Belmont Report was created as part of?
The national Research Act of 1974.
Who was the Belmont Report formulated by?
The National Commission for
... [Show More] the protection of human subjects in biomedical and behavioral research.
What year was the publication of the FDA regulations made?
1980 *1981 for the HHS and revised FDA Regulations.
What year was GCP and HIPAA created?
1996
What is the National Research Act?
A set of regulations for the protection of human participants in research, mandated by congress in 1974, which lead to the Belmont Report.
What is GCP?
Good Clinical Practice- Guidelines developed by the ICH for global implementation on April 30, 1996
EU, Japan, USA
Australia, Canada, Nordic Countries and WHO.
What is the purpose of ICH?
International Conference of Harmonization- an attempt to streamline the process for developing and marketing new drugs internationally. *Eliminate duplicate research.
What are the ethical standards the ICH documents are based off of?
Declaration of Helsinki
The ICH is concerned with harmonization of what three regions?
European Union, Japan, USA. *Additional countries include: Australia, Canada, Nordic countries and WHO.
Important ethical principals that were the result of experimentations in the concentration camps during WW||?
Nuremberg Code
The organization that developed the Declaration of Helsinki?
World Medical Association.
Who does the Declaration of Helsinki mainly address?
Physicians
Who is Peter Buxton?
The journalist that leaked Tuskegee to the press.
Who is Henry Beecher?
The journalist that published a manuscript in the New England Journal of Medicine presenting evidence of wide spread unethical and systematic problems in research.
How long did the Tuskegee Syphilis trials last?
1932-1972
The direct result of the Tuskegee Syphilis Trail of 1979.
Belmont Report
What two ethical works did the Nuremberg Code influence?
1. Belmont Report
2. Declaration of Helsinki
Importance of the Belmont Report (1974)?
Boundaries between Practice and Research.
Basic Ethical Principals:
-Respect for persons
-Beneficence
-Justice
Applications:
-Informed Consent
-Assessment of risk to benefit
- Selection of subjects
The 1947 Doctor's Trial Judgment resulted in what?
The Nuremberg Code
Exempt Research
Exempt from regulations described in the DHHS regulations. (46.104)
Curriculum Vitae
Also known as CV, statement of qualifications. (312.23)
Oral Consent
1. Requires a witness.
2. Subject must sign short form.
3. Witness will sign short form and summary of what was said.
(50.27)
Unanticipated Adverse Device Effect
Effecting safety/ health or any life- threatening problem or death caused by or associated to device. (812.3)
Historical Controls
Prior data from patients with a similar disease to be studied or data from the same patient in crossover study.
Essential Documents
Documents that individually and collectively permit evaluation of the conduct of a study and the
quality of the data produced. (GCP)
Digital signature
An electronic signature based upon cryptographic methods of originator authentication, computed
by using a set of rules and a set of parameters such that the identity of the signer and the integrity of the data can be verified. (11.3)
CAPA
Corrective and Preventive Action Plans. *IRB can request one. They can also be done proactively.
UPIRSO
Unanticipated Problems Involving Risk to Participants or Others.
SUSAR
Suspected Unexpected Serious Adverse Reactions.
Excipients
Inactive substances used as a carrier for the active ingredients of a medication.
Parallel Group
A study design that focuses on efficacy and safety.
Crossover
A study design that focuses on bioequivalence, can also help determine if generic drugs are interchangeable.
Pre- study Visit
SQV's; also knows as: site selection visit, site qualification visit.
Conducted to determined if the P.I. and clinical staff have the capacity to conduct a study. The P.I. and study coordinator must be present (at the very least), Pharmacy, if available.
Initiation Visit
SIV's
Where the research team will get adequate training from the sponsor (or CRO) on the protocol. This usually happens after all regulatory documents have been collected and IRB approval has been obtained.
Investigator meeting
P.I and other study staff invited to participate to go over the study details to the sponsor/ CRO.
Monitor Visits
Periodic monitor visits help by the sponsor/CRO will developed (determined by the complexity and enrollment of the study) a monitor plan. Verification of how the study is being conducted is the main focus. The contract agreement will have the frequency and length of visits.
Close- out visit
Conducted at the end/ completion of a study. This can sometimes be included within final monitor visit. This visit is used to tie up lose ends.
FWA
Federal wide Assurance; the only assurance accepted and approved by OHRP for institutions engaged in non- exempt human subject research conducted or supported by HHS. This indicated that the institution commits to HHS that they will comply with 45CFR46.
Inspection (ICHE6GCP)
Conducting an official review of documents, facilities,
records, and any other resources that are deemed by the authority(ies) to be related to the clinical
trial and that may be located at the site of the trial, at the sponsor's and/or contract research
organization's (CROs) facilities, or at other establishments deemed appropriate by the regulatory
authority(ies).
Audit (ICHE6GCP)
A systematic and independent examination of trial-related activities and documents to determine
whether the evaluated trial-related activities were conducted, and the data were recorded,
analyzed, and accurately reported according to the protocol, sponsor's standard operating
procedures (SOPs), good clinical practice (GCP), and the applicable regulatory requirement(s).
*Audits always independent of the clinical trail.
A.L.C.O.A-C
Attribute: Who creates record and when. If changes, why, when and by who?
Legible: Research record should be easy to read.
Contemporaneous: Observance/ results recorded as is. Signature/initials should be accompanied by date.
Original: No copies.
Accurate: Integrity, honest, thorough and correct.
Complete: adequate, accurate and complete source documents.
IEC
Independent Ethic Committee (312.3)
When can expedited review be used?
1. A study involving no more than minimal risk.
2. On the DHHS and FDA specific list of categories.
3. Minor changes in previously approved research during the period for which approval is authorized
*Only IRB chair or designated IRB member can conduct expedited review. (46.110)
CRF
A printed, optical, or electronic document designed to record all of the protocol required
information to be reported to the sponsor on each trial subject.
ICH E6
Guidelines for industry; GCP; Consolidated guidance
ICH E2A
Clinical Safety Data Management: Definitions and Standards for Expedited Reporting
Exempted Investigations
A device, other than a transitional device, in commercial distribution immediately before May 28, 1976, when used or
investigated in accordance with the indications in labeling in effect at that time. *one example (812.2)
PMA
Premarket Approval Application (812)
Class | Device
1. Present a low risk of harm
2. Subject to general controls.
3. Exempt from regulatory process.
Ex. elastic bandages, tongue depressors.
Class || Device
1. More complicated
2. Require special controls
3. most require a 501(k)
Ex. CT scanners, powered wheelchairs
Class ||| Devices
1. Sustain/ support life, implanted or present potential unreasonable risk of illness or injury.
2. Toughest regulatory controls
3. Most require a PMA
Ex. Pace-makers, implanted weight- loss devices, breast implants.
Compassionate use
the use of an investigational drug outside of a clinical trial to treat a patient with a serious or immediately life-threatening disease or condition who has no comparable or satisfactory alternative treatment options; also called expanded access
HHS
Department of Health and Human Services (46.101)
Research
A systematic investigation, including research development, testing, and evaluation, designed to develop
or contribute to generalizable knowledge. Activities that meet this definition constitute research for purposes of this policy, whether
or not they are conducted or supported under a program that is considered research for other purposes. For example, some
demonstration and service programs may include research activities. (46.102)
Office of Human Research Protection (OHRP)
Concerned with protection of human research subjects *Publication in 2000
Clinical investigation
!ny experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration. (50.3)
Clinical Trial
A research study in which one or more human subjects are prospectively assigned to one or more
interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral
health-related outcomes. (46.102)
Quorum
The minimum number of members who must be present to have IRB meeting.
Controverted Issue
An issue that causes a debate among the IRB members.
Biometrics
A method of verifying an individual's identity based on measurement of the individual's physical
feature(s) or repeatable action(s) where those features and/or actions are both unique to that individual and measurable. (11.3)
Exculpatory Language
Made to wave or appear to wave a subjects legal rights (46.116)
Phase ||| Studies
1. Efficacy
2. Safety
Patient numbers: Serval hundred to several thousand.
Phase | Studies
1. Safety
2. Tolerability
*Dose- escalating, open- label, non- placebo controlled.
Patient numbers: 20-80
Phase || Studies
1. Efficacy
2. Common short- term effects/ risks.
*Double- blinded, placebo.
Patient numbers: Several hundred.
IND
Investigational New Drug
*Allows drug to be shipped over state lines. (312.3)
Difference between applicate and sponsor?
Applicate- sponsor requesting market approval
Sponsor- sponsor conducting research.
Transitional Devices
A device subject to section 520(l) of the act, that is, a device that FDA considered to be a new
drug or an antibiotic drug before May 28, 1976. (812.3)
Implant
A device that is placed into a surgically or naturally formed cavity of the human body if it is intended to remain there for a period of 30 days or more. (812.3)
Significant Risk Device
An investigational device that 1) is intended as an implant and presents a potential for serious risk to the health, safety or welfare of the subject 2) is purposed or represented to be for a use in supporting or sustaining human life and presents a potential serious risk 3) is for a use of substantial importance in diagnosing, curing , mitigating or treating disease or otherwise preventing impairment of human health. (812.3)
Supplement Application
For device studies send in for protocol modifications.
*Similar to protocol amendments for drug studies.
Open System
An environment in which access is not controlled by the persons responsible for the content of electronic records that are on the system. (11.3)
Closed System
An environment in which system access is controlled by persons who are responsible for the
content of electronic records that are on the system. (11.3)
IDE
Permits a device that is not approved for marketing to be shipped lawfully over state lines. (812.1)
HUD
A medical device intended for the treatment or diagnosis of a disease that affects fewer than 8,000 individuals in the USA each year.
*HDE- similar to IDE.
Suspected Adverse Reaction
any adverse event for which there is a reasonable possibility that the drug caused the adverse event. Relationship between drug and AE.
The consent documentation differences between ICH and FDA
ICH: Requires signature and date from both subject and person obtaining consent. Requires that subject receive copy of signed/ dated documents.
FDA: Requires just date and signature of the subject. Requires that subject receive either a singed or unsigned copy of the consent.
What guidelines do the DHHS Regulations provide?
Ensure that the research plan makes adequate provisions for monitoring the data collected the ensure safety of the subjects.
21CFR314
New Drug Application (NDA).
21CFR814
Premarket Approval for medical devices (PMA).
21CFR11; Subpart B
Electronic Records.
21CFR11; Subpart C
Electronic Signatures.
21CFR50; Subpart B
Protection of Human Subjects: Informed Consent of Human Subjects.
21CFR50; Subpart D
Protection of Human Subjects: Additional Safeguards for Children in Clinical Investigations.
*D for diapers
21CFR56; Subpart B
IRB Organization and Personnel.
21CFR56; Subpart C
IRB Functions and Operations.
21CFR312
INVESTIGATIONAL NEW DRUG APPLICATION.
21CFR812
INVESTIGATIONAL DEVICE EXEMPTIONS.
21CFR56; Subpart E
IRB Administrative Actions for Noncompliance.
21CFR56; Subpart D
IRB Records and Reports.
45CFR46
PROTECTION OF HUMAN SUBJECTS.
21CFR11
Electronic Records; Electronic Signatures.
45CFR46; Subpart A
Basic HHS Policy for Protection of Human Research Subjects.
*Also known as the "Common Rule, published in 1991.
45CFR46; Subpart B
Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved
in Research.
*B for baby
45CFR46; Subpart C
Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects.
*C for convict/ cell
45CFR46; Subpart D
Additional Protections for Children Involved as Subjects in Research.
*D for diapers
45CFR46; Subpart E
Registration of Institutional Review Boards.
21CFR50
PROTECTION OF HUMAN SUBJECTS.
*Also knows as "Common Law"
21CFR50.24
Exception from informed consent requirements for emergency research.
Reporting; 312.32(IND safety reports.): Sponsor>>FDA/PI
IND safety report of potential serious risks, from
clinical trials or any other source, as soon as possible, but in no case later than 15 calendar days after the sponsor determines
that the information qualifies for reporting.
Reporting; 312.32(Serious and unexpected suspected adverse reaction.): Sponsor>>FDA/PI
The sponsor must report any suspected adverse reaction that is both
serious and unexpected in no case later that 7 calendar days.
Reporting; 312.64(Safety Report): PI>>Sponsor
An investigator must immediately (24Hrs) report to the sponsor any serious adverse event, whether or not
considered drug related, including those listed in the protocol or investigator brochure and must include an assessment of whether
there is a reasonable possibility that the drug caused the event.
Reporting; 812.150(Unanticipated adverse device effects): PI>>Sponsor
An investigator shall submit to the sponsor and to the reviewing IRB a report of any
unanticipated adverse device effect occurring during an investigation as soon as possible, but in no event later than 10 working
days after the investigator first learns of the effect.
Reporting; 812.150 (Unanticipated adverse device effects): Sponsor>>FDA/PI
A sponsor who conducts an evaluation of an unanticipated adverse device effect
under shall report the results of such evaluation to FDA and to all reviewing IRB's and participating investigators within
10 working days after the sponsor first receives notice of the effect.
Reporting; 812.150 (Significant risk device determinations): Sponsor>>FDA
If an IRB determines that a device is a significant risk device, and the sponsor had
proposed that the IRB consider the device not to be a significant risk device, the sponsor shall submit to FDA a report of the IRB's
determination within 5 working days after the sponsor first learns of the IRB's determination.
21CFR54
Financial Disclosure
21CRF56
INSTITUTIONAL REVIEW BOARDS
The purpose of essential documents for the P.I.
Demonstrate the compliance of the investigator, sponsor and monitor with standards of GCP and regulatory requirements.
When can a P.I. implement change without approval of the IRB?
Any time it would eliminate an immediate hazard to the trial subject.
*Must be reported to IRB and FDA within 5 working days.
Two GCP guidelines that should be followed by the P.I.
1. Inform subjects primary PCP about subjects trial participation.
2. Make a reasonable effort to understand the reasons a subject withdraws prematurely from a study.
Once IP is received on site, who is responsible for it?
The P.I.
A subject that does not meet Inclusion/ Exclusion criteria but is approved by the sponsor, who else will need to approve before the subject may go on trial?
IRB
Form 1572 is legally binding between the P.I. and?
The FDA
What does the P.I agree to when completing a 1572?
Personally will conduct and supervise the clinical trial.
Form 482
FDA Notice of Inspection
Form 483
Summary of observations from the inspection.
501(k) for devices
A form used to demonstrate substantial equivalence to a legally marketed device.
Form 1572
Under 21CFR312, this form is the statement of the investigator of a clinical trial. An agreement that the P.I will comply with the FDA regulations.
Form 1571
Investigational New Drug Application
Class || devices in market approval
Premarket notification 510(k) for devices.
Form 3455
Disclosure of financial interest and arrangements of clinical investigators
*Bias
**This form is completed by applicant/ sponsor.
***Also known as "financial Disclosure".
Form 3454
Certification of financial interest and arrangements of clinical investigators.
*non- bias
Form 3500
Volunteer reporting of adverse events and product problems
Form 3500A
Mandatory safety reporting by user facilities, distributors, and manufacturers
*All mandatory reports will have an A behind the number.
Waivers of HIPAA authorization must be kept for how long?
six years
Actions the IRB can take when reviewing a study?
1. Approve
2. Approve; with conditions
3.Disapprove
4. Defer; pending major modifications. [Show Less]