Lead Author: Kevin Outterson
Organization: Boston University School of Law
Country: USA

ABSTRACT

Due to antibiotic resistance, patients could lose access to the most important class of drugs in human history. But while resistance is a serious issue, equally troubling is the unwarranted death of 455,000 children each year from susceptible bacteria that could be treated with existing generic antibiotics. Antibiotics suffer from three simultaneous crises: access, conservation, and innovation. Solutions proposed include antibiotic delinkage, paying for antibiotic innovation based on value, not volume of sales.

Submission 

1. Impact on remedying policy incoherence
A number of initiatives are underway to address the crisis of antibiotic resistance. Some focus on innovation – creating new antibiotics to replace those lost to resistance (Chatham House 2015, AMR Review 2015a). Others focus on conservation - reducing the need for antibiotics through infection control, vaccines, clean food and water, and antibiotic stewardship (US National Action Plan 2015). Access to antibiotics is a third area that is important but frequently overlooked. More than 455,000 children under 5 die from susceptible bacteria that could be treated with existing drugs (Laxminarayan 2016).
The first policy incoherence is that all three of these goals – access, conservation, & innovation – undermine the others and therefore must be pursued in a coordinated fashion.

Second, antibiotic resistance spans both human and animal health. Many emerging infectious diseases have zoonotic origins and low-value use of antibiotics in agriculture drives resistance, but antibiotics also play an important role in animal health in the food supply. Any solution will require tradeoffs and coordination between these two sectors (AMR Review 2015b).
2. Impact on public health
In high-income countries, significant declines in infectious disease mortality pre-dated the introduction of antibiotics. Most of the declines in that period can be attributed to public health interventions, including clean water, clean food, infection control, and environmental control of waste. Nevertheless, the introduction of antibiotics was a signal event in the battle against infectious disease: antibiotics are perhaps the single most valuable drug class in human history. Much of modern medicine depends on it (Teillant 2015).
In many low- and middle-income countries, investment in public health infrastructure lags, resulting in a much higher burden of infectious disease. In these settings, antibiotics perform an additional function: compensating for the weaknesses in public health infrastructure (Laxminarayan 2015).
Therefore, preserving antibiotic effectiveness is a foundation for medical care, population health, and as a key interim tool while public health infrastructure is being improved around the world. Knowing that antibiotics are at risk should prompt additional investments in public health.
3. Impact on human rights
The unwarranted death of 455,000 children under five is a major violation of human rights.
4. Implementation
Conservation & Access: Solutions to the antibiotic access crisis do not require waiting for a new drug to arrive; existing treatments are effective. Nor are patents a major barrier; most of these drugs are off patent. In addition, the WHO Global Action Plan serves as a model for conservation and access efforts. Most of this foundational work is completed; we can focus on implementation immediately, although much work remains in coordination between human and agricultural uses.
Innovation: Despite our best efforts on conservation, new drugs will eventually be required, but they must be brought to the market with guaranteed global access and with incentives in place to support conservation. Access, conservation and innovation must be simultaneously addressed, across both human medicine and agriculture.
Political and civil society mobilization on antibiotic resistance has never been higher. Many stakeholder are currently involved – and more every day – including efforts at IMI/DRIVE-AB, BARDA, PACCARB, AMR Review, Chatham House, Center for Global Development, World Bank, European Investment Bank, Medical Research Council, G7, G20, WHO, DNDi, CDC, ECDC, NIH, Longitude Prize, ReACT, CDDEP, Wellcome Trust, Pew Charitable Trusts, the Bill & Melinda Gates Foundation, and others. Some key points about this process:
First, antibiotics suffer from a particular form of neglect, which is quite different from Chagas, human African trypanosomiasis, Ebola and other neglected diseases. Most diseases treated by antibiotics are globally prevalent. High-income markets, if properly functioning, should be sufficient to drive innovation. If so, some of the goals of the High-Level Panel might be met by articulating and supporting delinkage innovation reforms already in various stages of development (KEI/MSF 2016, AMR Review 2015a, DRIVE-AB 2016, Chatham House 2015, Love 2009, CEWG 2012), with the proviso that leadership is required to ensure that the fruits of that innovation are fully available at generic costs of production to low-income populations.
Second, for antibiotics in particular, coordination with diagnostics and vaccines are key. Most antibiotics are taken in a cloud of diagnostic uncertainty, which leads to significant waste and clinical failure. The best infection is the one that did not occur due to vaccination. The MSF Fair Shot campaign and the Longitude Prize should be amongst the most important near-term policy objectives for any global effort against resistant bacteria.
Third, the High-Level Panel should call for a global antibacterial threat assessment, building on the recent US CDC effort (CDC 2013) (and the ECDC effort currently underway), but with the world in mind. This threat assessment can be used to set research priorities, but more importantly it should guide priority setting at other research institutions like NIH and Wellcome Trust. Governments will increase funding for basic research on bacteria in the next few years. University labs are eager to get to work. A global threat assessment could help focus more than a billion dollars in research efforts over the next decade.

Fourth, the High-Level Panel can help design a sustainable financing mechanism for antibiotic-resistant bacteria. Three models include revisions to the flawed priority review voucher system (Outterson & McDonnell 2016), contractual funding for big science such as CERN and the International Space Station (DRIVE-AB 2016), and an antibiotic user fee (Hollis & Ziana 2013, 2014; Outterson & Hollis 2016). Resistance is a battle fought over decades; bacterial evolution will not resign the field. Our efforts must be similarly relentless and sustainable.
 

Bibliography and References

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