Event Information

As the prevalence of drug-resistant bacteria continues to rise, there is a pressing need for new drugs to combat infections by these organisms. However, research and development in this area has slowed, creating a public health concern that we lack the drugs necessary to treat multi-drug resistant infections. Challenges to promoting antibacterial drug development may be scientific, methodological, regulatory, or economic in nature.

On Wednesday, May 9, 2012, the Engelberg Center for Health Care Reform convened an expert workshop, "Facilitating Antibacterial Drug Development,” that explored solutions to methodological and regulatory challenges that could make the development process more efficient. This meeting brought together diverse multi-stakeholder experts—including medical product developers, health care professionals, researchers, patient advocates, representatives of the U.S. Food and Drug Administration, and other groups—to explore the following issues:

• Existing paradigms for antibacterial drug development;
• Novel approaches to further antibacterial drug development, including use of pharmacokinetics and pharmacodynamics, Bayesian methods, innovative clinical trial designs, new data sources, alternate clinical endpoints, and new regulatory tools; and
• Short- and long-term opportunities to advance the antibacterial drug development enterprise through collaboration among stakeholders, improved regulatory science, and other means.

For more information on FDA’s Antibacterial Drug Development Task Force, click here.

Event Materials

• May 9 Event Summary
• Antibacterial Drug Development Participant List
• Facilitating Antibacterial Drug Development Agenda
• Facilitating Antibacterial Drug Development Discussion Guide
• Panel 1 Brad Spellberg Presentation
• Panel 1 George Talbot Presentation
• Panel 1 John Powers Presentation
• Panel 1 Thomas Fleming Presentation
• Panel 2 George Drusano Presentation
• Panel 2 Scott Emerson Presentation
• Panel 3 Daniel Benjamin Presentation
• Panel 3 Edward Cox Presentation
• Panel 3 John Rex examples
• Panel 3 John Rex Presentation
• Panel 4 Helen Boucher Presentation

Event Information

As part of ongoing cooperative work with the U.S. Food and Drug Administration, the Engelberg Center for Health Care Reform has formed a council to bring together expert perspectives on the challenges facing antibacterial drug development. Designed to include representatives from academia, patient advocacy groups, industry, providers, and government agencies, the Brookings Council on Antibacterial Drug Development (BCADD), will convene twice a year to discuss pressing issues in the treatment of infectious diseases and potential steps to address them.  

The first BCADD meeting, held on August 30, 2012, brought stakeholders together to discuss the following:

• Ongoing antibacterial initiatives at FDA and the Clinical Trials Transformation Initiative
• Statistical and methodological approaches that could be harnessed to improve the efficiency of antibacterial drug development
• Balancing benefit-risk and uncertainty considerations with public health needs
• Next steps for council action

For more information on FDA’s Antibacterial Drug Development Task Force, click here.

Event Materials

• 30 antibacterial drug development summary
• Presentation Slides
• FINAL BCADD Discussion Guide 20120828
• FINAL May 9 Summary 20120828
• Participant List_Final

Event Information

As part of an ongoing cooperative agreement with the U.S. Food and Drug Administration (FDA), the Engelberg Center for Health Care Reform at Brookings has formed the Brookings Council on Antibacterial Drug Development (BCADD) to identify steps to address the major technical, regulatory, and financial barriers impeding antibacterial drug development. At the first meeting of the BCADD, stakeholders emphasized the importance of concentrating on discrete policy and program areas to revitalize the antibacterial drug development enterprise.

BCADD convened a diverse group of stakeholders, including FDA officials, industry and biotech representatives, payers, providers, clinicians, and academic researchers Wednesday, February 27, 2013, to discuss two of the economic challenges facing antibacterial drug development:

• Better understanding the potential role of incentives in drug discovery and development; and
• Identifying potential reimbursement models that can support both stewardship and expanded investment for antibacterial drug products.

Event Materials

• meeting summary 20130925 FINAL
• Discussion Guide
• Participant List
• Presentation

Event Information

Antibacterial drug resistance is a global public health threat poised to worsen due to the combination of the inappropriate use of existing drugs and a marked decline in innovative antibacterial drug development. In order to tackle this problem, stakeholders must consider comprehensive strategies that address both drug development and stewardship.

On February 7, the Engelberg Center for Health Care Reform convened an expert workshop, “Modernizing Antibacterial Drug Development and Promoting Stewardship” to explore a two-pronged approach to combating antibacterial drug resistance that includes: 1) the development of pathogen-focused antibacterial drugs that target the most serious public health threats; and 2) stewardship efforts for all antibacterial products in order to preserve their utility. Participating stakeholders included experts from the drug development and health care industries, the clinical community, government, and academia. These stakeholders shared their insights on potential frameworks and evidentiary considerations for pathogen-focused drug development, and efforts underway to promote the appropriate use of commonly used antibacterial drugs in the ambulatory care setting.

Event Materials

• Antibiotic Development Slides
• 07 antibacterial expert workshop discussion guide
• 07 antibacterial expert workshop public agenda
• 07 antibacterial expert workshop meeting summary

Event Information

Antibacterial drugs are a critical component of the nation’s public health armamentarium, and have saved millions of lives by preventing and treating a range of bacterial infections. However, antibacterial drug development has been hampered by challenges unique to the antibacterial drug market, which have stifled innovation and left patients and providers with fewer options to treat increasingly resistant infections. One consequence of the dwindling antibacterial drug pipeline has been a reduction in effective oral antibacterial drug treatment options, which are particularly important in the ambulatory and transitional care contexts. Recent proposals to re-invigorate the antibacterial pipeline are geared towards serious infections treated in the inpatient setting, which may lead to a greater focus on intravenous therapies. However, addressing both current and future needs in the infectious diseases space will require a balanced mix of both oral and parenteral antibacterial drugs.

In cooperation with the U.S. Food and Drug Administration (FDA), the Engelberg Center for Health Care Reform at Brookings held an expert workshop on November 20, 2014, to identify the most promising strategies to support oral antibacterial drug development. Participating stakeholders included experts from the drug development and health care industries, the clinical community, government, and academia. These stakeholders shared their insights on potential regulatory, scientific, and economic strategies to reinvigorate the oral antibacterial drug pipeline. 

Event Materials

• Reinvigorating the Oral Antibacterial Drug Development Pipeline Agenda
• Reinvigorating the Oral Antibacterial Drug Development Pipeline Discussion Guide
• Biographies 20141118
• Reinvigorating the Oral Antibacterial Drug Development Pipeline Slide Deck

An academic-industrial partnership published last January in the prestigious journal Nature the results of the development of antibiotic teixobactin. The reported work is still at an early preclinical stage but it is nevertheless good news. Over the last decades the introduction of new antibiotics has slowed down nearly to a halt and over the same period we have seen a dangerous increase in antibiotic resistant bacteria.

Such is the magnitude of the problem that it has attracted the attention of the U.S. government. Accepting several recommendations presented by the President’s Council of Advisors on Science and Technology (PCAST) in their comprehensive report, the Obama Administration issued last September an Executive Order establishing an interagency Task Force for combating antibiotic resistant bacteria and directing the Secretary of Human and Health Services (HHS) to establish an Advisory Council on this matter. More recently the White House issued a strategic plan to tackle this problem.

Etiology of antibiotic resistance

Infectious diseases have been a major cause of morbidity and mortality from time immemorial. The early discovery of sulfa drugs in the 1930s and then antibiotics in the 1940s significantly aided the fight against these scourges. Following World War II society experienced extraordinary gains in life expectancy and overall quality of life. During that period, marked by optimism, many people presumed victory over infectious diseases. However, overuse of antibiotics and a slowdown of innovation, allowed bacteria to develop resistance at such a pace that some experts now speak of a post-antibiotic era.

The problem is manifold: overuse of antibiotics, slow innovation, and bacterial evolution.

The overuse of antibiotics in both humans and livestock also facilitated the emergence of antibiotic resistant bacteria. Responsibility falls to health care providers who prescribed antibiotics liberally and patients who did not complete their prescribed dosages. Acknowledging this problem, the medical community has been training physicians to avoid pressures to prescribe antibiotics for children (and their parents) with infections that are likely to be viral in origin. Educational efforts are also underway to encourage patients to complete their full course of every prescribed antibiotic and not to halt treatment when symptoms ease. The excessive use of antibiotics in food-producing animals is perhaps less manageable because it affects the bottom line of farm operations. For instance, the FDA reported that even though famers were aware of the risks, antibiotics use in feedstock increased by 16 percent from 2009 to 2012.

The development of antibiotics—perhaps a more adequate term would be anti-bacterial agents—indirectly contributed to the problem by being incremental and by nearly stalling two decades ago. Many revolutionary innovations in antibiotics were introduced in a first period of development that started in the 1940s and lasted about two decades. Building upon scaffolds and mechanisms discovered theretofore, a second period of incremental development followed over three decades, through to 1990s, with roughly three new antibiotics introduced every year. High competition and little differentiations rendered antibiotics less and less profitable and over a third period covering the last 20 years pharmaceutical companies have cut development of new antibiotics down to a trickle.

The misguided overuse and misuse of antibiotics together with the economics of antibiotic innovation compounded the problem taking place in nature: bacteria evolves and adapts rapidly.

Current policy initiatives

The PCAST report recommended federal leadership and investment to combat antibiotic-resistant bacteria in three areas: improving surveillance, increasing the longevity of current antibiotics through moderated usage, and picking up the pace of development of new antibiotics and other effective interventions.

To implement this strategy PCAST suggested an oversight structure that includes a Director for National Antibiotic Resistance Policy, an interagency Task Force for Combating Antibiotic Resistance Bacteria, and an Advisory Council to be established by the HHS Secretary. PCAST also recommended increasing federal support from $450 million to $900 million for core activities such as surveillance infrastructure and development of transformative diagnostics and treatments. In addition, it proposed $800 million in funding for the Biomedical Advanced Research and Development Authority to support public-private partnerships for antibiotics development.

The Obama administration took up many of these recommendations and directed their implementation with the aforementioned Executive Order. More recently, it announced a National Strategy for Combating Antibiotic Resistant Bacteria to implement the recommendations of the PCAST report. The national strategy has five pillars: First, slow the emergence and spread of resistant bacteria by decreasing the abusive usage of antibiotics in health care as well as in farm animals; second, establish national surveillance efforts that build surveillance capability across human and animal environments; third, advance development and usage of rapid and innovative diagnostics to provide more accurate care delivery and data collection; forth, seek to accelerate the invention process for new antibiotics, other therapeutics and vaccines across all stages, including basic and applied research and development; finally, emphasize the importance of international collaboration and endorse the World Health Organization Action Plan to address antimicrobial resistance.

University-Industry partnerships

Therefore, an important cause of our antibiotic woes seems to be driven by economic logic. On one hand, pharmaceutical companies have by and large abandoned investment in antibiotic development; competition and high substitutability have led to low prices and in their financial calculation, pharmaceutical companies cannot justify new developmental efforts. On the other hand, farmers have found the use of antibiotics highly profitable and thus have no financial incentives to halt their use.

There is nevertheless a mirror explanation of a political character.

The federal government allocates about $30 billion for research in medicine and health through the National Institutes of Health. The government does not seek to crowd out private research investment; rather, the goal is to fund research the private sector would not conduct because the financial return of that research is too uncertain. Economic theory prescribes government intervention to address this kind of market failure. However, it is also government policy to privatize patents to discoveries made with public monies in order to facilitate their transfer from public to private organizations. An unanticipated risk of this policy is the rebalancing of the public research portfolio to accommodate the growing demand for the kind of research that feeds into attractive market niches. The risk is that the more aligned public research and private demand become, the less research attention will be directed to medical needs without great market prospects. The development of new antibiotics seems to be just that kind of neglected medical public need. If antibiotics are unattractive to pharmaceutical companies, antibiotic development should be a research priority for the NIH. We know that it is unlikely that Congress will increase public spending for antibiotic R&D in the proportion suggested by PCAST, but the NIH could step in and rebalance its own portfolio to increase antibiotic research. Either increasing NIH funding for antibiotics or NIH rebalancing its own portfolio, are political decisions that are sure to meet organized resistance even stronger than antibiotic resistance.

The second mirror explanation is that farmers have a well-organized lobby. It is no surprise that the Executive Order gingerly walks over recommendations for the farming sector and avoid any hint at an outright ban of antibiotics use, lest the administration is perceived as heavy-handed. Considering the huge magnitude of the problem, a political solution is warranted. Farmers’ cooperation in addressing this national problem will have to be traded for subsidies and other extra-market incentives that compensate for loss revenues or higher costs. The administration will do well to work out the politics with farmer associations first before they organize in strong opposition to any measure to curb antibiotic use in feedstock.

Addressing this challenge adequately will thus require working out solutions to the economic and political dimensions of this problem. Public-private partnerships, including university-industry collaboration, could prove to be a useful mechanism to balance the two dimensions of the equation. The development of teixobactin mentioned above is a good example of this prescription as it resulted from collaboration between the university of Bonn Germany, Northeastern University, and Novobiotic Pharmaceutical, a start-up in Cambridge Mass.

If the NIH cannot secure an increase in research funding for antibiotics development and cannot rebalance substantially its portfolio, it can at least encourage Cooperative Research and Development Agreements as well as university start-ups devoted to develop new antibiotics. In order to promote public-private and university-industry partnerships, policy coordination is advised. The nascent enterprises will be assisted greatly if the government can help them raise capital connecting them to venture funding networks or implementing a loan guarantees programs specific to antibiotics.  It can also allow for an expedited FDA approval which would lessen the regulatory burden. Likewise, farmers may be convinced to discontinue the risky practice if innovation in animal husbandry can effectively replace antibiotic use. Public-private partnerships, particularly through university extension programs, could provide an adequate framework to test alternative methods, scale them up, and subsidize the transition to new sustainable practices that are not financially painful to farmers.

Yikun Chi contributed to this post

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