Drug Regulatory Process

Question 1

A federal agency within the US Department of Health and Human Services that evaluates the quality of care in hospitals, particularly the care received by patients who are receiving ??
Meeting and exceeding the measures ___ initiates ensures that patients receive quality care and that their healthcare providers receive government reimbursement for the care of these patients.

Answer 1

Centers for Medicare and Medicaid Services (CMS)
Medicare or Medicaid
CMS

Question 2

~An independent, not-for-profit organization, established > 50 years ago? Governed by a board that includes MDs, RNs and consumers.

-Sets the standards by which ___ is measured in US and internationally.

Answer 2

~The Joint Commission

-health care quality

Question 3

The Joint Commission requires accredited healthcare providers to collect and submit ___ on a full set of core quality of care standards.

It ___ regularly to evaluate their performance against these standards and publishes the information to the public.

Answer 3

performance data

surveys hospitals

Question 4

National Hospital Quality Measures: Anesthesia Related
~Surgical Care Improvement Project National Hospital Inpatient Quality Measures
-___ received within one hour prior to surgical incision - overall rate
-Surgery patients with Peri-operative ___.
-Surgery patients on ___ prior to arrival who received a ___ during the peri-operative period.

Answer 4

• Prophylactic antibiotic
• Temperature Management
• Beta blocker therapy, beta blocker

Question 5

National Hospital Quality Measures: Anesthesia Related

Your ___ and ___ will determine your clinical site’s outcomes (and patient outcomes) very important!

Answer 5

charting and appropriate actions

Question 6

National Hospital Quality Measures: Anesthesia Related
~Examples of data element list you will contribute to with your charting:
-Anesthesia ___ and ___ and ___
-Surgical ___
-___ name, dose, route, time, allergy
-___ current medication, last dose, peri-op administration
-Reasons for not administering a ___ andddd -___

Answer 6

• Anesthesia start and end time and date
• Surgical incision time
• Antibiotic
• Beta blocker
• beta blocker peri-operative
• Temperature

Question 7

In 2002, the American Hospital Association (AHA), Federation of American Hospitals (FAH) and Association of American Medical Colleges (AAMC) launched a national public-private collaboration to encourage hospitals to voluntarily collect and report hospital quality performance information.

Intention is to make data about hospital performance accessible to the public and to inform and invigorate efforts to improve quality.

Answer 7

Hospital Quality Alliance (HQA)
Improving Care Through Information

(other participants include - CMS, JC, AMA, ANA, National Association of children’s hospitals)

Question 8

Surveillance: Medication Errors

• Medication errors cause at least one death everyday and injure approximately 1.3 million people annually in the US.
• Can occur anywhere in the ___:
  
  • Prescribing -Repackaging -Dispensing -Administering -Monitoring

Answer 8

distribution system

Question 9

Surveillance: Medication Errors
~Common Causes of Such Errors Include:
-Poor ___
-___ in product names, direction for use, medical abbreviations or writing
-Poor procedures or techniques
-Patient ___ because of poor understanding of the directions for use of the product
-Job stress, lack of knowledge or training, similar labeling or packaging can contribute

Answer 9

• Poor communication
• Ambiguities
• Patient misuse

Question 10

AANA and Med. Safety: Safe Practices -Needle and Syringe Use:
Position Statement 2.13 - NEVER:
-Administer medications from the ___ to multiple patients even if the needle is changed.
-Reuse a ___, even on the same patient.
-___ a syringe once it has been used even for the same patient.
-Use infusion or IV administration sets on more than one patient.
-Reuse a ___ or ___ to withdraw medication from a multi-dose med vial.
-Re-enter a single use medication vial, ampoule, or solution.

Answer 10

• same syringe
• needle
• Refill
• Reuse a syringe or needle

Question 11

AANA and Medication Safety: Securing Propofol
Position Statement 2.14
*___ to Propofol may contribute to “abuse, addiction and death” in anesthesia practitioners and other with access to the drug.
*Facilities who have Propofol on formulary need to ___ to prevent diversion of propofol and potential abuse of the drug (for ex: propofol should be kept in a secure environment).

Answer 11

• Ease of access

* develop programs

Question 12

List the steps of the FDA Approval Process, 6 total.

Answer 12

1) Pre-Clinical
2) IRB
3) Clinical
4) OTC (over the counter drug review process)
5) Generic
6) Post-Approval

Question 13

Division of Drug Development
___
•Center for Drug Evaluation and Research (CDER)
•Mission statement: To assure that safe and effective drugs are available to the American people.

Answer 13

Food and Drug Administration (FDA)

Question 14

Division of Drug Development - FDA

Divided into 3 Areas???

Answer 14

• New Drug Development Process
• Investigational New Drug (IND) Review Process
• New Drug Application (NDA) Review Process

Question 15

Ethics in Clinical Drug Investigation: A partnership between researcher and subject

• Balance of risk and benefit for the subject
• ___ to patient who could potentially benefit (offsets potential often “unknown” risks)

Answer 15

-Limit enrollment

Question 16

Ethics in Clinical Drug Investigation: A partnership btw researcher and subject:

• 4 major principles
• The trial must minimize ___ for subjects
• ___ must be made for overall care of the patient
• The investigator must terminate the trial when risk becomes ___
• ___ must be reported immediately to an ethics or safety committee

Answer 16

• the risks
• Provisions
• incompatible with goals
• Adverse events

Question 17

___: Not just a signature.
Patient must be:
~Aware of B/R/A
•If patient terminal must understand they are probably doing this for the benefit of future patients instead of for their own welfare
•Well informed before making a voluntary choice to participate

Answer 17

Informed Consent

Question 18

Institutional Review Boards (IRB)/Independent Ethics Committees:
•Located at hospitals & research institution - Mandated & monitored by? -Review ethical and legal issues
•Ensure
-participants are fully informed and have given their ___ before studies ever begin.
-oversee that the ___ and ___ of people participating in clinical trials both before and during are protected

Answer 18

• the FDA
• written consent
• the rights and welfare

Question 19

Institutional Review Boards (IRB) - Composition of IRB
•No less than ___ and ___ with varying backgrounds to ensure a complete and adequate review of activities
***3 of the 5 people need to be???

Answer 19

five experts 
lay people 
***someone with scientific expertise
someone with nonscientific expertise
someone who is not affiliated with the hospital at all

Question 20

•An IRB must be able to evaluate proposals in the context of:

• institutional ___ and ___
• ___ law
• standards of professional ___ and ___
• community attitudes

Answer 20

• commitments and regulations
• applicable
• conduct and practice

Question 21

IRBs/IECs: approve, require modification of, or disapprove of research proposals - Specific criteria evaluated:
•Minimizes ___ to human subjects
•Poses ___ that are reasonable relative to the anticipated benefit and potential scientific gain
•Includes ___ selection of subjects
•Contains an effective ___ process
•Safeguards ___, such as children and the mentally disabled

Answer 21

• potential risk
• risks
• equitable
• informed consent
• vulnerable populations

Question 22

Combined effort to publish a uniform set of national hospital quality measures?
-Created by who??

Answer 22

National Hospital Quality Measures
Centers for Medicare and Medicaid Services (CMS)
The Joint Commission

Question 22

Preclinical Research (i.e. authorization from FDA to initiate clinical trials)
•___ requirements
•Show that the drug is reasonable and safe for use in initial ___ clinical studies
•Compile data from ?? or ??
•Compile studies from ___ (if available)
•___ - Design studies to provide the evidence necessary to support the safety of administering the compounds to humans

Answer 22

• FDA
• small-scale
• in vitro or animal studies
• previous clinical testing
• Proposed protocol

Question 23

Preclinical Research
•Submission of ___
•Info submitted to FDA when a sponsor requests to proceed with ___ clinical trials.
•FDA reviews the preclinical research data and then makes a decision as to whether to allow the clinical trials to proceed within ___.
•Chemistry Review - Pharmacology/toxicology review - Medical review

Answer 23

Investigational New Drug Application (IND)
human
30 days

Question 24

Preclinical research: Goals
•Prior to Human Trials on a molecule (potential new drug):
-Establish potential ___ and ___ (toxicity)
-Determine ___ actions
-Chemical properties, Absorption, distribution, metabolism, excretion
-___ and ___ process
*Goals met through in vitro and in vivo lab ___ testing

Answer 24

• efficacy and safety
• biological
• synthesis and purification
• Animal

Question 25

Preclinical Research
•___ Testing
-Every effort made to use as few animals as possible
-Generally two or more species (one rodent, one non-rodent) are tested (variable effects among species)
-Used to measure drug absorption, metabolism, toxicity of the drug and its metabolites, and elimination of the drug and its metabolites
•___ Testing = 2 weeks-3 months, depending on the proposed use of the substance
•___ Testing = a few weeks-several years
-Some ___ continues after human tests begin to look for long-term AE (i.e. cancer or birth defects)

Answer 25

• Animal Testing
• Short Term Testing
• Long Term Testing
• animal testing

Question 26

***Clinical studies can proceed when:
•___ is active following FDA review
•IRB approves the ?
•___ testing phases in humans

Answer 26

IND
study protocol
3 Clinical drug testing phases

Question 27

***3 Clinical Drug Testing Phases in Humans:
~Phase 1 = (lasts several months) -Number of subjects? -Purpose?
~Phase 2 = (lasts several months to 2 years) -# of subjects? Purpose?
~Phase 3 = (lasts 1-4 years) -Number of subjects? -Purpose

Answer 27

Phase 1 = 20-100
-Safety
Phase 2 = several hundred
-Effectiveness and short term safety 
Phase 3 = several hundred to several thousand 
-Safety, dosage and effectiveness

Question 28

Clinical Trials •Phase 1 Studies:

• Involve 20-100 healthy subjects
• Safety and tolerability; major ___
• If high levels of toxicity are expected, such as cancer drugs, patients with ___ may be used in place of healthy volunteers
• Focus overall on max dose, absorption, distrib, metabolism, excretion
• Often ___ *Help to inform needs from phase II study designs

Answer 28

adverse effects
target condition
non-blinded

Question 29

Clinical Trials •Phase II
•50-several hundred pts with the ?
•Effectiveness of the drug for a ?
•Capable of detecting ?
•Dose-response and dosing regimens
•Several dosing options: \_\_\_ dose range and \_\_\_ information

Answer 29

medical condition of interest
particular disease
less common adverse events
optimum dose range and toxicity information

Question 30

Clinical Trials •Phase II (continued)
-Usually involve a ___ or ___
•drug of interest is evaluated against ___ and/or an ___.
***Can pinpoint additional data that must be collected in phase III trials such as LFTs if phase II data suggest possible hepatotoxicity

Answer 30

single-blind or double-blind trial
placebo
existing therapy

Question 31

Clinical Trials •Phase III = Involve hundreds to several thousands of patients at multiple sites
•Studies are based on specific ___ endpoints or ___ endpoints
•Employ ___, ___, ___ trials with multiple arms
•Results typically provide adeq basis to extrapolate results to?
•Commence after a ? •Safety of proceeding studies
•Objective and study design review
•Review of data up to this point and proposed labeling

Answer 31

• clinical endpoints or surrogate endpoints
• randomization, controlled, double-blind trials
• general population
• “End of Phase II meeting”

Question 32

Clinical Studies Overview:
•The ___ - drug sponsors formally propose that FDA approve a new pharmaceutical for sale in the US.
•A drug manufacturer submits
-___ (animal)
-___ (human) test data and analyses
-drug information -description of manufacturing procedures

Answer 32

The new drug application (NDA)

• nonclinical
• clinical

Question 33

Clinical Studies Overview continued:
•An ___ must provide enough information to permit FDA reviewers to reach key decisions:
-Is the drug safe & effective for its proposed use(s), with the benefits of the drug outweighing its risks?
-Is the drug’s proposed labeling appropriate, and, if not, what should the labeling contain?
-Are manufacturing methods and the quality controls used adequate to preserve the drug’s identity, strength, quality, and purity?

Answer 33

New Drug Application - NDA

Question 34

Clinical Trials: •Special Cases
•___ (accelerated development and approval status) for serious and life-threatening disease
•___ (defined as disease that affect less than 200,000 people in the US)
-Exclusive approval for orphan indication for 7 yrs post-approval
-Infliximab – crohn’s disease -Thalidomide – leprosy
-Atovaquone – for PCP -Orphan drug act in 1983
•Compassionate use ___

Answer 34

• Fast Track Status
• Orphan Drug
• protocols

Question 35

Clinical Trials: •Special Cases
•___ expand access to investigational new drugs
-the drug must show preliminary evidence of ___
-patients must be likely to die or suffer rapid disease progression within several months, or to die prematurely without treatment
-there must be no ___ to treat the disease at that stage.

Answer 35

• Compassionate use protocols (treatment INDs)
• efficacy
• comparable approved therapy

Question 36

Generic Drug Review Process
•An important part of CDER’s mission is to assure that safe and effective generic drugs are available to ___
•___ is filed

Answer 36

the American people

Abbreviated new drug application (ANDA)

Question 38

Generic Drug Review Process:
•To gain FDA approval, a generic drug must:
-Contain the same ___ as the innovator drug (___ may vary)
-Be identical in ___, ___ and ___
-Have the same use indications
-Be bioequivalent
-Meet same batch requirements for identity, strength, purity and quality
-Be ___ under same strict standards of FDA’s good manufacturing practice regulations required for innovator products

Answer 38

• active ingredients, inactive ingredients
• strength, dosage form, and route of administration
• manufactured