Clinical trials are an essential part of ongoing cancer treatment. Clinical trials are performed all across the United States with hope of translational medicine. If in the process of improving the lives of our patients, there is also the possibility of providing information and treatment options for human medicine.

What does clinical trials in veterinary medicine mean? It is the use of client-owned animals for the intention of gaining medical knowledge. This may be determined by evaluating dose, toxicity or efficacy of a new treatment, comparing a new treatment to standard of care treatment, comparing two available treatment options to one another or evaluating drug combinations for efficacy and toxicity in treatment of specific diseases.

The National Health Institute (NIH) breaks clinical trials down depending on the type of clinical trial being conducted. Prevention clinical trials are looking at a better way to prevent occurrence or recurrence of a disease. Screening clinical trials are improving ways of detecting a certain disease. Diagnostic clinical trials are finding better or improved diagnostic tests for diagnosing a certain disease. Treatment clinical trials are testing experimental treatments, new combination of drugs or using commonly used drugs in a new way. Quality of life clinical trials are increasing comfort in patients with chronic disease. Lastly, compassionate use clinical trials are providing unapproved treatments to patients who have failed all other treatment options.

All clinical trials start with an idea by a doctor, researcher, drug company, etc. With each clinical trial, there are essential key players. The first and by far the most important is the Principal Investigator (PI). This person(s) is the lead researcher and the person in charge of getting the grant funding in order to perform the trial. The PI also has direct responsibility for overseeing the clinical trial from start to finish, but this person may or may not be the person who actually came up with the idea for the clinical trial. The PI directs the research and reports back to the funding agency on the progress of the clinical trial. The Co-Investigator works closely with the PI and others involved in the implementation of the clinical trial. Each clinical trial has a sponsor, this is the funding agency who provides the money for the grant. It is beneficial to have a Clinical Trials Coordinator, but not always possible. This person(s) oversees conduct of the trial at the institution and keeps the trial running smoothly. The Clinical Trials Team/Personnel are those individuals who are conducting the trial; following the protocol to ensure adequate sample collection and processing is performed.

A study protocol provides the clinical trials team with all the pertinent information regarding each trial. This includes the objective and background information, design of the study, inclusion and exclusion criteria, description of each study visit, assessment of response if needed, criteria for withdrawal from a study and the sample collection/processing SOPs.

In order for a clinical trial to get started, there is an approval board called IACUC or the Institutional Animal Care and Use Committee. This is a federally mandated committee that oversees the care and use of animals at an institution. They ensure each institution abides by federal requirements related to the care and use of animals. In doing this, they inspect all facilities and animal use areas, review any concerns involving animal care and use, review any proposals for activities involving animal use/care, approve or withhold approval of any protocols and is authorized to discontinue any previously approved protocols if necessary. If there is a change in the protocol, this committee must first approve the change before it can be implemented.

Recruitment for clinical trials can be a challenge, but may be possible through internal hospital cases, using a website or social media, sending an announcement to local referring veterinarian’s or specialists, sending information to breed-specific organizations or using a consult service may be helpful. There are benefits and disadvantages to enrolling a patient in a clinical trial. The potential benefits include the use of a new treatment or drug, financial incentives such as diagnostic tests are paid for, compensation at the end of the study or at the time of withdrawal and the ability to contribute to research. Possible disadvantages may include the new drug/treatment may not provide any benefit to the patient, unknown side effects that could be severe, often there are eligibility requirements that require more invasive/staging tests prior to enrollment and additional visits or diagnostics may be required than normal.

In the world of clinical trials, there is a lot of jargon that is used. An Adverse Event (AE) is any change in the patient that occurs while the patient is enrolled in a clinical trial. Concomitant Medications (con meds) is any medication a patient receives while on a clinical trial that is not part of the study protocol. Maximally Tolerated Dose (MTD) is the highest dose of a drug or treatment that can be given without causing unacceptable side effects. Dose Limiting Toxicity (DTL) is a side effect that is server enough to prevent giving more of the treatment at the same dose. Placebo is an inactive substance used as a control to compare to effectiveness of the drug being tested. Pharmacokinetics (PK) is what the body does to the drug. Pharmacodynamics (PD) is what the drug does to the body. Randomized means each animal enrolled into the study is randomly assigned to receive either study treatment or standard of care/placebo. Masked/blinded means the owner does not know what treatment their pet is receiving. Double-masked/blinded means the owner and the study investigators do not know what treatment the patient is receiving. Placebo-controlled is when some patients are enrolled into the study will be randomized to receive a placebo treatment to isolate effects of the study treatment.

There are four phases of clinical trials and is dependent upon the study characteristics. A Phase I clinical trial is typically to gather data about a drug toxicity and evaluates how the drug is metabolized and excreted in the body. This helps to determine the maximally tolerated dose (MTD) and define the dose-limiting toxicities (DTL). A Phase II clinical trial helps determine preliminary data on efficacy. This data may be compared to patients receiving a different treatment such as the standard of care for that disease or a placebo. Secondary goals for Phase II trials continue to look at safety of the drug/treatment, evaluating additional dosing groups and expanding the data collected for pharmacokinetics (PK) and pharmacodynamics (PD). Phase II is the most common trial performed in veterinary medicine. A Phase III clinical trial uses a large group of patients to confirm effectiveness, monitor side effects, compare to commonly used treatments, and collect information that will allow the drug/treatment to be used safely. Often, these studies are randomized, blinded/double blinded and placebo-controlled. This phase is needed in order to get FDA approval for new drugs/treatments. Lastly, Phase IV clinical trials gain additional information on adverse events, safety, long-term risks, benefits and optimal use of the drug/treatment. These are less common in veterinary medicine, but may be required by the FDA.