Veterinary Clinical Studies

Veterinary clinical studies can be used to support the effectiveness and/or safety of a new product in a target species, or can be used for comparative medical purposes.  Veterinary studies are often categorized into studies used in support of the approval process (pivotal, confirmatory) or pilot studies.

Before initiating a veterinary clinical study or shipping veterinary investigational product, it is important to determine what regulatory requirements are necessary.

Key DifferencesVeterinary Clinical Trials Compared to Human Clinical Trials

Pre-Clinical

Although not necessarily required, human drugs are often evaluated for safety and pharmacology attributes (ADME) in lab animal models prior to entering human studies.  The veterinary drug development process may take into account lab animal studies, but veterinary drug registration is contingent on studies supporting target animal safety and effectiveness.  The target animal is the species in which the product is intended to be labeled for use.  For instance, to obtain a veterinary registration for dogs, the effectiveness and safety must be evidenced in the dog.

Trial Phases

Unlike human clinical studies, confirmatory veterinary clinical studies are not formally referred to as Phase I, II, III or IV.  Phase  I-IV are terms used for human clinical trials intended to support a NDA or BLA or during post-marketing.  Veterinary studies are sometimes referenced as Phase I, II, III or IV in the literature, but these terms are inaccurate in the context of the veterinary approval process.  The appropriate terms are Target Animal Safety Studies (TASS) and Target Animal Effectiveness Studies (TAES).

Patient Information

Veterinary medicine is not subject to The Health Insurance Portability and Accountability Act (HIPAA).  However, owner and patient information obtained during the course of a veterinary clinical study may be subject to certain obligations of the Sponsor, regulatory agency, clinic, and/or other stakeholders involved in the veterinary clinical study and registration process.  With that stated, certain states consider veterinary patient medical records subject to obligations of protected health information (PHI).

Types of Veterinary Clinical Studies

Veterinary clinical trials generally fall into several categories, ranging from small pilot studies (proof of concept (POC) veterinary studies) to confirmatory studies in support of a veterinary product registration.  Study sponsors that are just beginning their veterinary research endeavors may benefit from having a good understanding of the registration process and types of veterinary clinical trials required for each agency.

veterinary clinical trials

Pilot: Proof of Concept Veterinary Clinical Studies

Before starting pivotal / confirmatory veterinary clinical studies, many companies will conduct pilot clinical trials in the target species to:

  • obtain preliminary data of safety, efficacy, and effectiveness
  • determine optimal dosing schedule, and/or
  • obtain data to attract investors and strategic partners.

It is important obtain guidance before starting any study in a target species, as certain studies may be subject to state and federal authorizations before starting.

Good Clinical Practice: Veterinary clinical studies intended to support a veterinary registration must be conducted under strict conditions and the clinical trials sites are subject to regulatory agency auditing.  One resource is the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) VICH GL9- Good Clinical Practice (PDF – 356KB).

Pivotal: Confirmatory Veterinary Clinical Trials

Target Animal Safety Studies (TASS) are conducted to assess the safety of a veterinary product in the target species.  Safety studies may also include dose escalation in the target species depending on the type of product being evaluated (drug vs. biologic).  Often, target animal safety studies are performed by veterinary contract research organizations (CROs).  Veterinary safety is also evaluated during larger field efficacy studies in client-owned animals with the disease of interest.

Target Animal Effectiveness Studies (TAES) – Target animal effectiveness studies are performed in the target species having the disease or condition of interest.  These are normally conducted in client-owned animals under Good Clinical Practice (GCP) conditions.  Target animal effectiveness (efficacy) studies used to support registration require authorization and protocol concurrence with either by the FDA-CVM or USDA-CVB.

Veterinary Study Sites

veterinary clinical trials studies

Veterinary Trial Site Selection

Veterinarians often get little training on veterinary research and conducting clinical studies.  As such, many veterinary clinics are not familiar with conducting studies or the elements of Good Clinical Practices.  Therefore, it is important that sponsors, site management organizations, and/or veterinary contract research organizations select the right sites in order to perform the veterinary study.  With that stated, there are a number of private practices that have a strong track record of being involved with field effectiveness studies and are routinely involved with veterinary pilot and pivotal studies.

Feasibility of Veterinary Studies

Veterinary CROs should qualify veterinary clinical trials sites; which often begins with a feasibility assessment.  The feasibility assessment may involve a site qualification visit (SQV) and/or site questionnaire to verify the site has sufficient resources, training and expertise to conduct the veterinary study.   In addition to the site’s expertise and resources, the site feasibility should determine if the site has an adequate patient population, estimated patient accrual rates, hours of operation, and other factors before activating a clinical trial site (more information below).

Veterinary Study Personnel

veterinary clinical study personnel

Veterinary Clinical Study Investigators

Sponsors should qualify investigators based on a number of factors, including their training, experience, and familiarity with conducting veterinary clinical trials under Good Clinical Practice conditions.  Most sites will have a Principal Investigator (PI) that can further delegate responsibilities to site specific veterinary study team personnel.  These responsibilities are often reflected in a Delegation of Authority (DOA) log, signed by each veterinary clinical study team member.  The veterinary PI is ultimately responsible for all study activities at their respective veterinary trial site, but often have sub-Investigators who can manage the majority of the clinical procedures and other obligations occurring at the veterinary clinical trial site.

Veterinary Study Coordinators and Monitors

Veterinary Clinical Research Coordinators play a key role on the veterinary clinical trial team.  The veterinary clinical study coordinator is often assigned by the veterinary PI, and can provide study support through owner consenting, and patient screening, scheduling, data capture, source documentation and care.

Veterinary Clinical Study Monitors are used by the Sponsor or veterinary contract research organization to routinely monitor clinical trial sites.  Veterinary study monitors may visit the veterinary trial sites to review records, source documents, and other materials which are important for ensuring the integrity of the study.  Monitoring visits should occur before, during, and after a study has completed enrollment.

Additional Info: Veterinary Clinical Studies

Clinical Study Costs (Target Animal Safety and Effectiveness):  The cost of conducting a veterinary clinical studies can range from several thousand dollars to several hundred thousand dollars.  Veterinary study costs are often broken down into fixed and variable expenses.   Fixed costs can include site fees, document preparation, monitoring fees, data tabulation, and report generation while variable costs are often directly associated with patient procedures.  Veterinary clinical study costs are often influenced by several factors, including but not limited to:

Study Conditions: non-GCP, GCP or GLP. Proof of concept studies may often involved only a few number of subjects (10-30), and are often performed under non-GCP conditions. Pivotal studies that are used to support a products approval are most commonly performed under GCP or GLP conditions, and are typically more expensive owing to the degree of documentaiotn and QA/QC involved in these studies.

Duration: The duration of a veterinary clinical study can vary, from days to years, depending on the investigational product being evaluated.  For instance, a product that may only be used for acute and critical care situations or that may only be used once can often be evaluated over a few days. Other products that are anticipated to be used frequently over extended periods of time are often studied for months or longer.

Number of Subjects: Pilot studies often involve only a few number of veterinary patients, so the patient specific costs are often lower to complete the study. Confirmatory studies (safety and efficacy) may require a larger number of patients, sometimes several hundred patients.

Outcomes for Assessment: The outcomes for assessment often drive the information which will be used to evidence safety or efficacy.  There are a variety of subjective and objective data that can be obtained through physical exams, bloodwork, special diagnostics, imaging, etc.

What is the total cost of developing a new animal drug or new animal biologic? The registration process for a new veterinary drug or veterinary biologic in the United States may take 4-6 years of development work for companion animals, and may take longer for food production animals.  Although there are not published expenditures, Woods Consulting, LLC estimates the cost for conducting companion animal TAS and TEA studies are between $3-7 million dollars depending on the species, duration of treatment, and anticipated label claims.  This does not take into account the cost of drug/biologic failures or other factors such as licensing fees, etc.  The costs for developing minor use minor species (MUMS) products may be lower.

Study Feasibility

Feasibility: Veterinary clinical trial feasibility is essential in determining if a study and the anticipated sites have sufficient resources, veterinary subjects, training, etc. to effectively and efficiently perform the veterinary clinical study.  A veterinary clinical study should have a feasibility assessment that takes into account the overall study program, the sites, and the personnel involved in the veterinary clinical study.

Veterinary Clinical Study Program Assessment should evaluate target disease prevalence, ethical considerations of the new veterinary treatment or intervention, and regulatory aspects of the study.  Disease prevalence is key to understanding the anticipated veterinary study patient accrual rates.  For instance, if the disease prevalence is low, the veterinary clinical trial may need to be expanded to more sites in order to satisfy the patient accrual requirements.  Even if the disease prevalence is high, the veterinary study’s inclusion and exclusion may limit the number of qualifying veterinary study subjects that can be enrolled and also contribute to the number of sites that will need to participate.
This assessment should take into consideration:
  • the availability of comparator treatments to be used in the study,
  • patient inclusion and exclusion,
  • study data capture and management (electronic data capture methods),
  • veterinary acceptance of study related research procedures,
  • risks and benefits of the study intervention (veterinary study treatment),
  • logistics and operations of the study, and
  • competitive studies which may interfere with veterinary clinical trial patient recruitment.
Site and Veterinary Investigator Feasibility should be performed for each veterinary clinical trial site.  The site and the study personnel are critical components of performing veterinary research in an effective manner.  Veterinary study sites should be evaluated for:
  • existing patient population,
  • site resources, equipment and overall facilities,
  • hours of operation,
  • investigational product security and storage capabilities, and
  • allocation of sufficient space to store veterinary clinical study documents (regulatory binders, patient binders, etc.).
In addition to the site, the personnel involved with the veterinary clinical study (site study team) should be evaluated for their experience, dedication to the study, qualifications to perform the veterinary study related procedures, and each study team’s ability to effectively interact and coordinate the study protocol and procedures.  Site level feasibility is often conducted during a veterinary clinical trial site qualification visit (SQV).
  1. Common Acronyms used in Human and Veterinary Clinical Trials
    ADR: Adverse Drug Reaction
    AE: Adverse Event
    ALCOA: Attributable, Legible, Contemporaneous, Original, Accurate
    API: Active Pharmaceutical Ingredient
    CAPA: Corrective and Preventive Action
    CBER: Center for Biologics Evaluation and Research
    CDER: Center for Drug Evaluation and Research
    CDRH: Center for Devices and Radiological Health
    CFR: Code of Federal Regulations
    CMO: Contract Manufacturing Organization
    CRF: Case Report Form
    CRO: Contract Research Organization
    DHHS: Department of Health and Human Services
    eCRF: Electronic Case Report Form
    EDC: Electronic Data Capture
    EHR: Electronic Health Record
    EMR: Electronic Medical Record
    FDA: Food and Drug Administration
    FWA: Federal-wide Assurance
    GCP: Good Clinical Practice
    GDP: Good Documentation Practice
    HIPAA: Health Insurance Portability and Accountability Act
    ICF: Informed Consent Form
    ICH: International Council for Harmonization
    IDE: Investigational Device Exemptions
    IND: Investigational New Drug (Application)
    IRB: Institutional Review Board
    PHI: Protected Health Information
    PI: Principal Investigator
    QC: Quality Control
    SAE: Serious Adverse Event
    SMO: Site Management Organization
    SOE: Schedule of Events
    SOP: Standard Operating Procedure
    ANADA: Abbreviated New Animal Drug Application
    NADA: New Animal Drug Application
    INAD: Investigational New Animal Drug Application
    IACUC: Institutional Animal Care and Use Committee
    SIV: Site Initiation Visit
    SQV: Site Qualification Visit
    QA: Quality Assurance
    CMC: Chemistry, Manufacturing and Controls
    VSM: Veterinary Service Memorandum
    OLAW: Office of Lab Animal Welfare
    CVM: Center for Veterinary Medicine
    CVB: Center for Veterinary Biologics
    USDA: United States Department of Agriculture