1. Effectiveness Evaluation for Therapeutic Drugs for Non-Food Animals
Christopher Loss, DVM
Division of Therapeutic Drugs for Non-Food Animals
Office of New Animal Drug Evaluation
USFDA Center for Veterinary Medicine

2. Non-Food Animals Non-food (companion) animals
Dogs
Cats
Horses (in US considered a non-food animal)
Ferrets
Laboratory animals (rodents, primates)
Excludes any animal that is commonly used for food

3. Indications
Therapeutic drugs are drugs used in the diagnosis, cure, mitigation, treatment, or prevention of a disease or condition
Companion animal drugs include a wide range of therapeutic indications. Examples include:
Treatment, control, or prevention of internal and external parasites
Control of pain associated with osteoarthritis or post-operative pain (analgesics)
Treatment of infections (antimicrobials)
systemic and topical

4. Indications Indication examples (continued):
Induction and maintenance of anesthesia
Preanesthetics to general anesthesia
Reduction of hyperglycemia and hyperglycemia-associated clinical signs in diabetes mellitus
Management of cardiac disease
Treatment of otitis externa
Treatment of mast cell tumors (specific cancers)
Etc.

5. Purpose of Effectiveness Evaluation
To evaluate the indication(s) proposed for the new animal drug under expected conditions of use
Provide information for product labeling that is helpful to the user of the drug
Key component in risk:benefit assessment
This assessment is critical to approval decision

6. General Approach to Effectiveness
Basic understanding of the drug
Pilot studies (or literature) to determine dose
Intended dose, drug concentration, route of administration, frequency of treatment, and duration of treatment
Larger studies to establish effectiveness
Field effectiveness study in target population
Laboratory effectiveness studies
The regulatory approach should be open to considering new methods to appropriately address new technologies and indications

7. Types of Studies/Data to Establish Effectiveness
Clinical studies
Field study in client-owned animals to evaluate the safety and effectiveness of the drug for the proposed indication in the target population
Laboratory effectiveness studies
Pharmacokinetic studies
Weight of evidence approach
Utilize all available information to address the specific risk questions

8. Key Characteristics of Field Study Design
Study should be well-controlled
Protocol
Ensures the study is conducted consistently between sites
Study objectives should be clearly stated
Control group – placebo, active, historical
Methods to control bias
Masking
Multi-centered
Randomized

9. Key Characteristics of Field Study Design (continued)
Study should be appropriately powered
Include appropriate statistical analysis
Include enough animals to infer results to population
Animal removal or death should be taken into account
Study should evaluate drug in target population
Enrollment criteria (inclusion/exclusion) appropriate to define and select target population

10. Endpoint Selection and Effectiveness Criteria
Endpoints should be measurable, objective (if possible), and clinically relevant to the disease/condition in the proposed indication
Effectiveness/success criteria should be predefined in the protocol
Success may include statistical significance compared to control group, achievement of predefined percent success criteria, etc.
Secondary endpoints can be included to support label statements or explore other parameters of interest
Potential endpoints may include:
Clinical/veterinary assessment, owner assessment, scoring system, objective variable (such as change in laboratory value), etc.

11. Other Important Considerations for Field Studies
Field studies allow for evaluation of safety in the target population under conditions of use
Adverse events – incidence and severity
Measurements and Observations
Physical examinations
Clinical pathology
Body weight
Owner diaries
Etc.

12. Other Important Considerations for Field Studies (continued)
Consider user safety issues during the investigational use of the drug, especially for topical formulations and drugs with human safety concerns
Assess risks and means to control risks to user
Owner consent forms for field studies
Describe risks to animal and the user
Describe expectations of study

13. Other Important Considerations for Field Studies (continued)
Extended-use field studies
Assess safety in the target population
Allow animals to continue on the drug
Should use final market formulation
Final study report
Accurate and well organized

14. Label Language
Language relevant to the administration of a safe and effective dose for the product determined in the effectiveness and safety studies
Final labeling developed after all data to support the approval has been reviewed

15. Relevant International Guidelines
VICH GL9 - Good Clinical Practices
For specific classes of drugs:
VICH GL7 - Effectiveness of Anthelmintics: General Recommendations
VICH GL15 - Specific Recommendations for Equine
VICH GL19- Specific Recommendations for Canine
VICH GL20 - Specific Recommendations for Feline

16. Relevant CVM Guidances
For protocol development and data submission:
CVM GFI #56 Protocol Development Guideline for Clinical Effectiveness and Target Animal Safety Trials
CVM GFI #104 Content and Format of Effectiveness and Target Animal Safety Technical Sections and Final Study Reports For Submission
CVM GFI #215 Target Animal Safety and Effectiveness Protocol Development and Submission

17. Relevant CVM Guidances (continued)
For specific classes of drugs:
CVM GFI #38 Guideline for Effectiveness Evaluation of Topical/Otic Animal Drugs
CVM GFI #123 Development of Data Supporting Approval of NSAIDS for Use in Animals
CVM GFI #192 Anesthetics for Companion Animals

18. Summary