QUIZ 2 LEC Investigational Drugs and Drug Approval Process

Comprehensive practice flashcards covering drug laws, IND requirements, clinical trial phases, ethical frameworks, pharmacy roles, and case studies based on PHA6123.

Which act provided for the inspection and detention of imported drug shipments that failed to meet prescribed standards?

Import Drug Act of 1848

Which legislation required that drugs must not be mislabeled or adulterated?

Pure Food and Drugs Act of 1906

How did the Food, Drug, and Cosmetic Act of 1938 require the safety of drugs to be proven?

Through testing before marketing

Which amendment divided pharmaceuticals into over-the-counter (OTC) and prescription (Rx) classes?

Durham-Humphrey Amendment of 1951

What did the Kefauver-Harris Drug Amendment of 1962 mandate manufacturers demonstrate prior to marketing?

Proof of efficacy as well as safety

What is the FDA review target timeline for standard drugs?

$$10\text{ months}$$

What is the FDA review target timeline for priority drugs?

$$6\text{ months}$$

Which web-based system developed by the NIH provides information on ongoing clinical trials?

ClinicalTrials.gov

What is the main goal of the International Conference on Harmonisation (ICH)?

To provide a method to ensure simultaneous submission and rapid regulatory approval worldwide

Which historical code established that the voluntary consent of the human subject is absolutely essential?

Nuremberg Code

Which document re-emphasized the protection of human subjects and specified that subjects must be free from coercion?

Declaration of Helsinki (1964)

What was delineated in the Belmont Report of 1978?

The basic ethical principles underlying medical research on human subjects

What was the former name of the Food and Drug Administration (FDA) in the Philippines mentioned in the text?

Bureau of Food and Drugs (BFAD)

Which test subjects are primarily used during pre-clinical tests in drug discovery and development?

Animals

Who files a Commercial Investigational New Drug (IND) application with the FDA?

A corporate entity sponsor

Who is responsible for filing an Investigator IND?

An individual researcher

Which FDA form serves as the Cover Sheet for an Investigational New Drug (IND) application?

Form 1571

Which section of an IND application describes the rationale, indications, and types of trials to be conducted?

Introductory statement and general investigational plan

Which document provides investigators with all available information on a drug, including formula, pharmacokinetics, and safety?

Investigator's Brochure

What does the patient selection section in an IND clinical protocol describe?

Characteristics of eligible patients and exclusion factors

Which IND data section focuses on synthesis, preparation, and analytical methods to ensure purity and stability?

Chemistry, manufacturing, and control data

Although the FDA does not require placebos to be identical to the investigational drug, what must the lack of similarity not do?

Jeopardize the trial

Which IND submission is used to report a serious and unexpected suspected adverse reaction?

IND safety report

Within how many calendar days must a sponsor report a serious and unexpected suspected adverse reaction in writing to the FDA?

$$15\text{ calendar days}$$

Within how many days of the annual effective date must IND annual reports be submitted to the FDA?

$$60\text{ days}$$

Which clinical trial phase involves the first administration of an investigational drug in humans?

Phase I

How many subjects are typically enrolled in a Phase I clinical trial?

$$20\text{ to }80\text{ subjects}$$

What is the primary objective of a Phase II clinical trial?

Evaluate the efficacy of the agent in patients with the condition

How many patients are typically treated in a Phase III clinical trial?

Several hundred to $3,000\text{ patients}$

Which clinical trial phase is considered pivotal and serves as the primary basis for a New Drug Application (NDA)?

Phase III

What term defines the study of variations of DNA and RNA characteristics related to drug response?

Pharmacogenomics

Which expedited review process is used for drugs treating unmet medical needs by increasing communication with developers?

Fast Track Review

Which expedited FDA program allows approval based on a surrogate endpoint reasonably likely to predict clinical benefit?

Accelerated Approval

For what patient population does Expanded Access permit the clinical use of investigational drugs outside a clinical trial?

Patients with serious or life-threatening diseases

Under Expanded Access, what are manufacturers permitted to charge for an investigational new drug?

Recovery costs attributable to making the IND

What are post-marketing clinical studies initiated after a drug is approved called?

Phase IV

What does the FDA regulatory acronym REMS stand for?

Risk Evaluation and Mitigation Strategies

What does the acronym ETASU stand for within a REMS program?

Elements to Assure Safe Use

An orphan drug treats a rare disease affecting fewer than how many people in the United States?

Fewer than $200,000\text{ people}$

What period of marketing exclusivity is granted to the first sponsor of an approved orphan drug?

$$7\text{ years}$$

What is the mandatory membership affiliation requirement for at least one member of an Institutional Review Board (IRB)?

Must not be affiliated with the institution

Who acts as the official liaison between the Institutional Review Board (IRB) and the study sponsor?

The principal investigator (PI)

What requirement must clinical research protocols satisfy regarding patient risk?

Risks must be minimal and the risk/benefit ratio reasonable

Which specific actions constitute research misconduct in clinical studies?

Fabrication, falsification, or plagiarism

What preparation guidelines should a pharmacist verify are included in an investigational drug protocol?

Stability and compatibility information

What consideration can pharmacists evaluate during an economic review to help manage drug costs?

Whether the therapy can be converted from inpatient to outpatient

Which specific identifier must be documented on investigational drug accountability records?

Lot number of the drug

What is a study called when neither the clinical researchers nor the data analysts know which drug was administered?

Triple Blinded

Which recurring fee charged by an investigational pharmacy covers standard drug storage and inventory?

Monthly fee

What fee does an investigational pharmacy charge when services exceed the standard services included in the base fee?

Professional fee

What was the main function of the Import Drug Act of 1848?

Provided for inspection of imported drug shipments

What did the Pure Food and Drugs Act of 1906 require regarding drugs?

Required drugs not be mislabeled or adulterated

What did the Food, Drug, and Cosmetic Act (FD&C Act) of 1938 require prior to marketing?

Required safety to be proven before marketing

How did the Durham-Humphrey Amendment of 1951 divide pharmaceuticals?

Divided pharmaceuticals into OTC and Rx

What did the Kefauver-Harris Amendment of 1962 mandate before drug marketing?

Specified proof of efficacy and safety prior to marketing

What foundational principle was set forth by the Nuremberg Code?

Stated voluntary consent is absolutely essential

What core subject protection was emphasized in the Declaration of Helsinki?

Re-emphasized protection; subjects must be free from coercion

What was the primary contribution of the Belmont Report?

Delineated basic ethical principles for human research

What was the purpose of CFR Title 45 Part 46?

Designed to make protection of human subjects uniform in federal agencies

What does the International Council for Harmonisation (ICH) ensure for drug development globally?

Ensures simultaneous submission and rapid regulatory approval globally

What is FDA Form 1571 in an IND submission?

Cover sheet identifying the sponsor and CRO

What is contained within an Investigator's Brochure?

Contains all info on drug formula, pharmacokinetics, and safety

What does the Introductory Statement of an IND describe?

Describes the rationale, indications, and types of trials

What is projected in the General Investigational Plan of an IND?

Projects the number of patients and general approach

What components are detailed in an IND Clinical Protocol?

Details objectives, patient selection, and dosing

What does the Chemistry Data section of an IND outline?

Describes synthesis, preparation, and analytical methods

What data is presented in the Previous Human Experience section of an IND?

Summarizes data from US and foreign markets regarding safety

What is the purpose of an IND Protocol Amendment?

Used to amend study design or protocol details

What is an IND Safety Report, and what is its submission timeframe for serious adverse reactions?

Must be submitted within $15\text{ days}$ for serious adverse reactions

When must an IND Annual Report be submitted?

Submitted within $60\text{ days}$ of the effective date to show progress

What defines a Phase I clinical trial?

Uses normal healthy volunteers to determine safety

What defines a Phase II clinical trial?

Evaluates efficacy in a small number of patients with the disease

What defines a Phase III clinical trial?

Treats hundreds to $3,000\text{ patients}$ in multicenter studies

What defines a Phase IV clinical trial?

Post-marketing studies after drug approval

What is the target review timeframe for FDA Priority Review?

FDA sets target to review the drug in $6\text{ months}$

What criteria form the basis for Accelerated Approval?

Based on a surrogate endpoint likely to predict clinical benefit

Which investigational drugs are eligible for Breakthrough Therapy designation?

For drugs showing substantial improvement over available therapy

What is the purpose of Risk Evaluation and Mitigation Strategies (REMS)?

Safety measures required beyond labeling to outweigh risks

What is an investigational pharmacy Base Fee?

Pharmacy charge that is fixed based on patient population or complexity

What defines Double Blinding in clinical study methodology?

Neither the patient nor the researchers know the drug assignment

True or False: In drug discovery, the test subjects used in pre-clinical tests are usually human volunteers.

False (Pre-clinical testing uses animals or in-vitro laboratory tests, not humans)

True or False: An investigator IND is filed by a corporate pharmaceutical entity.

False (An investigator IND is filed by an individual researcher; a commercial IND is filed by a corporate entity)

True or False: The average time for a drug to go from initial synthesis to NDA approval is approximately 15 years.

True (It takes an average of approximately $15\text{ years}$ from initial synthesis to NDA approval)

True or False: Phase III clinical trials are typically multicenter studies.

True (Phase III trials are multicenter studies treating several hundred to $3,000\text{ patients}$)

True or False: ClinicalTrials.gov is a web-based system developed by the FDA.

False (It was developed by the National Institutes of Health [NIH], not the FDA)

True or False: The Belmont Report was established to judge the human experimentation conducted by Nazis.

False (The Nuremberg Code was used to judge Nazi experimentation; the Belmont Report delineated basic ethical principles)

True or False: An IND is always required, even if the drug is already marketed and being studied for its approved indication without increasing patient risk.

False (An IND is not required if the studied drug is marketed in the US and meets specific exemption requirements)

True or False: Under Expanded Access, the FDA allows manufacturers to charge for the drug to secure a large profit.

False (Sponsors can only charge recovery costs attributable to making the IND, not for profit)

True or False: Expanded access to investigational drugs is permitted for any minor condition.

False (It is only allowed for serious or immediately life-threatening diseases where no comparable therapy exists)

True or False: Pharmacogenomics studies the impact of a certain genotype or phenotype on drug response and adverse events.

True (Pharmacogenomics is defined as the study of DNA/RNA variations related to drug response)

True or False: An Orphan Drug is one used for the treatment of a disease affecting more than 500,000 people.

False (An orphan drug is for a rare disease affecting fewer than $200,000\text{ people}$ in the US)

True or False: The Orphan Drug Act directly speeds up the FDA's clinical trial approval timeline.

False (It provides incentives like tax breaks and $7\text{ years}$ of marketing exclusivity, but does not alter the approval timeline)

True or False: An Institutional Review Board (IRB) must include at least one individual who is not affiliated with the institution.

True (The IRB must have at least one individual not affiliated with the research institution)

True or False: The Principal Investigator has no direct interaction with the human subjects in a trial.

False (The investigator has direct communication with the human subjects, whereas the sponsor usually does not)

True or False: Informed consent in a clinical trial may be solely verbal and undocumented.

False (Informed consent must be documented in writing)

True or False: Research misconduct includes fabrication, falsification, or plagiarism in proposing or performing research.

True (Fabrication, falsification, or plagiarism constitutes research misconduct)

True or False: A pharmacy's Professional Fee is charged for drug storage and inventory.

False (A Monthly Fee covers drug storage and inventory; a Professional Fee is for services that exceed standard services)

True or False: Drug accountability records must be retained at the study site for 2 years after NDA approval or study discontinuation.

True (Records must be maintained for $2\text{ years}$ after approval or FDA notification of discontinuation)

True or False: In a single-blinded study, the researchers do not know what drug is given, but the patient does.

False (In a single-blinded study, the patients do not know what they are given, but the researchers do)

True or False: REMS must be assessed for adequacy at least by 18 months, 3 years, and 7 years after approval.

True (The text specifies REMS assessments at $18\text{ months}$, $3\text{ years}$, and $7\text{ years}$)