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What is a Clinical Trial?

In the United States, the Food & Drug Administration, or FDA, sets the guidelines and regulations surrounding clinical trials. Clinical trials are used to test the safety and efficacy of new treatment options, including drugs, behavioral modifications, diets, and medical devices [1]. Once approved, a therapy can be prescribed by doctors as a new treatment option for patients. This article will give a brief overview of the history, structure, and future of clinical trials.

History of Clinical Trials

Prior to the creation of the FDA, very little testing, if any, was performed on drugs being sold in the United States. Sadly, many of the rules and regulations that exist today to protect American citizens were created in the wake of tragic events and loss of human life. Two significant events that shaped the early FDA’s power to regulate the drug market: the sulfanilamide tragedy in 1937 and the thalidomide tragedy in 1961 [2]. 

Sulfanilamide, an antibiotic designed to treat strep throat and marketed as an “elixir”, had been reformulated with a poisonous compound, diethylene glycol, that killed over 100 people in 1937 [3]. After this event, the FDA required companies to test their drugs for safety, however, there was no standardized process for these trials, making it hard to compare one therapy against another.

Thalidomide, a drug broadly prescribed outside of the United States to alleviate morning sickness, was found to cause severe birth defects. This tragedy did not reach the United States, because an FDA employee, Frances Kelsey, felt that the safety data submitted by the manufacturer was not sufficient to approve the medication for widespread use, particularly in pregnant women [4]. Following these events, the FDA was granted more oversight and control over the drug approval process, supporting the creation of the clinical trial structure in place today.

Phases of Clinical Trials

Clinical trials are composed of several parts [5]:

  • Preclinical Studies (laboratory setting without human testing)
  • Phase I (safety and dosage in healthy volunteers)
  • Phase II (safety, dosage, and efficacy in intended patient population)
  • Phase III (pivotal trial)
  • Phase IV (post-approval)

Before any therapy is tested on humans, it undergoes rigorous pre-clinical study, typically in isolated cells in a laboratory, as well as in animal models, such as mice or non-human primates. If a therapy displays any safety or toxicity concerns, it cannot move on to Phase I clinical trials until they are addressed. In some cases a development program for a new therapy stops before it ever reaches humans. 

Phase I clinical trials focus on assessing the safety of a treatment and determining the appropriate dosage. In most cases, Phase I begins in healthy volunteers, rather than individuals with the conditions that the therapy is intended to treat. Some exceptions to this exist. Researchers monitor how the body reacts to the treatment and collect information on any side effects.

If a treatment passes Phase I, it moves on to Phase II, where its efficacy is tested in a larger patient population with the condition it intends to treat. Additional information regarding dosage and safety is also collected during Phase II. If significant safety issues arise, a treatment cannot move to Phase III.

Phase III trials are the final step in the process prior to FDA approval. Hundreds to thousands of patients are enrolled in Phase III studies to verify that the drug is safe and effective in a broad patient population. In most cases, the new drug is compared to a placebo, or harmless sugar pill, or the current standard of care (if applicable). Following approval, the treatment can then be prescribed to patients by physicians.

Phase IV trials are a more recent development, aimed at long-term monitoring of a drug’s performance. These efforts can identify if there is any discrepancy between how the drug performed in earlier trials, typically in hospitals or controlled settings, and how it performs in the “real world” with normal use [6].

The Future of Clinical Trials

  • Decentralized Clinical Trials

    Currently, most clinical trials are conducted in hospitals, academic medical centers, and care facilities. While effective, these trials can be limited to a specific region where the facilities are located. For less common diseases and medical conditions, this patient population may not be large enough to properly assess the treatment. A potential future trial design is a decentralized clinical trial, where the trial is conducted across many locations simultaneously. Such a design would require the help of technology to track outcomes, record data, and analyze results [7].

  • Genetic Testing & Clinical Trials

Scientists’ understanding of the role that genetics plays in human health evolves every day. Notably, progress has been made in linking certain changes in the genome called variants with diseases and health conditions. Recently, a drug approval for cystic fibrosis (CF) patients with a specific set of variants [8] has opened the door for similar studies to be conducted in the future. Furthermore, drug candidates are more likely to be successful if they target a gene linked to the disease. By using genetic information to recruit and classify patients, future clinical trials may be targeted to specific disease mechanisms, which is particularly relevant for patients suffering from complex and chronic disease [9]. 

  • Single Subject (n-of-1) Clinical Trials

Recently, attention has been brought to the idea of “individualized” or “personalized” medicine. A potential clinical trial design to support this new paradigm is the n-of-1 trial, where treatments are tested in an individual patient to determine the best option for their unique situation. For patients with rare conditions or uncommon genetic variants, this approach may lead to the development of a more effective treatment and management plan. 


Clinical trials have become the cornerstone of safe and effective treatment development across the world. The design of these trials changes as new information is made available and innovative approaches allow researchers to improve the efficiency of the process.

All clinical trials must be registered with the FDA in the United States, and this information is available to the public at ClinicalTrials.gov. Clinical trials specific to pancreatic diseases can be found via the Clinical Trial Resource Center of the National Pancreas Foundation (NPF). If you are interested in learning about clinical trials, speak to your physician to discuss your eligibility, as well as the associated risks and potential benefits with participating.