A meeting in Stockholm
On 21 October 2009, the eve of the European Development Days, close to 100 experts from across Europe met to discuss how to deal with the lack of funds and efforts to develop urgently needed new diagnostics and drugs for tuberculosis (TB). While the scope of the challenge seems clear to most, its urgency is not recognised by many, especially European governments and their politicians. As a result, possible technical solutions and funding models are not being matched by financial commitments. This lack of government attention – clearly manifest in the meeting organisers’ inability to secure adequate government representation and participation – has allowed TB, once believed a scourge of the past, to return with vigour.
At the meeting, Médecins Sans Frontières (MSF)presented recent studies demonstrating the significance of underfunding for TB across Europe. Europe’s biggest countries in economic terms are not spending their fair share (the amount of funding appropriate given their economy’s size) on the development of diagnostics, vaccines and drugs for TB. Except for Sweden who contributes 84%, all European countries analysed by MSF are in fact far from contributing their fair share, with France and the UK still doing significantly better (at 52 and 50% respectively) than Germany (22.5%) and Italy (11%). Europe as a whole contributes only a third of its fair share to TB research worldwide while the United States, whose health and social policies are often vehemently criticised on the continent, contribute two thirds.
Consensus on the problem
Experts at the meeting agreed that “fighting TB is a chronic challenge”, as described by Prof. Hans Rosling, founder and Director of gapminder.org and Professor for International Health at Karolinska Institute in Sweden. “TB today looks like an epidemic that is running out of control” stated Dr Frauke Jochims, who supports MSF TB programmes in several countries. This is despite the fact that when doctors like her attended medical school in the 1980s they learned that TB was a disease of the past. What has changed since is that, with HIV, new TB cases have almost tripled in some countries and drug-resistant strains have evolved to which pharmaceutical companies have been unwilling and academic researchers unable to respond adequately. “TB was already prevalent in ancient Egypt. What is new is not the disease but the drug resistance”, said Prof. Rosling, summing up the problem.
Multidrug-resistant TB (or MDR-TB) is defined as tuberculosis for which the two most powerful drugs out of the five available do not work. Its diagnosis is as challenging as its treatment. For example, diagnostic tests that are available in low-income settings, such as smear microscopy, require certain quantities of sputum, which some patients, such as children and people living with HIV, find difficult to produce. Furthermore, they do not detect drug-resistant patterns. More sophisticated tests do exist but they are expensive, difficult to use and only available in urban centres in a limited number of countries. This is not helpful to the 85% of patients who live in poor, rural areas. Dr Jochims pointed out that there is an “inverse relationship between where patients are and where lab facilities are located”. The numbers are shocking: only 3% of new MDR-TB cases globally have access to quality-assured treatment and only 1.7% of MDR-TB cases globally are being cured.
The current treatment for MDR-TB is long and difficult to tolerate. It takes up to two years and leads to intense side effects, including psychotic episodes, in some patients. The social consequences of current treatments are also extreme: while they are infectious, patients cannot go to work, have sex with their partner or play with their children.
Maybe all this is not surprising given that the tools currently used are “ancient”, according to Dr Pehrolov Pehrson, former President of MSF Sweden. The most common diagnostic test used in resource-poor settings is essentially the same as it was 130 years ago; the Calmette-Guerin Bacterium (BCG) vaccine was developed in the early 20th century; and treatment, too, relies on antibiotics developed decades ago. The reason why no newer tools to diagnose, prevent and treat TB are available is simple: people with TB do not represent an attractive market. “This represents a clear case of market failure” said Anders Ekholm, Chief Analyst at the Swedish Ministry of Health and Social Affairs.
Technical challenges and solutions
There are many technical challenges in improving TB diagnosis and treatment. For example, TB culture takes weeks, making the disease difficult to study and often discouraging research. Lack of access to treatment as well as weak health systems more generally also represent a considerable challenge. “New tools are important, but health systems need to know how to use them” argued Dr Nils Billo, Executive Director of the International Union Against Tuberculosis and Lung Disease. He added that “the three main reasons why there is TB are doctors, doctors and doctors”, thus underlining that health workers often do not use TB tools appropriately and hence sometimes compound the problem. Furthermore, he warned that if treatment is not standardised there is a danger of creating extensively drug-resistant TB (or XDR-TB) while treating MDR-TB. XDR-TB has already become a major challenge in the former Soviet Union.
Data collection and analysis is another challenge, according to Prof. Rosling who pointed out that there are four types of patients, which he acknowledged are not always easy to distinguish. “There are those that are healthy; those that are healthy but infected; those that are sick but not infectious; and those that are both sick and infectious”. Moreover, too many different indicators used in data collection and analysis make standardisation difficult. As a result, global TB data are poor.
Lack of industry attention to TB also represents a critical problem. Mr Ekholm from the Swedish Ministry of Health and Social Affairs spoke about the general problem of a lack of new antibiotics. He pointed out that industry lacks incentives to develop new antibiotics for a variety of reasons: a resistance from health authorities to pay high prices; the large number of existing competitive products; and limited treatment courses compared to chronic diseases which require life-long treatment.
Respondent Dr Hannu Laang, Scientific Officer at the European Commission (EC), agreed that new diagnostics, drugs and vaccines for TB are urgently needed, but referred to the complexity of TB as a major barrier. He stressed that the EC is currently funding eight diagnostics projects, some of which are likely to produce results soon. NGO representatives, however, expressed their scepticism with such optimism, arguing that the tools being developed would not be practical to use in resource-poor settings.
Michelle Childs, Director of Policy and Advocacy at MSF’s Access to Essential Medicines Campaign, stressed limitations of the current financial model for research and development (R&D) of new tools which relies on charging high prices to fund R&D protected by intellectual property rights. She explained that the current model breaks down when it is not possible to charge high prices for new treatments, as is the case in poor countries. As an alternative she introduced the concept of prize funds, an “old new idea” which delinks the price of a product from the cost of its development. Stating that the outlines of what a prize fund for a new point-of-care TB test should look like already exist, she explained that key elements of a prize fund would have to include accessibility by the poor and ease of use in peripheral environments. Moreover, a new point-of-care test for TB would need to be low-cost, provide quick and accurate diagnosis, be able to detect TB in HIV co-infection and children, and use something other than sputum, such as breath, urine or blood, for diagnosis.
There are many benefits of prize funds: besides divorcing price from R&D cost of a tool, they require payment only in the case of success; the possibility to establish goals without having to choose what the winning entry must look like in advance; they are flexible; and they encourage new solutions. Furthermore, prize funds are likely to increase the pool of researchers and companies looking into TB tools, and they encourage researchers to communicate with each other and share data. Last but not least, they generate publicity, attaching a certain prestige to the development of a solution.
It is estimated that a fund of 50 million Euro would encourage companies to take the risk. Organisations that could manage such a prize fund already exist and have been running prizes for various industries.
Mr Ekholm agreed with Ms Childs that new financing models are urgently needed to fund antibiotics in general. To this effect, his government, keen to help Europe find innovative incentives, has commissioned a study from the London School of Economics. The study sets out a number of possible options and states that a wide variety of measures to solve the problem is needed as taking one measure in isolation will not suffice. Recommended options range from push mechanisms (paying for inputs upfront) such as investing in research; direct funding; research tax incentives; and product development partnerships (which are often hybrids) to pull mechanisms (paying for outputs), which include prize funds; advance market commitments; patent pools; extended patent protection; regulatory mechanisms; call option for antibiotics; and others.
Several speakers and participants stressed that the Swedish government must ensure to proactively consider TB in its laudable efforts to address antibiotic resistance. So far, this important link has been missing from government debates, indicating perhaps that TB is not seen as a ‘European problem’.
Despite the existence of technical solutions and workable financial models, Europe spends only 25% (350 million Euro) of what is needed globally (1.45 billion Euro) for the development of TB tools; only 46% of this comes from private sources, and it is philanthropic organisations rather than industry which account for most of those private contributions.
This clearly shows that the ultimate problem is a lack of political commitment. Dr Pehrson reminded participants that “we are not talking about a lot of money”, stating that “in the case of Sweden living up to the fair share would mean spending one Euro per person per year, which is negligible compared to swine flu, for example, for which Swedes are currently paying 13 Euro per person per year” Dr Christophe Fournier, President of the MSF International Council, added that “swine flu has demonstrated that where there is political will, the problem can be solved” and Prof. Rosling, who produced powerful visuals demonstrating how much more funding swine flu has attracted than TB despite the number of deaths being much greater for TB, commented: “Swine flu demonstrates how diseases should be handled. If TB was handled like swine flu we would all be happy.”
The argument that TB is a ‘poor country problem’ and hence not as relevant for Europe as swine flu does not hold: while TB does disproportionately affect the poor, this includes the poor in rich European countries as well. In addition, the better-off are not immune to the disease. Oliver Moldenhauer from the MSF Access Campaign in Germany and co-author of several MSF studies on the issue stresses that “TB is still an important public health problem in Europe” and Dr Fournier added that “all big capitals in Europe are affected”. In WHO’s Europe region (which also includes Central Asia) 55 cases are diagnosed every hour, amounting to almost 500,000 cases annually.
Respondent Charlotte Goyon from Global Health Advocates expressed her disappointment with Europe as follows: “I am not very optimistic - the EC is giving so little, even less than France.” She argued that Europe’s institutions play an important role both in terms of funding TB research themselves and in influencing individual European Union (EU) member states to do so as well.
At the meeting, experts agreed that Europe providing more funds for TB is a necessity, albeit one that European governments do not yet seem to recognise. Asked whether he would be willing to advocate to Members of the European Parliament, Prof. Rosling replied: “Reaching the power structure of the world is not the problem, I have reached them”. He argued that advocates instead needed to reach the public as “power structures listen to the power of voters”. Dr Billo suggested that HIV advocates should lobby for TB too as co-infection is common and HIV advocates have traditionally been very strong and successful in changing policies.
Another key factor in driving research forward and developing appropriate TB tools are open access and open source approaches. This involves research taking place not in firms but in universities and other open research institutions. The fruits of R&D from the research community must be made available, affordable and accessible.
Referring to Italy’s poor results, MSF Italy President Raffaella Ravinetto stated that while she found it “not surprising that Italy does not do much”, she was “surprised that it had proved impossible to find data” and suggested to push Europe to develop guidelines for governments to become more transparent. Ms Goyon called for an EC resolution on innovative financing, and a Spanish NGO representative pointed out that the upcoming Spanish EU presidency is an important advocacy opportunity as well.
Speakers and participants called on the Swedish EU presidency to challenge the European Commission as well as EU member states to follow its positive example and pay their fair share for TB research. “50 million Euro for a prize fund is a very concrete ask” Dr Fournier summed up the calls. “What is needed now is only funding. We would like to see one or two European governments step up to the challenge”, specified Daniel Berman, Deputy Director of MSF’s Access to Essential Medicines Campaign.