This article was originally published on December 9, 2015, and was last updated on May 14, 2019.
Welcome to Pharma 101 with PharPoint Research, an article series to teach you all about how drugs make it to market. Today, we’re tackling the question: What is a clinical trial?
In today’s world, we have incredible healthcare at our fingertips—flu shots, allergy medicines, ibuprofen, vaccinations—all readily available, safe, and tested. But how did these medicines make it to where they are today? How do we know they work, or how much to take? The answer: Clinical research.
We have all directly benefited from the world of clinical research. From over-the-counter drugs to prescriptions, our medications have been meticulously tested to ensure safety and efficacy. Before a pill ever sees a store counter to treat your headache, it undergoes a long and rigorous journey – which takes, on average, twelve years – to make it perfect.
Modern medicine relies on clinical trials. The clinical research process has developed our current arsenal of advanced treatments and will continue to discover new ones. That’s why it’s important to understand all of the many pieces and people that make our medications possible. In this clinical trial overview, we’ll provide the foundation for your clinical research education.
WHAT IS A CLINICAL TRIAL?
Our clinical trial overview can’t start without a definition. So what is a clinical trial?
Simply put, a clinical trial is a study that aims to contribute to medical knowledge. As such, they test the effects of new and promising drugs and medical devices in human participants. Trials may also compare a new treatment to a currently available treatment to determine which is more effective. Occasionally, drugs are combined or reproduced in different forms (such as tablets, liquids, films, etc.), which also require testing. Overall, clinical trials aim to find the safest and most effective ways to prevent, diagnose, and treat diseases.
Clinical trials transform theories developed in the lab into real-world applications. Trials are performed to approve medical treatments in human patients – and this means that the stakes are high. It is essential that trials follow strict scientific standards and are carried out ethically. Because of this, clinical trials are multi-step processes that are highly regulated throughout. Each step relies on a variety of dedicated experts and volunteers to be performed successfully.
WHO IS INVOLVED IN A CLINICAL TRIAL?
It truly takes a village to carry out a clinical trial. Many diverse roles must be filled for a clinical trial to be performed successfully.
Undoubtedly, the most important people in clinical research are study participants. Human volunteers are used in clinical trials to study the effects of a medication on the body. While animal testing is occasionally performed to explore a drug’s effects in vivo (in a living organism), it is vital to examine medications in the human body before it is made widely available.
Each study will have different needs for human volunteers to meet. At the start of the clinical trial process, drugs are often tested in healthy, young volunteers that do not have any medical conditions and aren’t taking any conflicting drugs (also known as concomitant medications). It isn’t until later phases when trials will seek out participants with the condition that the drug is designed to treat. Clinical studies may also test a drug in specific demographics to better understand its effects in people of a particular age, race, or sex. In every study, there are inclusion and exclusion criteria – in other words, there are certain qualifications that a participant must meet, and traits that a participant must not have.
Human patients are absolutely essential to the clinical trial process. People participate in clinical trials for different reasons – some want to make a contribution to the advancement of medicine, and some want to try experimental treatments for their particular ailment.
Wherever there are patients, there must be doctors. Each clinical trial requires a clinical investigator, or someone who is qualified by training and experience to be an appropriate expert to investigate a drug. The investigator is almost always a physician who works with patients of the appropriate population. It is not an FDA requirement that the investigator be a physician; however, if he or she is a non-physician, there must be a physician to make medical decisions and serve as sub-investigator.
Clinical investigators are responsible for conducting clinical trials in such a way that veritable data is obtained, while simultaneously protecting patient rights. It is important that physicians follow GCP (Good Clinical Practice) guidelines.
Overall, physicians oversee the administration of trial medications to patients, make medical decisions related to the trial, and ensure that the patients’ rights are always prioritized.
Of course, there is no need for a clinical trial if there is no drug to test. The sponsor of a clinical trial may be a pharmaceutical company, research institution, or government agency – anyone who is willing to take the responsibility to manage or finance a clinical trial.
While drug developers are an essential aspect of clinical research, they may not have the experience, expertise, or manpower to find patients, collect data, run statistical analyses, and navigate the FDA approval process. This is where Contract Research Organizations (CROs) come in. CROs provide outsourced support to the clinical research process by offering services that greatly expedite and assist clinical trials.
This is where we fit in: PharPoint Research is a CRO that offers services in biostatistics, data management, clinical operations, and project management. Our clinical operations team aids in studies from Phase 1 to FDA approval, and ensures that trial sites carefully follow the protocol, or investigational plan, for the clinical trial. This supervision ensures that sites maintain study enrollment, are communicating with patients effectively, and are mitigating risks and obstacles as they occur. PharPoint’s data management staff helps trial sites collect data efficiently and accurately, whether it be electronically or paper-based. Our biostatistics team offers statistical analysis and reporting services, ensuring that the data obtained from studies is analyzed correctly to determine the safety and efficacy of a drug.
INSTITUTIONAL REVIEW BOARDS
As previously mentioned, it is essential that clinical trials be performed correctly and ethically. Because of this, an institutional review board (IRB) is required to review and approve all clinical trials. An IRB is a group that has been designated to monitor research that involves human subjects. To ensure that diverse backgrounds are represented, an IRB includes both scientific and nonscientific members, a member who is not affiliated with the research institution, and members of varying demographics.
IRB oversight is yet another mechanism to ensure that clinical trials are properly executed and are protecting the best interest of the patients.
FOOD AND DRUG ADMINISTRATION
Perhaps the most important contributor to the clinical trial process is the FDA. The FDA provides an overarching authority on clinical trials to protect the welfare of volunteers and to verify the integrity of research data. As such, the FDA often inspects clinical trial study sites and anyone who may be involved in the research process.
FDA regulations are in place to guarantee that all drugs that receive final approval are safe and effective. These extensive guidelines provide the framework for successful clinical trials.
WHAT DO CLINICAL TRIALS LOOK LIKE?
Clinical trials are carried out in phases – Phase 1 through 4 – that are designed to answer particular questions.
But before Phase 1 begins, preclinical research is often performed to test the drug in vivo in animals before it is introduced to humans. This provides information about the drug’s absorption, toxicity, and excretion within a living organism. While there is currently no sure-fire alternative to animal testing, the FDA is working diligently to reduce the need for animal testing.
Following preclinical testing, an Investigational New Drug Application (IND) is filed. This IND shows the results of animal testing, demonstrates the evidence for the drug’s success, and lays out the plans for a human trial. If approved by the FDA and an IRB, Phase 1 may begin.
- Animal trials to ensure that the drug is not toxic in a living organism. Information is obtained about absorption, toxicity, and excretion. If results show that a medication is safe enough to proceed to human trials, an Investigational New Drug Application (IND) must be approved by the FDA and an IRB.
- A Phase 1 trial is all about safety. It aims to answer questions about how the human body responds to the drug – side effects, metabolism, and excretion are all studied. The primary question to answer is this: Is the drug safe, and are the side effects reasonable?
Phase 1 studies are the first time that a new drug is introduced to human subjects, and are normally carried out in a small group of young, healthy volunteers.
- If healthy volunteers do not experience unacceptable toxicity from a medication in Phase 1, the process will proceed to Phase 2. Phase 2 trials answer this question: Is the drug effective? If a drug is safe but ineffective, it will not be approved.
For Phase 2 trials, the population consists of patients who have the particular disease or condition that the drug is aiming to treat. The number of subjects can range from a few dozen to more than 300 people. The protocol that is written before Phase 1 begins details the necessary criteria that the drug must meet in humans to be considered effective. Dosing is often fine-tuned during Phase 2 trials.
- If a drug is determined to be both safe and effective, it will move to Phase 3. Phase 3 trials want to answer this question: Are we sure the drug is safe and effective, and is it comparable or an improvement from the current standard of treatment?
The FDA often meets with the sponsor prior to the start of Phase 3 trials to determine the best way to proceed. Overall, Phase 3 trials aim to collect more information about the drug in different populations. They are much larger than Phase 1 and 2 trials, often enrolling as many as 100-3,000 patients.
- If a drug manages to make it past Phase 3, it will proceed to the fourth and final phase of the clinical research process. Phase IV trials occur after a drug is approved by the FDA and is made available to public. This approval process requires a New Drug Application (NDA).
Following drug licensing and marketing approval, the drug is studied by researchers over a period of time to obtain information about the drug’s long-term effects, risks, benefits, and optimal use. Because of this, Phase IV trials are often called post-marketing trials.
PharPoint Research has an extensive amount of experience managing clinical trials from Phase 1 through Phase 4. We have taken active roles in the development of industry guidelines and the preparation of numerous NDAs. Whether setting the tone for the rest of the study in a Phase 1 trial or collecting additional information during Phase 4, PharPoint utilizes our experienced management team to satisfy sponsor needs and to seamlessly integrate tools and services for a successful clinical study.
WHY ARE CLINICAL TRIALS SO IMPORTANT?
Clinical trials are responsible for placing the best medications on shelves for consumers. This means that drugs must absolutely be safe, and have to improve the quality of life for those who are afflicted.
From Phase 1 to Phase 4, it takes an average of 12 to 14 years for a new drug to be placed on the market.
In reality, very few drugs are approved to complete the entire trial process. In fact, only about 10% of drugs that begin preclinical testing are approved to proceed to Phase 1 trials; further, only about 21.5% of drugs that are studied in Phase 1 make it successfully to the NDA and marketing approval process.
If anything, this demonstrates the rigor of the clinical trial process. Only the best and safest drugs make it to store shelves. We owe all of our successful health treatments to the clinical trial process.
It is easy to take our healthcare for granted. But as evidenced by our clinical trial overview, our daily health is reliant upon the highly regulated clinical research process. Countless hours, resources, and people are poured into the approval of each drug.
For that reason, it is crucial that we contribute to the clinical trial process when possible. Whether you decide to participate in a clinical trial or to pursue research yourself, you will directly make a contribution to the world of medicine and to the rest of humanity. Our daily health rests upon the hard work and dedication of the individuals who aid in the drug development process.
- Pharma 101 with PharPoint: Phase 1 Clinical Trials
- What I Learned During my Clinical trial Internship
- Ask a Clinical Trial Expert: Study Rescues
- Thought Leader Spotlight: Jim Nance on Adaptive Trial Design and the Current CRO Landscape