The information from ADR cases when first received is generally incomplete. Ideally, comprehensive information would be available on all cases, but in practice efforts should be made to seek additional information on selected reports. In any scheme to optimize the value of follow-up, the first consideration should be prioritization of case reports by importance.
The priority for follow-up should be as follows: cases which are 1) both serious and unexpected, 2) serious and expected, and 3) non-serious and unexpected. In addition to seriousness and expectedness as criteria, cases "of special interest" also deserve extra attention as a high priority (e.g., ADRs under active surveillance at the request of the regulators), as well as any cases that might lead to a labeling change decision.
Follow-up information should be obtained, via a telephone call and/or site visit and/or via a written request. Efforts should be tailored toward optimising the chances to obtain the new information. Written confirmation of details given verbally should be obtained whenever possible. In exceptional circumstances, a regulatory authority might be able to assist an MAH to obtain follow-up data if requests for information have been refused by the reporter. The company should provide specific questions it would like to have answered.
In order to facilitate the capture of clinically relevant and complete information, use of a targeted questionnaire is encouraged, preferably at the time of the initial report. Ideally, healthcare professionals with thorough pharmacovigilance training and therapeutic expertise should be involved in the collection and the direct follow up of reported cases (particularly those of medical significance). For serious ADRs, it is important to continue follow-up and report new information until the outcome has been established or the condition is stabilized. How long to follow-up such cases will require judgment.MAHs should collaborate on follow-up if more than one MAH's drug is suspected as a causal agent in a case.
It is important that, at the time of the original report, sufficient details about the patient and reporter be collected and retained to enable future investigations, within the constraints imposed by local data privacy legislation.
Thursday, September 30, 2010
Single Case Evaluation- Good Case Management
The purpose of careful medical review is to ensure correct interpretation of medical information. Regardless of the source of an ADR report, the recipient should carefully review the report for the quality and completeness of the medical information. This should include, but is not limited to, consideration of the following:
Is a diagnosis possible?
Have the relevant diagnostic procedures been performed?
Were alternative causes of the reaction(s) considered?
What additional information is needed?
ADR terms should be used consistently and in accord with recommended standards for diagnosis. The report should include the verbatim term, which quotes the reporter. Staff receiving reports should provide an unbiased and unfiltered report of the information from the reporter. While the report recipient is encouraged to actively query the reporter to elicit the most complete account possible, inferences and imputations should be avoided in report submission. However, clearly identified evaluations by the MAH are considered acceptable and, for some authorities, required. Encouraging good communication on medical information with the reporter will serve to improve the quality of case documentation.
When a case is reported by a consumer, his/her description of the event should be retained, although confirmatory or additional information from any relevant healthcare professionals should also be sought and included. Ideally, supplemental information should be obtained from the healthcare professional directly involved in the care of the patient.
Is a diagnosis possible?
Have the relevant diagnostic procedures been performed?
Were alternative causes of the reaction(s) considered?
What additional information is needed?
ADR terms should be used consistently and in accord with recommended standards for diagnosis. The report should include the verbatim term, which quotes the reporter. Staff receiving reports should provide an unbiased and unfiltered report of the information from the reporter. While the report recipient is encouraged to actively query the reporter to elicit the most complete account possible, inferences and imputations should be avoided in report submission. However, clearly identified evaluations by the MAH are considered acceptable and, for some authorities, required. Encouraging good communication on medical information with the reporter will serve to improve the quality of case documentation.
When a case is reported by a consumer, his/her description of the event should be retained, although confirmatory or additional information from any relevant healthcare professionals should also be sought and included. Ideally, supplemental information should be obtained from the healthcare professional directly involved in the care of the patient.
Role of the Narratives
The objective of the narrative is to summarize all relevant clinical and related information, including patient characteristics, therapy details, medical history, clinical course of the event(s), diagnosis, and ADR(s) (including the outcome, laboratory evidence and any other information that supports or refutes an ADR). The narrative should serve as a comprehensive, stand-alone "medical story". The information should be presented in a logical time sequence; ideally this should be presented in the chronology of the patient's experience, rather than in the chronology in which the information was received. In follow-up reports, new information should be clearly identified.
Abbreviations and acronyms should be avoided, with the possible exception of laboratory parameters and units. Key information from supplementary records should be included in the report, and their availability should be mentioned in the narrative and supplied on request. Any autopsy or other post-mortem findings (including a coroner's report) should also be provided when available if allowed by local privacy protection laws. Terms in the narrative should be accurately reflected by appropriate coding.
Abbreviations and acronyms should be avoided, with the possible exception of laboratory parameters and units. Key information from supplementary records should be included in the report, and their availability should be mentioned in the narrative and supplied on request. Any autopsy or other post-mortem findings (including a coroner's report) should also be provided when available if allowed by local privacy protection laws. Terms in the narrative should be accurately reflected by appropriate coding.
Assessing Patient and Reporter Identifiability
Patient and reporter identifiability is necessary to avoid case duplication, detect fraud, and facilitate follow-up of appropriate cases. The term identifiable in this context refers to the verification of the existence of a patient and a reporter.
One or more of the following automatically qualifies a patient as identifiable: age (or age category, e.g., adolescent, adult, elderly), gender, initials, date of birth, name, or patient identification number. Additionally, in the event of second-hand reports, every effort should be made to verify the report source. All parties supplying case information (or approached for case information) are subject to the notion of identifiability: not only the initial reporter (the initial contact for the case), but also others supplying information.
In the absence of qualifying descriptors, a report referring to a definite number of patients should not be regarded as a case until the minimum four criteria for case reporting are met. For example, "Two patients experienced." or " a few patients experienced" should be followed up for patient-identifiable information before regulatory reporting.
One or more of the following automatically qualifies a patient as identifiable: age (or age category, e.g., adolescent, adult, elderly), gender, initials, date of birth, name, or patient identification number. Additionally, in the event of second-hand reports, every effort should be made to verify the report source. All parties supplying case information (or approached for case information) are subject to the notion of identifiability: not only the initial reporter (the initial contact for the case), but also others supplying information.
In the absence of qualifying descriptors, a report referring to a definite number of patients should not be regarded as a case until the minimum four criteria for case reporting are met. For example, "Two patients experienced." or " a few patients experienced" should be followed up for patient-identifiable information before regulatory reporting.
Good Case Management
Accurate, complete and bonafide information is very important for MAHs and regulatory agencies identifying and assessing ADR reports. Both are faced with the task of acquiring sufficient information to help ensure that the reports are authentic, accurate, as complete as possible, and non-duplicative.
- Assessing Patient and Reporter Identifiability
- Role of Narratives
- Single Case Evaluation
- Follow up Information
Pharmacovigilance software
The EMEA or the European Medicines Agency in Europe develops and maintains the pharmacovigilance database of probable serious adverse effect medicines in the market. This system is called EudraVigilance.
Similarly, the US medical society has its own pharmacovigilance branches namely; the FDA; the academic and non-profit organizations like RADAR and Public Citizen and the pharmaceutical manufacturers. Several companies like Aris Global, Relsys and Workflow have developed pharmacovigilance software to keep track of safety applications in the market.
Kinds of pharmacovigilance software:
PV Works for example is a pharmacovigilance software system that records report safety data keeping track of adverse event reporting. It is a commercial workflow engine providing management control of pharmacovigilance processes. Flexible data entry, risk management, safety system assessment, evaluation and submission of regulatory reports are some of its important features.
PV Works (Vet) is another software system made to support veterinary pharmacovigilance business and technical processes meeting the necessary safety standards. Data entry, reporting, audit trail are some of its main features.
The outsourced pharmacovigilance software develops drug development expertise, safety rules and regulatory necessities, securing client access to data and regular tracking and status updates to clients or to the authority. It is an economical project development process making using of the electronic medium for handling management purposes.
The Assured pharmacovigilance software provides Internet access to the server for the client’s use and operation of the system for management and customer use. This software meets the standards of pharmaceutical companies, regulatory authorities and medical personnel.
How effective is pharmacovigilance software?
- Pharmacovigilance software minimizes the risk of adverse events (ADR) by using genetic profiles.
- It makes accurate determinations as to whether a product is safe or not.
- It determines the benefit-risk ratio quickly
- It overcomes the challenges that small firms face as far as limited financial and personnel resources are concerned.
- Pharmacovigilance software helps maintain regulatory compliance and improve operational efficiency.
- Global information can be easily shared by means of this software.
- In the age of safety concerns, more need is being felt for software that can avert probable risks and also help in worldwide networking in the medical field. Pharmacovigilance software is designed just for this.
Adverse event reporting system(AERS)
(AERS) is a computerized database of adverse events that is designed to help drug regulation authority. Adverse event reporting systemrities in drug manufacturing and post-marketing safety surveillance program for all medicines and biological products produced. AERS can be used in monitoring activities such as looking for new safety concerns that might be related to a marketed product, evaluating a manufacturer's compliance to reporting regulations and responding to requests for drug information from consumers, medical practitioners or authorities.
AERS can be used to compile and enhance the set of standards set for manufacturing and marketing drugs. The pharmaceutical industry will be in turn notified about the revised drug standardizations. Based on this, they can manufacture products that do not cause any of the reported adverse drug reactions. This helps pharmaceutical industries produce safer products that in turn generates greater demand and increases sales.
AERS can be used to compile and enhance the set of standards set for manufacturing and marketing drugs. The pharmaceutical industry will be in turn notified about the revised drug standardizations. Based on this, they can manufacture products that do not cause any of the reported adverse drug reactions. This helps pharmaceutical industries produce safer products that in turn generates greater demand and increases sales.
FDA issues final rule on safety information during clinical trials
FDA is announcing a final rule that will improve the quality of safety reports and better protect people participating in clinical trials for drugs. The final rule clarifies the safety information that drug sponsors (drug manufacturers) must report to FDA for investigational new drug applications (INDs).
The final rule will help sponsors decide whether an adverse event that occurs in a participant during a clinical trial is related to the investigational drug being tested, or if it is related to other health problems in the trial participants. Reports that focus on the most significant adverse events help FDA, sponsors, and clinical investigators better understand how to use the drug safely.
The final rule defines new terms that help clarify when an adverse event should be reported to FDA rapidly - within 7 to 15 days. The rule explains that adverse events should be reported to FDA in an expedited manner only when there is a reasonable possibility that the drug caused the adverse event. The final rule also makes clear what information should not be reported to FDA because the information would not help the agency assess the safety of the drug being studied.
The final rule enhances the protection of clinical trial participants by requiring rapid reports to FDA of certain safety information that had not previously been required. For example, findings from clinical or epidemiological studies that suggest a significant risk or serious, suspected adverse reactions that occur more frequently than anticipated must now be reported rapidly to FDA.Another new requirement is that serious adverse events from bioavailability and bioequivalence studies, which are typically conducted for generic drugs, need to be reported rapidly to FDA.
Many clinical trials are conducted in countries outside the United States, so the revised definitions and reporting standards in this final rule are designed to be as consistent as possible with international definitions and standards. This should help lead to consistent, harmonized reporting for globally conducted clinical trials. Safety information from clinical studies conducted outside the United States can be evaluated along with information from U.S. clinical trials.
Reference:http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm227386.htm
The final rule will help sponsors decide whether an adverse event that occurs in a participant during a clinical trial is related to the investigational drug being tested, or if it is related to other health problems in the trial participants. Reports that focus on the most significant adverse events help FDA, sponsors, and clinical investigators better understand how to use the drug safely.
The final rule defines new terms that help clarify when an adverse event should be reported to FDA rapidly - within 7 to 15 days. The rule explains that adverse events should be reported to FDA in an expedited manner only when there is a reasonable possibility that the drug caused the adverse event. The final rule also makes clear what information should not be reported to FDA because the information would not help the agency assess the safety of the drug being studied.
The final rule enhances the protection of clinical trial participants by requiring rapid reports to FDA of certain safety information that had not previously been required. For example, findings from clinical or epidemiological studies that suggest a significant risk or serious, suspected adverse reactions that occur more frequently than anticipated must now be reported rapidly to FDA.Another new requirement is that serious adverse events from bioavailability and bioequivalence studies, which are typically conducted for generic drugs, need to be reported rapidly to FDA.
Many clinical trials are conducted in countries outside the United States, so the revised definitions and reporting standards in this final rule are designed to be as consistent as possible with international definitions and standards. This should help lead to consistent, harmonized reporting for globally conducted clinical trials. Safety information from clinical studies conducted outside the United States can be evaluated along with information from U.S. clinical trials.
Reference:http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm227386.htm
Pharmacovigilance- various inputs,processes and outputs
INPUTS: Safety data: spontaneous ADRs, epidemiology studies, clinical trials, pre-clinical data.
PROCESSES : Signal generation, Signal evaluation, Risk–benefit review, Expert advice, Decision-making
OUTPUTS:Decision, Communication, revised SPC, revised PIL, bulletin article.
PROCESSES : Signal generation, Signal evaluation, Risk–benefit review, Expert advice, Decision-making
OUTPUTS:Decision, Communication, revised SPC, revised PIL, bulletin article.
Essential activities in Pharmacovigilance
There are five broad activities that are essential to pharmacovigilance. These are:
- suspected ADR signal generation and formation of hypotheses,
- analysis of all issues around the signal, particularly confirmation (or refutation) of hypotheses,estimation of the size of the risk and whether susceptible patients exist,
- consideration of possible changed benefit-to risk issues in therapy,
- communication of information to health professionals and patients in a useful way and possible regulatory action;
- consequence evaluation.
CENTRAL DRUGS STANDARD CONTROL ORGANIZATION(CDSCO)- Pharmacovigilance In India
Under the Drug and Cosmetics Act, the regulation of manufacture, sale and distribution of Drugs is primarily the concern of the State authorities while the Central Authorities are responsible for approval of New Drugs, Clinical Trials in the country, laying down the standards for Drugs, control over the quality of imported Drugs, coordination of the activities of State Drug Control Organisations and providing enforcement of the Drugs and Cosmetics Act.
Drug Controller General of India is responsible for approval of licenses of specified categories of Drugs such as blood and blood products, I. V. Fluids, Vaccine and Sera.
Medicines in India are regulated by CDSCO - Central Drugs Standard Control Organization Under Ministry of Health and Family Welfare. Headed by Directorate General of Health Services CDSCO regulates the Pharmaceutical Products through DCGI - Drugs Controller General of India at Chair. Under Retail and Distribution:- Drugs classified under 5 heads
1. Schedule X drugs - Narcotics
2. Schedule H and L - Injectables, Antibiotics, Antibacterials
3. Schedule C and C1- Biological Products-example Serums and Vaccines
Under Manufacturing Practice: Schedule N
List of the equipment for the efficient running of manufacturing wing, Qualified personnel: Schedule M
Drug Controller General of India is responsible for approval of licenses of specified categories of Drugs such as blood and blood products, I. V. Fluids, Vaccine and Sera.
Medicines in India are regulated by CDSCO - Central Drugs Standard Control Organization Under Ministry of Health and Family Welfare. Headed by Directorate General of Health Services CDSCO regulates the Pharmaceutical Products through DCGI - Drugs Controller General of India at Chair. Under Retail and Distribution:- Drugs classified under 5 heads
1. Schedule X drugs - Narcotics
2. Schedule H and L - Injectables, Antibiotics, Antibacterials
3. Schedule C and C1- Biological Products-example Serums and Vaccines
Under Manufacturing Practice: Schedule N
List of the equipment for the efficient running of manufacturing wing, Qualified personnel: Schedule M
Uppsala Monitoring Centre
The principal function of the Uppsala Monitoring Centre is to manage the international database of ADR reports received from National Centres. In 2002 this database held nearly three million case reports. The majority of national contributing centres have easy electronic access to these. The UMC has established standardized reporting by all National Centres and has facilitated communication between countries to promote rapid identification of signals.
A sophisticated Bayesian confidence propagation neural network (BCPNN) programme was created in 1998, which partly automates the signal detection system, and provides earlier alert signals than previous methods.The effectiveness of this system depends on:
• the size of the database
• the quality of the reports received from the contributing centres
• the timeliness of such reporting
• an active and reliable reporting culture within participating countries.
An international advisory panel of clinical experts determines the validity and clinical importance of the signals generated. In recent years the UMC has expanded its role as a communications and training centre and clearing-house for information on drug safety. Through
• mail discussion groups,
• website development,
• newsletters
• annual National Centre meetings,
The UMC team, in collaboration with the WHO, facilitates and encourages the international collaboration, which was identified in 1972 as being vital for the success of pharmacovigilance. The terminologies developed within the WHO programme for coding adverse reactions and medicines have been widely adopted by National Centres, manufacturers and drug regulators. In recent years, the introduction of a new terminology known as MedDRA (Medical Dictionary for Drug Regulatory Activities) has replaced the World Health Organization Adverse Reaction Terminology (WHO-ART) in developed countries. WHO-ART remains the mainstay of communicating adverse reactions in most developing countries within the International Programme.
Another project at the UMC is the creation of an ADR monitoring system for herbal and traditional medicines.While the UMC has achieved much in improving the activities, support and recognition of individual National Centres, much more could still be done in providing training and encouraging expertise at a national level. There needs to be better consultation and communication between developed and developing countries when discussions on international harmonization of pharmacovigilance issues are taking place. More effective communication of information is being promoted and encouraged through the WHO International Drug Monitoring Programme and the UMC. They are working towards playing a more pro-active role in working together with countries in addressing specific safety concerns and establishing a system that would make possible an evaluation of safety concerns of international importance by a supranational body of experts.
A sophisticated Bayesian confidence propagation neural network (BCPNN) programme was created in 1998, which partly automates the signal detection system, and provides earlier alert signals than previous methods.The effectiveness of this system depends on:
• the size of the database
• the quality of the reports received from the contributing centres
• the timeliness of such reporting
• an active and reliable reporting culture within participating countries.
An international advisory panel of clinical experts determines the validity and clinical importance of the signals generated. In recent years the UMC has expanded its role as a communications and training centre and clearing-house for information on drug safety. Through
• mail discussion groups,
• website development,
• newsletters
• annual National Centre meetings,
The UMC team, in collaboration with the WHO, facilitates and encourages the international collaboration, which was identified in 1972 as being vital for the success of pharmacovigilance. The terminologies developed within the WHO programme for coding adverse reactions and medicines have been widely adopted by National Centres, manufacturers and drug regulators. In recent years, the introduction of a new terminology known as MedDRA (Medical Dictionary for Drug Regulatory Activities) has replaced the World Health Organization Adverse Reaction Terminology (WHO-ART) in developed countries. WHO-ART remains the mainstay of communicating adverse reactions in most developing countries within the International Programme.
Another project at the UMC is the creation of an ADR monitoring system for herbal and traditional medicines.While the UMC has achieved much in improving the activities, support and recognition of individual National Centres, much more could still be done in providing training and encouraging expertise at a national level. There needs to be better consultation and communication between developed and developing countries when discussions on international harmonization of pharmacovigilance issues are taking place. More effective communication of information is being promoted and encouraged through the WHO International Drug Monitoring Programme and the UMC. They are working towards playing a more pro-active role in working together with countries in addressing specific safety concerns and establishing a system that would make possible an evaluation of safety concerns of international importance by a supranational body of experts.
WHO Quality Assurance and Safety
The Quality Assurance and Safety: Medicines team is responsible for providing guidance and support to countries on drug safety matters. The team is part of the Department of Essential Drugs and Medicines Policy, within the WHO Health Technology and Pharmaceuticals cluster. The purpose of the department is:
to help save lives and improve health by closing the huge gap between the potential that essential drugs have to offer and the reality that for millions of people – particularly the poor and disadvantaged – medicines are unavailable, unaffordable, unsafe or improperly used.
WHO works towards fulfilling this mission by providing global guidance on essential drugs and medicines, and working with countries to implement national drug policies.These are designed to ensure:
• equity of access to essential drugs
• drug quality and safety
• rational use of drugs.
The explicit objectives of the Quality Assurance and Safety: Medicines team are:
• to ensure the quality, safety and efficacy of all medicines by strengthening and putting into practice regulatory and quality assurance standards.
For this policy to meets its objectives, the scope of pharmacovigilance needs to be extended to include the safety of all related health technologies, including medicines, vaccines, blood products, biotechnology, herbal medicines and traditional medicines.
Functions of the WHO Programme for International Drug Monitoring include: • Identification and analysis of new adverse reaction signals from the case report information submitted to the National Centres, and from them to the WHO database. A data-mining approach (BCPNN) is used at the UMC to support the clinical analysis made by a panel of signal reviewers.
Provision of the WHO database as a reference source for signal strengthening and ad hoc investigations. Web-based search facilities and customized services are available • Information exchange between WHO and National Centres, mainly through 'Vigiflow', an e-mail information exchange system • Publication of periodical newsletters , (WHO Pharmaceuticals Newsletter and Uppsala Reports), guidelines and books in the pharmacovigilance and risk management area • Supply of tools for management of clinical information including adverse drug reaction case reports. The main products are the WHO Drug Dictionary and the WHO Adverse Reaction Terminology • Provision of training and consultancy support to National Centres and countries establishing pharmacovigilance systems • Computer software for case report management designed to suit the needs of National Centres (VigiFlow) • Annual meetings for representatives of National Centres at which scientific and organizational matters are discussed • Methodological research for the development of pharmacovigilance as a science.
to help save lives and improve health by closing the huge gap between the potential that essential drugs have to offer and the reality that for millions of people – particularly the poor and disadvantaged – medicines are unavailable, unaffordable, unsafe or improperly used.
WHO works towards fulfilling this mission by providing global guidance on essential drugs and medicines, and working with countries to implement national drug policies.These are designed to ensure:
• equity of access to essential drugs
• drug quality and safety
• rational use of drugs.
The explicit objectives of the Quality Assurance and Safety: Medicines team are:
• to ensure the quality, safety and efficacy of all medicines by strengthening and putting into practice regulatory and quality assurance standards.
For this policy to meets its objectives, the scope of pharmacovigilance needs to be extended to include the safety of all related health technologies, including medicines, vaccines, blood products, biotechnology, herbal medicines and traditional medicines.
Functions of the WHO Programme for International Drug Monitoring include: • Identification and analysis of new adverse reaction signals from the case report information submitted to the National Centres, and from them to the WHO database. A data-mining approach (BCPNN) is used at the UMC to support the clinical analysis made by a panel of signal reviewers.
Provision of the WHO database as a reference source for signal strengthening and ad hoc investigations. Web-based search facilities and customized services are available • Information exchange between WHO and National Centres, mainly through 'Vigiflow', an e-mail information exchange system • Publication of periodical newsletters , (WHO Pharmaceuticals Newsletter and Uppsala Reports), guidelines and books in the pharmacovigilance and risk management area • Supply of tools for management of clinical information including adverse drug reaction case reports. The main products are the WHO Drug Dictionary and the WHO Adverse Reaction Terminology • Provision of training and consultancy support to National Centres and countries establishing pharmacovigilance systems • Computer software for case report management designed to suit the needs of National Centres (VigiFlow) • Annual meetings for representatives of National Centres at which scientific and organizational matters are discussed • Methodological research for the development of pharmacovigilance as a science.
WHO Key Dates & Establishments - Pharmacovigilance
1968 WHO Programme established. International ADR terminology and drug dictionary
1969 Definition of ADR
1978 Operations transferred to the UMC; setting-up of relational ADR database. Regular WHO Programme member meetings
1981 Computerised version of WHO Drug Dictionary available to all
1982 ATC classification coding of all medicinal products
1985 International expert review panel created
1991 On-line WHO database search programme available to national centres
1991 Definitions of adverse event, side effect and causality assessment terms
1993 Windows-based client server program for online database searches
1993 Regular training and educational activities
1994 Methodology for use of denominator data for calculation of ADR reporting rates
1997 Knowledge-detection tool for automated signal detection (BCPNN)
1997 Promotion of communication as a necessary discipline
1998 Internet discussion group for national centres
2001 Start of Vigibase Online project
2002 New database system (Vigiflow)
2003 New Drug Dictionary with expanded data fields; agreement with IMS Health to increase information in DD
2004 Pattern recognition using the BCPNN on health databases to find safety information.
1969 Definition of ADR
1978 Operations transferred to the UMC; setting-up of relational ADR database. Regular WHO Programme member meetings
1981 Computerised version of WHO Drug Dictionary available to all
1982 ATC classification coding of all medicinal products
1985 International expert review panel created
1991 On-line WHO database search programme available to national centres
1991 Definitions of adverse event, side effect and causality assessment terms
1993 Windows-based client server program for online database searches
1993 Regular training and educational activities
1994 Methodology for use of denominator data for calculation of ADR reporting rates
1997 Knowledge-detection tool for automated signal detection (BCPNN)
1997 Promotion of communication as a necessary discipline
1998 Internet discussion group for national centres
2001 Start of Vigibase Online project
2002 New database system (Vigiflow)
2003 New Drug Dictionary with expanded data fields; agreement with IMS Health to increase information in DD
2004 Pattern recognition using the BCPNN on health databases to find safety information.
MedDRA Changes - General Remarks
There are two possible types of changes in the MedDRA terminology: simple changes and complex changes. Simple changes are changes to the existing terminology that involve terms at the PT and LLT levels. There are two types of Simple changes: (1) changes introduced by subscribers request and (2) Maintenance changes (also referred to as Associate changes). Maintenance changes are generated as a by-product of other changes requested by subscribers, or changes introduced by the MedDRA Management Board to preserve consistency within the dictionary. Complex changes involve modifications within the entire hierarchy, including the HLT, HLGT, and SOC terminology. Currently, the initial MedDRA terminology version release in one specific year (12.0, 13.0) includes both simple and complex changes, and the subsequent release in the same year (12.1, 13.1) represents a simple change of terminology. These changes are based on MedDRA subscribers' terminology change requests and on MedDRA terminology maintenance needs identified by MedDRA's maintenance organization reviewers. Please note that as a consequence of implementing some of these changes (e.g. demoting a multi-axial PT, adding a new HLT, etc.) it may be necessary to break the multiaxial links, to re-link the replacement terms, and/or to enable additional terms to be included within a particular SOC. All these changes may require modifications to your existing MedDRA coding, guideline development, and data retrieval practices. Keep in mind that changes involve both MedDRA terminology updates as well as Standardized MedDRA Queries (SMQ).
Definition of SMQ(Standard MedDRA Queries)
Result of cooperative effort between CIOMS and ICH (MSSO).Groupings of terms from one or more MedDRA System Organ Classes (SOCs) related to defined medical condition or area of interest. Included terms may relate to signs, symptoms, diagnoses, syndromes, physical findings, laboratory and other physiologic test data, etc., related to medical condition or area of interest intended to aid in case identification.
SMQ – an additional analytical tool for MedDRA-coded data, it is used for:
Other than data presentation by SOCs, data retrieval was initially also addressed with 13 Special Search Categories (SSCs). These are simple groupings of associated PTs which pertain to the same medical concept. To better address the need for standardization of data retrieval queries, Council for International Organizations of Medical Sciences (CIOMS) and MSSO have been working together on developing an extensive set of SMQs. These are retrieval groupings with a more complex and thus useful structure, a narrow and broad scope, some with an inherent hierarchy, and some with an algorithm. MedDRA version 13.1 contains 8 SMQs in development or testing and 82 in production.
- Case identification
- Signal detection
- Potential scenarios:Regulators to monitor a newly-marketed product with a certain potential safety issue from late Phase III
- Safety monitors (pre- or post-marketing) could set up “surveillance” parameters in safety system to alert them to incoming cases whose events “belong” to an SMQ of interest
- Co-development/marketing safety issues (or potential issues) can be shared and compared readily
- PSURs (overdose, pregnancy exposure, drug abuse, etc.)
- Identify cases based on PSUR findings
- Volume 9A recommends using SMQs for signal detection and retrieving cases of interest
- EMEA and PMDA (Japan) currently testing SMQs for signal detection
- FDA exploring the use of SMQs in new drug review process.
Other than data presentation by SOCs, data retrieval was initially also addressed with 13 Special Search Categories (SSCs). These are simple groupings of associated PTs which pertain to the same medical concept. To better address the need for standardization of data retrieval queries, Council for International Organizations of Medical Sciences (CIOMS) and MSSO have been working together on developing an extensive set of SMQs. These are retrieval groupings with a more complex and thus useful structure, a narrow and broad scope, some with an inherent hierarchy, and some with an algorithm. MedDRA version 13.1 contains 8 SMQs in development or testing and 82 in production.
MSSO(Maintenance and Support Services Organization)
MedDRA is managed by the MSSO (Maintenance and Support Services Organization-as the repository, maintainer, and distributor of MedDRA as well as the source for the most up-to-date information regarding MedDRA and its application within the bio-pharmaceutical industry and regulators. MedDRA subscribers submit proposed changes to the terminology. The MSSO includes a group of internationally based physicians who review all proposed subscriber changes and provide a timely response directly to the requesting subscriber.), an organization that reports to the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA). MedDRA is free for regulators and priced according to company revenue for industry. MedDRA is also available in Japanese. The Japanese counterpart for MSSO is called JMO. The process of change requests is performed within 7 calendar days from initial receipt by the MSSO. Approved Change Requests are designated as supplemental changes to MedDRA and are posted on the MSSO Web site for review by all subscribers. It should be noted that supplemental releases are not considered “official” MedDRA releases. Supplemental terms, however, will be included in the “official”, scheduled version release.
The MSSO updates MedDRA from subscriber change requests to add a new medical concept that is yet to be in MedDRA or to change an existing concept. The decisions are made by international medical officers on how to map the terminology within the grouping categories according to a general consensus based on language considerations internationally.
The MSSO releases updated MedDRA versions twice a year - in March and September. The March release is the main annual release and contains LLT and PT changes, and changes at the HLT level and above. The September release typically contains changes only at the LLT and PT level. The September 2010 Version 13.1 release is the current version.
The MedDRA dictionary is organized by System Organ Class (SOC), divided into High-Level Group Terms (HLGT), High-Level Terms (HLT), Preferred Terms (PT) and finally into Lower-Level Terms (LLT). In addition, the MedDRA dictionary includes Standardized MedDRA Queries (SMQs). SMQs are groupings of terms that relate to a defined medical condition or area of interest. “The MedDRA dictionary itself poses significant challenges. It is new, complex, and roughly 10 times larger than COSTART or WHO-ART.” MedDRA also brings its own challenges concerning the performing of autoencoding failure resolution, dictionary updates, and version control.
The MSSO updates MedDRA from subscriber change requests to add a new medical concept that is yet to be in MedDRA or to change an existing concept. The decisions are made by international medical officers on how to map the terminology within the grouping categories according to a general consensus based on language considerations internationally.
The MSSO releases updated MedDRA versions twice a year - in March and September. The March release is the main annual release and contains LLT and PT changes, and changes at the HLT level and above. The September release typically contains changes only at the LLT and PT level. The September 2010 Version 13.1 release is the current version.
The MedDRA dictionary is organized by System Organ Class (SOC), divided into High-Level Group Terms (HLGT), High-Level Terms (HLT), Preferred Terms (PT) and finally into Lower-Level Terms (LLT). In addition, the MedDRA dictionary includes Standardized MedDRA Queries (SMQs). SMQs are groupings of terms that relate to a defined medical condition or area of interest. “The MedDRA dictionary itself poses significant challenges. It is new, complex, and roughly 10 times larger than COSTART or WHO-ART.” MedDRA also brings its own challenges concerning the performing of autoencoding failure resolution, dictionary updates, and version control.
Purposes of using MedDRA
To code (classify) ADR/AEs, history, indication, investigations, procedures, etc.Verbatim/reported information is linked to a MedDRA Lowest Level Term (LLT),LLTs have a parent concept Preferred Term (PT) Grouping terms and System Organ Classes (SOCs) logically group concepts for later retrieval and analysis.Used for coding, assessment, and reporting of safety data for both marketed products and clinical studies.
Purpose:
Purpose:
- To aggregate reported terms in medically meaningful groupings for the purpose of reviewing and/or analyzing safety data
- To facilitate identification of common data sets for evaluation of clinical and safety information
- To facilitate consistent retrieval of specific cases or medical conditions from a database
- To improve consistency in comparing and understanding “safety signals” and aggregated clinical data
- To facilitate electronic data interchange of clinical safety information
- To report adverse reaction/adverse event (ADR/AE)2 terms via individual case safety reports
- To include ADR/AEs in tables, analyses, and line listings for reports
- To identify frequency of medically similar ADR/AEs
- To capture and present product indications, investigations, medical history, and social history data
MedDRA or Medical Dictionary for Regulatory Activities
MedDRA or Medical Dictionary for Regulatory Activities is a clinically validated international medical terminology used by regulatory authorities and the regulated biopharmaceutical industry throughout the entire regulatory process, from pre-marketing to post-marketing activities, and for data entry, retrieval, evaluation, and presentation. In addition, it is the adverse event classification dictionary endorsed by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). MedDRA is used in the US, European Union, and Japan. Its use is currently mandated in US, Europe and Japan for safety reporting.
MedDRA was developed by the International Conference on Harmonisation (ICH) and is owned by the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) acting as trustee for the ICH steering committee.
MedDRA is managed by the MSSO (Maintenance and Support Services Organization).
MedDRA was developed by the International Conference on Harmonisation (ICH) and is owned by the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) acting as trustee for the ICH steering committee.
MedDRA is managed by the MSSO (Maintenance and Support Services Organization).
Why Is Medical Coding Necessary during processing a case
The need for coding however, continues and the reason being that in order to perform statistical analysis, clinical trial data needs to be structured in such as way that a computer program or human being are able to count data items that are “identical” (in clinical terms) and to be able to group items that are “similar” (in categorical terms). One of the requirements for being able to do this is found in the labeling that must be provided for all prescription medications. The labeling provides the consumer with information concerning possible adverse reactions they might experience in terms of probabilities, that is, the percentage of people that have experienced a particular reaction. In order to calculate these percentages, it is necessary to be able to count “identical” experiences and divide them by the total number of subjects that were in the clinical trial(s) that collected this safety information.
Counting these unintended reactions (i.e., experiences) is hard to do when data are collected in “free text” form. It is perhaps unfortunate that, by and large, the descriptions of unintended reactions or experiences incurred during a clinical trial need to be captured and entered into the clinical trial database in “free text” form. Adverse events such as “Slight headache”, “Very bad headache”, “Debilitating Migraine”, “Sinus headache”, “Stress headache”, “Earache”, “Achy right knee” may not be a description of the same thing in clinical terms, but how does one report on the occurrence of headaches, infections, and muscle and/or joint pains (as in our example) given the wide variety and variations in reporting adverse events? The answer is to code the verbatim terminology using a medical terminology dictionary that gives synonymous terms the same code (known as “equivalence”) and provides a mechanism whereby grouping and classification of terms can be performed.
Furthermore, it is necessary to provide a preferred wording for synonymous terms to use for reporting purposes, for example, “Headache” might be used for “Slight headache”, “Very bad headache”, and “Debilitating Migraine”. At a higher level, one might want to classify these terms based on the body system (or organ class) that they impact. For “Headache”, this might be the central nervous system. Coding, of course, is not limited to adverse event verbatim terminology. It is desirable to code other medical terminology such as medication names, medical procedures such as surgeries, and physical conditions.
Counting these unintended reactions (i.e., experiences) is hard to do when data are collected in “free text” form. It is perhaps unfortunate that, by and large, the descriptions of unintended reactions or experiences incurred during a clinical trial need to be captured and entered into the clinical trial database in “free text” form. Adverse events such as “Slight headache”, “Very bad headache”, “Debilitating Migraine”, “Sinus headache”, “Stress headache”, “Earache”, “Achy right knee” may not be a description of the same thing in clinical terms, but how does one report on the occurrence of headaches, infections, and muscle and/or joint pains (as in our example) given the wide variety and variations in reporting adverse events? The answer is to code the verbatim terminology using a medical terminology dictionary that gives synonymous terms the same code (known as “equivalence”) and provides a mechanism whereby grouping and classification of terms can be performed.
Furthermore, it is necessary to provide a preferred wording for synonymous terms to use for reporting purposes, for example, “Headache” might be used for “Slight headache”, “Very bad headache”, and “Debilitating Migraine”. At a higher level, one might want to classify these terms based on the body system (or organ class) that they impact. For “Headache”, this might be the central nervous system. Coding, of course, is not limited to adverse event verbatim terminology. It is desirable to code other medical terminology such as medication names, medical procedures such as surgeries, and physical conditions.
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