1 Christopher Loss, DVM - PowerPoint Presentation

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Christopher Loss, DVMDivision of Therapeutic Drugs for Non-Food AnimalsOffice of New Animal Drug EvaluationUSFDA Center for Veterinary Medicine

Effectiveness Evaluation for Therapeutic Drugs for Non-Food AnimalsSlide2

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Non-food (companion) animalsDogs CatsHorses (in US considered a non-food animal)FerretsLaboratory animals (rodents, primates)

Excludes any animal that is commonly used for food

Non-Food AnimalsSlide3

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Therapeutic drugs are drugs used in the diagnosis, cure, mitigation, treatment, or prevention of a disease or conditionCompanion animal drugs include a wide range of therapeutic indications. Examples include:Treatment, control, or prevention of internal and external parasitesControl of pain associated with osteoarthritis or post-operative pain (analgesics)

Treatment of infections (antimicrobials)

systemic and topical

IndicationsSlide4

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Indication examples (continued):Induction and maintenance of anesthesiaPreanesthetics 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.

IndicationsSlide5

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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 drugKey component in risk:benefit assessment

This assessment is critical to approval decision

Purpose of Effectiveness EvaluationSlide6

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Basic understanding of the drugPilot studies (or literature) to determine doseIntended 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

General Approach to EffectivenessSlide7

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Clinical studies Field study in client-owned animals to evaluate the safety and effectiveness of the drug for the proposed indication in the target populationLaboratory effectiveness studiesPharmacokinetic studiesWeight of evidence approach

Utilize all available information to address the specific risk questions

Types of Studies/Data to Establish EffectivenessSlide8

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Study should be well-controlledProtocol Ensures the study is conducted consistently between sitesStudy objectives should be clearly stated

Control group – placebo, active, historical

Methods to control bias

Masking

Multi-centered

Randomized

Key Characteristics of Field

Study Design Slide9

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Study should be appropriately poweredInclude appropriate statistical analysisInclude enough animals to infer results to populationAnimal 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

Key Characteristics of Field

Study Design (continued)Slide10

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Endpoints should be measurable, objective (if possible), and clinically relevant to the disease/condition in the proposed indicationEffectiveness/success criteria should be predefined in the protocolSuccess 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.

Endpoint Selection and Effectiveness CriteriaSlide11

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Field studies allow for evaluation of safety in the target population under conditions of useAdverse events – incidence and severityMeasurements and Observations

Physical examinations

Clinical pathology

Body weight

Owner diaries

Etc.

Other Important Considerations for Field StudiesSlide12

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Consider user safety issues during the investigational use of the drug, especially for topical formulations and drugs with human safety concernsAssess risks and means to control risks to userOwner consent forms for field studiesDescribe risks to animal and the user

Describe expectations of study

Other Important Considerations for Field Studies (continued)Slide13

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Extended-use field studies Assess safety in the target population Allow animals to continue on the drugShould use final market formulationFinal study report

Accurate and well organized

Other Important Considerations for Field Studies (continued)Slide14

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Language relevant to the administration of a safe and effective dose for the product determined in the effectiveness and safety studiesFinal labeling developed after all data to support the approval has been reviewedLabel LanguageSlide15

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VICH GL9 - Good Clinical PracticesFor specific classes of drugs:VICH GL7 - Effectiveness of Anthelmintics: General Recommendations VICH GL15 - Specific Recommendations for EquineVICH GL19- Specific Recommendations for Canine

VICH GL20 - Specific Recommendations for Feline

Relevant International GuidelinesSlide16

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For protocol development and data submission:CVM GFI #56 Protocol Development Guideline for Clinical Effectiveness and Target Animal Safety TrialsCVM 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

Relevant CVM GuidancesSlide17

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For specific classes of drugs:CVM GFI #38 Guideline for Effectiveness Evaluation of Topical/Otic Animal DrugsCVM GFI #123 Development of Data Supporting Approval of NSAIDS for Use in AnimalsCVM GFI #192 Anesthetics for Companion Animals

Relevant CVM Guidances (continued)Slide18

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Summary