General CIP Questions With Complete Solutions
21 CFR 312.50, 21 CFR 312.60, and ICH E6 Section 5
Responsibilities of sponsor-investigator include: Correct
Answer 1) Implement a system to manage quality throughout
the design, conduct, recording, evaluation, reporting, and
archiving of clinical trials (ICH 2016).
2) Implement research as approved.
3)Report all changes to the IND to FDA including:Protocol
changes, Technical changes to CMC or preclinical section
Annual reports, AEs requiring expedited reporting
4)Monitor conduct and progress of clinical trial (this can be
done through a risk-based approach) including documentation of
monitoring plan and monitoring results.
5) Maintain records of receipt, shipment, and other disposition
of the drug if the drug is considered investigational.
6) Review and evaluate information relevant to safety of the
drug.
7) Provide oversight to subcontractors (for example, contract
research organizations [CROs]).
8) Follow-up of non-compliance through root cause analysis and
corrective and preventative actions.
9)Maintain record of location of essential documents for clinical
trial.
46.503 When must an IRB be registered? Correct Answer An
IRB must be registered before it can be designated under an
assurance approved for federalwide use by OHRP under
§46.103(a). IRB registration becomes effective when reviewed
and accepted by OHRP. The registration will be effective for 3
years.
,510(k) Devices
Section 510(k) of the Food, Drug, and Cosmetic Act requires
Correct Answer a manufacturer to submit a Premarket
Notification (the so-called 510[k]) to the FDA at least ninety
(90) days in advance when the manufacturer wishes to market
many Class I devices that are not exempt and all Class II devices
in the U.S. The 510(k) must show that the device to be marketed
is substantially equivalent to a legally marketed similar device
by demonstrating that the new device is as safe and effective as
the legally marketed device. Occasionally, the FDA will require
a clinical investigation to determine the substantial equivalence.
The 510(k) premarket notification requirements apply to almost
all Class II devices, and Class I devices that are not exempt.
9. Question: Why must foreign sites abide by DHHS
regulations? Why isn't the Declaration of Helsinki or another
international code acceptable? Correct Answer Answer:
DHHS wants to ensure that all DHHS-supported or -conducted
research involving human subjects provides subjects with
protections that are at least equivalent to those afforded by
DHHS regulations. Many international guidelines, such as the
Declaration of Helsinki, provide general principles and are a
good place to start, but do not describe the specific procedures
through which those principles are to be realized. Through its
negotiations with the foreign institution, OPRR ensures that
those Assurances provide procedures that are equivalent to those
required by 45 CFR 46.
A "single patient use" allows a physician to obtain access to an
investigational drug for the treatment of a single patient.
,Usually, the patient is in a desperate situation and unresponsive
to other therapies, or in a situation where no approved or
generally recognized treatment is available. Further, there is
usually little evidence that the proposed therapy is useful, but
may be plausible on theoretical grounds or anecdotes of success.
Access to investigational drugs for use by a single, identified
patient may be gained either through the sponsor under a
treatment protocol, or through the FDA, by first obtaining the
drug from the sponsor, and then submitting a treatment IND to
the FDA requesting authorization to use the investigational drug
for treatment use [21 CFR 312.35]. Correct Answer
A 510(k) Premarket Notification is submitted:
Before any clinical trials of an investigational device can begin
When no alternative treatment exists for a life-threatening
condition
When the new device to be marketed is substantially similar
(equivalent) to one already on the market
When clinical trials of a Class III device are completed Correct
Answer When the new device to be marketed is substantially
similar (equivalent) to one already on the market
A double-blinded trial for a new indication is conducted under
an IND comparing two (2) marketed drugs, at twice the
approved prescribed doses. On Day 2, subject 603 had difficulty
breathing. Although it was life-threatening initially, subject 603
was treated and discharged directly from the emergency
department after complete recovery. On Day 5, subject 20 had a
headache, which led to hospitalization and required blood
pressure lowering medications. These episodes cannot be
explained on the basis of the pharmacological property of either
, drug or the subjects' medical histories. The investigator would
submit an SAE report for: Correct Answer Both of the
subjects
A double-blinded trial for a new indication is conducted under
an IND comparing two (2) marketed drugs, at twice the
approved prescribed doses. On Day 2, subject 603 had difficulty
breathing. Although it was life-threatening initially, subject 603
was treated and discharged directly from the emergency
department after complete recovery. On Day 5, subject 20 had a
headache, which led to hospitalization and required blood
pressure lowering medications. These episodes cannot be
explained on the basis of the pharmacological property of either
drug or the subjects' medical histories. The investigator would
submit an SAE report for: Correct Answer Both of the
subjects;
While subject 603 was admitted and discharged from the
emergency department which is not considered meeting the SAE
criteria of a hospitalization, the life-threatening nature of the
symptoms does meet SAE criteria. Subject 20 was hospitalized
which is reportable as an SAE
A researchers collecting survey and behavioral data from
children at school provide parents with information regarding
the study by mail and ask the parent(s) to return a form if they
do not want their child to participate. Sometimes this practice is
referred to as an opt out procedure, which is not consistent with
the regulatory requirement for seeking and obtaining parental
permission. If the IRB may determine? Correct Answer that
the conditions for waiver of parental permission can be met,
21 CFR 312.50, 21 CFR 312.60, and ICH E6 Section 5
Responsibilities of sponsor-investigator include: Correct
Answer 1) Implement a system to manage quality throughout
the design, conduct, recording, evaluation, reporting, and
archiving of clinical trials (ICH 2016).
2) Implement research as approved.
3)Report all changes to the IND to FDA including:Protocol
changes, Technical changes to CMC or preclinical section
Annual reports, AEs requiring expedited reporting
4)Monitor conduct and progress of clinical trial (this can be
done through a risk-based approach) including documentation of
monitoring plan and monitoring results.
5) Maintain records of receipt, shipment, and other disposition
of the drug if the drug is considered investigational.
6) Review and evaluate information relevant to safety of the
drug.
7) Provide oversight to subcontractors (for example, contract
research organizations [CROs]).
8) Follow-up of non-compliance through root cause analysis and
corrective and preventative actions.
9)Maintain record of location of essential documents for clinical
trial.
46.503 When must an IRB be registered? Correct Answer An
IRB must be registered before it can be designated under an
assurance approved for federalwide use by OHRP under
§46.103(a). IRB registration becomes effective when reviewed
and accepted by OHRP. The registration will be effective for 3
years.
,510(k) Devices
Section 510(k) of the Food, Drug, and Cosmetic Act requires
Correct Answer a manufacturer to submit a Premarket
Notification (the so-called 510[k]) to the FDA at least ninety
(90) days in advance when the manufacturer wishes to market
many Class I devices that are not exempt and all Class II devices
in the U.S. The 510(k) must show that the device to be marketed
is substantially equivalent to a legally marketed similar device
by demonstrating that the new device is as safe and effective as
the legally marketed device. Occasionally, the FDA will require
a clinical investigation to determine the substantial equivalence.
The 510(k) premarket notification requirements apply to almost
all Class II devices, and Class I devices that are not exempt.
9. Question: Why must foreign sites abide by DHHS
regulations? Why isn't the Declaration of Helsinki or another
international code acceptable? Correct Answer Answer:
DHHS wants to ensure that all DHHS-supported or -conducted
research involving human subjects provides subjects with
protections that are at least equivalent to those afforded by
DHHS regulations. Many international guidelines, such as the
Declaration of Helsinki, provide general principles and are a
good place to start, but do not describe the specific procedures
through which those principles are to be realized. Through its
negotiations with the foreign institution, OPRR ensures that
those Assurances provide procedures that are equivalent to those
required by 45 CFR 46.
A "single patient use" allows a physician to obtain access to an
investigational drug for the treatment of a single patient.
,Usually, the patient is in a desperate situation and unresponsive
to other therapies, or in a situation where no approved or
generally recognized treatment is available. Further, there is
usually little evidence that the proposed therapy is useful, but
may be plausible on theoretical grounds or anecdotes of success.
Access to investigational drugs for use by a single, identified
patient may be gained either through the sponsor under a
treatment protocol, or through the FDA, by first obtaining the
drug from the sponsor, and then submitting a treatment IND to
the FDA requesting authorization to use the investigational drug
for treatment use [21 CFR 312.35]. Correct Answer
A 510(k) Premarket Notification is submitted:
Before any clinical trials of an investigational device can begin
When no alternative treatment exists for a life-threatening
condition
When the new device to be marketed is substantially similar
(equivalent) to one already on the market
When clinical trials of a Class III device are completed Correct
Answer When the new device to be marketed is substantially
similar (equivalent) to one already on the market
A double-blinded trial for a new indication is conducted under
an IND comparing two (2) marketed drugs, at twice the
approved prescribed doses. On Day 2, subject 603 had difficulty
breathing. Although it was life-threatening initially, subject 603
was treated and discharged directly from the emergency
department after complete recovery. On Day 5, subject 20 had a
headache, which led to hospitalization and required blood
pressure lowering medications. These episodes cannot be
explained on the basis of the pharmacological property of either
, drug or the subjects' medical histories. The investigator would
submit an SAE report for: Correct Answer Both of the
subjects
A double-blinded trial for a new indication is conducted under
an IND comparing two (2) marketed drugs, at twice the
approved prescribed doses. On Day 2, subject 603 had difficulty
breathing. Although it was life-threatening initially, subject 603
was treated and discharged directly from the emergency
department after complete recovery. On Day 5, subject 20 had a
headache, which led to hospitalization and required blood
pressure lowering medications. These episodes cannot be
explained on the basis of the pharmacological property of either
drug or the subjects' medical histories. The investigator would
submit an SAE report for: Correct Answer Both of the
subjects;
While subject 603 was admitted and discharged from the
emergency department which is not considered meeting the SAE
criteria of a hospitalization, the life-threatening nature of the
symptoms does meet SAE criteria. Subject 20 was hospitalized
which is reportable as an SAE
A researchers collecting survey and behavioral data from
children at school provide parents with information regarding
the study by mail and ask the parent(s) to return a form if they
do not want their child to participate. Sometimes this practice is
referred to as an opt out procedure, which is not consistent with
the regulatory requirement for seeking and obtaining parental
permission. If the IRB may determine? Correct Answer that
the conditions for waiver of parental permission can be met,
