Introduction
Clinical trials are an essential aspect of modern medicine. Every drug, biologic, or medical device on the market needs to pass an important process of clinical trial testing to ensure the safety and efficacy of these innovations.
Clinical trials are the critical bridge between scientific research and real-world medical applications.
“We're trying to find ways to develop new therapies, usually for problems that can't be solved by over-the-counter or homeopathic remedies,” said Suzan Olson PhD, MHS, RN, and instructor at the UC San Diego Division of Extended Studies Clinical Trials Design and Management Program. “Most everyone has someone in their orbit that has had a healthcare challenge. When you don't have an available medication to solve the condition and quality of life may be compromised. And so a clinical trial helps us to use scientific methods to find help for these people.”
Unless the product passes these clinical trials, it won’t be approved for market by the US Food and Drug Administration (FDA).
In this article, we’ll explore the role clinical trials play in modern medicine, the four phases of clinical trials, and their importance in the drug development process.
What is a Clinical Trial?
A clinical trial is a carefully designed and controlled clinical research study that investigates the safety, efficacy, and potential benefits of medical interventions. These interventions can include drugs, biologics, vaccines, medical devices, or other therapies for humans.
Clinical trials provide a systematic and scientific approach to finding solutions and are a critical component of advancing medical knowledge and improving patient care.
“The primary goals of clinical trials are safety and efficacy,” said Olson. “We're going to look and see if the drug demonstrates safety and efficacy with the condition for which the product is labeled.”
The trials are very structured and systematic, both for the participants' safety and to ensure accurate results.
Researchers administer the therapy to participants and monitor them to see their effect on the target condition. They’re especially looking for any adverse effects, side effects, or potential risks associated with the intervention.
Data can be collected via physical examinations, laboratory tests, medical imaging, patient-reported outcomes, and other methods.
Participation in clinical trials is voluntary, and participants are provided with informed consent forms detailing the study's purpose, procedures, potential risks, and benefits before they are allowed to participate in the trial. In all cases, it needs to be confirmed that the benefits outweigh the potential risks before clinical trials may begin.
The results of clinical trials help inform healthcare decisions, influence medical guidelines, and may lead to the approval of new medications and treatments by regulatory agencies such as the U.S. Food and Drug Administration (FDA).
“By using the scientific method we're able to iteratively improve on the drugs, devices, and the biologics to make sure that it's safe and effective for the indication for which they are approved,” added Olson.
The trials are also important to collect real-world data on how therapies are metabolized by humans, interact with other foods or drugs, and determine the best dosage and administration of the therapy.
What Does It Take To Be A Clinical Trials Researcher?
Being a clinical trials researcher requires a unique mix of scientific knowledge and administrative acumen.
These professionals often work in contract clinical research organizations, and are responsible for executing the study, adhering to timelines, managing contracts, and maintaining regulatory compliance.
Olson highlights the importance of project managers with clinical expertise.
“There could be hundreds of people on a team doing this work, all on a timeline,” said Olson. “A person with project management skills is valuable to these kinds of studies because they know how to manage timelines and keep track of all the moving pieces.”
“It’s also helpful if they know how to work with regulatory folks and they have a good knowledge of clinical medicine. It takes years to develop these skills,” Olson added.
The Phases of Clinical Trials
Clinical trials typically have four phases. There are three phases of experimentation and one post-marketing phase of regulatory oversight.
It’s important to note that there are also some important steps that need to happen before a therapy even gets to humans for clinical trials.
“The very first step is you have a problem and you want to solve that problem,” shared Olson.
Ideas for new drugs or medical therapies are hypothesized as potential solutions for human health challenges.
The possibilities are run through a computer simulation called a high-throughput screening that seeks to determine what different kinds of chemicals might solve the problem. This gives researchers an idea of where to start.
“If we find something that might help, then we go to a laboratory setting to test it there,” Olson added.
During this phase, experiments are done with chemicals, biologics, radiation, and other elements to see how the potential therapy might actually work before it’s administered to actual test subjects.
“Once we move from the lab we will start to work with animals,” explained Olson. “There are different animal models for different problems. Like there are specific animal models that we would use for pain, and there are different animal models that we might use for certain kinds of cancers.”
Only after a potential therapy is deemed to be safe in this regard is it allowed to progress to humans for clinical trials.
“Once we gather the kind of information that we need, we can project a potential dose for a clinical trial that is not toxic or not harmful. Then we will use formulas to cater the first dose in humans,” explained Olson.
Throughout this whole process, researchers and the sponsoring company are working closely with regulatory agencies, such as the FDA and institutional review boards (IRBs), to ensure the safety of the products being developed and give them the best chance of passing clinical trials and eventually making it to market.
Phase 1: The Journey Begins
Phase 1 studies mark the inception of the clinical trials process.
These trials involve a small group of 20-80 healthy volunteers. The primary goal is to determine how the human body metabolizes and reacts to the experimental drugs. The focus is on assessing safety, dosage, and how the body processes the intervention.
The length of the study can be several months to a year. Approximately 70% of drugs that enter clinical trials pass this initial first phase.
An important aspect of this phase, and all phases of clinical trial research, is that they are typically carried out by contract, clinical research organizations that are independent of the treatment’s sponsor. This is to create space between the sponsor and the clinical research to ensure the most impartial results.
“There are places all over the United States that do first-in-human types of studies,” said Olson. “They have top-of-the-line technology there to measure any kind of output once a person has been injected or taken a pill. They collect saliva, stool, urine, blood, skin sweat, and any other output that’s deemed relevant. This is all to get readings on how the body is processing and metabolizing the treatment. By collecting all of these pieces of human data, we will then look and see if there is a potentially unsafe or unexpected output from that input.“
Phase 2: Probing Effectiveness
Once Phase 1 studies reveal acceptable safety profiles, Phase 2 comes into play.
Here the focus shifts to effectiveness in treating specific diseases or conditions. The participant group expands to include individuals with the target medical condition. They aim to gather data on the intervention's efficacy and side effects. Trials compare patients receiving the experimental drug with those receiving a placebo or a different treatment.
"Phase 2 is about gathering preliminary data on whether the drug works,” explained Olson. “We expand our participant pool to dozens or even up to 300 individuals, studying efficacy, short-term side effects, and monitoring safety. It's a crucial step toward understanding the potential benefits of the drug."
The length of the study can be from several months to several years. Approximately 33% of the treatments that begin this phase move to the next phase.
Phase 3: Confirming Safety and Effectiveness
Phase 3 studies represent the largest and most extensive phase of clinical trials.
This stage delves deeper into safety and effectiveness, exploring various dosages, populations, and drug combinations. These trials involve several hundred to several thousand participants. Comparisons of the new treatment with existing standard treatments or placebos are an important aspect of this phase too.
“When you move to phase 3, you're looking at thousands of patients and many different experiments,” said Olson. “We use the scientific method and ask different questions for different populations of patients to learn the different ways the treatment could potentially react.”
Studies at this phase can be incredibly expensive for the sponsoring company.
“There will be at least two or more of these phase 3 studies that must be done to test against different populations or different variables,” shared Olson. “It can cost over a billion dollars and take years, sometimes. I managed one study that was 135 sites all over the globe including 13 Asian countries. That one study alone was over 40 million dollars.”
Phase 3 studies can take many years to complete. Approximately 25-30% of the treatments that enter phase 3 studies advance to review.
Phase 4: After Clinical Trials
Once a treatment passes clinical trials, the sponsor submits a New Drug Application (NDA) to the FDA.
“This is the formal step a drug sponsor takes to ask that the FDA consider approving a new drug for market,” said Olson. “An NDA includes all animal and human data, analyses of the data, how the drug behaves in the body, and how it is manufactured.”
Another important aspect of this phase of treatment review is creating a label.
“The label says what kind of patient condition this drug can be used for, when you take it, how you take it, what foods, drugs, or other things the treatment doesn’t work with, and anything else needed to ensure it’s safe administration to a wider population,” shared Olson.
If a treatment passes all this review, it is then allowed to go to market.
Yet, just because it’s gone to market, doesn’t mean that the sponsor isn’t still required to review the ongoing safety and efficacy of the drug.
Post-marketing surveillance, sometimes called “phase 4”, occurs after the intervention has hit the market. The sponsor works with regulators to continue to monitor the long-term safety and effectiveness of the treatment in a larger population to make sure there are no additional adverse effects. These studies are usually conducted by the FDA.
“The FDA will also start doing inspections of places where the drugs are manufactured,” Olson added. “They're also looking at the data and whether or not the proper methodology to conduct a trial was performed.”
Serendipitous Discoveries
While the clinical trials process is specifically for testing the safety and efficacy of a drug, Olson also shares that it can sometimes lead to serendipitous discoveries that might not have emerged had the outcomes not been closely observed.
“A good example of that is when they were trialing a drug called minoxidil to deal with hypertension,” shared Olson. “The clinical researchers actually realized that men were growing hair all over their bodies from the drug. So guess what happened next? It was turned into a drug that’s being used by men and women today to regrow their hair. So sometimes we have serendipitous results that are an interesting surprise and a new indication for the product is discovered.”
How to Get Into Clinical Research
As the healthcare industry continues to grow, the demand for trained professionals to coordinate and manage clinical trials will only grow.
This could be a valuable skill to learn or develop for research managers and associates, scientists, database administrators, individuals with science degrees, or any other healthcare professionals who may be considering a career change.
Certificate programs such as the Clinical Trials Design and Management Program provided by UC San Diego Division of Extended Studies cover important topics, such as data management, site recruitment, project management, drug development, human subjects protection, regulatory compliance, and working with institutional review boards. The program provides a solid foundation for learning how to coordinate and manage clinical trials for those interested in entering the field.
Looking to earn your master’s? UC San Diego Master’s in Clinical Research helps students meet the demand for well-qualified clinical researchers in academia and industry. Students will delve into the nuances of clinical research methodologies, emphasizing data interpretation, statistical analysis, and results presentation.