Letter to the House of Representatives Energy and Commerce Committee and Health Subcommittee about the Generating Antibiotic Incentives Now (GAIN) Bill

The Honorable Fred Upton, Chairman, Energy and Commerce Committee
The Honorable Henry A. Waxman, Ranking Member, Energy and Commerce Committee
The Honorable Joe Pitts, Chairman, Health Subcommittee
The Honorable Frank Pallone, Jr., Ranking Member, Health Subcommittee

United States House of Representatives

Washington, DC 20515

March 8, 2012

Dear Chairman Upton, Ranking Member Waxman, Chairman Pitts, Ranking Member Pallone, and Members of the Health Subcommittee,

As members of the nonprofit Patient, Consumer, and Public Health Coalition, we share your concerns about the need for new antibiotics. The Generating Antibiotic Incentives Now (GAIN) bill focuses on providing incentives to pharmaceutical companies, which is important. However, some antibiotics are much more important than others. For example, approximately 20% of antibiotic prescriptions are used for sinus infections, and new research indicates they are completely ineffective because placebo works just as well. The bill as currently drafted does not focus on the areas of greatest public health need. Unfortunately, as currently written, this bill could have the unintended consequences of increasing antibiotic resistance and increasing health care costs while not addressing the need for new antibiotics to save the lives of patients when other antibiotics fail.

The following changes to the bill would help focus on the areas of most urgent need and ensure that the problem of antibiotic resistance is effectively addressed:

1. The focus of incentives should be on patients and their diseases, not organisms.

• Patients present with diseases, like pneumonia and meningitis, not with organisms. The organism that is causing a patient’s disease often is not known at the time an antibiotic is prescribed.

• Many organisms cause no problems at all. It is only when they cause disease that they harm human health.

• Antibiotics are needed for diseases where there are few treatments available. Resistance focuses on the percentage of organisms that are not killed by a drug (even when enough organisms are killed to save the patient), but the focus should instead be on which drugs work to cure a disease, and we should provide incentives in areas only where few safe and effective treatments are available.

• Organisms that cause disease will rapidly change over time so the list will be outdated quickly.

• FDA approves drugs based on “recognized diseases or conditions” and organisms are neither.

2. The focus should be on serious and life–threatening diseases, not on diseases that don’t require treatment.

• The impact on public health of “resistance” in the test tube is minimal in the many situations where patients recover regardless of whether they receive an antibiotic or not. Two recent NIH-funded studies of ear infections in children and one published last month on sinus infections in adults showed no benefit of antibiotics compared to placebo on patient-centered outcomes. This means that “resistance” in the test tube for antibiotics used for ear infections or sinusitis won’t have an impact on patients’ health. Use of antibiotics in these situations increases antibiotic resistance, increases side effects for patients, and increases health care costs without any benefit to patients. The GAIN Act as currently written would give priority to antibiotics for those uses as much as for life-saving uses.

• The lack of effective treatments for serious and life-threatening diseases results in death or serious disability; therefore, antibiotics that are effective for serious and life-threatening diseases will have the greatest impact on saving lives and the quality of life. Let’s revise the GAIN Act to focus on those antibiotics.

• There is no evidence that antibiotics administered for self-resolving diseases (such as ear infections and sinus infections) prevent “progression” to more serious disease. On the contrary, research shows that children who receive antibiotics for ear infections have more subsequent symptomatic ear infections than children who don’t receive antibiotics. An FDA analysis of all placebo-controlled trials of ear infections showed that antibiotics were no better than placebo in preventing other more serious infections in children with ear infections.

3. There should be valid scientific evidence that new antibiotics address an unmet medical need.

• FDA should focus its resources on quickly reviewing new drugs that offer benefits over existing drugs. This can mean better safety or convenience or improved effectiveness. Just being “another option” does not mean a drug meets an unmet medical need. A basic tenet of regulatory review is the drug should have evidence to support the pharmaceutical companies’ claims for it. Unfortunately, the GAIN Act does not focus FDA resources in this way.

• FDA should not approve drugs today hoping they will be effective for some unmet need sometime in the future. Resistance can develop for any antibiotic once it is approved and used. Therefore, a drug approved today won’t necessarily meet future needs. Unfortunately, the GAIN Act would provide incentives based on future promise and does not assure there is evidence for meeting today’s unmet needs.

• Approving drugs based on future promise subverts the Congressional intent in the Food Drug and Cosmetic Act that sponsors should provide evidence for the claims made for them under conditions of use in the label.

• The notion that all antibiotics inherently meet some need is not supported by evidence. Half of the antibiotics approved in the last 30 years are off the market either due to harms, lack of effectiveness, or lack of sales. The GAIN Act as currently drafted would give priority to many antibiotics that are unlikely to save lives or improve health in a meaningful way.

4. Any reassessment of FDA guidances should be based on the current regulatory standard of “substantial evidence” from “adequate and well-controlled trials” which is already spelled out in law and regulation.

• While the feasibility of trial designs is a matter of opinion, the scientific standard of evidence is clearly spelled out in law and FDA regulations as “substantial evidence” from “adequate and well controlled trials.” FDA should not approve antibiotics based on test tube tests and animal models if there are no data from clinical trials in humans with diseases. Unfortunately, the GAIN Act does not require clinical trials to show that the drugs that receive incentives address the problems of antibiotic resistant diseases. It is essential to add language to the GAIN Act to prevent use of test tube or animal studies or other exploratory analyses alone as the basis for approval for diseases due to resistant pathogens.

• Scientific validity is the basis for the ethics of the testing of drugs on humans; therefore, scientifically invalid trials are unethical even if they are “feasible.”

5. The bill should include provisions for antibiotic stewardship and appropriate use

• New drugs alone will not address the problem of antibiotic resistance. We need to judiciously use the drugs we already have.

• GAIN says nothing about using drugs wisely. It should include provisions to measure the appropriateness of drug use, and provide FDA with regulatory authority to develop and enforce risk mitigation strategies to prevent antibiotic resistance of currently available drugs as well as new drugs as they are approved.

The current broad definition of drugs eligible for the incentives in the GAIN Act would cost taxpayers and the government millions of dollars while worsening the problem of antibiotic resistance. Narrowing the definition in the bill based on valid scientific evidence would benefit patients while limiting the spread of antibiotic resistance.

For the above reasons, members of the Patient, Consumer, and Public Health Coalition listed below strongly oppose the GAIN Act as it is currently written. We would welcome the opportunity to work with you to make the small revisions that would make an enormous difference in the benefits of the bill to patients across the country.


Jacobs Institute for Women’s Health
National Research Center for Women & Families
National Women’s Health Network
Our Bodies Ourselves
THE TMJ Association