Adverse and serious adverse events (AE and SAEs)

 

Standard operating procedure (.pdf Nederlands/.pdf English)

 

Unblinding procedure (.pdf Nederlands/.pdf English)

 

Unblinding request form (.doc)


 

An adverse event (AE) is defined as any undesirable experience occurring to a subject during

this trial, whether or not considered related to the investigational drug. The difference

between adverse events and serious adverse events is that AE does not result in events as

desribed in the section serious adverse events.

All adverse events observed by the investigator or his staff will be recorded in the eCRF by the

local investigator. These adverse events will be reported annually to the authorities as

described below under section serious adverse events.

A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose

results in death;

is life threatening (at the time of the event);

requires hospitalization or prolongation of existing inpatients� hospitalization;

results in persistent or significant disability or incapacity;

other important events that may jeopardize the safety of the subject or may require

intervention to prevent one of the primary or secondary outcomes listed in the study

protocol.

All SAEs will be reported, as described in the flowchart (.pdf Nederlands/.pdf English), by the principle investigator to the Data Monitoring Committee (DMC) and to the accredited METC that approved the protocol, according to the requirements of that METC.

 

Definition of the different serious adverse events:

1. Context-specific SAE�s: This study population (critically ill preterm infants) has a high

risk of serious complications (so-called �context-specific SAE�s�), which are inherent to

their vulnerable condition and unrelated to the intervention which is under evaluation

in this trial.

The context-specific SAEs that will be identified include the following events:

treatment failure as defined in section 5.1.3 of the study protocol

mortality at 28 days PNA, 36 weeks PMA and at hospital discharge

BPD at 28 days PNA and 36 weeks PMA

failure to extubate 3, 7, 14 and 21 days after initiating therapy

duration of mechanical ventilation

use of �rescue treatment� with hydrocortisone outside the study protocol

total time on supplemental oxygen

length of hospital stay

incidence of hypertension

hyperglycaemia requiring the use of insulin therapy

nosocomial infection, like sepsis, meningitis and pneumonia

pulmonary hemorrhage, pneumothorax and pulmonary interstitial emphysema

hemodynamic significant patent ductus arteriosus

necrotising enterocolitis (NEC)

gastrointestinal bleeding

isolated gastrointestinal perforation diagnosed on abdominal radiography

intraventricular haemorrhage (IVH) and/or periventricular leucomalacia (PVL)

retinopathy of prematurity, including grading

weight, head circumference and length at 36 weeks PMA

long-term health and neurodevelopmental sequelae assessed at 2 years

These complications are included in the primary and secondary outcomes of this

study and are recorded in the Case Report Form and reported to the DMC on an

annual basis.

2a. "Unrelated" Serious Adverse Event (Unrelated-SAE's): Unrelated serious adverse events (or

reactions) are all untoward and unintended responses which are not related, or not likely related

to the study medication.

The definition of

� �not related�: There is no evidence of any causal relationship

�not likely related�: There is little evidence to suggest there is a causal

relationship (e.g. the event did not occur within a reasonable time after

administration of the trial medication). There is another reasonable

explanation for the event (e.g. the patients clinical condition, other

concomitant treatment)

2b. Suspected serious adverse reaction (SSAR): Serious adverse events (or reactions) are

all untoward and unintended responses which are possibly or likely or documented

related to the study medication as described in the SCP/IMPD (if you would to obtain the IMPD please contact the coordinating center).

The definition of

Possible related: There is some evidence to suggest a causal relationship (e.g.

because the event occurs within a reasonable time after administration of the trial

medication). However, the influence of other factors may have contributed to the

event (e.g. the patients clinical condition, other concomitant treatments).

Likely related: There is evidence to suggest a causal relationship and the influence

of other factors is unlikely.

Very likely related: There is clear evidence to suggest a causal relationship and

other possible contributing factors can be ruled out.

These serious adverse events (2a and 2b) are to be reported by the local investigator within 72

hours of the occurring of the event in the eCRF. By doing so, an e-mail with high priority will

automatically be sent to the stop-bpd@amc.nl. The principle investigator will report

expedited these SAEs through the web portal ToetsingOnline to the METC, competent

authority, Medicine Evaluation Board as well as to the competent authorities in other

Member States, according to the requirements of the Member States. The expedited

reporting will occur not later than 15 days after the PI has first knowledge of the

adverse reactions. For fatal or life threatening cases the term will be maximal 7 days

for a preliminary report with another 8 days for completion of the report.

2c. Suspected unexpected serious adverse reactions (SUSAR): Suspected unexpected

adverse reactions are adverse reactions, of which the nature, or severity, is not

consistent with the applicable product information (see SCP document/IMPD document) or the

context-specific SAEs as listed above.

Any SUSAR should be reported, as soon as it occurs, to the principle investigator and

the study coordinator via the study website within 24 hours after the event occurs. The

PI will report expedited all SUSARs through the web portal ToetsingOnline to the METC,

competent authority, Medicine Evaluation Board as well as to the competent

authorities in other Member States, according to the requirements of the Member

States. The expedited reporting will occur not later than 15 days after the PI has first

knowledge of the adverse reactions. For fatal or life threatening cases the term will be

maximal 7 days for a preliminary report with another 8 days for completion of the

report.