This document discusses signal detection and management in pharmacovigilance. It provides a brief history of pharmacovigilance programs internationally and in India. It defines pharmacovigilance and outlines the objectives, processes, and key steps involved in signal detection, validation, prioritization, assessment, and recommendation for action. These include ongoing monitoring of adverse event reports, signal detection methods, validation criteria, prioritization factors, signal assessment, and potential recommendations that may involve regulatory reporting, labeling changes, or additional studies. The goal is to identify potential safety issues and determine appropriate actions to prevent or minimize patient risk.
Signal detection and management activities are at the core of ensuring drug safety. A complex process of signal detection; through their validation and confirmation; analysis and prioritisation; and signal assessment to recommending action.
Find out more at out training: http://bit.ly/1W31NCF
Introduction to Aggregate Reporting in Drug Safety & Pharmacovigilance in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
Signal detection and management activities are at the core of ensuring drug safety. A complex process of signal detection; through their validation and confirmation; analysis and prioritisation; and signal assessment to recommending action.
Find out more at out training: http://bit.ly/1W31NCF
Introduction to Aggregate Reporting in Drug Safety & Pharmacovigilance in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
Pharmacovigilance Process Work Flow - Katalyst HLSKatalyst HLS
Introduction to Drug Safety & Pharmacovigilance Process Work Flow for Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
This Module provides guidance on planning and conducting the legally required audits, the role, context and management of pharmacovigilance audit activity.
The principles in this module are aligned with internationally accepted auditing standards, issued by relevant international auditing standardization organizations and support a risk-based approach to pharmacovigilance audits.
“Regulatory writing department at Turacoz have the expertise to develop various regulatory documents such as Investigator Brochures (IBs), Protocols, Clinical Study Reports (CSRs), Common Technical Documents (CTDs) and pharmacovigilance documents such as Periodic Safety Update Reports (PSURs) and Risk Management Plans (RMPs). In these slides, we have presented an overview on Periodic safety update reports (PSURs) and also the guidelines such GVP modules and ICH E2c. We have also discussed the changes from old PSUR format to new Periodic Benefit-Risk Evaluation Report (PBRER) format.”
Identifying Safety Signals by Data Mining the FDA Adverse Event Reporting Sys...Perficient, Inc.
Ever since the European Union (EU) introduced new legislation that requires life sciences companies to proactively detect, prioritize, and evaluate safety signals, there has been an increased interest, not only from sponsors and CROs in the EU, but globally, in pharmacovigilance systems that can assist with the signal management process.
Perficient's Chris Wocosky, an expert in signal detection and management, shows how your organization can use Empirica Signal, Oracle's state-of-the-art signal detection system to data mine the existing FDA Adverse Event Reporting System (FAERS) to determine safety signals. This presentation and demonstration willhelp you bettter understand how this solution can be used in daily pharmacovigilance activities.
The aim of Safety reports is describe the safety during the lifecycle of the medicinal product. These reports are necessary during development as well as during the authorization process or renewal. In addition, several of these reports may be required by Health Authorities in case of safety concerns.
This presentation contains a full overview about periodic safety update reports and all the information related with it.
This presentation is a brief overview of ICH-GCP guidelines. Although ICH-GCP is a very vast topic, still this presentation will cover almost all the points. The reader will be able to discuss about the roles and responsibilities of various personnel in clinical trials.
Signal detection is a process used in pharmacovigilance to identify potential safety issues or new safety information associated with a medicinal product. The goal of signal detection is to detect signals, or potential safety concerns, as early as possible in order to allow for timely risk management and safety interventions.
Signal detection typically involves analyzing large amounts of safety data, including adverse event reports, clinical trial data, post-marketing surveillance data, and other sources of safety information. The data is analyzed using statistical methods and algorithms to identify any patterns or trends that may suggest a potential safety concern.
Once a potential safety concern is identified, further investigation is typically required to confirm the signal and assess the magnitude of the risk. This may involve conducting additional studies, analyzing the available data in more detail, or consulting with regulatory agencies and other stakeholders.
Signal detection is an ongoing process that continues throughout the life cycle of a medicinal product. The process is critical for ensuring the ongoing safety and effectiveness of medicinal products, and is an important component of pharmacovigilance activities.
PHARMACOVIGILANCE
The World Health Organization (WHO) defines Pharmacovigilance as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.”
ADVERSE DRUG REACTION
According to WHO “ADR is a response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function.”
Introduction to ICSR Narrative Writing in Drug Safety & Pharmacovigilance in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
Pharmacovigilanc: The science & activities relating to the Detection, Assessment, Understanding and Prevention of adverse effects or any other drug related problems
The Thalidomide Tragedy (Lessons for Drug Safety and Regulation)
CLASSIFICATION OF ADRS (RAWLIN AND THOMPSON CLASSIFICATION)
Why PV is Necessary?
Objective of PV
Outcomes of Drugs
Causal Relationship
Adverse drug reaction and causality assessment scales
Classification of AE
Serious Adverse Event (SAE)
Sources of Adverse Events (AE) reports
Sources of AE Reports(Solicited Reports)
What to Report?
Who to Report?
When to Report?
Individual case data flow
Pharmacovigilance "Module I" Pharmacovigilance system & their quality systemMohamed Raouf
This Module contains guidance for the establishment and maintenance of quality assured Pharmacovigilance systems for marketing authorization holders (MAHs) and national medicine authorities (NMAs).
Reference:- Guideline on good pharmacovigilance practices (GVP) version no.3
Pharmacovigilance Process Work Flow - Katalyst HLSKatalyst HLS
Introduction to Drug Safety & Pharmacovigilance Process Work Flow for Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
This Module provides guidance on planning and conducting the legally required audits, the role, context and management of pharmacovigilance audit activity.
The principles in this module are aligned with internationally accepted auditing standards, issued by relevant international auditing standardization organizations and support a risk-based approach to pharmacovigilance audits.
“Regulatory writing department at Turacoz have the expertise to develop various regulatory documents such as Investigator Brochures (IBs), Protocols, Clinical Study Reports (CSRs), Common Technical Documents (CTDs) and pharmacovigilance documents such as Periodic Safety Update Reports (PSURs) and Risk Management Plans (RMPs). In these slides, we have presented an overview on Periodic safety update reports (PSURs) and also the guidelines such GVP modules and ICH E2c. We have also discussed the changes from old PSUR format to new Periodic Benefit-Risk Evaluation Report (PBRER) format.”
Identifying Safety Signals by Data Mining the FDA Adverse Event Reporting Sys...Perficient, Inc.
Ever since the European Union (EU) introduced new legislation that requires life sciences companies to proactively detect, prioritize, and evaluate safety signals, there has been an increased interest, not only from sponsors and CROs in the EU, but globally, in pharmacovigilance systems that can assist with the signal management process.
Perficient's Chris Wocosky, an expert in signal detection and management, shows how your organization can use Empirica Signal, Oracle's state-of-the-art signal detection system to data mine the existing FDA Adverse Event Reporting System (FAERS) to determine safety signals. This presentation and demonstration willhelp you bettter understand how this solution can be used in daily pharmacovigilance activities.
The aim of Safety reports is describe the safety during the lifecycle of the medicinal product. These reports are necessary during development as well as during the authorization process or renewal. In addition, several of these reports may be required by Health Authorities in case of safety concerns.
This presentation contains a full overview about periodic safety update reports and all the information related with it.
This presentation is a brief overview of ICH-GCP guidelines. Although ICH-GCP is a very vast topic, still this presentation will cover almost all the points. The reader will be able to discuss about the roles and responsibilities of various personnel in clinical trials.
Signal detection is a process used in pharmacovigilance to identify potential safety issues or new safety information associated with a medicinal product. The goal of signal detection is to detect signals, or potential safety concerns, as early as possible in order to allow for timely risk management and safety interventions.
Signal detection typically involves analyzing large amounts of safety data, including adverse event reports, clinical trial data, post-marketing surveillance data, and other sources of safety information. The data is analyzed using statistical methods and algorithms to identify any patterns or trends that may suggest a potential safety concern.
Once a potential safety concern is identified, further investigation is typically required to confirm the signal and assess the magnitude of the risk. This may involve conducting additional studies, analyzing the available data in more detail, or consulting with regulatory agencies and other stakeholders.
Signal detection is an ongoing process that continues throughout the life cycle of a medicinal product. The process is critical for ensuring the ongoing safety and effectiveness of medicinal products, and is an important component of pharmacovigilance activities.
PHARMACOVIGILANCE
The World Health Organization (WHO) defines Pharmacovigilance as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.”
ADVERSE DRUG REACTION
According to WHO “ADR is a response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function.”
Introduction to ICSR Narrative Writing in Drug Safety & Pharmacovigilance in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
Pharmacovigilanc: The science & activities relating to the Detection, Assessment, Understanding and Prevention of adverse effects or any other drug related problems
The Thalidomide Tragedy (Lessons for Drug Safety and Regulation)
CLASSIFICATION OF ADRS (RAWLIN AND THOMPSON CLASSIFICATION)
Why PV is Necessary?
Objective of PV
Outcomes of Drugs
Causal Relationship
Adverse drug reaction and causality assessment scales
Classification of AE
Serious Adverse Event (SAE)
Sources of Adverse Events (AE) reports
Sources of AE Reports(Solicited Reports)
What to Report?
Who to Report?
When to Report?
Individual case data flow
Pharmacovigilance "Module I" Pharmacovigilance system & their quality systemMohamed Raouf
This Module contains guidance for the establishment and maintenance of quality assured Pharmacovigilance systems for marketing authorization holders (MAHs) and national medicine authorities (NMAs).
Reference:- Guideline on good pharmacovigilance practices (GVP) version no.3
Introduction
•All medicinal products carry risks in addition to their possible benefits for developing a new medicine, a decision can only be made if both benefits & risks are addressed. Risk associated with the drug is minimized when medicines of good quality, safety & efficacy are used rationally by an informed health professional & by patients. Pharmacovigilance helps in reducing the risk of harm by ensuring use of good quality medicines appropriately. Need of international efforts to address drug safety were realized &
initiated in 1961, following the Thalidomide disaster. Guidelines were developed to monitor drugs, foods & environmental contaminants for adverse reactions & toxicity . In beginning, guidelines were restricted to local needs. Globalization -
recognized need of a system, accepted internationally, to ensure safety
of medicinal products.New drugs: marketed on basis of comparatively limited information, as clinical trials are designed to answer specific questions .•In US, ~ 500 to 2000 patients receive a new drug during clinical trials, & only a few hundred of them are treated > 3-6 months
• In clinical trials, critical efficacy endpoints are identified in advance
& sample sizes are estimated for assessment of effectiveness .
• Common AEs are generally identified & well characterized in
prospective trials
•Infrequent or delayed AE Characteristic depending on their severity
and importance to risk benefits and require special techniques
•Isolated report- definitive in associating a drug with an AE, if drug
administration and event are temporally related, de- challenging or
re-challenging.
•In contrast with few exceptions phase 2 3 trial are not designed to
test specified hypothesis about safety nor to measure identifying AE
with any specified hypotheses about safety nor to measure or identify
AEs with any pre-specified level of sensitivity.
• Exceptions occur when a particular concern related to drug or drug
class has arisen & when there is a specific safety advantage being
studied.
• Safety evaluation during clinical drug development is not expected to
characterize all the AEs, for example, those occurring in < 1 in 1000
patients
•Risks that may be missed include
• rare events
• events occurring after long-term use
• events occurring in special populations
• events occurring in association with specific diseases &
• events occurring in association with concomitant therapy Introduction
Presentation: Pharmacovigilance requirements inspected and example findingsTGA Australia
Presentations given at the TGA information sessions cover the pharmacovigilance inspection guidelines, preparing for inspections, inspection process, and close out of inspections.
Updates from the Pharmacovigilance and Special Access Branch TGA Australia
Presentation on using new sources of data in Pharmacovigilance, Pharmacovigilance Inspection Program (PVIP) update, International collaboration activities, Adverse Event Management System (AEMS)
Q and A
Presentation: Updates from the Pharmacovigilance and Special Access BranchTGA Australia
This presentation covers using new sources of data in Pharmacovigilance, Pharmacovigilance Inspection Program update, international collaboration activities and Adverse Event Management System.
ICH Guidelines for Pharmacovigilance.pdfNEHA GUPTA
The "ICH Guidelines for Pharmacovigilance" PDF provides a comprehensive overview of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines related to pharmacovigilance. These guidelines aim to ensure that drugs are safe and effective for patients by monitoring and assessing adverse effects, ensuring proper reporting systems, and improving risk management practices. The document is essential for professionals in the pharmaceutical industry, regulatory authorities, and healthcare providers, offering detailed procedures and standards for pharmacovigilance activities to enhance drug safety and protect public health.
Intentional re-challenge and the clinical data management of Drug Related pro...ClinosolIndia
Intentional re-challenge" refers to a deliberate decision to re-administer a drug to a patient who has previously experienced an adverse drug reaction (ADR) or drug-related problem. This is done under controlled circumstances to confirm whether the suspected adverse event was indeed caused by the drug and to assess the reproducibility of the reaction.
In clinical data management, intentional re-challenge involves collecting and analyzing data related to the re-administration of the drug to the patient. This process is often carried out in a clinical trial or controlled clinical setting, and the resulting data play a crucial role in understanding the causality of the adverse event and making informed decisions about the drug's use.
Signal Validation and Causality Assessment in Adverse Event ReportingClinosolIndia
Signal validation and causality assessment are essential components of pharmacovigilance, which is the science and activities related to monitoring, assessing, and preventing adverse effects or any other drug-related problems. Pharmacovigilance plays a crucial role in ensuring the safety of drugs and medical products after they have been approved and are available on the market.
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
1. SIGNAL DETECTION AND
MANAGEMENT
DR SEKHAR BABU BANDAR
post graduate 2nd year
Department of pharmacology
Moderator : Prof.k.Sankar MD;DTCD
1
2. • Dying due to disease is sometimes unavoidable
but Dying due to medicine is unacceptable.
Lepakhin V. Geneva 2005
• Primum non nocere
meaning FIRST DO NO HARM.
• HIPPOCRATES formulated first reason -
To do our utmost to minimise harm due to
pharmacotherapy.
2
3. HISTORY
• 1968-WHO program for International Drug monitoring was started .
• 1978- later moved to Uppsala after agreement between Sweden &
WHO.
• 1986-ADR monitoring system for INDIA proposed 12 regional centers.
• 1997-INDIA joined WHO-ADR reporting program based in Uppsala
,Sweden .
• 2004- National pharmacovigilance program officially inaugurated by
Central Health Minister at New Delhi.
3
4. • 2005- Ministry of Heath And Family Welfare in India initiated the NPP
,coordinated by the Central Drug Standard Control Organization (CDSCO).
• July2010-PVPI initiated - AIIMS ,New Delhi as National Co-ordination center
for monitoring ADRs .
• 15 April 2011,the NCC shifted from AIIMS ,Delhi to Indian pharmacopeia
commission ,Ghaziabad.
• July 8,2009- MCI made mandatory - EVERY MEDICAL COLLEGE IN INDIA
SHOULD HAVE PHARMACOVIGILANCE COMMITTEE
4
5. DEFNITION
• Pharmacovigilance (PV) is defined as the science and activities
relating to the
• Detection,
• Assessment,
• Understanding and
• Prevention of adverse effects or any other drug-related problem
5
6. OBJECTIVES
• Identify and analyse new signal from reported cases
• Benefit-risk ratio of marketed medications
• Evidence based information on safety of medicines
• Communicate the safety information on use of medicines
• Exchange of information and data management with other centres
• Provide training and consultancy support
• Rational use of medicines
6
7. MONITORING OF ADVERSE EVENTS
• Ongoing monitoring of adverse event reports comprises the retrieval
of data from the global safety database at monthly intervals for all
monitored products, and review of the data with the purpose of
timely identification of (potential) new safety signals requiring further
investigation. The monitoring also comprises data retrieval from the
clinical databases for the analysis of non-serious adverse events.
7
8. SIGNAL MANAGEMENT PROCESS
• Based on the examination of individual case safety reports (ICSR),
aggregate data from active surveillance systems or studies, and
literature information or other data sources.
8
9. SIGNAL MANAGEMENT PROCESS INCLUDES
• Signal detection
• Signal validation
• Signal prioritization
• Signal assessment
• Recommendation for action
• Exchange of information
9
11. • Tabulation of AEs / ADRs for the monitoring period including,
but not limited to,
1. Designated medical events (DME)
2. Targeted medical events (TME),
3. Relating to new cases over the time period under study.
• Cumulative summary tabulation listing all AEs / ADRs on the
database for the product.
11
12. • Aggregate reports (monthly requests) of adverse events including serious,
non-serious, and any other events of interest, obtained from:
1. Clinical studies
2. Regulatory reports
3. Commercial complaints
4. Preclinical in vitro and in vivo studies
5. Epidemiologic data
6. Media. Internal and external websites, and social media
7. Medical literature
8. Data from off-label use
12
14. • Retrieve tables and listings as defined in the Product Safety
Monitoring Plan
• Review the retrieved data set within 1 week
• accepted standards for identifying safety signals do not exist. Expert
knowledge and medical judgment are always required
• Consider the following elements during ongoing monitoring of case
reports for signal identification:
• Document the ongoing monitoring activities and any findings via the
Product Safety Signal Monitoring Tracking Sheet
14
15. FOLLOWING ELEMENTS ARE CONSIDERED
DURING SIGNAL IDENTIFICATION:
• Information from summary tabulations, for the monitoring period
and for cumulative data.
• Line listing information, as demographics (age, gender), dose of
suspect product, temporal relationship, information on de-challenge
and re-challenge.
• Causality assessment.
• Specific topics / medical concepts to be monitored, if applicable.
15
17. IDENTIFY POTENTIAL SAFETY SIGNALS THROUGH
VARIOUS PHARMACOVIGILANCE ACTIVITIES,
• Ongoing monitoring of AEs / ADRs.
• Individual medical review of ICSRs and customer product quality
complaints.
• Preparation of aggregate reports (as for example the Periodic Benefit
Risk Evaluation Report, PBRER)
• Review of scientific and medical literature.
17
18. • Data obtained from company-sponsored clinical and non-clinical
studies, including surveillance systems.
• Information obtained from a health authority.
• Other, such as data on quality, systematic reviews, meta-analyses,
internet and digital media under the management.
18
19. COMBINATION OF STATISTICAL AND CLINICAL
METHODS FOR THE EVALUATION OF A SIGNAL
• Careful review of individual case details.
• Comparing rates to an historical period of reporting rates.
• Using more reliable data sources such as incidence rates from
previous clinical studies.
• Preclinical studies from biologic effects, or pharmacokinetics or
pharmacodynamics effects.
• Search for additional cases that meet similar criteria (similar events)
of the signal.
19
20. DETERMINE IF A NEW OR POTENTIAL SAFETY
SIGNAL EXISTS THAT WARRANTS FURTHER
INVESTIGATION INCLUDING
• New AEs, not currently documented. Specially if they are serious and have
occurred in rare sub-populations.
• An apparent increase in the severity of an AE
• Occurrence of serious adverse events (SAE) known to be extremely rare in
the general population
• Previously unrecognized interactions with other products, supplements or
food.
• Identification of a previously unrecognized at-risk patient population or
subgroup of patients, such as patients with specific medical conditions,
comorbidities, or with specific racial or genetic predispositions.
20
21. • Adverse events arising from the way a product is being used either on
or off-label (e.g. adverse events seen at doses higher than those
normally prescribed or in sub-populations not recommended in the
label.
• Adverse events arising from user errors, or from medication errors.
• Other concerns that may be identified by PV department or a
regulatory agency.
• PV SCIENTIST ADDS THE DETECTED -POTENTIAL- SAFETY SIGNAL TO
THE PRODUCT SAFETY SIGNAL MONITORING TRACKING SHEET.
21
23. SIGNAL VALIDATION : CLINICAL RELEVANCE
• Strength of the association with the product
• Evidence of dose-response effect
• Frequency, that is, for example the number of spontaneous reports in
comparison to earlier periods and/or in relation to estimated patient
exposure; same type of information in the context of clinical trial
data.
• Quality of the reports. Completeness of data, plausibility of the
information, availability of data to substantiate reported diagnosis.
• Reporter and company causality assessment of individual cases.
23
24. • Temporal relationship of the product use and event, including information
on de-challenge and re-challenge.
• Consistency of data patterns indicating potential risk groups.
• Consistency of findings across available data sources.
• Specificity of a case series (for example, same histopathology or subtype of
a disorder is reported in all cases of a series of reports.
• Alternative medical or technical explanations.
24
25. • Seriousness and severity of the reaction and its outcome, relative to
the disease being treated.
• Drug-drug interactions.
• Potential to mitigate the risk in the population.
• Feasibility of a further study using controlled or observational
designs.
• Degree of benefit the product provides, including availability of other
therapies.
25
26. SIGNAL VALIDATION:PREVIOUS AWARENESS
• Biological plausibility of the event in light of the known or assumed
pharmacological properties of the suspect drug or the drug class.
• Extent to which information is already included
• Association has already been addressed in an aggregate report, or has
been subject to a regulatory procedure
26
27. • Richer set of data on the same AE /ADR:
1.Literature findings
2.Experimental findings or biological mechanisms
3.Screening of databases with larger datasets
27
28. After the investigation of the safety signal, the
conclusion can be:
• Validated and accepted: a causal association between the product and the
event is assumed
• Not validated and rejected: no causal association between the product
and the event is assumed, or
• Pending, not confirmed signal: no clear conclusions regarding causality can
be drawn. The signal is further monitored and re-evaluated at a defined
time point
28
30. FOR PRIORITIZATION OF A SIGNAL, CONSIDER
THE FOLLOWING ASPECTS
• Impact on patients depending on the severity, reversibility, potential
for prevention and clinical outcome
• Consequences on treatment discontinuation on the disease and the
availability of other therapeutic options
• Strength and consistency of the evidence supporting the association
• Clinical context
• Public health impact
• Enter the outcome of the signal prioritization process in the product
safety signal monitoring tracking sheet
30
32. STEPS TO BE PERFORMED FOR SIGNAL
ASSESSMENT:
• Review appropriate internal and external sources to obtain further
information
• Document the risk assessment of the signal per product safety signal
investigation report, and recommend no further action, or further
action to prevent or minimize patient risk as described in the next
section, Recommendation for Action.
• Assess the significance of a signal to obtain a potential link to a
complex disease, to a prior stage or a reaction or to clinical
complications of the adverse reaction of interest.
32
34. • Initiation of a Health Hazard Assessment (HHA) for potential field action
(field alert reporting evaluation)
• Request quality complaint investigation for further product evaluation
• Expedited reporting to regulatory agencies
• Direct healthcare professional communication / Dear Doctor Letters
• Updating safety related labeling or prescribing information
• Clinical expert statements
34
35. • Reporting to investigators, Institutional Review Boards (IRB), Ethics
Committees, updating study documents, or holding or stopping
ongoing studies early
• Continued assessment of the product benefit-risk balance
• Further investigation of the safety risk through additional studies
• Development of a pharmacovigilance plan focused on evaluating the
identified risk
• Reporting via periodic report submission
• Risk management document updates
• Additional educational materials or training
35
36. For all validated signals, and in accordance with
final recommendations from the committee:
• Modification of the ongoing monitoring strategy of the product
• Initiation of label change and/or other external communication
activities
• Initiation of recall/correction procedure
• Information to concerned health authorities
• Issuing or updating a Risk Management Plan
36
37. • Introduction of enhanced pharmacovigilance activities
• Introduction of additional risk minimization activities
• Conducting a post-authorization safety study
• Periodic review of the signal
37
39. • Communicate immediately to regulatory affairs as an Emerging Safety Issue
all validated signals pointing towards an implication for public health or the
benefit-risk profile of the specific product.
• Depending on the severity of the signal, communicate validated signals
representing a new potential signal or a new aspect of a known risk and
not having implications for the benefit-risk profile to applicable regulatory
authorities.
39
40. • Communicate the outcome of signal assessment involving new or
changed risks to the public including health care professionals and
patients as well as to the concerned marketing authorization holders.
40
Signal is essentially a hypothesis of a risk with a medicine with data and argument that support it. It is not a conclusive, and is only an early indication ,it may change substantially over time as more data accumulates.
This ongoing monitoring of adverse event reports comprises the retrieval of data from the global safety database at monthly intervals for all monitored products, and review of the data with the purpose of timely identification of (potential) new safety signals requiring further investigation. The monitoring also comprises data retrieval from the clinical databases for the analysis of non-serious adverse events.
Retrieval strategies (case selection criteria, format, and periodicity of retrievals from the global safety database, for example) should be defined in advance on a per-product basis. Retrieval strategies and results of all ongoing monitoring activities must be documented.
Generally accepted procedures for signal investigation, objective thresholds for accepting safety signals, or generalizable rules for subsequent action do not exist. Expert knowledge and medical judgment are always required.
Likewise, the timelines for processing a potential signal depend on the severity and potential public health impact on the population concerned. Potential safety signals that, if accepted, may pose a significant public health threat (e.g. an unexpected adverse event that is both serious and frequent) should be processed with priority until timelines are defined by the safety management team and/or regulatory authorities.
The signal management process is always based on the information available at the time of the review and may change over time.
Events which do not fall under the definition of a reportable (valid) ICSR but may affect the benefit-risk balance of a medicinal product and/or impact on public health shall be notified as Emerging Safety Issue, per applicable regulatory requirements.
The Pharmacovigilance Scientist defines the retrieval strategy on a per-product basis depending on the maturity of the safety profile and number of case reports for the concerned product. At a minimum, retrieves no less frequently than monthly a standard dataset comprising the following:
Aggregate safety data may include the following elements: MedDRA coded terms, by System Organ Class (SOC) and Preferred Term (PT); frequency of events; nature and type of events (serious, non-serious, events of special interest, expectedness, relatedness).
Also, it will be important to:
Define additional retrievals (additional datasets and/or higher monitoring frequency depending on, for example, regulatory commitments, an existent risk management plan (RMP), or known safety issues.
Document the retrieval strategy on a per-product basis via a “Product Safety Signal Monitoring Plan”.
Following are the steps PV scientist will perform, regarding ongoing monitoring:
PV personnel may identify potential safety signals through various pharmacovigilance activities, including the following:
Normally, the PV scientists performs the following steps for signal validation:
Evaluate the data supporting a detected signal in order to verify that the available source documentation contains sufficient evidence demonstrating the existence of a new potentially causal association or a new aspect of a known association, and therefore justifies further prioritization and assessment of the signal.
Depending on the nature and context of the signal investigation, the below describes aspects that will be considered when validating a signal:
Availability of other relevant sources of information providing a richer set of data on the same AE /ADR:
Document this conclusion in the product safety monitoring tracking sheet. Set deadline or threshold for re-investigation of pending signals and document in the product safety monitoring tracking sheet.
In collaboration with the PV physician, document each safety signal investigation depending on its context using the product safety signal investigation report, and sign the form. Include the documentation background, information sources and methods, results and conclusion of the investigation. Examples of additional sources of documentation include the company comments on the ICSRs, aggregate reports, or other documents submitted to health authorities.
The following steps are to be performed by the PV scientist:
The PV scientist will promptly identify validated signals with important public health impact or that may significantly affect the benefit-risk profile of the medicinal product in treated patients. These signals require urgent attention and need to be prioritized, that is, evaluated without delay.
For prioritization of a signal, consider the following aspects, if applicable:
The objective of signal assessment is to further evaluate the significance and potential risk of a validated signal so as to identify the need for additional data collection, risk mitigation or minimization activities in a timely manner, or for any regulatory action.
The next steps are performed by the PV physician:
Based on the level of safety risk or patient impact, recommend action and review recommendations with the product safety board. Recommended actions may include, but are not limited to, any of the following with appropriate time frame for action consistent with the nature and severity of the signal:
The product safety review committee will determine appropriate timelines for initiation and completion of suitable actions for all validated signals, which will be documented in the meeting minutes and in the individual product safety signal investigation report.
The PV scientist documents all detected signals including validation, prioritization, assessment, actions including timelines and reporting dates, as well as current status in the product safety signal monitoring tracking sheet.
The following steps will be performed by the PV physician: