Work Instruction Title: Adverse Event Reporting Work Instruction Number: 20 Version Number: V2 Effective Date: 24 January 2011 Author Name: Heather Leishman Title: PCRN-EoE Network Co-ordinator Date: 7 February 2010 Approved by Name: Helen Macdonald Title: Research Delivery Manager Date: 8 October 2014 Review date: 8 October 2016 Review History Version No. V1 V2 date amendments 01/07.13 Minor change: Removal of PCT reference 24.9.14 Minor changes plus participant responsibilities when consenting to a study in relation to safety reporting. HL WI 20 Adverse Event Reporting Page 1 of 7 Approved V2 1. Introduction, Background and Purpose Pharmacovigilance is the continuous process of monitoring, evaluating and improving the safety of medicines, which is ongoing throughout the period of drug development, from animal testing through to post-marketing surveys. In order to assess the safety of an investigational product it is important to: Collect baseline information on the health status of trial participants Be aware of and record all concomitant medications Ask about these, and about the subjects health status at every visit Record all untoward medical occurrences (AEs) as specified in the protocol Report AEs within the specified timeframes Collect all data as accurately as possible An Adverse Event ( AE) is defined by ICH GCP (Glossary 1.2) as: ‘Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An Adverse Event (AE) can therefore be any unfavourable or unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.’ Elective hospitalisations for pre-trial conditions are not adverse events An Unexpected Adverse Reaction (UAR) is said to have occurred when the nature or severity of the reaction is not consistent with the applicable product information (e.g. Investigator Brochure or an unauthorised investigational product, or Summary of Product Characteristics for an authorised product) All Adverse Events occurring during the study should be recorded in the participant case report form and the medical notes. An Adverse Reaction (AR) is defined as: Any untoward or unintended response to an investigational medicinal product (IMP) at any dose administered. This includes all adverse events judged by either the Principal Investigator or the Sponsor as having a reasonable causal relationship to the IMP. EudraVigilance is a data processing network and management system for reporting and evaluating suspected adverse reactions during the development and following the marketing authorisation of medicinal products in the European Economic Area (EEA). eudravigilance.ema.europa.eu All interventional research (involving drugs or devices - whether or not licensed) should have safety reporting procedures in place. These procedures should form part of the study protocol and be approved by the Research Ethics and Research Governance Departments. This document complies with the legal requirements of the EU Clinical Trials Directive (2001/20/EC) and the standards set out in the Research Governance Framework for Health and Social Care (second edition 2005). This Work Instruction (WI) relates to SOP 05 Safety Reporting and describes the procedure for Adverse Event Reporting. This does not include Serious Adverse Event/ Reaction (SAE/R), Suspected Serious Adverse Reaction (SSAR) or Suspected Unexpected Serious Adverse Reactions (SUSAR) reporting, which are covered in WI 21. WI 20 Adverse Event Reporting Page 2 of 7 Approved V2 2. Abbreviations See Reference Document: CRN Glossary of Terms and Abbreviations. 3. Scope This WI affects all CRN staff working on NIHR adopted studies. It should be read and applied in conjunction with relevant local policies and approved study protocols. 4. Responsibilities The overall responsibility for the accurate and timely reporting of Adverse Events and Adverse Reactions lies with the Principal Investigator for the site where the study visits are being carried out. The Principal Investigator may ask a delegated team member (as set out in the authorised delegation log) to undertake these duties. 5. Procedures The safety reporting procedures follow a general pattern but are study specific. The study protocol should be followed closely and any uncertainties raised with the study Sponsor or representative. The Sponsor will state at what point in the trial Adverse Event Reporting will start. It is essential to collect and complete accurate baseline data on the health status of trial participants to ensure that changes to health status will be detected. Planning When considering the hosting of a Clinical Trial of Investigational Medicinal Products (CTIMP) study the Principal Investigator and study nurse should take time to consider the study protocol, the Summary of Product Characteristics or the Investigator’s Brochure with respect to the safety reporting elements. An assessment of the exact reporting requirements should be made in relation to the time and space capacity that may be required to undertake the reporting procedures properly before accepting such as research project. Safety reporting requirements for an interventional study are subject to change as a result of an amendment 5.2 Reporting After initiation of the study treatment (this may not include run- in medication), participants receiving study drugs should be closely monitored for their clinical safety. They should be questioned about their health status at every visit. The study protocol should state clearly what Adverse Events needs to be reported and how this should be done. A study protocol may ask for symptoms and signs to be reported separately (i.e. 1 “sore throat” 2. ”sneezing” 3. “pyrexia”) or the protocol may ask for the adverse report to be reported as a diagnosis (“common cold”). Reporting of symptoms is generally more useful to the study sponsors but is more time consuming for the study staff to report. Each Adverse Event must be evaluated for seriousness, causality and expectedness, along with the action taken, including concomitant medications, and outcome. All adverse events judged by the Principal Investigator as having a reasonable causal relationship to the IMP will be classified as Adverse Reactions. See Appendix 1: Example of AE Reporting Form. Staff reporting Adverse Events must be aware of the more serious categories of adverse events which require expedited reporting. SAE’s and SUSARs are covered in WI 21 Serious Adverse Event Reporting. WI 20 Adverse Event Reporting Page 3 of 7 Approved V2 5.3 Informed Consent As part of the informed consent procedure (see SOP 01 Informed Consent) the potential study participant should be told in detail about the safety reporting requirements for the study. The potential participant, by consenting to take part in a study is also consenting to comply by the safety reporting procedures, which may include carrying a card and also informing family and friends of participation in a trial and keeping the contact details of the study team easily accessible. 5.4 Patient Diary Some studies supply the participants with REC approved study diaries to help them to record when they experience a new or recurring sign or symptom. Participants will be asked to record the event including start and end dates (these are often missed). The diary should be reviewed with the participant at a study visit and the information from the participant diary should be reported in line with the study protocol on the appropriate and approved reporting forms. Participant diaries must always be kept in the trial file. It is prudent to ensure that the participants ID number is used on the diary plus the date of the diary. The diary will be used in most cases as the source documentation for Adverse Events in the case of Source Data Verification (SDV). The study sponsor may ask for the diary to be scanned into the clinical notes or that the entries are transcribed into the clinical notes. Where a study diary is not supplied for a study, check with the sponsor prior to the study starting regarding how they wish the participants to record adverse events between visits and whether documents such as the participant’s own clinical records should be copied for SDV purposes. 5.5 Emergency Contact Details The participants who have given their consent to be part of an interventional study should always be given the contact information of the Principal Investigator or delegated study team member. This may be given on the emergency contact card, (See Appendix 2). This is particularly important for the period following randomisation when the participant may need help and guidance with any signs and symptoms they may experience (which may or may not be related to the study drug). 5.6 Follow up Prior to the next participant study visit, “open” Adverse Events (where the participant did not give an end date at the last visit) should be reviewed and followed up at the upcoming study visit. This is because the participant diary would have been handed in at the last visit and the participant would not have had the opportunity to report an end date within that diary. 5.7 Special Categories Some study protocols have special categories of reporting such as “Medically Attended Adverse Events”. In this case it may be possible that the study Sponsor only wishes you to report Adverse Events where participants consult a clinician. It is important that the study team in this case do not rely solely on attendances reported in the participant’s clinical record, but must always ask the participant if they have attended a clinician since the last visit in case the participant attended a clinician outside the practice/usual clinical service. WI 20 Adverse Event Reporting Page 4 of 7 Approved V2 6. Related SOPs, Work Instructions and Reference Documents 6.1 SOPs SOP 01 Informed consent SOP 05 Safety reporting 6.2 Work Instructions WI 21 Serious Adverse Event reporting 6.3 Reference Documents ICH Good Clinical Practice (GCP) EU Clinical Trials Directive (EUCTD) CRN Glossary of Terms and Abbreviations 7. Appendices Appendix 1: Example of Adverse Event report form Appendix 2: Example of an emergency contact card WI 20 Adverse Event Reporting Page 5 of 7 Approved V2 APPENDIX 1 ADVERSE EVENT CASE REPORT FORM STUDY NAME:_____________________________________ SITE ………………………………………………………………………… PT INITIALS……………..……. PRINCIPAL INVESTIGATOR …………………………………………….. PT STUDY No. …………….… AE Description 1 = Mild 2 = Moderate 3 = Severe 4 = Life threatening or disabling* 5 = Fatal* Submitted As On SAE Causality 1 = Unrelated 2 = Unlikely 3 = Possible 4 = Probable 5 = Definite 1 = Expected 2= Unexpected Severity Action Taken 1 = None 2 = Medication Therapy 3 = Procedure 4 = Hospitalization* 5 = Other 1 = No 2 = Yes Outcome 1 = Recovered 2 = Improved 3 = Ongoing 4 = Death* 5 = Unknown Date of AE Onset and Resolution (mm-dd-yyyy) Check box “on-going” if the AE is on-going at the time of report On-going (X or √) Start Date: _____ - _____ - 20_____ Resolution Date: 1 _____ - _____ - 20 _____ On-going Start Date: _____ - _____ - 20_____ Resolution Date: 2 _____ - _____ - 20 _____ On-going Start Date: _____ - _____ - 20_____ Resolution Date: 3 _____ - _____ - 20 _____ On-going Comments: Investigator Signature: Date: ____ - ____ - 20____ (mm-dd-yyyy) * If AE is life threatening, disabling or fatal please submit details to the sponsor within 24 hrs of becoming aware of the event WI 20 Adverse Event Reporting Page 6 of 7 Approved V2 Appendix 2 Example of wording on Emergency Contact Card: Patient Name: …………………… Patient Number:………………….. GP Name:………………………………. GP Number………………………….. WARNING This patient is taking part in a clinical trial, and may be on xxx (name of drug) To discuss obtaining a code-break, treating doctors should contact: Tel no: xxx (needs to be 24/7) WI 20 Adverse Event Reporting Page 7 of 7 Approved V2