ICH-E2A

Question 1

Definition of an AE

Answer 1

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Question 2

Can an abnormal lab finding be an AE?

Answer 2

Yes

Question 3

ADR Defintion for pre-approval clinical product

Answer 3

In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not be established:

all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions.

Question 4

ADR Definition for marketed medicinal products

Answer 4

A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for modification of physiological function.

Question 5

UADR-Unexpected Adverse Drug Reaction Defintion

Answer 5

An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator’s Brochure for an unapproved investigational medicinal product).

Question 6

What is the difference between the terms SEVERE vs. SERIOUS

Answer 6

The term “severe” is often used to describe the intensity (severity) of a specific event (as in mild, moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor medical significance (such as severe headache).

“serious,” which is based on patient/event outcome or action criteria usually associated with events that pose a threat to a patient’s life or functioning.

Question 7

What serves as a guide for defining regulatory reporting requirements?

A. Seriousness
B. Severity
C. All of the above

Answer 7

A. Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.

Question 8

A Serious Adverse Event (experience) or reaction is an untoward medical experience that at any dose causes what?

Answer 8

• results in death,
• is life-threatening
• requires inpatient hospitalisation or prolongation of existing hospitalisation,
• results in persistent or significant disability/incapacity, or
• is a congenital anomaly/birth defect.

Question 9

What does the term Life Threatening met an when defining “Serious” in adverse events

Answer 9

NOTE: The term “life-threatening” in the definition of “serious” refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe.

Question 10

What are the following documents or circumstances will be used to determine whether an adverse event/reaction is expected:

Answer 10

1. For a medicinal product not yet approved for marketing in a country, a company’s Investigator’s Brochure will serve as the source document in that country. (See section III.F. and ICH Guideline for the Investigator’s Brochure.)
2. Reports which add significant information on specificity or severity of a known, already documented serious ADR constitute unexpected events. For example, an event more specific or more severe than described in the Investigator’s Brochure would be considered “unexpected”. Specific examples would be (a) acute renal failure as a labeled ADR with a subsequent new report of interstitial nephritis and (b) hepatitis with a first report of fulminant hepatitis.

Question 11

What type of adverse drug reactions are subject to expedited reporting? (select all that apply)

A. Serious
B. Unexpected
C. Life-Threatening
D. All of the Above

Answer 11

A and B

Question 12

Which of the following are examples of sources of an Expedited ADR? select all that apply.

A. Spontaneous Sources
B. Cases not reported to sponsor.
C. ones found in regulatory authority generated ADR registries  
D. Publications
E. All of the above

Answer 12

E.

Question 13

Is expedited reporting of serious events, but expected appropriate?

Answer 13

No

Question 14

T/F: Expedited reporting is appropriate from clinical investigations that are considered not related to study product, whether the event is expected or not

Answer 14

False

Question 15

T/F: Non-serious adverse reactions, whether expected or not, will be subjected to expedited reporting

Answer 15

False

Question 16

T/F: Causality assessment is required for clinical investigation cases. All cases judged by either the reporting health care professional or the sponsor as having a reasonable suspected causal relationship to the medicinal product qualify as ADRs

Answer 16

True

Question 17

What is the term to describe,to convey in general that there are facts (evidence) or arguments to suggest a causal relationship

Answer 17

Reasonable Causal Relationship

Question 18

Phrases such as “plausible relationship,” “suspected causality,” or “causal relationship cannot be ruled out” are used to describe what?

Answer 18

cause and effect

Question 19

Many terms and scales are in use to describe the degree of causality (attributability) between a medicinal product and an event, such as: (6 potential answers)

Answer 19

certainly, definitely, probably, possibly or likely related or not related

Question 20

There are situations in addition to single case reports of “serious” adverse events or reactions that may necessitate rapid communication to regulatory authorities; appropriate medical and scientific judgement should be applied for each situation. In general, information that might materially influence the benefit-risk assessment of a medicinal product or that would be sufficient to consider changes in medicinal product administration or in the overall conduct of a clinical investigation represents such situations. Examples include:

Answer 20

a. For an “expected,” serious ADR, an increase in the rate of occurrence which is judged to be clinically important.
b. A significant hazard to the patient population, such as lack of efficacy with a medicinal product used in treating life-threatening disease.
c. A major safety finding from a newly completed animal study (such as carcinogenicity).

Question 21

What is the timeframe for reporting Fatal or Life-Threatening Unexpected ADRs?

a. 3 calendar days
b. 5 calendar days
c. 7 calendar dats

Answer 21

C. Fatal or life-threatening, unexpected ADRs occurring in clinical investigations qualify for very rapid reporting. Regulatory agencies should be notified (e.g., by telephone, facsimile transmission, or in writing) as soon as possible but no later than 7 calendar days after first knowledge by the sponsor that a case qualifies, followed by as complete a report as possible within 8 additional calendar days. This report must include an assessment of the importance and implication of the findings, including relevant previous experience with the same or similar medicinal products.

Question 22

What is the time frame for a followup report of Fatal or Life-Threatening Unexpected ADRs?

Answer 22

followed by as complete a report as possible within 8 additional calendar days. This report must include an assessment of the importance and implication of the findings, including relevant previous experience with the same or similar medicinal products.

Question 23

What is the time frame for reporting for Other Serious, Unexpected ADRs?

a. 7 calendar days
b. 15 calendar days
c. 21 calendar days

Answer 23

B. Serious, unexpected reactions (ADRs) that are not fatal or life-threatening must be filed as soon as possible but no later than 15 calendar days after first knowledge by the sponsor that the case meets the minimum criteria for expedited reporting.

Question 24

in regards to reporting requirements, For regulatory purposes, initial reports should be submitted within the prescribed time as long as the following minimum criteria are met: (4)

Answer 24

A. an identifiable patient;
B. a suspect medicinal product;
C. an identifiable reporting source;
D. an event or outcome that can be identified as serious and unexpected, and for which, in clinical investigation cases, there is a reasonable suspected causal relationship.

Question 25

What is the CIOMS-I form?

Answer 25

The CIOMS-I form has been a widely accepted standard for expedited adverse event reporting

Question 26

T/F: when a serious adverse reaction is judged reportable on an expedited basis, it is recommended that the blind be broken only for that specific patient by the sponsor even if the investigator has not broken the blind.

Answer 26

True

Question 27

There are several disadvantages to maintaining the blind under the circumstances described which outweigh the advantages, what are they?

Answer 27

By retaining the blind, placebo and comparator (usually a marketed product) cases are filed unnecessarily. When the blind is eventually opened, which may be many weeks or months after reporting to regulators, it must be ensured that company and regulatory data bases are revised. If the event is serious, new, and possibly related to the medicinal product, then if the Investigator’s Brochure is updated, notifying relevant parties of the new information in a blinded fashion is inappropriate and possibly misleading. Moreover, breaking the blind for a single patient usually has little or no significant implications for the conduct of the clinical investigation or on the analysis of the final clinical investigation data.

Question 28

Reactions Associated with Active Comparator or Placebo Treatment::

Who’s responsibility is it to decide whether active comparator drug reactions should be reported to the other manufacturer and/or directly to appropriate regulatory agencies

____________must report such events to either the manufacturer of the active control or to appropriate regulatory agencies. Events associated with placebo will usually not satisfy the criteria for an ADR and, therefore, for expedited reporting.

Answer 28

The sponsor (for both)

Question 29

Products with More than one Presentation or Use:

T/F:an ADR that qualifies for expedited reporting with one presentation of a product (e.g., a dosage form, formulation, delivery system) or product use (e.g., for an indication or population), should be reported or referenced to regulatory filings across other product presentations and uses.

Answer 29

True

Question 30

Products with More than one Presentation or Use:

To avoid ambiguities and uncertainties, an ADR that qualifies for expedited reporting with one presentation of a product (e.g., a dosage form, formulation, delivery system) or product use (e.g., for an indication or population), should be reported or referenced to regulatory filings across other product presentations and uses.
It is not uncommon that more than one dosage form, formulation, or delivery system (oral, IM, IV, topical, etc.) of the pharmacologically active compound(s) is under study or marketed; for these different presentations there may be some marked differences in the clinical safety profile. The same may apply for a given product used in different indications or populations (single dose vs. chronic administration, for example). Thus, “expectedness” may be product or product-use specific, and separate Investigator’s Brochures may be used accordingly. However, such documents are expected to cover ADR information that applies to all affected product presentations and uses. When relevant, separate discussions of pertinent product-specific or use-specific safety information will also be included.
It is recommended that any adverse drug reactions that qualify for expedited reporting observed with one product dosage form or use be cross referenced to regulatory records for all other dosage forms and uses for that product. This may result in a certain amount of overreporting or unnecessary reporting in obvious situations (for example, a report of phlebitis on IV injection sent to authorities in a country where only an oral dosage form is studied or marketed). However, underreporting is completely avoided.

Answer 30

sorry could’nt think of questions

Question 31

Post-study Events:

Although such information is not routinely sought or collected by the sponsor, serious adverse events that occurred after the patient had completed a clinical study (including any protocol-required post-treatment follow-up) will possibly be reported by an investigator to the sponsor. Such cases should be regarded for expedited reporting purposes as though they were study reports. Therefore, a causality assessment and determination of expectedness are needed for a decision on whether or not expedited reporting is required.

Answer 31

Info only, no question

Question 32

What are the 6 main categories to key data elements for inclusion in expedited reports of serous adverse drug reactions??

Answer 32

1. Patient Details
2. Suspected Medicinal Product(s)
3. Other Treatment(s)
4. Details of Suspected Adverse Drug Reaction(s)
5. Details on Reporter of Event (Suspected ADR)
6. Administrative and Sponsor/Company Details

Question 33

Reporting Requirements for:

Fatal or Life Threatening ADR’s
All other serious, unexpected ADR’s

Answer 33

• Fatal or Life Threatening ADR’s-ASAP but no later than 7 calendar days after first knowledge, Complete report with 8 additional calendar days
• ASAP but no later than 15 Calendar days after first knowledge by the sponsor