How New Drugs Are Developed and Approved

A patient recently asked, “Why do drugs cost so much?” He had read about a new medication that held promise for improving his wife’s chronic health condition. The candidate drug was just entering Phase 1 clinical trails and he wanted to know more about the process.

I explained the process starts when a trial sponsor, usually a company or group that developed the drug, submits data to the U.S. Food and Drug Administration (FDA). In this initial phase, data on animal models and proposed trial design are presented. This is known as an investigational new drug application. Once the FDA has reviewed and signed off on the proposal, the drug enters Phase 1 trials to demonstrate safety of the medication on humans. This usually involves testing on a small group of patients. Assuming Phase 1 is successfully completed, Phase 2 investigations can begin.

Phase 2 trials are designed to prove efficacy and further check for side effects. This stage normally includes a larger number of subjects, as well as a longer study period. If Phase 2 is completed successfully, the trial moves to Phase 3, during which the effects of the medication or treatment are evaluated on a large number of patients over a  longer period. The specific goal is to prove efficacy and identify long-term adverse events. Phase 2 and Phase 3 often include randomized control groups designed to compare the candidate drug to either a placebo or medication that is the current standard of care.

IT HAS BEEN ESTIMATED THAT ONLY 6% OF DRUG CANDIDATES ARE ALLOWED TO PROCEED WITH INITIAL HUMAN TRIALS

Once these trials are successfully completed, the company can petition the FDA for approval. While the entire process typically takes years, the rapid development and emergency use authorization of COVID-19 vaccines stands as a noteworthy exception. These new vaccines are a testament to the global scientific community’s commitment to accelerate drug development to address — and hopefully arrest — the pandemic.

In response to my patient’s question, however, I noted that under non-pandemic circumstances the considerable time and resources needed for drug development, testing and approval explain the high prices and slow approval times seen with most new medications. Additionally, it has been estimated that only 6% of drug candidates are allowed to proceed with initial human trials. This again speaks to the cost of developing new medications — costs that are compounded by the lengthy trials candidate drugs typically require in normal circumstances.

As part of efforts to speed up the process, a number of states have passed “right to try” legislation that allows terminally ill patients access to drugs not yet approved by the FDA. Although such use provides additional data during the study period, it raises the issue of defining which patients should be allowed to use these medications. It also leads to conjecture as to what impact, if any, the pandemic and accelerated development of COVID vaccines will have on the approval process in the future.

And that is something we’re all eager to learn.

Thomas G. Wilson Jr., DDS
Editor in Chief
twilson@belmontpublications.com

From Decisions in Dentistry. March 2021;7(3):8.