Clinical Trial FAQs

An Interview with Dr. Jennifer Vaughn

The Mast Cell Disease Society recently sat down with Dr. Jennifer Vaughn to demystify the world of clinical trials and to clarify how new treatments actually reach patients. While terms like “experimental study” and “FDA approval” can sound like medical jargon, the process is designed with patient safety at its core. In this interview, Dr. Vaughn breaks down the lifecycle of drug development, explains what happens during the regulatory review process, and shares how patients can navigate this landscape to safely advocate for their own care.

Here is a transcript of our interview with Dr. Vaughn

TMS: Let’s start at the beginning. When most people hear “clinical trial,” they probably think of someone volunteering for an experiment. Is that basically what it is?

DR. Vaughn: Technically, clinical trials are carefully designed “experiments” or “research studies” that are meant to determine whether a certain therapy (such as a drug) has efficacy among patients with a particular medical condition.  Any drug trial that is offered to patient participants must first be based on rigorous scientific research first conducted in the laboratory and (depending on where the drug is in development) earlier phase human trials. Federal and local regulatory agencies then evaluate whether these preliminary studies provide strong enough evidence that the drug may provide therapeutic benefit without leading to too many side effects. This initial assessment must be done before any patient is allowed to be enrolled.

TMS: We often hear clinical trials referenced according to what “Phase” it is in. Can you explain a little more about the phases and what they mean?

DR. Vaughn: Of course! The “Phases” of clinical trials increase as the drug or intervention moves further along in its development. For example, a “Phase 1” trial is usually the first time a drug is ever tried in humans. These may be healthy volunteers or patients with a disease of interest who don’t have a lot of available treatment options. In a “Phase 1” trial, the main goal is to determine the best dose of a drug and whether it has side effects.  Everyone who participates in a Phase 1 trial receives the drug/intervention. This is usually the case in “Phase 2” trials, as well. In these studies, we begin evaluating whether a new drug has any efficacy in a specific disease.   “Phase 3” trials are the last phase of drug development before it can be approved for use. In these studies, we are evaluating whether a new drug or treatment is BETTER than the current standard of care. Patient participants will often be randomized to receive the new drug OR the standard of care treatment.  Keep in mind that different trials (particularly Phase 2 and 3 studies) are designed differently depending on the clinical situation and can have some overlap in their design and intent.

TMS: So, if Phase three goes well, the next step is for the company to submit everything to the FDA, correct?  What does that look like?

DR. Vaughn: Once a company believes they have strong evidence from a Phase 3 clinical trial, they submit ALL of the data they have collected during development to the FDA. This includes everything from initial studies conducted in the laboratory to the results of all clinical trials that determine dose, efficacy and safety.  The application will also recommend an intended use (for example, what disease or stage of disease, when the drug should be used).

TMS: And what does it mean when the FDA “accepts” that application?

DR. Vaughn: Once the FDA determines that all the necessary information has been submitted by the company, they will accept the application and begin moving the drug through the approval process. This involves a rigorous investigation, including going to sites where the trial was conducted to ensure that all data were collected correctly and ethically.  At the end of this process, a multidisciplinary team of experts (including physicians, pharmacists, scientists, statisticians, etc.) will review the submission for approval and determine if the company has provided adequate evidence that the drug is safe and is likely to benefit patients with the disease of interest.

TMS: How long does the FDA’s review take?

DR. Vaughn: In general, the FDA has 6-10 months to review the information provided by a pharmaceutical company and decide whether the drug is approved for use.  The timeline for approval may be shorter in cases where no other treatment is available for a certain disease, and it may be subsequently lengthened if the FDA determines that more information or evidence is needed.

TMS: Our community has likely heard the term “PDUFA date.” Can you explain that term a little more?  What is PDUFA referring to?  What happens on this date?

DR. Vaughn: The acronym “PDUFA” stands for the “Prescription Drug User Fee Act”. This is a law that allows the FDA to collect fees from pharmaceutical companies to ensure the FDA has the resources it needs to perform its review for approval in a reasonable time frame. A “PDUFA date” is the date on which the FDA commits to deliver its decision in return for those fees. This does not always mean the drug will be approved on that date, but the FDA must provide a decision to the company – one way or another.

TMS: We know that there is a concept of expanded access, sometimes called compassionate use for drugs when they are in this window of time between their application and their PDUFA date. What is this exactly?

DR. Vaughn: Expanded access programs allow patients who may benefit from a drug to receive it during the time when the FDA is conducting its investigation for approval. Companies can make the decision to provide their drug to certain patients without cost, often in exchange for collecting additional data on the drug’s efficacy and safety profile.

TMS: What does the process look like from a patient’s perspective?

DR. Vaughn:  Certain healthcare centers will collaborate with companies to provide expanded access to a drug that is awaiting approval. These centers have often participated in clinical trials that led to the FDA submission and have some experience with the drug’s mechanism of action and toxicity.  One of the benefits to participation in EAP programs is temporary access to free drug, often without the same intensive travel and time commitment required for clinical trial participation. Patients who enroll in EAP programs also accept certain risks: while the company that produces the drug may feel that patients will benefit, the FDA has not completed a full review of the data and has not yet determined that the potential benefits of the drug outweigh the toxicities or side effects.

TMS: Is expanded access the same as being in a clinical trial?

DR. Vaughn: While EAP programs are under regulatory oversight, they are NOT the same as clinical trials. EAP programs usually provide the drug to patients in more of a “real world” setting—i.e. there are not usually as many labs, visits, scans or assessments. However, there is still some collection of data on patient safety and efficacy outcomes.

TMS: From where you sit as a clinician, what do you think patients most misunderstand about the clinical trial/ FDA approval process?

DR. Vaughn: As a clinician, one of the most disheartening moments is when a patient turns down an offer to participate in a clinical trial because they don’t want to be a “guinea pig” or because they are subjecting themselves to “experimentation” in a negative or dangerous way.  Clinical trials today are heavily vetted by both federal institutions like the FDA and by local investigational review boards that ensure that the patients who participate are treated fairly and safely.  Any proposed clinical trial must demonstrate that the potential benefits to participation are worth any possible side effects and the intensive monitoring that occurs for participants is meant to ensure that no concerning safety signals are missed. If you are a patient waiting on a drug to be approved, it is important to know that the FDA procedures are rigorous and are primarily driven by ensuring that any new drug that comes to market will provide reasonable benefit and safety to patients.

TMS: Any final thoughts for patients who are navigating this right now, maybe waiting on a drug that’s in late-stage trials?

DR. Vaughn: It’s an exciting time in drug development for mast cell diseases!  One important step you can take: if you learn about a drug that may be approved soon, bring this information to your physician as soon as possible. The pace of drug development in all diseases- particularly in hematology – is incredibly fast, and sometimes even we physicians struggle to keep up with it all! If you think a specific drug may benefit you, discuss it with your physician and have them review the available data from clinical trials to determine whether it will be a good fit once the drug does come to market. Also, I encourage you to be open to discussing clinical trial participation, as this is one of the best ways to gain access to cutting edge treatments.

TMS: Dr. Vaughn, this has been incredibly helpful. Thank you for breaking all of this down.

Navigating a mast cell disease takes an incredible amount of strength, and waiting for new treatments can feel both hopeful and exhausting. As Dr. Vaughn reminds us, staying in close communication with your doctor about new research is one of the best ways to advocate for your health.

If you need new options right now, you might not have to wait for a drug to officially hit pharmacy shelves. Even though the FDA final review process can take a while for clinical trials, Expanded Access Programs (EAPs) let eligible patients get promising new medications for free. They can be obtained at your doctor’s office without the extra travel and testing required by standard clinical trials.

The Mast Cell Disease Society keeps an updated list of open studies and early-access programs specifically for our community. To see what is available to discuss at your next doctor’s visit, go to tmsforacure.org/clinical-trials.

We hope you enjoyed this interview with Dr. Vaughn!

Dr. Jennifer Vaughn

Jennifer Vaughn, MD, MSPH is an Associate Professor of Hematology at The Ohio State University. She specializes in the care of patients with systemic mast cell disorders, myeloproliferative neoplasms and classical hematologic disorders.  She completed medical school at Emory University in Atlanta, Georgia, and residency and hematology/oncology fellowship at the University of Washington, Fred Hutchinson Cancer Research Center in Seattle, WA.