Safety monitoring and reportingin clinical trials – ensuringquality and effectiveness Author: Magdalena Matusiak Manager, Clinical DevelopmentPharmacovigilance Team Lead, KCR

Adverse event reporting to authorities

product in EU:

• Sponsor must obtain EudraCT number and MedDRA access

• Sponsor must be registered with Eudravigi-lance database (EV registration procedure usually takes about 20 working days to be

-quest submission together with an applica-ble document)

• Sponsor must be registered with the eXtended EudraVigilance Medicinal Product Dictionary (XEVPRM)

• Safety management procedures have to be

in the clinical trial are aware of their responsibilities

SUSAR reports may be submitted:- via Eudravigilance database only- via Eudravigilance database and

additionally electronic submission to local Competent Authorities may be required

- in some countries only paper versions of safety reports are acceptable still - submit-ted by post/courier or submitted in person

CONCLUSIONS:

Pharmacovigilance systems have become recently more and more regulated due to hard work of global and national health agencies. New requirements have been established to assure that patients’ safety is properly moni-tored, all safety data is valid and credible, and the process of safety reporting is fast and

Despite the number of guidelines and recom-mendations released for national regulators, clinical trial Sponsors, CRO companies with regard to pharmacovigilance processes, common human errors, report omissions,

reporting process still appear to be the most important factors potentially leading to patients’ safety threats, protocol deviations,

Human mistakes and failures made at early stages of the safety reporting procedure may

safety and may lead to improper conclusions

is more, it may become a potential global threat to patients' safety and public health in the future.

by Sponsors and CRO companies at the clinical site level could have an enormous impact on

-covigilance system for the entire clinical trial duration.

REFERENCES:

EMA, Guidelines on Good Pharmacovigilance Practices (GVP) available at: www.ema.eu-ropa.eu/ema/index.jsp?curl=pages/regulation/-document_listing /document_listing_000345.jsp

Communication from the Commission — De-

and presentation of adverse event/reaction re-ports arising from clinical trials on medicinal products for human use (‘CT-3’) 2011/C 172/01, European Commission 2011;

-tion and standards for expedited reporting E2E 1994;

ICH, Good Clinical Practice E6(R1) 1996;

WHO, The importance of pharmacovigilance safety monitoring of medicinal products, 2002

Adverse event reporting to sponsor

After receipt of the SAE report from the investi-gator a medical review of the report is per-formed to verify completeness and quality of data. After assessing the SAE reports obtained

during the clinical trials conduct, the most common omissions are analyzed. Graph no 1

-ciencies. Table no 2 summarizes the key factors

and timelines.

Potential risk to be minimized Key element to consider Recommendation

Patients may not fully understand the risk relatedto the study drug

Informed Consent Form/Patient’s Information

Patients should be informed in a detailed, clear and understandable manner not only about possible adverse reactions, but also about any symptoms patients may experience, which conditions should be particularly observed.

Patients may not remember about potential threat to their health

Re-consentoption (especially during long-term clinical trials). Re-consent is obligatory if new safety information is available.

Patients may not remember about adverse events occurred between visits

Patient diaries,Phone contacts

Paper patient’s diaries, commonly used, might be lost or forgotten by patient. An electronic patient’s

and store safety data, allows for the safety monitor-ing at the time the entry was made. Phone contacts with patients between visits may be crucial for monitoring patient’s safety status.

Patients may not understand what information is crucial for the investigation

Detailed interview with patient during the visit

Patient’s perception of information and level of un--

cantly. Each patient should be treated individually.

medical data to feel comfortable with sharing their private information with investigators.

not be available if patient is hos-pitalized or after patient’s death

Patient’s family members

Patient’s family member may be a valuable source of medical information, especially if patient’s health condition is very poor, or after patient’s death.

Table no 1:

Potential risk to be minimized Recommendation

Seriousness criteria not recognized by investigators

Detailed training on seriousness criteria should be conducted for investiga-

the situations should be considered serious. Independent medical review of patient’s safety parameters in study database should be every day practice during clinical research.

Missing minimum information criteria on the SAE report report template making them more visible. Detailed step-by-step SAE report-

process.

on the SAE report, hospital discharge or other documents send to the Sponsor/CRO

All site study personnel involved in the trial should be regularly trained in

and dedicated fax for safety reporting should be limited and controlled.

Bad quality of scanned SAE report Equipment and software crucial for safety reporting should be tested and validated before the study. Back-up methods of safety reports transmission should be always available.

Use of obsolete version of SAE report template or SAE report template dedicated for other trial

Obsolete versions of safety reports should be removed from sites. Sites should be provided with pre-printed with site and project details templates,

Table no 2:

IMP batchnumber

Outcomeof the event

Patient’smedical history

Actiontakenwith studydrug

Study druginformation(dose, route)

Relationshipto study drug

35%

19%17%

11%

11%7%

Graph no 1: The most frequent SAE reports source: KCR)

PATIENT

INVESTIGATOR medicinal producton the market

CRO, SPONSOR COMPETENTAUTHORITIES

PATIENT PATIENT PATIENT

Adverse events detection

Adverse events reporting Risk assessment andmarketing approval

Adverseevents reporting

OBJECTIVE:

The main goal of the article is to present critical points in safety monitoring and reporting at dif-ferent stages of the clinical trial, with a main focus on the early stages of the process. The

by medical personnel and clinical team during their everyday practice, and attempts to identi-fy relevant solutions and answer the question how to get the plausible and precise safety data maintaining the highest ethical standards during clinical development.

RESULTS:

Safety monitoring processes start at the level of observing patient’s symptoms as well as

performed by investigators. Table no 1

adverse event detection.

METHOD:

Based on KCR’s knowledge and experience in clinical monitoring, medical monitoring and pharmacovigilance, the most important aspects and processes of safety monitoring and report-ing have been assessed.

Copyright © 2015 KCR S.A.All rights reserved.

Quality of data, time of data obtainment and

for proper safety reporting processes.

Almost 20 years of clinical experience have made KCR an expert for identi�cation and in-depth analysis of those critical points that may in�uence negatively on patients' safety, as well as for implementation of e�ective tools to assure that safety and wellbeing of patients are adequately maintained and controlled during clinical trials.