The document discusses adverse event and serious adverse event reporting in clinical trials. It provides definitions for key terms like adverse event, serious adverse event, and unexpected adverse reaction. It outlines ICH-GCP guidelines for safety reporting, including immediate reporting of SAEs to sponsors. Finally, it presents a case study describing a subject's experience of accelerated hypertension as an SAE during a clinical trial and the appropriate reporting steps taken.

1. ADVERSE EVENT/
SERIOUS ADVERSE
EVENT REPORTING
IN CLINICAL TRIALS
Ashish Singh parihar

2. OVERVIEW
 Important Terms and Their Definitions
 ICH-GCP Guidelines for AE/SAE
Reporting
 Case

3. Terms And Their Definitions
 Adverse Event
 Any untoward or unfavorable medical occurrence in a
human subject, including any abnormal sign,
symptom, or disease, temporally associated with the
subject’s participation in the research, whether or not
considered related to the subject’s participation in the
research.
 An AE may be expected or unexpected, related or
unrelated to the subject’s participation in the research,
local or non-local, and serious or not serious.
 The study investigator is responsible for determining
the status of an event.

4. Conti…
 Adverse Reaction (AR)
 Any untoward and unintended responses to an
investigational medicinal product related to any
dose administered
 Unexpected Adverse Reaction (UAR)
 An adverse reaction, the nature or severity of
which is not consistent with the applicable
product information (e.g. investigator’s brochure
for an unauthorized investigational product or
summary of product characteristics for an
authorized product)

5. Conti…..
 Serious Adverse Event (SAE) or Serious
Adverse Reaction (SAR) or Suspected
Unexpected Serious Adverse Reaction
(SUSAR)
Any AE, AR or UAR that at any dose:
◦ results in death
◦ is life-threatening*
◦ requires hospitalization or prolongation of
existing hospitalization
◦ results in persistent or significant disability or
incapacity
◦ consists of a congenital anomaly or birth
defect

6. Common Terminology Criteria for
Adverse Events v3.0 (CTCAE
 SAE/AE will be assessed as per the
following grades
 Grade 1: Mild AE
 Grade 2: Moderate AE
 Grade 3: Severe AE
 Grade 4: Life-threatening or disabling
AE
 Grade 5: Death related to AE

7. ICH-GCP Guidelines for Safety
Reporting
 All serious adverse events (SAEs) should be reported
immediately to the sponsor except for those SAEs that the
protocol or other document (e.g., Investigator's Brochure)
identifies as not needing immediate reporting.
 The immediate reports should be followed promptly by
detailed, written reports.
 The immediate and follow-up reports should identify
subjects by unique code numbers assigned to the trial
subjects rather than by the subjects' names, personal
identification numbers, and/or addresses.
 The investigator should also comply with the applicable
regulatory requirement(s) related to the reporting of
unexpected serious adverse drug reactions to the regulatory
authority(ies) and the IRB/IEC.

8. Conti….
 4.11.2 Adverse events and/or laboratory
abnormalities identified in the protocol as
critical to safety evaluations should be reported
to the sponsor according to the reporting
requirements and within the time periods
specified by the sponsor in the protocol.
 4.11.3 For reported deaths, the investigator
should supply the sponsor and the IRB/IEC with
any additional requested information (e.g.,
autopsy reports and terminal medical reports)

9. Notification guidelines
 Regulation 32 sets out the following responsibilities for
the notification of adverse events to sponsors:
1. An investigator shall report any SAE that occurs in a
subject at a trial site immediately* to the sponsor
(unless covered by point 2 below). This immediate
report may be made either orally or in writing as long
as detailed written report follows the immediate
report.
2. The sponsor may specify in the protocol certain
SAEs that an investigator does not have to report
immediately. The protocol should state how and when
these events should be reported.

10. Appendix XI Template
 Data Elements of AE/SAE should be filled in Appendix
XI form and submitted

11. case
study
on Accelerated Hypertension

12. Case Details
The Subject was Screened on 25/mar/2014 and he
underwent placebo Run-in and Lipid stabilization
on 25/mar/2014 & he is still in screening period.
The subject experienced left sided chest pain
which was non-radiating and not associated with
sweating on 9/Apr/2014 at 8.30 and he went to a
local hospital where ECG and other physical
examination were done. Upon examination the
subjects BP was found to be 150/100mm/Hg and his
ECG showed possibilities of IMWI( Inferior Wall
Myocardial Infraction).

13. Conti….
 He was given the following medications
 Tablet Asprin 300mg Stat
 Tablet Clopidogrel 600mg Stat
 Tablet Atorvastatin 80mg Stat
 Tablet Isosorbide Dinitrate 5mg Stat
 Tablet Metoprolol 25mg Stat
The subject called to the site at 13:00 and
he was asked to come to the hospital
immediately

14. Conti…
..as per PI’s discretion. He came to the site at
17:25. he was examined by the PI who advised
the patient to get admitted to medicine
department for further treatment and
consultation under the PI’s observation. After
considering the lab results and symptoms ,
subject was diagnosed of Accelerated
Hypertension

15. Conti…
After 4 days of hospitalization the subject got
discharged since he has shown improvement.
 Discharge Medications
• Tablet Isosorbide Mononitrate 30mg OD
• Tablet Metmorfin 500mg OD
• Tablet Ramipril 2.5mg OD
• Tablet Metoprolol 25mg OD
• Tablet Aspirin 75mg OD

16. Risk Assessment
Assessment was done by PI to check
whether it was SAE/AE.
• The subject got hospitalized as per
PI’s discretion therefore this is
termed/considered as an Adverse
Event (As per Drug and Cosmetic act
definition).
• On assessment PI found that the SAE
was not related to Study drug so any
action was not taken on the study
drug.

17. Conti…
 According to the standard grading system the
SAE was graded as
 GRADE 3 – Severe (Require Hospitalization)
 Appendix XI form
 As per the guidelines the Appendix XI form was
filled for reporting of SAE

18. SAE Reporting – Appendix XI
 Appendix XI details
Details in Appendix XI were filled as follows
1. Patient Details
• Initials and other relevent identifier – KMS, IP
524002
• Gender – Male
• Age and DOB – 52 years, DOB-08/JAN/1962
• Weight - 58kgs
• Height – 170cm

19. Conti…
2. Suspected Drug : SAE not related to the IP
• Generic name of the drug – blinded ADT 124
• Indication for which suspect drug was
prescribed – dyslipidemia
• Dosage form and strength – Auto-Injector 140
mg/ml
• Daily dose and regimen – Blinded information
• Route of Administration – IV
• Starting Date and Time of day – NA (Subject
was still undergoing screening)

20. Other Treatments..
3. Other Treatments – provide same information for
concomitant drugs
Generic
name
Indication
s for drug
was
prescribd
Dosage
Form and
strength
Daily
dose and
regimen
Route of
administr
ation
Starting
date and
time of
day
Stopping
Date and
time
Isosorbide
Mononitrat
e
Chest
Pain
30mg OD Oral 9/APR/14 Cont.
Metformin Diabetes
Mellitus
500mg OD Oral 9/APR/14 Cont.
Asprin Myocardia
l
Infraction
75mg OD Oral 9/APR/14 Cont.
Ramipril Hypertensi
on
1.25mg OD Oral 9/APR/14 Cont.
Metaprolol Hypertensi
on
25mg OD Oral 9/APR/14 Cont.

21. Appendix XI
 4. Details of Suspected Adverse event were
written in detailed manner (as per patient details
in previous slides), full description of reaction
including body site and severity, as well as the
criterion for regarding the report as serious . In
addition to a description of the reported signs
and symptoms, diagnoses for the reaction were
written in a detailed form. Medications
prescribed and details of hospitalization were
mentioned.

22. Conti…
 Start date of onset of reaction – 9/Apr/14
 Stop date or duration of reaction – 12/Apr/14
 Setting – Hospital
5. Outcome – Resolved
6. Details of the Investigator, name, Phn no,
profession, address were mentioned.
Date of reporting – 18/Apr/14
Date of reporting to EC – 18/Apr/14 and
investigator signed the form

23. Safety Reporting
 After the phone call from the subject PI assessed
the event as SAE and reported it to the members
of sponsors/CRO by mail.
 PI prepared a Submission letter for SAE , filled
the details of appendix XI form, CIOMS form,
filled and updated the event in e-CRF and in
CRF
 Submission letter and covering letter was
submitted to EC and DCGI for reporting the
SAE on 10th April 2014 i.e. next day of the
event( as per guidelines and regulatory
requirements)

24. Conti…
 EC and DCGI reviewed the SAE report and
acknowledged it and sent a Receipt .
 After the discharge of subject from the hospital
PI prepared a follow up report and submitted it
to EC and DCGI.
 Outcome - SAE was resolved as the subject
recovered from Accelerated Hypertension

25. Conti…
 All the forms, acknowledgments, lab
reports, Letters and other documents
were filed in patient file for further
monitoring and audits.
 Subject was randomized and he
continued his participation in the study