Betting on hepatitis C: how financial speculation in drug development influences access to medicines
BMJ 2016; 354 doi: https://doi.org/10.1136/bmj.i3718 (Published 27 July 2016) Cite this as: BMJ 2016;354:i3718All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
The progress of drugs for Hepatitis C is indeed a milestone in the history of human medicine. Especially for countries and areas stricken by Hepatitis C, it appears like the light at the end of the tunnel. However, the high cost of the drugs acts as the darkness before the dawn, making the target appear available but far away. Just as Roy & King said, “the public is paying twice”1. This has become a serious problem for different health systems in the world2. Roy & King pointed out, the high prices have led many public systems across the US and Europe to treat only the sickest patients. But for Taiwan, the higher prevalence rate poses a serious dilemma (see Table).
In Taiwan, every type of viral hepatitis is prevalent. Though the National Health Insurance system is near perfect3, even today new drug treatment for hepatitis is not covered, let alone for the sickest patients. This is the first time that an effective drug is not covered just because of financial pressure since the National Health Insurance system was set up 21 years ago. Taiwan is the world’s first country to implement Hepatitis B vaccination nationwide, marking its 30th anniversary last month. The great irony is that the drugs for Hepatitis are not covered.
The pricing strategy has impact not only on medicine industries, but also on health systems. The value-based pricing, which decides the price of drug by its effects and values, is a tendency4 5. Thus, the drugs for Hepatitis C which enjoy 90% of cure rate should deserve higher prices.
However, once the overall health cost is too high, it will affect the allocation of resources in a country. In Taiwan, a doctor who enjoys high popularity in social media satirized the proposed coverage of new drugs for Hepatitis C by National Health Insurance in a national newspaper column, saying the proposal will be a disaster for the medical personnel6.
This kind of viewpoints is not uncommon. The proposed coverage of drugs for Hepatitis C accidentally sparked off the debate among doctors who as professionals fight for life of patients and as survivor under resources exclusion fight for the living of their own. Doctors by profession traditionally enjoy an altruistic image which faces challenge posed by the proposed coverage of drugs for Hepatitis C.
According to various economic indexes, Taiwan is among the developed countries7. Judged by robust economic performances and prosperous industries, Taiwan should not be included in “CHARITY PROGRAM” which enjoys the benefit of special drug prices. But Taiwan’s 4.4% of prevalence rate of Hepatitis C is three times the rate of the world average. Compared with those of the OECD countries, Taiwan’s prevalence rate is from triple to eightfold8.
The lowest price so far available by Ministry of Health and Welfare9 coincides with the fact that 0.66 million people need treatment8, so Taiwan will almost consume all the medicine expenses under National Health Insurance a year on the cost of drug for Hepatitis C. This is not the case of resources exclusion, but total replacement. If we give consideration to the price of drugs for Hepatitis C, the number of patients, the purchasing power of people and overall medicine expanses, we will have a reflection on the pricing of medicine from different angles. So far, for some developing countries, the price of medicine is lower10, mostly based on financial considerations. If only national finance is taken into consideration, it probably can’t include the overall impact on medical systems. Although Taiwan is among the developed countries, the prevalence rate is too high, leading to an impact on the resources and finance just like the developing countries.
Neither Taiwan nor Hepatitis C is alone. In the future, there will be more hard nuts to crack. By different cultural and geographic circumstances, some countries will face a similar problem which high prevalence rate will eventually wear down the nation’s finance. They don’t need a merciful pricing, but do need a pricing strategy which offers low unit price to let more people enjoy the fruits of medicine development.
References
1. Roy V, King L. Betting on hepatitis C: how financial speculation in drug development influences access to medicines. BMJ 2016;354.
2. Iyengar S, Tay-Teo K, Vogler S, et al. Prices, Costs, and Affordability of New Medicines for Hepatitis C in 30 Countries: An Economic Analysis. PLoS Med 2016;13(5):e1002032.
3. Reinhardt UE. Humbled in Taiwan. BMJ 2008;336(7635):72.
4. Bach PB, Pearson SD. Payer and Policy Maker Steps to Support Value-Based Pricing for Drugs. JAMA 2015;314(23):2503-4.
5. Reinhardt U. Probing Our Moral Values in Health Care: The Pricing of Specialty Drugs. JAMA 2015;314(10):981-2.
6. http://www.appledaily.com.tw/appledaily/article/headline/20160328/37132124/ (accessed 2016/08/08,in Chinese).
7. World Bank. World Bank list of economies, 2016.
8. Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014;61(1 Suppl):S45-57.
9. http://www.cna.com.tw/news/firstnews/201607300142-1.aspx(accessed 2016/08/08,in Chinese).
10. Andrieux-Meyer I, Cohn J, de Araujo ES, et al. Disparity in market prices for hepatitis C virus direct-acting drugs. Lancet Glob Health 2015;3(11):e676-7.
Competing interests: No competing interests
Roy and King provide a perceptive analysis illuminating the challenges faced by the National Health Service with regard to the price of patented drugs. However it is important to adopt a panoramic view of the socioeconomic situation. Both the NHS and Gilead exist in a global healthcare nexus. It cannot go unmentioned that Gilead in 2014 entered a licensing agreement with manufacturers in India to produce generic versions of sofosbuvir much more cheaply for distribution to now 101 third world countries(1). This includes in excess 100 million people, around 54% of the global population suffering from hepatitis. In addition, most third world countries have been awarded much more favourable arrangements with regard drug pricing. In 2014, of nations profiting from such agreement the lowest cost per 28-tablet bottle of sofosbuvir was $300 in India and Pakistan; compared to in excess of $15,000 and $18,000 in the US and UK respectively(2). On this analysis it could be argued that more affluent countries are subsidising treatment in the third world. Indeed viewed through this prism, Gilead is acting as a contemporary "Robin Hood": taking from the rich and giving to the poor; with western affluence coming at an unexpected price.
The license agreement is a step lauded by the World Health Organisation. However WHO recognises that even with these subsidised prices, the cost of newer hepatitis C therapy remains prohibitively expensive(3). The cost of 3-months treatment with sofosbuvir-daclatasvir is $1350 in Egypt(2). On one calculation treating every patient in Egypt afflicted with hepatitis C would still cost five times the Egypt's 2011 public health budget(4). This is all the more difficult to justify given that the production cost of a 12-week course of treatment with sofosbuvir-daclatasvir is estimated at $121 for Gilead(5). In addition a number of middle income countries with high hepatitis C burdens, such as Brazil, China, Georgia, Mexico, Thailand and Ukraine are excluded from such agreements(3).
Even this analysis is in some ways imperfect. Profits are theoretically recycled into the economy in the form of corporation tax. It is estimated that Gilead's corporation tax for the year ending 2015 was in excess of £3.5billion, predominantly on anti-viral sales totalling in excess of $30 billion(6,7). However at least some part of the due tax contribution may remain theoretical. It has been inferred from Gilead’s tax report that up to $28.5 billion of revenue is potentially sequestered in off-shore accounts. On repatriation to the USA this money would could be subject to a $9.7 billion tax bill(8).
Roy and King suggest that the patients pay twice, however more accurately they pay 2.5 times. One for drug development, secondly to subsidise cheap generics in the third world, thirdly for expensive drugs aiding profits; finally they are partially compensated by Gilead's tax contribution. The first two payments are commendable; however some consider the third in many ways objectionable.
(1) http://www.who.int/phi/implementation/ip_trade/sofosbuvir_report.pdf
(2) Andrieux-Meyer I, Cohn J, de Araújo ES, Hamid SS. Disparity in market prices for hepatitis C virus direct-acting drugs. Lancet Glob Health. 2015 Nov;3(11):e676-7. doi: 10.1016/S2214-109X(15)00156-4
(3) http://www.who.int/bulletin/volumes/93/11/15-157784/en/
(4) Londeix P. New treatments for hepatitis C virus, strategies for achieving universal access. Brussels: Médecins du Monde; 2014. Available from: http://hepcoalition.org/IMG/pdf/web_daas_strategies_for_achieving_univer...
(5) Hill A, Khoo S, Fortunak J, Simmons B, Ford N. Minimum costs for producing hepatitis C direct-acting antivirals for use in large-scale treatment access programs in developing countries. Clin Infect Dis. 2014 Apr;58(7):928–36
(6) https://www.stock-analysis-on.net/NASDAQ/Company/Gilead-Sciences-Inc/Ana...
(7) http://www.gilead.com/news/press-releases/2016/2/gilead-sciences-announc...
(8) http://www.forbes.com/sites/christopherhelman/2016/04/15/what-americas-m...
Competing interests: No competing interests
Access to medicines,particularly the recently introduced and expensive ones poses a huge challenge to public health systems with obligatory duties , and tends to produce a frustrating situations for clinicians where diagnosis is established and treatment remains elusive or compliance incomplete. The strategies employed by companies have discussed at length ; markets fluctuate and shareholders have to be kept satisfied. Limiting the buyback or setting standards for a fixed ratio between R&D and buyback could a possible solution.The non Europe/US situation can be different; low priced generics will invariably emerge..
Competing interests: No competing interests
We would like to clarify a few points addressed in this week’s BMJ analysis.
First, our focus is to improve care for HCV-infected individuals. We have accomplished this by bringing to market three breakthrough therapies that offer a cure to the vast majority of patients suffering from hepatitis C, a life threatening and debilitating disease. In two and a half years, more than one million HCV patients have been treated with our HCV therapies throughout the world. We believe we have cured more patients in this timeframe than in the previous 20 years.
Second, our therapies were developed by Pharmasset and Gilead – with no funding from the NIH, the Veterans Association or Emory. Pharmasset did receive a small grant from the IRS for $244,479 under the Qualifying Therapeutic Discovery Project program for the development of sofosbuvir as a tax incentive. In addition, we continue to innovate and improve upon our own medicines. We are actively working on a third single tablet regimen being evaluated in four Phase 3 trials among patients who have previously failed direct-acting antiviral treatment.
Third, the statement that Gilead set a price based solely on internal deliberations is not accurate. Giead conducted extensive research with a broad group of private and public payers to determine a fair and reasonable price. After these discussions, Gilead set the wholesale acquisition cost (WAC) for Sovaldi at $84,000. At this price, a regimen using 12 weeks of sofosbuvir and 12 weeks of pegylated interferon and ribavirin cost $94,000, a price that was neutral to the price of the standard of care at the time (protease inhibitor, pegylated interferon and ribavirin), even though the Sovaldi regimen provided significant improvements over the prior standard of care in terms of cure rates, safety and duration of therapy. Companies set a WAC price, a list price at which wholesale distributors purchase drug products. The WAC price then serves as the basis for negotiated discounts and rebates between manufacturers and payers as competition develops in a therapeutic space. Mandatory discounts are also given to payers like Medicaid. This process is standard in the industry and in this case most payers receive substantial discounts off the list price with the steepest discounts going to government payers like Medicaid and the VA. Both the VA and Medicaid, for example, currently receive discounts in excess of 50% on Harvoni.
One point of clarity -- the statement that Pharmasset initially considered a price of $36,000 for sofosbuvir is misleading. First, the final version of the document you reference provided a range of $36,000-$72,000. Second, based on a review of Pharmasset’s materials and discussions with key Pharmasset officials, it is clear that Pharmasset anticipated initial pricing of the regimen sofosbuvir would be used in would be priced neutral to the average standard of care regimen at the time. As of late 2011, that cost was approximately $72,000 for up to a 48 week duration of therapy. Pharmasset assumed that when sofosbuvir was launched the regimen price would remain at $72,000. Therefore, if sofosbuvir was approved for use as monotherapy, it would cost $72,000. If sofosbuvir was approved for use with other agents, Pharmasset assumed sofosbuvir would merit at least 50 percent of the regimen’s value at a minimum cost of $36,000, while an additional $36,000 would cover the use of other agents. In other words, Pharmasset used the exact same methodology as Gilead for creating a pricing model for sofosbuvir. With the discounts currently in place, most payers pay well below the prices contemplated by Pharmasset.
Fourth, the analysis fails to mention that Gilead took a considerable risk when acquiring Pharmasset. At the time of the acquisition, Pharmasset only had data from Phase 2 studies in genotype 2 and 3 patients. Pharmasset did not have data on genotype 1 patients, which present 60 percent of patients who have chronic hepatitis C and by far the biggest opportunity to cure the most patients.
Finally, we stand behind the pricing of our therapies because of the benefit they bring to patients and the significant value they represent to payers, providers and our entire healthcare system by reducing the long-term costs associated with managing chronic HCV. Our medicines save the healthcare system money while curing patients of a deadly disease. Enabling patient access to our HCV therapies is a top priority for Gilead. In the U.S., most payers receive substantial discounts off the list price with the steepest discounts going to government payers like Medicaid and the VA. In Europe, we have negotiated sustainable and affordable agreements that have resulted in significantly increased treatment rates, even in countries with challenging economic circumstances. In the UK, we have established a price that NICE agrees meets the value threshold. We remain ready and willing to continue discussions with the government and NHS England to bring our HCV treatments to patients as quickly as possible.
However, drug pricing cannot be looked at in isolation, but rather must be placed in the context of a country’s healthcare system, the cost incurred to the healthcare systems with no treatment or inferior treatment, and how countries successfully incentivize and allocate research and development costs to spur pharmaceutical innovation. From 1994-2014, the pharmaceutical industry had invested $50 billion in the development of HCV drugs. The overwhelming majority of these drugs failed within the preclinical and Phase II stages of development, and only 1.9% made it to the market. This investment continues as companies look for ways to improve upon existing therapies.
It's clear that governments, healthcare providers, healthcare systems, payers and healthcare advocacy groups recognize the opportunity to treat and cure many more hepatitis C patients now that we have simple, safe, and highly effective medicines. Gilead is working together with these groups on a number of fronts with the aim of bringing all diagnosed yet untreated patients into care over time while recognizing capacity and budget constraints.
Gregg Alton
Executive Vice President
Commercial and Access Operations ALA, Corporate and Medical Affairs
Gilead Sciences, Inc.
Competing interests: Gregg Alton is Executive Vice President Commercial and Access Operations ALA, Corporate and Medical Affairs at Gilead Sciences.
We thank Victor Roy and Lawrence King for pointing out that the acquisition strategies of drug companies magnify development costs and leave the public paying twice. While this is no doubt true – and we entirely agree with the authors’ thesis in this respect – in Gilead's case it is difficult to argue that the either the development costs or the prices of its sofosbuvir-based medicines were driven by the costs of the acquisition of Pharmasset.
Gilead paid $11.1 billion for its Pharmasset acquisition (though goodwill was estimated at only $74.8 million [1] and only $62.4 million attributed to sofosbuvir development over 2009-2011. [2]. Gilead then accounted for almost the entire non-goodwill component as the ‘fair value’ of sofosbuvir.[1]
But rather than being expensed, the $11.1 billion was classified as an intangible asset and is being amortized as such.[3] As long as it enjoys the benefit of this substantial depreciation it cannot be argued that the cost of the acquisition contributed to the costs of Sovaldi and Harvoni - even if that were reasonable. Which it isn’t.
Furthermore, while Gilead’s own R&D expenditure was reported as $1.76 billion in 2012 ($830 million on clinical trials) and $2.12 billion in 2013 ($1.15 billion)[1], its clinical trial costs for sofosbuvir prior to FDA approval would seem to have amounted to less than US$150 million.[4]
That Gilead is returning much of its spectacular profits to shareholders rather than reinvesting in R&D adds insult to injury. We agree that this underscores the need for new organisational and business models for drug development, particularly “de-linkage” mechanisms that quarantine R&D costs from the price of the medicine.
However the suggestion that “mechanisms have been proposed to give health systems greater bargaining power to determine price and value” fails to take into account that such approaches have been applied outside the US for some time – in Australia, for example, for over 20 years, with the result that the Australian Government is able to provide access to direct acting antivirals for hepatitis C without restriction.[5]
1. Gilead Sciences, Inc. Form 10-Q SEC Report For the quarterly period ended March 31, 2012, at http://www.sec.gov/Archives/edgar/data/882095/000144530512001487/gild201... accessed 2 August 2016
2. Pharmasset, Inc. Form 10-K Report for the Fiscal Year ended September 30, 2011, at http://www.sec.gov/Archives/edgar/data/1301081/000119312511311300/d22571... accessed 2 August 2016
3. Gilead Sciences, Inc. Form 10-Q SEC Report For the quarterly period ended June 30, 2014, at https://www.sec.gov/Archives/edgar/data/882095/000088209514000038/q214fo... accessed 2 August 2016
4. Authors’ estimates, based on data from clinical trials cited in FDA evaluation documents and www.clinicaltrials.gov, and using average clinical trial costs as reported in PAREXEL International. PAREXEL Biopharmaceutical R&D Statistical Sourcebook 2012/2013. (Parexel Intl Corp; July 1, 2012): ISBN-10: 1882615972
5. Hepatitis Australia. Australia shows an alternative to rationing hepatitis C treatment. Media release, June 08, 2016. At: http://www.hepatitisaustralia.com/newsarticles/australia-shows-an-altern...
Competing interests: No competing interests
A focus on acquisitions and buybacks
Mr. Alton’s response fails to address our main argument: the financial environment in which Gilead operates drives a cycle of late-stage acquisitions, blockbuster sales through high prices, followed by significant distribution of profits to shareholders via buybacks instead of research. John Milligan, Gilead’s current CEO, captured this in a recent earnings call with investment analysts: “For us it’s fairly simple. We have the flexibility to do both things; that is, return shareholder value through stock repurchases and dividends and of course continue to be opportunistic in M&A” (1). In the first half of 2016, Gilead spent $9 billion in share buybacks (almost triple their entire R&D budget from last year), with pressure mounting from the financial community to pursue a late-stage acquisition (2) (3).
We now respond to each of Mr. Alton’s claims.
(1) Gilead’s medicines have treated more than 1,000,000 people in 2.5 years.
This represents a small fraction of those diagnosed and less than 1% of those infected globally. Along with scaling-up health delivery capacity, the affordability of these breakthrough medicines remains a central challenge as evidence of rationing persists (4)(5).
(2) No public funding supported Pharmasset or Gilead in sofosbuvir’s development
We documented the role of private finance in our original article. However, long-term funding from the National Institutes of Health was crucial to all Hepatitis C drug development. During the 1990s development efforts stalled as scientists could not grow the virus in cell culture. The publicly developed replicon tool helped overcome this barrier. Furthermore, Ray Schinazi of Emory University received long-term funding from the NIH and the Veterans Affairs Administration (VA) to provide the scientific basis on which he founded Pharmasset. He continued to receive a salary from the VA during his time with the company (6)(7). Both the company commercializing the replicon (Apath) and Pharmasset received over $2 million from the NIH in small business funding (8) (9). Though the award amounts are small compared to later capital investments, these early stages contain a high level of uncertainty that can repel private investment. Public funding serves as an important signal to crowd-in venture capital (10).
(3) Gilead took a substantial risk by purchasing Pharmasset because there was no Phase II data on genotype 1, the most prevalent type of Hepatitis C
First, Mr. Alton himself states that early research and clinical trials have the greatest failure rates. Our point is not that late-stage acquisitions contain a complete absence of risk, but that large companies use them as a risk-reduction strategy. Second, Gilead’s own modeling before the acquisition anticipated a high probability of success and executives expressed confidence in the early genotype 1 response data (11, pg. 858 – 863). Gilead’s willingness to escalate their bid for Pharmasset by 37% in the weeks leading up to the acquisition reflects this confidence (11, pg. 16-17). Gilead’s head research and development official echoes our point: “Philosophically, we prefer to wait for more certainty and pay more money, which is what we did with Pharmasset, rather than getting something cheap with uncertainty” (12).
(4) Sofosbuvir cannot be viewed in isolation, as the industry spent $50 billion developing treatments for Hepatitis C for a 1.9% success rate in approved drugs
First, the data behind the $50bn figure is not presented, so readers cannot verify its sources and how it was derived. Second, what proportion went towards pursuing pivotal early-stage science? Or did an escalation in anticipated profits induce late-stage racing on similar compounds and speculative acquisitions? We documented, for example, three late-stage acquisitions that cost $17 billion. A widely cited study (13) chronicles the falling rate of innovation efficiency in the industry (billions of dollars spent per drug approval since the 1950s). This should be understood in the context of average profit margins in the pharmaceutical sector that are more than 4x that of other industries since 1995, based on the Fortune 500 list (as we highlight in Figure 1 of the original article). These trends cast doubt on the extent to which profit incentives are tightly linked to efficiencies in innovation.
(5) Gilead set the price based on several industry-appropriate considerations (wide-ranging consultation, “neutral price” for a substantially superior treatment in-line with Pharmasset’s approach, significant discounting, and the value it represents to patients and health systems)
First, given the limited response space, we refer readers to the U.S. Senate Investigation report (11) which offers a differing interpretation, particularly with regards to Pharmasset’s valuation and projected pricing (pg. 18-22), as well as the purpose of Gilead’s engagement with various stakeholders (Section 3, beginning on pg. 29). Second, Mr. Alton’s main argument is that Gilead’s pricing approach was based on comparing their new therapy against the price of the prior standard of care, which was also highly priced in this case. We acknowledge this approach and the therapy’s cost-effectiveness, but point to the potentially avoidable conundrum that it created: a pricing level previously applied to a much smaller patient population was applied to a large patient pool (all Hepatitis C patients). (14)(15) Evidence from the Senate report show that Gilead anticipated the budget pressures and access restrictions this would create, with a chart (linked below) demonstrating their evaluation of potential reactions of various groups (including the U.S. Congress) at different price points. This has been partially mitigated for publicly-financed health systems, as Mr. Alton highlights, via discounts and rebates from the list price. However, evidence of access limitations remain in many health systems. Ultimately, the value of these therapies is maximized for patients and health systems when they are affordable and accessible, regardless of disease stage.
Chart link: http://freepdfhosting.com/a2c143ee11.pdf
In conclusion, we return to our central argument: long-term pricing power in the hands of large companies is used to primarily fund a cycle of late-stage acquisitions and share buybacks (see Fig 2 in our original article). As breakthroughs in drug development rely on long-term early-stage capital (both public and private), the consequences of the prevailing model invites a search for improvements and alternatives for innovation and affordable patient access.
(1) Gilead Sciences. FQ1 2016 earnings call transcripts. S&P Capital IQ. 26 April 2016.
(2) Gilead Sciences Announces Second Quarter 2016 Financial Results. 25 July 2016. Available at: http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=...
(3) Silverman, E. As hepatitis sales decline, Wall Street wonders what Gilead will do for its next act. STAT. 26 July 2016. Available at: https://www.statnews.com/pharmalot/2016/07/26/hepatitis-wall-street-gilead/
(4) Iyengar, S., Tay-Teo, K., Vogler, S., Beyer, P., Wiktor, S., de Joncheere, K., & Hill, S. (2016). Prices, Costs, and Affordability of New Medicines for Hepatitis C in 30 Countries: An Economic Analysis. PLoS Medicine, 13(5), e1002032. http://doi.org/10.1371/journal.pmed.1002032
(5) Dying at These Prices: Generic HCV Cure Denied. Treatment Action Group and Mèdicines du Mondes. July 2016. Available at: http://mapcrowd.org/public/pdf/EN_mapCrowd_Report2.pdf
(6) Roy, V., & King, L. (2016). Betting on hepatitis C: how financial speculation in drug development influences access to medicines. BMJ, 354, i3718. http://doi.org/10.1136/bmj.i3718
(7) Cohen, J. (2015). King of the pills. Science, 348(6235), 622–625. http://doi.org/10.1126/science.348.6235.622
(8) See pg. 24 in Gilead Sciences: Price Gouger, Tax Dodger. July 2016. Americans for Tax Fairness. Available at: http://freepdfhosting.com/e8476beb4e.pdf (For further insight into Schinazi and Pharmasset’s NIH grants, see report.nih.gov)
(9) Apath. Company profile 2016. http://apath.com/Company.htm
(10) Keller, M. R., & Block, F. (2013). Explaining the transformation in the US innovation system: the impact of a small government program. Socio-Economic Review, 11(4), 629–656. http://doi.org/10.1093/ser/mws021
(11) The Price of Sovaldi and its Impact on the US Healthcare System. US Senate, Committee on Finance. December 2015. Available at: http://www.finance.senate.gov/ranking-members-news/wyden-grassley-sovald...
(12) Cash-rich Gilead hits acquisition trail. Financial Times. 2015. Dec 7. https://next.ft.com/content/8a8e383e-9abc-11e5-a5c1-ca5db4add713
(13) Scannell, J. W., Blanckley, A., Boldon, H., & Warrington, B. (2012). Diagnosing the decline in pharmaceutical R&D efficiency. Nature Reviews Drug Discovery, 11(3), 191–200. http://doi.org/10.1038/nrd3681
(14) Silverman, E. Hepatitis C Drugs are Cost Effective but Affordability is Another Matter. The Wall Street Journal. 17 Mar 2015. Available at: http://blogs.wsj.com/pharmalot/2015/03/17/hepatitis-c-drugs-are-cost-eff...
(15) Chhatwal, J., Kanwal, F., Roberts, M. S., & Dunn, M. A. (2015). Cost-Effectiveness and Budget Impact of Hepatitis C Virus Treatment With Sofosbuvir and Ledipasvir in the United States. Annals of Internal Medicine, 162(6), 397–406.
Competing interests: No competing interests