Respuesta ante eventos adversos en el NCHQ

Many of the definitions of NTDs are on the related problems of poverty or under-development and their lack of attention from governments, NGOs and pharma companies. The solution is often also presented alongside the need for prioritization, using existing safe and cost-effective 'tools' or developing new treatments. The lack of attention has been presented in terms of R&D for NTDs through the so-called '10/90 gap', which refers to resource allocation of global R&D compared with the disease burden.

The 10/90 gap is the finding of a report by 'The Global Forum for Health Research' i(2004) that says only 10% expenditure on global R&D is dedicated to problems that primarily affect the poorest 90% of the world's population.¹⁰⁷ The 10/90 gap only reflects R&D, with the argument

107Critiques of the 10/90 gap have argued that there has been a change in the epidemiology of developing countries, change in global health actors and also dispute of the size of the burden (Stevens, 2004).

c. Prioritize to

CDC also present a 'Fast Facts' section on their website (CDC http://www.cdc.gov/globalhealth/ntd/, Accessed 2/4/14):

• 1bn people across 149 countries/territories are affected (by at least one NTD)

• 100% of low-income countries are affected by at least five simultaneously

• 534,000 people are killed worldwide every year

• major disease burden, approx. 57 million years life lost to disability or death

• treatment cost for most NTD MDA est. at less fifty cents per person, per yr

"Many neglected tropical diseases can be prevented, eliminated or even eradicated with improved access to existing safe and cost-effective tools.

Control relies on simple interventions that can be carried out by non-specialists" (WHO Features,

http://www.who.int/healthinfo/global_burden_disease/metrics_daly/en/, 2012, Accessed 2/4/14)

"NTDs are infectious diseases that generally are rare or absent in developed countries, but are often widespread in the developing world... The availability of new safe and effective drugs for NTDs could provide public health benefit for overall global health, but because these diseases are found primarily in developing countries, existing incentives have been insufficient to encourage development of new drug therapies" (FDA, 2014).

that the market share of pharmaceutical businesses is too small for the 90% of the world who are poor, as pharma lacks profit incentive (Liese et al., 2010). Smith calls the 10/90 gap "(A) staggering example of neglect... International aid couldn't just be the distribution of existing cures. It needed broad innovation" (Smith, 2015). Here it is a mismatch between needs and investment that mark NTDs out. So the 10/90 gap became a part of the argumentation that the problem of NTDs lies in R&D, which would require a change in the innovation system from NGOs and the WHO to academics (Bosman & Mwinga, 2000; Hotez & Pecoul, 2010; Kilama, 2009).¹⁰⁸ Even if the 10/90 gap is not explicitly mentioned the unequal research spending by pharma is frequently referred to in media articles on NTDs (see Balasegaram et al., 2008).

R&D disparity is an important inclusion because it is in this context that neglect becomes striking. The WHO in 2007 stated: "Lack of reliable statistics on the burden of NTDs has hampered raising awareness of decision-makers on NTDs and zoonoses.¹⁰⁹ Accurate assessment of the disease burden is crucial to prioritize use of limited resources, provide timely treatments and prevent diseases" (WHO, 2007, p. 14). However, it is more than simply representing reality. The neglect of NTDs is highlighted through the numbers of people affected. NTDs compare with the small numbers of people affected by rare diseases (sometimes referred to as orphan diseases), which can lack attention and investment as their rarity means they only affect a small proportion of people. Additionally, orphan diseases sometimes include common diseases without a drug company 'adopting them'. The US Orphan Drug Act for example includes non-rare diseases and the European Organisation for Rare Diseases includes neglected diseases.

The 10/90 gap as a measure, marked the beginning of metrics being used in relation to NTDs, to make a policy case for attention. Christopher Murray, the health economist, has been an influential figure behind the drive for better tools for measurement in health. The Gates Foundation invested in the Seattle-based 'Institute for Health Metrics and Evaluation' where Murray is Director. In some part NTDs have also been influential for Murray. In fact Murray met Kenneth Warren the director of the GND in the mid-1980s. These were his thoughts on the program:

“I think the GND program had a great effect. He coined the term and it has stuck, and now people compete to call their disease ‘neglected’; there is a bit of a war about what the borders are, what is in and what is not. Is leprosy neglected? Is rabies? There are a lot of different definitions of what is neglected, and I think that the concept can reasonably be traced back to Ken” (Keating, 2014, p. S28).

108Unite for sight, http://www.uniteforsight.org/global-impact-lab/global-health-research, Accessed 5/6/13.

109"A zoonosis is any disease or infection that is naturally transmissible from vertebrate animals to humans" (WHO, 2015).

Furthermore, the NTD schistosomiasis was somewhat of a catalyst for Murray in his journey to create the 'DALY' metric, which stands for disability-adjusted life year'. The DALY is described as a "...measurement of the gap between current health status and an ideal health situation where the entire population lives to an advanced age, free of disease and disability".¹¹⁰ In the part biographical account Epic Measures (Smith, 2015), which charts Murray's career in global health, a defining moment was when Murray travelled with his family to South Africa where they ran a hospital. One day Murray found a sick man and had been horrified after he had brought the man in and his stomach had exploded, a severe complication of schistosomiasis. It stuck with him that the disease was one he had not even heard about before and that it could be so devastating.

DALYs were developed by the World Bank and WHO in 1993, through the Global Disease Burden Study led by Murray with Alan Lopez (Smith, 2014). Murray describes that: “The original idea was you want a metric that can also be used in economic studies: If you spend X amount of money, this is how much health you’ll get” (ibid.). The intention has been also said to be in assisting health priority setting otherwise influenced by politics and other pressures. It is also through the DALY measure that NTDs can be exposed, by estimating the burden of disease. These estimates renewed interest in the underlying epidemiological parameters. For example as NTDs mainly cause morbidity rather than mortality, the assessment of the average disability incurred by a diseased individual is crucial for correctly compiling data to global burden estimates. The disability weights (DW) are based on a non-expert or patient opinion but were developed through "highly educated" focus groups (Zhou et al. 2010, Part B, p. 59).

DALYs form a way to support a particular description of the world and how to act upon it.

Through the description supplied by the DALY, morbidity is put on par or to a raised position as mortality, working in favour of NTDs to emphasize the size of this problem (ibid., p. 3). Now we have DALYs NTDs can be described as: "...the fourth most devastating group of communicable diseases behind lower respiratory infections, HIV, and diarrheal diseases – ranking higher than either malaria or tuberculosis" (The Henry J. Kaiser Family Foundation, 2015). How NTDs are more debilitating and disabling than life-threatening can be captured, and further constructed as a grouping. This measure provides standardized estimates for years of life lost due to disease, injury and risk factors over time. One DALY is equal to the loss of one healthy life year, as the sum of: Years of Life Lost (YLL) due to premature mortality in the population and Years Lost due to Disability (YLD) for people living with the health condition or its consequences.¹¹¹ As shown in Figure 9 below, NTDs tend to cause more of the 'Years Lost due to Disability' than 'Years of Life Lost'.

110WHO Programmes, http://www.who.int/healthinfo/global_burden_disease/metrics_daly/en/, 2015b, Accessed 2/4/14.

111WHO Programmes, http://www.who.int/healthinfo/global_burden_disease/metrics_daly/en/, 2015b, Accessed 2/4/15.

Figure 9 YLDs and YLL of NTDs in 'The Global Burden of Disease Study 2010'

(Hotez et al., 2014)

Of course as the NTD grouping is not completely coherent there are four outliers in rabies, dengue, leishmaniasis and African trypanosomiasis. These are more fatal than disabling but it can be argued that these diseases should not be fatal if control measures are followed:

(1) Rabies is preventable, with the existence of a vaccination also available post-exposure;

(2) Dengue has less than a 1% fatality rate if detected early with access to proper medical care. While there is currently no known cure or treatment, several vaccine candidates are in clinical or pre-clinical development with the most advanced candidate in Phase III clinical trials (WHO Programmes, 2015a);

(3) There are three types of leishmaniasis. Only one of these, visceral leishmaniasis (also known as kala-azar) is fatal if untreated but all are treatable and curable;

(4) Lastly African trypanosomiasis (also know as HAT or sleeping sickness) is both difficult to diagnose and treat but has been controlled on the African continent in the past through surveillance methods. It should be noted that there are two forms of HAT depending on the parasite involved, one (Trypanosoma brucei gambiense) accounts for over 98% of reported cases causing a chronic infection for months or even years without major signs or symptoms and when more evident symptoms emerge the patient can be in an advanced disease stage (WHO Factsheet N°259, 2015). The other (Trypanosoma brucei rhodesiense) only represents 2% of cases but causes an acute infection that develops rapidly and invades the central nervous system (ibid.). The YLL may be due to the low survival rates if surveillance to prevent the disease transmission fails.

Therefore, these four diseases are not strictly disabling, unless we count the repeated illness and recovery times of several months. Rabies is the one that clearly does not fit this profile because it will almost always lead to death, if a person is not vaccinated before infection or vaccinated immediately post-infection before symptoms appear (this has only been challenged more recently by survival by inducing coma, called the 'Milwaukee Protocol' Aramburo et al., 2011). However, the point is that all are preventable and do not need to be fatal.

DALYs were an evolution of the earlier QALY (quality-adjusted life years) measure proposed by Zeckhauser and Shepard in 1976 and widely used in cost-effectiveness analyses for health interventions. The two health economists invented the QALY in 1956 to "...determine the value for money of a medical intervention by quantifying the quality of life gained in relation to the cost of that intervention" (Adams, 2016, p. 26). Where DALYs are a measure of the, "health loss in populations against a normative standard" QALYs tend to be used to, "quantify health gains for interventions" (Mathers, Ezzati, & Lopez, 2007, p. 2).

Some regard QALYs as a better measure of "subtle morbidities and long-term chronicity" (Zhou et al., 2010, Part A, p. 16) but Adams makes the interesting observation that it was "...a crisis of funding produced the QALY in the Global North, but I would argue that it was the crisis of data that produced its counterpart, the DALY, in the Global South" (Adams, 2016, p. 27). In determining which diseases to bring attention to, the DALY has been crucial, while the QALY has told us more about which interventions to take.

I have outlined that the DALY has the capacity to measure the disabling and debilitating nature of NTDs as a developing country concern. However, does the DALY have an impact in highlighting NTDs within the Global Burden of Disease (GBD)? In the early years NTDs did not show up very highly on overall disease burden (despite some surprise appearances) and "...the NTD community was dismayed by the previous WHO estimates between 1999 and 2004, which assigned DALYs that were equivalent to conditions of comparatively minor global health importance for major diseases such as schistosomiasis" (Hotez et al., 2014, p. 2). The year 2002 was deemed particularly bad as no NTD appeared in the 20 leading DALYs and led to a full revision of burden estimates for 2005. Hotez and Musgrove in 2009 made the argument that because NTDs contribute or are underlying rather than identified as the direct cause of deaths they were overlooked. For example schistosomiasis may lead to death by bladder cancer or deaths attributable to anemia from an NTD. They also argued that uncertainty about prevalence and incidence led to under-reporting of YLDs.

Later estimates calculated that the DALYs attributable to NTDs was US$56 million, however estimates dropped again in the 2012 GBD study it to be only US$26.05 million (See Molyneux, 2014, p. 176). This is quite a fall and constitutes only 1% of the total global disease burden.

There are several reasons for such a discrepancy. The first is in the geographic spread and

how this is measured as NTD rates vary (by nearly 1000-fold) across regions because of a concentration in the poorest countries. A second point is that burden for diseases associated with long-term morbidity, is determined by DWs and "(T)here is considerable dispute of the DWs attributed to NTDs, and some case studies have seriously challenged both the DWs for different diseases, but also the numbers of people afflicted" (ibid., p. 5). Also direct pathologies associated with NTDs that are not included in the NTD burden such as for cancer and neurological conditions and factors have been ignored in calculating the burden of NTDs, such as mental illness.

At the other extreme, "...the higher DALY estimates for NTDs elevate the status of these diseases to a level at which they could be thought of as the fourth leg to a table built on HIV/AIDS, tuberculosis, and malaria" (Hotez et al., 2014, p. 2). Collectively constructed, NTDs can be counted together adding up the number of DALYs that are attributable. As Hotez et al.

document the 2010 measure attempted to resolve earlier difference in estimate and also include more diseases, to provide a resulting figure of 48 million DALYs for NTDs, compared with tuberculosis (49 million), malaria (83 million) and HIV/AIDS (82 million), the later two accounting for two of the world’s major diseases (ibid.).

It is important to remember the DALY measurement is a 'calculus of credibility',¹¹² in that as I described previously, evidence is placed by policy actors on a hierarchy, with RCTs tending to be at the top. DALYs are similarly statistically quantifiable metric and furthermore, they do not sit in isolation and go toward creating the 'Global Burden of Disease index', which ranks diseases according to their DALY score. Therein comes the importance of measuring and creating metrics at all, to be able to list hierarchal and relationally problems for policy that allows on a managerial level comparison and prioritization of funding and resources, on a possibly more ideological level to determine need apart from so-called political pressures. This is where much contention lies, as political process of democracy demands advocacy and different groups to petition elected representatives on the interests, values and causes they support. To 'follow the numbers' may suppress these activities or these activities will adopt the measurement language through the DALY metric.

The Gates Foundation now uses the concept of DALYs on a wide basis to help determine priorities and evaluate potential projects. By quantifying years lost to poor health, disability,, an economic valuing of human life is made by measuring morbidity in addition to mortality. The measure tends not to be used in economic analysis of benefit but rather for cost-effectiveness (Smith, 2015, p. 145). Gates recounted the influence of the 1993 World Development Report with preliminary Global Burden of Disease findings: "...'It was just a graph that had, you know, these twelve diseases that kill,' said Gates. These included leishmaniasis,

112'Calculus of credibility' is a phrase used by Epstein to refer to how different news sources chose what they determine to be credible claims to make for their audiences.

schistosomiasis, trachoma–the leasing scourges, preventable at low cost, whose names he'd also never seen before" (ibid.).

Following the Gales and Lascoumes definition (2007), DALYs are a tool for statistical categorization within the wider instrument of estimating the global burden of health. However, there is a difference between the type of tool described within the NTD community referring to interventions and a metric such as a DALY. This also resonates with public policy instrumentation in the problems posed and chosen path to make policy 'material and operational', orientating relations between political society and civil society. Devices mix technical components (measuring, calculating, the rule of law, procedure) and social components (representation, symbol) (ibid). Instrumentation is expressed in a standardized form, combining obligations, financial relations, and methods of learning about populations through statistical observations (ibid.).

Even if NTDs do not reach the top of the Global Burden of Disease (GBD), DALYs have increased awareness. Activist scientists and NGOs have faired well in playing the measurement game. Measurement advocacy started with the '10/90 gap', a narrative argument of neglect of R&D, especially from big pharma. However this narrative was largely about the injustice of funding for health research and not matching needs. More persuasively, DALYs have taken into account the particular needs associated with NTDs through their disabling nature, which had previously been overlooked on priority lists. The quantification of disability is novel in public health, and so the interweaving of DALYs and NTDs has been more successful.

The argument says why we should care about these diseases and why they are important.

Already the second WHO (2013) report on NTDs referenced the 10/90 gap and the DALY measurement. DALYs transformed NTDs into commensurable diseases to be measured alongside the big killers: HIV/AIDS, TB and malaria, where "(T)he calculated economic rates of return suggest that investment in control/elimination of neglected diseases produces an economic rate of return of 15–30%, and is capable of delivery on a large scale" (WHO, 2005, p.

19). However, as Moran et al. have identified, the "DALY approach has clear limitations and should be used with caution as a tool to allocate R&D spending" and they see deviation¹¹³ caused by the mechanism (2006, p. 23).