Presentation on theme: "Effectiveness Evaluation for Therapeutic Drugs for Non-Food Animals"— Presentation transcript:
1 Effectiveness Evaluation for Therapeutic Drugs for Non-Food Animals Christopher Loss, DVMDivision of Therapeutic Drugs for Non-Food AnimalsOffice of New Animal Drug EvaluationUSFDA Center for Veterinary Medicine
2 Non-Food Animals Non-food (companion) animals DogsCatsHorses (in US considered a non-food animal)FerretsLaboratory animals (rodents, primates)Excludes any animal that is commonly used for food
3 IndicationsTherapeutic 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
4 Indications Indication examples (continued): Induction and maintenance of anesthesiaPreanesthetics to general anesthesiaReduction of hyperglycemia and hyperglycemia-associated clinical signs in diabetes mellitusManagement of cardiac diseaseTreatment of otitis externaTreatment 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 useProvide information for product labeling that is helpful to the user of the drugKey component in risk:benefit assessmentThis assessment is critical to approval decision
6 General Approach to Effectiveness Basic understanding of the drugPilot studies (or literature) to determine doseIntended dose, drug concentration, route of administration, frequency of treatment, and duration of treatmentLarger studies to establish effectivenessField effectiveness study in target populationLaboratory effectiveness studiesThe 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 studiesField 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 approachUtilize all available information to address the specific risk questions
8 Key Characteristics of Field Study Design Study should be well-controlledProtocolEnsures the study is conducted consistently between sitesStudy objectives should be clearly statedControl group – placebo, active, historicalMethods to control biasMaskingMulti-centeredRandomized
9 Key Characteristics of Field Study Design (continued) Study should be appropriately poweredInclude appropriate statistical analysisInclude enough animals to infer results to populationAnimal removal or death should be taken into accountStudy should evaluate drug in target populationEnrollment 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 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 interestPotential 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 useAdverse events – incidence and severityMeasurements and ObservationsPhysical examinationsClinical pathologyBody weightOwner diariesEtc.
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 concernsAssess risks and means to control risks to userOwner consent forms for field studiesDescribe risks to animal and the userDescribe expectations of study
13 Other Important Considerations for Field Studies (continued) Extended-use field studiesAssess safety in the target populationAllow animals to continue on the drugShould use final market formulationFinal study reportAccurate and well organized
14 Label LanguageLanguage 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 reviewed
15 Relevant International Guidelines VICH GL9 - Good Clinical PracticesFor specific classes of drugs:VICH GL7 - Effectiveness of Anthelmintics: General RecommendationsVICH GL15 - Specific Recommendations for EquineVICH GL19- Specific Recommendations for CanineVICH 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 TrialsCVM GFI #104 Content and Format of Effectiveness and Target Animal Safety Technical Sections and Final Study Reports For SubmissionCVM 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 DrugsCVM GFI #123 Development of Data Supporting Approval of NSAIDS for Use in AnimalsCVM GFI #192 Anesthetics for Companion Animals