Study Start Up Flashcards
The voluntary consent of human subjects is essential
Nuremberg Code
The duty and responsibility for ascertaining the quality of consents rests upon each individual who initiates, directs or engages in the experiment
Nuremberg Code
The experiment should be conducted only by scientifically qualified persons with highest degree of skill and care
Nuremberg Code
Protection of subjects human rights
The core of the Nuremberg Code
The primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interest of individuals research subjects
Declaration of Helsinki
The responsibility for the protection of research subjects must always rest with the physician or other health care professionals and never with the research subjects
Declaration of Helsinki
The 3 basic principles in ethics of research involving human subjects.
2
1. Respect for Persons
2. Beneficence
3. Justice
Belmont Report
Informed Consent
-Subject enter into research voluntarily and with adequate info
-Individual treated as autonomous agent
Respect for Persons
Do not harm
Maximize possible benefits and minimize possible harms
Assess risk and benefits
Beneficence
Selection of subjects
Fairness in distribution of burdens and benefits
Justice
Informed consent
FDA- 21 CFR 50 Subpart B
&
HHS- 45 CFR 46 Subpart B
Institutional Review Board
FDA- 21 CFR 56
&
HHS- 45 CFR 46.107-46.115 Subpart E (IRB Registration)
Protection pregnant women, fetuses
Only HHS- 45 CFR 46 Subpart B
Research with prisoners
Only- 45 CFR 46 Subpart C
Research with children
FDA- 21 CFR 50 Subpart C
& HHS- 45 CFR 46 Subpart D
Exception from general requirement for Emergency Research
Only- FDA 50.23(a)-(c)
Exempt Research
Only -HHS- 45 CFR 46.104
Waiver of IRB requirement
Only- FDA 45 CFR 46.104
Process that must happen before clinical research begins
IND- Investigational New Drug Process
- Animal study data and toxicity
- Manufacturing info
- Clinical protocols for studies to be conducted
- Data from prior human research
- Information about investigator and other experts involved in study
Investigational New Drug (IND) application to FDA before beginning a clinical trial
Tightly controlled in-patient setting. Usually single center studies. Range from 20-80 participants
Phase 1
Obtain short-term data, multicenter, well-controlled studies. A relatively small number of subjects.
Phase 2
Researchers confirm its effectiveness, monitor side effects, compare commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.
Phase 3
Delineate additional information about the drug’s risk, benefits, and optimal use; continue assessing overall therapeutic value. Surveillance for less common adverse events. May be similar to the phase 2 and phase 3 study design.
Phase 4
To avoid subconscious bias in assigning subjects to treatment. Subjects are assigned by chance to a treatment group. Sponsor assigned schedules and balanced to assure even assignments across groups.
Randomization
Minimize potential subconscious bias in evaluating treatment response-efficacy and safety outcomes. Blinding conceals randomization assignment from one or more participants (subjects and investigators). Procedure for blinding is determined by sponsors
Blinding
What does a control group tell us?
What would have happened to patients if they had not received the test treatment or if they had received a different treatment known to be effective.
What should a investigational New Drug Application need to include?
•Cover sheet (Form FDA 1571)
•Table of contents
•Introductory statement and general investigational plan
•Protocol(s) for clinical trials
•Chemistry and manufacturing information
•Pharmacology and toxicology information
•Previous human experience with investigational drug
•Additional information e.g- drug dependence and abuse potential, exposure to radiation plans for pediatric studies.
How does an IND determination occur?
•Upon FDA notification
•OR 30 days after the FDA acknowledges receipt if no notification is received
•OR after clinical hold is resolved
What is a Clinical Hold?
An order issued by the FDA to the Sponsor to delay a proposed clinical investigation or to suspend an ongoing investigation.
What happens during a Clinical Hold?
•subjects may not be given the investigational drug
•No new subjects may be given the investigational drug and subjects already taking the drug should discontinued unless continuation is specifically permitted by FDA.
What is Expanded Access
Aka… “compassionate use” is a pathway for a patient with an immediately life-threatening condition or serious disease to gain access to an investigational medical product for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.
What are categories for expanded Access?
- Emergency Use
- Compassionate Use
- Treatment Use
- Continued Access
What are the requirements for Emergency Use?
•Informed consent
•Report to IRB within 5 days of use
•Report to Sponsor
>before or after initiation of a clinical trial
What are the requirements for Compassionate Use?
•Prior FDA approval of IND supplement
> During a clinical trial
What are the requirements for Treatment Use?
•Prior FDA approval of treatment IND
> During a clinical trial
What are the requirement for continued Access
•Prior FDA approval of IND supplement
> After completion of clinical trial
FDA Regulatory Submission Path for pharmaceuticals?
- Preclinical
- IND
- Phase 1,2,3
- NDA
FDA Regulatory Submission Path for Medical Device
- If needed Pre-IDE
- If clinical trials are needed; IDE via IRB Approval or FDA approval
- Pilot, Pivotal
- Letter to file 510 (k), PMA
What is the development timeline for drugs/biologics?
*10-12 years and thousands of subjects.
*Phase 1,2,3
What is the development timeline for medical devices?
*hundreds of subjects
*1+ years
Lowest risk, clinical trials generally not required
Class I
Moderate risk usually requires 510 (k) and might require PMA. Generally requires clinical trials
Class II
Highest Risk; PMA is usually required, and clinical trials absolutely necessary
Class III
An approved IDE Permits a device to be shipped lawfully for the purpose of conducting investigations of the device without complying with other requirements for the food, Drug, and Cosmetic Act that would apply to devices in commercial distribution
Investigational Device Exemption.
Are there special labeling requirements for investigational devices?
Yes, 21 CFR 812.5 the label must include:
- Name and place of business of the manufacturer, packer, or distributor;
-the quantity of contents, if appropriate; and
-the statement, “CAUTION Investigational device. Limited by Federal (or United States) law to investigational use”
IDE reports
*Sponsor must report the results of an evaluation of an unanticipated adverse device effect to FDA and all reviewing IRBS and investigators within 10 working days after the sponsor first received notice of the adverse effect.
-Withdrawal of IRB approval (5 working days)
-Withdrawal of FDA approval (5 working days)
-Current list of investigators (every 6 months)
-Progress reports (at least yearly to IRB and SR to FDA
What is a closed system
An environment in which access is controlled by persons who are responsible for the content of the electronic records that are on the system.
Children who are wards of the State or any other agency, institution, or entity can be included in clinical investigations
approved under §50.53 or §50.54 only if such clinical investigations are:
(1) Related to their status as wards; or
(2) Conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as
subjects are not wards.
(b) If the clinical investigation is approved under paragraph (a) of this section, the IRB must require the appointment of an
advocate for each child who is a ward.
(1) The advocate will serve in addition to any other individual acting on behalf of the child as guardian or in loco parentis.
(2) One individual may serve as an advocate for more than one child.
(3) The advocate must be an individual who has the background and experience to act and agrees to act in, the best
interest of the child for the duration of the child’s participation in the clinical investigation.
(4) The advocate must not be associated in any way (except in the role of advocate or member of the IRB) with the clinical
investigation, the investigator(s), or the guardian organization.
Even where the IRB determines that the subjects are capable of assenting, the IRB may still waive the assent requirement for children if it finds and documents that:
(1) The clinical investigation involves no more than minimal risk to the subjects;
(2) The waiver will not adversely affect the rights and welfare of the subjects;
(3) The clinical investigation could not practicably be carried out without the waiver; and
(4) Whenever appropriate, the subjects will be provided with additional pertinent information after participation.
According to FDA guidelines, the financial disclosure form should be completed by all study personnel who have a significant role in the study.
True:
Principal investigator and Sub-investigator
What does the content of a protocol need to contain?
- Trial Objectives & Purpose
- Assessment of Efficacy
- Data Handling & Record Keeping
