By Ashley Hattle
Most people never give a second thought to the months, years, and even decades it may take for a new drug to pass stringent Food and Drug Administration (FDA) standards. There are countless safeguards and testing processes involved in developing a new medication or device that ensure an approved drug works as advertised and doesn’t cause harm.
William Schmidt, PhD, is a researcher who works as the head of NorthStar Consulting, LLC. The company specializes in providing advice on pre-clinical and clinical studies of novel analgesic drugs. Robert Gereau, PhD, is vice chair for research in Anesthesiology and director of the Washington University Pain Center. They both have both seen many drugs go from theory to pharmacy. Acute and chronic pain are two areas sorely in need of new treatment options, and these experts focus their efforts on helping make those options a reality.
“There’s a growing appreciation that we may need different medicines to treat acute pain versus chronic pain,” says Gereau. “Companies would like one drug that could treat all pain, as this is a huge market, but the fact is there are so many different drivers for clinical pain, so different approaches are needed.”
How a new drug goes from concept to your local pharmacy
All medications and devices go through the same five steps for approval in the United States.
1. Discovery and development: Researchers dive into how and why a new drug or device may work in a laboratory setting.
2. Pre-clinical research: The treatment is tested on animals and cells in a lab to assess its basic safety and to ensure humans can tolerate the drug.
3. Clinical research: People with the associated condition are enrolled in clinical trials to test the drug’s or device’s safety and efficacy in humans.
4. FDA review: The company submits its data to the FDA review team, which examines all the details and decides whether or not to approve the new treatment.
5. Post-market drug safety monitoring: The FDA closely watches all approved devices and drugs to ensure they’re safe once they’re widely available to the public.
The process may vary, depending on the type of treatment. For example, a novel biological drug, such as a regenerative medicine, may require specialized biosafety committee approval before research even begins.
Clinical trials must prove a new drug works safely
Once a drug makes it through pre-clinical research with compelling evidence it could be safe and effective for humans, it then goes through several phases of clinical trials.
“Some of the most exciting recent news in this space has been around the success of the Nav1.8 inhibitor in postoperative pain,” says Gereau. Nav1.8 is a sodium channel that signals pain in the peripheral nervous system. “There were significant reductions in pain scores in two surgical populations, and Phase III trials are now launching.”
Schmidt is currently advising on a medication different from existing analgesics for treating painful diabetic peripheral neuropathy.
“What I’m working on right now in a Phase III clinical trial is a compound that has the potential to turn the clock back,” Schmidt explains. “It takes a long time to do these trials because, in this case, the trial length is 12 months. … Just in the last few weeks, we finished recruiting 160 subjects for the second Phase III trial. It will be a year from now before that last subject completes the trial.”
How a patient joins a clinical trial
Patients must fit the inclusion and exclusion criteria for any clinical trial, and the FDA requires all of them to be listed on ClinicalTrials.gov, a website run by the National Institutes of Health (NIH). You can type in the name of your painful disease, and dozens, perhaps hundreds, of studies pop up that fit that profile.
“You may get the active drug, or you may get an inactive drug or even a standard medication that’s used to treat that particular disease that’s used as a reference for the new drug,” says Schmidt. “You may not know [which medication you’re treated with] when you’re in the trial, but you will get excellent medical care and standard of care for your treatment that will be paid for by the company sponsoring the clinical trial.”
Some individuals may not qualify due to comorbid conditions, certain medications, or participation in previous drug trials. Your lifestyle or the stability of your disease or injury can impact your candidacy as well. For example, someone with diabetes needs to have a stable HbA1c baseline to qualify for a clinical trial. People who qualify for a clinical trial and see it through to the end often feel that they’ve contributed to science and given other people living with the same disease a chance at a better quality of life.
Barriers for patients with acute vs. chronic pain in clinical trials
“There are different types of clinical trials that would need to be done to target acute pain versus chronic pain conditions, so this makes the clinical development process quite expensive and complicated,” says Gereau.
Long-term clinical trials face the most obstacles, because it’s common for about 10% of participants to drop out. They may have an acute medical issue or surgery, or they may move away from the geographic area of the research team. Sometimes, older patients or individuals with fatal diseases pass away during the clinical trial.
Sometimes a company ends a study. Some clinical trials must start over because of a complication or a new safety risk. Many studies fail to recruit enough participants according to inclusion and exclusion criteria, especially for rare pain conditions. Luckily, the development of ClinicalTrials.gov has made patient recruitment a less daunting process.
A waiting game with the FDA
When clinical trials have ended and met their desired safety and efficacy endpoints, the company assembles and submits its data to the FDA for review. The approval process and timeline differ for medications, vaccines, devices, and other treatment types. A typical FDA review process is nine months, although the clock may reset if additional safety checks are found to be needed, especially for brand-new types of medications.
Companies may apply for a faster, six-month priority review if the drug is considered groundbreaking, or if an emergency use authorization is involved, such as with COVID-19 vaccines. The FDA’s “Fast Track” program expedites the review process for treatments for conditions such as AIDS, Alzheimer’s disease, heart failure, cancer, epilepsy, depression, and diabetes, as well as treatments that may affect survival, day-to-day functioning, or the progression of a disease to severe, according to information from the FDA. Although the Fast Track process moves more quickly, the extent of the review remains detailed and thorough.
A drug may take three to six months after approval to reach your local physician and pharmacy.
It’s an exciting time to be in pain research
In 2017, the NIH recruited researchers to determine how to change the process of developing non-opioid drugs to treat acute or chronic pain. The NIH funneled billions of dollars into pain research to encourage companies, academic laboratories, and people worldwide to create new compounds for pain conditions.
“They set up a system at NIH to be able to advise on how those pre-clinical studies or even clinical studies could be conducted in a more standardized manner. For pain medicine, that’s particularly important,” says Schmidt, who serves on an NIH oversight committee for this pain program.
“The NIH HEAL (Helping to End Addiction Long-term) Initiative does this specifically for pain researchers, but there are other programs in place as well,” says Gereau. “The NIH Blueprint Neurotherapeutics Network and IGNITE programs, together with HEAL’s suite of programs supporting the entire pipeline from target identification to clinical trials, has created energy and excitement in the research community, motivating people to focus on therapeutic development.”
Research is how doctors learn more about the safety and efficacy of drugs, propelling an idea from theory to the shelves of your local pharmacy and improving the lives of patients with acute and chronic pain. The coming years show great promise for pain research and may revolutionize treatments.