Other HSR Regulations

Question 1

What is the main idea of the Belmont Report?

Answer 1

It has 3 main principles covering protection of human subjects involved in research. The 3 principles are respect for persons, beneficence, & justice.

Question 2

What is the first principle of the Belmont Report?

Answer 2

Respect for persons; subjects must be treated as autonomous agents, & for those with diminished autonomy, additional protections are observed. The principle is activated through use of ICFs & allowing subjects (or LARs) to make decisions on participating.

Question 3

What is a LAR?

Answer 3

Legally authorized representative. Subject’s with diminished autonomy will often have LAR to help them make decisions.

Question 4

What does the Belmont Report principle of beneficence mean?

Answer 4

The benefits of participating should outweigh any risks. This also prompts researchers to minimize risk/harm as much as possible.

Question 5

What does the Belmont Report principle of justice mean?

Answer 5

Potential risks should be distributed equally & subjects should be recruited to research studies in a diverse way that is representative of the population being studied.

Question 6

What is the declaration of Helsinki?

Answer 6

Set of ethical principles for medical research involving human subjects, adopted by WMA in 1964. Note: most recently amended in 2013.

Question 7

Per the declaration of Helsinki, are placebos ever allowed to be used in clinical research?

Answer 7

Placebos are allowed to be used if:
1. there is no proven method for the medical condition being investigated OR
2. withholding active treatment does not cause harm/suffering

Question 8

Per the declaration of Helsinki, what do protocols need to include regarding intervention arrangements post-trial?

Answer 8

Study protocols must include a section describing how subjects can access interventions deemed beneficial after the trial has ended.

Question 9

What is the Nuremberg Code?

Answer 9

Code of 10 ethical principles for medical research involving human subjects. Developed during/after Nuremberg trials in Germany after World War II in 1947 where physicians were experimenting on prisoners in concentration camps.

Question 10

What is ICH-GCP E6 (R2)?

Answer 10

ICH = International Council for Harmonization
GCP = good clinical practice
Established as a set of guidelines in 1996 for expectations & responsibilities of all parties involved in human subjects research; in line with Declaration of Helsinki.

Question 11

Per ICH-GCP guidelines, the rights, safety, & wellbeing of subjects is _____ ______ over the interests of science & society.

Answer 11

first priority

Question 12

ICH-GCP guidelines are practiced where?

Answer 12

US, EU, Japan, Canada, Switzerland

Question 13

IRBs/IECs should retain records for at least ___ years after study completion; investigators should retain records for at least ___ years after the last marketing application.

Answer 13

3, 2

Question 14

Investigators must report unexpected SAEs related to IP to regulatory authorities ________

Answer 14

immediately!

Question 15

Per ICH-GCP guidelines, investigators are responsible for _______ trial tasks to qualified, trained, experienced individuals, & for ensuring _______ with the protocol, GCP, & other regulations.

Answer 15

delegating, ensuring

Question 16

Investigators may implement a protocol deviation PRIOR to _____ ________ IF the deviation is necessary to avoid a ________ to the subject.

Answer 16

IRB/IEC approval, hazard

Question 17

Per ICH-GCP guidelines, subjects & _______ must sign & date the consent form (if wanting to participate), and they must be provided with a ______copy afterwards.

Answer 17

coordinators/consenters, signed
(NOT required by FDA guidance!)

Question 18

Per ICH-GCP guidelines, what are the sponsor’s main responsibilities? Hint: there a 5 groups listed.

Answer 18

1. select qualified investigators for the trial
2. provide investigators with protocol, IB, etc.
3. storage/handling/shipping of IP
4. design & supervise trials based on previously collected data, while ensuring safety & wellbeing of subjects
5. provide investigators with SOPs, using a quality management system with a risk-based approach

Question 19

Sponsors may delegate tasks to a _____, but the oversight of integrity and quality of trial data is ultimately the responsibility of the _______.

Answer 19

CRO, sponsor

Question 20

Monitors are appointed by the _______.

Answer 20

Sponsor

Question 21

Per ICH-GCP guidelines, what are the 3 main purposes of trial monitoring?

Answer 21

1. rights & wellbeing of research subjects are protected
2. reported trial data are accurate, complete, & verifiable from source docs
3. trial is conducted in accordance with GCP, study protocols, etc.

Question 22

What is centralized monitoring?

Answer 22

Remote monitoring. This is now okay to accommodate investigators & sponsors; dependent on specific trial protocol.

Question 23

While it is the investigator’ job to ensure each participant is consented, data collected is accurate, IP is stored/distributed appropriately, & compliance maintained, it is the ________’s job to ensure this is actually happening.

Answer 23

monitor

Question 24

Additional monitoring responsibilities include …. (Hint: there are 3 items listed).

Answer 24

1. reports recruitment #’s & stats
2. informs investigators of data queries, PDs/AEs, etc.
3. submit monitoring reports to sponsor

Question 25

What should the sponsor do if noncompliance is found with an investigator/institution?

Answer 25

Conduct a root-cause analysis & implement appropriate preventive/corrective actions as necessary. If noncompliance is serious and/or persistent, the investigator may be terminated from participation in the trial (regulatory authorities should be notified of this promptly).

Question 26

What information is required in protocols per ICH-GCP guidance? (Hint: there are 15 sections!)

Answer 26

1. general info (protocol title, #, sponsor/monitor/investigator info)
2. background info of the IP (including prior data & statement of compliance with GCP)
3. trial purpose & objectives/aims
4. trial design (what is the intervention & what are the study procedures?)
5. selection (population of interest & inclusion/exclusion) & withdrawal criteria of subjects
6. treatment of subjects (how will intervention be administered & procedures for monitoring subject compliance)
7. efficacy & safety assessments of IP & procedures for reporting AEs
8. statistical analysis plan, including ideal sample size
9. statement providing sponsor/IRB/regulatory authorities access to source docs/data
10. quality assurance & control measures
11. statement of ethical considerations for the trial
12. data handling & record-keeping procedures
13. financing & insurance info (if not provided in other docs)
14. publication policy (if not provided in other docs)
15. any supplemental info

Question 27

What is an IB?

Answer 27

IB = investigator’s brochure
This is a compilation of nonclinical & clinical data on the IP of interest; provides recommendations on dosage & administration, observed side effects, known risks/benefits.

Question 28

It is the responsibility of the ______ to provide investigators with updated IBs.

Answer 28

sponsor

Question 29

Regulatory authorities will allow a simple leaflet or label instead of a full IB if …

Answer 29

The IP is already widely understood and/or it has already been marketed.
Note: products already on the market being studied for a new indication need an IB

Question 30

IBs should include these 8 sections:

Answer 30

1. title page with name of sponsor & name of each IP
2. confidentiality statement
3. table of contents
4. summary of what is known about the IP
5. introduction on rationale for using this IP for this reason
6. physical, chemical, & pharma properties/formulation
7. results & info from prior nonclinical studies, & its relevance to use in humans
8. results & info from prior clinical studies where IP was used in humans