Presentation For:

Safety Reporting

Protocol: PBL/CR/2013/02/CT/ESIX

Contents

Definitions

Solicited Reactions

Causality Assessment

AE Reporting Timelines

Definitions

Adverse Event

Definition: Any untoward medical occurrence

in the subject administered a pharmaceutical

product

• Causal relationship not necessary

• Can be any unfavorable sign (including an

abnormal laboratory finding, for example).

• Can be inter-current illnesses or injuries

• Can be exacerbation of pre-existing

conditions.

Serious Adverse Event

Any AE that:

Results in the death of the subject

Is life-threatening

Requires inpatient hospitalization or

prolongation of existing hospitalization

Results in persistent or significant disability or

incapacity

Results in Congenital anomaly

Other Important medical events (Which as

per PI opinion can be considered serious)

Grading of Adverse Events

• Mild(Grade I): Usually transient in

nature and generally not

interfering with normal activities

• Moderate(Grade II): Sufficiently

discomforting to interfere with

normal activities

• Severe(Grade III): Prevents

normal activities

Solicited Reactions

Solicited Local Reactions

None Mild (Grade 1) Moderate

(Grade 2)

Severe (Grade 3)

Pain None Minor reaction to touch Cries/protests on

touch

Cries when limb is

moved/

spontaneously

painful

Redness

*

<2.5

cm

2.5- 5 cm 5.1 to 10 cm > 10 cm

Swelling

*

<2.5

cm

2.5- 5 cm 5.1 to 10 cm > 10 cm

* based on the largest diameter

Solicited Systemic ReactionsNone Grade 1 Grade 2 Grade 3

Fever

(Axillary)

< 38°C 38.0-38.4°C > 38.5-38.9°C > 39.0°C

Acute

allergic

reaction

None Localized urticaria

(wheals) with no

medical intervention

Localized urticaria with

medical intervention

OR Mild angioedema

with no medical

intervention

Generalized urticaria

OR Angioedema with

medical intervention OR

Symptomatic mild

bronchospasm

Excess

Sleepiness/

Drowsiness

Behavio

r as

usual

Drowsiness easily

tolerated

Drowsiness that

interferes with normal

activity

Drowsiness that

prevents normal activity

Solicited Systemic ReactionsNone Grade 1 Grade 2 Grade 3

Irritability/

restlessne

ss/

fussiness

Behavior

as usual

Crying more than

usual/ no effect on

normal activity

Crying more than

usual/ interferes

with normal

activity

persistent crying and the

child could not be

comforted

/ prevents normal activity

Poor

eating

Appetite

as usual

Eating less than

usual/ no effect on

normal activity

Eating less than

usual/ interferes

with normal

activity

Not eating at all

Solicited Systemic Reactions

None Grade 1 Grade 2 Grade 3

Vomiting None Occasional but able to

eat/drink

normal amounts

Repeated with limited

oral intake

Continuous, unable to

keep down liquids or

solids

Diarrhea None Transient or

intermittent episodes

of unformed stools OR

Increase of ≤ 3 stools

over baseline

per 24-hour period

Persistent episodes of

unformed to watery

stools OR Increase of

4 – 6 stools over

baseline per 24-hour

period

Bloody diarrhea OR

Increase of ≥ 7 stools

per 24-hour period OR

IV fluid replacement

indicated

Causality Assessment

Causality Assessment (WHO Guidelines)

1. Case with adequate information for causality

conclusion

A. Consistent causal association to immunization

A1. Vaccine product-related reaction

A2. Vaccine quality defect-related reaction

A3. Immunization error-related reaction

A4. Immunization anxiety-related reaction

B. Indeterminate

B1. Temporal relationship is consistent but insufficient

definitive evidence that vaccine caused the event (it may

be a new vaccine-linked event). This is a potential signal.

B2. Conflicting trends of consistency and inconsistency (i.e. it

may be vaccine-associated as well as coincidental and it

is

not possible clearly to favour one or the other).

Causality Assessment (WHO Guidelines)

Causality Assessment (WHO Guidelines)

1. Case with adequate information

A. Consistent causal association to immunization

B. Indeterminate

C. Inconsistent causal association to immunization

(coincidental)

2. Case without adequate information

C. Inconsistent causal association (coincidental):

Due to underlying condition or conditions caused by

exposure to something other than vaccine.

2. Case without adequate information (Unclassifiable)

• Requires additional information for causality assessment.

Case should be classified if information is available.

Causality Assessment (WHO Guidelines)

AE Reporting Timelines

Solicited/Local and Systemic Reactions:

• Will be recorded up to 30 minutes on the day of each

vaccination and for 7 days post-vaccination.

• Will be noted in subject diary card by the parent and copied

on to relevant section of the CRF pages by the Investigator

at subsequent visit.

Unsolicited Adverse Reactions

• Will be recorded in the ‘Adverse Event’ pages in the CRF

for 28 days after vaccination.

AE will be followed up till the satisfactory resolution or

stabilization

AE Reporting

SAE Reporting

Initial Report:

– As soon as it happens

– Must contain:

• An identifiable patient

• An identifiable reporter (Investigator)

• A suspect drug/ biological product

• Description of event (max information available)

SAE Reporting

All SAE

Investigator with in

24 Hrs occurrence

DCGI Sponsor Ethic Committee

DCGI: dci@nb.nic.in. / dci@cdsco.nic.in. Fax: 91-11-23236973 / Courier:

DCGI, DGHS, CDSCO, FDA Bhawan, Kotla Road, New Delhi – 110002

Sponsor: PVG@panaceabiotec.com; atulgupta@panaceabiotec.com

PVG no: +91-9650138282, 9717287654 Fax No.: +91-11-41578085

SAE reportingAnalyzed Report of SAE

By Sponsor & Investigator

Separately

EC Head of institute DCGI

With in 10 days of

occurrence

Also to DCGI Expert Committee in case of Death

SAE reportingAssessment of SAE by

Ethics Committee

DCGI

With in 21

calendar days

Also to DCGI Expert Committee in case of Death

SAE Reporting

DCGI Determine cause of SAE and Quantum of

compensation and pass order to Sponsor

within 3 months of receipt of report of SAE

from EC

Sponsor to pay within 30 days of receipt

of order

Submits details of compensation

paid to DCGI

Medical Management of AE

• Medical Management: Free medical management as long

as it is required or till such time it is established that the

injury is not related to the clinical trial, whichever is earlier.

• Compensation: In case the injury is related to the Clinical

trial, such subject shall also be entitled for financial

compensation (over and above medical management). In

case there is no permanent injury, the quantum of

compensation shall commensurate with the nature of the

non-permanent injury, loss of wages and transportation.