FDA Clinical Trials

When new drugs and devices are being evaluated for safety and effectiveness in humans, researchers conduct clinical trials. Clinical trials are the final stages of a research process designed to determine new ways to prevent, detect or treat diseases. They are at the core of the health care industry, an essential step in obtaining medical knowledge and achieving medical advancement.

As of Dec. 2, 2022, ClinicalTrials.gov lists 434,977 trials. These trials are taking place in all 50 states and 221 countries. About 53% are occurring outside the U.S., 31% are in the U.S. and 5% are both in and outside of the U.S.

Conducted after laboratory and animal testing, clinical studies rely on human volunteers who meet certain eligibility requirements. These studies are not without risks. Therefore, participants should be knowledgeable about what to expect and what safeguards are available. They should weigh the benefits of participating against any potential risks, or even risks that may be undetermined at the start of the trial.

Finally, patients taking new drugs and receiving other forms of treatment should be aware that clinical trials are not fail-proof, and that funding, bias, trial errors and other factors can affect results. Additionally, clinical studies continue after FDA approval, meaning new side effects and/or complications, especially previously unknown long-term risks, can always later present themselves.

According to the National Institutes of Health (NIH), a clinical trial is “a research study in which one or more human subjects are prospectively assigned to one or more interventions to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.” Clinical trials are important in determining which medical approaches work best for certain types of illnesses or specific groups of people.

Each trial answers a specific scientific question (theory or hypothesis), aimed at finding new or better ways to prevent, screen for, diagnose and/or treat various diseases. Trials can also look for comparisons between new and existing treatments.

Clinical trials provide the evidence. In order to make the best decisions about the care of individual patients, health care providers should combine their clinical knowledge, gained through experience, with evidence obtained by studying the results of clinical trials.

“Good doctors use both individual clinical expertise and the best available external evidence, and neither alone is enough,” authors wrote in a 1996 paper entitled Evidence based medicine: what it is and what it isn’t.

Each process begins in a lab, where scientists first develop and test new ideas. At this stage, most of the experimentation is performed in a test tube. If results seem to be promising, scientists move on to animal testing. This helps show researchers how an approach to a treatment or new drug responds in a living organism. This is the preclinical phase. But just because experimentation is successful in a lab or in an animal, that does not guarantee it will be successful in a human. That is why research in humans is the next necessary step in the process.

However, in the U.S., before a drug is tested in humans, an investigational new drug (IND) application must be filed with the FDA. The IND includes a comprehensive report on all the data on animal studies, the composition of the drug, how the drug is absorbed and eliminated, side effects, and other information.

The FDA reviews the application before allowing (or stopping) the trials to proceed in humans.

A protocol is an action or research plan in a clinical trial. It explains what will be done in the trial, how it will be done and why each step in the trial is necessary. Clinical trials use volunteers, or participants, to take part in each study and to follow the protocols. Sometimes the trial requires certain specifications to be met, such as only males or only females, or those already affected by certain diseases or ailments. Other times, the studies require healthy individuals. The protocol is designed to answer specific questions and to safeguard the health of the participants in a clinical trial.

Different types of clinical trials are used depending on what researchers are studying. Each type of clinical trial has a different focus.

In drug development, clinical trials consist of four phases, with each phase having a different purpose to aid in providing scientists answers to proposed scientific questions. Researchers start with smaller groups of people and more focused objectives, gradually working up to larger trials aimed at collecting additional useful information regarding not only the drug’s safety and effectiveness, but also its risks, benefits and best uses.

Conducting clinical trials can help researchers find new drugs, devices and treatment strategies, but results may also show that the new form of medical intervention offers no benefit or causes harm.

Some reasons why clinical trials may be conducted include:

• Evaluating various interventions, such as drugs, devices or other treatments and therapies, for treating certain diseases or conditions.
• Finding ways to prevent the development or recurrence of certain diseases or conditions, including vaccines and lifestyle changes.
• Evaluating various interventions designed to identify or diagnose certain diseases or conditions.

Clinical trials are overseen by a principal investigator, who is typically a medical doctor. A research team made up of doctors, nurses, pharmacists, social workers and other health care professionals will also aid in carrying out the clinical trial protocol and recording of data.

The sponsoring and funding of clinical trials often comes from the pharmaceutical companies manufacturing the drugs, devices and other treatments. Academic medical centers, voluntary specialty groups and governmental agencies, such as the National Institutes of Health, as well as doctors and other health care providers, can also sponsor trials.

The U.S. Food and Drug Administration requires certain clinical trials to register with and submit results information to the ClinicalTrials.gov databank. Clinical trials that are subject to these requirements include trials conducted on both drugs and devices. Every clinical trial that receives funds from the NIH is automatically required to register and submit results information to ClinicalTrials.gov. The goal of sharing the information is to avoid unnecessary and duplicative trials.

Participant Protection

In addition to those conducting the clinical trials and the governmental agencies regulating the trials, an Institutional Review Board (IRB) is put into place to review, monitor and approve biomedical research involving human subjects. An IRB is an independent committee made up of physicians, statisticians and other members of the community. Its primary role is to make sure that the study is being conducted ethically. It protects the rights and well-being of the participants and ensures that the benefits outweigh the risks.

One way an IRB ensures participant protection is with its review of informed consents. A signed informed consent is evidence that the document and other pertinent information regarding the study has been provided to the prospective individual seeking to participate in the research. An IRB review of informed consents also ensures an institution’s compliance with appropriate regulations.

New medical treatments are typically tested in the people they are designed to help. This wasn’t always the case, with most new drug testing historically performed only in white males. Women, blacks and minorities were not adequately represented, even though more recent studies have shown that drugs often work differently in people of varying ages, races, ethnicities and genders. The FDA is now tasked with ensuring that different groups are included and represented accordingly in clinical trials.

Each clinical trial has its own eligibility standards. These standards are listed in the protocol and specify whether individuals must be healthy or whether they must already be diagnosed with certain diseases or conditions.

Any criteria that disqualifies a person’s participation is called exclusion criteria, and can include various factors relating to age, gender, type and stage or progression of certain diseases or conditions, prior treatment history, and other medical conditions that may put individuals at risk by participating in the trial.

Being selected to participate in a clinical trial does not guarantee that an individual will receive the drug or other medical treatment being studied. While some people volunteer simply to help advance medical knowledge, others volunteer for these types of intervention trials because they have been unsuccessful in treating a disease or condition from which they are already suffering. But often, trials are randomized, some even blindly, meaning there’s no way for either the participant or the researcher to know who is taking the drug being tested and who is taking the other intervention, which may be a placebo.

The FDA reported in a 2000 Harris Poll of cancer clinical trial participants that 76 percent of the individuals surveyed said they decided to participate because “they believed that the trial offered the best quality of care for their disease.”

But FDA pharmacist David Banks warned against participating in clinical trials simply due to the potential of free treatments or other compensation. Banks said individuals attracted to a study for those reasons may overlook known risks associated with the new drug or treatment or fail “to adequately appreciate the potential for discovery of serious new side effects during clinical testing of a new treatment.”

In addition, patients could be taking placebo and therefore would not experience the benefits of the active drug.

One resource to find more information on a clinical trial is ClinicalTrials.gov. This government site contains easy-to-maneuver search tools to find studies by topic or by phrases. Patients can also speak with their doctors and other medical professionals who contribute to their care about what studies might be available to them for participation for certain diseases, conditions or chronic illnesses.

Some Things to Consider

Oftentimes, the safety and efficacy of an experimental approach of a new drug, device or other treatment, may not be fully known at the start of the trial. Some trials may be able to provide participants with prospective medical benefits, while others cannot.

Trials often involve some type of risk or potential harm or injury to its participants. Trials will also often require participants to go through additional procedures, tests and assessments based on the particular study protocol. All of these risks and requirements should be included in the informed consent document provided to participants prior to the start of the research.

Once a clinical trial is completed, the researchers carefully examine all of the collected data before making a final determination as to the meaning of the findings or whether further testing may be needed. Following Phase 1 and Phase 2 trials, researchers have to decide whether to stop testing if it is determined that the new drug, device or other treatment being tested was found to be unsafe or ineffective. After Phase 3 trials, researchers make conclusions regarding the medical importance of the new treatment approach to certain diseases or conditions.

Clinical trial results are often published in what is called a peer-reviewed scientific journal. Peer review refers to the evaluation of a manuscript by experts in that particular field to determine if it is appropriate for publication. Peer review is vital for maintaining the quality of scientific literature.

If the results of a clinical trial are particularly significant, they may be widely discussed among members of the news media, at scientific meetings and by patient advocacy groups. If a new treatment approach has been determined to be safe and effective during a clinical trial, it may become accepted as the new standard of care for a certain disease or condition.

A publication focused on clinical research, recently reported that according to industry findings, almost 90 percent of new drugs and treatments that reach the clinical testing stage never make it to FDA approval status. Many factors can contribute to clinical trial failure, including delays and setbacks due to not maintaining proper protocols imposed by the FDA and/or not meeting predetermined criteria and timelines, also set by the FDA.