Quiz 5 Flashcards
What is the general flow of the drug approval process?
Drug discovery and development
pre-clinical research and development
clinical trial
FDA reviews NDA
manufacturing
Investigational New Drug (IND)
drug must be the subject of an approved marketing application before it is transported/distributed across state lines
sponsor has screened molecule for pharmacological activity
New Drug Application
sponsor believes enough evidence has been obtained to meet FDAs marketing approval requirements
Abbreviated New Drug Application (ANDA)
application process for generic drugs
not required to include preclinical and clinical data
must demonstrate product is bioequivalent
Fenfluramine
appetite suppressant
increased risk of pulmonary hypertension
24 cases of valvular heart disease in women
withdrawn from market in 1997
Rofecoxib
treated osteoarthritis, acute pain, and dysmenorrhea
4 fold increased risk of acute MI
caused between 88000 and 139000 heart attacks
withdrawn in 2004
Dabigatran
prevented stroke in non-valvular atrial fibrillation
risk of bleeding increased
pharmacoepidemiology
study of the use of and effects of drugs in large numbers of people
What contributes to pharmacoepidemiology?
higher precision studies
new patient groups
comparative effectiveness evaluations
undetected adverse/beneficial effects
allows for a longer follow-up
study in real-world settings
reassurances in drug safety
fulfillment of ethical/legal obligations
Exposure types
actual: chemical, microorganism
behavioral: environmental factors
individual attributes: age, sex, race, socioeconomic status
outcome types
economic: impacts of intervention on total health resource utilization
clinical: changes in health status
humanistic: patient-centered satisfaction
Type 1 error
rejecting the null hypothesis when it was really true
false positive
controlled by setting the significance level
Type 2 error
failing to reject the null hypothesis when it is really false
false-negative
reduced by increasing sample size
Selection bias
Certain subjects are more likely to be included in the study compared to others, leading to a sample that is non- representative
Misclassification bias
Data is incorrectly categorized/recorded, leading to incorrect assumptions and/or conclusions
Surveillance bias
Monitoring differs across subjects, leading to measurements of outcomes which may not fully capture the data
Recall bias
subjects have different memory of past events leading to incorrect data
Interviewer bias
collection methods differ across subjects, leading to incomplete data
confounding bias
situation in which a non-casual association between a given exposure and an outcome is observed as a result of the influence of a third variable
Type A ADR
augmented; dose related
exaggeration of desired/undesired effect
predictable, usually not serious but relatively common
sedation, diarrhea, nausea
Type B ADR
non-dose related; bizarre
idiosyncratic
largely unpredictable, more serious and less common
anaphylaxis, metabolic intolerances
Type C ADR
chronic; dose and time related
HPA axis suppression, osteonecrosis
Type D ADR
delayed; time related
tardive dyskinesia, teratogenesis
Type E ADR
end of use; withdrawal
anxiety after cessation of benzodiazepines
Type F ADR
failure; unexpected failure
antibiotic resistance
Pure Food and Drug Act (1906)
passed in response to excessive adulteration/misbranding
no requirements for safety/efficacy of marketed drugs
Food Drug and Cosmetic Act (1938)
mandated pre-clinical toxicity testing and clinical data on drug safety prior to marketing to the public
response to 100 deaths from sulfanilamide elixir
Kefauver-Harris Amendment
strengthened requirements for proof of drug safety in preclinical pharmacological and toxicological testing
required IND before clinical trials and substantial evidence
response to thalidomide disaster
Risk Evaluation and Mitigation Strategy (REMS)
required from manufacturers to ensure benefits of a drug outweigh risks
may require based on seriousness of known/potential ADRs, expected benefit of the drug, seriousness of the disease, whether the drug is new, expected duration of treatment, and size of population using drug
