The threat of the development of drug resistant bacterial infections has cast a shadow over public health systems and hospitals for several years. According to Dr Keiji Fukuda, WHO’s Assistant Director-General for Health Security, describes antibiotic resistance as "one of the most serious global health threats of our time". The UK Review on Antimicrobial Resistance, chaired by Jim O'Neill, seeks to bring to the fore the human and economic costs of inaction and has set forward proposals to encourage the development of new antibiotic products.
The development of penicillin in the 1930s opened up our toolkit to treat bacterial infections. The 20th century saw the development of treatments for tuberculosis, HIV and malaria, amongst others. The development of antimicrobial resistance to existing treatments has the potential to undermine the advancements made and leave patients with no effective treatments against a previously curable disease. The first paper published by the Review on Antimicrobial Resistance (the "O'Neill Review") in December 2014 estimated that drug resistant strains of malaria, HIV, tuberculosis and other bacterial infections could lead to the loss of 10 million lives annually by 2050.
The economic cost of antimicrobial resistance is based on the reduction in GDP caused by premature deaths resulting from increased drug resistance. Research commissioned by the O'Neill Review estimated that this could amount to a loss of US$60-100 trillion between now and 2050. While there are no doubt some difficulties with accurately predicting economic consequences over the course of the next 35 years, the staggering financial cost makes a compelling case for investing now in the development of new antibiotics.
caduceusThe issue is not limited to developing countries, although the impact may be different in different geographic regions. The rise of "superbugs" in Western hospitals would increase the risk of any surgery or hospitalisation due to the risk associated with infection and potentially raise infection rates amongst healthcare workers. A resurgence of malaria in China and Brazil would impact export sectors. The research suggests that 40% of deaths in 2050 would be in Africa – undermining the work done now to overcome the human and financial costs of HIV, malaria and TB on the continent. The World Health Assembly in May 2015 endorsed a global action plan to tackle antimicrobial resistance, reflecting a global consensus that antimicrobial resistance poses a profound threat to human health.
The antibiotics market generates annual global sales of US$40 billion. Despite this large market, the latest report of the O'Neill Review published in May 2015 identifies why investment in the development of new antibiotics is not necessarily a commercially attractive opportunity for research. To minimise drug resistance, antibiotics should only be used when necessary. In particular, when a new antibiotic is developed its use needs to be limited to counter drug resistant strains rather than being prescribed to all patients immediately. Where a company's profits are linked to the sales of a drug, the nature of best practice for prescribing antibiotics means that the commercial return following the launch of the product is unpredictable. The clinical need for the drug may only occur after patent protection has expired, meaning the innovator could be unable to recoup its R&D costs through sales. Extending market exclusivity (through the means of supplementary protection certificates or orphan designation) are incentives that still rely on the volume of sales of the product in the years immediately after product launch.
The O'Neill Review has proposed that upfront payments to successful drug developers could de-link the profitability of drugs from the volume of sales. An upfront payment would mean that the drug developer shared the risk of development with public funders. The O'Neill Review estimates a lump sum of between US$1-1.3 billion to cover the average development costs of a new drug. The system could also vary the upfront payments to be higher in areas of greater unmet need. Implementation throws up various challenges – what conditions are placed on the drugs supported by the system? Would there be an obligation to offer the drugs at an affordable price in low and middle income countries? Who funds the upfront payments and who decides the amount?
The O'Neill Review also proposed the establishment of an Innovation Fund to boost funding for early stage research into new products and diagnostic tools. Two of the most significant funders of research in the area are the US NIH and the European Commission. For example, the EU Innovative Medicine's Initiative ("IMI") has seven projects directed to antimicrobial resistance under the banner of "New Drugs 4 Bad Bugs" (ND4BB) with a total budget of €703 million. The O'Neill Review proposes that the Innovation Fund would be funded by industry (in the amount of US$2 billion over five years). The fund would create opportunities for industry in the medium term, particular if other commercial incentives such as upfront payments are implemented.
The O'Neill Review will publish further reports later this year, culminating in its final report to be published by summer of 2016.
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