The President’s Council of Advisors on Science and Technology (PCAST) released a report to the president Sept. 18 recommending steps the federal government can take to combat antibiotic resistance.
The PCAST report includes action steps in key components of this issue—human health care, animal agriculture, drug development, and surveillance and response—and includes eight recommendations.
Recommendation 1: Ensure strong federal leadership. The report recommends substantial federal coordination and oversight of efforts to combat antibiotic resistance, including development of a national strategy. It also notes that “[s]uccess in combating antibiotic resistance will require elevating the issue to a national priority.”
In testimony before the council, Pew has advocated for such an initiative, with the goal of preventing infections, improving surveillance, encouraging appropriate use of antibiotics in people and animals, and developing new drugs. Pew was pleased that the administration released, along with the report, a national strategy and executive order setting forth a plan to elevate the issue of antibiotic resistance as PCAST recommended.
- Recommendation 2: Effective surveillance and response for antibiotic resistance. The report recommends that the Centers for Disease Control and Prevention provide $90 million of new funding to support 60 grants to states and major cities to enhance their surveillance, prevention, and response capabilities. It also recommends $190 million a year to establish a national capability for pathogen surveillance based on genome analysis, to include a national laboratory network and reference collection of genome sequences.
This effort would be coordinated by the CDC, with input from the Food and Drug Administration, U.S. Department of Agriculture, National Institutes of Health, Department of Defense, U.S. Department of Veterans Affairs, and National Institute of Standards and Technology. Surveillance of pathogens originating in agricultural operations was not mentioned but acknowledged to be a source of resistant organisms. Pew has encouraged the administration to undertake more comprehensive surveillance of infectious organisms, which would help to inform efforts to curb antibiotic resistance in health care settings and agriculture.
- Recommendation 3: Fundamental research. The report recommends investment in two areas of fundamental research. First, it recommends that the president request $150 million over seven years for research aimed at understanding and overcoming antibiotic resistance, to be supported by NIH, FDA, the Defense Advanced Research Projects Agency, and the Defense Threat Reduction Agency. In testimony to the president’s science advisers that focused on the barriers to drug development, Pew referenced the fundamental scientific questions impeding the ability to combat resistance and mentioned its ongoing work with experts from academia and industry to prioritize the key scientific issues that are hindering drug discovery.
The report also recommends a USDA initiative to develop alternatives to antibiotics in agriculture, including $25 million a year for the Innovation Institute, a collaboration of nonprofit health care organizations, contained in the president’s fiscal year 2015 budget. In response to the need to pursue novel approaches to disease prevention, Pew has worked since 2008 to promote judicious use of antibiotics on farms, because resistant strains of bacteria that develop in food animals can spread to people, and encourages greater engagement by USDA in supporting FDA policy implementation and pursuing important research.
Recommendation 4: Clinical trials with new antibiotics. The report recommends investing $25 million a year in the establishment of a robust national clinical trial infrastructure and common protocols. Pew has pointed to the problems facing clinical trials in antibiotic drug development. For example, the need to start treatment urgently often precludes enrollment in trials and treatment often begins before cultures are available, posing challenges for subject selection. In comments to the House Energy and Commerce Committee’s “21st Century Cures” initiative, Pew proposed a clinical trials network that could be utilized by industry as well as academics to facilitate drug development, particularly for small companies.
The report also recommends new regulatory pathways to evaluate urgently needed antibiotics. Although the report recommends that FDA use its authority to approve products for specific populations with resistant strains (and discourage use in other populations), it also recommends that the administration support legislation authorizing a “Special Medical Use” pathway for antibiotics. Pew has advocated for legislation to authorize FDA to approve antibiotics for limited populations of patients with unmet medical needs and to ensure that physicians understand the promise and limitations of such products.
- Recommendation 5: The federal government should significantly increase economic incentives for developing urgently needed antibiotics. PCAST estimates that an $800 million federal investment would be required to yield one new antibiotic a year. Pew has applauded the Generating Antibiotics Incentives Now (GAIN) Act as an important first step toward increasing economic incentives for antibiotic development. The law increases the potential profits from new antibiotics by giving companies more time to recoup their investment costs by selling their drugs without generic competition. In addition, Pew has called for legislation to establish a regulatory pathway for drugs targeting a limited population; at a conference exploring such a pathway, participants generally agreed that the narrow market established by the pathway would set the stage for premium pricing.
- Recommendation 6: Improving stewardship of existing antibiotics in health care. PCAST recommends implementation of stewardship programs in inpatient and outpatient settings through the use of Medicare levers—such as a Condition of Participation and quality measures, and federal grant requirements—as well as by adopting stewardship programs in federal facilities. It also recommends prizes in the range of $25 million each to stimulate the development of breakthrough diagnostics. Because formal antibiotic stewardship programs in hospitals have been shown to lower antibiotic usage and reduce C. difficile infections, Pew has encouraged the administration to instate such programs on a larger scale.
- Recommendation 7: Limit the use of antibiotics in animal agriculture. The report recommends FDA implementation of its guidance promoting judicious use of antibiotics in agriculture, USDA efforts to educate meat producers and veterinarians regarding compliance with FDA policies, and assessment of the policies’ effectiveness. Pew has recognized the important step FDA made, in Guidance for Industry 213, to eliminate the use of antibiotics for growth promotion but made note of that guidance’s limitations in reining in all inappropriate antibiotic uses. For example, FDA does not make explicit restrictions on what uses merit disease prevention labels, nor does the agency outline when and how it will reevaluate the adequacy and accuracy of disease prevention labels to ensure they effectively prevent bacterial infection and are used no longer than necessary.
In concordance with the report’s claim that a decrease in the overall sales of medically important antibiotics is an important measure of whether FDA’s policies are effective, Pew has demonstrated that the trend of high antibiotics sales for meat and poultry production is indicative of the compounds’ overuse. However, Pew has also made note of the lack of alternative forms of data collection that would more clearly indicate how the drugs are used—in which animals and for what purpose.
- Recommendation 8: Ensure effective international coordination. PCAST recommends support for the World Health Organization’s Global Action Plan and other mechanisms to raise antibiotic resistance as a worldwide priority. In comments to inform WHO’s plan, Pew supported greater international coordination on this issue, because Americans use more antibiotics than people in other industrialized nations—with rates more than twice as high as those in Germany and the Netherlands, for example—and more antibiotics in food animals than many other nations, as well, with U.S. livestock receiving about six times the amount of drugs that Norway and Denmark separately administer.