Sometimes, trial and error just doesn’t cut it—like when you’re determining the effective dose for vaccines and therapies for deadly diseases. You can’t just expose people to anthrax or Ebola and see what happens.
So how do researchers know what dosages will be effective in humans? The Battelle Health & Analytics team applies advanced statistical methods to help answer some of these critical questions. Since 1987, the team has supported studies on many of the most deadly pathogens and chemical agents, including nerve agents and other chemicals used in warfare, deadly pathogens like Ebola and anthrax, and dangerous strains of flu. Their work has been instrumental in assessing the effectiveness of treatments and vaccines and determining the correct dosage for human use.
The Battelle Analytics team supports both government agencies and commercial pharmaceutical companies to accelerate the development and validation of effective treatments for some of today’s most urgent public health and military threats. Using sophisticated analytical, computational and bioinformatics methods, they are able to quickly find meaningful patterns in large volumes of information from non-clinical trials. This work helps researchers target efforts to the most promising treatment options and bridge the gap between alternative models and humans.
Many of the agents and pathogens the team works with are considered too dangerous for traditional human clinical trials, or have natural outbreaks that are too rare to test the efficacy of vaccines and therapies. While it may still be possible to conduct safety testing in humans for these products, there is no direct way to know whether a certain dose of the therapy or vaccine will be effective without exposing people to the chemical or pathogen—which of course would be highly unethical.
Since 2002, the FDA has provided an alternative regulatory pathway for proving the efficacy of therapies and vaccines for deadly pathogens and chemicals. Passed in response to concerns about bio- and chemical warfare after 9/11, the FDA Animal Rule, as it has come to be known, allows alternative models to be used to determine efficacy of new products.
Extrapolating the data from these alternative models to determine potential efficacy and appropriate dosages for humans requires advanced analytical methods. The Battelle Analytics team provides support at every stage of the process:
- validating alternative models to determine whether they provide an appropriate stand-in for human response to the pathogen or chemical under study;
- analyzing data from non-clinical trials to measure response to the therapy or vaccine and efficacy of the product against the pathogen or chemical;
- correlating response to dosage in the alternative model; and
- extrapolating the dosage requirements in the alternative model to determine appropriate human dosages.
For example, to support development of a new vaccine for a deadly pathogen, the analytics team first helps researchers to validate animal models by demonstrating that response to the pathogen is substantially similar to human response. During non-clinical trials of a candidate vaccine, data must be collected and analyzed to determine the level of immune response provoked with different doses of the vaccine. Then additional data is collected to determine how these different measurements of immune response correlate to actual protection if exposed to the pathogen. When the vaccine is tried in humans, researchers look for biomarkers that indicate a similar level of immune response. Similar immune response can be assumed to provide similar levels of protection as seen in the animal model, without exposing human subjects to the disease.
Without the alternative models and statistical methods, development of effective treatments and vaccines for deadly agents would be nearly impossible. Many of the projects that the Battelle Analytics team supports are considered critical for military force readiness and protection of troops against bio-warfare and chemical agents. Other projects have broader implications for public health, such as a flu vaccine study for a potentially deadly strain of flu supported by the National Institutes of Health (NIH) National Institute of Allergies and Infectious Diseases (NIAID). By applying advanced analytical methods, the team is doing their part to make the world a safer and healthier place.