spending per capita Difference in spending per capita
$217.1 $71.6 203%
$52.3 $9.7 436%
$51.1 $17.0 200%
$38.9 $10.0 290%
$31.6 $18.3 72%
$26.9 $8.3 223%
$16.2 $8.1 100%
Domestic days per capita Comparator days per capita Effect of difference in volume of treatment
223.2 253.8 −12%
21.0 20.0 5%
20.4 17.5 16%
34.2 36.5 −6%
91.5 119.2 −23%
24.3 34.7 −30%
31.9 25.9 23%
Effect of difference in broad mix of therapies 24% Effect of difference in narrow mix of therapies 20% Choices - subtotal 44%
12% 1% 13%
38% 34% 73%
−12% 4% −8%
−14% −2% −17%
37% 11% 48%
−3% 56% 52%
Effect of difference in generic utilization Effect of difference in transaction prices Price effects - subtotal
83% 336% 418%
−39% 150% 111%
4% 300% 304%
34% 78% 112%
15% 190% 205%
−47% 71% 24%
19% 152% 171%
Note: “Comparator” represents the per capita average of ten non-US comparator countries: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom.
Table 2 Aggregate impacts of differences in the use and cost of all six categories of primary care medicines in the US vis-à-vis international comparators ($ billions).
At US use and cost levels At comparators’ use and cost levels Total difference in spending Volume (days of therapy) Broad mix of therapies Narrow mix of therapies Choices subtotal Generic use Prices Price effects - subtotal
Unadjusted US prices
With 30% brand rebates in US
With 50% brand rebates in US
$69.8 $23.0 $46.8 -$5.4 $9.2 $7.7 $15.4 $7.5 $38.9 $42.0
$54.9 $23.0 $31.9 -$4.7 $6.0 $4.6 $9.9 $1.5 $28.1 $28.8
$44.9 $23.0 $21.9 -$4.2 $4.2 $2.8 $6.7 -$0.5 $20.4 $20.1
Note: “Comparator” represents the average of ten non-US comparator countries: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom.
comparator drug use and cost profiles. Assuming US purchasers receive average rebates equal to 50% on all branded products brings prices of medicines in the US closer to those in comparator countries – and significantly reduces the estimated cost impact of therapeutic choices because US brands are then closer in price to lower-cost therapeutic alternatives. However, even at that rebate level, Americans would have spent an estimated $21 billion more on primary care medicines in 2015 than they would have if they faced the average prices, prescribing volumes, and therapeutic choices found in the ten comparator countries. 8. Discussion The US spends significantly more per capita than comparable countries on the six categories of commonly-used, primary care medicines studied here. Using best available sales and volume data and an empirical framework for studying pharmaceutical cost drivers, we found that the volume of prescription drug use is not a primary driver of comparatively high US expenditures on primary care medicines. In four of the six therapeutic categories studied, Americans purchased fewer days of prescription drug therapy on average than did residents of the ten comparator countries. This finding is not surprising since greater out of pocket expenses for pharmaceuticals – either because of lack of coverage or copayments in the US – have been shown to correlate with lower adherence to prescribed therapies [16,17].
The primary drivers of relatively high expenditures on medicines in the US were the price and type of medicines selected for treatment. In four of the six therapeutic categories studied, patients in the US received a costlier mix of drug products, reflecting a tendency to receive newer, higher-cost therapeutic options for treatment of given conditions. This not likely to be driven by lower price sensitivity of patients, as the populations in all comparator countries except Canada receive comprehensive drug coverage through their public or statutory health systems. It may, however, be driven by lower price sensitivity of prescribers in the US in comparison to countries with more integrated drug budgeting in primary care, greater presence of direct-to-consumer advertising in the US, or a combination of these and other factors. In all six therapeutic categories studied, prices were significantly higher in the US than in comparator countries. Prices remained a significant driver of US expenditures relative to comparators even under conservative assumptions about the scale of off-invoice price rebating in the US vis-à-vis comparator countries. These differences are greater than would be expected by the modest difference in national incomes: GDP per capita was almost 20% higher in the US than the average for comparator countries in 2015, but price differences were much greater. The lack of statutory price regulations in the US may be a contributor to higher-than-average prices. However, countries like New Zealand achieve relatively low prescription drug prices through negotiation rather than through regulation; and countries like Canada have relatively high drug prices (compared to most countries except the US) despite having price regulations in place for patented drugs [18]. The US also lacks the consolidated purchasing power that comparator countries with single-payer health systems and/or effective national formularies use in negotiations with drug manufacturers. Indeed, US policies over recent decades have increased the market power of pharmaceutical firms by expanding their protections from competition while simultaneously limit the capacity of the Medicare system – what would have been the single largest purchaser or medicines in the US – to exert countervailing market power though single-payer negotiations for the population covered by it.31 Our finding that high US expenditure is primarily a function of the type and price of drug selected is comparable to a 2013 study of cross-national differences in pharmaceutical spending by Kanavos and colleagues, who concluded the effects of international differences in volumes of medicines purchased were smaller than the effects of differences prices and uptake of new drugs [19]. Our find-
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ings concerning the relative prices of drugs in the US compared to the countries studied are also consistent with regularly published price comparisons by Canada’s Patented Medicine Prices Review Board [20,21]. As any analysis of international differences in pharmaceutical use and cost, this study has some important limitations. The datasets used exclude confidential rebates in the US and other countries. However, price remained the most significant driver of higher expenditures in the US under conservative sensitivity analyses that assumed 50% reductions in the US. It is important also to note that we have assumed no price reductions negotiated in comparator countries, despite evidence that rebates are common and often significant in these other countries [15]. This study does not account for differences in morbidity of the populations in each country. Though the US population is not significantly older on average than the population in the comparator countries, the American population may be less healthy. Such a difference in health status would be expected to result in greater volumes of therapy purchased in the US. However, we find that Americans used fewer treatment days of the medicines studied, which may be a result of cost-related barriers to prescription drug adherence in the US [22]. If average morbidity per user of therapy is worse in the US than in the comparator countries, Americans might need highercost types of medicine (e.g., more expensive pharmacologic classes and active ingredients) from within therapeutic categories, which may explain all or part of our findings concerning the costlier mix of treatments selected in the US. Direct-to-consumer advertising, which is legal only in the US and New Zealand, is another potential driver of the more costly mix of therapies in the US, as such advertising is almost exclusively for newer, patented drug products for which manufacturers can recoup costs of promotions [23]. Finally, price may be a greater determinant of product selection in systems where financing of medicines and medical care are more closely integrated, such as through fundholding or regional block budgeting for medical and pharmaceutical care, which is not generally the case in the US health care system. Finally, an important caveat to the US results is the fact that averages of national use and cost of medicines do not differentiate among the different US payers – Medicare, Medicaid, the Department of Veterans Affairs (VA), Department of Defense, and commercial insurers. Some of these systems have levers to manage utilization and expenditures similar to national health systems in comparator countries. To illustrate the scale of variations in costs in the US, we obtained fiscal year 2015/16 data on total volume of and spending on medications in the six therapeutic categories dispensed to enrollees of the VA health system (VA Pharmacy Benefits Management Group, Hine, IL). Average expenditures per patient in the VA health system – an approximation of per capita costs – was approximately $74.0, approximately equal to the ten-comparator average for 2015. Approximately 550 days of therapy were dispensed per patient in the VA health system, which is roughly double the population-wide average for the ten comparator countries. The higher volume of therapy used within the VA is not surprising given the age and health needs of the population of VA health system enrollees. However, the average cost per day of treatment in the VA was approximately half that of the ten comparator countries, and approximately 85% below the nationwide US average. Though individual prices were not available to us, it is highly unlikely that branded product price discounts alone explain the comparatively low cost per day of therapy in the VA. Relatively low generic prices and more frequent use of lower-cost therapeutic options (almost always generics) likely also contribute to low average treatment costs within the VA.
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9. Conclusion The US spends disproportionally more on drugs used to treat common medical conditions than comparator countries. Most of the difference between estimated actual US expenditures on the primary care medicines included in this study and potential US expenditures at comparator country levels of use and costs stems from higher prices of medicines in the US. A common feature of most of the comparator countries in this study is that they either have a single-payer system for pharmaceuticals or use national processes for drug pricing and reimbursement decision-making, which can mimic single-payer purchasing power within the context of multi-payer social health insurance markets. If these decision-making authorities are prepared to say “no” to covering medicines that do not price at levels acceptable to their health care systems, the concentration of negotiation power at national levels in comparator countries may be a key driver of lower prices in those markets. Some systems within the US – such as the VA and, likely, some private health insurers – appear to have such negotiation capacity within the American market. Conflicts of interest Morgan, Good, Leopold and Kaltenboeck have no conflicts of interest to declare. Wagner has received support for training courses on pharmaceutical systems and policies from the Beijing Xuanwu Hospital, German Government (GIZ), Harvard University, Harvard Pilgrim Health Care Institute, Harvard China Fund, Novartis AG, Shanghai Shenkang Hospital Development Center, UK Department for International Development, WHO country and regional offices, and Xi’an Jiaotong University. Bach reports personal fees from Association of Community Cancer Centers, America’s Health Insurance Plans, AIM Specialty Health, American College of Chest Physicians, American Society of Clinical Oncology, Barclays, Defined Health, Express Scripts, Genentech, Goldman Sachs, McKinsey and Company, MPM Capital, National Comprehensive Cancer Network, Biotechnology Industry Organization, the American Journal of Managed Care., the Boston Consulting Group, Foundation Medicine, Anthem Inc., Novartis, and Excellus Health Plan; as well as grants from NIH, Kaiser Foundation Health Plan, Laura and John Arnold Foundation. Acknowledgements This work was supported in part by a research grant from the Commonwealth Fund [20160646], a national, private foundation based in New York City. The views presented here are those of the author and not necessarily those of The Commonwealth Fund, its directors, officers, or staff. The funding agency had no role in study design, analysis, or preparation of the paper. Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.healthpol.2018. 07.005. References [1] Dafny LS, Ody CJ, Schmitt MA. Undermining value-based purchasing — lessons from the pharmaceutical industry. New England Journal of Medicine 2016;375(21):2013–5. [2] Alpern JD, Song J, Stauffer WM. Essential medicines in the United States — why access is diminishing. New England Journal of Medicine 2016;374(20):1904–7. [3] World Health Organization. Medicines in health systems: advancing access, affordability and appropriate use. Geneva: World Health Organization; 2014.
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[4] IMS Institute for Healthcare Informatics. Global medicines use in 2020 – outlook and implications. Parsippany, NJ: IMS Health Incorporated; 2015. [5] Osborn R, Moulds D, Squires D, Doty MM, Anderson C, November 19 International survey of older adults finds shortcomings in access, coordination, and patient-centered care. New York: the Commonwealth fund; 2014; 2014. [6] Barnes S, Anderson L. Low earnings, unfilled prescriptions: employer-provided health benefit coverage in Canada. Toronto: Wellesley Institute; 2015. July. [7] IMS Health. IMS MIDAS - global analysis made easy. London: IMS Health Incorporated; 2012. [8] PMPRB. The drivers of prescription drug expenditures – a methodological report. Ottawa: Patented Medicine Prices Review Board; 2013. [9] Morgan S. Drug spending in Canada: recent trends and causes. Medical Care 2004;42(7):635–42. [10] Morgan SG. Sources of variation in provincial drug spending. CMAJ: Canadian Medical Association Journal 2004;170(3):329–30. [11] Hwang TJ, Kesselheim AS. Public referendum on drug prices in the US: will it bring relief? BMJ 2016;355. [12] QuintilesIMS Institute. Outlook for global medicines through 2021. Parsippany, NJ: QuintilesIMS Institute; 2016. December 2016. [13] Vogler S, Zimmermann N, Habl C, Piessnegger J, Bucsics A. Discounts and rebates granted to public payers for medicines in European countries. Southern Medical Journal 2012;5(1):38–46. [14] Morgan SG, Daw JR, Thomson PA. International best practices for negotiating’ reimbursement contracts’ with price rebates from pharmaceutical companies. Health Affairs (Millwood) (Project Hope) 2013;33(4):771–7. [15] Morgan S.G., Vogler S., Wagner A.K., Payers’ experiences with confidential pharmaceutical price discounts: A survey of public and statutory health systems in North America, Europe, and Australasia. Health Policy.
[16] Jin J, Sklar GE, Min Sen Oh V, Chuen Li S. Factors affecting therapeutic compliance: a review from the patient’s perspective. Therapeutics and Clinical Risk Management 2008;4(1):269–86. [17] Briesacher BA, Gurwitz JH, Soumerai SB. Patients at-risk for cost-related medication nonadherence: a review of the literature. Journal of General Internal Medicine 2007;22(6):864–71. [18] Morgan SG, Leopold C, Wagner AK. Drivers of expenditure on primary care prescription drugs in 10 high-income countries with universal health coverage. CMAJ 2017;189:E794–9. [19] Kanavos P, Ferrario A, Vandoros S, Anderson GF. Higher US branded drug prices and spending compared to other countries may stem partly from quick uptake of new drugs. Health Affairs 2013;32(4):753–61. [20] PMPRB. Generic drugs in Canada. Ottawa: Patented Medicine Prices Review Board; 2013. p. 2014. [21] PMPRB. Patented medicine prices review board: annual report. Ottawa: Patented Medicine Prices Review Board; 2014, 2015 November. [22] Kennedy J, Wood EG. Medication costs and adherence of treatment before and after the affordable care act: 1999–2015. American Journal of Public Health 2016;106(10):1804–7. [23] Morgan SG, Mintzes B, Barer M. The economics of direct-to-consumer advertising of prescription-only drugs: prescribed to improve consumer welfare? Journal of Health Services Research and Policy 2003;8(4):237–44.
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Health Policy journal homepage: www.elsevier.com/locate/healthpol
An analysis of expenditures on primary care prescription drugs in the United States versus ten comparable countries Steven G. Morgan a,∗ , Chester B. Good b , Christine Leopold c , Anna Kaltenboeck d , Peter B. Bach d , Anita Wagner c a
School of Population and Public Health, University of British Columbia, #267 – 2206 East Mall, Vancouver, BC, V6T 1Z3, Canada UPMC Center for Value-Based Pharmacy Initiatives, and University of Pittsburgh, School of Pharmacy and School of Medicine, Pittsburgh, PA, USA c Drug Policy Research Group, Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, USA d Center for Health Policy and Outcomes, Memorial Sloan Kettering Cancer Center, New York, USA b
a r t i c l e
i n f o
Article history: Received 13 March 2017 Received in revised form 5 July 2018 Accepted 6 July 2018 Keywords: Pharmaceuticals Expenditures Cost-drivers Prices International comparisons Prescription drugs
a b s t r a c t Objective: We sought to estimate size and sources of differences in per capita expenditures on primary care medications in the US versus ten comparable countries combined: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom. Methods: Using market research data on year 2015 volumes and sales of medicines, we measure total per capita expenditures on six categories of primary care prescription drugs: hypertension treatments, pain medications, lipid lowing medicines, non-insulin diabetes treatments, gastrointestinal preparations, and antidepressants. We quantified the contributions of five drivers of the observed differences in per capita expenditures. Results: We estimated that the US spent 187% more per capita on primary care pharmaceuticals than did the ten comparable countries. Despite the difference in spending levels, on average, Americans actually purchased 14% fewer days of related therapies than residents of the comparator countries. Most of the observed difference in expenditures was due to higher transaction prices of medicines and the use of a more expensive mix of medicines in the US. Conclusions: If utilization patterns and pharmaceutical prices in the US were similar to those in the 10 comparator countries combined, total spending on primary care pharmaceuticals would fall by 30% or more. Such evidence on the level and drivers of US pharmaceutical expenditures should inform policies in this sector. © 2018 Published by Elsevier B.V.
1. Introduction Concern about the cost of prescriptionmedications in the United States (US) is growing, in large part due to recent increases in the prices of new drugs and older ones. [1,2] Prudent management of pharmaceutical expenditures is important so that health systems can ensure universal and affordable access to available medicines [3], and so that the pricing system provides appropriate incentives for valued innovation. While most recent attention has focused on the rising cost of specialty pharmaceuticals, health systems must also manage the cost of more commonly used primary care prescription medicines. Because of the large volume of use, primary care pharmaceuti-
∗ Corresponding author. E-mail address: [email protected] (S.G. Morgan).
cals are expected to account for the majority of pharmaceutical expenditures in the US and comparable health systems for the foreseeable future [4]. Further, competition within primary care drug categories with many off-patent medicines can create savings to expand coverage of medicines still on patent, including specialty medicines. In this study, we quantify the level and drivers of US expenditures on primary care pharmaceuticals relative to ten comparator countries. We do so using economic price and quantity indexes developed to compute cost-drivers in the pharmaceutical sector. Our focus on primary care categories of medicine illustrates differences in these high-volume therapeutic categories. This focus also facilitated the selection of categories wherein drugs are typically sold in oral solid dosage forms (as compared to drug classes where medicines frequently come in varied dosage forms), and are predominantly purchased from community pharmacies (as opposed to institutional settings such as hospitals or cancer clinics). Both
https://doi.org/10.1016/j.healthpol.2018.07.005 0168-8510/© 2018 Published by Elsevier B.V.
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of those characteristics of the drugs classes under study increase the reliability and comparability of market research data across countries.
2. Design and methods This is a comparative economic analysis of 2015 prescription drug sales and volume for the US and ten comparator countries: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom. These countries were chosen because their combined population in 2015 was similar to the US population of (318 million versus 321 million) and they are all high-income countries (average GDP per capita of US$45,018 in 2015) whose health care systems are used for comparison to the USA in the annual Commonwealth Fund’s International Health Policy surveys [5]. Residents of all of the comparator countries except Canada were eligible for universal health coverage that included universal coverage of outpatient prescription drugs. Residents in Canada were eligible for universal public health insurance for medical and hospital care (including inpatient prescription drugs) but may or may not have access to either public or private coverage for prescriptions used in the community setting depending on their age, occupation, income, and province of residence [6]. The systems of drug coverage in Australia, New Zealand, Norway, Sweden, and the United Kingdom can be described as universal public systems. In these countries, prescription medicines are financed predominantly by government and either government or an arms-length public body manages the selection and the price setting of medicines to be covered by the universal system of public financing. Prescription drugs in France, Germany, the Netherlands, and Switzerland are financed through multiple-payer, social insurance systems with various statutory policies governing minimum coverage and pricing for originators and generics.
3. Data sources The local currency value and volume of sales of medicines in the US and comparator countries were obtained from the IMS MIDAS sales database, which captures more than 95 percent of the value of the global pharmaceutical market [7]. These data reflect transaction prices that exclude rebates received from manufacturers of branded products by institutional purchasers in the US and other countries. Foreign sales were converted to US$ by applying a constant exchange rate (Q1 2016). A sensitivity analysis found that the alternative use of purchasing power parities PPPs did not alter findings because ratios of exchange rates to PPPs varied across the comparator countries. The database tracks sales volumes in terms of standard units of a medicine and kilograms of the primary active ingredient. IMS converted these figures into standardized days of therapy using average daily doses for each medicine as computed from IMS Prescribing Insights, which draws on information from a panel of office-based physicians in each country. Although differences are small, estimated average daily doses of some medicines vary by country, reflecting local prescribing behaviors. Sensitivity analyses based showed that differences in average daily doses by country altered overall findings of price versus volume effects by five percent. As rebates paid to institutional purchasers are typically confidential, we were unable to measure them directly. Instead, we estimated spending given ranges of relative price rebates for the US in sensitivity analyses.
4. Drug categories included in the analysis We study the use of and expenditure on six therapeutic categories of primary care prescription drugs based on primary indication. In order of their frequency of use in the United States, these categories were as follows: hypertension treatments; lipid lowing medicines; antidepressants; gastrointestinal preparations (primarily drugs for ulcers and heartburn); non-insulin diabetes treatments; and pain medicines, including nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. Details concerning the drugs within each category are provided in Appendix A. We selected these primary care categories of medicines because they are widely used, typically sold in oral solid dosage forms, and predominantly sold through community pharmacies (as opposed to inpatient settings). All of these factors increase the reliability and comparability of market research data across countries. We focus on medicines with prescription-only status in the United States, which excludes pharmaceuticals commonly sold over-the-counter (e.g., plain acetaminophen for pain) and herbal therapies (e.g., caraway for digestive problems). A total of 1035 different products were included in the study, identified by active ingredient(s) and whether they were branded or generic. These products were assigned into hierarchical, mutually exclusive groupings using the World Health Organization’s Anatomical Therapeutic Chemical (ATC) classification system. In total, the dataset contained 614 different drugs (merging brand and generic versions of the same active ingredients together) that fell into 81 pharmacological classes within the 6 broad therapeutic categories. Collectively, these therapeutics categories account for approximately 25% of prescription drug expenditures in the US.
5. Drivers of variation in expenditure For each therapeutic category, we quantify mutually exclusive sources of the difference in prescription drug expenditures between the US and the combined comparator countries using economic indexes that were developed to compute cost-drivers in the pharmaceutical sector [8–10]. We estimated the effects of five sources of difference in expenditures that fall into three broad categories: volume, choice, and price effects (Fig. 1). Volume reflects the average amounts of prescription drug therapy received by a population. It depicts how much of the difference in expenditures per capita between the US and comparator countries is the result of differences in the average number of days of therapy purchased per capita. The remaining cost-drivers estimate the sources of differences in costs per day of therapy. Choices describe the differences in average daily cost of treatment that stem from differences in the average mix of medicines selected from within therapeutic categories, holding the relative prices of treatment options constant. Other things being equal, prescribing higher cost therapeutic options will result in higher overall spending. The “broad mix” cost-driver reflects the cost impact of the pharmacologic classes selected from within each broad therapeutic category. This includes such choices as whether or not to use diuretics or ACE inhibitors for hypertension treatment. The “narrow mix” cost-driver reflects the cost impact of the selection of specific active ingredients within a particular pharmacologic class. This includes such choices as whether or not to use enalapril or ramipril within the class of ACE-inhibitors; it is, in effect, a choice between a narrower range of therapeutic options than is captured by the broad mix cost-driver.
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6. Statistical and sensitivity analyses This analysis relies on non-stochastic measures; standard tests of statistical significance therefore do not apply. In advance of analysis, we decided that differences of less than 5% in absolute value would not be considered significant. To test for sensitivity of results to the measure of daily doses, analyses were conducted separately for three different measures of quantity: physical units of medicines purchased, kilograms of active ingredient, and days of therapy. To test for sensitivity of results to the exclusion of US rebates, we performed analyses on hypothetical US sales figures under two rebated scenarios based on estimated rebate levels for major purchasers in the US: one scenario in which average rebates for branded products in the US represented 30% of all branded product sales in the US, and one in which US rebates for branded products were assumed to equal 50% of all sales [11,12]. In both cases, we assumed there were no rebates in the comparator countries, which biases results toward understating US prices relative to comparator countries given that confidential rebates are now common and sizable in the comparator countries studied here [13–15].
7. Findings
Fig. 1. Framework for determining the drivers of differences in spending on six primary care medication categories.
Price effects are factors that influence the average unit cost of treatments without altering the quantity or type of active ingredient used. These cost-drivers include “generic use”, which captures the average difference in unit costs of particular types of drug that stem from differences in the rate of generic use of those types of drug, when multi-source products are prescribed. Price effects also include simple differences in “prices”, as measured by a salesweighted average of differences in the unit prices of branded or generic versions of a product. These cost-drivers are computed based on a series of Fisher’s ideal economic price and quantity indexes that have the desirable property of “adding up” in the sense that they explain the total difference in spending between jurisdictions without residuals. The methods are described in detail elsewhere [8,9]. For ease of interpretation, we used logarithms to convert the multiplicative results of the analysis into additive percent changes for each component. The individual cost-drivers will add up exactly to the three respective main cost-driver sub-totals, and those sub-totals will add up to the total differences observed.
As shown in Table 1, total per capita expenditures on the six therapeutic categories of primary care medicines included in this study were $217.1 in the US, compared to $71.6 among the combined comparator countries. In total, expenditures per capita were 203% higher in the US than the comparators. The US spent more per capita on each of the six therapeutic categories, with the greatest differences observed for non-insulin diabetes treatments (436% difference), lipid lowering medicines (290%), and gastrointestinal preparations (223%). Differences in the volume of therapy purchased in US and comparator countries did not explain the differences in expenditures per capita. In total, per capita use of the primary care therapies studied was 12% lower in the US than in the comparator countries (223.2 days of therapy compared to 253.8). Antidepressants were the only therapeutic category studied from which Americans purchased more days of therapy on average than did residents of comparator countries (31.9 days versus 25.9, respectively, a 23% difference). Results were similar in order and magnitude when quantities were measured using standardized units or kilograms of primary active ingredient. The average cost per day of primary care prescription drug therapy in the US was 245% higher than in comparator countries. This was partially due to the selection of higher cost therapeutic options, which increased costs per capita in the US by approximately 44% relative to comparators. However, the biggest driver of higher primary care pharmaceutical expenditure per capita in the US was the higher average prices paid for the products selected. This was primarily due to higher prices of products in these therapeutic categories, rather than differences in generic substitution rates for multi-source drugs. Total estimated expenditures in the US were $69.8 billion in 2015 at transaction prices. This total would be $54.9 billion if branded product sales are rebated at an overall average of 30% in the US, and $44.9 billion if branded products are rebated at an average of 50%. As shown in Table 2, Americans would have spent an estimated total of $23.0 billion on these medicines if the US had per capita expenditure levels equal to that of the comparator countries combined. (The comparator figure is unaffected by assumptions about US branded product price rebates.) The total value of the difference in expenditures in the US under different assumptions about domestic price rebates ranges from $21.9 billion higher to $46.8 billion higher than it would be under
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Table 1 Level and drivers of differences in estimated 2015 spending per capita in the US versus all comparator countries combined. All six therapeutic categories
Non-insulin diabetes treatments
Pain medi- Lipid lowering cations medications
Hypertension medications
Gastrointestinal preparations
Antidepressants
Domestic spending in US per capita Comparator spending per capita Difference in spending per capita
$217.1 $71.6 203%
$52.3 $9.7 436%
$51.1 $17.0 200%
$38.9 $10.0 290%
$31.6 $18.3 72%
$26.9 $8.3 223%
$16.2 $8.1 100%
Domestic days per capita Comparator days per capita Effect of difference in volume of treatment
223.2 253.8 −12%
21.0 20.0 5%
20.4 17.5 16%
34.2 36.5 −6%
91.5 119.2 −23%
24.3 34.7 −30%
31.9 25.9 23%
Effect of difference in broad mix of therapies 24% Effect of difference in narrow mix of therapies 20% Choices - subtotal 44%
12% 1% 13%
38% 34% 73%
−12% 4% −8%
−14% −2% −17%
37% 11% 48%
−3% 56% 52%
Effect of difference in generic utilization Effect of difference in transaction prices Price effects - subtotal
83% 336% 418%
−39% 150% 111%
4% 300% 304%
34% 78% 112%
15% 190% 205%
−47% 71% 24%
19% 152% 171%
Note: “Comparator” represents the per capita average of ten non-US comparator countries: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom.
Table 2 Aggregate impacts of differences in the use and cost of all six categories of primary care medicines in the US vis-à-vis international comparators ($ billions).
At US use and cost levels At comparators’ use and cost levels Total difference in spending Volume (days of therapy) Broad mix of therapies Narrow mix of therapies Choices subtotal Generic use Prices Price effects - subtotal
Unadjusted US prices
With 30% brand rebates in US
With 50% brand rebates in US
$69.8 $23.0 $46.8 -$5.4 $9.2 $7.7 $15.4 $7.5 $38.9 $42.0
$54.9 $23.0 $31.9 -$4.7 $6.0 $4.6 $9.9 $1.5 $28.1 $28.8
$44.9 $23.0 $21.9 -$4.2 $4.2 $2.8 $6.7 -$0.5 $20.4 $20.1
Note: “Comparator” represents the average of ten non-US comparator countries: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom.
comparator drug use and cost profiles. Assuming US purchasers receive average rebates equal to 50% on all branded products brings prices of medicines in the US closer to those in comparator countries – and significantly reduces the estimated cost impact of therapeutic choices because US brands are then closer in price to lower-cost therapeutic alternatives. However, even at that rebate level, Americans would have spent an estimated $21 billion more on primary care medicines in 2015 than they would have if they faced the average prices, prescribing volumes, and therapeutic choices found in the ten comparator countries. 8. Discussion The US spends significantly more per capita than comparable countries on the six categories of commonly-used, primary care medicines studied here. Using best available sales and volume data and an empirical framework for studying pharmaceutical cost drivers, we found that the volume of prescription drug use is not a primary driver of comparatively high US expenditures on primary care medicines. In four of the six therapeutic categories studied, Americans purchased fewer days of prescription drug therapy on average than did residents of the ten comparator countries. This finding is not surprising since greater out of pocket expenses for pharmaceuticals – either because of lack of coverage or copayments in the US – have been shown to correlate with lower adherence to prescribed therapies [16,17].
The primary drivers of relatively high expenditures on medicines in the US were the price and type of medicines selected for treatment. In four of the six therapeutic categories studied, patients in the US received a costlier mix of drug products, reflecting a tendency to receive newer, higher-cost therapeutic options for treatment of given conditions. This not likely to be driven by lower price sensitivity of patients, as the populations in all comparator countries except Canada receive comprehensive drug coverage through their public or statutory health systems. It may, however, be driven by lower price sensitivity of prescribers in the US in comparison to countries with more integrated drug budgeting in primary care, greater presence of direct-to-consumer advertising in the US, or a combination of these and other factors. In all six therapeutic categories studied, prices were significantly higher in the US than in comparator countries. Prices remained a significant driver of US expenditures relative to comparators even under conservative assumptions about the scale of off-invoice price rebating in the US vis-à-vis comparator countries. These differences are greater than would be expected by the modest difference in national incomes: GDP per capita was almost 20% higher in the US than the average for comparator countries in 2015, but price differences were much greater. The lack of statutory price regulations in the US may be a contributor to higher-than-average prices. However, countries like New Zealand achieve relatively low prescription drug prices through negotiation rather than through regulation; and countries like Canada have relatively high drug prices (compared to most countries except the US) despite having price regulations in place for patented drugs [18]. The US also lacks the consolidated purchasing power that comparator countries with single-payer health systems and/or effective national formularies use in negotiations with drug manufacturers. Indeed, US policies over recent decades have increased the market power of pharmaceutical firms by expanding their protections from competition while simultaneously limit the capacity of the Medicare system – what would have been the single largest purchaser or medicines in the US – to exert countervailing market power though single-payer negotiations for the population covered by it.31 Our finding that high US expenditure is primarily a function of the type and price of drug selected is comparable to a 2013 study of cross-national differences in pharmaceutical spending by Kanavos and colleagues, who concluded the effects of international differences in volumes of medicines purchased were smaller than the effects of differences prices and uptake of new drugs [19]. Our find-
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ings concerning the relative prices of drugs in the US compared to the countries studied are also consistent with regularly published price comparisons by Canada’s Patented Medicine Prices Review Board [20,21]. As any analysis of international differences in pharmaceutical use and cost, this study has some important limitations. The datasets used exclude confidential rebates in the US and other countries. However, price remained the most significant driver of higher expenditures in the US under conservative sensitivity analyses that assumed 50% reductions in the US. It is important also to note that we have assumed no price reductions negotiated in comparator countries, despite evidence that rebates are common and often significant in these other countries [15]. This study does not account for differences in morbidity of the populations in each country. Though the US population is not significantly older on average than the population in the comparator countries, the American population may be less healthy. Such a difference in health status would be expected to result in greater volumes of therapy purchased in the US. However, we find that Americans used fewer treatment days of the medicines studied, which may be a result of cost-related barriers to prescription drug adherence in the US [22]. If average morbidity per user of therapy is worse in the US than in the comparator countries, Americans might need highercost types of medicine (e.g., more expensive pharmacologic classes and active ingredients) from within therapeutic categories, which may explain all or part of our findings concerning the costlier mix of treatments selected in the US. Direct-to-consumer advertising, which is legal only in the US and New Zealand, is another potential driver of the more costly mix of therapies in the US, as such advertising is almost exclusively for newer, patented drug products for which manufacturers can recoup costs of promotions [23]. Finally, price may be a greater determinant of product selection in systems where financing of medicines and medical care are more closely integrated, such as through fundholding or regional block budgeting for medical and pharmaceutical care, which is not generally the case in the US health care system. Finally, an important caveat to the US results is the fact that averages of national use and cost of medicines do not differentiate among the different US payers – Medicare, Medicaid, the Department of Veterans Affairs (VA), Department of Defense, and commercial insurers. Some of these systems have levers to manage utilization and expenditures similar to national health systems in comparator countries. To illustrate the scale of variations in costs in the US, we obtained fiscal year 2015/16 data on total volume of and spending on medications in the six therapeutic categories dispensed to enrollees of the VA health system (VA Pharmacy Benefits Management Group, Hine, IL). Average expenditures per patient in the VA health system – an approximation of per capita costs – was approximately $74.0, approximately equal to the ten-comparator average for 2015. Approximately 550 days of therapy were dispensed per patient in the VA health system, which is roughly double the population-wide average for the ten comparator countries. The higher volume of therapy used within the VA is not surprising given the age and health needs of the population of VA health system enrollees. However, the average cost per day of treatment in the VA was approximately half that of the ten comparator countries, and approximately 85% below the nationwide US average. Though individual prices were not available to us, it is highly unlikely that branded product price discounts alone explain the comparatively low cost per day of therapy in the VA. Relatively low generic prices and more frequent use of lower-cost therapeutic options (almost always generics) likely also contribute to low average treatment costs within the VA.
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9. Conclusion The US spends disproportionally more on drugs used to treat common medical conditions than comparator countries. Most of the difference between estimated actual US expenditures on the primary care medicines included in this study and potential US expenditures at comparator country levels of use and costs stems from higher prices of medicines in the US. A common feature of most of the comparator countries in this study is that they either have a single-payer system for pharmaceuticals or use national processes for drug pricing and reimbursement decision-making, which can mimic single-payer purchasing power within the context of multi-payer social health insurance markets. If these decision-making authorities are prepared to say “no” to covering medicines that do not price at levels acceptable to their health care systems, the concentration of negotiation power at national levels in comparator countries may be a key driver of lower prices in those markets. Some systems within the US – such as the VA and, likely, some private health insurers – appear to have such negotiation capacity within the American market. Conflicts of interest Morgan, Good, Leopold and Kaltenboeck have no conflicts of interest to declare. Wagner has received support for training courses on pharmaceutical systems and policies from the Beijing Xuanwu Hospital, German Government (GIZ), Harvard University, Harvard Pilgrim Health Care Institute, Harvard China Fund, Novartis AG, Shanghai Shenkang Hospital Development Center, UK Department for International Development, WHO country and regional offices, and Xi’an Jiaotong University. Bach reports personal fees from Association of Community Cancer Centers, America’s Health Insurance Plans, AIM Specialty Health, American College of Chest Physicians, American Society of Clinical Oncology, Barclays, Defined Health, Express Scripts, Genentech, Goldman Sachs, McKinsey and Company, MPM Capital, National Comprehensive Cancer Network, Biotechnology Industry Organization, the American Journal of Managed Care., the Boston Consulting Group, Foundation Medicine, Anthem Inc., Novartis, and Excellus Health Plan; as well as grants from NIH, Kaiser Foundation Health Plan, Laura and John Arnold Foundation. Acknowledgements This work was supported in part by a research grant from the Commonwealth Fund [20160646], a national, private foundation based in New York City. The views presented here are those of the author and not necessarily those of The Commonwealth Fund, its directors, officers, or staff. The funding agency had no role in study design, analysis, or preparation of the paper. Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.healthpol.2018. 07.005. References [1] Dafny LS, Ody CJ, Schmitt MA. Undermining value-based purchasing — lessons from the pharmaceutical industry. New England Journal of Medicine 2016;375(21):2013–5. [2] Alpern JD, Song J, Stauffer WM. Essential medicines in the United States — why access is diminishing. New England Journal of Medicine 2016;374(20):1904–7. [3] World Health Organization. Medicines in health systems: advancing access, affordability and appropriate use. Geneva: World Health Organization; 2014.
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