What Happens Before Clinical Trials Happen?

Before a product, such as a medication, enters clinical trials, researchers conduct rigorous and in-depth analysis. Preclinical testing is done in two distinct ways:

• In vitro research: This type of research is conducted with cells under a microscope and in test tubes. It’s in a controlled environment where researchers can study specific factors up close.
• In vivo research: This type of research is conducted in animal models. They look at how the product interacts with a living animal to gather more insight.

Such research occurs before the start of clinical trials to gather important data about what could happen in people. However, while these are important steps in developing new medications and solutions, they cannot replace testing products in the human body.

With drugs, researchers must work with the Food and Drug Administration (FDA) throughout development, starting with the creation of an Investigational New Drug (IND) process. This requires a company or sponsor to provide details and results from all the preclinical studies to demonstrate that the drug should move into clinical trials.

Designing and Building Clinical Trials

Once a product is ready for testing, the research team must begin the IND. This process will include the following, as noted by the FDA:

• Animal study data is gathered, and toxicity to animals is considered, including any side effects that may cause significant harm.
• Manufacturing information must be noted.
• Clinical protocols are outlined for clinical studies, which serve as study plans detailing what will be examined and monitored.
• Data from any prior human research must be presented.
• Information about the investigator(s) is presented.

This initial step is meant to ensure a complete understanding of what people are getting into when it comes to clinical study.

A team of scientists and others is created by the FDA to review the IND application. It is an extensive process to ensure the safety and scientific integrity of the project. The FDA IND review team will include contributions from several professionals, which may include:

• Overseeing project manager: This person’s job is to coordinate activities throughout the process. They become the primary contact for the sponsor of the research.
• Medical officer: A medical officer reviews initial clinical study information and data being presented before clinical trials, as well as during and after completion of the trial(s).
• Statistician: As the numbers person, the statistician interprets clinical trial designs and data, working to ensure that trials have clearly defined protocols, safety standards, and efficacy data.
• Pharmacologist: The pharmacologist’s main objective is to review preclinical trial studies to validate, from a medication standpoint, the worthiness of the medication.
• Pharmacokineticist: This person’s job will be to collect data on the drug’s function in a person, including absorption, distribution, metabolism, and excretion. They will also investigate data about time intervals within the trials, dosing guidelines, and administration schedules.
• Chemist: The chemist provides a review of the drug’s chemical compounds, analyzing factors including manufacturing stability, quality-control strategies, continuity of the medication, impurities or risks of them, and other aspects.
• Microbiologist: This team member will take submitted data and assess potential response across various classes of microbes, if applicable, to the system.

The FDA may stop or delay a clinical trial through a clinical hold or halt investigation. This can be done if the FDA finds any error or lack of authenticity in any component of the IND, such as:

• Too much risk to participants based on exposure
• The investigator in the clinical trial does not satisfy the required qualifications
• Materials for volunteer participants are unclear or misleading
• The application does not include enough information about risks

Clinical holds are uncommon because most researchers take the necessary steps to avoid these concerns. You can expect the FDA to be thorough for the protection of participants.

Phases of Clinical Trials

Clinical trials undergo numerous phases, and the amount and type of work done in each are often influenced by what happens in the trial prior. Data from the National Institutes of Health shows that you can expect the following phases of clinical trials as you participate.

Phase 1 Clinical Trials

Phase 1 clinical trials are not designed to test effectiveness, but rather to assess the safety of a drug. They typically include a small group of people, usually healthy volunteers, to test reactions and experiences humans have when using a drug. Most Phase 1 clinical trials involve 20 to 100 participants.

Phase 1 trials may include participants with certain diseases, often those who have not found success in other treatments and have no other options. During this phase, researchers are looking at the following questions:

• Are there adverse side effects?
• How does the body break down the drug?
• How fast does the drug clear the body?
• What dosing may be appropriate for use of the drug?
• What is the best method for ingestion, such as by mouth, in tablets, infusions, or injections?

Most trials begin with a very small dose and gradually increase it to determine if any concerns arise. These studies continue for several months. Data is then submitted to the FDA for approval of the next phase.

Phase 2 Clinical Trials

In the next phase, a larger group of people, typically those with the disease or condition, will be introduced to the drug. The objective here is to test the drug’s safety and effectiveness—is it doing what you expect it to do? It also continues to examine any side effects that may not have been evident in the initial phase.

Phase 2 clinical trials typically have 25 to several hundred participants. This larger population sampling creates opportunities to observe how various individuals, such as those of different ages or genetic backgrounds, may react. This study typically includes a control group, which receives a placebo treatment that mimics the drug. This may include an injection of saline or a sugar pill instead of the actual drug to facilitate scientific accuracy.

Researchers will consider:

• Does the drug work as expected?
• Does the drug have numerous toxic side effects?
• Are there competitive products much like the drug on the market?

These phases can take several months to several years to complete. They are the most intense stage because they tend to shape decisions on how the next phase will unfold.

Phase 3 Clinical Trials

The third phase brings with it the largest study of a drug’s use. It is the last step before a drug is approved by the FDA and made available. These studies typically include hundreds to thousands of people who have a relevant disease or condition and who will now receive treatment with the drug under development.

These drug trials are typically randomized, meaning a control group is established to receive a placebo or standard care for the disease. Doctors and participants do not know who is getting the actual drug to protect the integrity of research data.

In this phase, researchers are testing to learn:

• If the drug works
• What safety risks exist

Approximately 25% to 30% of drugs will progress beyond Phase 3 to approval. If unsuccessful, some drugs may go back, make changes, and try again.

Final Review

The final phase requires submitting all research and testing data to the FDA for a thorough review to be completed. Before a decision, the FDA will consider all clinical data as well as information about potential dependency, safety updates from clinical trials, and studies from other countries.

After the drug is approved, the FDA continues to monitor its use, even after the medication is made available to the public. Additional trials may also be conducted as a treatment for related or other conditions as appropriate.

This process takes time—the FDA needs ample data to answer every question before it determines if a drug is safe enough to recommend.