Cancer care burden : aiming at the Achilles heel

Cancer is the one of the major causes of death worldwide. More than 16 million new cancer cases are expected by 2020, and it is estimated that cancer will then be the cause of more than 10 million deaths per year1. Cancer has become the leading cause of death in Canada. According to the Canadian Cancer Society, 40% of men and 45% of women are expected to develop cancer during their lifetime2. With recent advances in cancer management and research, the outcomes of cancer patients—specifically in developed countries—have improved. However, since the early 2000s, the cost of cancer care has exponentially gone up. Cancer care encompasses a wide range of costs—including financial, social, and psychological burdens—that are difficult to estimate. The worldwide cost of cancer attributable to premature death and disability (not including direct medical costs) has been estimated to be US$895 billion3. Mounting rates of new cancers, drugs used in cancer care, high-cost innovations and technologies, overutilization of care and futile disease-directed care, and financial hardship for the patients and families are equally contributing to the cancer care burden.


INTRODUCTION
Cancer is the one of the major causes of death worldwide.More than 16 million new cancer cases are expected by 2020, and it is estimated that cancer will then be the cause of more than 10 million deaths per year 1 .
Cancer has become the leading cause of death in Canada.According to the Canadian Cancer Society, 40% of men and 45% of women are expected to develop cancer during their lifetime 2 .With recent advances in cancer management and research, the outcomes of cancer patients-specifically in developed countries-have improved.However, since the early 2000s, the cost of cancer care has exponentially gone up.
Cancer care encompasses a wide range of costs-including financial, social, and psychological burdens-that are difficult to estimate.The worldwide cost of cancer attributable to premature death and disability (not including direct medical costs) has been estimated to be US$895 billion 3 .Mounting rates of new cancers, drugs used in cancer care, high-cost innovations and technologies, overutilization of care and futile disease-directed care, and financial hardship for the patients and families are equally contributing to the cancer care burden.

More Cancers, More Expenditure
Cancer incidence rises as the population ages.Ironically, total spending on cancer care is driven mostly by secondary and tertiary care (the cost to treat individual patients); little attention has been paid to primary prevention at the population level.

Novel Cancer Drugs and High-Cost Innovations
The cost of health care has been driven by innovations in medicine.Novel drugs and innovative therapies, new approaches to early detection and staging, new surgical devices, new methods to deliver radiation treatments, and new technologies for diagnosis and surveillance have contributed to rising cancer costs.For instance, the drugs associated with cancer care are estimated to cost approximately US$40 billion per year globally 4 .In Europe between 1993 and 2004, total sales for cancer drugs alone increased from €840 million to €6.2 billion 3 .The Canadian Cancer Society estimates that cancer drugs cost an average of CA$65,000 annually per patient.About 1 in 12 patients is not adequately covered to fund that cost 5 .Currently, more than 100 new molecules are in phase iii trials.Most new molecules are priced at CA$4,000 per month or more (Table i).Likewise, imaging costs for computed tomography, positron-emission tomography, and magnetic resonance imaging are increasing twice as fast as the overall cost of cancer care.

Overutilization and Professional Services
Specialists influence the greatest proportion of cancer care costs, through use and choice of drugs, types of supportive care, frequency of imaging, and number and extent of hospitalizations 6,7 .Overutilization is driven by false expectations, non-evidence-informed practice, defensive medicine, financial incentives, off-label use of cancer medicines, and impetus of ability to do everything [7][8][9] .For example, routine surveillance testing with serum tumour markers and imaging in asymptomatic patients have not been shown to have clinical value for most solid cancers, but are commonly performed 10 .False-positive tests can lead to harm through unnecessary invasive procedures, overtreatment, unnecessary radiation exposure, and misdiagnosis.Likewise, the American Society of Clinical Oncology guidelines recommend the use of white cellstimulating factors when the risk of febrile neutropenia secondary to a recommended chemotherapy regimen is approximately 20% and equally effective treatment programs that do not require white cell-stimulating factors are unavailable.And yet, the appropriate use of granulocyte colony-stimulating factors for the primary prophylaxis of febrile neutropenia still varies widely in clinical practice 7,11 .Furthermore, consumer demand and willingness to accept and pay for interventions with marginal benefits also play a causal role in overutilization of cancer care.

Futile Disease-Directed Care
Evidence suggests considerable expenditure for cancer care in the last weeks of life [12][13][14] .Estimates suggest that at least 20% of patients with solid tumours are receiving chemotherapy within 2 weeks of death 14 .Patients and their families can have false expectations despite receiving information on prognosis 15 .Overly aggressive cancer treatment near the end of life results in high rates of emergency room visits, hospitalization, or stays in the intensive care unit in parallel with delay in referral to palliative care.

Financial Hardship for Patients and Families
In conjunction with rising cancer costs, people living with cancer are facing a significant financial burden.Lost wages are a major contributor to the financial hardship experienced by cancer patients and their families.A Canadian study revealed that 91% of households suffer a loss of income or a rise in expenses as a direct result of a cancer diagnosis 16,17 .Medical appointments are very often uncoordinated and time-consuming, and hence it becomes impossible to hold a job.Inability to work during treatment or while caring for a loved one can result in a dramatic decline in family income.Furthermore, 1 in 5 Canadians have no private supplemental health insurance, and about 20%-30% of Canadians rely solely on government benefit programs or have no coverage at all 18 .However, government assistance might be unavailable until nearly all personal savings have been depleted.Gaps and inconsistencies in coverage and services can leave individuals responsible for tens of thousands of dollars in additional costs.

INTERVENTIONS TO ADDRESS THE CANCER CARE BURDEN
Cancer treatment is complex, often involving a variety of services, health care professionals, and settings.Hence, a combination of top-down and bottom-up approaches at various levels is required to overturn the rise in cancer care costs.We propose a framework to harness those cost.Its components include value-based care, behavioral approaches, innovative research and transformed policies, and a focus on the root causes of cancer (Figure 1).

Value-Based Care
Value-based care involves a comprehensive assessment of the outcomes and costs of care and a comparison with other approaches and modalities.Responsiveness to valuebased care is increasing, as is the development of new price-value models promoting drugs and technologies that would substantially improve outcomes but discourage the expansion of marginally effective treatment.Costeffectiveness is typically evaluated using an incremental cost-effectiveness ratio that compares the experimental treatment with the standard treatment.Usually, the incremental cost-effectiveness ratio is expressed as an incremental cost per life-year gained.The optimal threshold   for cost-effectiveness is not known.In many developed countries, $130,000 or less is considered an appropriate price at which to buy excellent care for an extra year of life 19 .
Little correlation is evident between the actual efficacy of a new drug and its price as measured by cost-efficacy ratios 9,[20][21][22] .For example, in advanced pancreatic cancer, erlotinib has demonstrated a 0.33-month median improvement in survival at an estimated incremental cost of about $500,000 per life-year gained.Despite that limited clinical benefit, erlotinib is endorsed by Health Canada and the professional societies 23 .Fojo and Grady 22 estimated that 18 weeks of cetuximab treatment for nonsmall-cell lung cancer, which was found to extend life by 1.2 months, costs an average of $80,000, which translates into an expense of $800,000 to prolong the life of a patient by 1 year.
Although industry-sponsored estimates place the average cost of research to bring a drug to market at $1.3 billion, Light and Kantarjian 20 showed that such estimates are substantially inflated.Re-evaluation of the methodologic of economic decision-making in cancer careparticularly the systematic determination of patient values and what constitutes meaningful benefit-are essential for successful implementation of the value-based approach.Notably, that model of care is more applicable in the setting of incurable than in early-stage cancer.For instance, a new drug in an adjuvant setting that prevents recurrence of cancer and saves a life thereby eliminates the cost of treating advanced disease in the future.
To effectively implement the value-based model, researchers and professional societies have the responsibility to seek better results and to stop endorsing treatments with marginal benefit.Seizing that responsibility will ease the pressure on oncologists when they discuss treatment options.Furthermore, empowering patients through education and shared decision-making, and promoting public education about the evaluation and validation of cancer technologies and the idea that value-based care is not synonymous with poor care can potentially improve care and lower costs.In Canada, the Pan-Canadian Oncology Drug Review and the Pan-Canadian Pharmaceutical Alliance are early steps to guide provinces and territories in making informed drug funding decisions and to promote equal access to cancer drugs across Canada.

Evidence-Informed Care: Behavioral Approach
Physician education is informed by evidence-based medicine.Poor-quality care is described as practices of known effectiveness being underused, practices of known ineffectiveness being overused, and services of equivocal effectiveness being used in accordance with provider rather than patient preference 13 .
Cancer specialists are obligated to provide evidencebased care that is cost-effective so as to minimize waste and eliminate insufficiency.These key recommendations 6,8,9,24 , in concert with oncologist attitudes and practice, can bring down the cost of cancer care: n Using shared decision-making and patient engagement during various phases of care n Using lower-priced options, if available n Selecting treatment schedules that minimize travel time or time away from work n Limiting disease-directed therapy on the basis of performance status n Discontinuing investigations for staging and surveillance that are not evidence-based n Limiting use of growth factors n Integrating palliative care into oncology care early Improving education for health-care professionals with respect to the use of marginally effective or futile treatment is a component that can bend the cancer cost curve.Tools are available to help reset expectations and to assist patients, families, and providers to accept the transition from active treatment to supportive care 25,26 .Nonetheless, the best method of educating health care professionals and patients to be cost-conscious is a challenge and remains to be investigated.Integration of cost-effectiveness knowledge into the medical oncology curriculum and continuing medical education is a relatively simple task that could positively affect health costs.Physician education could be linked to their Maintenance of Certification program.For instance, using various quality indicators to assess practice in relation to the Maintenance of Certification program is an important means of identifying weakness in practice and addressing the practice gap.

Transformed Policies and Innovative Research
A successful behavioral approach is linked with good policies.Major changes in cancer policies at various levels are required for cancer control and improved access to affordable care while new models of care are applied to control costs by integrating an informed regulatory system, value-based pricing of cancer therapies, compensation for cognitive services, reduction in regulatory bureaucracy on cancer research, and better access to supportive care and home hospice.
New approaches to reimbursement for cognitive services-such as discussing participation in a clinical trial or advanced medical directives, and managing unrealistic expectations in family conferences-are essential.In many cases, cancer care involves uncoordinated sequential visits to multiple providers, departments, and specialties.Minimization of fragmented care and a move to integrated practice units that encompass all the skills and services required for the cancer journey are both needed.Health outcomes measurement should become an integral part of every provider's practice.To eliminate bias against patients with complex needs, outcomes must be adjusted for initial conditions when patients present to the provider 27 .Moreover, healthy public policy that creates supportive environments, strengthens community action, develops personal skills, and refocuses health services is essential to promote healthy living and to reduce the burden of cancer.Furthermore, integration of economic and costeffective health research with novel designs using multilevel frameworks (phase 0, iv, and adaptive trials; complex multimodal clinical trials), prognostic and predictive biomarker studies, quality monitoring programs, assessment of value-based models using real-world patients, and accounting for indirect costs and effect on family are vital to harnessing cancer care costs.Many early-phase trials do not produce information of the quality needed for a confirmatory phase iii trial.Improved clinical trial designs will help to make the clinical trial enterprise more efficient, primarily by earlier detection of inadequate benefit.For example, adaptive designs use interim data to modify an ongoing trial without undermining its validity and integrity, or introducing bias.Bayesian approaches allow for continual reassessment of trial findings.A point-of-care approach involving basic research scientists and clinicians would hasten adoption of treatment improvements and allow researchers to leverage the resources of the clinical service.Furthermore, innovative future clinical study designs based on molecular tumour signatures across multiple tumour sites ("histology-independent trials") will accelerate drug development and reduce costs and duplication.

Primary Prevention: Aiming at the Achilles Heel
Although most cancer results from a complex interaction of genetic susceptibility and environmental factors, a major proportion of malignant diseases is known to be preventable 28 .It has been estimated that more than 30% of cancer deaths could be prevented by modifying or avoiding key risk factors, including tobacco, obesity, unhealthy diet, lack of physical activity, alcohol use, infection with viral hepatitis and human papillomavirus, and air pollution.Many risk factors add to the cost of other chronic diseases.For instance, recent estimates indicate that tobacco-related illness costs Canadians CA$4.4 billion in direct health care costs, with an estimated social cost of CA$17 billion per year 29 .Differential exposure to modifiable determinants can result in differential rates of cancer incidence and mortality 30 .Notably, health gradients can be related to poverty, rural or remote location, and language and cultural barriers in various high-risk populations, including socioeconomically disadvantaged people, rural residents, and aboriginal, ethnic minority, and immigrant groups.Consequently, a broad vision with a focus on the environmental and social determinants of health, changes in inequitable resource distribution, and dedicated and coordinated efforts informed by principles of equity, collaboration, participation, and capacity-building are prerequisite for reducing the growing cancer burden and, consequently, the uncontrolled costs of cancer care.
Primary prevention care is fragmented and often ineffective and inefficient.Reorganization of prevention, wellness, and routine health maintenance services with sustained funding and a workforce reimbursed for preventive care, the establishment of wellness programs in various sectors, and health promotion are long-term investments in tackling the burden of cancer and other chronic diseases.A comprehensive global tobacco control policy would be an effective and simple way to protect future generations from the rising cancer burden.
The foundation for lifelong good health is set in childhood.Hence, a life-course approach that addresses factors influencing behavior and choices relating to balanced diets and physical activity is vital in tackling the cancer burden.Efforts in primary prevention can be further amplified by using effective screening programs for early detection of cancers at their most treatable stage.

FIGURE 1
FIGURE 1 Proposed framework to reduce cancer care costs in the short and long term.The cost of cancer care has risen exponentially, with the major contributing factors being the mounting rates of new cancers, the escalating prices of novel cancer therapies, the emergence of high-cost innovations and technologies, and overutilization and futile disease-directed care.A combination of top-down and bottom-up approaches involving value-based and evidence-informed care, shared decision-making, innovative research, transformed policies, and a focus on environmental and social determinants of health are required to overturn the rising costs.

a
One course of treatment with radiation.Prices are based on labelled dosing for an average adult at the Canadian selling price; retail drug costs could be higher.CTLA4 = cytotoxic T lymphocyte-associated protein 4; EGFR = epidermal growth factor receptor; IMD = immunomodulating drug; GIST = gastrointestinal stromal tumour; HER2 = human epidermal growth factor receptor 2. e136 Current Oncology, Vol.22, No. 3, June 2015 © 2015 Multimed Inc.

TABLE I
Comparative costs of targeted therapy in Canada for various cancers