Clearing the air: towards agreement about access to high cost cancer medicines
Authors: W. Lipworth, I. Kerridge, N. Ghinea, J. Zalcberg
Journal: Annals of Oncology (2018)

Oncologists have an important role to play in debates about access to high cost cancer medicines. But in order for oncologists to be able to fulfil this role they need to have a solid understanding of the contexts of debates about access to high cost medicines, of the parameters that everyone can agree upon, and of the points of disagreement that need to be resolved. In this article, we offer a conceptual framework that oncologists (and other stakeholders) could use to guide more focussed, systematic and ultimately mutually beneficial discussions about the subsidisation of high cost cancer medicines. The subsidisation of new cancer medicines by public and private insurers (henceforth payers) is a hotly debated topic. According to some, the coverage of new cancer medicines provides unprecedented hope for patients, redresses inequities for those with rare diseases, and provides the basis for further innovation that will, in the long-term, help win the battle against currently incurable diseases. Others, however, argue that many new cancer medicines are over-hyped and over-priced, that the benefits they confer are often small, and that the subsidisation of these medicines undermines—rather than stimulates—genuine innovation. Debates about the subsidisation of cancer medicines have become increasingly polarised. Those who want faster access to more medicines frequently portray apparently conservative payers as adversaries in their fight for access to lifesaving or life-changing drugs. Supporters of rigorous funding systems, in turn, counter that those advocating for greater access to medicines are naïve to the limitations of emerging therapies and the economic realities of sustainable healthcare systems. When, e.g. England's Cancer Drugs Fund was converted to a managed entry scheme because it was deemed to be (among other things) 'expensive', 'unsustainable' 'inequitable', 'partisan', and a representation of 'political failure across the board' [1.Cohen D. Most drugs paid for by £1.27bn cancer drugs fund had no "meaningful benefit".BMJ. 2017; 357: j2097Crossref PubMed Scopus (8) Google Scholar, 2.Thornton S. Cancer Drugs Fund is not a fair allocation of NHS resources.BMJ. 2011; 342: d621Crossref Scopus (2) Google Scholar], patients and advocates were vocal in their claims that such moves were a 'tragedy for patients' [3.B. Adams Charities and pharma decry 'disgraceful' changes to England's Cancer Drugs Fund. https://www.fiercebiotech.com/financials/charities-and-pharma-decry-disgraceful-changes-to-england-s-cancer-drugs-fund (17 July 2018, date last accessed).Google Scholar], with advocacy groups claiming that: The creation of the Cancer Drugs Fund was a huge step forward. Since its establishment, doctors have been able to offer their patients some of the best treatments available in the world. These treatments have greatly improved the quality of patients' lives, giving them precious extra months and even years of additional life with their families [4.Breast Cancer Now . Leading cancer charities call on PM to reform 'outdated' NICE drug appraisal process. http://breastcancernow.org/news-and-blogs/news/leading-cancer-charities-call-on-pm-to-reform-outdated-nice-drug-appraisal-process (17 July 2018, date last accessed).Google Scholar]. And that: Disaster now looms on the horizon for some living with incurable… cancer- the nightmare of having fewer available drugs could become a reality [5.B. Spencer Anger as funding for terminal breast cancer drug that can extend life by months faces the axe: decision is branded a 'disaster' by campaigners. http://www.dailymail.co.uk/health/article-3746203/Funding-terminal-breast-cancer-drug-faces-axe.html (17 July 2018, date last accessed).Google Scholar]. Practicing oncologists have an ambiguous role to play when it comes to debates about access to high cost cancer medicines: on the one hand, they are expected to advocate for individual patients, but at the same time, they are expected to act as stewards of scarce healthcare resources. While this ambiguity can create a moral quandary for oncologists, it also places them in the unique position of being able to see—and argue for—both 'sides' of debates about access to high cost cancer medicines. They can, therefore, contribute crucial perspectives to debates in ways that industry, payers and consumer advocates cannot. But in order for oncologists to make a meaningful contribution to debates about access to high cost cancer medicines, there is a need to be clear about the points that everyone can agree upon, and the points of disagreement that need to be resolved. In this article, we offer a framework that oncologists (and other stakeholders) could use to guide more focussed, systematic and mutually beneficial discussions about the subsidisation of high cost cancer medicines. One of the challenges that makes it difficult to identify points of agreement and disagreement in debates about access to cancer medicines is that the medicines themselves, the diseases they are intended to treat, and the patients to be treated are heterogeneous and people often have different patient groups and diseases in mind when they enter into discussions about funding. The first step in progressing debates about subsidised access to any cancer medicine is, therefore, to be clear about: •Whether the disease that would be treated is life-threatening or impacts seriously upon quality of life.•Whether patients have other similarly effective therapeutic options.•Whether the medicine being proposed for subsidisation has been shown to be safe and effective according to the usual standards of evidence-based medicine; and•whether the medicine is priced in such a way that it is broadly considered to be both affordable and cost-effective (i.e. representing 'value for money'). In order to focus the remainder of this framework and reflect the context in which most debates occur, we will assume that the cancer medicines in question are intended to treat patients with serious diseases and provide a potentially significant therapeutic option for these patients. The next step in navigating debates about access to high cost cancer medicines is to be as clear as possible about the safety, efficacy, cost-effectiveness, and affordability of the therapies in question, as these parameters determine both the direction that debates need to take, and how debates might be resolved. Broadly speaking, there are three scenarios here: •Cancer medicines that have shown to be safe and effective and are broadly considered to be both affordable and cost-effective (type 1);•cancer medicines that have been shown to be safe and effective but have not been shown to be cost-effective and/or affordable according to the standards and circumstances of a particular jurisdiction (type 2); and•cancer medicines that appear to work in early phase studies, but have not (yet) been shown conclusively to be safe and effective in phase III trials (type 3). Once the clinical and therapeutic contexts have been clarified, the next step is to identify points of agreement. Although this seems obvious, this is a step that is often missed in debates about access to cancer medicines, which contributes significantly to their polarisation. For type 1 interventions (known to be safe, effective, cost-effective, and affordable), it seems likely that everyone would agree that subsidisation should take place without undue delay. Consequently, every effort should be made to facilitate this including by adequately resourcing of health technology assessment agencies and promoting collaboration, mutual recognition, and harmonisation in order to avoid unnecessary duplication among jurisdictions. For type 2 interventions (known to be safe and effective, but not cost-effective and/or affordable based on local criteria) it seems likely that there would be some broad areas of agreement. These include: •the need to be compassionate which, depending on the context, might be achieved through access to medicines, or through the provision of alternative forms of care;•the need to respect patients' desires for what might be considered by others to be small benefits in terms of length or quality of life;•the need to promote equity and address existing inequities by attempting to fund medicines for patients who are already disadvantaged because of their disease (e.g. those with rare cancers) or their financial situation;•the need to support clinical innovation, recognising that new treatments are seldom revolutionary, but might open up new therapeutic approaches and generate significant cumulative benefits;•the need to reward pharmaceutical companies for their investment in research and development, and stimulate further innovation;•the need for decisions about access to be systematic rather than ad hoc; and•the need to consider the economic realities of health systems; while these realities would vary depending on the ways in which prescription medicines are regulated and subsidised, there would likely be broad agreement on the need to attain 'value for money', distribute resources fairly across populations (however, this might be defined), and ensure that cancer medicines are affordable, and that systems (whether public or private) are sustainable. For type 3 interventions (not yet shown to be safe and effective through phase III studies), the above points of agreement would still apply, but discussions would also need to centre on the 'experimental' nature of the intervention. Here, it seems likely that most people would agree that: •patients with serious diseases should not be denied a chance to benefit, provided the intervention is not futile and not likely to cause more harm than benefit;•providing hope can be a moral good, provided that patients are also truthfully informed about their prognosis, the true likelihood of benefit, the possibility of harm, and the availability of other interventions, such as palliative care; and•patients in this situation should have some say in how much risk they are willing to assume. At the same time, everyone would recognise the importance of (somehow) generating conclusive evidence of the safety and efficacy of medicines. Once common ground has been reached, the next step is to address points of disagreement. Here, much can be gained by reasoning systematically about the numerous intersecting issues. For type 1 interventions, where efficiency is the key issue, there is likely to be disagreement about how much (insurer versus industry) money should be devoted to the resourcing of health technology assessment agencies and how much cross-jurisdictional recognition and harmonisation is possible and desirable given the wide variety of economic conditions and value systems in which funding decisions are made [6.Hutton J. Trueman P. Facey K. Harmonization of evidence requirements for health technology assessment in reimbursement decision making.Int J Technol Assess Health Care. 2008; 24: 511-517Crossref PubMed Scopus (41) Google Scholar]. In this regard, it is noteworthy that despite efforts towards harmonisation, public and private payers remain largely isolated from one another, and agencies assessing cancer medicines and companion diagnostics often struggle to complete assessment of medicines in a timely manner [7.Akehurst R.L. Abadie E. Renaudin N. Sarkozy F. Variation in health technology assessment and reimbursement processes in Europe.Value Health. 2017; 20: 67-76Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar]. For type 2 interventions—where there are good reasons to want to facilitate access but there are questions regarding the value or affordability of the medicine (either because of the price of the drug or the size of the target population), there are three key issues that need to be discussed, each of which raises its own series of substantive questions: •How much money should be spent on cancer medicines?•Do governments (and perhaps even private insurers) have a 'duty' to rescue those in need? Do people have a 'right' to access the cancer medicines they want or need? [8.Parliament of Australia . Availability of new, innovative and specialist cancer drugs in Australia http://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/Cancer_Drugs/Report (8 November 2015, date last accessed).Google Scholar, 9.Harper C. Ghinea N. Lipworth W. The Right to Health: implications for the funding of medicines in Australia.J Law Med. 2017; 24: 640-655PubMed Google Scholar, 10.Fleck L.M. Controlling healthcare costs: just cost effectiveness or "just" cost effectiveness?.Camb Q Healthc Ethics. 2018; 27: 271-283Crossref PubMed Scopus (7) Google Scholar].•What other (health and non-health) goods should be foregone in order to subsidise cancer pharmacotherapies? [11.A Belloni , DMorgan, V. Paris OECD health working papers: pharmaceutical expenditure and policies. https://www.oecd-ilibrary.org/content/paper/5jm0q1f4cdq7-en (18 July 2018, date last accessed).Google Scholar].•How should we determine which healthcare interventions represent 'value for money'? Should such assessments be based on population averages given that a subset of patients may benefit substantially? [12.Fleck L.M. Personalized medicine's ragged edge.Hastings Cent Rep. 2010; 40: 16-18Crossref PubMed Scopus (15) Google Scholar, 13.Aggarwal A. Fojo T. Chamberlain C. et al.Do patient access schemes for high-cost cancer drugs deliver value to society? Lessons rom the NHS Cancer Drugs Fund.Ann Oncol. 2017; 28: 1738-1750Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar].•What is a fair price to pay and should prices be negotiated?•Is there such as thing as a 'fair price' for a drug and, if so, how should this be determined? [14.Avorn J. The $2.6 billion pill - methodologic and policy considerations.N Engl J Med. 2015; 372: 1877-1878Crossref PubMed Scopus (210) Google Scholar, 15.Kantarjian H. Fojo T. Mathisen M. Zwelling L. Cancer drugs in the United States: Justum Pretium—the just price.J Clin Oncol. 2013; 31: 3600-3604Crossref PubMed Scopus (256) Google Scholar].•To what extent, if at all, should companies be rewarded for their investment, given the risks they take in developing medicines and their role in creating employment, improving the health of the community and driving scientific discovery? [16.PhRMA . Industry Profile. https://www.phrma.org/industryprofile/ (18 July 2017, date last accessed).Google Scholar].•Should payers be able to negotiate drug prices and, if they can, to what extent, if at all, should delays in access be accepted as payers negotiate prices, rebates and risk-sharing agreements? [8.Parliament of Australia . Availability of new, innovative and specialist cancer drugs in Australia http://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/Cancer_Drugs/Report (8 November 2015, date last accessed).Google Scholar, 17.Kantarjian H. Steensma D. Sanjuan J. et al.High cancer drug prices in the United States: reasons and proposed solutions.J Oncol Pract. 2014; 10: e209-e211Crossref PubMed Scopus (87) Google Scholar, 18.Ghinea N. Lipworth W. Affordable access to innovative cancer medicines—don't forget the prices.Med J Aust. 2016; 204: 214-215Crossref PubMed Scopus (8) Google Scholar].•Equity for whom?•What, if any, kinds of comparisons can be made between access to cancer medicines in different jurisdictions, where public and private insurance is organised differently and there are differences in access to non-pharmaceutical interventions? [19.Bigdeli M. Jacobs B. Tomson G. et al.Access to medicines from a health system perspective.Health Policy Plan. 2013; 28: 692-704Crossref PubMed Scopus (170) Google Scholar, 20.Elwood J.M. Aye P.S. Tin ST. Increasing disadvantages in cancer survival in New Zealand compared to Australia, between 2000–05 and 2006–10.PLoS One. 2016; 11: e0150734.Crossref PubMed Scopus (14) Google Scholar].•What should happen when so many groups begin to demand special consideration that their calls for access begin to threaten system sustainability (e.g. as more cancers become defined according to rare molecular subtypes and fall into the category of 'rare diseases')? [21.Schey C. Milanova T. Hutchings A. Estimating the budget impact of orphan medicines in Europe: 2010–2020.Orphanet J Rare Dis. 2011; 6: 62.Crossref PubMed Scopus (93) Google Scholar].•Which, if any, disadvantaged groups should be privileged in initial efforts to address unjust inequalities? For example, should the focus be on those with rare cancers, or those who are socio-economically disadvantaged? Type 3 interventions, which have not been shown conclusively to be safe and effective, bring into sharper focus all the debates relating to equity and sustainability discussed above. However, even if the medicines that are funded through these schemes are not enormously expensive, there are several points of disagreement stemming from the 'experimental' nature of the medicines that are being subsidised, including: •Is there such as thing as a 'right to try' experimental therapies and, if so, who (if anyone) should subsidise these therapies? [22.Cohen-Kurzrock B.A. Cohen P.R. Kurzrock R. Health policy: the right to try is embodied in the right to die.Nat Rev Clin Oncol. 2016; 13: 399-400Crossref PubMed Scopus (8) Google Scholar].•Can patients make fully informed and un-coerced decisions about access to cancer medicines given that (i) the information about these medicines is often highly complex and may be distorted by 'hype' that often surrounds new therapies, and (ii) patients may experience social and psychological pressure to 'try everything' that is on offer? [23.Lipworth W. Kerridge I. Stewart C. The necessity for a commitment to beneficence and prudence in clinical innovation with autologous stem cells.Perspect Biol Med. 2018; 61: 90-105Crossref PubMed Scopus (5) Google Scholar].•Are there any limits to the risks that even adequately informed patients should be allowed to assume given that doctors have a duty of care and medicine is not simply a marketplace in which goods are provided to completely autonomous consumers? [23.Lipworth W. Kerridge I. Stewart C. The necessity for a commitment to beneficence and prudence in clinical innovation with autologous stem cells.Perspect Biol Med. 2018; 61: 90-105Crossref PubMed Scopus (5) Google Scholar].•To what extent, if at all, should patients be denied access to experimental therapies (outside the context of clinical trials) for the good of future patients–patients who will lose out if fewer patients are willing to enrol in phase III trials and pharmaceutical companies have less incentive to conduct them? [24.Salter B. Zhou Y. Datta S. Hegemony in the marketplace of biomedical innovation: consumer demand and stem cell science.Soc Sci Med. 2015; 131: 156-163Crossref PubMed Scopus (42) Google Scholar].•To what extent (if at all) should the burden of generating evidence about risks and benefits of cancer medicines be shifted from industry to the public purse or to private insurers? [25.London A.J. Kimmelman J. Accelerated drug approval and health inequality.JAMA Intern Med. 2016; 176: 883-884Crossref PubMed Scopus (6) Google Scholar]. The above framework has been designed to apply to debates about the funding of any cancer medicine—with a particular focus on those that are expensive and used to treat serious or life-threatening diseases. The framework has also considered some moderating factors, such as disadvantage stemming from rarity or socio-economic disadvantage. There are, however, a number of other factors that could potentially shift the balance of decision-making in particular contexts. While it is beyond the scope of this framework to consider these issues in depth as each raises its own set of complex moral and practical questions [26.Chim L. Salkeld G. Kelly P. et al.Societal perspective on access to publicly subsidised medicines: a cross sectional survey of 3080 adults in Australia.PLoS One. 2017; 12: e0172971Crossref PubMed Scopus (21) Google Scholar], the following questions would need to be asked about the funding of any cancer medicine: •What population is being treated? For example, is the treatment intended to be used for paediatric cancers or young parents? If so, should this impact upon the funding decision?•What kinds of outcome/s can the treatment achieve (e.g. increased overall survival, increased progression-free survival, prolonged treatment-free period, improved quality of life, improved occupational function, and/or reduced carer burden)? How (if at all) should this change the funding decision?•Does the medicine in question represent a significant therapeutic innovation? That is, does it work according to a novel mechanism of action and/or represent a new 'class' of cancer therapeutic? Should this make it any more worthy of funding? A final issue that needs to be discussed in any debate about access to high cost cancer medicines is more one of process than of substance, and centres on who should make decisions about access to medicines. In private healthcare systems, where funding decisions reflect both public values and commercial imperatives and are in the hands of insurance companies and benefit managers, there may be relatively little room to move with respect to 'who decides'. However, perhaps even in these systems, those who pay for insurance (patients), those who advise them (physicians), and those who have a broader interest in the distribution of resources (cancer support and advocacy groups) should have a greater say in how funding decisions are made. In public healthcare systems, it is already a given that funding decisions should reflect public values and it is increasingly accepted that all stakeholders should be engaged. There is, however, much debate about precisely how this should be achieved. Some advocate strongly for cancer patients, clinicians, patient advocates, and/or the public being involved in coverage decisions on the grounds that this increases the legitimacy of these decisions [27.Wortley S. Street J. Lipworth W. Howard K. What factors determine the choice of public engagement undertaken by health technology assessment decision-making organizations?.J Health Organ Manag. 2016; 30: 872-890Crossref PubMed Scopus (10) Google Scholar]. Others counter that such involvement—while desirable in theory—does not improve the legitimacy of funding decisions because stakeholders may not be adequately represented or have sufficient knowledge to contribute meaningfully to funding decisions that have long-term social, medical, and financial implications. Furthermore, it may be the case that preferential treatment is given to those with the 'loudest' voices, and that participants are 'captured' by special interest groups with their own political or commercial agendas [28.Rose S. Highland J. Karafa M. Joffe S. Patient advocacy organizations, industry funding, and conflicts of interest.JAMA Intern Med. 2017; 177: 344-350Crossref PubMed Scopus (78) Google Scholar, 29.Conklin A. Morris Z. Nolte E. What is the evidence base for public involvement in health‐care policy? Results of a systematic scoping review.Health Expect. 2015; 18: 153-165Crossref PubMed Scopus (106) Google Scholar]. The mere fact that there are merits to both positions suggests that resolution might lie in the creation of process that meet the criteria for procedural justice—i.e. relevance, responsiveness, inclusiveness, transparency, and accountability [30.Daniels N. Accountability for reasonableness - establishing a fair process for priority setting is easier than agreeing on principles.BMJ. 2000; 321: 1300-1301Crossref PubMed Scopus (463) Google Scholar]. This framework makes clearer the points of agreement and disagreement about the funding of high cost cancer medicines. There are a number of reasons why this is valuable. First, it moves us away from generalisations, which are almost always unhelpful. Second, it makes clear the shared values that can overcome policy paralysis. And finally, it tells us specifically what disagreements need to be resolved in particular contexts, thereby paving the way towards greater agreement. This framework does not offer any simple solutions—indeed, each issue tackled is likely to uncover a set of even more complex empirical uncertainties and deeper moral disagreements. For example, debates about drug prices uncover complex underlying questions about (among other things) the real cost of drug development [14.Avorn J. The $2.6 billion pill - methodologic and policy considerations.N Engl J Med. 2015; 372: 1877-1878Crossref PubMed Scopus (210) Google Scholar], and whether paying more for drugs does in fact stimulate subsequent pharmaceutical innovation [31.Fojo T. Mailankody S. Lo A. Unintended consequences of expensive cancer therapeutics-the pursuit of marginal indications and a me-too mentality that stifles innovation and creativity: the John Conley Lecture.JAMA Otolaryngol Head Neck Surg. 2014; 140: 1225-1236Crossref PubMed Scopus (227) Google Scholar]. However, what ultimately matters in debates and negotiations about access to expensive cancer medicines is not that people reach complete agreement, but that people can see that there are complex arguments on both 'sides' and that the various views need to be listened to, respected and understood. This research was supported by the National Health & Medical Research Council (grant numbers 1141943 and 1080673).