Quality Assurance in Clinical Research at RM/ICR GCP Compliance Team, Clinical R&D Slide 1 of 13
What is Quality Assurance? The maintenance of a desired level of quality in a service or product, especially by means of attention to every stage of the process of delivery or production. Oxford Dictionary All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and the applicable regulatory requirement(s). ICH (E6) Good Clinical Practice Slide 2 of 13
Why are we here? Clinical research must be conducted consistently to high standards Research Governance Framework (2005) A quality research culture is essential for proper governance of health and social care research. Responsibilities (of NHS Trust / Sponsor)- -Ensure legislation relating to research is followed within the organisation -Put and keep in place systems to identify and learn from errors or failures associated with any research undertaken through or within the organisation. -Permit and assist with monitoring, audit or inspection by relevant authorities -Demonstrating the existence of clear codes of practice in other areas for their staff, and mechanisms to monitor and assess compliance; -Ensuring that investigators and other research staff are aware of, understand and comply with this framework; -Discharging their agreed role in the management and monitoring of work undertaken by their organisation; This applies to all clinical research! (not just clinical trials of investigational medicinal products [CT-IMPs]) Slide 3 of 13
CT IMPs and Devices The Clinical Trials Regulations (The law!) Medicines for Human Use (Clinical Trials) Regulations (2004) as amended The necessary procedures to secure the quality of every aspect of the trial shall be complied with. the sponsor of a clinical trial shall put and keep in place arrangements for the purpose of ensuring that with regard to that trial the conditions and principles of GCP are satisfied or adhered to. Responsibilities (of NHS Trust / Sponsor)- -Ensure that the conditions and principles of Good Clinical Practice are satisfied or adhered to -Ensure that the trial is conducted in accordance with the protocol and subsequent amendments -Notify any serious breaches of Good Clinical Practice or the protocol, or any urgent safety measures taken to the appropriate authorities -Keep records of all adverse events relating to that trial which are reported by investigators -Provide annual list of suspected serious adverse reactions and a safety report to the appropriate authorities -Ensure inspection readiness at all times Summarised responsibilities as set out in MHRA Good Clinical Practice Guide, TSO 2012. NB: Clinical investigations of medical devices must be conducted in accordance with Medical Devices Regulations (2002) and Good Clinical Practice as set out in ISO 14155:2011 Slide 4 of 13
Input from GCP Compliance Team Key Stages of a Clinical Research Project: Concept & Design (CTIMPs & devices) Set-up and Management Closure, analysis, publication & archiving Slide 5 of 13
Guidance, Policies and SOPs Generic SOPs are written and approved by SOP Working Group SOP Working Group chaired by GCP Compliance Officer & meets ~6monthly SOP Overview Group chaired by QA manager & meets ~quarterly Team inputs into research-specific Trust Policies Development of forms and templates to help make administrative tasks simpler Maintains RM and ICR intranet SOP pages, uploading relevant forms Point of contact for all staff for queries relating to GCP / regulatory issues Slide 6 of 13
Trial Set up Stage Committee for Clinical Research (CCR) Risk Assessment (PV & GCP) Identify compliance risks Suggest mitigations Liaise with other stakeholders Ethics / consent risks Logistics / management / tissue Resources & capacity GCP review Regulatory compliance Clarity / consistency Defined responsibilities Oversight arrangements Patient rights protected Eligibility clear Pharmacovigilance (PV) Review Regulatory obligations clearly stated Safety risks identified & mitigated Consistency of safety reporting Adequacy of safety monitoring Patients given sufficient info about drug Precautions for drug-drug interactions Slide 7 of 13
Management & Delivery 1. Risk-based audit programme 2. Pharmacovigilance audits (Scheduled according to DSUR) 3. Oversight of monitoring (RM/ICR Sponsored Trials) 4. Monitoring of DATIX Incidents (and trend analysis) 5. Information from research teams, e.g. concerns / queries etc 6. Information & findings from audits / inspections by external organisations Lessons learned, influences- CCR review & risk assessment Triggered audits, or next year s audit programme Providing additional training where required Updating quality management system (New SOPs / forms etc) Recommendations to management- e.g. resource needed Slide 8 of 13
Audit Programme Risk assessment includes individual risks of studies, resourcing, intelligence from monitoring, audits, DATIX etc. Different types of audits depending on risks/dept. Approximately 1-2 audits scheduled per month. PV audits are performed per-trial, and timed to the dates of their MHRA authorisation. Audit programme approved by CCR and goes to research leads for information. Usually 1 month notice, although might be less notice for triggered audits. Findings categorised critical (response required within 1 week), major (response within 2 weeks) and other (response in 4 weeks). Planning Visit Report and responses Approval Certificate issued Slide 9 of 13
How you can help us Please ensure any errors, e.g. deviations from protocol are reported on DATIX according to gsop-38 Notify us as early as possible if you are being inspected or audited Let us know of major findings at monitoring visits and if monitors have issues with a Trust process / SOP Inform us of errors in SOPs, guidance (e.g. intranet) or research-specific Policies Let us know about changes (e.g. staffing) likely to influence risk assessment We welcome suggestions for new forms, templates or processes Help us with information gathering, like error checking Edge reports Please adhere to the deadlines agreed Slide 10 of 13
Closure and Archiving End of trial notification must be sent when study closes. The results should be documented in a clinical study report which must be sent within 12 months to the REC. For CT-IMPs, EudraCT must be updated. A summary of the results should also be uploaded to a publically accessible database, e.g. www.clinicaltrials.gov and Royal Marsden website. Once the clinical study report has been submitted, the trial documentation should be archived for a minimum of 5 years. Note that the study is still subject to audit / inspection at any time, so the files must be easily retrievable. Periodical reviews to ensure RM/ICR sponsored trials closed and reported. If there are issues / difficulties in closing out, please contact us. We may need to provide access to computer systems e.g. CESP or provide an authorisation letter on behalf of the sponsor to upload results. Slide 11 of 13
Other duties Help coordinate & facilitate regulatory inspections, e.g. MHRA Support Immunotherapy Governance Group & CCR Collate responses and input into consultations on behalf of the Trust Support teams when being audited by external sponsors Help prepare & circulate R&D bulletins Set up & authorise access to some computer systems, e.g. Common European Submissions Platform (CESP) and RM PV database. Provide authorisation letter to submit to EudraCT on behalf of sponsor. Deliver quarterly training Practical Aspects of GCP and other ad-hoc training. Can provide specific training to particular teams upon request. Investigate potential serious breaches and report confirmed serious breaches to regulators and REC on behalf of Trust / ICR Slide 12 of 13
Questions? Email: gcpcomplianceteam@rmh.nhs.uk Tel: Ext 6509 Cordless: Ext 4414 Slide 13 of 13