What is an ICSR: A report that contains information describing a suspected adverse drug reaction related to the administration of one or more medicinal products to an individual patient is termed as individual case safety report.
Safe use of medicines continues to be a crucial issue globally and is the prime responsibility of stakeholders of the health system. Besides the patient identification data, it should also specify time frames of the adverse reactions, details of medications used, dechallenge and re-challenge details to mention a few. These ICSRs need to be submitted within rigid time frames as specified by the regulatory authorities.
Fact: EU Pharmacovigilance laws state that all spontaneous reports regarding serious adverse reactions must be expedited within 15 days. In addition, from November 2017 all non-serious adverse reactions, with an origin within the EU, require expediting to EMA within 90 days.
This implies that all reactions need to be fast tracked to meet the timelines. It is interesting to note that failure to be compliant with expedited reporting is one of the common causes for penalty and losses to MAH.
It is inevitable that submission of the report in the exacting format within the short challenging period can be a cause of demurral in services many a time. What is required is a team which believes in flight and fright reaction at the appropriate times and doesn’t dawdle in these tricky situations. The team at Gratisol Labs thoroughly knows the intricacies of the regulations and has systems and processes in place to help prioritize their action. They are well equipped to cut the Gordian knot efficiently and will ensure smooth delivery of services at your end.
Pharmacovigilance comprises of
- Safety data management
- Signal detection for any new altered safety issue
- Signal evaluation and making decisions with regard to safety issues
- Actions, including regulatory, to protect public health
- Informing all concerned parties or stakeholders
Safety Data Management
A Serious Adverse Event for a molecule could be generated during the preregistration or postmarketing phase. They could occur during clinical trials or be reported spontaneously by a patient, caregiver, relation, doctor, nurse or pharmacist. Another regulatory body or a licencee company could also be the informant. It could be received on phone, mail, fax, journals, newspapers or the latest social media.
Unexpected adverse events could arise anytime in the life of a product. These could put the user to serious risk and could curtail the life of the product. As part of the risk management plan, safety data is gathered throughout the life of a product. Consequently, every company that markets even a handful of products across many countries, gathers thousands of reports per year. The only way to manage this load is using latest software and automation.
The steps in safety data management are
- Data collection and verification
- Coding of adverse reaction descriptions
- Coding of drugs
- Case causality assessment
- Timely reporting to authorities
Data Collection and verification:
Acknowledgement : A valid case needs to have four elements; an adverse event, a reporter, a patient and a drug. Every report needs to be acknowledged, more so the valid reports. Acknowledgement establishes a contact with the reporter for more information whenever required . It builds company image with the stakeholder and also protects from litigation. A consentious reporter may continue to send the same report repeatedly till it is acknowledged, hence this simple action avoids duplication.
Duplicate search: Due to, greater awareness , stringent regulations and multiple reporting sources, duplicate reports is a common phenomenon. Every safety management software has a facility to identify and delete duplicates. . Certain characteristics of a case (sex, age or date of birth, dates of drug exposure, clinical trial code, country, etc.) may be used to identify duplicate reporting. This action is of significance for further processing of the case. The duplicate could actually be follow up information that could alter the seriousness and hence reporting timeline of the case. Missed out duplicates could send misleading information to signal detection systems.
Triage: Collins dictionary defines triage as
- (Medicine) the principle or practice of sorting casualties in battle or disaster or other patients into categories of priority for treatment
- (Government, Politics & Diplomacy) the principle or practice of allocating limited resources, as of food or foreign aid, on a basis of expediency rather than according to moral principles or the needs of the recipients
Triage in safety means prioritizing the case for reporting to authorities. An oversimplification of triage would be to report deaths and life threatening unexpected reports in 7 days and other adverse reactions in 15 days as there are also other occasions where expedited reporting is required.
Data Entry: A seemingly repetitive and inconsequential step in the process but something that forms the basis of good reporting. The quality of data entry affects the further processing of the case. Details of the four pillars of a valid case have to be reported meticulously. Patient information has to follow the HIPPA code for confidentiality. Reporter information has to clear and detailed enough to be able to contact the person if necessary. Drug identifiers like name, formulation and dose have to be captured correctly. Event report has to be detailed enough for the evaluator to decide on the cause of the adverse event. This would include chronological description of the event or events, nature, localisation, severity, characteristics of the event, results of investigations and tests, start date, course and outcome, concomitant medications and other risk factors .
Case narrative: Provides summary of events to readers who do not have access to original data sets. During the course of safety data management, it is seen and used by various groups like case reviewers to decide seriousness, upgrade etc , affiliate companies to triage for their countries, , during preparation of PSURs and other summary reports and also by regulatory authorities. One should ensure completeness, chronology and sufficient detail in a narrative so that the reader is able to come to a conclusion.
Coding of adverse reactions: This step ensures that everyone is talking the same language and the data can be shared internationally, Most commonly used system is the MedDRA( Medical Dictionary for Regulatory Activities). Use of MedDRA has lead to a global standardization across regulatory agencies, across companies & across countries. This step usually needs oversight by a medically qualified person.
Coding for drugs: Both the suspect drug and concomitant medication have to be coded. The principle is again to be talking the same language across countries, companies and regulatory bodies. Most common dictionary is the WHO Drug Dictionary enhanced. This is provided as a product by the Upsala Monitoring centre of the WHO. Entries are updated 4 times a year. The majority of entries refer to prescription-only products, but some over-the-counter (OTC) preparations are included. The dictionary also covers biotech and blood products, diagnostic substances and contrast media. For chemical and therapeutic groupings the WHO drug record number system and ATC classifications are considered.
Causality assessment: Non spontaneous case reports usually indicate whether an adverse drug reaction is suspected due to the administered drug. In these circumstances and even otherwise, a causality assessment is required to be conducted. Various approaches have been developed for the structured determination of the likelihood of a causal relationship between drug exposure and adverse events. These systems are largely based on following considerations:
- the chronology or association in time (or place) between drug administration and event
- current knowledge of nature and frequency of adverse reactions due to the suspect molecule; or the pharmacology
- medical or pharmacological plausibility based on signs and symptoms, laboratory tests, pathological findings, mechanism of action
- likelihood or exclusion of other causes for the same adverse events; often the disease condition or concomitant medication.