Guidance producer subject to accreditation Process subject to accreditation Medicines and Healthcare products Regulatory Agency (MHRA) Pharmacovigilance Public Assessment Reports Date: 18 June 2010 Draft Accreditation Report for consultation
Contents Introduction... 3 Accreditation recommendation... 3 Implementation... 4 Reapplication for accreditation... 6 Appendix A: NHS Evidence accreditation analysis... 8 Appendix B: Bibliography... 17 Appendix C: Advisory Committee members, external advisers and NHS Evidence accreditation team... 18
Introduction The NHS Evidence Accreditation Scheme recognises organisations that demonstrate high standards in producing health or social care guidance. Evidence users can therefore have high confidence in the quality of the information. Organisations can publicly display a seal of approval called an Accreditation Mark for three years after their processes have been accredited. The process for accrediting producers of guidance and recommendations for practice is described in the process manual 1. Accreditation recommendation It is proposed that the process to produce Pharmacovigilance Public Assessment Reports (PPAR) by the Medicines and Healthcare products Regulatory Agency (MHRA) Vigilance and Risk Management of Medicines (VRMM) Division is recommended for NHS Evidence accreditation. This draft decision is subject to public consultation before a final decision is made. Background to the guidance producer The MHRA was set up in April 2003 from a merger of the Medicines Control Agency and the Medical Devices Agency. The MHRA is an executive agency of the Department of Health (DH). The MHRA is the government agency responsible for ensuring that medicines and medical devices are effective and acceptably safe. The MHRA monitors the use of medicines and devices, and takes any necessary action to protect the public if there is a problem. The MHRA aims to make as much information as possible publicly available. 1 http://www.nice.org.uk/nhsevidence/aboutaccreditation/aboutaccreditation.jsp?domedia=1&mid= 27C232A0-19B9-E0B5-D4A11FA899F4C219
Summary Drug safety guidance is one of the ways in which the MHRA protects and promotes public health through the VRMM Division. PPAR are guidance bulletins providing information and clinical advice to healthcare professionals about the safe use of medicines. They are one of the outcomes of the pharmacovigilance process and explain the rationale behind the MHRA s assessment of the risks associated with any individual medicine or group of medicines. The production of PPAR involves a systematic analysis of a variety of sources of drug safety information. Health professionals and patients are encouraged to report adverse effects they suspect are associated with one or more medicines; this forms a significant component of UK pharmacovigilance activity. As well as public domain information, as a regulator the MHRA has access to confidential data on quality, safety and efficacy, and can ask pharmaceutical companies to provide further data to resolve important questions about the safety of a medicine. PPAR reflect the scientific assessment but they omit information given to the MHRA in confidence. The process for the evidence search in the production of PPAR is robust and fit for purpose as is the editorial independence. Suggestions to further strengthen the MHRA VRMM Division processes for developing the PPAR include: clarifying the role of lay members, including how the Public and patient engagement strategy is used, in developing the PPAR clearly documenting how the evidence strength is assessed within each piece of guidance This draft decision is now going out for consultation, and the decision will be reviewed by the committee in the light of any feedback received before making a final recommendation.
David Haslam Chair, Advisory Committee June 2010
Implementation If accreditation is awarded, guidance from the accredited producer will be identified on NHS Evidence by the Accreditation Mark. The accredited guidance producer is also granted a royalty-free, worldwide licence to use the NHS Evidence Accreditation Mark in accordance with the Conditions and Terms of Use 2. Providing these conditions are met, a guidance producer's accreditation will last for three years from publication of approval on the NHS Evidence website. Accredited guidance producers must take reasonable steps to ensure the accredited processes are followed when generating the type of evidence for which they are accredited. Accredited guidance producers should have quality assurance mechanisms in place and must inform NHS Evidence of any significant change to a process within 30 days. Figure: The NHS Evidence Accreditation Mark 2 http://www.nice.org.uk/nhsevidence/?domedia=1&mid=5ae1d938-19b9-e0b5- D471CA81220F57DA
Reapplication for accreditation If accreditation is not granted, guidance from the non-accredited producer will still be available on the NHS Evidence site but will not be identified by the accreditation mark graphic. Guidance producers that are not accredited following the accreditation process have the opportunity to reapply from one year after the previous assessment. It is assumed that the organisation will have addressed any concerns highlighted in the original assessment before reapplying. The NHS Evidence team will provide detailed feedback and advice on areas where improvement is required to meet the criteria in a future application.
Appendix A: NHS Evidence accreditation analysis The Advisory Committee considered the following analysis of the guidance producer s compliance with NHS Evidence accreditation criteria, which covers six discrete domains. The full analysis leading to the accreditation decision is shown below. Domain Criterion Evidence for meeting the criterion Accreditation decision Does the guidance producer have a policy in place and adhered to that requires them to explicitly detail: Scope and purpose 1.1 Overall objective The process document a section 4.1.3 states that the careful definition of 1.2 The clinical, healthcare or social questions covered the issue for assessment should provide focus for the assessment report. The title of the guidance b-e indicates the subject of the assessment. The clinical, healthcare or social questions posed are the topics covered as no actual clinical conditions are covered by the guidance b-e. The guidance updates safety information relating to medicines. The clinical questions are the safety issues for each drug or class of drugs in the guidance product. Pharmacovigilance Public Assessment Reports: Draft Accreditation Report
Domain Criterion Evidence for meeting the criterion Accreditation decision 1.3 Population and/or target audience to whom the guidance applies The target audience is documented as healthcare professionals and the public in the Executive summary at the start of each individual piece of guidance b-e. The guidance is aimed at healthcare professionals when using specific drugs and relates to their safe use in patient populations encountered in clinical practice. 1.4 Guidance includes clear recommendations in reference to specific clinical, healthcare or social circumstances The process document a section 3.3.4 states that conclusions will flow from the critical evaluation of the data. It should be possible for the reader to easily link each of the conclusions to the section on data evaluation. In addition the section 3.3.5 Making recommendations states that recommendations should be clear and specific. Evidence of this process in practice is shown in all of the examples of guidance b-e reviewed, mainly in the Conclusions section. Does the guidance producer have a policy in place and adhered to that means it includes: Stakeholder involvement 2.1 Individuals from all relevant stakeholder groups, including patient groups, in developing guidance The make-up of the Vigilance and Risk Management of Medicines division, Commission on Human Medicines and Expert Advisory Groups show that individuals from many relevant professional groups are involved in the production of the guidance. Pharmacovigilance Public Assessment Reports: Draft Accreditation Report
Domain Criterion Evidence for meeting the criterion Accreditation decision 2.2 Patient and service user representatives and seeks patients views and preferences in developing guidance The composition of the Expert Advisory Groups and the Commission on Human Medicines include patient representatives. In addition a Public and patient engagement strategy is available on the website which further promotes the views of patients and patient representatives being sought. 2.3 Representative intended users in developing guidance. The intended users of MHRA PPAR guidance b-e are documented as healthcare professionals who work in the UK. The composition of the Expert Advisory Groups and the Commission on Human Medicines shows that these groups are made up of a wide range of different speciality healthcare professionals. Does the guidance producer have a clear policy in place that: Rigour of development 3.1 Requires the guidance producer to use systematic methods to search for evidence and provide details of the search strategy The process document a Annexe 1 describes the list of data sources searched. In addition section 3.3.2 of this document describes the data collection and evaluation process. It states when the assessment requires a systematic search of the literature the Information Centre s expertise can be recruited. Clear search criteria should be developed and recorded. The systematic searches are performed within the scope of the safety questions set. Pharmacovigilance Public Assessment Reports: Draft Accreditation Report
Domain Criterion Evidence for meeting the criterion Accreditation decision 3.2 Requires the guidance producers to state the criteria and reasons for inclusion or exclusion of evidence identified by the evidence review The method used to produce the guidance b-e relies on updates in safety information. Some exclusions may be indicated in the scope of the assessment. Section 3.3.2 of the process document a explains that the assessor should gather all of the data that fall within the scope of the assessment. In addition the guidance producer states that all available data are reviewed and assists in the compilation of recommendations. 3.3 Describes the strengths and limitations of the body of evidence and acknowledges any areas of uncertainty 3.4 Describes the method used to arrive at recommendations (for example, a voting system or formal consensus techniques like Delphi consensus) In the process document a, section 3.3.3 describes the critical evaluation of the data for the production of the assessment reports on which the PPAR are based. The information supplied by the guidance producer can be found in point 8 of the document Code of practice for Expert Advisory Groups. This documents that an Expert Advisory Group may formulate its recommendations by consensus of people present at the meetings. Pharmacovigilance Public Assessment Reports: Draft Accreditation Report
Domain Criterion Evidence for meeting the criterion Accreditation decision 3.5 Requires the guidance producers to consider the health benefits against the side effects and risks in formulating recommendations The guidance producer s website states no product is risk free. Underpinning all our work lie robust and fact-based judgments to ensure that the benefits to patients and the public justify the risks. The balance between risks and benefits is shown in the Aims and objectives section of the website. The principal aim of the PPAR guidance b-e product is to balance health benefits against risks by providing healthcare professionals with up to date drug safety information to better equip their decision-making. 3.6 Describes the processes of external peer review This is performed via a combination of Expert Advisory Groups and the Commission on Human Medicines, all of which contain lay representatives. The scientific assessment reports on which PPAR are based are peer reviewed, rather than PPAR themselves. Pharmacovigilance Public Assessment Reports: Draft Accreditation Report
Domain Criterion Evidence for meeting the criterion Accreditation decision 3.7 Describes the process of updating guidance and maintaining and improving guidance quality PPAR b-e provide updated safety advice driven by new findings regarding possible safety issues for specific medicines. PPAR advice is used to update drug information literature packages produced by pharmaceutical companies. Rather than being date driven PPAR are data driven and therefore no regular updating schedule is available. The information produced in a PPAR is added to the drug product information when the information is updated. Does the guidance producer ensure that: Clarity and presentation 4.1 Recommendations are specific, unambiguous and clearly identifiable Section 4.2.8 of the process document a shows how the recommendations within the PPAR should be written. This states recommendations should state what specific actions can be considered as a result of the assessment. Each recommendation should be numbered and carefully worded to remove any ambiguity about ensuing actions. Ideally the recommendation should stand out from the body of the text. 4.2 Different options for the management of the condition or options for intervention are clearly presented PPAR guidance b-e is related to safety issues for a single drug or group of drugs rather than the management of a condition. Therefore this criterion is not applicable. Not applicable Pharmacovigilance Public Assessment Reports: Draft Accreditation Report
Domain Criterion Evidence for meeting the criterion Accreditation decision 4.3 The date of search, the date of publication or last update and the proposed date for review are clearly stated The subject of the guidance b-e is updates of drug safety driven by new evidence, the guidance is event- rather than date-led, therefore the guidance producer s process does not include proposed dates for review. The information contained within the PPAR goes into the product literature as and when the information is updated. The guidance producer s pharmacovigilance processes ensure that guidance is current. 4.4 The content of the guidance is suitable for the specified target audience. If patients or service users are part of this audience, the language should be appropriate. The PPAR are produced for healthcare professionals and the public and the content is suitable. The guidance b-e examples reviewed confirm this response. Does the guidance producer routinely consider: Applicability 5.1 Publishing support tools to aid implementation of guidance An email alert process ensures that this guidance reaches its target audience. Since the guidance is a dissemination of safety information from the MHRA s pharmacovigilance process it describes how to use a medicine with a revised safety review and is considered obligatory. Pharmacovigilance Public Assessment Reports: Draft Accreditation Report
Domain Criterion Evidence for meeting the criterion Accreditation decision 5.2 Discussion of potential organisational and financial barriers in applying its recommendations 5.3 That their guidance is current, with review criteria for monitoring and/or audit purposes within each product Does the guidance producer: This criterion is not applicable. External organisations must overcome any financial and organisational barriers to implementation because the MHRA s PPAR contain obligatory safety information. The information provided shows that this criterion is not applicable for this type of guidance product. As documented in criterion 5.2, the guidance relates to safety issues so implementation is mandatory. Not applicable Not applicable Editorial independence 6.1 Ensure editorial independence from the funding body Section 5 MHRA framework document details the process of how the funding is collated and disseminated. In addition to the dispersed funding mechanism, the guidance is developed via a number of multidisciplinary groups, such as the Commission on Human Medicines and it is peer reviewed. Pharmacovigilance Public Assessment Reports: Draft Accreditation Report
Domain Criterion Evidence for meeting the criterion Accreditation decision 6.2 Demonstrate transparency about the funding mechanisms for its guidance The MHRA is an executive agency of the DH with trading fund status. The agency is funded by fees charged for fulfilment of statutory obligations, charges for non-statutory services and the DH. Section 5 (Finance) of the MHRA framework document describes how the MHRA generates and disseminates its finances and its accounting and auditing arrangements. 6.3 Record and state any potential conflicts of interest of individuals involved in developing the recommendations 6.4 Take account of any potential for bias in the conclusions or recommendations of the guidance Section 7.14 of the MHRA framework document states that all MHRA employees are required to state any potential conflicts of interest. The declarations of interests are published on the website. A combination of conflict of interest declarations, guidance decisions determined by multidisciplinary groups, peer review and transparency in the way the work is funded ensures this criterion is satisfied. The webpage What principles inform the decisions? point 10 also documents the agency s decisions will as far as possible be transparent and open to public scrutiny; a reasonable person reviewing our decisions should understand the rationale. a Guidance on conducting and presenting assessment, dated September 2009 (process manual) b Statins: updates to product safety information, November 2009 c Vigabatrin use: risk of movement disorders and brain MRI abnormalities, November 2009 d Warfarin: changes to product safety information, December 2009 e The risk of male breast cancer with finasteride, December 2009 Pharmacovigilance Public Assessment Reports: Draft Accreditation Report
Appendix B: Bibliography Appendix B lists the additional information taken into account in the analysis and considered by the Committee. Document name Description Location VRMM assessments Guidance on conducting and presenting assessments UK Public Assessment Reports guidance for VRMM: potential topics and work flowchart The risk of male breast cancer with finasteride December 2009 Statins: updates to product safety information November 2009 Vigabatrin use: risk of movement disorders and brain MRI abnormalities November 2009 Warfarin: changes to product safety information December 2009 MHRA Framework document Policy document for the Provided as pdf production of PPAR Flowchart for the production Provided as pdf process by the VRMM PPAR used as an example PPAR used as an example PPAR used as an example PPAR used as an example Document outlining the MHRA framework http://www.mhra.gov.uk/safetyinformation/s afetywarningsalertsandrecalls/safetywarnin gsandmessagesformedicines/con065504 http://www.mhra.gov.uk/safetyinformation/s afetywarningsalertsandrecalls/safetywarnin gsandmessagesformedicines/con062559 http://www.mhra.gov.uk/safetyinformation/s afetywarningsalertsandrecalls/safetywarnin gsandmessagesformedicines/con062532 http://www.mhra.gov.uk/safetyinformation/s afetywarningsalertsandrecalls/safetywarnin gsandmessagesformedicines/con065506 http://www.mhra.gov.uk/searchhelp/search/ Searchresults/CON008369
Appendix C: Advisory Committee members, external advisers and NHS Evidence accreditation team NHS Evidence Advisory Committee Members The NHS Evidence Advisory Committee operates as a standing advisory committee of the Board of the National Institute for Health and Clinical Excellence (NICE). The Committee provides advice to the Institute on a framework for accrediting sources of evidence that should be recognised as trusted sources of information for the NHS. The Chair of the Committee is appointed by the Institute s Board and the meetings are conducted by the Chair or in his/her absence the vice chair. The current Chair is David Haslam. A full list of the Advisory Committee membership is available on the NICE website 3. The members have been appointed for a period of 18 months. This may be extended by mutual agreement to a further term of 3 years and up to a maximum term of office of 10 years. The decisions of the Committee are arrived at by a consensus of those members present. The quorum is set at 50% of committee membership. The Committee submits its recommendations to the Institute s Guidance executive which acts under delegated powers of the Institute s Board in considering and approving its recommendations. Committee members are asked to declare any interests in the guidance producer to be accredited. If it is considered that there is a conflict of interest, the member(s) is excluded from participating further in the discussions. A list of the committee members who took part in the discussions for this accreditation decision appears below. 3 http://www.nice.org.uk/nhsevidence/nhseac.jsp Page 18 of 21
Title Name Surname Role Organisation Ms Judy Birch Lay member Mr Richard Brownhill Clinical Development & Nurse practitioner Calderdale and Huddersfield NHS Trust and Kirklees PCT Ms Parul Desai Director of Population Health NHS Information Centre Ms Amanda Edwards Head of Knowledge Services Social Care Institute for Excellence (SCIE) Ms Joyce Epstein Lay member Dr Brian Fisher General Practitioner NHS Alliance (GP and national patient/public lead) Professor David Haslam National Clinical Advisor Care Quality Commission Dr Bobbie Jacobson Dr Monica Lakhanpaul Professor Stuart Logan Dr Donal O Donoghue Professor Sandy Oliver Director of London Health Observatory, Vice Chair of Association of PH Observatories Senior Lecturer / Consultant Paediatrician / Clinical Director Professor of Paediatric Epidemiology National Clinical Director for Kidney Care and consultant renal physician Professor of Public Policy, Deputy Director, Social Science Research Unit London Health Observatory Health Education Research and Development Unit (HERADU), Department of Medical Education and Social Care, University of Leicester Peninsula College of Medicine and Dentistry Salford Royal NHS Foundation Trust Cochrane Consumers and Communication Review Group, University of London Page 19 of 21
Dr Mahendra Patel Senior lecturer in pharmacy practice, school of applied sciences/consultant Pharmacist University of Huddersfield Mr Adrian Reyes- Hughes Associate Clinical Director NHS Direct Dr Karen Ritchie Ms Sasha Shepperd Dr Mark Strong Ms Gill Swash Lead Health Services Researcher Senior Research Scientist, Department of Public Health MRC Fellow, Section of Public Health Head of knowledge and Library Services NHS Quality Improvement Scotland University of Oxford School of Health and Related Research (ScHARR) University of Sheffield NHS Western Cheshire Dr Sara Twaddle Director Scottish Intercollegiate Guidelines Network Advisory Committee Deputies Title Name Surname Role Organisation Deputising for Ms Lynda Cox Head of Knowledge Sharing and Learning North East Strategic Health Authority Stephen Singleton External Advisers for MHRA Vigilance and Risk Management of Medicines Division Pharmacovigilance Public Assessment Reports accreditation application Mark Strong, MRC Fellow, Section of Public Health, School of Health and Related Research, University of Sheffield, UK Aideen Mary Tarpey, Epilepsy Specialist Nurse- Dorset, Poole Hospital NHS Foundation Trust, UK Page 20 of 21
Dr Timothy E Bates, Chief Scientific Officer, New-Use Therapeutics Limited, Nottingham, UK NHS Evidence accreditation team for MHRA Vigilance and Risk Management of Medicines Division Pharmacovigilance Public Assessment Reports accreditation application Stephanie Birtles, Accreditation Technical Analyst, NHS Evidence, National Institute for Health and Clinical Excellence, Manchester, UK Dr Paul Chrisp, Associate Director Accreditation, NHS Evidence, National Institute for Health and Clinical Excellence, Manchester, UK Page 21 of 21