Clinical trials and the FDA’s role

We hear the term “clinical trials” quite regularly, but what do these entail and who decides whether these newly developed drugs make it to our pharmacies?

What is a clinical trial?

A clinical trial is essentially a “test drive” on real people who volunteer to evaluate whether a new drug or treatment would be successful or not to treat a particular condition, and should be marketed for mass consumer availability.

The criteria for enrollment in a clinical trial varies, but a common denominator is having the underlying condition or being one who could benefit from the treatment being tested.

“Protecting the rights, safety and welfare of people who participate in clinical trials is a critical aspect of the (Federal Drug Administration) FDA’s mission.”* 

A perfect example includes the clinical trials underway to find the first treatment available for individuals living with elevated Lp(a) levels – an indicator of the likelihood of cardiovascular events. My previously published interview with Dr. Steven Nissen explained the status of three ongoing clinical trials.

Those participating in clinical trials are doing so under what is called informed consent. From inception to completion, participants are informed of all aspects of the study, including expected duration, any testing / procedures, potential benefits, possible risks – everything that can be shared. Participants may leave a clinical trial at any time. 

“Clinical trials of drugs provide information about:

  • Whether the drug has the effect it is supposed to have.
  • How much of the drug to give to a patient and how often.
  • What side effects are associated with the drug and how they can best be managed.
  • How a drug is broken down in the body, and how long it stays in the body.
  • Which foods, drinks, or other drugs can be used at the same time or should be avoided.
  • Clinical trial results allow the FDA to make decisions about whether or not a drug should be approved for marketing.”**

In the US, what criteria must be met to have access to clinical trials?

Prior to initiating clinical research and then a clinical trial, sponsors or drug developers must submit an Investigational New Drug (IND) application to the FDA. Any time administration of a drug to humans is involved, unless it falls into the exempt category (such as dietary supplements and food, radioactive or cold isotopes), an IND is required. 

The IND application includes: animal study data (including toxicity), manufacturing information, study plans, data from any prior human research, and information about the investigator.**

The FDA’s IND Review Team covers all the bases and includes: a project manager, statistician, medical officer, pharmacologist, chemist, microbiologist, and pharmacokineticist.

Each of these individuals play a pivotal role during the 30-day timeframe to determine if the IND should be approved. It’s at this point when either a clinical trial is allowed to begin or does not get the green light and must not proceed.

How are clinical trials regulated?

“American consumers benefit from having access to the safest and most advanced pharmaceutical system in the world.”****

“The main consumer watchdog in this system is FDA’s Center for Drug Evaluation and Research (CDER).”** CDER does not perform testing itself, but evaluates the proposed drug, provides vital information for both doctors and patients, and ensures the health benefit of the proposal outweighs any known risks.

Once CDER is provided with evidence from all the testing of a drug, “a team of CDER physicians, statisticians, chemists, pharmacologists and other scientists review the company’s data and proposed labeling.”****

The FDA’s structure for drug approval includes:

  • “Analysis of the target condition and available treatments;
  • Assessment of benefits and risks from clinical data;
  • Strategies for managing risks.”****

How long is the FDA review and approval process?

To start off, there are two primary review systems: Standard Review (with a 10-month goal) and Priority Review (with a six-month goal).  This was established by the 1992 Prescription Drug User Fee Act.

Now, when a drug or treatment is in the pipeline and could potentially treat serious diseases (including if it’s the first treatment or highly advantageous over an existing option), the FDA developed four distinct approaches with a common goal to make the drugs available as soon as possible, detailed below.

Priority Review: This “designation means FDA’s goal is to take action on an application within 6 months.”****

Accelerated Approval: “Regulations allowed drugs for serious conditions that filled an unmet medical need to be approved based on a surrogate endpoint,”***** which enables the FDA to approve them faster. “A surrogate endpoint used for accelerated approval is a marker – a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit.”******

A surrogate endpoint saves a significant chunk of time. An example the FDA gives provides clarity: “Instead of having to wait to learn if a drug actually extends survival for cancer patients, the FDA may approve a drug based on evidence that the drug shrinks tumors, because tumor shrinkage is considered reasonably likely to predict a real clinical benefit.”******

Fast Track: “Designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet need.”*****

Breakthrough Therapy: “Designed to expedite the development and review of drugs which may demonstrate substantial improvement over available therapy.”*****

How many phases are there in clinical trials?

Four phases.

The initial stage is comprised of research. The National Institutes of Health states, “The idea for a clinical trial often starts in the lab. After researchers test new treatments or procedures … the most promising treatments are moved into clinical trials.”

Sponsors play a role in clinical trials and can include institutions, government agencies, organizations, companies, institutions, etc. that initiate, manage or finance it.

Prior to even getting to Phase I of a clinical trial, scientists perform tests both in labs and sometimes studies on animals to identify if it could be a potential therapy.

The FDA has a lengthy, rigorous process designed to examine and ultimately hope to release new drugs to the market in an ethical, systematic way.

Phase I – The treatment or drug is tested on a very limited number of people (typically under 100). This helps researchers understand side effects, how safe or unsafe it is, and more.

It’s important to note that after each phase researchers determine if it is wise and in the best interest of the public to move forward to the next phase.

Phase II – Once the treatment or drug “graduates” from Phase I, the number of individuals in the study pool increases (usually up to 300). By casting a wider net, researchers can understand any additional side effects, its safety and effectiveness.

Phase III – Once a treatment or drug reaches Phase III, a large group of participants are involved (usually up to 3,000). This allows researchers to collect a plethora of information.

As Dr. Steven Nissen said, “These are what we call event driven” trials, “meaning that they run until you collect sufficient number of events to answer the scientific question. So there is not a fixed timeframe.”

“The faster you accumulate events the quicker the trial ends,” he continued.

If the desired result is reached – i.e. if there is efficacy – the company and leading doctors/scientists are informed and the clinical trial stops. This is best case scenario. It is nearly impossible to guess how long a clinical trial will go on for.

Phase IV – This is when post-marketing studies are conducted after FDA has granted approval thereby providing additional information about drug risks, benefits, and best use.

The NIH’s link for literature, if of interest to you, is: You need to know either the study’s official name or Protocol ID number.

If efficacy is reached, the drug makes it way to gain approval by the FDA – ultimately leading to the public’s hands.


Next up, let’s talk about accountability. Does the FDA require continuous feedback on a drug once it has been released to the public?

The process is a bit different than I anticipated.

The FDA refers to this as its Adverse Event Reporting System (FAERS). FAERS “is a database that contains adverse event reports, medication error reports and product quality complaints resulting in adverse events” that are submitted by “healthcare professionals, consumers and manufacturers.”******* This is a voluntary process by which physicians, pharmacists, nurses, and consumers can submit a report to the FDA. If you would like to submit an issue with a drug you take, here is the link for more:

To learn about data submitted via FAERS:

This is the place to check for any new or updated safety concerns or side effects once a drug has been on the market.

When items are submitted to FAERS, a team (clinical reviewers in the Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research) continues to monitor and review safety of the drug.

The FDA provides this useful database: Drugs@FDA. By typing in any drug name it will explain side effects, the drug label, approval letters and more.

What happens when a potential drug has a positive outcome from a clinical trial? 

If efficacy is achieved and a clinical trial called off, the next step is FDA approval / clearance.

The steps at the FDA******** are as follows:

  • The pre-NDA period occurs before a new drug application (NDA) is submitted. At this stage the FDA and drug sponsors meet.
  • NDA is submitted i.e. requesting the FDA consider the drug for marketing to the public.
  • The FDA has 60 days to decide whether to file the NDA once it is received – which would lead to it being reviewed.
  • If the NDA is filed, an FDA review team is assigned to evaluate the drug and all of its aspects.
  • The FDA reviews labeling for the drug – which advises you, the patient, how to use it.
  • The FDA inspects the facilities where the drug would be manufactured.
  • The FDA determines whether to approve or issue a letter in response to the NDA based on these factors and conditions.

What happens if a potential drug does not have a positive outcome from a clinical trial?

A clinical trial can be called off at any time, during or after any phase, for a multitude of reasons.

What we can assume is that it has been called off for our benefit; in the best interest of our health. What happens next? Researchers continue their steadfast work to find the drug or treatment that could play a positive, pivotal role in any health condition or unmet need.

If you’re interested in participating, learning more, or just researching clinical trials, the FDA’s portal – Clinical Trials Search – is a great resource.











Coming next: Bone health, innovations in imaging explained by Dr. Stephen Honig