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Director Owner Author Alison Davis June Raine Mick Foy Paul Barrow Status Version Version Date Draft 0.3 22/08/11 Electronic Yellow Card Reporting Integration into GP Systems General contact: Subject Matter contact: Mick Foy Medicines and Healthcare products Regulatory Agency (MHRA) Paul Barrow Medicines and Healthcare products Regulatory Agency (MHRA) Tel: 020 3080 6633 [email protected] Tel: 020 3080 6655 [email protected] Yellow Card reporting in GP Systems Page 1 of 22 Commercial in Confidence Amendment History Version 0.1 0.2 0.3 Change Summary First Draft Updated draft Updated draft Date 05/07/2011 07/07/2011 22/08/2011 Change author Paul Barrow Paul Barrow Paul Barrow Reviewers: This document must be reviewed by the following (delegated as necessary). Name Title / Responsibility Date Version Approvals: This document requires the following approvals: Name Signature Title / Responsibility Date Version Date Version Distribution: Reviewers and approvers plus: Name Title / Responsibility Yellow Card reporting in GP Systems Version 3.0 draft Page 2 of 22 Commercial in Confidence Acronyms Acronym ADR CHM CQC dm+d DTD E2B(R2) EC EMA FOIA GP ICH ICSR NHS NPSA MHRA SNOMED CT XML Term Adverse Drug Reaction Commission on Human Medicines Care Quality Commission Dictionary of Medicines and Devices Document Type Definition (Not an acronym) International messaging standard for adverse drug reactions European Commission European Medicines Agency Freedom of Information Act General Practitioner International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Individual Case Safety Report National Health Service National Patient Safety Agency Medicines and Healthcare products Regulatory Agency Systematized Nomenclature of Medicine Clinical Terms eXtensible Mark-up Language Executive summary The Medicines and Healthcare products Regulatory Agency (MHRA) is the agency responsible for ensuring the safety of medicines, and runs the Yellow Card Scheme which receives reports of suspected adverse drug reactions. A new requirement to improve reporting rates is for GP systems to include a Yellow Card reporting function enabling users to report of suspected adverse drug reactions identified in primary electronically. This is to address a reducing contribution of Yellow Cards received from GP reporters. Increased numbers of Yellow Cards received ultimately increases the data available for identification of possible drug safety issues, and so allows the MHRA to take prompt action to project public health. Yellow Card reporting in GP Systems Version 3.0 draft Page 3 of 22 Commercial in Confidence Contents 1. INTRODUCTION ...................................................................................... 5 1.1 1.2 1.3 1.4 2. Purpose ............................................................................................. 5 Audience............................................................................................ 5 Scope ................................................................................................ 5 Definitions .......................................................................................... 5 BACKGROUND ....................................................................................... 6 2.1 About the MHRA ................................................................................ 6 2.2 Yellow Card Scheme and reporting of Adverse Drug Reactions ....... 6 2.3 Using Yellow Card data ..................................................................... 7 2.4 Adverse Drug Reaction reporting requirements ................................. 8 2.5 Under-reporting of Adverse Drug Reactions and Strengthening the Yellow Card Scheme .................................................................................... 8 2.6 Developments in electronic Yellow Card reporting ............................ 9 3. BENEFITS .............................................................................................. 10 4. REQUIREMENTS ................................................................................... 11 4.1 Overview.......................................................................................... 11 4.2 Message format ............................................................................... 11 4.2.1 Medical terminologies .................................................................. 11 4.2.2 Medicines terminologies............................................................... 11 4.2.3 Parsing and Validation ................................................................. 11 4.3 Workflow .......................................................................................... 12 4.4 Audit Requirements ......................................................................... 13 4.5 Frequency of transmission............................................................... 14 4.6 Data items to be returned ................................................................ 14 4.6.1 Patient data .................................................................................. 14 4.6.2 Reporter data ............................................................................... 15 4.6.3 Drug/vaccine data ........................................................................ 15 4.6.4 Reaction data ............................................................................... 16 4.7 Yellow Card Webservice and Webservice security .......................... 16 4.8 Testing ............................................................................................. 17 APPENDICES................................................................................................ 19 4.9 Impact of the Yellow Card Scheme ................................................. 19 4.10 Yellow Card Data Privacy ................................................................ 21 4.10.1 Data provision .......................................................................... 21 4.10.2 Access to Yellow Card data within the MHRA .......................... 22 4.10.3 Potential for cross-linkage of Yellow Card data ........................ 22 Yellow Card reporting in GP Systems Version 3.0 draft Page 4 of 22 Commercial in Confidence 1. Introduction This Document specifies the requirements for electronic Yellow Card reporting of suspected adverse drug reactions (ADRs) from GP systems to the Medicines and Healthcare products Regulatory Agency (MHRA). 1.1 Purpose Individual suppliers of GP systems have been encouraged to develop electronic Yellow Card reporting functionality in order to help improve access to Yellow Card reporting in primary care. Improving access to reporting is one route currently pursued to strengthen reporting to the Yellow Card Scheme, and hence to help the MHRA better protect public health. The improvement in numbers of reports received from primary care resulting from introduction of such a system has been demonstrated. There is a need for Yellow Card reporting to be included in the GP System of Choice requirements to a consistent implementation across multiple GP systems. 1.2 Audience The audience for this document is primarily system architects, system developers and other supplier staff involved with the design, build and test of GP systems. 1.3 Scope The scope of this document covers workflow, data and message format requirements required to enable Yellow Card reporting of suspected adverse drug reactions from GP systems. 1.4 Definitions Where used in this document set, the keywords MUST, SHOULD and MAY are to be interpreted as follows: MUST: This word, or the terms "REQUIRED" or "SHALL", means that the definition is an absolute requirement of the specification. SHOULD: This word, or the adjective "RECOMMENDED", means that there may exist valid reasons in particular circumstances to ignore a particular item, but the full implications MUST be understood and carefully weighed before choosing a different course. MAY: This word, or the adjective “OPTIONAL”, means that an item is truly optional. One implementer may choose to include the item because a particular implementation requires it or because the implementer feels that it enhances the implementation while another implementer may omit the same item. An implementation which Yellow Card reporting in GP Systems Version 3.0 draft Page 5 of 22 Commercial in Confidence does not include a particular option MUST be prepared to interoperate with another implementation which does include the option, though perhaps with reduced functionality. In the same vein an implementation which does include a particular option MUST be prepared to interoperate with another implementation which does not include the option (except, of course, for the feature the option provides). 2. Background 2.1 About the MHRA The Medicines and Healthcare products Regulatory Agency (MHRA) – www.mhra.gov.uk – is an executive agency of the Department of Health. Its role is to „enhance and safeguard the health of the public by ensuring that medicines and medical devices work and are acceptably safe‟. The MHRA has the following aims: Protecting public health through regulation, with acceptable benefit-risk profiles for medicines and devices. Promoting public health by helping people who use these products to understand their risks and benefits. Improving public health by encouraging and facilitating developments in products that will benefit people The agency therefore has a regulatory and licensing role for both medicines and medical devices; it issues advice and guidance and monitors suspected adverse drug reactions and adverse incidents involving medical devices. 2.2 Yellow Card Scheme and reporting of Adverse Drug Reactions Before a medicine is granted a licence so that it can be made available in the United Kingdom, it must pass strict tests and checks to ensure that it is acceptably safe and effective. All effective medicines, however, can cause side effects (also known as adverse drug reactions), which can range from being minor to being very serious. For a medicine to be granted a licence, the expected benefits of the medicine must outweigh the possible risks of the medicine causing adverse effects in patients. Sometimes it is difficult to tell whether a suspected adverse drug reaction is due to a medicine or another underlying reason. Even if it is only a suspicion that a medicine or combination of medicines has caused a side effect, the MHRA asks patients and health professionals to report this on a Yellow Card. The MHRA (and its predecessor organisations) have collected reports of suspected adverse drug reactions through the Yellow Card scheme for over 40 years. Since the establishment of the Yellow Card scheme in 1964 over 600,000 UK reports have been collected. Currently approximately 25,000 Yellow Card reports are received each year, with about half of these being Yellow Card reporting in GP Systems Version 3.0 draft Page 6 of 22 Commercial in Confidence from the pharmaceutical industry, and the remainder from health professionals and patients. The Yellow Card Scheme meets data protection requirements for collecting and storing confidential patient information, as well as having appropriate access controls in place. 2.3 Using Yellow Card data Information gathered from Yellow Card reports made by patients and health professionals is continually assessed at the MHRA by a team experts made up of doctors, pharmacists and scientists who study the benefits and risks of medicines. Yellow Card reports on suspected side effects received by MHRA are evaluated, together with additional sources of information such as clinical trial data, medical literature or data from international medicines regulators, to identify previously unidentified safety issues or side effects. If a new side effect is identified, information is carefully considered in the context of the overall side effect profile for the medicine, and how the side effect profile compares with other medicines used to treat the same condition. The MHRA takes action, whenever necessary, to ensure that medicines are used in a way that minimises risk, while maximising patient benefit. Where an issue is identified the agency can take a range of regulatory actions to protect public health. This most commonly involves changes to the product information (the patient information leaflet, or summary of product characteristics); although in extreme cases a medicine can be withdrawn where risks are considered to outweigh the benefits. In assessing the safety of medicines, the MHRA is advised by the Commission on Human Medicines (CHM), which is the Government‟s independent scientific advisory body on medicines safety. The CHM is made up of experts from a range of health professionals and includes lay representatives. Spontaneous adverse reaction reporting schemes, such as the Yellow Card Scheme is common source for identification of drug safety signals, and often provides and early warning of possible hazards. The value of the scheme has been demonstrated many times and it has helped to identify numerous important safety issues. For example, warnings were added to the product information for the smoking-cessation drug varenicline after we received Yellow Cards reporting patients experiencing suicidal thoughts. Advice was issued that patients taking varenicline who develop suicidal thoughts or who develop agitation, depressed mood, or changes in behaviour that are of concern for the doctor, patient, family, or caregiver should stop their treatment and contact their doctor immediately. Further examples are provided in Appendix 4.9. The MHRA publishes cumulative and anonymised summary information on adverse drug reactions collected from the Yellow Card Scheme. Anonymised data is also shared with the European Medicines Agency – the European Yellow Card reporting in GP Systems Version 3.0 draft Page 7 of 22 Commercial in Confidence regulatory agency, and with the pharmaceutical industry under the MHRA‟s legal obligations. 2.4 Adverse Drug Reaction reporting requirements Health professionals and patients submit Yellow Card reports on a voluntary basis, whereas there is a regulatory requirement on the MHRA to collect them and disseminate the information in an anonymised form to other regulators and the pharmaceutical industry. Article 106 of Directive 2001/83/EC specifically requires the European Commission in consultation with the European Medicines Agency (EMA – “the Agency”), Member States and interested parties to draw up guidance on the collection, verification and presentation of adverse reaction reports in order to facilitate the exchange of information about human pharmacovigilance within the Community. Similarly, Article 26 of Regulation (EC) No 726/2004 includes a requirement for the Commission, in consultation with the Agency, Member States and interested parties to draw up a guide. This guidance document is „Volume 9A (Human Pharmacovigilance)1‟ New pharmacovigilance legislation, due to be implemented by July 2012, states that national medicines agencies such as the MHRA should work to strengthen spontaneous adverse drug reaction reporting systems: “Article 102 The Member States shall: (1) take all appropriate measures to encourage patients, doctors, pharmacists and other health-care professionals to report suspected adverse reactions to the national competent authority…” The Care Quality Commission criteria for assessing core standards in primary care (2009-2010)2 include a requirement for reporting – in the first domain: safety, element one states: “Incidents are reported locally and nationally via the appropriate reporting route/s to the National Patient Safety Agency (NPSA), Health and Safety Executive, Medicines and Healthcare products Regulatory Agency (MHRA)…” The Yellow Card Scheme is therefore vital in helping the MHRA monitor the safety of medicines and vaccines used in the UK. 2.5 Under-reporting of Adverse Drug Reactions and Strengthening the Yellow Card Scheme The scheme does not provide comprehensive coverage of adverse drug reactions – many studies have investigated this and it is estimated that less 1 2 http://ec.europa.eu/health/documents/eudralex/vol-9/index_en.htm Accessed at http://www.cqc.org.uk/publications.cfm?fde_id=12757 on 23/06/2011 Yellow Card reporting in GP Systems Version 3.0 draft Page 8 of 22 Commercial in Confidence than 10% of adverse drug events are recorded through the scheme. Additionally there is evidence that the number of reports from general practice is falling, perhaps because of GP workload issues. A recent analysis of Yellow Card data showed that for the first time since the establishment of the Yellow Card Scheme, in 2010 GPs were no longer the largest reporter group. The Yellow Card strategy aims to strengthen reporting of suspected adverse drug reactions to the Yellow Card Scheme. To achieve this, activities to increase both the number and quality of Yellow Cards received from healthprofessionals, patients, parents and carers are required. Increased numbers of promptly received and well-completed Yellow Cards received ultimately makes more data available to the MHRA for the identification of possible drug safety issues. The ranges of activities aim to address the four main elements outlined in the original strategy. These are also listed in the Heads of European Medicines Agencies strategy document from 20103: Facilitation - making reporting easy and accessible Education - raise understanding of the purpose and value of the scheme Motivation - making reporters more likely to report Promotion - developing and maintaining promotion and communication strategies for the scheme 2.6 Developments in electronic Yellow Card reporting Amongst a range of activities to improve reporting, one of the most significant efforts under „facilitation‟, is in the development of methods for health professionals to report ADRs electronically through healthcare information systems. Much of the information required for a Yellow Card is held within a clinical system such as patient information, medical history and drugs. These data could therefore quickly be populated onto an electronic Yellow Card at the touch of a button reducing effort for the reporter. It is anticipated that making reporting as simple and quick as possible will help increase the number of Yellow Cards received. In 2010, the MHRA developed a system for receiving electronic Yellow Cards in an electronic format through a web-service. Electronic Yellow Cards created using the ICH E2B(R2) international standard format within a clinical system can be securely transmitted to the MHRA through the web-service. The data can also be promptly populated automatically into the MHRA pharmacovigilance database reducing the need for manual data entry. Currently two systems are transmitting Yellow Cards electronically to the MHRA using this system. SystmOne, developed by The Phoenix Partnership is used in approximately 15% of GP practices across the UK. This was the 3 A Strategy for the Heads of Medicines Agencies, 2011-15. Accessed at http://www.hma.eu/fileadmin/dateien/HMA_joint/HMA_Strategy_Paper_II/HMA_Strategy_final_version_ _2_.pdf on 28 April 2011. Yellow Card reporting in GP Systems Version 3.0 draft Page 9 of 22 Commercial in Confidence first system to include an electronic Yellow Card reporting feature and over 1000 Yellow Cards have been received since late November 2010. Testing of electronic reporting with MiDatabank, a medicines information hospital based database, has also been completed. Work continues on nationwide implementation of the software. Discussions on introducing similar electronic Yellow Card reporting methods into other clinical systems used by health professionals and discussions with other systems suppliers are continuing. 3. Benefits GPs have historically been the largest contributor of Yellow Cards but the proportion they contribute has been reducing and it is of concern that a recent trends analysis showed that in 2010 nurses contributed more than GPs. It is anticipated that introducing electronic Yellow Card reporting into GP systems will significantly improve reporting from GPs; introducing this function makes reporting significantly easier and quicker for this key reporter group. Defining Yellow Card reporting within the GP System of choice requirements will allow us to ensure MHRA requirements are met including that data provided meets validation requirements through involvement in data provision requirements. Experience of developing Yellow Card reporting with SystmOne, where this was completed at no cost to the MHRA, meant MHRA input into development was limited and scope for further even minor changes are extremely limited. This will: Improve ease of access to reporting - known to be a major factor leading in under-reporting. Underreporting is estimated at 10% means the significant majority of ADRs are not reported. Improve ease of Yellow Card completion –automatic population of information directly from the system. Improve ease of transmission of data – transmitted quickly and securely via an electronic link prevents need for posting paper forms and enables prompt electronic acknowledgment of receipt. Lead to development of electronic Yellow Card reporting in greater numbers of GP systems. Improve consistency of adverse drug reaction data provision in electronic Yellow Cards. Have the potential to improve completeness of data provided on Yellow Cards (e.g. including patient medical history, drug indications). Receipt of greater numbers of Yellow Cards allows earlier detection of drug safety issues, therefore enabling the MHRA to take more prompt action to protect public health. Improved data quality may mean fewer Yellow Cards are required to provide enough evidence for the MHRA take action to protect public health, and also can reduce false positive or false negative drug safety issues detected. Yellow Card reporting in GP Systems Version 3.0 draft Page 10 of 22 Commercial in Confidence 4. Requirements 4.1 Overview The requirement is for GP systems to provide a function by which an electronic Yellow Card can be populated and transmitted to the MHRA. A user of a GP system must be able to request that a Yellow Card is created when they suspect an adverse drug reaction has occurred. The Yellow Card created must have the majority of information automatically populated from within the GP system/patient record. A number of additional fields may require the user to specify information, for example selecting a reaction term(s) and entering an optional free text description. The system should also provide a prompt to the user as to when it might be appropriate to complete a Yellow Card – for example when a medication is being stopped or sensitivity to a drug recorded. Once completed the Yellow Card would then be transmitted to the MHRA using the secure web-service. 4.2 Message format Yellow Card must be created as an ICH E2B(R2) Individual Case Safety Report format xml file. Please see the ExampleICSR.xml file for example content. Field definitions for the ICSR xml can be found in the spreadsheet E2BX_CfH.xls and E2B_ICSR.dtd provides the document type definition (DTD). 4.2.1 Medical terminologies Medical terms, including suspected reactions, patient history, and medicine indications should be coded using SNOMED CT term IDs or term names. READ terms should be mapped to SNOMED CT. Comment [b1]: Yet to be decided/discussed with DS&P 4.2.2 Medicines terminologies GP systems are recognised as using the Dictionary of Medicines and Devices (dm+d) for coding medicines. Medicines should be reported using the most detailed level term from dm+d available i.e. Actual Medicinal Product (AMP) names. If AMP is not available, then Virtual Medicinal Product is preferable, followed by Virtual Therapeutic Moiety. Field length restrictions of 70 or 100 alphanumeric characters defined in the field definitions spreadsheet should be complied with. 4.2.3 Parsing and Validation All Yellow Cards transmitted as an xml file to the Yellow Card webservice must parse against the DTD in order to be accepted. Data provided in the xml is also compared against a number of „common sense‟ validation rules to ensure a Yellow Card is a valid report. The MHRA Yellow Card reporting in GP Systems Version 3.0 draft Page 11 of 22 Comment [b2]: We will not reject values exceeding this, but it is most helpful it entries met this limit. We are investigating whether we will be able to receive dm+d term ids as an alternative Commercial in Confidence reserve the right to reject YCs which do not meet these requirements. A list of validations is included in the field definition spreadsheet. Req ID CR101 CR102 CR103 CR104 CR105 Requirement Text The system MUST create an electronic Yellow Cards using the ICH E2B(R2) xml format Medical terms MUST be populated using SNOMED term IDs Medicines MUST be populated using DM+D entries, using the most detailed term level available (AMP>VMP>VTM) and observing field length restrictions (of either 70 or 100 alphanumeric characters depending on whether the <medicinalproduct> or <activesubstance> field is populated) Yellow Cards transmitted as an xml file to the Yellow Card webservice MUST parse against the DTD Data field values MUST meet data validation requirements Status Must Must Must Comment [b3]: See above Must Must 4.3 Workflow A typical workflow for creation and transmission of an electronic Yellow Card is as follows: 1. A user records a drug side-effect or sensitivity in a patient record upon which dialog is displayed, asking if they want to submit a Yellow Card OR 2. A user manually requests a Yellow Card to be created for a patient 3. If the user wants to submit a Yellow Card, a further dialog or dialogs are shown to capture the Yellow Card details which cannot be derived automatically from the patient record 4. The user completes dialog(s) 5. The clinical system then creates an XML document from the fields on the dialog and the patient record 6. The XML is then transmitted to the MHRA via the webservice 7. The clinical system then detects the web-service response code and can tell the user whether the Yellow Card submission was successful or failed as appropriate. 8. If successful, the XML sent is added to the patient record to form part of an audit trail. Yellow Card reporting in GP Systems Version 3.0 draft Page 12 of 22 Commercial in Confidence Figure 1 - Workflow for creation and transmission of an electronic Yellow Card Start Manual request to create Yellow Card MHRA webservice loads XML Drug stopped on patient record Dialog displayed to user Parse ok? Yes Create No End Yellow Card? Validate ok? Yes Dialog displayed for entry of additional data Send to administrator No Yes Load code received Load code received + warnings Transmission confirmed to system user Transmission confirmed to system user XML added to patient record for audit trail XML added to patient record for audit trail XML created from dialog fields and patient record XML transmitted to the MHRA via webservice Fail code received No User advised to report online at eYC End NB If an xml fails validations a user will receive a positive acknowledgment accompanied by warnings of the validations which the file has failed. No further action is required by the user in this instant. Req ID CR201 CR202 CR203 CR204 Requirement Text A user MUST be able to request a Yellow Card is created for a specific patient at any time. The system SHOULD prompt a user to report a Yellow Card when a medication is stopped for a patient or when drug side effect or sensitivity is recorded on the patients record The Yellow Card MUST have the patient details and reporter details automatically populated from the patient record/GP system After the user has requested a Yellow Card be created, the system MUST provide a dialog or series of dialogs for user entry of information which cannot be populated automatically from the patient record/GP system Status Must Should Must Must 4.4 Audit Requirements Yellow Card reporting in GP Systems Version 3.0 draft Page 13 of 22 Commercial in Confidence The fact that a Yellow Card has been completed, transmitted and successfully received should be recorded within the GP system. Req ID CR301 Requirement Text When a Yellow Card has been processed and transmission to the MHRA webservice acknowledged, the local audit trail MUST include an entry reflecting this, including a timestamp Status Must 4.5 Frequency of transmission Electronic Yellow Cards are sent to the web-service individually and should be sent the same day as completed by the reporter in order that the information is available for analysis and assessment as quickly as possible. Req ID CR401 CR402 Requirement Text A Yellow Card MUST be transmitted to the MHRA webservice immediately once it is created. The transmission MUST be reattempted if an acknowledgement or rejection code is not received Status Must Must 4.6 Data items to be returned Mapping of data fields from GP systems to the electronic Yellow Card must be completed individually for each system. A Yellow Card requires four main areas of data to be included in order for the report to be considered valid – patient, reporter, drug and reaction. Detailed information on data field requirements and validations are provided in the field definition spreadsheet. 4.6.1 Patient data At least one of the following patient data must be required in order for a Yellow Card to be considered a valid report. Age (at time of reaction) Sex General Unique Identification (GUID) – this would be a unique ID generated specifically for the Yellow Card and patient which maps to the patient ID using a local database mapping table. Access to this table will be restricted to local system administrators only. Where available the following may also be provided: Weight Height Name, date of birth and NHS number are not collected and it is not considered that the patient information above is sufficient to identify an individual (See Appendix 4.10 for information on Yellow Card data confidentiality). Inclusion of a local identification number allows follow-up for additional information if required for assessment of the case. Yellow Card reporting in GP Systems Version 3.0 draft Page 14 of 22 Commercial in Confidence Req ID CR501 CR502 4.6.2 Requirement Text A Yellow Card MUST be automatically populated with patient age, sex and a General Unique Identification A Yellow Card MAY automatically populate patient weight and height when this is available in the patient record Status Must May Reporter data Contact details of the reporter are required. The MHRA consider reporter confidentiality to be important and data is not shared with any other organisation without explicit permission from the reporter. Reporter name Reporter address (surgery address, including ONS GP practice code) Reporter telephone Reporter email Req ID CR601 CR602 4.6.3 Requirement Text A Yellow Card MUST be automatically populated with reporter name, address, telephone and email from the information held within the system. A Yellow Card MAY include GP practice LSOA code in the reporter details where this is available. Status Must May Drug/vaccine data One or more drug or vaccines suspected to have caused a reaction are required. Additional information including dates of treatment, indication (as MedDRA LLT), and concomitant medications are also useful. Suspect drug(s) Where available: Concomitant drug(s) given in the last three months Routes of administration Doses Indications Start dates Stop dates Req ID CR701 CR702 Requirement Text A Yellow Card MUST include at least one suspect drug/vaccine entry using DM+D. The user MUST be able to select a suspect drug or drugs from listed on the patient record, given in the last three months. A Yellow Card SHOULD automatically populate route of administration, dose, start and stop dates, and indications for the selected suspect drug when available Yellow Card reporting in GP Systems Version 3.0 draft Status Must Should Page 15 of 22 Commercial in Confidence Req ID CR801 CR802 4.6.4 Requirement Text A Yellow Card MUST automatically populate concomitant drugs from the patient record when available For concomitant drugs populated, a Yellow Card SHOULD automatically include route of administration, dose, start and stop dates, and indications when available from the patient record Status Must Should Reaction data One or more reactions suspected to be caused by a drug or vaccine are required as well as the outcome. Reactions should be provided using SNOMED CT IDs. Reaction Reaction outcome Where available: Reaction start date Reaction stop date Reaction narrative (free text) Req ID CR901 CR902 Requirement Text Status A Yellow Card MUST include at one or more suspect Must reactions and reaction outcome(s) as selected by the user A Yellow Card SHOULD include reaction start and Should stop dates and reaction narrative when provided by the user 4.7 Yellow Card Webservice and Webservice security The webservice has been implemented using Simple Object Access Protocol (SOAP). Two operations are supported: ValidateE2B – validation rules are applied to the Yellow Cards submitted, however the Yellow Card is not saved by the webservice into the MHRA system. UploadE2B – Yellow Cards submitted are first passed through the validation steps after which the data is saved into the MHRA system. Secure Sockets Layer (SSL) cryptographic protocol is used to encrypt the network connection over which the Yellow Card data is transmitted, via HTTPS. Systems providers must access the webservice using a username and password. (Please see https://ehr-services.mhra.gov.uk/default.asmx?op=UploadE2B and https://ehr-services.mhra.gov.uk/default.asmx?op=ValidateE2B for example SOAP 1.1 and SOAP 1.2 requests and responses.) Yellow Card reporting in GP Systems Version 3.0 draft Page 16 of 22 Commercial in Confidence The URLs are as follows: Testing - http://mhra-ehr-uat.web10.redantdev.com/default.asmx Production - https://ehr-services.mhra.gov.uk/default.asmx 4.8 Testing A period of testing with the MHRA is required from each individual system. This includes checking Yellow Card messages are correctly formed and meet data validation requirements, transmission to the MHRA webservice as well as ensuring messages receive an acknowledgment code. An E2B ICSR test form is available for testing validation and parsing at http://mhra-ehr.web10.redantdev.com/test.aspx. After pasting xml content into the form, any errors resulting from a failure to parse, or warnings from failed validations are displayed. Screenshot showing warnings received due to failed validations – a ‘load’ response would be received by the sender Yellow Card reporting in GP Systems Version 3.0 draft Page 17 of 22 Commercial in Confidence Screenshot showing errors received due to a failure to parse – a ‘fail’ response would be received by the sender Yellow Card reporting in GP Systems Version 3.0 draft Page 18 of 22 Commercial in Confidence Appendices 4.9 Impact of the Yellow Card Scheme The following table shows some of the safety issues which Yellow Card reports have helped identify: Year Medicine June 2010 Dec 2009 Adverse Reaction Rivastigmine (Exelon) Finasteride (Proscar, Propecia) Jun 2009 Antipsychotics Medication errors Apr 2009 Adverse effects on bone Antiepileptics Potential risk of male breast cancer Venous thromboembolic events Jan 2009 Tacrolimus /Dec (Advagraf and 2008 Prograf) Risk of serious medication errors Dec 2008 April 2008 Hedrin (dimeticone) Unlicensed herbal product marketed for diabetes Hair fire accident Feb 2008 Varenicline (Champix) Depression, suicidal thoughts and behaviour Nov 2007 St John‟s wort, Hypericum perforatum Interaction with all antiepileptics Nov 2007 Aristolochia in Chinese herbal remedies Renal failure, transitional-cell carcinoma Yellow Card reporting in GP Systems Version 3.0 draft Resulting action or advice Warning issued in Drug Safety Update (DSU) Product information for prescribers updated Product information for prescribers updated Vitamin D supplementation should be considered for at risk patients Prograf and Advagraf are not interchangeable and should not be substituted without careful therapeutic monitoring Warning to keep hair away from fire Dangerous advice to patients to stop taking prescribed medication Warnings issued and monitoring of patients with history of psychiatric illness advised current warnings about interactions should extend to include all antiepileptic medicines Reminder of warnings, and ban Page 19 of 22 Commercial in Confidence 2006 Linezolid (Zyvox) Optic neuropathy 2006 Chinese herbal remedy: Polygonum multiflorum Black cohosh (Cimicifuga racemosa) Rosuvastatin (Crestor) Hepatotoxicity Improved warnings and monitoring recommendations Warnings Hepatotoxicity Improved warnings Rhabdomyolysis 2003 Warfarin 2003 Aspirin 2003 Kava-kava (Piper methysticum) Ergot derived dopamine receptor agonists; pergolide (Celance), bromocriptine (Parlodel), cabergoline (Cabaser), lisuride Bupropion (Zyban) Interaction with cranberry juice leading to changes in INR values and bleeding episodes Reye‟s Syndrome in children under 16 years Hepatotoxicity Revised dosing instructions and improved warnings Warnings 2006 2004 2002 2001 Yellow Card reporting in GP Systems Version 3.0 draft Statutory label warning Supply prohibited in the UK Fibrotic reactions Class warnings added to product information Seizures Improved warnings and revised dosing instructions Page 20 of 22 Commercial in Confidence 4.10 Yellow Card Data Privacy 4.10.1 Data provision Information at patient level, i.e. a report about a patient who has experienced an adverse drug reaction, is routinely provided to pharmaceutical companies under the MHRA's statutory obligations. This information is considered anonymised, and may include, if reported, initials, age, sex, and an identification number. This local identification number is requested so the original reporter can identify the patient if further information is sought, but is not a recognisable patient ID otherwise. Requests from health professionals and the public for adverse drug reaction data is subject to a data provision policy. Following the 2004 Independent Review of Access to the Yellow Card Scheme systems were established to ensure that any information included in the database is subject to release under the Freedom of Information Act (FOIA) while at the same time protecting the confidentiality of individuals and their personal data as the Data Protection Act (DPA) require. Requests for provision of data are divided into a number of categories. Category 1a data is cumulative listings and these are publicly available from the MHRA website. Category 1b data case details listed below are releasable under the Freedom of Information Act (FOIA). Provision of these data will depend on the number of cases held by the Agency. The MHRA will not release any data subset in which there are five or fewer cases per cell. This is necessary to prevent identification of patients and/or reporters. Where there are less than five cases per cell the data will be aggregated with adjacent cells with any aggregation clearly marked on the dataset. Category 1b data fields are: Patient age categories (<18, 18-24, 25-34, 35-44, 45-54, 55-64, 6574, 75-84, >85 years) Patient gender (number of female and male patients) Suspect drug(s) Dose of suspect drug Route of administration Duration of treatment Suspected adverse drug reaction(s) Reaction outcomes Onset times Patient medical history Year of report (if requested) If more detailed information than can be provided under category 1b, or there are 5 or fewer cases, then the request is classed as a Category 2 request. For Category 2 requests a form must be completed for consideration by the Independent Scientific Advisory Committee for MHRA database research (ISAC). This includes questions on what purpose the data is for, how it is to be used and how it is to be securely stored. Yellow Card reporting in GP Systems Version 3.0 draft Page 21 of 22 Commercial in Confidence 4.10.2 Access to Yellow Card data within the MHRA Yellow Card data is securely stored at the MHRA and user access rights and permissions are maintained on an individual user basis, and only users with appropriate access and training are able to access Yellow Card data. The users who have access to this information are those who use the data for drug safety monitoring or the associated supportive system administration. All users are signatories of a declaration acknowledging and accepting the restrictions dealing in securities and other assets and disclosure of information. 4.10.3 Potential for cross-linkage of Yellow Card data It is not possible to link ADR data from the MHRA to other datasets, as no cross-linkable case level identifier is recorded. A local identifier can be completed on a Yellow Card; however this is only interpretable by the original reporter and is recommended to only be an arbitrary reference. If an NHS number is reported, this is not entered into the database. Yellow Card reporting in GP Systems Version 3.0 draft Page 22 of 22