Clinical trials are done to ensure that medications and vaccines work and that their benefits outweigh the risks. We know these trials work because we can find examples where trials were paused or stopped due to concerns with safety and efficacy.
Clinical trials are done to ensure that medications or vaccines work (officially called efficacy) and to determine their safety (e.g. do their benefits outweigh the risks?). Clinical trials are carefully monitored and controlled by the Federal Drug Administration (FDA) in the USA, or by similar organizations in other countries, we call this regulation!
One of the ways we know clinical trials are doing their job is because oftentimes they DO find issues with how well the product works or with safety. Most things fail in clinical trials and never get approved. Part of the trial process includes reviewing the data being collected throughout the steps of the clinical trial. If issues are detected, the trial will be paused or ended.
What determines whether a clinical trial is successful?
During the phases of a trial, researchers and regulatory agencies are monitoring the safety and efficacy of all medications and vaccines (we are calling them products here). Determining safety involves looking for things like side effects (e.g. fever, rashes, stomach pain) and how well the body can handle the product (tolerance). Efficacy is looked at in different ways depending on the product. For example, does the product actually do what was intended – such as reducing levels of pain or protecting against an infectious disease. If a product already exists, then trials look at whether this new product is better and/or safer than the alternatives. For a clinical trial to be successful, the product has to be both effective and safe, which here means that their benefits outweigh the risks!
Clinical trials go through multiple phases
All products go through clinical trial testing. These trials help ensure the product works and that the benefits outweigh the risks!
- Phase 1: Study the safety and amount of the product to use. Usually done with <100 people.
- Phase 2: Study how well the product works (efficacy) while still monitoring for safety in around 300 people.
- Phase 3: Usually studies the product in thousands of people to get more complete data on how well it works and its safety. If the drug made it this far, then the company will apply for FDA approval to make the product available to people outside the trial. Depending on the data the product may or may not get approved.
- Phase 4: Monitoring data after a product is approved to ensure continued safety as more people use the product. This post-approval safety monitoring does sometimes catch rare side effects that cause re-evaluation of the product. Sometimes warning labels are added, or approval is taken away.
Any FDA medication or vaccine you have used has gone through this process and been successful. But there are plenty of examples from real life where issues have been detected that result in trials being paused or cancelled. These help show us that the system works!
Five examples of regulation in action
- Pfizer oral GLP-1 agonist – Danuglipron:
Earlier this year Pfizer decided to stop giving patients one of their trial oral GLP-1 agonists to treat obesity. They made this decision because one person in the trial experienced signs of liver injury that improved after they stopped taking the drug. Even though it was only one person, after examining all of the data from multiple trials, Pfizer decided to stop working on this drug and explore other oral GLP-1 agonists. This is an example of why drugs are carefully studied at different doses and forms. Changes can impact how well the drug works and its safety.
- Gene editing treatment for high-LDL cholesterol – Verve 101:
The company Verve Therapeutics stopped enrolling new patients in a Phase I trial testing a gene editing drug. This was because 1 of 6 patients tested at a certain dose experienced a serious increase in a specific liver enzyme and a decrease in blood platelet counts (important for blood clotting). This resulted in the patient being hospitalized and observed for 2 days. Even though the patient recovered, it was enough to stop the trial and notify regulators.
- Lupus treatment – Zetomipzomib:
Late last year Kezar Life Sciences was told to stop their Phase 2 trial of a drug for Lupus after 4 patients died during the study. An independent FDA committee determined that 3 of the 4 deaths were similar and happened close to when they were given the trial drug. Kezar hadn’t expected any safety concerns because they tested this drug for a different condition (autoimmune hepatitis) and saw no serious side effects. This shows it’s important to keep a close eye when a new drug is being tested for multiple diseases.
- RSV vaccine for pediatric patients – mRESVIA:
In 2024 Moderna paused their pediatric RSV vaccine trial and notified the FDA of a potential safety issue. They saw more severe RSV in the vaccine group (5 children) compared to the control group (1 child). This signal could have been due to chance since the numbers were very small, or it could have been because the vaccine wasn’t working as intended. Regardless, the trial was stopped and the FDA paused enrollment in all infant RSV vaccine trials. The maternal and adult RSV vaccines now available do not have this issue. Nor do the monoclonal antibodies given to infants after birth. This example shows that you must be sure the benefits outweigh risks to proceed. Even if there is uncertainty about the cause, or small numbers of people are impacted.
- Huntington disease treatment – Branaplam:
In 2022 Novartis announced it had stopped testing a drug for Huntington’s disease because some patients experienced nerve damage. This was particularly disappointing because there is currently no cure, and the drug was showing that it could help reduce the mutant protein that caused patient symptoms. Given the seriousness of the side effect, the company predicted no dose would be safe enough. This shows that even when a drug is effective, it must also be safe or it will not progress through trials.
Bottom line: Clinical trials work!
Clinical trials are critically important for determining how well medications or vaccines work and their safety. Four of the five examples here happened in the last year. This shows that it is pretty common for concerns to be flagged during one of the trial phases, leading to the trial failing and the product never being used.
It’s also important to recognize that the FDA (and companies themselves) regularly stop important and costly trials even when safety events are found in just a few patients, or sometimes even just one. Making sure treatments work and their benefits outweigh risks matters more than making money. The job of the FDA, and similar agencies worldwide, is to evaluate new drugs to make sure the public has useful and safe health tools.
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