1. The Clinical Research Nurse as an expert resource in the protocol development and implementation of a research study – a case report Polly Tarrant, Lead Research Nurse Kornelia Hathaway, Education & Training Manager Contacts: polly.tarrant@addenbrookes.nhs.uk; kornelia.hathaway@addenbrookes.nhs.ukpolly.tarrant@addenbrookes.nhs.ukkornelia.hathaway@addenbrookes.nhs.uk Background A research team from a University Department of Psychiatry had approval to run an experimental/observational study at the WTCRF Cambridge. The proposed study sought to investigate theories of mania/psychosis by pharmacological manipulation of the dopaminergic system in healthy volunteers. The study proposed a within-subject, placebo controlled, double blind study design wherein during 3 study visits each, 30 healthy volunteers received a randomised different treatment combination of a. IV methamphetamine (enhances dopamine release), b. oral amisulpride (a dopamine receptor blocker) c. placebo. This was to be followed on each visit by cognitive testing and fMRI scan. The two drugs used act as chemical probes to safely and temporarily model symptoms of mania or psychosis and their subsequent treatment. However, despite having received a favourable ethics opinion and approval from the Trust R & D department, it became apparent that a number of aspects of the study were still unclear and required development. A Clinical Research Nurse proved to be an expert resource in the ensuing stages of the study. Clinical Research Nurse (CRN) The role is reflected in the core competencies identified by the Clinical Research Nurse Competency Framework (RCN 2008) To demonstrate knowledge and understanding of the evolution of clinical research. To apply knowledge and skills in the clinical research environment. To work within and adhere to the requirements of research ethics, research governance and legislation. To understand the principles and practice of obtaining and maintaining valid informed consent. Clinical Research Nurse (CRN) The role is reflected in the core competencies identified by the Clinical Research Nurse Competency Framework (RCN 2008) To demonstrate knowledge and understanding of the evolution of clinical research. To apply knowledge and skills in the clinical research environment. To work within and adhere to the requirements of research ethics, research governance and legislation. To understand the principles and practice of obtaining and maintaining valid informed consent. Discussion The intervention of the CRN had a direct formative effect on the development and implementation of a research protocol, clearly demonstrating the specialist skills identified as intrinsic to the CRN Role. The collaboration between research team and CRN was recognised by both parties to have been of benefit to the integrity of the research and the safety of the research participants. The number of CRNs in the UK is expanding. Given the range of knowledge and skills specific to the clinical research field that are required when working in this area, a national formally recognised training pathway for nurses working as CRNs is desirable. This is still to be established… Method The WTCRF Clinical Research Nurse assigned to coordinate the study set-up and implementation had crucial input in guiding the research team through the process of ensuring safe practice. The case study identifies how ongoing liaison with the study team and others addressed key issues in specific areas of the study, and how the CRN identified and implemented strategies and measures to resolve problems and ensure compliance with Good Clinical Practice. Drug administration issues that needed clarification and had to be addressed - Rate of IV administration - Dilution/ concentration/ drug compatibility - Procedure for administration - Equipment training The Clinical Research Nurse’s role and contribution Setting up pilot study visit There was no IV monograph or IV medicine information sheet for methamphetamine, so liaised with Trust Pharmacy to establish monograph (eg, by providing evidence of precedents of practice of similar studies) Established, reviewed and amended the drug administration procedure - informed by clinical experience of IV drug administration and awareness of Trust and regulatory requirements in relation to equipment competence. Participant safety issues - Managing side effects of all study drugs - Rigorous monitoring of participant vital signs required as methamphetamine has known cardiovascular and other effects. - Drug screening originally excluded participants only if methamphetamine use detected and not use of other recreational drugs Participant safety issues - Managing side effects of all study drugs - Rigorous monitoring of participant vital signs required as methamphetamine has known cardiovascular and other effects. - Drug screening originally excluded participants only if methamphetamine use detected and not use of other recreational drugs Patient advocacy integral part of CRN’s role Clarified and documented expected side effects of study drugs Initiated and arranged provision of rescue drugs – including procyclidine hydrochloride in case of muscle rigidity due to amisulpride Established process for participants to receive discharge medication of zopiclone x 2 doses (to be taken as required), as pilot study identified insomnia following methamphetamine administration Robust monitoring standards established during and following infusion Initiated exclusion criteria being extended to incorporate any use of recreational drugs Logistics - Screening on same day as study visit resulted in loss of some fMRI slots when participants failed screening - Not feasible for WTCRF – a multi user facility – to accommodate 90 visits in 12 weeks - Guidelines for sample handling and processing had to be established Logistics - Screening on same day as study visit resulted in loss of some fMRI slots when participants failed screening - Not feasible for WTCRF – a multi user facility – to accommodate 90 visits in 12 weeks - Guidelines for sample handling and processing had to be established Drew up Standard Operating Procedures (SOPs) for drug preparation and administration Agreed and implemented documentation encompassing study process, sample handling, and collection of study monitoring data Ensured all processes and interventions given clear and auditable trail Ensured training records in place for all staff involved in study Implemented randomisation process to be followed to ensure participant safety while maintaining researcher and participant blinding Established secure but accessible location of unblinding code in case of emergency Regulatory compliance issues - Study specific documentation - Need for standardisation in practice to ensure research is robust and integrity maintained - Randomisation and un-blinding processes had to be specified Regulatory compliance issues - Study specific documentation - Need for standardisation in practice to ensure research is robust and integrity maintained - Randomisation and un-blinding processes had to be specified Rescheduled screening to take place several days prior to 1st study intervention. This allowed for re-booking of ‘replacement’ participants if screening showed that inclusion criteria was not met Liaised to receive advance notification of fMRI bookings in order to ensure availability of CRF resources Negotiated and implemented more realistic timeframe for study visits Drew on specialised clinical experience to establish sample handling, processing centrifuge and storage strategy and to ensure robust data collection. Rescheduled screening to take place several days prior to 1st study intervention. This allowed for re-booking of ‘replacement’ participants if screening showed that inclusion criteria was not met Liaised to receive advance notification of fMRI bookings in order to ensure availability of CRF resources Negotiated and implemented more realistic timeframe for study visits Drew on specialised clinical experience to establish sample handling, processing centrifuge and storage strategy and to ensure robust data collection.