The incidence of cancer is increasing worldwide. In developed countries, longer life expectancy but also better diagnostic abilities explain this increase, whereas in developing and middle-income countries, the time bomb of tobacco-related and viral-induced cancer is starting to show its toll. Projections estimate 15 million new cancer cases every year by 2020. Over the past decades, cancer research has led to astonishing progress in prevention, cure (especially in childhood cancers), and extending lives and improving quality of life.

However, whether and to what extent patients benefit from this progress depends on where they live. In large parts of Africa, cancer is only diagnosed in the late stages, pain relief is lacking, and palliative care is in its infancy. The diagnosis of cancer means a slow and painful death. At a 2-day conference in London, UK, last week—organised by Oxford University researchers—African Health Ministers, international health and development organisations, physicians, UK government officials, and cancer charities came together to shine a spotlight on Africa’s growing cancer crisis. With a declaration and a resolve to put cancer firmly on donors’ and African governments’ agendas, a first and important step to allow African people to benefit from progress in cancer prevention and treatment has been made.

In developed countries with modern health-care systems, access to new and effective treatments and preventive interventions should not be an issue. However, in an in-depth report published last week as a supplement to theAnnals of Oncology, Bengt Jönsson, an economist from the Stockholm School of Economics, and Nils Wilking, a clinical oncologist from the Karolinska Institute, Stockholm, Sweden, assessed access to new cancer drugs in 25 countries. They then linked differences in availability to differences in cancer mortality. Of fi ve major European countries, France had the highest overall 5-year cancer survival rate with 71% for women and 53% for men, and the UK had the lowest, with 53% for women and 43% for men. The UK, together with New Zealand, Poland, the Czech Republic, and South Africa, had the lowest and slowest uptake for many new drugs, whereas Austria, France, Switzerland, and the USA had the highest uptake. This is in stark contrast with the finding that the UK is, together with

In the report, the UK was singled out for particular criticisms. With its cost-eff ectiveness analyses by the National Institute for Health and Clinical Excellence (NICE) it is a world leader, or so the authors argue, in creating yet another barrier or hold-up to making new drugs widely and quickly available. NICE shot back with an immediate press release and called the report fl awed and inaccurate, and pointed out that the drug-industry sponsored report failed to recognise the introduction of its rapid approval process. “It is the job of NICE to put the health of patients and the public fi rst, not the profi ts of the pharmaceutical industry”, said Andrew Dillon, NICE’s Chief Executive. In reality, NICE has to look beyond the health of people and weigh up how aff ordable a particular treatment is by estimating the costs per life-year gained.

Yes, the authors did compile their report with an unrestricted grant by Roche Pharmaceuticals, which is clearly acknowledged, and some—but by no means all— of the drugs they assess in detail, such as trastuzumab for breast cancer and bevacizumab for colon cancer, are made or marketed by Roche. But to dismiss this very detailed report that looks beyond pure usage data and tries to assess outcomes in three different ways is premature and petulant.

Linking differences in survival to access to new drug treatments is, of course, not the whole explanation. A paper, published by authors from the Royal College of Radiologists inClinical Oncology, concluded that radiotherapy activity needs to be increased by 92% in England to allow adequate access to radical or adjuvant postoperative radiotherapy in all patients. In 2005, 55% of patients did not have radiotherapy within the maximum recommended wait of 28 days. Clearly, cancer treatment in the UK has lagged behind. The Department of Health has recognised this and released a report last week, outlining a strategy for developing a world class radiotherapy service for England.

All countries with publicly funded health care need to decide on comprehensive national plans and strategies to achieve the maximum possible gain in survival and quality of life for cancer patients. If costs are the predominant consideration, health systems are failing their people.■ The Lancet

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the survival of children under 5 years of age. The report assesses the progress made towards reducing child mortality rates in 60 countries, which together account for 94% of all child deaths. There are some reasons to be hopeful. Egypt, Indonesia, Bangladesh, Nepal, and the Philippines have all cut child death rates substantially during the past 15 years. These countries have invested in better health care for mothers and better nutrition and care for children. Despite limited financial resources, Malawi, Tanzania, Madagascar, Nepal, and Bangladesh have also made impressive gains in child survival, showing that governmental commitment matters more than national wealth when it comes to child survival.

But not all the news is promising. None of these 60 countries are doing well across all child health indicators, and 20 countries have either made no progress in reducing deaths in children under 5 years, or their rates have increased since 1990. These reversals are linked to armed conflict or HIV/AIDS epidemics in

countries such as Iraq and Botswana, respectively. In other countries, child health is clearly not receiving the attention it deserves, despite nations signing up to the fourth Millennium Development Goal (MDG-4)—to reduce under-5 mortality by two-thirds by 2015. Aside from the moral imperative, governments need to realise the importance of child survival for the future of their countries. Healthy children do better in school and grow up to be more productive adults, who contribute to the economic growth and development of their countries.

Governments can reassert their commitment to MDG-4 by developing a national plan for maternal, newborn, and child health. To produce and implement such plans, technical and financial support will be needed from international organisations and major donors. Currently, funding for child survival programmes is far below what is needed to achieve the child and maternal MDGs. Ministers of rich and poor countries must now raise the bar considerably, in terms of commitment and action, to ensure mothers, newborns, and children thrive worldwide.■ The Lancet

http://www.savethechildren.org.
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WHO’s constitution states that “the extension to all peoples of the benefits of medical, psychological and related knowledge is essential to the fullest attainment of health”. Well-implemented high-quality guidelines for member states can realise this aim through the equitable sharing of best practice in a locally-appropriate form. However, despite a decision by WHO in 2000 to make guidelines evidence-based, and the publication of internal guidance in 2003 to standardise procedures, the quality of the 200 recommendations produced by WHO each year has been inconsistent. On May 9, The Lancet published Andy Oxman and colleagues’ investigation into how WHO recommendations are formulated, which identified shortcomings in both process and products. Thus, WHO’s response, to create a Guidelines Review Committee, is swift, unequivocal, and welcome.

The Guidelines Review Committee will be a crucial mechanism to advise staff on guideline development. It will seek to strengthen the capacity of all WHO staff to produce good guidelines. In other words, the Committee

is not only about quality assurance, it is about triggering an institution-wide change in culture and behaviour. The changes will, in time, extend to WHO’s most vulnerable outposts—its regional offices. And they will feed into the creation of a WHO-wide research strategy to be presented to the World Health Assembly in 2009.

The creation of a Guidelines Review Committee is good news for WHO, and provides an example of transparency to the UN, and of accountability to its stakeholders. The World Health Assembly, convening in Geneva this week, can take pride in these actions, but must recognise that the synthesis, implementation, and evaluation of science-based guidelines will require considerable resources if the commitment is to be sustained as a core activity. Establishing the Guidelines Review Committee confi rms new Director-General Margaret Chan’s commitment to “decisions based on evidence” and her own vision to make WHO “absolutely authoritative in our guidance…to use health as a lever for making this world a better place for all humanity”.■ The Lancet

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Replacement of ovarian hormones after menopause is a practice in decline, largely because of several credible reports that link postmenopausal hormone use and breast cancer. In today’sLancet, Valerie Beral and colleagues report the latest findings from the Million Women Study. Women who used hormone- replacement therapy (HRT) also faced an increased risk of ovarian cancer, at least while on the drug.1 The effect size was small (relative risk 1·2 [95% CI 1·09–1·32]), and the investigators followed up nearly 1 million women, half of whom took HRT. 2273 new cases of ovarian cancer were recorded in the cohort, leading to 1591 deaths. Because of the large number of women in this study, we can examine the results in some detail. The risk was raised for serous ovarian cancers (ie, most of them) and in women who were treated for at least 5 years. No residual risk was seen in women who had taken HRT at some time in the past, or for those who took HRT for fewer than 5 years.

HRT seems to be unique among risk factors for ovarian cancer in that it targets postmenopausal women. Other risk factors—oral contraceptives, parity, and breastfeeding—all programme the ovaries of young women in a way that protects them against ovarian cancer much later in life. The average age of the patients in the Million Women Study was 57 years, but women who use oral contraceptives are young and premenopausal. What would happen if we gave an oral contraceptive to a postmenopausal woman? Would the risk of ovarian cancer go up or down? Although no one is likely to try this experiment, we can speculate. Oestrogen could block early events in ovarian cancer but promote later steps of carcinogenesis—or accelerate the growth of an existing tumour. If early hormone exposure were to reduce the number of healthy cells that were at risk of becoming cancerous (perhaps by depletion of the stem-cell compartment), we would expect to see a long- lasting protective effect. If oestrogen exposure were to advance the clinical presentation of a pre-existing cancer or a precancerous lesion, and if the tumour growth rate were rapid, we would expect to see an adverse effect in current users. Unfortunately, this model does not explain why at least 5 years of HRT exposure were needed to generate a significant increase in risk. Of course, the differences between the effects of hormones

given to premenopausal and postmenopausal women might also be due to differences in the doses and formulations used. We should also remember that the comparison group in studies of exogenous hormone use in premenopausal women consists of women with high concentrations of circulating oestrogen, whereas for postmenopausal women, baseline oestrogen concentrations in the comparison group are low.

What can we say about progesterone? Progesterone has been proposed as a plausible candidate for chemoprevention of ovarian cancer, on the basis of studies of women who used birth-control pills and studies in animals.2,3

Progesterone induces apoptosis of ovarian epithelial cells.2 Because no significant difference was recorded in the relative risk of ovarian cancer in the subgroups of women who used oestrogen only and those who used combination pills, progesterone was also implicated as a possible carcinogen. But we can look at this result in another way—when progesterone was added to the formulation, the odds ratio fell from 1·3 to 1·1—this observation is also consistent with a protective effect.

The situation is similar for endometrial cancer. Young women who take oral contraceptives are protected against endometrial cancer later in life.4 After the menopause, progesterone is added to prevent the carcinogenic eff ect of oestrogen on the uterus. For breast cancer, combination pills are thought to be more hazardous than oestrogen alone.5–8 In both the Women’s

PublishedOnline
April 19, 2007
DOI:10.1016/S0140-
6736(07)60535-2

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