My name is Dr. Margaret Dayhoff-Brannigan and I am a senior fellow at the National Center for Health Research. Our research center scrutinizes scientific and medical data and provides objective health information to patients, providers and policy makers. We do not accept funding from drug companies, and therefore I have no conflicts of interest.
Thank you for the opportunity to speak here today.
I completed my Ph.D. in Biochemistry and Molecular Biology at the Johns Hopkins School of Public Health. A few years ago I lost my grandfather to a hospital acquired antibiotic resistant infection. I bring a perspective as both a researcher and someone personally affected by the need for safe and effective antibiotics today.
Antibiotic resistance and the inability to treat common infections is an increasingly urgent public health crisis which affects everyone, especially some of the most vulnerable in our society. Finding treatment options for unmet populations is urgently important but ineffective antibiotics lead to an increase in antibiotic resistance. Noninferiority trials provide limited information – not enough to provide the best treatment for patients and certainly not enough to reduce resistance. Unfortunately, the benefits of new antibiotics over existing antibiotics are not well established by clinical trials.
Many drugs approved based on data from noninferiority trails are subsequently withdrawn from the market. Examples include fluoroquinolones and cephalosporins many of which were withdrawn for safety concerns. In fact, among 61 new antibiotics approved between 1980-2009, 43% were later withdrawn for safety or efficacy reasons. This rate is about 3 times as often as the 13% of non-antibiotics drugs approved over the same time period.
Withdrawn antibiotics pose risks for patients receiving them, and increase the risk of developing resistant pathogens that could spread. We must ensure that proper clinical trials are preformed to reduce the number of antibiotics that are unsafe and ineffective.
Ten new antibiotics by 2020 will not help us if they are withdrawn later for safety of efficacy.
Superiority trials are the best way to test new antibiotics for use in patients with unmet needs. New antibiotics need to be tested in patient populations like those that will be getting the drug, not in healthy populations. This is important because often bacterial infections can be self-resolving in healthy populations, therefore biasing the results. Also, patients with resistant infections do not react to treatments in the same way as patients with susceptible infections. The health of the patient and whether they have other diseases play a large role in the effectiveness of the treatment. So, studying the right type of patients is crucially important.
The proposed “streamlined” approach, which would increase the noninferiority margin in order to do smaller trials, means that patients would take on more risk and will not benefit from the drug. That is not ethical since other options already exist.
To avoid delays in treating populations with resistant infections, we need to develop better methods for accurate diagnosis of particular pathogens. Better diagnostic tools will improve the ability of industry to design clinical trials in appropriate populations.
In conclusion, we want to provide the best treatment for patients and reduce the number of patients put at risk by taking antibiotics that are later withdrawn from the market due to their lack of safety or efficacy. The best way to accomplish both of those goals is to improve the standards for clinical testing. Superiority trails are critical because they will require that these drugs show effectiveness in the population most likely to benefit from the drug.