IMPACT REPORT: CANCER prepared by
in association with
Hayden Wilkinson, BSc • Juliet Bowater, MRes • James Snowden, MSc Per-Erik Milam, PhD • Hauke Hillebrandt, PhD
CONTENTS Report Summary
2
Impact Summary
3
1. What is cancer?
4
2. How does Cancer affect people?
4
3. How can you address the problem?
6
4. Research
7
5. Prevention
9
5.1 Vitamin A fortification (stomach cancer)
10
5.1.1 How does it work?
10
5.1.2 Tractability and cost-effectiveness
11
5.1.3 Positive wider impacts
13
5.1.4 Due diligence: Possible offsetting/negative impacts
15
5.1.5 Neglectedness
16
5.1.6 Charity recommendations
18
5.2 Tobacco control (tracheal, bronchus, and lung cancer)
20
5.2.1 How does it work?
22
5.2.2 Tractability
22
5.2.3 Cost-effectiveness
23
5.2.4 Positive wider impacts
24
5.2.5 Due diligence: Possible offsetting/negative impacts
25
5.2.6 Neglectedness
26
5.2.7 Charities working in this area
28
5.3 Hepatitis B vaccination, treatment of parasites (liver cancer, bladder cancer)
29
5.4 Screening, HPV vaccination (cervical cancer)
31
5.5 Screening, awareness raising (breast cancer)
32
6. Treatment
33
References 34
This report was prepared by the research team at Giving What We Can, part of the Centre for Effective Altruism, in association with Founders Pledge. www.givingwhatwecan.org www.founderspledge.org © 2016 Centre For Effective Altruism, all rights reserved. The Centre for Effective Altruism is a registered charity in England and Wales, Registered Charity Number 1149828. 1
REPORT SUMMARY Cancer makes a sizeable contribution to the global disease burden and is therefore a major health challenge. There currently exist a variety of treatment and prevention methods which may alleviate this burden, in addition to conducting further research which might well uncover additional methods. Although we consider a variety of interventions and funding opportunities in this report, we find that many of them do not provide the opportunity to have a sizeable impact through donations. For instance, cancer research is an extremely crowded area (see Section 4), direct treatment generally has low cost-effectiveness (see Section 6), and prevention methods such as tobacco control (see Section 5.2) are not currently carried out on a large scale by any highly effective charities which also have a large funding gap. The most promising intervention we have found for the reduction of cancer mortality and morbidity is the implementation of national vitamin A fortification programs (see Section 5.1). Increasing the vitamin A intake of those who currently have low intake levels, as much of the developing world does, greatly reduces the incidence of stomach cancer - which has the second-highest global death toll of all forms of cancer. Through national fortification programs, low levels of vitamin A can easily and inexpensively be fortified into staple foods such as wheat flour, oil, sugar, and so on. Doing so is extremely tractable, and also extremely high-impact, with the potential to reduce total child and maternal mortality by approximately 30% in countries in which it is implemented. For this intervention, and for cost-effectively reducing cancer incidence, we recommend
2
Project Healthy Children (PHC), which advises and assists local governments and manufacturers in various countries, predominantly in sub-Saharan Africa, to implement such fortification programs. PHC is able to do so at an average cost of approximately $0.07 per additional person who receives fortified foods. PHC also focuses its work on relatively small countries, with high rates of nutritional deficiencies, which are otherwise quite neglected by bigger foundation. Given this, we expect donations to PHC to have an extremely high marginal impact. We also estimate, albeit with a large degree of uncertainty, that donations to PHC will prevent deaths due to stomach cancer at an average cost of $19,100 each, and avert disability-adjusted life years (DALYs) at a rate of $720/DALY (in other words, it costs $720 per year of health), which is more cost-effective than other cancer interventions we are currently aware of (see Section 5.1.2). In comparison, cancer treatment in the United Kingdom is performed at an average cost of £30,000 per year of treatment, with the average cost per death prevented being far higher. However, these estimates are restricted to only the benefits related to stomach cancer. Including the enormous co-benefits of decreased child and maternal mortality, reduction in vitamin A deficiency, reductions in stunting and so on, the cost-effectiveness might increase to less than about $40/ DALY averted, on average. In some of the countries in which PHC operates, this drops to less than $20/ DALY. We are reasonably confident that at least one DALY is averted for every $40 spent on PHC’s programs and therefore strongly recommend it as an opportunity to both cost-effectively reduce cancer incidence and also cost effectively improve health overall.
IMPACT SUMMARY
Cause area Charities
Cost-effectiveness (cancer)
Robustness of evidence (cancer)
Cost-effectiveness (overall)
Robustness of evidence (overall)
Quality of implementation
Room for more funding
Unknown
Tractability N/A
•••••
X
Neglectedness
••••• ••••• •••••
•••••
•••••
✓
Scale
Research (all cancers)
•••••
•••••
•••••
✓
Project Healthy Children
•••••
•••••
•••••
Unknown Unknown
•••••
••••• ••••• •••••
N/A
•••••
•••••
•••••
•••••
•••••
Micronutrient fortification (stomach)
••••• ••••• •••••
Deworm the World Initiative
•••••
•••••
•••••
•••••
Tobacco control (lung)
••••• ••••• •••••
GAVI Alliance
•••••
Unknown
•••••
Liver fluke treatment (liver)
••••• ••••• •••••
Schistosomiasis Control Initiative
•••••
•••••
Hepatitis B vaccination (liver)
••••• ••••• •••••
World Child Cancer
X
Schistosomiasis treatment (bladder)
••••• ••••• •••••
Intervention
Cancer
Treatment (all)
3
1. WHAT IS CANCER? Cancer is a collection of related diseases, all of which involve the uncontrolled division of cells within the body.16 These cell growths, also referred to as neoplasms, can spread to surrounding tissues and the rest of the body. Many common cancers can be treated, particularly if they are
detected quickly, through methods such as radiotherapy, chemotherapy, and surgery. Many cancers can also be prevented by reducing or eliminating exposure to external agents, such as carcinogens found in tobacco smoke.17
2. HOW DOES CANCER AFFECT PEOPLE? Worldwide, cancer is a major contributor to both mortality and morbidity. Each year, approximately 14 million new cases are recorded,18 along with 8.24 million deaths attributable to cancer.19,20 This equates to approximately 8% of disability-adjusted life years (DALYs incurred) and approximately 15% of all deaths.21 See Figure 1 below for a breakdown of how different types of cancer contribute to this total. Cancer is commonly thought of as “...a disease of the rich…”,22 and it is indeed true that it makes up a significantly larger proportion of deaths in richer countries (see Figure 2). Even in age-standardised figures, cancer accounts for a greater relative number of both deaths (24.93% compared to 12.45%) and DALYs (13.97% and 7.45%) in developed nations than in developing nations, and this difference holds across every available age group (0-5, 5-14, 15-49, 50-69, and 70+ years),23 although this difference may be partly explained by the comparatively high incidence of communicable, maternal, neonatal, and nutritional diseases in the
developing world (26.6%, compared to 5.36% in the developed world).24 Still, most of the burden of cancer falls on the developing world. The World Health Organisation reports that more than 60% of new cancer cases occur in Africa, Asia, and Central and South America, due to their higher populations.26 Approximately 70% of all deaths attributable to cancer also occur in these regions27 and, in developing nations more widely, cancer accounts for 12.17% of all deaths (see Figure 3).28 This is potentially exacerbated by a lack of medical infrastructure, doctor training, and international funding for cancer treatment in the developing world.29 Cancer predominantly affects older people, with the average years of potential life lost being comparatively small - only 12.5 years per cancer death,31 as opposed to diseases that affect infant mortality such as malaria. As a comparison against other diseases, cancer makes up only 11.3% of years of potential life lost despite causing
Type of cancer
Annual deaths1
% of total deaths2
% of total DALYs3
Lung
1,590,000
2.99
1.42
Liver
745,000
1.49
0.85
Stomach
723,000
1.53
0.73
Colorectal
694,000
1.41
0.65
Breast
521,000
0.86
0.54
Oesophageal
400,000
0.80
0.40
Figure 1: Deaths and DALYs incurred, by type of cancer. 4
Figure 2: Residents of developed nations are, generally, more likely to die of cancer than those in developing nations.25
Figure 3: Neoplasms (outlined in yellow) as a proportion of total mortality in developing nations in 2013;30 5
15% of all deaths. Thus, cancer incidence is therefore expected to increase as life expectancy increases. It is expected that the number of new cancer cases each year will rise by approximately 70% over the next two decades, resulting in 22 million new cases each year in 2034.32 At present, annual deaths due to cancer are growing approximately 50% faster in the developing world than in the developed world, and a large proportion of the additional mortality and morbidity can hence be expected to occur in developing nations.33
3. HOW CAN YOU ADDRESS THE PROBLEM? Interventions to reduce mortality and morbidity due to cancer may be broadly categorised into: further research into the causes and treatment of cancer; activities which focus on the prevention of cancer cases; and the direct treatment of cancer. Another useful distinction is between interventions which focus on treating or preventing cancer in developed nations and those which focus their efforts on developing nations. In this report, we recommend contributing donations towards interventions which focus on the prevention and treatment of cancer cases, specifically in developing nations. This is due to the more favourable cost-effectiveness of these areas in terms of dollars per life saved, and their relative neglectedness.
6
4. RESEARCH As the cancer burden is large and growing, the benefits of successful cancer research could be substantial. Of the three types of cancer intervention identified in this report, research is the area for which the benefits can most easily be experienced by both developed and developing nations. New treatments and medicines which are discovered in one nation may later be used around the world.34 However, although the potential benefits of successful cancer research are very large and transferable across different nations, the area is already extremely well-funded relative to other diseases. Therefore, we do not recommend funding research as a means of reducing morbidity and mortality due to cancer. There already exist a variety of cost-effective methods to greatly reduce cancer cases (see the following sections). Cancer research is very well-funded in comparison to other diseases. The National Cancer Institute in the United States has spent approximately $90 billion over the past 40 years on cancer research.35 As for charitable funding, there are 260 different nonprofit organisations in the US alone, with a combined annual budget of $2.2 billion.36 Even more impressively, pharmaceutical and biotechnology companies spend approximately $51.2 billion on research and development each year, with cancer a primary focus.37 Likewise,in the UK, spending on cancer research by the National Cancer Research
Institute’s member organisations doubled between 2002 and 2010 to £500 million and has continued to grow.38 Although this makes sense due to the high prevalence of cancer in developed nations and hence the greater incentive to research cancer treatments, it is in sharp contrast to the $70 million of funding to developing countries to prevent deaths due to tobacco,39 and to the mere 10% of global research funding which is estimated to be allocated to those diseases (including Neglected Tropical Diseases such as schistosomiasis) which are specifically relevant to the poor and which cause the majority of the global disease burden.40,41 Therefore, it is unlikely that donations to this area will have as high an impact as research into other areas, or as high an impact as direct action such as malaria prevention,42 deworming,43 development media,44 or tobacco control.45 Another major consideration is that there are a variety of cost-effective methods of cancer prevention already available and that further research into treatments (which dominates the field of cancer research) is unlikely to provide any methods of treatment which are more cost-effective than basic prevention. Research has already provided methods of diagnosis and treatment of early-stage cancers, as well as numerous highly effective prevention strategies such as tobacco control, Hepatitis B vaccination, breast cancer screening, and schistosomiasis treatment (see Section 5). However, when it comes to research 7
into new treatments, even if a new drug were developed which completely cured a particular form of cancer, its sale price would likely be quite high given initial development cost of, on average, $2.6 billion46 as well as the financial interests of private companies which conduct the majority of cancer research and drug development. This has also been demonstrated in practice - 12 out of the 13 new cancer drugs approved in the United States in 2012 cost more than $100,000 per year of therapy.47 In comparison, the Against Malaria Foundation, one of the top charities recommended by Giving What We Can, prevents the death of a child under the age of 5 for every $2,838 donated.48 For cancer specifically, it happens to be the case that tobacco control could potentially prevent a death for as little as $1462 (see Section 5.2 below) and existing micronutrient fortification charities currently provide the opportunity to prevent deaths from stomach cancer for $19,100 each, in addition to producing a multitude of other health benefits (see Section 5.1). It is exceedingly unlikely that any type of cancer research or development of new treatments in the near future will reveal a more cost-effective intervention than those available for malaria or those already available for cancer prevention. Thus, cost-effectiveness alone may exclude cancer research from being an effective method to save lives through charitable donations. Given its crowdedness, we do not recommend donating to research as an effective method of reducing mortality and morbidity due to cancer, nor an effective method of reducing mortality and morbidity overall.
8
5. PREVENTION The World Health Organisation details highly cost-effective strategies (which they call “Best Buys”) to tackle cancer which could save millions of lives in the coming century, and which require relatively little infrastructure.49 These strategies focus primarily on the prevention of cancer cases, which is considered a significantly more cost-effective method to reduce both morbidity and mortality in this area, and include: tobacco control to reduce lung cancer incidence (see Section 5.1); vaccination and treatment of related diseases (see Section 5.2); screening and vaccination specifically against cervical cancer (see Section 5.3); as well as screening and awareness raising for breast cancer (see Section 5.4). Cancer prevention is likely to be more cost-effective in developing nations. Like treatment, the cost of preventative interventions are likely to be substantially higher in developed nations due to higher costs and because much of the low-hanging fruit may already be funded by governments and charitable organisations (for example, the Centers for Disease Control and Prevention in the United States and Public Health England). Only 5% of global resources devoted to cancer - $320 billion in total each year (on both treatment and prevention) - are spent in developing countries despite their higher total disease burden.50 Interventions are also unlikely to be as tractable in developed countries, due to public awareness already being relatively high, screening already being performed on a large scale, and
vaccines and treatment for those conditions which commonly lead to cancer already being widely available.51,52 This also establishes cancer prevention in the developing world as a highly neglected area, as will be discussed further in the following sections (see Section 5.1.6 in particular). Unsurprisingly, cancer incidence is also increasing at a faster rate in developing countries. While cancer rates do remain high in high-income countries (HIC), “...they are plateauing or decreasing for the most common cancers due to decreases in known risk factors, screening and early detection, and improved treatment…”.53 Meanwhile, a number of low- and middle-income countries (LMICs) are experiencing increased rates of these same cancers, particularly “...due to increases in smoking, excess body weight, and physical inactivity…” as well as lack of knowledge about risk factors, lack of early detection, and lack of high-quality treatment.54 LMICs also have a disproportionately high incidence of cancers stemming from infections, for example liver cancer, bladder cancer and cervical cancer (see below).55,56 We have examined many of the different interventions in this area, many of which have the potential to be highly cost-effective but not all of which are under-funded at present or being carried out effectively by charitable organisations. We recommend vitamin A fortification as a method for reducing cancer morbidity and mortality which may be highly cost-effective, as well as both neglected and tractable.
9
5.1 Vitamin A fortification (stomach cancer) As the second largest contributor to cancer morbidity and mortality, stomach cancer constitutes a sizeable portion of the total disease burden of cancer worldwide. It causes 841,000 deaths each year, as well as 17.9 million DALYs57 - that is, 1.53% of all deaths, and 0.73% of all DALYs worldwide (see Figure 4 below).58 In addition, 600,000 of those deaths (71%) occur in developing nations, as do 77% of the DALYs incurred by stomach cancer.60 The United Kingdom’s National Health Service even describes it as “...a fairly uncommon type of cancer…”.61 This suggests that it may provide an opportunity for cost-effective interventions to improve health and decrease mortality in developing nations. However, stomach cancer is typically only treatable through chemotherapy, radiotherapy, and surgery62,63 which, in the United States, is at an average cost of more than $70,000 for the first year of treatment (and $4000/year thereafter).64
More promisingly, several prominent risk factors have been identified for stomach cancer, including high sodium intake,65,66,67 ionising radiation,68,69 high alcohol consumption,70 and exposure to tobacco smoke.71,72,73 More recent research, including a meta-analysis of 47 different studies which spanned 1,221,392 human participants aged 18-98 years, has found that vitamin A deficiency is also a major risk factor, as it can cause DNA damage and thereby lead to the development of stomach cancers.74,75,76,77,78,79 Thus, simply by supplementing the dietary intake of vitamin A in some regions and thereby reducing vitamin A deficiency, it may be possible to cost-effectively reduce the incidence of stomach cancer.
5.1.1 How does it work? It is possible to improve the dietary intake of particular micronutrients, such as vitamin A, in LMICs by either directly providing vitamin supplements or by fortifying key products in the food supply.
Figure 4: Stomach cancer (outlined in yellow) as a proportion of total global mortality in 2013;59 10
The latter is the far more cost-effective option directly supplementing zinc, for example, costs more than five times as much as raising zinc intake through fortified foods.80 Micronutrient fortification, such as with vitamin A, can be performed during manufacture, and may be encouraged or mandated by national governments or company executives. The charity we recommend for this intervention, Project Healthy Children (PHC), also provides technical assistance to manufacturers and assists in training inspectors to continue to monitor the implementation of its fortification schemes.
sub-Saharan Africa may prevent 8,362 deaths and avert 211,565 DALYs, from the above. Theoretically, the total cost of doing so, through Project Healthy Children, would be approximately $68.87 million for entire sub-Saharan population of 988,088,000 86 . Note that this estimate is merely to showcase how cheap micronutrient fortification is - currently not all people in sub-saharan Africa have access to staple foods that are produced on an industrial scale and that could be fortified at a such a low price. In other words, there will be diminishing marginal returns.
This initial estimate therefore begins to suggest that such an intervention would prevent deaths 5.1.2 Tractability and cost-effectiveness at an average cost of $8,236 per life saved and avert DALYs at an average cost of $326/DALY. In It appears that micronutrient fortification is a high- particular, these benefits are only due to stomly cost-effective, and readily tractable, method of ach cancer and therefore exclude the majority of decreasing disease burden - from cancer specifihealth benefits due to micronutrient fortification cally and also more widely. The issue of tractability (see Section 5.1.3 below), which makes such is a minor one, as there are few major obstacles to estimates extremely impressive. After all, among establishing micronutrient fortification schemes the most cost-effective charities that we know of, it in developing nations. This section will therefore is considered extremely cost-effective to be able to focus mainly on the cost-effectiveness of impleimprove health at a cost of approximately $2,838 menting such schemes. per life saved and $78/DALY averted,87,88 and this is through the direct benefits rather than relatively In regards to the efficacy of micronutrient supplesmall co-benefits such as cancer prevention. mentation, recent research has demonstrated that increasing micronutrient supplementation greatly However, there are several factors that make these decreases the risk of stomach cancer - vitamin A estimates potentially overly optimistic. There are by 29%, vitamin C by 26%, and vitamin E by 24% several mitigating factors: (It is worth noting that the meta-analysis which produced this result included 1,221,392 human • PHC may potentially not provide vitamin A subjects aged between 18 and 98, and considered fortification in all countries in which it is active the effects of micronutrient supplementation (this turns out not to be the case - see Figure 5 over time-scales of between 1 and 14 years).81 In below); sub-Saharan Africa, vitamin A deficiency in partic- • The countries in which PHC is active (preular is extremely prevalent, with up to 75% of predominantly small countries in which nutrition school-age children affected by it in some counis highly neglected) may not have rates of tries82 (see Figure 5 below). Stomach cancer, while stomach cancer as high as the sub-Saharan not constituting the majority of worldwide mortalaverage (again, this is not the case - see Figure ity, still kills 28,836 people per year in this region 5 below); (and incurs 729,535 DALYs).83Meanwhile, micronu- • PHC may not be entirely responsible for the trient fortification can be performed for approximicronutrient schemes in the countries in mately $0.07 per person reached by PHC,84,85 so we which they operate, with other actors contribcan make a rough estimate of the cost of saving uting, although this does not impact on the lives from stomach cancer. If vitamin A supplecost-effectiveness of micronutrient fortification mentation reduces the risk of stomach cancer by overall (and the overall costs, which are fairly 29% then supplementing the entire population of 11
minor, are included in estimates of overall cost-effectiveness in the following section); • Vitamin A fortification may not decrease the risk of stomach cancer for those already receiving sufficient vitamin A (the aforementioned meta-analysis may have predominantly considered populations with high levels of vitamin A deficiency) and, given this, the effectiveness of fortification may be restricted to only the portion of the population experiencing inadequate vitamin A intake; The above data addresses several of the above concerns: PHC’s programs do provide vitamin A fortification in all of the countries in which they currently operate, and are likely to do so in the three countries in which they are currently establishing new programs (Sierra Leone, Nepal, and Tanzania); and the rates of stomach cancer in the countries in which they operate are still quite high (particularly in Nepal and Tanzania, to which additional donations are most likely to contribute). In addition, we do believe that the national schemes contributed to by PHC are largely a product of their intervention due to the relatively small size and neglectedness of those countries. We also
Country4
Population5
Vitamin A included?
do not believe that the additional costs borne by local governments and other actors affect the cost-effectiveness estimates significantly as they are both fairly minor and are already taken into account by the overall cost-effectiveness estimates for improving general health which are considered in the following section. Also, the rates of vitamin A deficiency in the countries in which they operate are not a great deal lower than the 40% average for the developing world (in fact, the prevalence in Sierra Leone, Malawi and Liberia is far higher), so this does not reduce their cost-effectiveness more than comparable micronutrient fortification organisations. Taking the above considerations into account, the estimates of $8,236/life and $326/DALY above are not likely to be inaccurate by more than one order of magnitude, but a more conservative estimate would likely be more accurate. The first improvement we can make, to produce a conservative estimate at least, is to replace the cost-per-person figure of $0.07 with a cost-per-country figure (from which the cost-per-person figure originates), for which $697,000 appears to be the maximum.90 Also, country-specific estimates of vitamin A deficiency can be used to conservatively estimate of
Stomach Stomach Coverage cancer cancer mortality DALYs
Vitamin A deficiency in preschool-age children
Rwanda
11,341,544 –
80%
276
6,971
6%6
Malawi
16,695,253 –
80%
127
3,748
60%7
Liberia
4,396,554 –
Unknown
175
4,996
>50%8
Burundi
10,816,860 -
~80%
333
8,855
~25%9
Zimbabwe
15,245,855 -
80%
322
6,693
~35%10
Honduras
7,961,680 -
Unknown
783
16,755
14%11
Sierra Leone
6,315,627 Very likely
Unknown
286
8,850
75%12
Nepal
28,174,724 Very likely
Low
1,043
27,454
~30%13
Tanzania
51,822,621 Very likely
Unknown
1,105
27,453
24%14
Figure 5: National fortification programs to which PHC has contributed to date. Note that the fortification and supplement programs in Honduras (2000-2010), Rwanda(2007-present) and Malawi (2009-present)89 are now relatively well-established and PHC now only assists with the continuing monitoring of fortification. This may already contribute to lower incidence figures for vitamin A deficiency in these countries. 12
what portion of the population will benefit, as this portion of the population will certainly be comparable to the control groups used in experiments.91 From this, as well as the above considerations, we are able to make the following estimates (albeit with a large degree of uncertainty due to incomplete and/or slightly outdated data): • the fortification programs run by PHC result in deaths from stomach cancer being prevented at a rate of $24,220/death and avert DALYs at a rate of $920/DALY; • if the relatively well-established programs are excluded, this drops to $19,100 per stomach cancer death averted and $720/DALY; • in Tanzania in particular, PHC may save a life for every $11,330 spent and avert a DALY for every $460; • and meanwhile, in some countries with well-established programs such as Rwanda and Malawi, the cost rises to $181,420 and $39,420 per death prevented, but this is likely due to the levels of vitamin A deficiency having already dropped substantially and therefore that the countries are warping overall data. (Other countries where PHC has begun to improve fortification rates may be doing so as well, but to a lesser extent and only in the direction of decreased cost-effectiveness, thereby simply producing a more conservative estimate.) Given this, our best guess of the cost-effectiveness of stomach cancer prevention through the type of programs administered by PHC is $19,100/ death averted and $720/DALY. However, this is still subject to a great deal of uncertainty and the true figure may be much higher or much lower. When considered together with the wider benefits of vitamin A fortification on health beyond just cancer, this cost drops enormously - to less than $40/DALY (see the following section).
5.1.3 Positive wider impacts The many other health benefits There is extensive evidence of the wide-ranging health benefits of micronutrient
fortification.92,93,94,95 Much of the total benefit provided is not, however, through the prevention of stomach cancer specifically, nor through the fortification of vitamin A in particular (as against iodine, zinc, folate and so on). This applies equally to PHC’s programs, which fortifies with a variety of micronutrients and which, of course, does not focus on stomach cancer specifically. When we include the co-benefits of other micronutrients and wider health impacts are included the cost-effectiveness of fortification improves greatly. For example, deficiencies in vitamin A, iodine, iron, zinc, and folic acid contribute greatly to the prevalence and severity of the following conditions (see also Figure 6 below): • iodine deficiency, which, by itself, accounts for 0.56% of all years lived with a disability in developing countries96 and which interferes greatly in mental development, causing an average loss of 6.9-10.2 IQ points in children under 5;97 • iron deficiency anemia, which makes up 6.76% of all years lived with a disability and 0.4% of all deaths in developing countries;98 • maternal hemorrhage, maternal sepsis and other maternal infections, which make up 0.17% of deaths and 0.19% of DALYs in developing countries and arise largely from iron deficiency;99 • diarrheal diseases, which makes up 2.96% of deaths and 3.51% of DALYs in developing countries, approximately 5-8% of which can be attributed to vitamin A deficiency and 3-5% can be attributed to zinc deficiency;100 • measles, which makes up 0.23% of all deaths and 0.39% of DALYs in developing countries, approximately 23% of which is attributed to vitamin A deficiency;101 • lower respiratory infections, which make up 5.18% of all deaths and 5.21% of DALYs in developing countries, approximately 2% of which is due to zinc deficiency; • neural tube defects, which affect 320,000 newborns worldwide each year102 and which can be prevented by increasing maternal folic acid intake.103,104
13
It is estimated that 80% fortification coverage in Rwanda, Malawi, Zimbabwe and similar countries would result in: a 30% reduction in vitamin A deficiency; a 20% reduction in childhood anemia; a 30% increase in adult productivity; a 4-30% reduction in maternal mortality; and a 30% overall reduction in neglected tropical diseases such as schistosomiasis.105,106,107 Research has indicated that vitamin A fortification improves health at a cost of less than $40/DALY averted in many areas,108,109,110 and some estimates place this cost as low as $11 in Malawi and $31.78 in Zimbabwe (both specifically for wheat flour).111 In other countries, it has been found that micronutrient fortification (including nutrients other than vitamin A) can produce health benefits for as little as $2/DALY (in Nigeria), $3/DALY (Democratic Republic of Congo), $4/DALY (Myanmar), and less than $100/DALY in more than 30 different developing countries.112,113 PHC operates in several of these, as listed below in Figure 7, and we believe that these approximations are reasonably accurate to the total costs incurred by PHC’s programs.114
All of these estimates, however, do not include the benefits provided through stomach cancer prevention, and hence may be even lower. Continuation of programs into the future For policy-based and manufacturing-based fortification programs such as that implemented by PHC, the benefits for local populations continue long after they are implemented. Unless government policy or manufacturing process changes (which is unlikely due to the extremely low cost of the programs), foods will continue to be fortified indefinitely into the future, thereby potentially providing fortification to a greater number of people in future generations. It also means that the health benefits will aggregate year upon year, so the cost per death prevented ($19,100 from stomach cancer alone) will decrease enormously when considered over the span of several decades. Even just over 10 years, which seems quite a conservative estimate of how long the programs might stay in place after PHC establishes them, the cost-effectiveness might improve to $1,910/death prevented ($2,180 at a 3% p.a. discount rate). However,
Figure 6: DALYs in all developing nations, with those attributable to child and maternal malnutrition (for all categories) shaded. 14
Rank
Country
Food
Total cost (US$)
Cost per DALY averted (US$)
16
Malawi
wheat
1,344,446
25
21
Zimbabwe
sugar
2,218,527
33
30
Zimbabwe
wheat
1,872,396
43
46
Rwanda
oil
6,623,699
68
47
Sierra Leone
oil
10,601,950
69
52
Malawi
oil
9,738,123
105
54
Burundi
oil
5,500,917
106
Figure 7: Cost-effectiveness rankings of the countries in which PHC is active (and products which they fortify), taken from a table of 60 different countries’ micronutrient interventions, and arranged by the cost per DALY averted .115 this does not include the relatively minor costs of ongoing monitoring and follow-ups, so should not be considered an accurate estimate but instead merely illustrative.
5.1.4 Due diligence: Possible offsetting/ negative impacts Over-consumption of micronutrients It seems intuitively plausible that delivering micronutrients through fortification rather than direct supplementation may put some of the population at risk of consuming excess amounts, and potentially experiencing adverse health effects. This intuition does indeed hold true in extreme cases, specifically for stomach cancer prevention, when vitamin A intake greatly exceeds the tolerable upper intake,116 but we are quite confident that PHC’s fortification efforts will result in neither a significantly greater prevalence of such high intake nor a degree of negative health effects which compare to the positive effects described in Sections 5.1.2 and 5.1.3. In particular, such adverse effects are extremely unlikely to occur when sufficient prior research is performed. For instance, before implementing fortification programs in a new country, PHC consults existing nutrition and food consumption surveys (and also conducts their own) in order to establish the optimal level of fortification, including which
nutrients are not required, therefore minimising the risk of adverse health effects.117,118 Also, regardless of whether fortification is tailored to particular countries, PHC’s programs result in levels of fortification which are well within safe limits.119,120 There is a great deal of evidence supporting the overwhelmingly positive effects of fortification at levels such as these, including extensive meta-analyses.121,122,123,124 Given this, we do not believe that this reduces the cost-effectiveness of micronutrient fortification, or the activities of PHC, by a considerable amount. Discounting future benefits Whether to discount lives saved (or DALYs averted) with time is a controversial moral question. Despite this, if this is done at any rate (e.g. 3%p.a. as is the standard rate used by economists), the benefits of micronutrient fortification may be somewhat mitigated. When simply aggregating the lives saved over time, it is unlikely that this will be a considerable problem, as we have not considered the long-term benefits in our calculations in Section 5.1.2 and, therefore, the total benefits will be greater than we have already supposed whether a discount rate is applied or not. As mentioned briefly in Section 5.1.3 above, the total impacts over 10 years are reduced by less than 15% when a 3% discount rate is applied. Over 100 years the reduction becomes approximately 68% but, still, we have not 15
considered effects this far into the future in our analysis so the true total benefits are likely much higher than we have estimated, even if the value of future benefits is discounted in this way. A greater concern is that the delay between fortification and the prevention of stomach cancer deaths may be quite a long time, and that therefore even the initial benefits may be subject to heavy discounting. After all, the average age of those diagnosed with stomach cancer is 69125 and vitamin A deficiency primarily affects children and expectant mothers. Nonetheless, the primary meta-analysis on which our cost-effectiveness estimate is based does not include any studies conducted over a time-scale greater than 14 years, and many much shorter (as well as subjects aged from 18 to 98 years, all of whom could be expected to benefit from fortification).126 At a discount rate of 3%, even if all of the benefits take an entire 14 years to occur (which is almost certainly a considerable overestimate), this reduces the value of those benefits by only about 33%. It also does not include the much broader and much more immediate benefits of reducing child mortality, maternal mortality and micronutrient deficiencies. Thus, we do not believe that discounting greatly reduces the cost-effectiveness of micronutrient fortification for reducing cancer incidence. Uncertainty This is likely the single greatest problem for fortification programs. In our calculations of cost-effectiveness, there is a great deal of uncertainty and it is hence entirely possible that the health benefits of micronutrient fortification are less than we estimate, both for stomach cancer prevention and for health in general. For instance, the causes of stomach cancer are numerous, and the predicted 29% reduction may vary greatly by country or according to other factors. The estimates of prevalence of vitamin A deficiency across populations may also be inaccurate, with some sourced from studies conducted in 2011 (see Figure 5 above). To a lesser extent, the wider impacts of micronutrient fortification are somewhat uncertain, with estimates of child mortality reduction varying from more than 30% to 11% and below.127 We are extremely confident that micronutrient fortification will have 16
a net positive impact, though it is possible that our estimates of the exact extent of the impact are not wholly accurate. Still, the cost-effectiveness estimates which we have made above are still ‘best guesses’ of the true cost-effectiveness, based on some fairly conservative assumptions.
5.1.5 Neglectedness Micronutrient fortification and supplementation is a relatively neglected intervention area, particularly in the areas which are the focus of PHC’s activities. There are other charities and other organisations working on micronutrient fortification (of vitamin A in particular) including the Global Alliance for Improved Nutrition,128 the Golden Rice Project,129 Vitamin Angels,130,131 the Iodine Global Network,132,133 and UNICEF.134 Still, despite the potential for cost-effectively obtaining major health benefits, in general, nutrition is still severely underfunded. Compared to other health interventions (such as for HIV/AIDS) as well as to emergency food aid (see Figures 8 and 9 below). In addition, vitamin A deficiency remains extremely high in many developing countries,137 producing extremely high disease burdens in some areas.138 In many more countries, adequate fortification programs have yet to be established.139 Both of these facts hold true of numerous nations across sub-Saharan Africa, including Zimbabwe, Burundi, Sierra Leone, Liberia and a large number of other countries to which PHC could scale their operations in future. In particular, PHC generally focuses their efforts on relatively small countries in which severe nutritional deficiencies are prevalent, thereby having a greater marginal impact.140,141,142 Meanwhile, a study from the World Bank has estimated that an additional $10.3 billion could be productively used each year to scale up nutrition interventions143 - an estimate which has largely been confirmed elsewhere.144 The indicates that fortification as a whole is still a sufficiently neglected area.
In particular, the World Bank has estimated that, for technical assistance, initial subsidies for fortificant and social marketing, an additional $1 billion is required, as well as $200 million for monitoring, evaluation and operations research.145 These are precisely the areas on which PHC works, therefore
indicating that the area of their work is sufficiently neglected to allow for the marginal impacts of donations to remain high. Given this, we are quite confident that the micronutrient fortification work performed by PHC is otherwise quite neglected, despite the presence of other charities.
Figure 8: Official Development Assistance Commitments for Health, HIV/AIDS, and Nutrition, 1995–2007.135
Figure 9: Official Development Assistance Commitments for Nutrition and Emergency Food Aid, 1995–2007.136 17
5.1.6 Charity recommendations
Project Healthy Children Donor fit
Cost-effectiveness
• • • • • (5/5)
International development, public health and cancer prevention
Cost-effectiveness (specifically for cancer prevention)
• • • • • (3/5)
What do they do?
Robustness of evidence
• • • • • (4/5)
Project Healthy Children (PHC) works with local governments and manufacturers to fortify staple foods such as flour, sugar, rice and oil. The process adds micronutrients such as folic acid, iodine, iron, vitamin A and zinc in order to tackle micronutrient deficiency. This follows a comprehensive “country assessment” before they begin operations, including surveys of health and nutrition, consumption patterns, food imports, and the political environment. Based on these assessments, PHC identifies the best foods to fortify and the micronutrients which are most needed. They then then provide technical assistance to governments in designing and implementing fortification programs, and in drafting national fortification standards, as well as technical assistance to manufacturers and inspectors to ensure that highly effective methods and monitoring systems are used.
Robustness of evidence (specifically for cancer prevention) • • • • • (3/5)
Overall evaluation Project Healthy Children is a highly cost-effective charity, and has previously been evaluated as such by Giving What We Can.146 A large volume of evidence supports the efficacy and cost-effectiveness of PHC’s activities, and monitoring indicates that PHC’s work to date has been highly effective. In addition to greatly improving general health at a rate of less than $40/DALY, we also believe that PHC is able to prevent a death due to stomach cancer for approximately every $19,100 donated.
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From Sections 5.1.2 and 5.1.3 above, we are quite confident that PHC’s activities are indeed highly cost-effective in improving health in the countries in which they operate. We also have reason to believe that they are also cost-effective, to a lesser degree, specifically for the prevention of stomach cancer. We estimate that donations to PHC improve general health at a rate of less than $40/DALY averted, and this claim is supported by a considerable body of evidence. Specifically for stomach cancer, we estimate that donations to PHC may potentially save lives for approximately $19,100/life and reduce disease burden at a rate of $720/DALY, although these estimates are subject to a large degree of uncertainty and there is less evidence for this effect than for the general benefits of micronutrient fortification. Still, this compares favourably to the other cancer interventions for which there is currently a funding gap (see the following sections) and we therefore recommend donating to PHC as an opportunity to cost-effectively reduce cancer morbidity and mortality.
Quality of implementation
• • • • • (4/5)
We are impressed with the quality of PHC’s implementation of programs so far, and their success to date in number of countries. The policy and institutional changes that PHC has accomplished in many countries give clear indications that they have been highly successful.147,148,149 In addition, PHC’s evaluation and monitoring activities have also demonstrated that implementation in these countries has so far been quite successful,150 and believe that such monitoring leaves only a very low probability that their programs are not having a substantial impact. Room for more funding
which may also be renewed.153 Moreover, PHC is only active in small African countries with small populations (<17 million), whereas GAIN is not currently active in these countries.154 This supports the claim that donations made to PHC will have a greater marginal impact than donations made to other charities in the same area.
✓ (Yes)
As of September 2015, PHC held about $200,000 in reserves,151 which translates to about 3-4 months of operational costs, which we think is not excessive. Thus, in the short-term there is room for more funding. PHC has told us that with additional funding they would intensify their monitoring efforts, which is one of the most critical components to any national fortification program. In the longer term, based on PHC’s development plan, we expect that PHC could productively use an additional $2.5 million to further expand its programs. Also, in comparison to other organisations working on micronutrient fortification, PHC does appear to have more room for additional funding. For instance, the Iodine Global Network received approximately $500,000 in funding from USAID in 2015152 and the Global Alliance for Improved Nutrition (GAIN) has received funding from the Bill and Melinda Gates Foundation through mid-2015,
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5.2 Tobacco control (tracheal, bronchus, and lung cancer) Lung cancer is the single largest contributor to cancer deaths, resulting in 1.59 million deaths each year.155 Tobacco use is the single most important risk factor for cases of lung cancer, to which 70% of those 1.59 million deaths can be attributed.156 Indeed, smoking is the single greatest identifiable risk factor for cancer deaths worldwide (see Figure 10), resulting in 20.89 cancer deaths per 100,000 - 2.73% of all deaths from any cause.157 Including conditions other than cancer specifically, tobacco kills up to half of all people who use it (i.e. shortens their lifespan), and has a global death toll of almost 6 million people per year (600,000 of whom are non-smokers exposed to secondhand smoke).159,160 This figure is expected to rise to 10 million deaths per year by the middle of this century.161 In response to these figures and the detrimental effect of tobacco use, a variety of anti-smoking mass media campaigns have been conducted in many developed nations and seem to have resulted in decreases in incidence of lung
cancer.162 Meanwhile, however, deaths due to lung cancer are increasing in many developing countries (see Figure 11).163,164,165,166 The total health burden is also particularly large in developing countries. Due to the uneven distribution of population between developed and developing nations, a large proportion of total deaths due to tobacco use occur in nations such as India and China (see Figure 12). While tobacco and lung cancer may constitute a greater proportion of deaths in developed nations, the absolute number of deaths in nations still in the process of developing provides a problem of greater scale, and hence of potentially much greater impact. Due to the generally lower cost of interventions and neglectedness of public health in these nations, a greater impact can be achieved by improving awareness of and controls on tobacco in these countries than by doing so elsewhere (see Section 5.1.2, 5.1.3, and 5.1.6 below).
Figure 10: Risk factors (all categories) for deaths due to neoplasms in 2013, separated by type of neoplasm;158 20
Figure 11: Rate of change of deaths attributed to tobacco smoke between 1990 and 2013;167
Figure 12: Total deaths attributed to tobacco smoke by country in 2013;168 21
In developing countries more widely, tobacco use accounts for 9.92% of all deaths (and 4.9% of DALYs incurred), as shown below in Figure 13, which is a greater proportion than all deaths from malaria (2.05%), from HIV (3.1%), from nutritional deficiencies (1.56%), or even from all physical injuries (9.5%).169 These deaths due to tobacco are largely made up of cancer deaths (1.63% of all deaths in developing countries and 16.39% of deaths due to tobacco smoke)170 but also includes various other diseases for which tobacco use increases incidences or chance of death. Similarly for DALYs incurred by tobacco use, 14.73% are due to cancer (0.72% of all DALYs incurred).171 This constitutes several considerable co-benefits of interventions which reduce tobacco use and these co-benefits will be considered in cost-effectiveness estimates below. Given the high mortality figures due to lung cancer and also other tobacco-related conditions, as well as the potential tractability and neglectedness, it is not surprising that tobacco control features on the WHO’s Best Buys list.173 The 2015 Disease
Control Priorities 3rd Edition (DCP3), which details highly cost-effective intervention and treatment strategies for various diseases, also recommends tobacco control. It explicitly identifies tobacco taxes, in particular, as “...the most important single cancer intervention at a practical level…”.174
5.2.1 How does it work? The most effective large-scale interventions are primarily those available to national governments - taxation of tobacco, health education, restrictions on sales, advertising and packaging, and various other legislative methods. For private philanthropists, it is likely that the greatest opportunities lie in funding lobbying and advocacy efforts, as well as in the funding of awareness campaigns to curb smoking uptake.
5.2.2 Tractability Tobacco control may be tractable or intractable in two distinct senses: tractable in that certain highly effective policies or initiatives are yet to be
Figure 13: Deaths attributed to tobacco smoke in developing nations in 2013, by cause of death;172 22
implemented (and hence there remain simple improvements which may be made); and tractable in that lobbying efforts and awareness campaigns might be likely to lead to such changes in policy or in general awareness. Reducing smoking through tax increases, thereby increasing cigarette price, has been shown to be quite tractable on a governmental level, particularly when it comes to reducing smoking amongst young people.175,176,177,178 A report by the World Bank estimated that for every 10% increase in cigarette cost, tobacco consumption would drop by 4% in HICs and 8% in LICs (on a global scale, such a 10% increase would hypothetically result in between 240,000 and 480,000 lives saved every year, approximately 15% of which would be from cancer).179,180,181 Young people are also more likely to quit and less likely to start when prices are high.182 The WHO therefore recommends that excise taxes should account for 70% of cigarette cost.183 A report by the Asian Development Bank stated that increasing the price of cigarettes by 50% through taxation would avert 27 million tobacco-related deaths in China, India, Thailand, the Philippines and Vietnam alone.184 Alongside price increases, education and awareness campaigns are methods of reducing tobacco use which appears quite tractable. The WHO Global Adult Tobacco Survey for China showed that only 23% of Chinese adults knew that smoking caused lung cancer, heart attacks and strokes.185 Another study, also conducted in China, found that only 40% were aware that smoking causes coronary heart disease, only about 20% were aware that it causes stroke, and only 7% were aware of all eight of the major health effects considered.186,187 This lack of awareness affects the poorest in a population in particular, with those who are illiterate unable to read warning labels. Thus, targeted education initiatives (conducted by governments) and awareness campaigns (conducted by either governments or other organisations) may hence be extremely tractable as there is a large portion of the population yet to be reached. Pictorial warnings are one method of government-initiated awareness-raising which have been
used to try and re-balance this inequality in some countries,188 and there is evidence that pictorial warnings significantly improve awareness of dangers of smoking and reduce the number of young people taking up the practice.189 Packaging controls are also important in reducing the impression that some cigarette brands are less harmful than others.190 Unfortunately, however, 125 countries (out of 198) do not require pictorial warnings on tobacco products, and developing nations are significantly overrepresented in this number, suggesting that this is quite a tractable area for improvement in developing nations. Total advertising bans have also been effective in reducing cigarette consumption,191,192 especially in LMICs,193 including bans on smoking in the workplace.194,195 Of course, there is the additional issue of the tractability of lobbying and advocacy - while it might be quite tractable to secure health improvements through policy changes, bringing about those changes through advocacy may be less tractable. Tractability and cost-effectiveness are both extremely difficult to estimate for advocacy, due to the comparatively high uncertainty and sometimes low chance of success,196 although there has already been some success in tobacco control advocacy in the Philippines197 and elsewhere,198,199 though this may not be representative of future efforts. Ideally, given a particular advocacy organisation, we might be able to provide some suggestion of the tractability of their work based on the exact context and the approach they take. Unfortunately, however, we have not identified any promising charitable organisations in this area with a sizeable funding gap and hence are unable to provide such a suggestion.
5.2.3 Cost-effectiveness Research has recently suggested that taxes on tobacco are “...the single most cost-effective way to save lives in developing countries...”.200 DCP3 also explicitly identifies them as “...the most important single cancer intervention at a practical level…” based on their low cost and high effectiveness.201 As mentioned above, The World Bank estimates that for every 10% increase in cigarette 23
cost, tobacco consumption would drop by 4% in HICs and 8% in LICs,202 particularly among young people for whom the lifelong impact is greater. Given this, the WHO recommends that excise taxes should account for 70% of cigarette cost.203 This cost-effectiveness of such an approach has been estimated at $3-$70 per DALY averted,204,205 which appears to compare quite favourably to the most effective humanitarian interventions (for example, approximately $78 per DALY averted through insecticide-treated mosquito nets to protect against malaria).206 As for lives saved, one estimate puts the cost of saving a life by diminishing tobacco use at $1462 (5.5 million lives saved over 10 years at an annual cost of $804 million dollars).207 If 1/3 of the lives saved are due to price increases from higher taxes, which probably underestimates the relative impact of this measure, then the cost of saving a life by raising taxes is about $795 (1.8 million lives saved over 10 years at an annual cost of $143 million).208 Again, this appears to rank increased taxation of tobacco among the most effective interventions available, with the Against Malaria Foundation estimated to prevent the death of a child under the age of 5 for every $2,838 donated.209
total smoking deaths (109,000 per year)211 and generally high intervention costs, such campaigns may add a quality-adjusted life year (QALY), on average, for every $71 spent.212 Given that a QALY (a positive measure) equates to an added year of perfect health and that a DALY (a negative measure) equates to the sum of years of life lost and years lived with a disability, it is likely that the $/ DALY figure for such media campaigns is significantly lower. Given the lack of awareness and greater population of smokers in countries such as India and China (see above), it is extremely likely that the figure for awareness campaigns in developing countries is far lower.
Of course, again, there is the issue of the cost-effectiveness of lobbying and advocacy - while it might be quite cost-effective to secure health improvements through policy changes, bringing about those changes through advocacy may be less effective and more expensive. Like tractability, the cost-effectiveness of advocacy is extremely difficult to estimate, due to the comparatively high uncertainty and sometimes low chance of success.213 Ideally, given a particular advocacy organisation, we might be able to provide some estimate of the cost-effectiveness of their work based on the exact context and the approach they It is worth noting that the above estimates include take. Unfortunately, however, we have not identideaths and DALYs incurred by tobacco use through fied any promising charitable organisations with diseases other than cancer. Given that 14.73% of a sizeable funding gap working in this area and the DALYs attributable to tobacco occur through hence are unable to provide such an estimate. cancer, and 16.39% of deaths,210 we can roughly estimate the cost-effectiveness of tobacco taxa5.2.4 Positive wider impacts tion for cancer prevention specifically. Such an As mentioned above, and as already incorporatestimate implies that tobacco taxation can avert ed into our cost-effectiveness estimates, cancer a DALY, specifically due to cancer, for every makes up only 16.39% of deaths due to tobacco $20-$475 spent. Likewise, the above estimated smoke (and 14.73% of DALYs incurred) in decosts of saving a life, from cancer specifically, rise veloping nations (see Section 5.1). Apart from to $8922 and $4851, respectively. These figures cancer prevention, tobacco control has sizeable still suggest that tobacco control is a highly cost-effective method of both saving lives and co-benefits including the reduction of ischemic heart disease, stroke, hypertensive heart disease, averting DALYs due to cancer, even if we ignore diabetes, chronic obstructive pulmonary disease, the sizeable co-benefits which make up approxiasthma, lower respiratory infections, and tubermately 85% of the total benefit. culosis (see Figure 14 below).214 Thus, it is perhaps Mass-media campaigns to raise awareness and unsurprising that tobacco control is an effective dissuade children from smoking have also been method of not only reducing cancer incidence but assessed as highly cost-effective. Even in the also greatly improving health overall. This overall United Kingdom, with relatively low numbers of 24
benefit is incorporated into the the cost-effectiveness analysis above (see the previous section).
directly fund domestic tobacco control or other cost-effective public health interventions could substantially improve the overall cost-effectiveIn addition, although not included in the analysis ness of tobacco taxes in the short term, while in the previous section or in Figure 14, smoking strengthening domestic public health services. Of is a major risk factor for Alzheimer’s disease and course, simply increasing excise taxes on tobacco dementia more broadly. may not necessarily have this effect but, nonetheless, it does have the potential to increase govAnother major factor which may add to the ernment spending on public health in developing cost-effectiveness specifically of increased tobacco nations, even if only by a small amount. taxation is the use of the revenue raised on public health. Currently, on average, LMIC governments 5.2.5 Due diligence: Possible offsetting/ collect $10.74 per capita in revenue from excise negative impacts taxes on tobacco products but spend only $0.0078 per capita on tobacco control (development assis- Would more funding decrease smoking at the tance provides another $0.011 per capita).216 This same level of cost-effectiveness? may well be justified. Directing just 1% more of Tobacco consumption decreases by 4% for every these revenues (or $0.1074 per capita) to tobacco control would increase total spending on tobacco 10% increase in price,218 so if additional funding would achieve higher tax increases over the control by more than 500%.217 Increasing funding same time period, it would do even more good. in this way may diminish or even eliminate the However, it is unclear whether the cost-effectiveneed for additional development assistance for ness of doing so would remain constant after tobacco control, including charitable donations, already achieving several tax increases - does in the long term. In fact, designing policies that
Figure 14: Deaths attributed to tobacco smoke in developing nations in 2013, by cause of death;215 25
achieving a 20% increase in price costs twice as much as achieving a 10% increase within the same time period, or does it cost half or 4 times or 10 times as much? Advocacy work is particularly vulnerable to this uncertainty - is there a point of diminishing returns, or perhaps some level of taxation beyond which a serious public backlash might occur? This is a difficult question and the answer is unclear.
protection worth $1·8 billion ($1·2–2·3 billion), mainly concentrated (74%) in the lowest income quintile.225
Are the benefits of tobacco control too far in the future? (If discounted with time, are they still greater than for other interventions?)
In regards to direct action, it appears that tobacco control is indeed relatively neglected, and that there is the capacity for a high marginal impact. Tobacco control is underfunded relative to the harm it causes (see Figure 15 below). HIV/AIDs prevention and treatment received 10 times more funding in LMICs than tobacco control despite the fact that tobacco causes 3 times more deaths in those countries. Of course, without that funding the number of HIV/AIDS deaths would have been higher, but this negates the neglectedness which this demonstrates.
It is worth noting, firstly, that whether to discount lives saved (or DALYs averted) with time is a controversial moral question. Secondly, at least one of the estimates given above discounts projected future DALYs at between 3% (the standard rate used by economists) and 10% (a far more conservative estimate), and still claims that tobacco taxation averts DALYs for a maximum of $70/DALY.219 Moreover, even if we accept such a discount rate, increasing tobacco taxes has both short term benefits (for those who quit smoking) and long term benefits (both for those who quit smoking and those who never start.220 Indeed, it has been estimated that minor increases in tax rates could save 5.5 million lives within the first decade (this estimate was for the period from 2006-2015).221 Are tobacco taxes regressive, disproportionately burdening the poor? This is an important question to ask given that we’re proposing taxes in LMICs on a product used mostly by the poor. However, the evidence strongly suggests that the tax is not regressive. It has been shown that, while poor people smoke more than affluent people, they are also more sensitive to price increases.222 This means they are more likely to smoke less or quit in response to price increases. As a result, most of the health benefits of tobacco taxes will accrue to low-income individuals, while most of the tax burden will be borne by richer smokers who continue to smoke even when the price has increased.223,224 Moreover, poorer smokers would quit and actually save money: in China, a tax increase would save people from the lowest income quintile $21 billion (−$83 to $5 billion) and would also provide financial risk 26
5.2.6 Neglectedness Like tractability and cost-effectiveness, neglectedness may vary between government/direct action and lobbying.
In addition, in regards to lobbying and educational campaigns, tobacco control receives far less funding than the tobacco industry provides for lobbying and promotion of the opposing message. It has been reported that, in the United States alone, more than $20 million was spent on tobacco lobbying in 2015227 and approximately $9.6 billion is spent on promotion and advertising.228 This also extends to the developing world, with lobbying, misinformation and lawsuits proving effective in some instances.229,230 Given that worldwide lobbying and promotion of tobacco control receive far less than $9.6 billion each year, it might therefore be claimed that this area is still significantly underfunded. There is still some indication, however, that tobacco control might not be overly neglected. The Bill and Melinda Gates Foundation and Bloomberg Philanthropies have recently begun to fund tobacco control at a higher level (the latter has provided $600 million since 2007).231,232 Given the extent of this funding, one might potentially suggest that tobacco control is not a neglected cause. If it remains cost-effective to increase funding, Gates and Bloomberg might be likely to do so. If this is true, then our money would be better spent elsewhere. However, it seems unlikely that
Figure 15: Aid and philanthropic funding relative to deaths for various causes.226 these contributions have crowded the area to the point of lowering the marginal impact of donations. Even accounting for Gates’ and Bloomberg’s contributions, tobacco control is certainly not overfunded relative to the harms caused by smoking. Nor is there much evidence to suggest that there is not room for more funding. Hana Ross and Michal Stoklosa consider the possibility that Gates and Bloomberg might be “crowding out” other Development Assistance for Tobacco Control (DACT) - after 2006, when Bloomberg and Gates committed to funding tobacco control, some other organizations reduced or ended their funding. However, this drop in funding might be due instead to the effects of the global financial crisis.233 For now, the academic research suggests that spending more would be highly cost-effective. Gates and Bloomberg have contributed $600 million since 2007, which represents about half of total DACT.234 However, one estimate of the amount needed for the four “best buys” in tobacco control, which includes tobacco taxation, is $600 million per year (or $0.11 per capita per year).235 Another estimate puts the cost of decreasing smoking prevalence in key LMICs to 5% by 2040 at $6 billion
per year. Tobacco control accounts for about 10% of those costs, or $600 million per year.236 Given that this is the level of funding required annually, there does indeed appear to be a sizeable shortfall in current funding (of approximately $4.2 billion between 2007 and 2015) despite the Gates and Bloomberg contributions. Given the lack of charities working on such direct action, and that government action is generally not directly funded by private donors, the neglectedness of advocacy and lobbying is perhaps the more relevant factor. This is much more difficult to estimate. A portion of the Gates and Bloomberg contributions is put towards advocacy but it is unlikely to, by itself, be sufficient to cover all promising opportunities. There are also several quite promising charities working on tobacco control advocacy, which appear to be relatively well-funded - the Campaign for Tobacco-Free Kids,237 the World Lung Foundation,238 the International Union Against Tuberculosis and Lung Disease,239 and the Resource Centre for Tobacco Free India.240 The Campaign for Tobacco-Free Kids runs on an annual budget of $18.23 million,241 while the World Lung Foundation has a program budget of $32.3 million,242,243 the International Union Against 27
Tuberculosis and Lung Disease has received more than $500 million in funding since 2000,244 and the Resource Centre for Tobacco Free India does not appear to directly solicit donations (nor does its parent organisation, the Voluntary Health Association of India).245 It therefore does not appear that that these organisations are especially neglected, as this indicates that their combined annual funding already exceeds the $70 million in total global aid and philanthropic funding to directly deal with the health effects of tobacco in LMICs.246
5.2.7 Charities working in this area Of the charities we identified in this area as fairly promising, none appeared to have a sizeable funding gap and also agreed to provide information for this report. As mentioned above, among the most promising charities considered were: • the Campaign for Tobacco-Free Kids; • the World Lung Foundation; • the International Union Against Tuberculosis and Lung Disease; • the Resource Centre for Tobacco Free India / Voluntary Health Association of India; • as well as Action on Smoking and Health, a formerly taxpayer-funded charity which works on anti-smoking advocacy and lobbying specifically within the United Kingdom. Unfortunately, we do not feel that we have sufficient information to identify any of these organisations as both highly cost-effective and underfunded. Although tobacco control is an extremely promising intervention area, with cost-effectiveness estimates to rival our top recommended charities and severe negelectedness in overall funding (specifically, a $4.2 billion shortfall), we cannot currently recommend any particular charities through which there is a good opportunity for donations to have a large impact.
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5.3 Hepatitis B vaccination, treatment of parasites (liver cancer, bladder cancer) Liver cancer has one of the highest mortality rates of any primary cancer. In 2012, it caused 746,000 deaths out of 782,000 cases.247 In addition, 83% of new cases occur in developing countries, where diagnosis and treatment is particularly difficult.248 Some highly cost-effective interventions are available to reduce the number of people who get the disease, as recommended by both WHO and DCP3, and which may have significant co-benefits. Similar interventions are also available for bladder cancer. To prevent liver cancer, Hepatitis B vaccination is the first line of defence. Hepatitis B is a cancer-causing virus responsible for around 60% of hepatocellular carcinoma (the most common type of liver cancer) in LICs.249 The virus attacks the liver, sometimes setting up an infection which can last for years. 15-45% of those with long-term infection will develop serious complications such as cirrhosis and liver cancer during their lifetime.250,251 The majority of countries now aim to vaccinate children at birth, but coverage at birth is still low in some areas.252 Initial vaccination within 24 hours is very important in preventing transmission from mother to child, which often results in dangerous long-term infection.253,254 Increasing vaccine coverage would greatly decrease Hep B infection rates and hence liver cancer incidence.255 The WHO has previously found that Hepatitis B vaccinations carried out by the GAVI Alliance avert a disability-adjusted life year (DALY) for approximately US$47.256 This compares favourably with our top recommended charities - for example, the Against Malaria Foundation is estimated to avert a DALY for approximately every $78 in donated funds.257,258 However, GAVI is extremely well funded, receiving $4.3 billion in pledged donations for 2011-2015 despite their target of only $3.7 billion.259 In addition, GAVI already receives 76% of its funding from various governments and 18% from the Gates Foundation.260 Hepatitis B vaccinations are therefore far from neglected, and we do not currently recommend donating to such initiatives as it is therefore unlikely that additional
donations will have a substantial impact. Likewise, we have not found any other organisations which focus on immunisation which we can currently recommend as both highly cost-effective and sufficiently neglected.261 However, targeting other region-specific causes of liver cancer may also be promising. High rates of liver fluke infection occur in some areas of eastern Asia, especially within the Mekong River Basin in Southeast Asia, where around 40 million people are infected.262,263 The worms can infect a host for many years, causing damage to the liver’s bile ducts which can eventually lead to cancer.264 Treatment of liver fluke with Praziquantel can clear the infection and prevent incidence of liver cancer, though people in the area are often quickly reinfected by eating raw fish dishes.265 The Deworm the World Initiative (DtWI) is one charity which administers Praziquantel in Vietnam, where liver fluke are extremely prevalent266 and liver cancer causes 4.81% of all deaths (three times the developing world average).267 However, Vietnam forms only a small proportion of DtWI’s operations (less than 5% of total spending)268 and donations to DtWI, overall, are hence unlikely to cost-effectively reduce liver fluke infection or liver cancer. Another contributor to liver cancer in the developing world is poor food storage. Parasites can infect staple foods during cultivation, including peanuts, rice and corn.269 In areas where these foods are then stored in warm, high humidity environments, the fungus is able to grow, producing the highly potent aflatoxin. This toxin causes DNA mutations and is associated with both liver and lung cancer.270,271 In people with chronic Hep B infection, exposure to aflatoxin increases their chances of liver cancer by 30 times.272,273 Improved grain storage and cultivation methods can reduce the amount of the toxin that people consume. With 4.5 billion people currently exposed to aflatoxin, the potential for reducing suffering through changing grain storage practices is enormous. Again, we are not aware of any charities working in this area with sufficient evidence to demonstrate their cost-effectiveness in preventing cancer cases. 29
Bladder cancer can also potentially be prevented through similar means. Much like liver flukes for liver cancer, infection with Schistosoma haematobium has long been associated with bladder cancer,274 and is recognised as a cause of cancer by the IARC.275,276 Studies in the 1970s and 80s noted that bladder cancer was more common in areas in which Schistosoma haematobium infection was common277 and biopsies of tumours showed high incidence of schistosome infection.278,279 In one area in South Africa, 53% of those carrying schistosoma haematobium were also found to have developed bladder cancer.280 Across sub-Saharan Africa, Yemen, Sudan, and Egypt, 41-42% of those suffering from bladder cancer also have schistosoma parasites present,281 and hence might be responsible for up to 42% of bladder cancers in this region. Fortunately, schistosomiasis is easily and cheaply treatable, and two highly effective charities - the Schistosomiasis Control Initiative282 and Deworm the World Initiative283 - can provide treatment for approximately $2 per person per year.284,285 Less fortunately, however, schistosomiasis treatment is unlikely to be a cost-effective and efficient method of reducing the incidence of bladder cancer. The annual death toll of bladder cancer in sub-Saharan Africa is only 7,376 (slightly less than Germany alone, which experiences 7,491 each year).286 Given that approximately 42% of cases were due to schistosomiasis, this gives an estimated death toll of approximately 3,100 from bladder cancer in patients who also carry schistosoma parasites. Even supposing, quite conservatively,
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that schistosomiasis is the direct cause of bladder cancer in all 3,100 patients, this still results in an exceedingly low rate of bladder cancer among schistosomiasis patients. Across sub-Saharan Africa, approximately 120 million people carry the parasite and display symptoms,287 20 million display chronic symptoms,288 and 11.7 million receive treatment each year.289 Even assuming, quite conservatively, that schistosomiasis is the direct cause of bladder cancer in all of those 3,100 patients who die from bladder cancer, only 1 in approximately 38,700 schistosomiasis patients will develop bladder cancer and subsequently die from it. Thus, approximately 38,700 treatments would be required to save one life and, even at $2 per treatment, the cost per life saved is more than $77,000. Admittedly, this figure is not entirely rigorous and almost certainly an underestimate, but it does indicate very strongly that schistosomiasis treatment is not a cost-effective method of reducing the incidence of bladder cancer. In comparison, the Against Malaria Foundation290 prevents a death from malaria for approximately $2,838 and, from above, Project Healthy Children prevents a death specifically from stomach cancer for $19,100 (see Section 5.1). (Of course, when the more direct benefits of schistosomiasis treatment are considered, the operations of the Schistosomiasis Control Initiative and Deworm the World Initiative are shown to be highly cost-effective. However, here we are restricting our focus to their effect on reducing cancer mortality.)
5.4 Screening, HPV vaccination (cervical cancer) The WHO and DCP3 also identify methods of reducing deaths from cervical cancer as highly cost-effective, particularly screening and vaccination against Human Papilloma Virus (HPV). However, due to its crowdedness and/or low cost-effectiveness, we do not recommend donations in these area.
recommendations, though not the WHO “Best Buys” list. HPV-16 and -18 are responsible for more than 70% of cervical cancers,298 with HPV-16 detected in 57% of cervical cancers and HPV-18 detected in 17%.299 Along with 6 less common strains, these HPV types are responsible for over 90% of cervical cancer cases.300
For instance, screening and treatment for early cervical lesions have been shown to be cost-effective by both DCP3 and the WHO. In particular, opportunistic screening with an acetic acid test is low-cost and cancerous/precancerous lesions can be removed on the same day.291,292
The HPV vaccine is relatively high-cost and does require two follow-ups, so it may not be cost-effective in all areas.301 However, heavily subsidised vaccines, such as those offered by GAVI alliance, make vaccination much more cost-effective (vaccines at $5 per dose are available to 37 countries in Sub-Saharan Africa).302 The vaccine requires a cold chain, making some areas of sub-Saharan Africa difficult to cover, but it has been estimated that 70% coverage of 9-year old girls for 5 years could avert 670,000 cases of cervical cancer in the region.303
Since high-risk strains of HPV are responsible for up to 98% of cervical cancer cases,293,294 HPV screening can also be highly effective in averting deaths from cervical cancer.295 Screens are lowcost and some can be done at home, so women who do not want to come to the clinic or undergo a cervical examination can still be screened.296 Vaccination against HPV strains 16 and 18 (those most commonly associated with cervical cancer) is also highly cost-effective in some areas.297 These vaccinations are included in the DCP3
Again, however, we are not aware of any charitable organisations working in this area which are both highly cost-effective and experiencing a sizeable funding gap. Additional donations to the GAVI Alliance, for instance, are unlikely to have a large impact.
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5.5 Screening, awareness raising (breast cancer) Included in the DCP3,304 but not the WHO recommendations, is screening for breast cancer. This prevents patients from going untreated for extended periods of time and thereby from advancing to later-stage cancer, and may be greatly improved by increasing awareness and understanding of the disease. Since presentation with advanced-stage tumour is more common in low/middle income countries,305 examination by medical professionals and education in breast self-awareness may decrease death rates, as treatment earlier in the disease course is far easier and has a higher success rate.306 A case study in Malaysia found that incidence of patients presenting at late stage breast cancer decreased from 77% to 37% after a country-wide drive to increase awareness. As part of the drive, nurses began to visit rural areas to give talks, demonstrate breast awareness and perform examinations.307 We are not aware of any charitable organisations working in this area which are both highly cost-effective and experiencing a sizeable funding gap. However, Development Media International (DMI) is one charity which raises awareness of various health issues in developing countries and which is supported by rigorous evidence and independent evaluations.308 DMI targets its awareness campaigns at the most tractable, neglected and high-impact areas and health practices. Based on these priorities, DMI has not focussed on breast cancer awareness thus far but instead prioritised those health practices which have greater potential to save and improve lives. This might indicate: a) that breast cancer awareness simply is not as high-impact or tractable as other interventions in DCP3 and recommended by the WHO; and b) that a lack of funding has not permitted DMI or other charities in this area to pick the ‘low-hanging fruit’ of higher-impact awareness initiatives and move on to breast cancer and others.
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6. TREATMENT Cancer costs in developed nations are generally quite high. In the United States, for instance, the mean cost of treatment of patients in their initial year after diagnosis is above US$50,000 in most categories of cancer, and exceeds US$100,000 for some categories.309 Including ongoing costs in subsequent years of treatment, the cost of cancer treatment in the United States is exceedingly high - in comparison, donations to the the Against Malaria Foundation (one of the top charities recommended by Giving What We Can) prevent deaths of children under the age of 5 in sub-Saharan Africa for approximately $2,838 per person.310 The situation is similar in the United Kingdom (with an average annual treatment cost of £30,000 per person, predominantly borne by the government)311 and elsewhere, with the additional consideration that government initiatives such as the National Health Service, or private insurers, often cover the costs of treatment. Indeed, funding has even been allocated for those cancer treatments which fail to meet cost-effectiveness standards £416 million per year in the UK.312 The relatively high per-capita income in such developed nations313 also makes it plausible that many patients would simply pay for their own treatment if no other funding were available. Thus, the impact of donations towards cancer treatment in such nations is unlikely to have any sizeable impact as, not only is the cost of treatment extremely high but, patients are likely to be treated with or without further donations. Hence, it is neither cost-effective nor neglected. In developing nations, however, the situation is quite different. DCP3 does identify cancer treatment in the developing world among its listed priorities.314 It offers an “Essentials Cancer Intervention Package” designed to reduce deaths from cancer, both through treatment and through prevention, and which is tailored to the wealth and infrastructure of the country in question. In particular, DCP3 highlights the cost-effectiveness of treating some childhood cancers. The very high cure rates seen in some childhood cancers in HICs are often dependant on intensive supportive care which is not available in LICs315. However, some
studies have shown less intensive treatments of certain cancers to be highly cost-effective, with a combination drug treatment of Burkitt’s Lymphoma, for instance, costing less than $1000 per successful treatment.316,317,318,319 One study even showed that a 28-day treatment cycle, costing less than $50 per patient to perform, had a 50% survival rate320 - hence suggesting that a life might be saved for less than $100. Unfortunately, however, we are not aware of any underfunded charitable organisations which focus on providing highly cost-effective treatments such as this. One strategy which may facilitate improved and broader treatment of childhood cancers in developing nations is the use of twinning programs. That is, the linking of hospitals in low income countries (LICs) with specialist hospitals in high income countries (HICs) to allow expertise to be shared and thereby improve treatment and survival rates.321 DCP3 also notes that this may have positive flow-on effects - the success seen in childhood cancer can act as a strong motivator to encourage governments to pursue cancer treatment programs and give early stage patients the hope required to seek help as soon as they discover symptoms of disease. Twinning programs are one of several interventions performed by World Child Cancer,322 an international cancer treatment charity which does appear promising and which also treats Burkitt’s Lymphoma, however they admit that they do not focus on the most cost-effective treatments and programs. Even though some of their interventions such as twinning programs may be highly effective, we do not believe that a large portion of donations will be spent on such interventions and, therefore, that donating to World Child Cancer is not a highly cost-effective method of having an impact. In addition, we are not aware of any other underfunded charities carrying out treatment interventions which have a sufficient focus on the most cost-effective treatments.
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REFERENCES 11 Stewart, BW, and CP Wild. “World Cancer Report 2014. International Agency for Research on Cancer.” World Health Organization (2014). 22 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 3 Feb. 2016 33 ibid. 44 “How We Work - Project Healthy Children.” 2015. 24 Feb. 2016 55 “Population, total | Data | Table - The World Bank.” 2010. 24 Feb. 2016 66 “rwanda - Documents & Reports - World Bank.” 2013. 24 Feb. 2016 77 “Malawi - Documents & Reports - World Bank.” 2013. 24 Feb. 2016 88 “Liberia - Documents & Reports - World Bank.” 2013. 24 Feb. 2016 99 “Burundi - Documents & Reports - World Bank.” 2013. 24 Feb. 2016 1010 “Zimbabwe - Documents & Reports - World Bank.” 2013. 24 Feb. 2016
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1111 “Documents & Reports - World Bank.” 2013. 24 Feb. 2016 1212 “Sierra Leone - Documents & Reports - World Bank.” 2013. 24 Feb. 2016 1313 “Nepal - Documents & Reports - World Bank.” 2013. 24 Feb. 2016 1414 “Nutrition at a glance: Tanzania | HESP News Briefing – RSS ...” 2014. 24 Feb. 2016 15Notes 16 “What Is Cancer? - National Cancer Institute.” 2015. 8 Feb. 2016 17 “WHO | Cancer.” 2015. 8 Feb. 2016 18 Stewart, BW, and CP Wild. “World Cancer Report 2014. International Agency for Research on Cancer.” World Health Organization (2014). 19 ibid. 20 “GBD 2013 - Global Health Data Exchange - Institute for ...” 2015. 15 Feb. 2016 21 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 3 Feb. 2016 22 “Cancer: Not only a rich-world disease - BBC News.” 2012. 9 Feb. 2016
23 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 3 Feb. 2016
36 Cuomo, Margaret I. A World Without Cancer: The Making of a New Cure and the Real Promise of Prevention. Rodale, 2012.
24 ibid.
37 “PhRMA Member Companies Invested $51.2 Billion in R&D ...” 2015. 10 Feb. 2016
25 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 3 Feb. 2016 26 Stewart, BW, and CP Wild. “World Cancer Report 2014. International Agency for Research on Cancer.” World Health Organization (2014). 27 ibid. 28 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 9 Feb. 2016 29 “Cancer: Not only a rich-world disease - BBC News.” 2012. 9 Feb. 2016 30 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 3 Feb. 2016 31 Burnet, NG et al. “Years of life lost (YLL) from cancer is an important measure of population burden—and should be considered when allocating research funds.” British Journal of Cancer 92.2 (2005): 241-245. 32 Stewart, BW, and CP Wild. “World Cancer Report 2014. International Agency for Research on Cancer.” World Health Organization (2014). 33 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 9 Feb. 2016 34 Even for any particular forms of cancer which disproportionately affect developed nations, medical research conducted now may still lead to considerable benefits for other nations when they do reach similar levels of development in future. 35 “NCI Director Harold Varmus to address National Press Club ...” 2015. 10 Feb. 2016
38 “Near-doubling of UK cancer research funding in less than ...” 2011. 11 Feb. 2016 39 Eriksen et al. 2015. The Tobacco Atlas 5th ed. The American Cancer Society. 40 Team, C. “Assessing the Efficacy of Health Research as a ...” 2014. 41 Ethiopia Poverty Reduction Strategy Paper. 2002. 42 “Against Malaria Foundation - Giving What We Can.” 2015. 10 Feb. 2016 43 “Schistosomiasis Control Initiative - Giving What We Can.” 2015. 10 Feb. 2016 44 “Development Media International | GiveWell.” 2014. 10 Feb. 2016 45 “Is tobacco control a “best-buy” for the developing world ...” 2015. 10 Feb. 2016 46 “Cost of Developing a New Drug - Tufts Center for the Study ...” 2014. 10 Feb. 2016 47 Kantarjian, Hagop et al. “High cancer drug prices in the United States: reasons and proposed solutions.” Journal of Oncology Practice 10.4 (2014): e208-e211. 48 “Against Malaria Foundation (AMF) | GiveWell.” 2010. 11 Feb. 2016 35
49 “Best Buys - World Health Organization.” 2011. 21 Dec. 2015 50 Ngoma, T. “World Health Organization cancer priorities in developing countries.” Annals of oncology 17.suppl 8 (2006): viii9-viii14. 51 Torre, Lindsey A et al. “Global cancer incidence and mortality rates and trends—an update.” Cancer Epidemiology Biomarkers & Prevention 25.1 (2016): 16-27.
63 “How is stomach cancer treated? - American Cancer Society.” 2013. 23 Feb. 2016 64 “Annual Costs of Cancer Care | Cancer Prevalence and Cost ...” 2016. 23 Feb. 2016 65 Parkin, DM. “5. Cancers attributable to dietary factors in the UK in 2010.” British journal of cancer 105 (2011): s24-S26.
52 “Cancer Rates Decline in Many High-income Countries, but ...” 2015. 11 Feb. 2016
66 Wang, Xiaoqin, and Hong Yan. “Stomach cancer in 67 Chinese counties: evidence of interaction between salt consumption and helicobacter pylori infection.” Asia pacific journal of clinical nutrition 17.4 (2008): 644.
53 Torre, Lindsey A et al. “Global cancer incidence and mortality rates and trends—an update.” Cancer Epidemiology Biomarkers & Prevention 25.1 (2016): 16-27.
67 Beevers, D Gareth, Gregory YH Lip, and Andrew D Blann. “Salt intake and Helicobacter pylori infection.” Journal of hypertension 22.8 (2004): 1475-1477.
54 ibid. 55 ibid. 56 “Cancer Rates Decline in Many High-income Countries, but ...” 2015. 11 Feb. 2016 57 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 3 Feb. 2016 58 ibid. 59 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 3 Feb. 2016
68 Cogliano, Vincent James et al. “Preventable exposures associated with human cancers.” Journal of the National Cancer Institute 103.24 (2011): 1827-1839. 69 Cogliano, Vincent James et al. “Preventable exposures associated with human cancers.” Journal of the National Cancer Institute 103.24 (2011): 1827-1839. 70 Tramacere, I et al. “A meta-analysis on alcohol drinking and gastric cancer risk.” Annals of oncology (2011): mdr135. 71 ibid. 72 Trédaniel, Jean et al. “Tobacco smoking and gastric cancer: Review and meta-analysis.” International Journal of cancer 72.4 (1997): 565-573.
60 ibid.
73 Parkin, DM. “5. Cancers attributable to dietary factors in the UK in 2010.” British journal of cancer 105 (2011): s24-S26.
61 “Stomach cancer - NHS Choices.” 2008. 23 Feb. 2016
74 Ames, Bruce N. “Micronutrient deficiencies: A major cause of DNA damage.” Annals of the New York Academy of Sciences 889.1 (1999): 87-106.
62 “Stomach cancer - Treatment - NHS Choices.” 2012. 23 Feb. 2016
75 Kong, Pengfei et al. “Vitamin Intake Reduce the Risk of Gastric Cancer: Meta-Analysis and Systematic Review of Randomized and Observational Studies.” PloS one 9.12 (2014): e116060.
36
76 “An Update on Project Healthy Children - Giving What We Can.” 2015. 22 Feb. 2016
87 “Against Malaria Foundation - Giving What We Can.” 2015. 24 Feb. 2016
77 Correa, Pelayo et al. “Dietary determinants of gastric cancer in south Louisiana inhabitants.” Journal of the National Cancer Institute 75.4 (1985): 645-654.
88 “Against Malaria Foundation (AMF) | GiveWell.” 2010. 24 Feb. 2016
78 Correa, Pelayo et al. “Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-Helicobacter pylori therapy.” Journal of the National Cancer Institute 92.23 (2000): 1881-1888.
89 “How We Work - Project Healthy Children.” 2015. 24 Feb. 2016
79 Li, Jun-Yao et al. “Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia.” Journal of the National Cancer Institute 85.18 (1993): 1492-1498. 80 Horton, Sue, Harold Alderman, and Juan A Rivera. The challenge of hunger and malnutrition. Copenhagen Consensus, 2008. 81 Kong, Pengfei et al. “Vitamin Intake Reduce the Risk of Gastric Cancer: Meta-Analysis and Systematic Review of Randomized and Observational Studies.” PloS one 9.12 (2014): e116060. 82 “Sierra Leone - Documents & Reports - World Bank.” 2013. 24 Feb. 2016 83 “(GBD 2013) Data Downloads - Full Results - Global Health ...” 2016. 24 Feb. 2016 84 “Project Healthy Children - Giving What We Can.” 2016. 24 Feb. 2016 85 This cost is a conservative estimate based on a 2015 analysis of PHC’s Development Plan. 86 “Population Pyramid of Sub-Saharan Africa in 2016.” 2015. 24 Feb. 2016
90 From private communications and financial statements from PHC. 91 We are estimating this proportion from the rates of vitamin A deficiency among children of preschool age which, although different from the rate populationwide, does give a rough indication of what proportion of the population are not receiving adequate levels of vitamin A and are therefore well-placed to benefit from fortification. 92 Das, Jai K et al. “Micronutrient fortification of food and its impact on woman and child health: a systematic review.” Systematic reviews 2.1 (2013): 1. 93 Eichler, Klaus et al. “Effects of micronutrient fortified milk and cereal food for infants and children: a systematic review.” BMC public health 12.1 (2012): 1. 94 Best, Cora et al. “Can multi-micronutrient food fortification improve the micronutrient status, growth, health, and cognition of schoolchildren? A systematic review.” Nutrition reviews 69.4 (2011): 186-204. 95 “Fortification Impact Studies - GiveWell.” 25 Feb. 2016 96 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 26 Feb. 2016 97 Bougma, Karim et al. “Iodine and mental development of children 5 years old and under: a systematic review and meta-analysis.” Nutrients 5.4 (2013): 1384-1416. 98 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 26 Feb. 2016 37
99 ibid.
112 ibid.
100 ibid. 101 ibid.
113 see https://docs.google.com/spreadsheets/ d/1lMzXga5d3-WPvsUgpFNoTR64CFmYHLfT3fBABA5 jN60/edit?usp=sharing
102 Pachón, H et al. “Folic acid fortification of wheat flour: A cost‐effective public health intervention to prevent birth defects in Europe.” Nutrition Bulletin 38.2 (2013): 201-209.
114 Hillebrandt, H. “An Update on Project Healthy Children - Giving What We Can.” 2015. 24 Feb. 2016
103 Liu, Jufen et al. “Plasma folate levels in early to mid pregnancy after a nation‐wide folic acid supplementation program in areas with high and low prevalence of neural tube defects in china.” Birth Defects Research Part A: Clinical and Molecular Teratology 103.6 (2015): 501-508.
115 ibid.
104 Castillo-Lancellotti, Cecilia, Josep A Tur, and Ricardo Uauy. “Impact of folic acid fortification of flour on neural tube defects: a systematic review.” Public health nutrition 16.05 (2013): 901-911.
117 “National Fortification Programs - Project Healthy Children.” 2012. 25 Feb. 2016
105 “Before and after analysis of PHC’s impact - GiveWell.” 24 Feb. 2016
118 “Project Healthy Children | GiveWell.” 2011. 25 Feb. 2016
106 “Project Healthy Children | GiveWell.” 2011. 24 Feb. 2016 107 Awasthi, Shally et al. “Vitamin A supplementation every 6 months with retinol in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial.” The Lancet 381.9876 (2013): 1469-1477. 108 Horton, Sue. “The economics of food fortification.” The Journal of nutrition 136.4 (2006): 1068-1071. 109 “WHO | WHO Statistical Information System (WHOSIS).” 24 Feb. 2016 110 “An Update on Project Healthy Children - Giving What We Can.” 2015. 24 Feb. 2016 111 Fiedler, John L, and Barbara Macdonald. “A strategic approach to the unfinished fortification agenda: feasibility, costs, and cost-effectiveness analysis of fortification programs in 48 countries.” Food and nutrition bulletin 30.4 (2009): 283-316. 38
116 Kong, Pengfei et al. “Vitamin Intake Reduce the Risk of Gastric Cancer: Meta-Analysis and Systematic Review of Randomized and Observational Studies.” PloS one 9.12 (2014): e116060.
119 Allen, Lindsay H. et. al. “Guidelines on food fortification with micronutrients.” World Health Organisation (2006). 120 “PHC Before and After Analysis Regarding PHC’s Impact - GiveWell.” 25 Feb. 2016 121 Das, Jai K et al. “Micronutrient fortification of food and its impact on woman and child health: a systematic review.” Systematic reviews 2.1 (2013): 1. 122 Eichler, Klaus et al. “Effects of micronutrient fortified milk and cereal food for infants and children: a systematic review.” BMC public health 12.1 (2012): 1. 123 Best, Cora et al. “Can multi-micronutrient food fortification improve the micronutrient status, growth, health, and cognition of schoolchildren? A systematic review.” Nutrition reviews 69.4 (2011): 186-204. 124 “Fortification Impact Studies - GiveWell.” 25 Feb. 2016
125 “What are the key statistics about stomach cancer?.” 2010. 4 Mar. 2016 126 Kong, Pengfei et al. “Vitamin Intake Reduce the Risk of Gastric Cancer: Meta-Analysis and Systematic Review of Randomized and Observational Studies.” PloS one 9.12 (2014): e116060. 127 Awasthi, Shally et al. “Vitamin A supplementation every 6 months with retinol in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial.” The Lancet 381.9876 (2013): 1469-1477. 128 “About Gain - Global Alliance for Improved Nutrition.” 2014. 25 Feb. 2016
138 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 25 Feb. 2016 139 “Global Progress- Food Fortification Initiative.” 2012. 25 Feb. 2016 140 “Project Highlights - Project Healthy Children.” 2012. 25 Feb. 2016 141 “A conversation with Laura Rowe, February 19 ... GiveWell.” 2015. 25 Feb. 2016 142 “An Update on Project Healthy Children - Giving What We Can.” 2015. 25 Feb. 2016
129 “Vitamin A Deficiency - The Golden Rice Project.” 2012. 25 Feb. 2016
143 Shekar, Meera. Scaling up nutrition: what will it cost?. World Bank Publications, 2010.
130 “Reducing Global Malnutrition | Vitamin Angels Global Impact.” 2015. 25 Feb. 2016
144 Bhutta, Zulfiqar A et al. “Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost?.” The Lancet 382.9890 (2013): 452-477.
131 “Conversation with Amy Steets about Vitamin Angels ...” 2013. 25 Feb. 2016
145 Shekar, Meera. Scaling up nutrition: what will it cost?. World Bank Publications, 2010.
132 Of the organisations listed, the Iodine Global Network is the only one which does not work on vitamin A fortification, but instead focuses its attention on iodine.
146 “Project Healthy Children - Giving What We Can.” 2015. 23 Feb. 2016
133 “Iodine Global Network (IGN) - About the IGN.” 25 Feb. 2016
147 “Project Healthy Children - Giving What We Can.” 2016. 25 Feb. 2016
134 “Eliminating Vitamin A deficiency.” 2004. 25 Feb. 2016 135 Shekar, Meera. Scaling up nutrition: what will it cost?. World Bank Publications, 2010. 136 ibid. 137 “Nutrition at a glance - Documents & Reports - World Bank.” 25 Feb. 2016
148 “PHC Report - Giving What We Can.” 25 Feb. 2016 149 “Where We Work - Project Healthy Children.” 2012. 25 Feb. 2016 150 ibid. 151 Personal communication and financial statements of PHC
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152 “A conversation with Dr. Michael Zimmermann ... GiveWell.” 25 Feb. 2016 153 “Global Alliance for Improved Nutrition (GAIN) GiveWell.” 2014. 25 Feb. 2016 154 “Programs - Global Alliance for Improved Nutrition.” 2014. 25 Feb. 2016 155 Stewart, BW, and CP Wild. “World Cancer Report 2014. International Agency for Research on Cancer.” World Health Organization (2014). 156 ibid. 157 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 3 Feb. 2016 158 ibid. 159 World Health Organization. “WHO report on the global tobacco epidemic, 2008: the MPOWER package.” (2008). 160 “WHO | Tobacco.” 2010. 12 Feb. 2016 161 Jha, Prabhat. “Avoidable Deaths from Smoking: A Global Perspective.” Public Health Reviews (2107-6952) 33.2 (2011). 162 Torre, Lindsey A et al. “Global cancer incidence and mortality rates and trends—an update.” Cancer Epidemiology Biomarkers & Prevention 25.1 (2016): 16-27. 163 ibid. 164 “Cancer Rates Decline in Many High-income Countries, but ...” 2015. 11 Feb. 2016 165 World Health Organization. “WHO report on the global tobacco epidemic, 2008: the MPOWER package.” (2008). 166 Boyle, Peter. Tobacco and Public Health: Science and Policy, Chapter 16. Oxford: Oxford Press. 2004. 40
167 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 3 Feb. 2016 168 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 3 Feb. 2016 169 ibid. 170 ibid. 171 ibid. 172 “GBD Compare | IHME Viz Hub - Data Visualizations.” 2014. 3 Feb. 2016 173 “Best Buys - World Health Organization.” 2011. 21 Dec. 2015 174“DCP3.” 2012. 21 Dec. 2015 p15. 175 Kostova, Deliana et al. “Is youth smoking responsive to cigarette prices? Evidence from low-and middle-income countries.” Tobacco Control (2011): tc. 2010.038786. 176 “Effectiveness of Tax and Price Policies for Tobacco ... - IARC.” 2015. 21 Dec. 2015 177 Chaloupka, Frank J, Ayda Yurekli, and Geoffrey T Fong. “Tobacco taxes as a tobacco control strategy.” Tobacco Control 21.2 (2012): 172-180. 178 World Health Organization. “WHO report on the global tobacco epidemic, 2008: the MPOWER package.” (2008). 179 Jha, Prabhat, and Frank J Chaloupka. Curbing the epidemic: governments and the economics of tobacco control. Prabhat Jha & Frank J Chaloupka. World Bank Publications, 1999. 180 World Health Organization. “WHO report on the global tobacco epidemic, 2008: the MPOWER package.” (2008). 181 “WHO | Tobacco.” 2010. 12 Feb. 2016 182 Jha, Prabhat, and Frank J Chaloupka. Curbing the epidemic: governments and the economics of tobacco
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291 Sauvaget, Catherine et al. “Accuracy of visual inspection with acetic acid for cervical cancer screening.” International Journal of Gynecology & Obstetrics 113.1 (2011): 14-24.
304 Also included is the treatment of early-stage tumours.
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