In 2002, approximately 7.6 million people worldwide died of cancer. These deaths accounted for 13% of all deaths worldwide in that year and, perhaps surprisingly, exceeded the number of deaths from HIV–AIDS, tuberculosis, and malaria combined (which totaled approximately 5.6 million). The World Health Organization (WHO) has estimated that if current trends continue, the global cancer burden will increase from 10 million new cases per year in 2000 to 16 million by 2020. Remarkably, 70% of these cases will be in the developing world, where the number will grow from 5.2 million annually to 8.8 million by 2020.1 Currently, a cancer diagnosis in the developing world is likely to mean a painful and distressing death. Although there is growing awareness of the magnitude of the increasing cancer problem in low-income countries, the challenges of producing comprehensive national cancer plans are substantial; not least of these is the need for financial prioritization.2 The estimated amount spent on health care through Britain’s National Health Service in 2008 was approximately $3,000 per capita — considerably more than that spent for health care for citizens of Kenya, about $8.30 per capita annually. In high-income countries, we are becoming accustomed to the public debate surrounding the licensing of expensive new anticancer agents, many of which are associated with marginal clinical benefits. Government-sponsored health care systems may deny patients access to such medications, judging them cost-ineffective — moves that tend to prompt patient advocates to exert political pressure on the funding bodies, often engaging the media in an effort to get the decisions reversed. Britain’s National Institute for Health and Clinical Excellence (www.nice.org.uk), for instance, has ruled against the use of a number of recently licensed, expensive anticancer agents such as bevacizumab. This debate must appear rather odd to oncologists who practice in low-income countries, where the simplest generic treatment is often beyond the reach of the average citizen. And yet those oncologists have access to the latest online clinical guidelines promulgating “optimal” therapy and are no doubt invited by the pharmaceutical industry to international meetings to hear the latest trial results. Moreover, every country will always have an elite that will demand the “best care that money can buy.” Although the “top end” of the therapeutic spectrum is well covered by myriad guidelines (e.g., those of the National Comprehensive Cancer Network, www.nccn.org), very little has been done to develop evidence-based guidelines for cost-effective cancer treatment or recommended therapeutic algorithms for use in poorly funded health care systems. The WHO has established a database on the cost-effectiveness of more than 700 health-related interventions, using a standard measure, disability-adjusted life-years (DALYs),3 which permits the comparison of interventions within a particular field (e.g., the cost for treating early-stage breast cancer is $78 per DALY with surgery and radiotherapy vs. $4,986 per DALY with systemic chemotherapy for metastatic disease)4 as well as interventions across specialties (e.g., cataract extraction and lens implantation costs $89 per DALY). These sorts of data allow health and finance ministers to focus investment on interventions that provide a cost-effective benefit and to conclude, for example, that it is rational to detect and treat early breast cancer. Economists have methods of charting the relative benefits of any new therapy by comparing both its costs and its efficacy with those of existing treatments — by means of the so-called cost-effectiveness plane. Such an approach could be modified to assess the cost-effectiveness of previously established chemotherapy regimens — for example, for breast cancer, the combination of oral cyclophosphamide, methotrexate, and fluorouracil versus single-agent intravenous doxorubicin or paclitaxel; or for Burkitt’s lymphoma, single-agent cyclophosphamide versus complex combination therapy. Preference could be given to the agents on the WHO’s list of 17 “essential drugs for cancer therapy,” most of which have generic equivalents that offer the possibility of less expensive treatment. Plots of efficacy versus cost could be used in various ways to define acceptable benefits for optimal resource use. For example, a national health authority could first fix a budget and then decide whether the associated health improvement warranted the cost or, if there was a clear point of inflection in the curve suggesting marginal benefits for any additional cost, could use this information to define a cost-effective regimen. We believe that the first step forward is to establish an interdisciplinary task force that could develop cancer-treatment guidelines for low-income countries. Such a task force would need to include experts in oncology, local and international health economics, and clinical pharmacology who would consider the impact of pharmacogenetics, pragmatic definitions of acceptable toxicity levels, nutritional status, and intercurrent illnesses; where data are lacking, this group could recommend the types of clinical trials and studies that need to be performed to fill the gap. At the same time, we should not stop attempting to solve specific problems through “lateral thinking”: for instance, the Africa Oxford Cancer Foundation (www.afrox.org) is currently planning a trial of nurse-dispensed tamoxifen for Ghanaian women 50 years of age or older who, at informal breast-examination clinics held in village churches, are discovered to have breast lumps that are clinically adjudged to be cancer. Women who can afford the cost of formal investigation (a minority) will be referred to one of Ghana’s cancer centers (each of which serves a population of about 10 million), and the remaining women will receive (free of charge) a 2-to-3-month course of tamoxifen, which might be expected to stabilize or reduce the tumor burden in about 40 to 50% of the patients. Tamoxifen will continue to be dispensed in the community every 3 months by the nurses to patients with stable or responsive disease. This highly utilitarian approach will lead to the overtreatment of some women with breast lumps who may not have cancer, but tamoxifen is a very safe drug that can at least offer some chance of palliative benefit to women who attend the clinic for informal breast screening but who cannot afford to obtain formal health care. Does this mean that cancer medicine in low-income countries will always be rooted in the past? Not necessarily, for we have seen some innovative and successful projects in which pharmaceutical companies have provided new drugs free of charge to poorer countries — for example, the Glivec International Patient Assistance Program for patients with chronic myeloid leukemia.5 More could be made of these open-access projects, especially if they are sufficiently flexible to answer key research questions about tolerability, efficacy, and pharmacokinetics, to help refine treatment regimens that would be feasible for treatment of people in developing countries who have cancer. So will we be able to treat cancer for a dollar a day? At one level, the answer might be yes, but we need to develop an evidence base that is appropriate to the capacity of available health funds. This, we believe, will require a multidisciplinary approach through international alliances, such as the Breast Health Global Initiative (www.bhgi.info), that bring individuals, health organizations, government agencies, and corporations together in a concerted effort to improve cancer care in resource-poor countries.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
SOURCE INFORMATION From the Sidra Medical and Research Center, Doha, Qatar (D.J.K.); and the Department of Clinical Pharmacology, University of Oxford, Headington, Oxford, United Kingdom (R.M.).
1) Lingwood R, Boyle P, Milburn A, et al. The challenge of cancer control in Africa. Nat Rev Cancer 2008;8:398-403
2) Kerr F, Kerr DJ. Do we bear any moral responsibility for improving cancer care in Africa? Ann Oncol 2006;17:1730-1731
3) Tan-Torres ET, Baltussen R, Adam T, et al. Making choices in health: WHO guide to cost-effectiveness analysis. Geneva: World Health Organization, 2003.
4) Groot MT, Baltussen R, Uyl-de Groot C, Anderson BA, Hortobagyi GN. Costs and health effects of breast cancer interventions in epidemiologically different regions of Africa, North America, and Asia. Breast J 2006;12:Suppl 1:S81-S90
5) CanTreat International. Scaling up cancer diagnosis and treatment in developing countries: what can we learn from the HIV/AIDS epidemic? Ann Oncol 2010;21:680-682
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