By Arielle Kloss ***
Ever wonder about the journey those pills you swallowed this morning took before getting to you? How the contents of the capsule went from mixing in a beaker to becoming a once-a-day regimen for your headaches and stomach issues? This process is like trying to wake up in the morning without coffee — long, complicated and often ending in failure. Once a company discovers a compound that has potential to become a marketable drug, the process becomes similar to a relay race. There are checkpoints, obstacles and competition involved in the drug companies’ race to get medications approved by the Food and Drug Administration (FDA). Get on your mark. Get set. Go!
Companies must first show that the medication is safe before they can even think about giving it to humans. This involves determining the basic physical, biological and chemical characteristics of the compound, potential toxicities, route of administration, and starting doses. Animal models are used to gain the above understanding about the investigational medication. After the evidence shows that the drug is safe and possibly efficacious, the company files an Investigational New Drug Application with the FDA. The FDA then has 30 days to give it’s disapproval. If the FDA does not disapprove, the company can begin clinical studies.
On to the next set of obstacles! Human clinical trials involve three to four phases, all of which have different objectives. Phase I is the first challenge, aiming to determine a safe dosing range in a small amount of healthy volunteers, about 20 to 100 people. There is close monitoring by medical personnel, and the studies often occur in special testing facilities to ensure subject safety and controlled environments. This phase must show that the drug is safe first and foremost. If so, the study can expand to include a few hundred healthy study participants with the target disease. This is what happens in phase II. This stage aims to establish efficacy in the target disease and to continue determining appropriate dosing. These studies also often involve a placebo control. After the above two phases have sufficient data, companies can initiate the final stage required before submitting for FDA approval.
Take a breath; we are getting closer to the end of the race. Phase III trials sometimes involve thousands of participants from around the world who are likely to undergo the treatment once it is on the market. The goal of this phase is to show long-term safety and efficacy, and assess the treatment risk-to-benefit relationships. The Digestive Disease Institute at Virginia Mason is involved in many of these types of trials, closely monitoring patients as they take their experimental medication. We compile data collected from the patients, including drug side effects, vital signs and any other pertinent information about their experience taking the medication. Drug companies wait to collect our data that they need to make the final push to the end.
Finally, the finish line is in sight after the phase III data show good results. The companies submit a New Drug Application to the FDA, who must actively approve the medication to be available on the market. Congratulations, you’ve finished! Only a small amount of research efforts make it to this point, however. The many steps increasingly introduce variables that could affect the efficacy or safety of the drug, forcing companies to terminate their studies and go back to square one. Millions of dollars are spent throughout these phases in the hope that the drug will pass each checkpoint. Even after reaching the market, the FDA is free to ask companies to complete phase IV trials to compare the medication to other drugs on the market and determine additional safety information. Whew!
So the next time you grab your morning medication from the bedside table, think about the energy that went into making those pills available. The industry involves coordinators, study participants, scientists and a lot of funding that contribute to developing a successful drug. While there is critique about pharmaceutical companies and the high cost of medication, think about the research and development efforts that often fail and the costs of bringing one little pill to the market. I invite you to imagine different ways that the process could work, perhaps methods that could lower prices or promote cooperation among the competing companies. This is an interesting and hot topic for discussion so challenge yourself to ponder the possibilities. How would you change the race?
Arielle is a clinical research assistant with the Digestive Disease Institute at Virginia Mason.