Understanding Clinical Trials

What are clinical trials?

A clinical trial is a highly-regulated research study that can take month or even years to conduct, often including multiple phases to determine safety, dosage, efficacy, and outcomes. Participants in these types of studies undertake new procedures, diagnostic tools, or medical treatments to determine if they are both safe and effective in treating specific conditions. In planning the study, researchers take careful precautions to ensure that the processes, procedures, and treatments are safe for the individuals participating in the trials. However, because trials often involve untested processes and materials, the trial may show results that the treatment is effective, ineffective, or identify risks such as side effects that may impact any approved uses.

As one example, a 1990s studies of Highly Active Antiretroviral Therapy, or HAART, was designed to determine the effectiveness in treating HIV and AIDS patients with a combination of antiretroviral drugs, at that time a deadly global pandemic. Today, the epidemic has since been brought under relative control. The most successful of these trials used a combination of three drugs to significantly improve immune response and suppress HIV replication, a dramatic breakthrough that became the modern standard of care and was responsible for turning a life-threatening disease into a manageable medical condition (Hammer et al., 1997).

Clinical trials vs. research studies

If you have heard about research studies and clinical trials, you may be wondering how they differ. Research studies can cover a wide range of approaches to improve understanding of a topic. These approaches can include clinical trials as well as observation and survey studies. A clinical trial is one type of research study. Research studies can also include observations, such as demonstrating that people who practice different types of hygiene, exercise, or nutrition may have superior health outcomes in specific areas.

In one of the earliest clinical trials, British Navy surgeon James Lind of Scotland demonstrated in 1753 that individuals who consumed citrus juice during long voyages would not develop or could be cured of scurvy, a disease caused by Vitamin C deficiency. So effective was this demonstration that citrus fruit became common food on so many sailing vessels that British sailors gained the nickname "limeys." By Lind’s death in 1794, citrus fruit as a treatment and preventive for scurvy was a standard for medical care in the British Navy. (Bhatt, 2010)

Why are clinical trials needed?

For medical science to advance, research studies are needed to determine which compounds, techniques, treatments, and tools work. The effectiveness and safety of these new techniques, procedures, treatments, or tools must be tested before they are released for use on the public. This is where clinical trials come in. By undertaking clinical trials in a safe, careful, well-studied manner with a small number of individuals, the results of the study can be reviewed before the product is approved for use.

As these clinical trials are attempted, any side effects are recorded, including their severity. At the same time, the efficacy of the treatment is also studied, helping medical researchers determine whether any side effects are mild enough to justify the benefits of the treatment. For a clinical treatment to be deemed successful, it must qualify as both safe and effective in the treatment of a specific disease, injury, or illness. In many cases, clinical trials are undertaken to determine whether an existing medication can be used for a new purpose.

When are clinical trials needed?

Clinical trials are undertaken when a medical researcher recognizes the possible benefit of a new diagnostic tool, treatment, or procedure for individuals with a specific condition or illness. This often includes new uses for an existing medication, such as noticing a specific side effect in an initial clinical trial that can be considered a benefit in other circumstances.

However, as medicine continues to evolve and advance, this can include a range of specific factors such as genetics, disease stage, combination of treatments, and similar approaches that can create a synergistic effect for the patients in the trial.

One example of this is a clinical study testing the use of Endari, a medication used to treat sickle-cell anemia in pancreatic cancer patients. Endari is a clinical-grade form of the amino acid glutamine and has already been approved by the FDA for anemia. Researchers had discovered that when starved of glutamine, cancer cells grew faster, but when flooded with glutamine and combined with chemotherapy, the cells shrank. The clinical trial of Endari for stage 4 pancreatic cancer combined with specific chemotherapy is now being tested for a new use in cancer patients. (Wong 2023)

The approval process

For a clinical trial to be approved, it must have protocols developed either by the industry, which is referred to as a sponsor-initiated clinical trial, or by a researcher, referred to as an investigator-initiated clinical trial. Typically undertaken for approval of new drugs or new use of existing drugs, an application for an appropriate clinical trial must be submitted to the FDA for review.

This same approach is taken for new devices, techniques, treatments, or procedures. Once the FDA has approved the protocols and application for the initial clinical trial, the trial may proceed, in an attempt to identify new treatment options for many patients. In most cases, treatment will start with non-complicated cases to ensure the clearest possible results.

How are trials funded?

There are typically two possible sources of funding for clinical trials. The first is research institutions, typically universities or research-based hospitals, focusing on the cutting edge of treatments for a range of illnesses, injuries, or diseases. These institutions are able to bring in donations based on their past research to fund future research, in many cases.

The second source of funding is biotechnical or pharmaceutical companies that are developing new drugs, treatments, devices, and similar treatment options for patients. In these cases, funding often comes from past breakthrough medications or devices that fund the new research, with the hope of a new moneymaking product for the company.

There are a lot of factors that come into play when a clinical trial is planned, applied for, approved, and carried out. These steps are in place to ensure your safety when you sign up for a clinical trial, providing you with protection against foreseeable harm from the drug, treatment, device, diagnostic tool, or procedure.

Sources

Hammer, S. M., Squires, K. E., Hughes, M. D., Grimes, J. M., Demeter, L. M., Currier, J. S., ... & Mellors, J. W. (1997). A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. New England Journal of Medicine, 337(11), 725-733. https://www.clinicalconnection.com/blogs/d65a1ba4-7905-4bdb-b540-7981778161a0/exploring-famous-clinical-trials-lessons-from-success-and-failure

Tejwani, R., Wu, C. F., & Bass, J. (2019). The thalidomide tragedy: lessons from the past for drug safety and regulation today. Journal of the American Academy of Dermatology, 80(6), 1713-1720. https://www.clinicalconnection.com/blogs/d65a1ba4-7905-4bdb-b540-7981778161a0/exploring-famous-clinical-trials-lessons-from-success-and-failure

Wang, Guo. (2021). How optical isomers uncovered the horrors of Thalidomide. I, Science, Spectrum, Fall 2021, The Science Magazine of Imperial College. https://isciencemag.co.uk/features/how-optical-isomers-uncovered-the-horrors-of-thalidomide/

Bhatt A. Evolution of clinical research: a history before and beyond james lind. Perspect Clin Res. 2010 Jan;1(1):6-10. PMID: 21829774; PMCID: PMC3149409.

Gong J, Osipov A, Lorber J, Tighiouart M, Kwan AK, Muranaka H, Akinsola R, Billet S, Levi A, Abbas A, Davelaar J, Bhowmick N, Hendifar AE. Combination L-Glutamine with Gemcitabine and Nab-Paclitaxel in Treatment-Naïve Advanced Pancreatic Cancer: The Phase I GlutaPanc Study Protocol. Biomedicines. 2023 May 8;11(5):1392. doi: 10.3390/biomedicines11051392. PMID: 37239063; PMCID: PMC10216251. https://pulse.cedars-sinai.org/news/new-uses-for-existing-treatments-the-practice-of-drug-repurposing