Around 12 million people are diagnosed with cancer each year, causing 7.5 million deaths. With an ageing global population and an endless conveyor belt of expensive new drugs and technologies and increasing financial pressures, the cost of cancer care in high-income countries (HIC) is becoming unsustainable. The first Lancet Oncology Commission is being presented to the 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden*. It brings together 37 experts from HIC countries in a comprehensive analysis that points out where these countries have their lost their way in managing cancer costs, and future challenges. The Commission lead author is Professor Richard Sullivan from the King's Health Partners Integrated Cancer Centre, a collaboration between King's College London and its partner NHS Foundation Trusts – Guy's and St Thomas' and King's College Hospital, London, UK.
While some issues are very specific, such as the huge development costs for new cancer medicines, other cost drivers are common across the spectrum of cancer care, such as over-use, rapid expansion of demand, and shorting life cycles of medical technologies: both drugs and imaging techniques. There has also been a tendency towards more defensive medical practice, a less informed regulatory system, and a declining degree of fairness to all patients with cancer.
Globally, the costs due to lost productivity from cancer (not including health-care costs) is just under US$1 trillion. While different HIC have varying levels of GDP devoted to overall health (USA 16%, UK 8%), many HIC have similar proportion of health-care spending directed to cancer care (between 4 and 7%, apart from Japan: 9%). The authors say: "The issue that concerns economists and policy makers is not just the amount of money currently spent on health, but also the rate of increase of health care spending." Taking one of these drivers, overuse, the authors point out it can be quicker and easier for a doctor to provide treatment than to investigate other possible causes of their symptoms (and not treat). In the USA, physicians are paid for what they do, not what they don't do, potentially driving costs up. Furthermore, physicians can, in many cases, be unaware of costs of the procedures they are ordering. The authors also touch on a sensitive area for many families: when is the most appropriate time to stop giving drugs/therapies to people who are beyond the help of any treatment, both to save the dying person from toxicity side-effects and also to cut costs. A combination of education for doctors and patients, research, personalised medicine, and a focus on end-of-life care are among the weapons needed to confront these issues.
In terms of rationing limited resources, the Commission looks at the role of bodies such as the UK's National Institute for Health and Clinical Excellence (NICE). NICE acts as a role-model for both other HIC and developing countries in estimating cost-effectiveness of new technologies—these other nations often adjust NICE modelling to their own specific circumstances. Generally, NICE sets a maximum cost-effectiveness threshold of £30,000 per Quality-Adjusted Life Year (QALY) saved. In the USA, treatments are approved if they are safe and effective, no matter what the cost. The authors suggest that the way ahead is value-based pricing, in which cost-effectiveness would be assessed using an explicit assessment of the drug's value. This links the price of medicines to the country's ability to pay (based on such factors as GDP) and levels of societal equity. Drug companies would then decide whether or not they wished to market the drug at that price. In the UK, NICE is already attempting to use this new method. But the authors point out that since the change of government in the UK in 2010, NICE faces an uncertain future. In the USA, off-label use of therapies that provide no or limited benefit are causing huge cost burdens, and this practice is not prohibited or regulated by the country's Food and Drug Administration (FDA). To help counter costs, the authors say that tailoring therapies by use of prescreening with molecular biomarkers should become the norm, and imaging methods should also be used to select patients who could benefit from a treatment and exclude those who won't. Research should move away from large phase 3 trials to intelligently designed phase 0, 1 and 2 studies that will help to more quickly discard marginally effective or ineffective drugs.
The Commission also looks at cancer costs in the UK, Australia and the USA. In the UK, following a change of government and criticism the nation was not adopting new cancer drugs fast enough, a special £200 million cancer fund was set up to improve access, but this will lead to a postcode lottery since decisions on access are regional. The Commission also points out that in the UK there is evidence that past levels of spending on new anticancer medicines have been much lower than those recorded in nations of similar wealth.
In the debate about cancer care costs, people focus most often on drugs (when drugs take up only a small proportion of total spending); yet it is surgery that is mainstay of curative treatment, with 70% of patients with solid tumours undergoing surgery. In order to make sure surgery is effective and cost-effective, it must first be established that the cancer has not spread using imaging techniques. And what of developments in surgical techniques? The authors say some studies show that minimally invasive surgery with robotics (while more appealing to the patient) can actually be much more expensive. But would these costs be balanced by the shorter hospital stay compared with traditional 'open' surgery? And care must be taken to prevent technology driving demand: robot-assisted prostatectomies are increasing, despite lower incidence of prostate cancer, and thus driving costs with no clear evidence of improved outcomes or quality of life. The authors say: "The robotic surgical community has a responsibility to design large-scale, multicentre randomised controlled trials to identify which patients will benefit from open surgery versus robotic-assisted procedures." Cancer surgery generally is becoming unaffordable, say the authors, because of unrealistic expectations about what surgery can do. "In developed countries, cancer treatment is becoming a culture of excess. We overdiagnose, overtreat, and overpromise." They add: "We are heading towards a crisis in medical-care delivery."
Radiation therapy is also a highly effective form of treatment, and some 60% of patients (in the USA) receive radiotherapy during their course of treatment. It can be used with surgery or on its own, and has proven very effective as the sole treatment for cancers of the head and neck and other areas. Huge advances have been made in accuracy and effectiveness in radiation-based care. Currently, researchers are excited about the potential of the most advanced radiation-delivery techniques in combination with tailored drug therapies. However, they note that the reality is that advanced radiation therapy is complex and costly to deliver. Bodies such as NICE may often view these techniques as prohibitively expensive, yet the improved tumour control, lower toxicity and shorter courses of treatment could help balance this. Technologies are also not as comprehensively assessed as drugs, but many critics argue they should be.
Imaging costs are also explored by the Commission. The use of PET-CT scanners (to image both the location of the cancer and its activity) have hugely improved diagnostic accuracy, but at much higher operating and capital costs than conventional scanners. And use of FDG-PET is helping identify metastatic disease is present in cases where disease was thought to be local and the patient was being prepared for surgery.
Reimbursement for new imaging technologies has become and important issue for the medical profession and for patients, who can face substantial out of pocket expenses when these tests are not covered by medical insurance. The authors say: "We have increasingly devolved responsibility for these processes to epidemiologists, statisticians, and clinicians who are not directly involved in clinical practice, and who are increasingly in the employ of bodies that seek to constrain rather than deliver quality health-care. We should take back the health technology assessment agenda, potentially achieving both cost savings and quality care, for the benefit of our patients and society."
Part of the Commission explores genomics and how they are likely to fit into the future of cancer care. Genomics has long been lauded as the key to personal medicine—indeed several tests are part of clinical practice today: HER2 testing for use of herceptin (trastuzumab) in women with breast cancer, and KRAS testing for use of cetuximab and panitumumab in colorectal cancer. But the authors say that overall, the despite the promise of genomics, the science has not yet lived up to expectation. But there are high hopes the situation will evolve.
One of the most controversial areas of the Commission discusses the cost of new drugs to battle cancer. Available research suggests that the overall benefits of medicines (for all conditions, not just cancer) developed up to the start of the current century have exceeded the amounts paid for them by an order of magnitude. But nowadays the reduced flow of blockbuster drugs is putting pressure on drug companies, and, consequently, prices. The authors say: "Additionally, the number of patients likely to require any one personalised treatment is relatively low. Such trends are economically important. The combination of high research and development costs, and limited patient populations, largely explains why the pricing and cost of new anticancer medicines is controversial in many countries, particularly those in which the allocation of health resources is most strongly affected by short-term utilitarianism (ie, the greatest good for the greatest present number). It is against this background that the authors consider issues relating to the supply of cancer medicines to patients, and the future funding of oncological research and innovation. Despite all the above, the proportion of GDP HIC spend on cancer drugs is in the range 0.1% to 0.2%, which could appear surprisingly low to the general public.
Uniquely for a paper like this, the Commission also provides an invaluable patient perspective on cancer care. In Europe, 3.2 million Europeans are diagnosed with cancer each year. The authors say: "Cancer affects the individual financially, and often a whole family. The effect is largest when the principal earner has cancer, but can also be substantial if close relatives must provide care and cannot continue employment. On average, the salary of European patients with cancer falls by 25% in the first year after diagnosis." They also point out that the employment discrimination laws in place to protect people against discrimination in HIC often don't include chronic disease, leaving employees diagnosed with cancer in a vulnerable position.
Summarising the Commission, the authors say: "We are at a crossroads for affordable cancer care, where our choices—or refusal to make choices—will affect the lives of millions of people. Do we bury our heads in the sand, keep our fingers crossed, and hope it turns out fine, or do we have difficult debates and make hard choices within a socially responsible, cost-effective and sustainable framework?" They conclude: "We believe that value and affordable cancer care can be introduced into the cancer policy lexicon without detracting from quality, and that the management tools, evidence, and methods are available to affect this transformation across all developed countries."
For Professor Richard Sullivan from the King's Health Partners Integrated Cancer Centre, London, UK via email to arrange interview. E) Richard.sullivan@kcl.ac.uk
Or via Mary Rice (contact at top of release)
Alternative contact: Emma Reynolds, Media Relations, King's College London, UK T) +44 (0)207 8484334 E) emma.reynolds@kcl.ac.uk
Alternative author contacts: USA: Jeffrey Peppercorn (Duke University, NC, USA) jeffrey.peppercorn@duke.edu; Australia John Zalcberg (Peter MacCallum Cancer Centre, Melbourne, Australia University of Melbourne, Victoria, Australia ) John.Zalcberg@petermac.org; Canada: Ian F Tannock (University Toronto, ON, Canada) ian.tannock@uhn.on.ca; Germany: Jan Geissler (European Cancer Patient Coalition, Munich, and International Chronic Myeloid Leukaemia Foundation, Munich, Germany) jan@leukaemie-online.de, France Professor David Khayat (Salpetriere Hospital Paris, France dk@cancermed.fr / Alexander Eggermont (Institut Gustave Roussy, Paris, France) Alexander.EGGERMONT@igr.fr; Italy Gordon McVie ( European institute of oncology, Milan, Italy) gordon.mcvie@ieo.it'; Sweden Peter Naredi, Umeå University, Sweden peter.naredi@surgery.umu.se
Notes to editors: *Abstract no 8LBA: Presidential Session III: Best and Late-Breaking Abstracts, Monday 12.15 hrs CEST, Hall A1
LINKED COMMENTS
Pharma companies must contribute to the debate: why haven't they?
In the first Comment accompanying the Commission, Lancet Oncology Editor Dr David Collingridge applauds the wide diversity of involvement in the project, including clinicians, pharmacists, academics, health economists, health-systems analysts, regulators, societies, trade bodies, patient advocacy groups, and governmental organisations.
However, he laments the absence of one key player: the pharmaceutical industry, who, like the others mentioned above, were warmly invited to participate. Dr Collingridge says: "Unfortunately, the pharmaceutical industry decided not to contribute, despite numerous attempts to secure their involvement. Among the pharmaceutical companies we contacted, a reticence to participate did not come from the clinicians or scientists within the organisations, rather, it was from legal teams worried about company self-interests instead of the leadership role they should have in this important debate. The commercial sector is central to these discussions, and their input and vision will be essential in formulating solutions that all stakeholders can agree too."
On the Commission overall, Dr Collingridge concludes: "We hope this Commission acts as a catalyst for further debate and helps deliver solutions before procrastination irreversibly damages the provision of high-quality care for patients with cancer."
The Lancet Oncology Press Office, T) +44 (0) 20 7424 4949 E) pressoffice@lancet.com
Prevention could be one of the biggest weapons to control costs
In the second Comment, Professor Dean Ornish, Preventive Medicine Research Institute, and Department of Medicine, University of California, San Francisco, CA, USA, discusses how prevention could be one of the biggest weapons in cost control. He says: "Although we tend to think of advances in medicine as being a new drug, device, or procedure—something high-tech and expensive—increasing evidence shows that comprehensive lifestyle changes are not only medically effective, but also cost-effective. Simple choices in lifestyle may cause powerful changes in outcomes…Making comprehensive lifestyle changes substantially improves quality of life very quickly, which is what makes these changes sustainable and meaningful."
Professor Dean Ornish, Preventive Medicine Research Institute, and Department of Medicine, University of California, San Francisco, CA, USA. T) +1-415-332-2525 ext. 222 E) dean.ornish@pmri.org
Palliative care: a delicate area that must be addressed
The difficult subject of palliative care is addressed in the third Comment, written by Professor Stein Kaasa, European Association for Palliative Care Research Network (EAPCRN), NTNU, Trondheim, and Trondheim University Hospital, Norway; Professor Sheila Payne European Association for Palliative Care (EAPC) and University of Lancaster, UK; and Dr Per Sjøgren, Section for Acute Pain Management and Palliative Medicine, Rigshospitalet, Copenhagen, Denmark.
As noted in the Commission, a substantial proportion of the cost of cancer care is spent during the last months and years of a patient's life; it also says patients should be spared toxic effects and false hope. The authors say: "An integrated and coordinated palliative medicine and oncology approach (based on collaboration) might be a better way to organise modern oncology care. How to set up such an organisational structure is undecided. Integration, collaboration, and the timing of switching from cancer care to palliative care need to be empirically tested. One key element should be that patients have only one responsible doctor at any given time. Such a structure will hopefully prevent futile treatment, improve symptom control and quality of life, and give patients access to high-quality home care."
Professor Stein Kaasa, MD PhD, NTNU, Trondhiem; Director of the Cancer Department, Trondheim University Hospital, Director of the European Palliative Care Research Centre, and National Cancer Director, Norwegian Directorate of Health T) + 47 72 82 63 29 / +47 91 89 70 01 / + 47 72 82 64 86 E) Stein.Kaasa@ntnu.no
Overtreatment of children and lack of specialist palliative care among key issues for paediatric oncology
The fourth Comment addresses the often emotionally charged issues around treatment of children with cancer. It is written by Dr Gabriele Calaminus, International Society of Paediatric Oncology (SIOP), and University of Muenster, Germany.
Dr Calaminus says that on the whole in HIC, there are long established treatment structures in place for children with cancer. However, the evidence base is struggling to expand due to the increasing regulatory hurdles researchers face. She says: "Another issue to discuss is the danger of overtreatment in children, and to accept that adjusting to a palliative situation is very difficult for the child, family, and treating physician. In developed countries, available treatments are continually increasing with new, targeted therapies, and it is becoming difficult to accept that cure might not be the endpoint"
She adds: "The awareness, concept development, and implementation of palliative care for paediatric oncology patients will help to avoid unnecessary prolongation of ineffective and cost-intensive treatments that have no benefit for patients, and will support the establishment of child-oriented or adolescent-orientated end-of-life care, which should be embedded in a non-hospital environment."
Dr Gabriele Calaminus, International Society of Paediatric Oncology (SIOP), and University of Muenster, Germany. E) gabriele.calaminus@ukmuenster.de
Cancer treatment gives returns as well as costs
In the fifth Commission Comment, Dr Robin Foà, (Medical Univesity of Vienna, Austria), and Dr Ulrich Jaeger (Sapienza University, Rome, Italy), both representing the European Hematology Association, say: "Novel therapies for haematological malignancies have often changed paradigms in cancer treatment. Examples include the introduction of stem-cell transplantation or targeted drugs for leukaemias and lymphomas, which have increased cure rates or prolonged life by transforming life-threatening diseases into manageable chronic illnesses."
They add: "In addition to the costs associated with treatment of cancer, there are also financial returns. One example is the many patients with chronic myeloid leukaemia whose disease can be controlled with tyrosine-kinase inhibitors, without chemotherapy or transplant, who live much longer and lead a normal life. Ultimately, it would also be relevant to develop rehabilitation programmes for the roughly 50% of haematological patients who are cured, so that they can return to an active working life."
Robin Foà, Medical University of Vienna, Austria, and European Hematology Association. E) foa@bce.uniroma1.it
How regulatory bodies can play a bigger role in cost issues
The penultimate Comment with the Commission focuses on the debate of cost-effectiveness and regulatory hurdles, and is written by Dr Francesco Pignatti, European Medicines Agency (EMA), London, UK, and colleagues. The authors say: "Regulators in Europe have moved away from the concept that non-validated surrogates such as PFS might be used for approval with the expectation that relevant benefits in terms of overall survival (OS) would later materialise."
They add: "Although approval of new cancer drugs in Europe will probably continue to be based on the current paradigm, there is an opportunity for regulators and payers to agree on pre-marketing and post-marketing evidentiary standards for relative effectiveness, and when relative-effectiveness trials should be available at the time of licensing."
They highlight that EMA has recently begun a collaboration with the European Network for Health Technology Assessment (EUNetHTA) to consider how the scientific assessment reports published by the Agency could contribute better to the assessment of relative effectiveness by health technology assessment bodies (such as NICE in the UK).
Dr Francesco Pignatti, European Medicines Agency (EMA), London, UK. T) +44 (0) 20 7523 7031 E) francesco.pignatti@ema.europa.eu
Some parts of Commission NICE, others not so NICE
In the final Comment, Professor Sir Michael Rawlins, Chairman of NICE, UK, and his colleague Dr Kalipso Chalkidou, director of NICE International*, give a critical appraisal of the Commission. While they praise the Commission in places, they say it does not adequately address a number of issues, among them why the cost of anti-cancer drugs has ballooned over the last 40 years. The authors say: "The cost of developing new drugs, generally, has increased substantially over the past decades and is becoming unsustainable. This is partly due to the escalating costs and inefficiencies of clinical trials themselves, together with the increasing additional burdens imposed by national drug regulatory authorities. The lengthening development times, and resulting erosion of products' patent lives, mean that companies must necessarily charge high prices to recoup their investment in research and development."
They add that some of the criticisms of health technology assessment (HTA) agencies such as NICE are not based on evidence. Furthermore, they say, the Commission takes too little account of the opportunity costs often incurred by use of some expensive new anticancer drugs that offer modest benefits.
Professor Rawlins and Dr Chalkidou provide some of their own ideas that could contribute to cost control, including recent proposals by an international group of academic clinical investigators suggest that clinical trial costs could be decreased by 40% without detriment to their quality. Simple measures to reduce costs include electronic data capture, reduction in the length of case-management forms, and modified site-management practices. They add; "Rather than criticise organisations such as NICE for declining reimbursement on grounds of cost-effectiveness, clinicians and patient advocates should start challenging pharmaceutical companies about the high prices they seek for products with modest benefits."
Dr Kalipso Chalkidou, NICE, UK. T) +44 (0)7786 510256 E) Kalipso.Chalkidou@nice.org.uk
Notes to editors: Prof Rawlins is travelling and not contactable during the period of publication
*NICE international is the international work programme of NICE. The department offers, on a cost-recovery basis, technical support to national governments interested in strengthening evidence-informed policy-making arrangements in their own healthcare systems.
Journal
The Lancet Oncology