Federal approval for a new drug can take a decade or more, but researchers at the Johns Hopkins University are studying a way to shave years off the process for medications designed for serious outbreaks of flu, Ebola or other infectious diseases.
The researchers want to conduct trials in emergency rooms where large numbers of people sick with these sometimes deadly diseases often end up. The doctors are poised to launch a trial run at Hopkins during the coming flu season — and using already approved antiviral drugs such as Tamiflu — to show volunteers can quickly and properly be pooled in such environments.
"Normally you do trials in doctors' offices or inpatient wards with 100 or 200 sites often needed over several seasons because each site may only enroll one to three people," said Dr. Richard Rothman, a professor of emergency medicine in the Johns Hopkins University School of Medicine who is co-leading the study. "Here in the emergency department, a lot of people come in sick. That creates an opportunity."
Rothman and Dr. Andrea Dugas, an assistant emergency medicine professor at Hopkins, want to show that emergency departments can cut drug study time while not threatening the built-in protections for volunteers in the U.S. Food and Drug Administration's drug approval process.
Drugs typically go through several rounds of increasingly larger clinical trials to ensure they are first safe and then effective.
The study leaders believe emergency rooms could accelerate the process, especially for drugs further along in the approval pipeline. That could quickly bring the most promising new therapies to large numbers of people ahead of, or even during, a public health emergency, Rothman said.
In the Hopkins study, emergency room staff will evaluate patients for flu no matter their primary complaint and test those with symptoms, Rothman said. They will use a screening process previously developed at Hopkins that has proved effective in identifying flu patients who could benefit from the antivirals.
The test and screening results will be entered into electronic medical records, where doctors will be able to identify good study candidates. Flu patients will be provided all the standard information about the drug's risks and benefits. Those who could benefit from the drugs will get them whether they participate in the study or not. But those who volunteer will be followed by researchers for two weeks and provided follow-up care if needed.
Everyone with the flu also will be instructed on how to care for themselves and prevent spread of the virus, Rothman said.
Most doctors' offices and hospitals don't bother to test for the flu, which typically passes after a miserable week or so of coughing, achiness and fever.
Public health officials track flu outbreaks by logging those who display influenza-like illnesses during visits to doctors and hospitals. The U.S. Centers for Disease Control and Prevention reports that flu sickens millions every year across the country, hospitalizes hundreds of thousands and contributes to the deaths of thousands.
Rothman doesn't anticipate trouble enrolling enough people for the study because the emergency room overflows with sufferers every flu season, which typically begins in late fall and lasts until spring
If researchers are able to show that this is an effective means of enrolling trial participants, the structure could be replicated at other hospitals and the time needed for drug approval could be slashed by two to five years, Rothman said.
Rothman said emergency rooms haven't been considered as study sites in the past because so-called rapid tests didn't exist five years ago for flu or other infections, and emergency rooms weren't equipped to bring patients back to learn their results days or a week later.
Ethical considerations were also a factor; emergency departments can be chaotic and scary, and people who go there feel sick enough to seek immediate care, said Dr. Matthew Wynia, director of the Center for Bioethics and Humanities at the University of Colorado, who has studied trials conducted during emergencies.
These patients might be less able to understand they are being asked to enter a study, Wynia said. Or they might be especially susceptible to what he called the "therapeutic misconception"— that they are definitely going to benefit medically, which is not always the case in a study.
"The last thing you want is distrust in the community," he said.
Getting community buy-in ahead of time would be useful in the event of a deadly outbreak such as Ebola, in which patients in the emergency room might be too incapacitated or frightened to give true consent, Wynia said. Hopkins likely would seek such community consent by conducting meetings with people in the areas it serves.
For the proof-of-concept study with the flu, he said, there's not much downside. Volunteers are likely to get better care because everyone would be tested and screened for approved antivirals and no one would get the drugs who shouldn't.
He also said there is a pressing need to speed approvals for new therapies, especially those meant for outbreaks of serious infectious diseases. Flu offers an invaluable opportunity to prepare for future public health emergencies because so many are sickened each year.
Wynia also serves on the National Academy of Medicine's Forum on Medical and Public Health Preparedness for Catastrophic Events, which he said has held workshops on how to conduct rapid research during public health emergencies. The Hopkins study would be an example for others, he said.
"It's actually unethical not to do these kinds of projects," he said. "When Ebola is at our shores, it's not the same as a flu epidemic. The level of fear changes, the capacity to walk people into a room and get consent gets harder. This [study] will show what you can do in a real epidemic."
Another potential benefit of cutting the approval time for essential new drugs aimed at disasters is reducing their development cost, often estimated at more than $1 billion, Wynia said. That could lure more pharmaceutical companies to develop therapies that might rarely be needed but are dangerous to go without.
The Hopkins study is being undertaken with $4.2 million in federal funding under a cooperative agreement with the Biomedical Advanced Research and Development Authority, or BARDA, a division of the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services.
In a statement, BARDA officials agreed that time and expense could be cut significantly by more efficiently enrolling patients in trials, which also could make drugs available to patients sooner. Such a process could become especially important in reducing the level of disease and saving lives during an emerging pandemic because vaccines are unlikely to be available.
Other efforts are underway to shorten the development time for drugs and vaccines, such as using the same platform, or technology, for therapies for similar virulent infections, the officials said. Researchers also use challenge studies, in which volunteers are infected with a virus so researchers don't have to wait for people to become sick to test a treatment. The University of Maryland used such a study for a recently approved cholera vaccine it developed and is using it to test a Zika vaccine candidate.
Emergency departments may offer another means to cut timelines, BARDA officials said, and the Hopkins study is beginning to address how to do it properly.
"The ED environment presents an ideal environment in some respects for the studies," the officials said. "Cost savings can be tremendous for more efficiently enrolling subjects into clinical trials needed to develop new and more effective therapeutics (and diagnostics) for patients."