Misguided research

In a recent issue of the medical journal The Lancet, two British doctors severely criticised the launch of Hereceptin, a new cancer medication. Alastair Munro and Paddy Niblock (2010) complained about the new drug not healing patients, but merely allowing them to live 11 weeks longer on average. The authors also stated that the price of around 1,000 pounds per week was too much even for a rich country like the United Kingdom.

The authors doubt it makes sense to research such medicines at all. As they pointed out in their comment, patients in China, Costa Rica, Guatemala, Peru and Turkey were treated in the drug trials that were the basis to allow the drug on the market, even though annual per capita public expenditure on healthcare ranges from a mere $ 49 to at most $ 365 in these countries according to WHO statistics. Munro and Niblock do not believe such treatment should be on offer at all given that it merely allows a single person to live a few weeks longer at the expense of radically shrinking the healthcare budget for everyone else.

The doctors stressed that the new cancer medicine was developed because, in spite of negligible benefits, it will generate revenue. They argued that the same medical effect, if not better ones, might be achieved by combining drugs that were on the market already, but that there was no commercial interest in that kind of research.

Their article sheds light on the problems of today's medical research. It sets the wrong priorities in research and pricing, and pushes the state-run healthcare systems even of rich nations to their limits.

No patent solution

Obviously, something is amiss in the way humankind is currently funding medical research. People increasingly wonder whether the protection of intellectual property rights truly promotes the development of the drugs we need. For instance, an independent assessment of 3,000 new active ingredients and applications over 24 years found that only 0.2 % could be considered therapeutic breakthroughs, with another two percent qualifying as clear progress. In contrast, two thirds (68 %) were nothing new, and three percent were already considered unacceptable by the time they were ­approved because they did more harm than good (Prescrire International, 2005).

Under such conditions, research can do harm:
– If it focuses on already treatable diseases, no major progress is to be expected, but funds get tied up that could serve more important research into illnesses for which there still is no good therapy.
– New medicines always pose greater risks than established drugs, because their potential to do harm cannot be entirely understood at the time of drug approval. While that risk may be acceptable in exchange for real therapeutic progress, it is not in the case of drugs with no clear additional benefit.
– New drugs tend to be especially expensive. So unless they bring health benefits, they unnecessarily burden budgets. After all, even innovations without merit will find buyers. Corporations spend considerable money on advertising to ensure that. Such expenses are ultimately passed on to the patients and the public in general that funds government-run health insurances. According to estimates, the pharma industry spends roughly twice as much money on advertising as it does on research (Gagnon und Lexchin, 2008).

Poor countries are especially hard hit. Too little research is done on diseases that affect them (Trouiller et al., 2010 / Cohen et al., 2010). Moreover, these countries often struggle to get the drugs that are already on the market. High pharma prices hurt them more than rich nations.

The patent system does not offer any remedies; to the contrary, it compounds the problem (see box). Today, even industrialised countries are beginning to realise how expensive and ineffective the business model is. The idea of patents is to grant a limited monopoly in order to fund urgently needed healthcare research through high prices. This idea plainly does not work out.

Funding corporate research

There are models that try to provide commercial incentives to stimulate necessary research. But they rarely succeed. The European programme for “orphan drugs” is a telling example. It is about promoting medicines for rare diseases by
– offering governmental consultation services,
– lowering requirements for drug studies, and
– facilitating faster approval, lower fees, and longer data protection.
Nonetheless, only 44 orphan drugs were approved for some 7,000 rare diseases from 2000 to 2007. Most of them turned out to have little or no additional benefits for patients (Joppi, Bertele and Garattini, 2009 / Prescrire International, 2007).

In recent years, the range of (mostly not-for-­profit) research ventures, that focus on the needs of poor countries, has grown considerably. Some of these initiatives concentrate on a specific disease (like HIV/AIDS, tuberculosis, malaria et cetera) or on a certain strategy (like vaccinations, for instance). The Drugs for Neglected Diseases initiative (DNDi) is outstanding: It is based on cooperation of research institutes in the South and the North, and they are working on medicines not only for one single disease, but rather for several under-researched diseases.

Many research ventures are funded by philanthropic foundations and governments. The pharma industry contributes know-how and libraries of active ingredients. All of these projects are subsumed under the category of public-private partnerships (PPP), even though most of these PPPs differ quite a bit from the DNDi in terms of composition and ­objectives.

Some projects are outright dubious. For example, the GAVI Alliance focuses on promoting vaccinations and has tried out a method called “advanced market commitment”. The idea is to create an artificial market by promising to purchase, at a guaranteed price, a large amount of a vaccine that has yet to be developed. There are several snags, however:
– The money is only disbursed once the product is delivered, so only large corporations can afford to finance projects upfront; small research labs, which tend to be quite productive, cannot afford to do so.
– It is very hard to set a price that will cover, but not drastically exceed, development costs.
– Instead of promoting new research GAVI has resorted to a controversial pneumococcal vaccine that had already been developed (Light, 2009). GAVI is now struggling financially because this vaccine is devouring large sums of money that would be better spent on standard vaccines.

When pharmaceutical firms are allowed to take part in setting priorities, it must be kept in mind that they always have their eyes on the bottom line. However praise-worthy the commitment of private donors may be, they also have their preferences. That is why there is a lot of concurrent research on diseases like HIV/AIDS or malaria, which attract a lot of public attention. Diseases like leprosy and dengue fever, however, remain neglected (Cohen et al, 2010).

Corporate research is also haunted by flawed results. Some studies are designed from the outset to cast a positive light on a particular medication. One way of doing so is simply to not compare this new product with standard therapies and direct competitors. Studies that cast doubt on a particular product, moreover, are rarely published at all – and misinterpreted if they are published. A study of 12 antidepressants once revealed that two thirds of all of the test-series with negative results had never been published. In view of such figures it is no surprise that, though 94 % of the studies that were published demonstrated the effectiveness of new pharmaceuticals, the US Food and Drug Administration only found half of them useful (Turner et al., 2008).

Furthermore, pharma-research PPPs suffer from an underlying paradox. They try to mobilise funds or provide incentives for corporations to make additional money through research, but they do not challenge the dysfunctional research system itself. The point is that it is always society and patients who fund all medical research by paying patent-inflated prices. No doubt, the public should therefore have more say in the direction of pharmaceutical research.

More state research

A lot is being done to promote corporate research into pharmaceuticals, but it is typically overlooked that most basic research is funded by the public purse. Researchers from universities and government-run institutes were the pioneers in many therapeutic breakthroughs. The active ingredients for five of the first six medicines for HIV/AIDS, for instance, were discovered in public research facilities. According to the Global Forum for Health Research, some 41 % of expenditures on health research worldwide was funded by public bodies in 2005. If tax exemptions for corporations are considered too, the share of public funding rises to 57.4 % of the total (Light, 2006).

Medical research therefore has to be revisited. Governments have to play a greater role in deciding what is funded and which priorities are set. Currently, the model of prize funds is being discussed. Public as well as private researchers would be allowed to apply for money from such funds, and the funds would reward useful new medicines. The research results would then be a public good (Love and Hubbard, 2009).

A growing number of researchers are also warming to the idea of open-source models without patents. Many are frustrated because the mushrooming of patents on active ingredients and procedures means that they do not have access to small, but important building blocks they need to do further research.

For poor countries in particular, it matters very much to become more involved in defining research goals. After all, local experts are better at setting priorities than some far-away researchers. In rich nations, moreover, it is generally understood that public funding must always include an overhead for the institute concerned. In developing countries, how­ever, the money is often earmarked exclusively for the project in question. Such difficulties add to the brain-drain of researchers moving to rich nations.

Practical action

As a way of promoting pharmaceutical research, patents have failed large parts of humanity. They are increasingly causing problems in rich countries too. Even the World Health Organisation is now demanding a reform of healthcare research.

It will take time for new approaches like prize funds and open source to take root. Small steps, however, can also help to bring research back onto a more promising track. For instance, the approval criteria for new medicines should become stricter, especially in advanced nations. New medications should only be allowed to go on sale if they have an evident additional benefit. In other words, they would have to perform better than the best standard therapies in terms of reducing mortality and fighting disease.

It is essential to establish a public register for drug studies, and labs should be forced to publish all of their results completely. That would help to assess whether a medicine does more good than harm. Indeed, such registers should also cover medicines already on sale so they could be objectively assessed too. Independent and transparent cost-benefit analyses would be another way to encourage better healthcare and provide incentives to develop more useful medicine. Research should only be subsidised if it results in better drugs, and prices should only be set in view of their additional benefits for patients.

Germany’s Federal Ministry of Education and Research (BMBF) plans to provide greater support to research on neglected and poverty-related diseases. At the World Health Forum in Berlin in October, it announced that it will allocate ­€ 20 million to fund product-­development partnerships (PDPs) over a term of four years.

PDPs link know-how from science, industry and civil society in order to develop methods for prevention, diagnosis and treatment. The most important poverty-related diseases are tuberculosis, malaria and HIV/AIDS. Dengue fever, leprosy and African sleeping sickness are regarded as diseases neglected by science, along with 11 other tropical diseases which also mainly affect people in developing countries.

The pharma industry is not interested in researching these diseases. The people most affected only have little purchasing power. Therefore, corporations cannot hope to charge high prices and rake in huge profits while research results enjoy patent protection. Experts speak of a 10:90 gap, with only 10 % of global resources for health research being devoted to diseases which affect
90 % of humankind.

Non-profit PDPs are typically funded by public donors and private philanthropists. The Bill & Melinda Gates Foundation is a prominent player in this area. The PDPs are able to make research results and products available to those affected at low prices.

The German Foundation for World Population (DSW), a non-governmental organisation, supports the BMBF’s research initiative on neglected diseases. DSW’s executive director Renate Bähr said: “I am pleased that the BMBF is finally making a contribution towards closing the gap in research for neglected diseases and is including product-development partnerships in its activities.”

Nonetheless, she is critical of the ministry because it did not include research on tuberculosis and HIV/AIDS in its new initiative. According to the DSW, women in particular need preventive ­methods such as microbiocides so they are able to protect themselves against HIV/AIDS irrespective of their partner. Bähr has called on the Federal Government to include “research on HIV/AIDS prevention and tuberculosis” in the next funding round. She points out that the results of recent studies on microbiocides and HIV/AIDS vaccines were promising. (cs)