Intro to Clinical Trials Exam 1

Fundamentals

gold standard of clinical trials

controlled randomized, double blind

Nuremburg Code 1946

principles for medical research on human subjects

Kefauver Harris Amendment

drug manufactures required to prove to FDA the effectiveness, new safety standards

Declaration of Helsinki

basis of good clinical practices used today

goal of IRB

protect humans

Belmont report

respect for persons, beneficence, justice

respect for persons example

informed consent

beneficence example

risk/benefit analysis - important for IRB approval

justice example

equitable selection of participants

belmont report laws

title 21 Code of federal regulation

current regulations three provisions

definition of drug, definition of new drug, criteria new drugs needs to meet to gain marketing approval

basic concepts of compliance

laws, regulation, guidance (non binding, interpretations)

ICH GCP means

international conference of harmonization good clinical practice

ICH GCP principles

overarching ethical and scientific expectations

CFR means

citations for federal regulations

non-clinical testing

variety of testing to support use in humans

toxicology and FDA

testing must be performed in two species before it can be submitted to FDA

good laboratory practice 7 basic areas

organization, testing facility, facility operation, article characterization, non clinical protocol, records, equipment design

GLP inspections

surveillance/routine, directed (from complaints or questionable data)

investigational new drug application (IND)

drug sponsor alerts FDA of intention to start clinical trials

IND characteristics

request of exemption from federal statute, product of successful preclinical development

IND broad areas

animal pharmacology/toxicology, manufacturing, clinical protocol and investigator info

IND response timeline

FDA has 30 days to respond or sponsor may begin

treatment protocol/IND phase availability

phase 3, can be as early as phase 2

protocol seven elements

objectives, investigator info, patient criteria, dose and duration exposure, study design, observations/measurements, clinical procedure

clinical hold phase

1 (dangerous, unqualified), 2-3 (deficient protocol)

phase 1

20-100 volunteers, pharmacokinetic and pharmacodynamic, initial safety estimate, days to week

phase 2

100-500 volunteers, dosing requirements, study efficacy, more frequently observed side effects, week to months

phase 3

1000-5000 volunteers, pivotal study, long term efficacy and safety, year or longer

drug discovery and development

discovery > preclinical > (IND) > clinical trials > (NDA) > FDA review > scale up manufacturing > post market

NDA objectives

safety and efficacy, drug insert, prove adequate methods, show benefit outweigh risk

NDA adequate product

quality, stability, strength, purity

NDA sections

12- summary, chemistry, clinical data, statistics, case report, FDA356h

NDA clinical data section

most important, complex, largest

NDA expedited options

fast track, breakthrough therapy, accelerated approval

NDA fast track

meet an unmet need or show superior results over current drug for serious illness

NDA breakthrough

show superior promise over current market and effect on clinical endpoint

advisory committees

core members appointed by FDA, 2 experts on drug (can’t vote), no FDA or gov employees

validity of data dependent on

power of the study, need 95% CI

study design objectives

superiority, equivalence, non-inferiority

common study designs

dose escalation, crossover, parallel group, dose range, uncontrolled

common control groups

placebo, dose comparison, no treatment, active, historical

who’s in trouble if study goes wrong

investigator, NOT sponsor

IRB primary objective 21 CFR 56

safeguards rights, safety, and well being of all trial participants

IRB members

min 5, diverse, one with expertise, one lay person (attorney/advocate), one not affiliated

vulnerable participants

prisoners, pregnant women, children, handicapped/disabled, economically/educationally disadvantaged, students, non english speakers

research deviation

no changes without approval from IRB unless eliminates an immediate hazard

Consent lasts from

first interaction to the very last, even after study closes

informed consent (21 CFR 50) describes

foreseeable risks, benefit to participant and others, alternative procedures or treatment, maintain confidentiality, any compensation

consent process

discussion, review, concerns, time, signatures, re-consenting when necessary

physician need consent for

perform surgery, chemo/radiation, blood transfusion, insert surgical device, experimental medication/device/manner

goal of clinical research

good and clean data that can be analyzed to change the standard of care

who is the only one able to exempt a participant from certain criteria

medical monitor

is the medical monitor exemption FDA approved

no, will be flagged in an audit

compensation is

any perception of financial gain

sponsor role

oversight and monitor, set up info needed to conduct study, select investigators, reports and quality assurance

CRO

contract research organization, helps sponsor

monitor role

verify all info, communicate between sponsor and investigators

investigator role

directly responsible for conduct, assemble team, adhere to GCP, budget, consent

What is 1572

contract between physician and FDA to use most current protocol w/o deviation from their patients

study coordinator role

gate keeper of data and records, IRB communication

FDA mission

safety, efficacy, and security of human and veterinary drugs, biological products a medical devices

FDA type I error

risk of approving a drug that is not safe and people are harmed

FDA type II error

delays/prevents approval of a drug that saves lives

how FDA monitors

on site inspections and data audits

consumer safety officer (CSO)

FDA investigator (CI), check signatures and documentations, protocol procedures

Form FDA 482

note of inspection, given to PI and IRB chairperson

Form FDA 483

any significant observations during inspections, 15 days to respond

establishment inspection report (EIR)

no action needed, voluntary action, official action