Have ever wondered what’s the process to get a drug approved by the Food and Drug Administration (FDA) and why those glaring boxed warnings get added? It seems mysterious to a lot of people, even prescribers. So, here’s the scoop:
First, a drug maker develops the medication and tests it to see if it works. If it appears to be a go, then the drug maker will submit an Investigation New Drug Application (NDA) to the FDA. This form describes how the company will study the drug in clinical trials. Clinical trials are done in three phases (add link to clinical trial blog) and this process can take several years to complete. After the clinical trials are completed, the drug maker submits a New Drug Application to the FDA for drug approval. Then the FDA evaluates the data and then makes a determination for approval. When the FDA evaluates the data from the clinical trials, the FDA will require certain things to be included with the labeling of the drug like indications, dosing, monitoring and possibly a boxed warning. Ultimately, the drug manufacturer does not decide the details. So if you ever wondered who made the recommendations for particular labs to check, it was the FDA panel, not the drug maker.
After a medication hits the market, the FDA continues to monitor its safety and efficacy. If new side effects or issues arise, the FDA can require the drug maker to update its label. If a drug needs to be pulled from the market, the FDA can also issue a drug recall. The FDA also monitors drug facilities that manufacture medications to ensure they follow safety and quality standards.
So what about the boxed warning, formerly called a black box warning? Sounds scary, huh? Boxed warnings are the highest safety-related warning that the FDA gives a medication and usually are given to a group of drugs in the same class. A boxed warning isn’t forever and can be added, taken away or updated even after the drug has been approved and on the market. The criteria used for a box warning was developed by the FDA in 1979. A boxed warning is typically based on clinical data but animal toxicity can be used if clinical data is lacking. What’s important to highlight is that a causal relationship between the drug and the side effect does not have to be proven for a boxed warning. To get a boxed warning, the FDA commissioner may refer it to the Center for Drug Evaluation and Research (CDER), which may convene an advisory committee for further review, but this is not a requirement, and many boxed warnings are issued without undergoing this review. Currently, there are over 400 medications with a boxed warning in the United States. And there’s a good chance you’ve taken a drug with a boxed warning. Ever had Botox? Yep, it’s got one. Did you take ibuprofen for a headache or muscle strain lately? Oh, yes, non-steroidal anti-inflammatory drugs (NSAIDS), like aspirin, ibuprofen and naproxen, have a boxed warning too.
If you see a boxed warning, should you run? No! A boxed warning is not a contraindication to prescribe the drug. Rather it’s a call out for potentially serious side effects that might occur. The dilemma is interpreting the boxed warning, especially with context of the studies the warnings are based on, and communicating the risk effectively to patients. In fact, just having a boxed warning may deter a prescriber from using the medication and instill unwarranted fear in patients. There needs to be a balanced conversation on risk and benefits and clear communication so that both the patient and prescriber can feel comfortable that the medication is the right choice for them.
Trotter’s Take: The FDA ensures the quality and safety of medications and uses tools like the black box warning to educate prescribers and patients on risk but just because a drug has a boxed warning, it does not mean that you avoid it at all costs.
Now that you understand boxed warnings, listen to Dr. Raj Chovatiya as we break down boxed warnings and tackle JAK inhibitors,a powerful class of drugs that has changed the landscape for inflammatory skin conditions.
