Understanding the Value, Complexity of Clinical Trials in the US
Clinical trials in the US study new drug developments and evaluate the effects in humans.
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- Clinical trials are an integral part of new product discovery and development. These trials (or clinical studies) test and assess potential treatments such as drugs, medical devices, or biologics (vaccines, gene and cellular therapies, insulin, etc.) in human volunteers to determine approval for widespread use.
Researchers must complete numerous steps to ensure product safety and efficacy. FDA clinical trials regulations guide the process of safe medical product development and ensure quality evidence generation. Therefore, clinical trials begin with years of laboratory research to examine the effect of treatment on cells and animals, and promising treatments deemed safe are progressed into clinical trials.
What Is a Clinical Trial?
Clinical trials comprise four phases and contribute to medical knowledge related to treating, diagnosing, and preventing diseases or conditions. The FDA actively mitigates risks to participants, but all risks cannot be eliminated entirely due to the uncertainties inherent in clinical research.
Phase I
The experimental treatment is tested on a small group of healthy individuals (20–80 people) to determine the correct dosage and the product’s safety and side effects.
Phase II
The experimental treatment is tested on a larger group of individuals (100–300 people) who are known to have a particular disease or condition. This phase is used to collect preliminary effectiveness data. Because this trial continues to monitor treatment safety and short-term side effects, this phase can last several years.
Phase III
The experimental treatment is tested on an even larger group of different populations (several hundred to ~3,000 people) using different dosages and in combination with other drugs to assess safety and effectiveness further. If the FDA determines the trial results are positive, the experimental drug or device will be approved.
Phase IV
This phase occurs after the FDA has granted approval for the experimental treatment. The effectiveness and safety continue to be monitored in large, diverse populations. Unfortunately, the side effects of some treatments are not noticed until a much larger number of individuals have taken the treatment over more extended periods of time.
The US FDA approval process is complex, and studies show that approximately only 1 in 10 drugs that begin the clinical phase will make it to the market.
The Role of Placebos
Occasionally, a placebo — an identical, inactive substance that holds no therapeutic effect — is used to compare the results from two groups.
A randomized and placebo-controlled study is the gold standard for clinical trials, meaning participants are randomly assigned to a control group or test group. The test group receives experimental intervention, while the control group receives standard care or a placebo. In most trials, not even the research team has knowledge of which participants receive the placebo, treatment, or an alternative intervention. A double-blind, placebo-controlled clinical trial is when participants and staff are unaware of the treatment details throughout the study.
Who Conducts Clinical Trials?
The FDA monitors clinical studies, ensuring they are designed, conducted, analyzed, and reported according to good clinical practice (GCP) and federal regulations. In addition, every clinical study is led by a principal investigator (PI) — often a medical doctor — with the help of a research team consisting of healthcare professionals such as doctors, nurses, social workers, among others.
All clinical studies follow a research plan created by the PI known as the protocol, which is designed to protect the health and safety of participants and answer related research questions. The protocol establishes the study’s reasoning, participant eligibility criteria, number of needed participants, scheduling and dosage details of interventions and procedures, study duration, and a list of information to be gathered from patients.
To protect participant safety, the protocol is used to explain details of the study and possible benefits and risks. The research team must gain the approval of an Institutional Review Board (IRB), which is responsible for protecting the study participants. The IRB reviews the study plans and monitors the study. If the research team or IRB suspects that the study risks outweigh the benefits, the study will be terminated, and the study initiator will be notified.
Observational Studies
This type of study is used to examine a specific kind of group or activity, like a survey. According to a research plan or protocol, the PI analyzes health data in participant groups. Interventions and procedures that are included in the patient’s routine medical care may be given to participants, but no clinical trial interventions or procedures are provided.
Who Can Participate in Clinical Trials?
Standards outlining who can participate can be found in the research protocol. Inclusionary and exclusionary criteria dictate qualified participants, often based on characteristics like gender, age, type and stage of illness, health history, and other existing medical conditions. While some research studies seek healthy individuals, some research studies pursue participants who have the specific illness or condition being studied. Some studies are restricted to a predetermined group of participants who are asked to join.
Expanded Access (Compassionate Use)
For individuals unable to participate in clinical trials, experimental drugs/devices may be available through expanded access outside of a clinical trial setting. When no comparable treatment exists, expanded access — also called compassionate use — allows for an investigational medical product for individuals with severe or life-threatening conditions.
A participant may qualify for expanded access if the patient has a life-threatening condition or severe disease, if no other comparable alternative treatment option exists to diagnose, monitor, or treat the condition, if clinical trial enrollment is impossible, or if the patient’s potential benefits justify the potential risks.
Who Funds Clinical Trials?
The National Institutes of Health (NIH) and the pharmaceutical industry fund a vast majority of research; however, most funding is provided by the pharmaceutical industry. Research America found that the industry supplies 64% of all applied biomedical research and development funding, while only around 22% comes from the federal government. Annually, the National Institutes of Health invests around $41.7 billion in biomedical research and development.
While pharmaceutical companies, federal organizations, academic medical centers, and voluntary groups can sponsor clinical research, doctors and other healthcare providers can also fund clinical studies.
Location and Duration of Clinical Trials
Because the location depends on who conducts clinical research, studies can be performed in hospitals, universities, physician practices, and community clinics.
There is no standard timeframe since the length of the clinical study depends on the treatment being studied.
Demographics of Clinical Trials
Unfortunately, most clinical trials do not accurately represent those with a specific illness or the general population. Although the FDA encourages diversity, clinical trials predominately consist of white males.
Clinical trials severely underrepresent females, the LGBTQIA community, the elderly, and people of color, predominantly Black and Hispanic. According to the 2020 US Census Bureau, 13.4% of the population is Black or African American and 18.5% is Hispanic or Latino. Still, in Phase I oncology trials, Camidge et al. found that just 3.9% and 1.2% of the participants identify as Black/African American and Hispanic, respectively.
Despite efforts by research institutions, people of color often don’t volunteer to participate in clinical studies due to medical distrust stemming from past victimization and exploitation, financial barriers, and logistical challenges.
While drug development is a lengthy and costly regulated process, it is instrumental in moving the industry forward and improving healthcare.
