Drug Development Flashcards
Of the compounds that enter clinical testing, how many are approved by the FDA?
only 19%
How long does it take to bring a new medication to market? What’s the estimated cost?
10 to 15 years at an estimated cost of $800 million to $1.7 billion
Steps in drug development: Discovery and characterization
- Isolate or synthesize new drug.
- Determine the chemical and pharmaceutical properties of new drug.
Steps in drug development: experimental studies
- Determine pharmacokinetic and pharmacodynamic properties of drug.
- Test for toxicity, teratogenesis, carcinogenesis (in animals)
Steps in drug development: investigational new drug (IND) application
- outline properties of drug
- report results of studies to date
- propose clinical studies (proposed protocols, methods of data analysis, sites, investigators)
A drug must be approved by the FDA before…
conducting studies in humans.
Clinical studies: Phase 1
Pharmacokinetic and safety in healthy volunteers (20 to 80 patients).
Pharmacokinetic studies provide a basis for estimating doses to be used in next phase of studies and to determine if drug is safe for use.
Clinical studies: Phase 2
Data on efficacy, safety, proper dosage in a small group (several hundred patients)
- Human subjects have the particular disease.
- Establishes a dosage range for further clinical studies.
Clinical studies: Phase 3
Statistical evidence of efficacy and safety (several hundred to several thousand patients)
- compare the safety and efficacy of the investigational w/ that of another substance or treatment approach.
- Rigorously designed to prevent bias and re double-blind and placebo-controlled.
Steps in Drug Development:
- outline properties of drug
- report results to all studies
- propose labeling of drug and indication
- requires months to review before approved by FDA.
Steps in drug development: approval of NDA
New Drug Application
Steps in drug development: Postmarketing surveillance
FDA seeks voluntary reports of adverse effects submitted by healthcare professionals. The gate opens when we send the drug out to the entire population, we still need to monitor it.
Orphan drugs
drug that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease (not worth for companies to invest in it)
- affects less than 200,000 Americans
- 7 years of exclusive market for the indication
Orphan drugs generally follow the same regulatory development path.
Statistical burdens are lessened.
EX: Orphan drug regulations generally acknowledge the fact that it may not be possible to test 1000 patients in phase III.
Examples of Outcomes of post-market ADE (adverse drug events) Reporting
- product recall or withdrawal
- boxed warning included
- contraindications modified
- new warnings, precautions, or adverse reactions
- monitoring recommendations for patients
- dosage adjustments
- medications guides used
- letters to healthcare professionals
Drug safety
Half of the drug withdrawals from the market occurred within 2 years of their introduction.
True efficacy and safety of drug can be established only w/ extensive use.
Currently, healthcare professionals are not required by federal law or regulations to submit repors of ADEs on any medical product but we SHOULD REPORT ADVERSE EFFECTS.
Risk Evaluation and Mitigation Strategy Programs (REMS)
Strategic safety program designed to meet specific goals and objectives in minimizing risks while preserving the product’s benefit.
Has been required for ~120 medications.
REMS elements: Medication guide
Document (paper handouts) written for patients highlighting important safety information about the drug; required to be distributed by the pharmacist w/ the prescription.
REMS elements: Communication plan
plan to educate healthcare professionals on the safe and appropriate use of drugs and consists of tools and materials that will be disseminated to the appropriate stake holders.
REMS elements: Elements to ensure safe use (EASU)
strictly controlled systems or requirements put into place to enforce appropriate use of a drug.
EX: Physician certification requirement in order to prescribe the drug, patient enrollment in a central registry, distribution restriction (specialty pharmacists)
Rems elements: Implementation system
System to monitor and evaluate implementation for and work to improve implementation of elements to assure safe use.
- Manufacturer will monitor compliance and intervene as necessary to improve compliance
Medication error:
any preventable even that may cause or lead to inappropriate medication use or patient harm while medication is in control of the healthcare professional, patient, or consumer.
What is medication error related to?
prescribing, order communication, product labeling, packaging, compounding, dispensing, distribution, administration, education, monitoring, use
Adverse drug reaction (ADR)
response to a drug that is not desired, is potentially harmful, and can occur at usual therapeutic doses.
ADR categories
side effects (predictable) organ toxicity (not always predictable) toxic reactions (predictable) drug allergy (hypersensitivity; not predictable) idiosyncratic unexpected reaction caused by genes.
