Medicines and Healthcare products Regulatory Agency (MHRA) Public Assessment Reports

Transcription

1 Guidance producer: Medicines and Healthcare products Regulatory Agency (MHRA) Guidance product: Public Assessment Reports Date: 18 June 2010 Version: 1.4 Draft Accreditation Report for consultation Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports

2 Contents Introduction... 3 Accreditation recommendation... 3 Implementation... 4 Reapplication for accreditation... 6 Appendix A: NHS Evidence accreditation analysis... 8 Appendix B: Bibliography Appendix C: Advisory Committee members, external advisers and NHS Evidence accreditation team Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report

3 Introduction The NHS Evidence Accreditation Scheme recognises organisations that demonstrate high standards in producing health or social care guidance. Users of the accredited guidance 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 Public Assessment Reports (PAR) guidance by the Medicines and Healthcare products Regulatory Agency (MHRA) Licensing 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 which is responsible for ensuring that medicines and medical devices work, and are acceptably safe. The MHRA monitors medicines and devices. The MHRA has ten divisions one of which is the Licensing Division. In general it is responsible for assessing and approving applications for marketing C232A0-19B9-E0B5-D4A11FA899F4C219 Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report

4 authorisations. These may be new medicinal products (new active substances), new routes of administration or new formulations for existing drugs, generic drugs, parallel import applications, and non-safety variations to existing licenses for medicinal products. Summary The Public Assessment Report informs the public and healthcare professionals of how the MHRA came to the decision of granting a marketing authorisation for a given medicinal product. Public Assessment Reports are produced to provide information to guide decisions to improve health and wellbeing, and are therefore eligible for NHS Evidence accreditation, although several criteria are not applicable to this guidance product. The licensing process requires the applicant pharmaceutical company to produce information in accordance with fixed MHRA protocols. Medical, clinical and preclinical assessors at the MHRA thoroughly evaluate the evidence for the pharmaceutical product to ensure that all information required has been provided and that there are no flaws in the data. These assessors each produce an assessment report which are combined and all commercially sensitive information removed to produce the Public Assessment Report. Before being made available to the public, all Public Assessment Reports are sent to the marketing authorisation holder for comment. The work performed to produce the assessment reports on which the Public Assessment Report are based is comprehensive, rigorous and fit for purpose. The clear, transparent funding methods and the thorough conflicts of interest policy assists in the elimination of bias. Aspects of the MHRA Licensing Division development processes for Public Assessment Report that are not clear include: how lay members are involved in the process of granting a marketing application, and ensuring that this is made apparent and shown in the process that results in a Public Assessment Report, including how the Public and patient engagement strategy is used Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report

5 how the evidence strength is assessed within each piece of guidance, and more providing greater transparency around the process of this assessment 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 Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report

6 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 D471CA81220F57DA Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report

7 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. Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report

8 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 Standard Operating Procedure (SOP) a section 2 states that the release of a PAR has two aims; to allow transparency of the regulatory process and to provide information on the product and the data supporting its authorisation. 1.2 The clinical, healthcare or social questions covered The clinical settings in the PAR are more applicable than clinical questions for this type of guidance. These clinical settings can be found in the Summary of product characteristics section of the guidance which meets the overall objective of this guidance. Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports

9 Domain Criterion Evidence for meeting the criterion Accreditation decision 1.3 Population and/or target audience to whom the guidance applies PARs are produced to disseminate information with regard to a specific medicinal product. The target audience is documented as any member of the public or healthcare professional. The patient population to whom the guidance applies is detailed within the PAR. 1.4 Guidance includes clear recommendations in reference to specific clinical, healthcare or social circumstances As described in criterion 1.2 the clinical settings in the PAR are more applicable than clinical questions for this type of guidance. In the Summary of product characteristics section of the guidance a number of recommendations are shown with reference to particular patient groups. Where the medicine which is the subject of the PAR can be used for more than one therapeutic indication, this is clearly documented and this follows into the recommendations. In addition dosage recommendations are shown in response to specific clinical circumstances. 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 PARs are written by medical writers at the MHRA, using assessment reports from pharmaceutical, clinical and preclinical assessors, and papers from independent scientific expert advisory groups, such as the Commission on Human Medicines. Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 9 of 22

10 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 It is noted that a Public and patient engagement strategy is available on the website which further promotes the views of patients and patient representatives being sought, but it is not fully clear how this strategy is involved in the production of PARs. Some uncertainty The lay summary which appears at the start of a PAR is based on a patient information leaflet which has had patient input and therefore the guidance producer indicated this criterion is met. While this is acknowledged, on its own it is insufficient to address the criterion fully. The guidance producer indicated that it believed lay involvement could compromise confidentiality and / or delay process. Lay involvement in the decision making process is particularly important where there are commercial interests and reasons for confidentiality. Confirmation that lay members are involved in the process of granting a marketing application is sought from the MHRA. In addition the role of the Public and patient engagement strategy and the process for involving lay members in the process that results in a PAR requires clarification. Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 10 of 22

11 Domain Criterion Evidence for meeting the criterion Accreditation decision 2.3 Representative intended users in developing guidance. The intended users are health professionals and the public in the UK. The composition of the expert advisory groups ensures this criterion is met. In addition the PARs are written by medical writers at the MHRA, using assessment reports from pharmaceutical, clinical and preclinical assessors, and papers from independent scientific expert advisory groups, such as the Commission on Human Medicines. 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 Information provided by the pharmaceutical company applying for a licence provides the evidence for the assessment reports. The MHRA assesses the information provided by the pharmaceutical company which in the case of this type of guidance product means this criterion is considered met. The assessment process of the information provided should be transparent. 3.2 Requires the guidance producers to state the criteria and reasons for inclusion or exclusion of evidence identified by the evidence review No evidence is excluded. All information provided by the pharmaceutical company is assessed and included. Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 11 of 22

12 Domain Criterion Evidence for meeting the criterion Accreditation decision 3.3 Describes the strengths and limitations of the body of evidence and acknowledges any areas of uncertainty The body of evidence is assessed by expert advisers in independent scientific advisory committees. If any of the required information is missing or the assessors require more information the request is passed on to the company applying for the licence and they must produce this information. 3.4 Describes the method used to arrive at recommendations (for example, a voting system or formal consensus techniques like Delphi consensus) 3.5 Requires the guidance producers to consider the health benefits against the side effects and risks in formulating recommendations The authorship process for the production of PARs demonstrates that no voting occurs, however there is a clear description of the method used to arrive at recommendations in the guidance development process. The criterion is satisfied as the information provided is the overall objective of the MHRA. The balance between risks and benefits is shown in the Aims and objectives section of the website. The principle aim of the guidance product is to balance health benefits against risks by providing healthcare professionals with up to date information so that they can make better choices. Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 12 of 22

13 Domain Criterion Evidence for meeting the criterion Accreditation decision 3.6 Describes the processes of external peer review 3.7 Describes the process of updating guidance and maintaining and improving guidance quality The original assessment reports upon which the PARs are based are reviewed by pharmaceutical, preclinical and clinical assessors at the MHRA, and by independent scientific advisory committees at the MHRA. The PARs are based on these original assessment reports. External peer review is performed by the marketing authorisation holder (pharmaceutical company) for that product for confidentiality purposes and an internal review at the MHRA. The process is detailed in the SOP a page 6. If new information about a particular licensed drug is discovered, the medical writer will produce an update to the PAR. If this is a significant update an assessor may also be involved. Updates of the PAR will be ed to the appropriate representative of the pharmaceutical company for comment. Clarity and Does the guidance producer ensure that: Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 13 of 22

14 Domain Criterion Evidence for meeting the criterion Accreditation decision presentation 4.1 Recommendations are specific, unambiguous and clearly identifiable The Summary of product characteristics section of the guidance shows a number of recommendations with reference to particular patient groups. Where the medicine which is the subject of the PAR can be used for more than one therapeutic indication, this is clearly documented and is specified in recommendations. In addition dosage recommendations are shown for specific clinical circumstances. All examples of guidance reviewed showed specific and unambiguous recommendations. 4.2 Different options for the management of the condition or options for intervention are clearly presented 4.3 The date of search, the date of publication or last update and the proposed date for review are clearly stated This criterion is not applicable to this guidance producer because each guidance product relates to use of a specific drug product rather than management of a condition. In all PARs reviewed a Table entitled Steps taken during assessment shows dates relating to the initial application, acceptance of the application, assessment, further information (update) and the date of determination of the application. The date of determination is also the date of authorisation / revision. Not applicable The SOP a appendix 4 states The assessment report will be updated whenever new information becomes available which is of importance for the evaluation of the quality, safety and efficacy of the medicinal product. Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 14 of 22

15 Domain Criterion Evidence for meeting the criterion Accreditation decision 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 SOP a annex 1 indicates that the process described by the guidance producer in its submission is followed. The PARs are produced to give transparency to the regulatory process and to provide information on the product. This means that the language used needs to be suitable for a wide range of audiences. To do this the PARs are split into distinct sections. Lay audiences benefit from the language and layout of the Lay summary and PIL sections. The other sections contain a more scientific / medical language aimed at healthcare professionals. Does the guidance producer routinely consider: Applicability 5.1 Publishing support tools to aid implementation of guidance PARs are produced to disseminate information regarding the licensing decisions of a particular medicinal product. Therefore due to the nature of this guidance this criterion is not applicable. Not applicable 5.2 Discussion of potential organisational and financial barriers in applying its recommendations PARs are guidance documents that provide summaries of non confidential regulatory information for a new medicine and the reasoning why the MHRA has granted a licence. Therefore there are no recommendations to implement. Not applicable Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 15 of 22

16 Domain Criterion Evidence for meeting the criterion Accreditation decision 5.3 That their guidance is current, with review criteria for monitoring and/or audit purposes within each product. Since the guidance stems from the licensing process and contains non confidential regulatory information, monitoring and audit are not considered applicable. Not applicable Does the guidance producer: 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, and is independent of funding body. In addition to the transparent funding mechanism, guidance is developed via a number of multidisciplinary groups, such as the Commission on Human Medicines and is peer reviewed. Editorial independence 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 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. Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 16 of 22

17 Domain Criterion Evidence for meeting the criterion Accreditation decision 6.4 Take account of any potential for bias in the conclusions or recommendations of the guidance In this case 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 Standard Operating Procedure Generation and maintenance of Public Assessment Reports (process manual). b PAR Gemcitabine 200mg and 1g powder for solution for infusion c PAR: Irinotecan 20mg/ml solution for infusion d PAR: Dexamethasone 2mg tablets e PAR: Tamoxifen 20mg tablets Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 17 of 22

18 Appendix B: Bibliography Appendix B lists the additional information taken into account in the analysis and considered by the Committee. Document name Description Location SOP Generation and maintenance of public assessment reports SOP which describes the production and updates for PARs UK Public assessment Additional information reports guidance for regarding the use and VRMM production of PARs PAR: Dexamethasone Example guidance used as 2mg Tablets evidence PAR: Tamoxifen 20mg Example guidance used as Tablets evidence PAR: Gemcitabine Example guidance supplied 200mg and 1g powder by the guidance producer for solution for infusion PAR: Irinotecan 20 Example guidance supplied mg/ml solution for by the guidance producer infusion MHRA Framework Document outlining the document MHRA framework SOP Generation and Maintenance of Public Assessment Reports Flowchart for UK Public Assessment Reports v 3 (2)_Final_for submission to NHS Evidence AssessmentReports/CON AssessmentReports/CON AssessmentReports/CON AssessmentReports/CON Searchresults/CON Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports

19 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 Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 19 of 22

20 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 Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 20 of 22

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 Licensing Division Public Assessment Reports accreditation application Dawn Freshwater, Professor, University of Leeds, School of Healthcare, Editor, Journal of Psychiatric and Mental Health Nursing, Leeds, UK Pauline Roebuck, Quality Assurance Unit Team Leader, Intertek ASG, Manchester, UK Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 21 of 22

22 NHS Evidence accreditation team for MHRA Licensing Division 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 Medicines and Healthcare products Regulatory Agency: Licensing Division; Public Assessment Reports: Draft Accreditation Report Page 22 of 22