ICD-10 is the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD), a medical classification list by the World Health Organization (WHO). It contains codes for diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases.
International Conference of Harmonisation (ICH)
ICSR in Pharmacovigilance
Individual Case Study Report (ICSR) is an adverse event report for an individual patient and is source of data in pharmacovigilance.
The main focus of ICSRs are reports from healthcare providers and patients in member countries of the WHO Programme. A WHO global individual case safety report database (VigiBase) is maintained and developed on behalf of the WHO by the UMC.
VigiBase is the single largest drug safety data repository in the world. Since 1978, the Uppsala Monitoring Centre (UMC; established in Uppsala, Sweden) on behalf of WHO, have been maintaining VigiBase. Vigibase is used to obtain the information about a safety profile of a medicinal product. These data are used by pharmaceutical industries, academic institutions and regulatory authorities for statistical signal detection, updating periodic reports, ICSR comparisons with company databases and studying the reporting patterns. The data is collected from each of its 110 member states. About a hundred thousand ICSRs are added each year.
Adverse event reporting
One of the fundamental principles of adverse event reporting is the determination of what constitutes an Individual Case Safety Report (ICSR). During the triage phase of a potential adverse event report, it is important to determine if the “four elements” of a valid ICSR are present:
- an identifiable patient
- an identifiable reporter (called the “verbatim”)
- a suspect drug
- an adverse event
Although somewhat intuitive, there are a set of criteria within pharmacovigilance that are used to distinguish a serious adverse event from a non-serious one. An adverse event is considered serious if it meets one or more of the following criteria:
- results in death, or is life-threatening
- requires inpatient hospitalization or prolongation of existing hospitalization
- results in persistent or significant disability or incapacity
- results in a congenital anomaly (birth defect)
- or is otherwise “medically significant” (i.e., that it does not meet preceding criteria, but is considered serious because treatment/intervention would be required to prevent one of the preceding criteria.)
ISO ICSR standard
Coding of adverse events
Adverse event coding is the process by which information from an adverse effect reporter, is coded using standardized terminology from a medical coding dictionary, such as MedDRA (the most commonly used medical coding dictionary). The purpose of medical coding is to convert adverse event information into terminology that can be readily identified and analyzed. For instance, Patient 1 may report that they had experienced “a very bad headache that felt like their head was being hit by a hammer” [Verbatim 1] when taking Drug X. Or, Patient 2 may report that they had experienced a “slight, throbbing headache that occurred daily at about two in the afternoon” [Verbatim 2] while taking Drug Y. Neither Verbatim 1 nor Verbatim 2 will exactly match a code in the MedDRA coding dictionary. However, both quotes describe different manifestations of a headache. As a result, in this example both quotes would be coded as PT Headache (PT = Preferred Term in MedDRA).
Safety monitoring of medicines in the European Union (EU)
The European Medicines Agency (EMA) has published a guide to support the implementation of a new international standard for the safety monitoring of medicines in the European Union (EU). The so-called ISO ICSR standard improves the reporting of suspected side effects of medicines in Individual Case Safety Reports (ICSRs). The use of the new international standard has taken effect on 1 July 2016. EMA is herewith closing the circle between ICSR and XEVMPD by using the ISO IDMP´s controlled vocabularies. It requires the use of the new ISO IDMP standards when they become available for use in the EU.
MPID – Medicinal Product Identifier
The interesting part for closing the circle between XEVMPD and ISCR is the so called MPID – Medicinal Product Identifier – also part of IDMP standard ISO 11615 identifying the product with ist entire liefe cycle (development, authorisation, post-Marketing and renewal or withdrawal from the market. Further it is stated that ‘until such a time as the ISO IDMP standards are implemented worldwide the support for free text will be required.
However, when the circle will be closed, then the aim of IDMP to increase the patients´safety will be reached.
ISO ICSR aims at establishing the same format for the reports on individual cases of suspected side effects in patients due to a medicine across the world. It also is expected to include better information on medicines that might be associated with an adverse drug reaction and on the therapeutic uses of those medicines. In addition, the standard also strengthens personal data protection in the records of ICSRs collected by pharmaceutical companies and regulatory authorities.
This will improve the quality of data collected, and increase the ability to search and analyse them. Regulatory authorities will be able to detect and address safety issues with medicines more quickly, and therefore better protect patients.
EMA´s ICSR Implementation Guide
The new guide developed jointly by EMA and the Heads of Medicines Agencies (HMA) will be of interest to pharmaceutical companies and medicines regulatory authorities in EU Member States and will support them to prepare for the use of the standard. The guide specifically defines the electronic transmission process of ICSRs, the format and content of the ICSR, the business rules for report validation as well as classification and data quality principles. It will also assist software providers and IT developers as pharmacovigilance databases are being developed.
IDMP Definition of Identification of Medicinal Products
IDMP defines the data elements and structures for the unique identification and exchange of medicinal products´ information.
ISO IDMP Standards
The set of fife ISO international standards has been developed by the ISO in response to a worldwide demand for internationally harmonised specifications for identification and description of medicinal products.
IDMP provides the basis for the unique identification of medicinal products, which facilitates the activities of medicines regulatory agencies worldwide by jurisdiction for a variety of regulatory activities (development, registration and life cycle management of medicinal products, pharmacovigilance, and risk management). They can also be applied to Investigational Medicinal Products.
Messaging specifications are included as an integral part of the IDMP Standards. They describe and protect the integrity of the interactions for the submission of regulated medicinal product information in the context of the unique product identification; they include acknowledgement of receipt including the validation of transmitted information. Health Level Seven (HL7) Message Exchange are normative within the IDMP Standards.
IDMP Standards are completed with Implementation Guides which are currently in development (2015), as well as with Technical Specifications (TS) 16791 (provides guidance for the identification of medicinal products by using intenational supply chain Standards, securing traceability, safe supply chain and other market requirements) and Technical Requirements (TR) 14872 (Requirements for the implementation of the Standards for the identification of medicinal products for the exchange of regulated medicinal product Information), the latter being in development.
Implications for Marketing Authorisation Holders (MAHs)
In order to submit the data all branches of a company should share a common language, from pharmacovigilance to product supply to comply with the controlled vocabulary dedicated.
The structured substance information, and controlled vocabularies for pharmaceutical dose forms, units of presentation, routes of administration, and packaging will be challenging to integrate.
Furthermore the terminology needs to be aligned throughout the company.
You will find more details here
The data required for XEVMPD was predominantly already held by regulatory affairs, although for the majority of companies, some additional data had to be collected from within regulatory affairs. In addition, a typically limited amount of information came from pharmacovigilance and drug safety.
Collation and provision of IDMP data will have significant ramifications for industry but also potential opportunities for the ways companies manage and share data. Overall, IDMP is not data that sits solely in regulatory affairs, and significant parts of it are—or should be—corporate data. Essentially there is the potential that IDMP can drive or support master data management initiatives in industry as well as at the European Medicines Agency. The need to address provision of additional information can be a driver for rationalising the ways companies manage their own data whereby they establish a single authoritative source that is aligned with the ISO standards rather than create yet another instance of data that might have to be manipulated and then maintained independently.
Challenges for most companies in terms of data will be:
- Locating an appropriate source of the relevant data
- Ensuring that the data aligns with the granularity, vocabularies, and data types of IDMP
- Establishing a mechanism to maintain the data
- Ensuring consistency of the data to be submitted with that which may be identified during pharmacovigilance
The chart below illustrates that the combined actual cost of XEVMPD across 14 companies exceeded €28M; cost of the ISO IDMP switch is conservatively forecasted to exceed €38M across these same companies. Therefore, a sampling of 14 European Federation of Pharmaceutical Industries and Associations (EFPIA) member companies indicates a combined expenditure of at least ~ €70M for implementing XEVMPD and IDMP.
The chart is drawn out of the Position Paper from the EFPIA:
“Principles for the Implementation of ISO IDMP Standards for EudraVigilance and Development of a Road Map – Final, 6th Oct. 2014”