Monitoring of Scientific Literature

Transcription

1 Effective date: 01 December 2016 Page: 1 of 14 Monitoring of Scientific Literature 1 Purpose and Scope 1 2 Responsibilities 1 3 Definitions 2 4 Procedure General aspects Review of PRAC meeting minutes and recommendations Review of scientific and medical literature Identification of case reports: Identification of PSUR relevant information Identification of a potential signal Search profiles Search in international scientific literature Search in local scientific literature Weekly literature review Medline weekly search National scientific literature 7 5 Search for ICSRs identified by EMA MLM Service 9 6 Archiving 11 7 References 11 8 Change Log 12 1 Purpose and Scope The purpose of this instruction is to describe the roles and responsibilities related to weekly literature searches of local and worldwide scientific literature for adverse events (AEs) on human medicinal product substances for which A-consult is responsible. For human medicinal products, the weekly surveillance also includes check of PRAC recommendations. This instruction includes the description of surveillance and download of ICSRs generated from EMA s weekly Medical Literature Monitoring (MLM) Service. Roles and responsibilities shall be described in an agreement with the Client. 2 Responsibilities This instruction must be read and understood by: Literature Monitoring Assistant Case Processor Case Assessor PV Responsible Literature Monitoring Assistant carries out a literature search in Local Literature, orders articles and archives documents from the weekly literature surveillance. In addition to the responsibilities of Literature Monitoring Assistant, a Case Processor handles ICSRs identified in the weekly searches. Case Assessor can perform all tasks described in this instruction.

2 Effective date: 01 December 2016 Page: 2 of 14 3 Definitions Abbreviations and definitions are described in QI02 Definitions and Abbreviations. 4 Procedure 4.1 General aspects Literature searches shall be initiated from the time of submission of the marketing authorisation application and shall be conducted for all products with a marketing authorisation, irrespective of commercial status. Reports of suspected adverse reactions from the scientific literature should be reviewed in order to identify and record ICSR s originating from spontaneous reports or noninterventional studies. All case reports are considered possible Adverse Events (AEs), including if the medicinal product source and/or the invented name is not specified and ownership of the product cannot be excluded on the basis of the medicinal product name, active substance name, pharmaceutical form, batch number or route of administration. Exclusion of AEs based on the primary source country or country of origin of the adverse reaction is possible if the marketing authorisation holder can demonstrate that the suspected medicinal product has never been supplied or placed on the market in that territory or that the product is not a travel medicine (e.g., anti-malarial medicinal product). If an AE is excluded based on the primary source country or country of origin (see above) it should still be evaluated whether the AE constitutes a potential signal. Full articles will be ordered in the following circumstances: When no available abstract When it cannot be judged from an available abstract if the article has relevance for the safety surveillance of the product. At time of PSUR writing, available archived abstracts of PSUR relevant articles will be reviewed for inclusion in the PSUR and if finally considered relevant, full articles will be ordered. Additionally, the monitoring of scientific literature is a significant source of information for the monitoring of safety profile and of the risk-benefit balance of medicinal products, particularly in relation to detection of new safety signals or emerging safety issues. For further description regarding detection of new safety signals or emerging safety issues, see QI31 Signal Detection and Evaluation. 4.2 Review of PRAC meeting minutes and recommendations Recommendations by Pharmacovigilance Risk Assessment Committee (PRAC) and meeting minutes published at EMA s websites, should be reviewed weekly for possible new safety information and proposed actions, relevant to human medicinal products for which A-consult is responsible.

3 Effective date: 01 December 2016 Page: 3 of Review of scientific and medical literature Identification of case reports: Non-valid cases do not qualify for expedited reporting, however, they should be recorded in the safety database for signal detection purposes, and efforts to obtain follow-up information should be made. The following special situations should be treated as case reports and entered in the safety database, whether or not an adverse reaction occurred (categorised here as Adverse Event (AE)): Use outside the terms of the marketing authorization including overdose, misuse, abuse, medication errors, off-label use Transmission of infectious agent(s) from medicinal product Lack of effect Interactions between drug(s) Unexpected therapeutic or clinical benefit from use of the medicinal product Reports describing use of the medicinal product during pregnancy and/or lactation Occupational exposure Solicited reports: Solicited reports are derived from organised data collection systems, which include clinical trials, non-interventional studies, registers, post-approval named patient use programs, other patient support and disease management programs etc. Adverse reaction reports from these programs should have an appropriate causality assessment, to consider whether they refer to suspected adverse reactions and therefore meet the criteria for reporting. These solicited reports should be classified as study reports in the safety database Identification of PSUR relevant information New and significant safety findings, for which reporting is not required, should be discussed in the relevant sections of the next periodic safety update report (PSUR/PBRER). The following should be considered for inclusion: Relevant studies with no AEs (relevant studies may include studies performed with the same active substance(s) manufactured by a different MAH). Safety information from use in both authorised and unauthorised indications and from use which is not in line with the product information Clinically important safety information from other therapeutic use from MAH programmes (compassionate use, named patient use) Efficacy/benefit information for authorised indications. New information on efficacy and effectiveness in uses other than the authorised indications should not be considered PSUR relevant unless assessed as relevant for the benefit-risk evaluation in the authorised indications. Reports of significant effect of alternative therapies for the authorised indication(s) of the product being monitored. All PSUR relevant articles should be logged in PSUR relevant article log for the relevant product. The PSUR relevant article log is placed under the relevant products for each Client on the K-drive.

4 Effective date: 01 December 2016 Page: 4 of Identification of a potential signal A potential signal may arise from information in e.g. single case reports and scientific information (e.g. articles) concerning the use of medicinal products including quality, nonclinical, clinical, pharmacovigilance and pharmacoepidemiological data. Any A-consult pharmacovigilance staff member identifying a Potential Signal informs the QPPV and Deputy QPPV immediately (within 24 hours)! Please refer to QI31 for further guidance. 4.4 Search profiles An Individual Search Profile must be developed for all medicinal products for which A- consult has literature surveillance obligations. These are placed as appendices to this instruction and cover international or local scientific literature or both (as described in the agreement with the Client). Individual Search Profile shall be approved by the QPPV, the dqppv or the Client Search in international scientific literature The search is performed in Medline. Product specific Individual Search Profiles shall be constructed without MeSH terms. Standard search profile: The following standard search profile should be used: ([Substance names divided by OR] OR [Proprietary names divided by OR]) AND ("last 8 days"[edat]) All substance names, proprietary names and all other search terms must be enclosed quotation marks to prevent PubMed from automatically transforming them to MeSH terms. Example: ( citalopram OR cipramil ) AND ("last 8 days"[edat]) The text marked bold+italic in the above standard search strings must be replaced by the name(s) of the active substance and all proprietary names of the product. Limited search profile: In order to manage an extensive output of the search results, it might be useful to construct a more precise search. The following terms with enclosed quotation marks are recommended to be included in the search profile: case, cases, compassionate use, named patient, patient program, expanded access, off-label, unlabeled indication, unlabeled use, poisoning, intoxication, abuse, toxicity, adverse effect, injurious effects, undesirable effect, side effect, adverse reaction, adverse event, adverse drug reaction, overdose, clinical trial, clinical study, pregnancy, pregnant, gestation, breast feed, breastfeeding, nursing, lack of efficacy, lack of effect, lack of effectiveness, medication error, drug use error, prescription error, administration error, dispensing error, safety, exacerbation, misuse, occupational exposure, interaction, transmission of infectious agent, paternal exposure, death.

5 Effective date: 01 December 2016 Page: 5 of 14 Example: ( citalopram OR cipramil ) AND ( case OR cases OR compassionate use etc.) AND ("last 8 days"[edat]) Creating automatic weekly Medline search Log into My NCBI account on PubMed using login information stored in Outlook. Follow these steps to create an automatic weekly search: 1. Perform the desired search once 2. Click Save search 3. Add a name for the search 4. Adjust the search profile with the following settings: a. Name of search profile: as appropriate b. Would you like updates of new search results: i. Yes ii. Weekly iii. Monday c. Report format: abstract d. Number of items: 200 e. Send even when there aren't any new results: yes f. address: pharmacovigilance@a-consult.dk. g. The text field is optional. 5. Save the search profile Once created, an will be sent by PubMed every Monday to the specified address Search in local scientific literature The Literature Surveillance Agreement may also describe that A-consult must screen relevant local scientific and medical literature once a week/ by every publication for possible ICSRs, potential signals and potential impact on the product benefit-risk profile. This will appear from Individual Search Profiles. 4.5 Weekly literature review Medline weekly search 1. Case Assessor Received PubMed search results are reviewed for possible adverse events. Each hit is assessed individually: Valid case Non-valid case (s) No case / not relevant PSUR relevant Potential signal Assessment Forward the to pharmacovigilance@a-consult.dk. Include the

6 Effective date: 01 December 2016 Page: 6 of 14 assessment of each hit in the top of the . Print and sign the you just forwarded. 2. Case Assessor Full articles will be ordered for: Articles with no available abstract When assessment cannot be based on the abstract alone At time of PSUR writing, archived abstracts of PSUR relevant articles will be reviewed for inclusion in PSUR and ordering of full article. Ordering of full articles Articles are either downloaded (if freely available) or ordered from e.g. Copenhagen University Library, Natural and Health Sciences. Documentation of an order shall be kept in the pigeonhole Ordered Articles until all included articles have been received. 3. Case Processor The containing the assessment is Archived electronically on the k-drive in the Client s Literature Search folder Archived as signed hard copy in the Client s Literature Search binder Place an additional electronic copy in the product PSUR folder if articles relevant for the PSUR were identified. Archiving Abstracts of PSUR relevant articles are archived in the product PSUR folder (pdf from abstract located in PubMed). 4. Case Processor Identified AEs and non-valid cases are printed and the single case handling process is initiated. Case handling Non-valid cases are entered to the database for signal detection purposes. For reportable case reports from the literature, the article shall be submitted at the time of case submission: the article in PDF format to EVLIT@ema.europa.eu The file name of the literature article shall match exactly the World-wide unique case identification number.

7 Effective date: 01 December 2016 Page: 7 of 14 When follow-up is reported, the same file name must be maintained but should include a sequence number separated with a dash National scientific literature 1. Literature Monitoring Assistant or Case Processor Screen the journals for articles mentioning the active substance or product name. Screening of journals 2. Literature Monitoring Assistant or Case Processor Complete the Local Literature Monitoring Form for the Client. 1. Year and week no. 2. Potential cases identified Yes/No 3. Add Literature reference if potential cases are identified 4. Add comments as appropriate 5. Add link to or copy of potential relevant articles Screening documentation 3. Literature Monitoring Assistant or Case Processor 4. Literature Monitoring Assistant or case processor Send the Local Literature Monitoring Form to pharmacovigilance@a-consult.dk. When no hits appear from the search, proceed to step 4. When hits appear from the search, proceed to step 5. The from inbox is: archived electronically on the K drive in the Client s Literature Search folder archived as signed hard copy in the Client s Literature Search binder Distribution Archiving 5. Case Assessor Review the Local Literature Monitoring Form received in pharmacovigilance@a-consult.dk for possible adverse events. Each hit is assessed individually: Valid case Non-valid case (s) No case / not relevant PSUR relevant Potential signal Assessment Forward the to pharmacovigilance@a-consult.dk including the assessment in the top of the . Print and sign the just forwarded.

8 Effective date: 01 December 2016 Page: 8 of Literature Monitoring Assistant or Case Processor Order full articles for: Articles with no available abstract When assessment cannot be based on the abstract alone At time of PSUR writing (applicable for archived abstracts of PSUR relevant articles). Articles are either downloaded (if freely available) or ordered from e.g. Copenhagen University Library, Natural and Health Sciences. Order confirmations shall be kept in the pigeonhole Ordered Articles until all included articles have been received. Ordering of full articles 7. Case Processor The containing the assessment is archived electronically on the K drive in the Client s Literature Search folder archived as signed hard copy in the Client s Literature Search binder Place an additional electronical copy in the product PSUR folder if articles relevant for the PSUR were identified. Archiving Abstracts of PSUR relevant articles are archived in the product PSUR folder (pdf from abstract located in PubMed) 8. Case Processor Identified AEs and non-valid cases are printed and the single case handling process is initiated. Case handling For reportable case reports from the literature, the article shall be submitted at the time of case submission: the article in PDF format to EVLIT@ema.europa.eu The file name of the literature article shall match exactly the World-wide unique case identification number. When follow-up is reported, the same file name must be maintained but should include a sequence number separated with a dash.

9 Effective date: 01 December 2016 Page: 9 of 14 5 Search for ICSRs identified by EMA MLM Service EMA MLM Service monitors medical literature (journals covered in EMBASE/EBSCO) for ICSRs and enters ICSRS from the selected medical literature into the EudraVigilance database. A list of medicinal products (active substances) covered by this service is published at EMA s website and also to be found under the topic MLM Service at EudraVigilance restricted area in Substances. For products where EMA performs MLM service, it is still required that MAHs monitor scientific and medical journals with regards to the benefit-risk profile of the products, particularly in relation to the detection of new signals or emerging safety issues. In addition, MAHs shall still monitor scientific and medical journals, which are not covered by EMA s MLM service. The practical procedure to be undertaken for those medicinal product substances for which A- consult is responsible and which are subject to the monitoring activities by EMA is outlined below. 1. PV Responsible Inform the PV team about new products and investigate whether these products are covered by the EMA s MLM Service. Every quarter (i.e. first week in January, April, July and October) check if there are changes in product coverage by MLM Service for products which A- consult is responsible for. Send an to at pharmacovigilance@a-consult.dk for documentation purposes. 2. Case Processor Search for potential / identified ICSRs Monday, Wednesday and Friday. Open the Medical Literature Monitoring section in the EudraVigilance restricted area. Open the spreadsheet MLM Search result Filter on active substance name. Review the result of the latest search for ICSR relevant to the territory (countries) of the Client. Look for new potential / identified ICSRs and updates to previously listed potential ICSRs. NB. Retrospective searches should be done as well in order to cover all weekdays/ MLM Search result lists. Searches on Monday: Search list published Friday and Monday Searches on Wednesday: Search list published Monday, Tuesday and Wednesday Searches on Friday: Search list published Wednesday, Thursday and Friday Fill in QI21AP09 MLM ICSR Log Investigation regarding product coverage by MLM Service Search for ICSRs

10 Effective date: 01 December 2016 Page: 10 of 14 No new relevant information identified: process completed New relevant information identified: continue from step 2 3. Case Processor Follow the status of a potential / identified ICSRs in MLM search result. Follow the status of ICSRs An ICSR having the status Valid ADR in the spreadsheet should be searched in the spreadsheet MLM ICSRs. EMA MLM Service adds the Worldwide Case ID (WWID) to the spreadsheet MLM ICSRs and the date of creation indicate when upload of the ICSR to EudraVigilance has taken place. MLM Service updates the status of ICSRs in the spreadsheet MLM ICSRs when new information is available. 4. Case Processor Order the full article relating to the confirmed (C) ICSR. Ordering of full articles Articles are either downloaded (if freely available) or ordered from e.g. Copenhagen University Library, Natural and Health Sciences. 5. Case Processor Inform the PV team and the QPPV about the confirmed ICSR and day 0 of the ICSR. Day 0 is the date when Valid ADR is informed of by the MLM Service. In practice this means that for records of confirmed ICSRs, the clock starts for marketing authorisation holders at the time of the publication of the outcome of the literature screening result MLM Search Results on the dedicated area of the EudraVigilance website. For records of potential ICSRs, the day zero is the date when the minimum information for an ICSR to be valid is available. 6. Case Assessor Case Assessor shall plan resources for case processing, medical assessment (if relevant) and timely reporting to partners (if relevant). Informing the PV team and the QPPV Planning ICSRs are created by EMA MLM Service within the following timelines: Valid SAEs immediately and no later than seven calendar days from day zero.

11 Effective date: 01 December 2016 Page: 11 of 14 Valid Non-SAEs originating from the EEA within 21 calendar days from day zero. 7. Case Processor Download the ICSRs using the EV ICHISCR Export Manager ( ICSR Export ). The ICSR export tool allows for filtering based on the following parameters: substance groups, individual substance or substance combinations, dates, pharmaceutical forms and country/region. Download of ICSRs As secondary choice is it possible to download the ICSR via EVWEB (Press ICSRs, then search under MLM Reports ). When is the ICSR available for download: In the MLM EVWEB area, the ICSRs can be accessed immediately as soon as the individual cases have been entered in EudraVigilance. In the EudraVigilance ICH ICSR Export Manager, the ICSRs can be downloaded at the next calendar day from 9.00 a.m. UK GMT following the day of the entry of individual cases in EudraVigilance. Case handling for MLM ICSRs is described in QI34 and the reporting responsibilities in QI24. 6 Archiving Archiving shall be done according to QI05 Archiving at A-consult a/s. s with review documentation sent to PV inbox shall be saved electronically in the respective Client s folder on the K-drive and in the physical binder. 7 References 1) QI05 Archiving at A-consult a/s 2) QI24 Reporting Matrix 3) QI31 Signal Detection and Evaluation 4) QI34 Case handling in PV247

12 Effective date: 01 December 2016 Page: 12 of 14 8 Change Log Version Change description Effective date 10.0 Section 4: o clarification regarding start of monitoring o clarifications regarding scope of reviews o addition regarding solicited reports o clarification regarding non-valid cases o addition regarding changes in benefit-risk o addition regarding pre-selection of PSUR relevant articles o addition of limited search profile o clarification on sending attachments to EMA Section 5: Addition of checks for MLM Service coverage Update of Appendix 10 New Appendix December Adverse event replaced by Valid case Appendix 03 update of current products Appendix 05 and 08 deletion due to termination of the PV Agreement 8.0 New Section 5.0 Search for ICSRs identified by EMA MLM Service Update of appendix 5 New Appendix 9 Monitoring of veterinary products deleted. 7.0 Section 4.4 added Text changed in section and to Identified AEs and non-valid cases are printed and the single case handling process is initiated. QI31 added to References Appendix 6 is obsolete due to withdrawal of alendronate in DK/NO/SE. 6.0 Section 4.2.1: Change of the standard search profile. MeSH terms is no longer used. 01 April October March November 2014 Update of appendix 1, 2, 3,4, 5, and Appendixes: Updated by inclusion of new product. 4.0 Section 4.1: A superscript of human medicinal products and veterinary medicinal products indicate when reporting rules are specific for human or veterinary products, respectively 01 July February 2014 Added Potential signal as search category and a list of events which should be treated as case reports

13 Effective date: 01 December 2016 Page: 13 of 14 Added circumstances when full articles should be ordered. Updated PSUR relevant events section Added check for recommendations from PRAC for human medicinal products. Added a list of categories for safety information for veterinary medicinal products Section : Added a search profile for veterinary products. Section 4.3.1: Potential signal is added as category. Ordering of Full articles is updated. Section : Updated process flow, by adding an archiving step performed by literature monitoring Assistant, when no potential cases has been identified. Potential signal is added as category. Ordering of Full articles is updated. Appendixes: Updated by inclusion of new products and appendixes added for additional customers. Added weekly check for PRAC recommendations This includes both Individual Search Profiles and Local Literature Monitoring forms. 3 Addition of the title Literature Monitoring Assistant 15 August 2013 Section 3: all definitions moved to QI02. Reference to QI02 added. Section 4.1: updated with description of PSUR relevant reports Section 4.2: the QPPV and dqppv now allowed to approve Individual Search Profiles Section 4.2.1: compassionate use / named patient use / infant / adolescent / poisoning added to the standard search profile. Overdose (Mesh) updated to Drug Overdose (Mesh) The section Creating automatic weekly Medline search moved from section 4.3 to 4.2. The screen dump from Pubmed showing setup settings has been replaced by a narrative description. The settings are unchanged. Section 4.3 Addition of step-by-step description of the review of Medline and local scientific literature. Section 4.4, 4.5, and 5: Replaced by the step-by-step description added in section 4.3.

14 Effective date: 01 December 2016 Page: 14 of 14 2 The word SOP has been replaced by instruction In section 3 Definitions, Case Assessor and Case Processor have been defined 01 March 2013 Section 4.1 General aspects: criteria for exclusion of cases updated Section 4.2.1: Standard search profile updated. Section 6: Reference to Eudralex vo. 9A replaced by reference to GVP module VI. 1 New document 25 May 2011

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