SITE INITIATION VISITsites.dundee.ac.uk/.../10/RAINDroP-SIV-Slides-with-notes.pdf · 2021. 2....
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SITE INITIATION VISIT
Transcript of SITE INITIATION VISITsites.dundee.ac.uk/.../10/RAINDroP-SIV-Slides-with-notes.pdf · 2021. 2....
SITE INITIATION VISIT
Meet the TeamCo-Sponsors University of Aberdeen & NHS Grampian
CI Professor Phyo Myint
Trial Co-ordinator Bolanle Birkinns
TCTU Trial Manager Pauline Armory
TCTU Trial Co-ordinator Fiona McLaren-Neil
Statistician Professor Amanda Lee
Health Economist Professor Paul McNamee
Haematologist Dr Katherine Hands
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RAINDroP Team EmailsCI, Prof Phyo Myint [email protected]
RAINDroP Trial Coordinator [email protected]
RAINDRoP Trial Manager [email protected]
Sponsor [email protected]
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PIs & Site Map
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Dr Roy Soiza & Dr Alison DonaldsonDr Vera CvoroProfessor Miles WithamDr Helen May
Research Nurses: Blinded & Unblinded
NHS Grampian
NHS Fife
Newcastle upon Tyne NHS FT
Norfolk & Norwich NHS FT
Tayside CTU
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Presentation Notes
RNs – blinded and Unblinded required
Study DesignPilot Randomised Controlled Trial
Non-CTIMP: routine care interventions
84 participants / 4 sites
Three arms:• Treatment as usual
• Stop oral iron treatment
• Stop oral iron and give IV iron (as per local formulary).
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Presenter
Presentation Notes
to identify what is the best way of finding and recruiting older people who do not respond to oral iron supplementation, and to compare the three current strategies of care. Treatment for 3 months
Key Outcomes
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The co-primary outcomes are:1) the rate of randomisation per month across the pilot sites
2) the proportion recruited from each route of recruitment
• how long it takes to recruit enough people to the study
• which method(s) of recruitment (clinic, adverts or GP letters) is/are most efficient
• Improvement in haemoglobin level (a measure of anaemia) in each treatment arm
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Presentation Notes
Key outcomes will include 1,2,3 The results will allow us to plan a large, multicentre trial to find out which of the three options should become routine clinical care in this situation.
Secondary Outcomes1) change in haemoglobin and ferritin levels at 3 months
2) number of eligible patients per site
3) proportion of eligible patients agreeing to take part and passingscreening
4) feasibility of collecting primary (physical functioning and health-related and general quality of life) and secondary outcomes for maintrial
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Recruitment: IC/EC searches Inclusion ≥ 65 yearsOral Iron Prescribing – minimum 8 weeks txHaematology results: Before iron Hb ≥85g/L ≤110g/LHb after 8wks tx <20g/L improvement or still below lower limit of normal (male 130 / female 120) Biochemistry results: Before iron ferritin <100ug/L
Excluded× Ongoing anaemia investigations× Active GI cancers× Active peptic ulcer× Oral anticoagulants except antiplatelet agents (asprin, dipyridamole, clopidogrel)× eGFR <30× Symptomatic chronic heart failure× Require human assistance to mobilise× Severe congnative impairment× Terminally ill× Another clinical trial
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Presenter
Presentation Notes
Oral iron liquid or tablets Haemoglobin & Ferritin results before oral iron and after min 8wks treat
Recruitment Channels & AccrualsDatabase / Patient List SearchesGP Practice lists / PCN searchHospital clinics / RN searchLaboratory results lists / RNResearch volunteer databases / RNTargeted local advertising / RN
UKCRN Accruals◦ In Scotland to NRSPCN ◦ In England to NIHR Ageing CRN.
Screening Log / Data
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Presenter
Presentation Notes
Four channels of recruitment will be employed for database (participant list) searches using the inclusion and exclusion criteria; searches will be conducted by Primary Care Network (PCN) or Research Nurse (RN) To identify potentially eligible participants, and with permission from the clinician / participants’ doctor, the following searches will be carried out: prescribing searches will be performed by PCN / GP and RN / hospital clinician. biochemistry and haematology results listings created by the NHS laboratory will be reviewed by PCN / GP or RN / hospital clinician Inclusion and exclusion criteria: medical notes will be screened by the PCN / GP and RN / hospital clinician. Primary care recruitment will be carried out with the assistance of the NRS and NIHR PCNs. In England the NIHR Ageing CRN will assist with secondary care recruitment. UKCRN portfolio recruitment accruals will be allocated according to country Screening log
RAINDroP Training & SOPs• Protocol• Operations Manual• User Guides – Recruitment Tracker, TRuST, OpenClinica, LabKey• Sponsor agreed SOPs• Laminate Pack – WPGs for Physical Assessments• Approved Study Documents
• Delegation Log• Study Specific Training Log & SOP Sign-off Sheet
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Presentation Notes
Protocol - PI sign-off Study Specific Documents – training log – Ops Man, User Guides, SOPs Dummy data /Recruitment Tracker & OC – certificate issued OC Cascade Training
PI RESPONSIBLITIES
UK Policy Framework / GCP
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Investigator and site staff qualifications Site agreementsAdequate resources to conduct the studyMedical care of trial subjectsCompliance with the protocol Knowledge of interventions / SmPC including Reference Safety InformationRandomisation Procedures (and Unblinding)Informed consent of trial subjectsRecords and ReportsSafety Assessment & ReportingICH GCP section 4 details the investigator responsibilities: http://ichgcp.net/4-investigator
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Presentation Notes
Delegation of responsibilities Deviations and monitoring too SOPS / WPGs Training logs
Participant Pathway Flowchart
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Centralised Invitation Letters & Pt TrackerPCNRN / Hospital ClinicianPoster Advert contact / Hosptial Clinician
Recruitment Tracker
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Presenter
Presentation Notes
All invitation letters will be managed and mailed by HIC. Invitation packs contain: Invitation letter – from GP or Clinician RAINDroP brochure (brief information) Reply slip Pre-paid HIC addressed return envelope. If required, one reminder letter will be sent. Tracker has three primary functions : Management and Mailing of Participant Invitations Management of Participant Visits Collection and Reporting of Screening Activity. RN account
Protocol & Study Matrix
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RAINDroP Visits: PI Activities
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Visit 1Informed Consent: PI or RN / Delegated activity Pre & Visit 2Pre-Randomisation Lab results & Final Eligibility Assessment & Sign-offPost-Telephone Call - IV Iron Prescribing; V3 appt date/timeVisit 3Arrange / provide medical oversightVisit 4Lab results review and sign-off
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Presentation Notes
Responsibility for taking informed consent The PI has responsibility for obtaining informed consent at each recruiting centre. The PI can delegate obtaining consent to a RN, on the condition that the RN has received training in the informed consent process (GCP training) and Protocol specific training to ensure that they are sufficiently knowledgeable about the trial. This must also comply with the local Trust’s Research Governance Policy. The delegation of taking consent by the RN will be entered in the Delegation of Responsibilities Log and filed in the Investigator Site File. Written consent will be taken at Visit 1 (the combined screening and baseline visit) prior to any trial related activity Date of PIS provision, date and time of informed consent, and name of person taking consent will be recorded in the medical record Pre v2 PI is responsible to assess eligibility, review and sign lab results, confirm in CRF Post v2 call, iv iron prescribing – knowledge of V3 apt date / time / location – medical oversight / safety V4 Lab results review . Sing off & Data review / signoff (post data cleaning)
PI: Adverse EventsAE definition: event requiring advice or treatment from a Health Care Professional (HCP)
Duration: Informed Consent – End Visit 4.
Collect @ V2 & after V4 assessments (V3 retrospective)
Recording: AE Log & Medical Notes
PI assess: severity, causality, expectedness and seriousness
PI review and sign each AE
Follow-up: till resolution or until V4 + 30 days (whichever is first)
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Presenter
Presentation Notes
AE – safety assessment, reporting and followup (conclusion of 30 days past V4) Assessment of AESs - AEs will be assessed by the PI / medically qualified delegate for: severity, causality and seriousness. 1. Severity Mild: an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with every day activities. Moderate: an event that is sufficiently discomforting to interfere with normal everyday activities. Severe: an event that prevents normal everyday activities. The term ‘severe’, used to describe the intensity, should not be confused with ‘serious’ which is a regulatory definition based on participant/event outcome or action criteria. For example, a headache may be severe but not serious, while a minor stroke is serious but may not be severe. 2. Causality Unrelated: where an event is not considered to be related to the intervention. Possibly: although a relationship to the intervention cannot be completely ruled out, the nature of the event, the underlying disease, concomitant medication or temporal relationship make other explanations possible. Probably: the temporal relationship and absence of a more likely explanation suggest the event could be related to the intervention. Definitely: The known effects of the intervention, or based on challenge testing, suggest that the intervention is the most likely cause. 3. Expectedness / Reaction based on knowledge of the reaction and the relevant product information documented in the SmPC. 4. Seriousness AEs will be collected at Visit 2, Visit 3 (if applies) and Visit 4. AEs and SAEs will be recorded from the time of written informed consent until the last study visit. Only AEs which have resulted in the participant seeking advice or treatment from a healthcare professional will be recorded. The PI or delegate will ask about the occurrence of AEs and hospitalisations at each and every study visit. Once the Investigator becomes aware that an AE or SAE has occurred in a study participant, they must enter the information into the CRF AE Log and entered (in a timely fashion) into the OpenClinica database. Participants with unresolved AEs at the last study visit will be followed up until resolution or 30 days after their last study visit, whichever is sooner.
PI: Serious AEsDefinition – Related and Unexpected
and not exempt
Report to CI (cc TM) within 24 hours
Email form
Exceptions are recorded on AE log
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Presenter
Presentation Notes
Definition: A serious adverse event (SAE) is defined as an untoward occurrence that: (a) results in death; (b) is life-threatening; (c) requires hospitalisation or prolongation of existing hospitalisation; (d) results in persistent or significant disability or incapacity; (e) consists of a congenital anomaly or birth defect; or (f) is otherwise considered medically significant by the investigator. Serious Related and Unexpected event except ( Due to the large amount of comorbid disease and very high levels of illness and adverse events that we expect to be present in this population, we will record all Adverse Events but not report to REC those classified as SAEs) the following categories Any death or hospitalisation due to a new cardiovascular event Any death or hospitalisation due to new diagnosis or treatment of cancer Any death or hospitalisation due to exacerbation of an existing medical condition Any admission for elective or planned investigation or treatment Any death or hospitalisation due to nausea, vomiting, constipation or diarrhoea Any death or hospitalisation due to a fall. SAE flowchart
PI: Deviations & Breaches
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•Breach is a departure from the approved protocol, research project documentation, SOPs or any other information relating to the conduct of the trial•Deviation is a minor deviation from an SOP or a planned event. •Signalling
Reporting: Deviations on Log; Breaches on Log and ReportMonthly log to trial coordinatorBreaches to CI and RAINDroPTM; CI inform/report to Sponsor.
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Presentation Notes
PI assessment of Breaches / discuss report to CI without delay / within 24hrs Assessment of deviations and breaches / communication & reporting to CI Breaches - A Non-Serious Breach may be considered a ‘minor non-conformance’ or ‘violation’ and has no impact on a participant’s safety or wellbeing, and/or the scientific integrity of the research. No substantial amendment is required to the approved protocol, trial documentation or trial SOPs. Examples of A Non-Serious Breach include: A study visit out with a defined schedule. , Boxes on the consent form ticked rather than initialled. Misplaced consent form (completed but mis-filed). A Non-Serious Breach may be upgraded, upon review, to a Serious Breach. It should be noted that repeated Non-Serious Breaches which become systematic, or impact multiple participants, may be regarded as a Serious Breach and should be reported as such. A Serious Breach is defined as a Breach which is likely to affect, or have the potential to affect, to a significant degree: The safety, physical or mental integrity of the research participants and/or The scientific value of the research. Examples of a Serious Breach include: Persistent non-compliance with GCP or protocol, Fraud relating to clinical trial records or data. Breach leading to the death, hospitalisation or permanent disability of a participant. Failure to report serious adverse events. Lack of essential approvals. Signalling: Deviations, Breaches and Urgent Safety Measures shall be recorded in such a way that their impact on the research project can be independently assessed during the conduct, reconstruction and reporting of the trial. Full details shall include any corrections and Corrective and Preventive Actions (CAPA) identified. Discussed at TMG Potential / Serious Breaches – inform / Report then assessment by Sponsor - A Deviation shall be reviewed by the Research Governance Team and/or Quality Assurance and may be upgraded to a Non-Serious Breach. CI to Sponsor within 24 hours: A Non-Serious Breach shall be reviewed by Research Governance Team and/or Quality Assurance and may be upgraded to a Serious Breach, or downgraded to a Deviation. A Serious Breach shall be reviewed by Research Governance Team and/or Quality Assurance and may be downgraded to a Non-Serious Breach, or a Deviation.
PI: Completion / Withdrawals
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Withdrawals – clinical judgement
CRF completion sign-off
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Presentation Notes
Withdrawals loss of capacity; clinical judgement (AE, symptom re participation or intervention, exclusion onset, any judgement Any physician using their clinical judgement may withdraw a participant from their randomised treatment. This may occur due to occurrence of: Adverse Event (log on AE log) Onset of a symptom deemed related to study participation or procedures Onset of an exclusion criteria Any other reason which in their clinical judgement requires withdrawal. With consent participants will continue with safety follow up and outcome measure assessments. CRF completion signoff – when data cleaning completed
Monthly Logs & Essential Site Activities
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Monthly Email Logs: Screening Enrolment & RandomisationData Verification (Visual Verification)Deviations Delegation (if any team changes)
Recruitment Tracker – live tool and event capture
OpenClinica data entry – within 2 weeks of study visit
Lab Key Completed CRF pagesData queries / cleaningQuarantined Data Uploads: Oral Iron Use Iron Treatment Data Pt Experience Questionnaire
ISF filing – printed documents; correspondence.
Presenter
Presentation Notes
RN will receive monthly request to email the following RAINDroP Logs to BB Screening Enrolment & Randomisation Deviations Data Verification – VV tool provided Delegation (if any team changes) RN is responsible for providing data via OpenClinica, Recruitment Tracker and Lab Key: Completed CRF pages upload via LabKey Data queries / cleaning Quarantined Data Uploads: Oral iron Use and Iron Treatment Data Excel Spreadsheets Participant Experience Questionnaire Data entry is required within 2 weeks of a study visit. Where this is exceeded a deviation should be recorded on the Deviation Log. The RN, or delegate, is responsible for Investigator Site File maintenance. Printed documents, including correspondence with TM and RAINDroP Trial Coordinator will be filed according to the ISF index. Data queries – ongoing – 2 week turnaround
Monitoring: Purpose
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To verify that the rights and well-being of participants are protected
To ensure that reported trial data is accurate, complete and verifiable from source data
To ensure that the trial is compliant with the protocol, Research Governance Framework /Good Clinical Practice (GCP), SOPs and regulatory requirements
Presenter
Presentation Notes
Monitor from Sponsor monitor by TCTU
Monitoring Schedule
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Risk based / non-CTIMPSIVOn-site / RemoteClose out visit
Informed Consent FormsSAEs
Independent audit by Sponsor or REC
Presenter
Presentation Notes
On-site / remote monitoring – as per Sponsor Monitoring Plan; depending on the number of patients recruited at site and performance of the site. Additional on-site monitoring visits may be arranged if it is deemed necessary. Separate to Sponsor Trial Monitoring TCTU will carry out remote data monitoring; this will require site to upload completed CRF pages, via LabKey. Informed Consent Forms – 100%. Source document verification of critical data (endpoint data, iron treatment data / concomitant medications). Source document verification of adverse event reporting (AE, SAE) – 100% of SAEs. Source document verification of eligibility.
Monitoring visit requirements
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Email to arrange visit date – PI and RNAccess to Investigator Site FilePatient notes / source dataCompleted Informed consent formsOpenClinica and Excel spreadsheets: Oral Iron Use, Iron Treatment
Actions sent to site for completion within 4-8 weeks
RAINDroP PI Meetings
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Trial Management Group – First Tuesday each month @ 3pm
PARTICIPANT PATHWAY
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Research nurse activity
Participant Pathway Flowchart
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Presenter
Presentation Notes
Secondary care prescreening – electroninc and paper medical notes/results add to screening log
HIC: Search Validation
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Presenter
Presentation Notes
All invitation letters will be managed and mailed by HIC. Invitation packs contain: Invitation letter – from GP or Clinician RAINDroP brochure (brief information) Reply slip Pre-paid HIC addressed return envelope. If required, one reminder letter will be sent.
HIC: Centralised Invitations
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Recruitment Tracker
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The Recruitment Tracker has three primary functions :• Management and Mailing of Participant
Invitations• Management of Participant Visits• Collection and Reporting of Screening
Activity.
Access is via https://hicservices.dundee.ac.uk/Recruitment/
Training site, dummy data and then live accounts will be provided for RNs.
RAINDroP Recruitment Tracker User Guide
Presenter
Presentation Notes
Live training via Training site / and user guide
RN: Telephone Pre-screeningRAINDroP participation
Confirm eligibility
Mail / email PIS
Taxi / travel costs
Book V1 or thank / decline
Screening Log
Recruitment Tracker
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Presenter
Presentation Notes
Following a request from a potential participant, for study team contact, the study team will use the Recruitment Tracker to access participant details. The research nurse will: telephone / email the potential participant to describe and discuss RAINDroP participation carry out pre-screening; check inclusion and exclusion criteria provide RAINDroP PIS via mail or email; potential participants should have the PIS for 24 hours before Visit 1 / informed consent. inform potential participants that a taxi will be provided to bring them to the appointment and return them home or if they prefer travel costs to the research visits will be reimbursed. This has been proven to help recruitment and retention of trial participants, in this age group. where appropriate, book Visit 1 OR if potential participant is not eligible or decline to participate, thank them for their time and make them aware that this will not affect their future medical care.
Study Matrix
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Visit 1: Informed Consent
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PI or RN / Delegated activity – suitably trained and qualified
Copies
Enrolment & Randomisation Log
Medical notes
CRF
Presenter
Presentation Notes
Responsibility for taking informed consent The PI has responsibility for obtaining informed consent at each recruiting centre. The PI can delegate obtaining consent to a RN, on the condition that the RN has received training in the informed consent process (GCP training) and Protocol specific training to ensure that they are sufficiently knowledgeable about the trial. This must also comply with the local Trust’s Research Governance Policy. The delegation of taking consent by the RN will be entered in the Delegation of Responsibilities Log and filed in the Investigator Site File. Written consent will be taken at Visit 1 (the combined screening and baseline visit) prior to any trial related activity Date of PIS provision, date and time of informed consent, and name of person taking consent will be recorded in the medical record Consent will be recorded by the RN on the Enrolment & Randomisation Log Date of consent will be recorded in the CRF The Participant ID is provided by the HIC Recruitment Tracker (Cohort ID) Complete the Enrolment and Randomisation Log in the Investigator Site File when you consent / enrol participants into the trial. Every participant consented to the trial should be included on the Enrolment and randomisation Log. Monthly, the Enrolment & Randomisation Log will be emailed by the RN to the RAINDroP trial coordinator.
Visit 1: Informed Consent
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PIS and Consent – Approved version & Headed paper
Fully informed participant
Adequate time to read and consider participation
Opportunity to ask questions / encourage
Prior to any trial related activity
Pt initial boxes; signed and dated by both on same day
Visit 1: Informed Consent
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Common Errors
Wrong version ICF / PIS
Ticked boxes
Signed in wrong place
Dates that don’t match
Missing information
Illegible writing
Researcher completing name and date for pt
Data Collection: CRFCompleting the Case Report Form (CRF)
• Ensure participant ID is entered at the top of each page
• Write clearly within the boxes provided
• No abbreviations
• Instructions for completion of each page
are given on the facing page
Source Data
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Presenter
Presentation Notes
Brief detour re CRF – will come back
Visit 1: Screening & Baseline
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Approx 2 hours
IC / EC – tick yes or no
Demographics – DOB, gender, home circumstances, walking aids
Height & Weight / BMI
Concomitant Medications – Oral iron & Other tx
Medical HistoryBlood Samples Physical AssessmentsQuestionnaire Tools
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Presentation Notes
Ensure that participants are aged 65 or over on the date of Visit 1, to comply with inclusion criteria 3. Medical notes will be reviewed to assess eligibility. Blood results obtained from medical record / laboratory report: Haemoglobin and ferritin results prior to starting oral iron; these results are required to determine eligibility: Where results are not available to participant is ineligible. Haemoglobin and ferritin results after a minimum of 8 weeks oral iron therapy. If available, and within 12 months of Visit 1, creatinine and eGFR will be used to assess eligibility; otherwise baseline sample results are required for eligibility assessment – see Section 3.6. Participant will be asked to describe their home circumstances (record all that apply e.g. if living alone and in sheltered housing record both) and use of care services, and where applicable number of hours per week. Walking aids used outside the home, record those used at Visit 1 e.g. if zimmer and stick are brought to the visit record both. Height and weight will be measured using local equipment and protocol; flat shoes and indoor clothing (no coats / heavy jackets) can be worn. BMI will be calculated using the NHS BMI calculator. Note cm used on NHS site / m in CRF www.nhs.uk/Tools/Pages/Healthyweightcalculator.aspx
Visit 1: Concomitant MedicationsIron treatment name, dose, unit and frequency are captured at Visit 1
All other prescribed medications Concomitant Medication page of the CRF: Generic nameIngredients of combined medications should be listed separately Abbreviations should not be usedOver-the-counter medications are not recorded.
Frequency code:OD; BD; TID
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Presenter
Presentation Notes
Iron treatment name, dose, unit and frequency are captured at Visit 1 on separate pages of the CRF. All other prescribed medications are recorded using the generic name, at Visit 1 and Visit 4, on the Concomitant Medication page of the CRF: Concomitant Medication taken after Visit 1 and before Visit 4 are not recorded, e.g. antibiotics. Over-the-counter medications are not recorded Ingredients of combined medications should be listed separately e.g. for Co-dydramol list codeine and paracetamol. Abbreviations should not be used.
Visit 1:Medical History
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Relevant Medical History from medical notes / participant – tick
‘Other’ include:currently active medical conditionif con meds are taken
or past medical condition that impacts ADL
Please NO abbreviations
Presenter
Presentation Notes
The Medical History, collected from pts and medical notes, section should be completed as fully as possible and should be as diagnosed by a doctor. Relevant medical history will be recorded in the CRF, using a tick for yes or no tick against each listed condition. Date of diagnosis is not required. Additional details are not required, i.e. do not annotate CRF to provide extra information. Only where other medical conditions are reported (i.e. not listed on CRF page) is a written response required. The “other medical history” should include: Currently active medical conditions Medical conditions which the participant is receiving concomitant medications Past medical conditions which impact on the participants’ Activities of Daily Living or ability to complete the trial assessments. Abbreviations should not be avoided. Medical History CRF page definitions: TIA: Transient Ischaemic Attack Diabetes = Type 1 or Type 2 Chronic Kidney Disease Stage 3a eGFR = 45-59mlL/min (NICE CG182) Fragility fractures: Fractures that result from low-level (or ‘low energy’) trauma that is caused by mechanical forces that would not ordinarily result in a fracture. The World Health Organization (WHO) has quantified this as forces equivalent to a fall from a standing height or less. Ref: February 2012, NICE, Osteoporosis: assessing the risk of fragility fracture, NICE guideline, Draft for consultation. BCC: Basal Cell Carcinoma SCC: Squamous Cell Carcinoma COPD: Chronic Obstructive Pulmonary Disease Liver disease: yes if either (or both) cirrhosis or chronic hepatitis Other: see above
Visit 1:Blood Samples
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Local lab 10ml venous blood:
Hb
Ferritin
C-reactive protein, *creatinine, *eGFR
Results - numbers
Presenter
Presentation Notes
As per local laboratory guidance / policy samples will be collected for local laboratory haematological and biochemical analysis: Up to 10ml of non-fasted blood for haemoglobin, ferritin, c-reactive protein, creatinine and estimated GFR (using CKI-EPI equation). Record taking of baseline / screening samples and results (when available) in CRF. Creatinine and eGFR screening sample results are required to assess eligibility if results are not available within 12 months of Visit 1: If these results are out with the inclusion criteria then the participant is ineligible; they should be informed and thanked for their time and made aware that this will not affect their future medical care. The Completion of Trial / Early Withdrawal Form should be completed. If results are within inclusion criteria proceed to Randomisation / Visit 2. Results should be recorded as numbers – except eGRF – letters in one box i.e. if GT60 (OC gives this option) Where sample/s are not obtained, this will be recorded as a deviation; use Breach and Deviation Log; if creatinine and eGRF are required for eligibility and not obtained the participant is ineligible
Visit 1: Physical Assessments
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Requirement: stopwatch, chair, 3 metre walking course, 30 metre flat walking area with 3m interval markings, marker, measuring tape, emergency equipment / facilities
Short Physical Performance Battery
6 minute Walk Test – min/secs
3
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Presentation Notes
CRF describes and provides verbatim text to instruct participant – laminates will be provided Time 0.01 – 5.59 (i.e. 5 min 59 secs) not 100ths of a minute
Questionnaire Tools: up to 1 hourParticipant refreshment
Quiet space
Table or Clipboard
Pen
SELF-REPORTED
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Presenter
Presentation Notes
Funded refreshment Self-reported ??s
Visit1:Questionnaire Tools
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Presenter
Presentation Notes
The following questionnaires and scoring tools should be completed by the participant and returned to the RN at the end of Visit 1 Oral Iron Use Scale Fatigue Severity Scale Participant Reported Anaemia Symptoms Additionally completed at the end of Month 1 and Month 2 At end of Visit 1, RN to provide Participant Reported Anaemia Symptoms Questionnaire for Month 1 and Month 2. EQ-5D (Quality of Life) 15D (Health Related Quality of Life) Activities of Daily Living (Nottingham EADL score) Health & Care Use questionnaire. Indicate completion in the CRF
Visit 1: Participant Information
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Schedule Visit 2
Advise possible dates for Visit 3
Schedule Visit 4
Provide Study Participant Card
Participant Reported Anaemia Symptoms Questionnaires for completion at end of Month 1 and Month 2
Provide copy of PIS and signed Informed Consent Form.
Visit 1: Medical Notes & Data
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Document in medical notes include for source data verification:◦ Copy of signed Informed Consent Form & PIS◦ Date of visit◦ Confirmation that the patient has had the PIS for at least 24 hours.◦ Confirmation of how patient identity was verified.◦ Details of any notable findings at the visit and any action taken.◦ Confirmation that all inclusion/exclusion criteria were met; any results
awaited.◦ Height and weight.◦ Confirmation that the visit was carried out as per protocol.◦ Name and Signature of Research Nurse completing the visit.
CRF
Iron Treatment Data / Excel Spreadsheet
Presenter
Presentation Notes
For SDV
Adverse EventsAE definition: event requiring advice or treatment from a HCP
Duration: Informed Consent – End Visit 4.
Collect @ V2 & after V4 assessments (V3 retrospective)
Recording: AE Log & Medical Notes
PI assess: severity, causality, expectedness and seriousness
PI review and sign each AE
Follow-up: till resolution or until V4 + 30 days (whichever is first)
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Presenter
Presentation Notes
AEs will be collected at Visit 2, Visit 3 (if applies) and Visit 4. AEs and SAEs will be recorded from the time of written informed consent until the last study visit. Only AEs which have resulted in the participant seeking advice or treatment from a healthcare professional will be recorded. The PI or delegate will ask about the occurrence of AEs and hospitalisations at each and every study visit. Once the Investigator becomes aware that an AE or SAE has occurred in a study participant, they must enter the information into the CRF AE Log and entered (in a timely fashion) into the OpenClinica database. Participants with unresolved AEs at the last study visit will be followed up until resolution or 30 days after their last study visit, whichever is sooner. AEs will be assessed by the PI / medically qualified delegate for: severity, causality and seriousness. 1. Severity Mild: an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with every day activities. Moderate: an event that is sufficiently discomforting to interfere with normal everyday activities. Severe: an event that prevents normal everyday activities. The term ‘severe’, used to describe the intensity, should not be confused with ‘serious’ which is a regulatory definition based on participant/event outcome or action criteria. For example, a headache may be severe but not serious, while a minor stroke is serious but may not be severe. 2. Causality Unrelated: where an event is not considered to be related to the intervention. Possibly: although a relationship to the intervention cannot be completely ruled out, the nature of the event, the underlying disease, concomitant medication or temporal relationship make other explanations possible. Probably: the temporal relationship and absence of a more likely explanation suggest the event could be related to the intervention. Definitely: The known effects of the intervention, or based on challenge testing, suggest that the intervention is the most likely cause. 3. Expectedness / Reaction based on knowledge of the reaction and the relevant product information documented in the SmPC. 4. Seriousness
Serious AEsDefinition – Related and Unexpected
and not exempt
Report to CI (cc TM) within 24 hours
Email form
Exceptions are recorded on AE log
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Presenter
Presentation Notes
Definition: A serious adverse event (SAE) is defined as an untoward occurrence that: (a) results in death; (b) is life-threatening; (c) requires hospitalisation or prolongation of existing hospitalisation; (d) results in persistent or significant disability or incapacity; (e) consists of a congenital anomaly or birth defect; or (f) is otherwise considered medically significant by the investigator. Serious Related and Unexpected event except ( Due to the large amount of comorbid disease and very high levels of illness and adverse events that we expect to be present in this population, we will record all Adverse Events but not report to REC those classified as SAEs) the following categories Any death or hospitalisation due to a new cardiovascular event Any death or hospitalisation due to new diagnosis or treatment of cancer Any death or hospitalisation due to exacerbation of an existing medical condition Any admission for elective or planned investigation or treatment Any death or hospitalisation due to nausea, vomiting, constipation or diarrhoea Any death or hospitalisation due to a fall.
Visit 2: Randomisation
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PI final eligibility assessment & sign-off
Unblinded RN
TRuST: Site codes: ARI FIF NWC NUHHaemoglobin result after 8 weeks of oral ironFerritin prior to starting oral iron6 minute walk test distance
Allocation: Treatment as usual Stop oral iron treatment Stop oral iron and give IV iron (as per local formulary).
Visit 2:Telephone Call
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Unblinded RNTreatment Arm InstructionGroup 1: Continue oral iron
1. Telephone participant and instruct to continue oral iron
1. Send recruited letter to GP informing Group 1 allocationOral iron continuing for study duration
Group 2: Stop oral iron
1. Telephone participant and instruct to stop oral iron
1. Send recruited letter to GP informing Group 2 allocation Oral iron stopping for study duration
Group 3: Stop oral iron & give IV iron
1. Arrange appointment with Day Hospital / Clinical facilityFollowing discussion with participant this may need to be re-arranged
1. Telephone participant, instruct to stop oral iron.2. Advise and confirm appointment to attend for IV infusionIV infusion visit should be within 2 weeks of randomisation
1. Send recruited letter to GP informing Group 3 allocation Oral iron stopping & IV iron therapy for study duration and not to restart oral iron for 3 months
Presenter
Presentation Notes
Telephone participant. Confirm continued participant consent. If participant wishes to continue, follow the process detailed in the Intervention Instructions Table (below) according to which group the participant has been allocated to. (arrange visit 3 for IV iron where required) If withdrawal, complete Study Withdrawal page, indicate reason for Early Withdrawal. Record any adverse events. GP letter – recruited / copy in med notes
Visit 2:Medical Notes & Data
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o Date and time of visito Treatment allocation / Print TRuST notificationo GP letter – Recruitedo Name and Signature of RN completing the visit.
CRF
Recruitment Tracker
Visit 3:IV Iron Administration
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Within 2 weeks of V2
Approx 90 minutes
Local Policy
PI prescribe: dose, time & Hb
Registered Nurse administer
Unblinded RN attend
Clinical Location & Emergency Facilities
Record after V4 assessments – Iron Treatment Log & Excel spreadsheet
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Presentation Notes
The local NHS IV iron policies and procedures will apply during and after the procedure, this can include: medical notes record of the procedure (to avoid unblinding, where possible the blinded RN should avoid reviewing the medical record until after Visit 4 assessments are completed). the patient receiving NHS IV iron infusion information prior to discharge repeat haemoglobin and ferritin levels where response is sub-optimal a repeat infusion may be required. NO AE collected – retrospective at V4
V3:Medical Notes & DataoDate and time of visito IV iron prescription filed as per local policy
oDetails of any notable events at the visit and any action taken.
oName and Signature of RN completing the visit.
NO CRF DATA
NO RECRUITMENT TRACKER
V3 treatment retrospective Iron Treatment Data / excel spreadsheet
AEs – retrospective @V4
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Presentation Notes
Worksheet for notes
V4: Assessments Approx 2 hoursBlinded RN
Blood samples: Hb & ferritin
Physical Assessments: SPPB. 6 minute walkQuestionnaire Tools (refreshment)
AE / con meds after assessments
Iron specific dietary adviceInform participant to contact GP
Travel expenses
Oral iron pts – Unblinded RN call for Oral Iron Use Tool / Spreadsheet
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Presentation Notes
If samples not obtained - deviation SPPB & 6 min walk QQs Oral Iron Use Scale Fatigue Severity Scale Participant Reported Anaemia Symptoms Additionally completed at the end of Month 1 and Month 2 At end of Visit 1, RN to provide Participant Reported Anaemia Symptoms Questionnaire for Month 1 and Month 2. EQ-5D (Quality of Life) 15D (Health Related Quality of Life) Activities of Daily Living (Nottingham EADL score) Health & Care Use questionnaire Participant experience and views. Follow-up concomitant medications are collected at Visit 4. To maintain blinding iron treatment / oral iron use data is collected after Visit 4 assessments are completed; record on iron tx spreadsheet For participants randomised to receive oral iron the UNBLINDED RN will telephone the participant to complete the Oral Iron Use Scale. Dietary advice Pt contact GP – resume care (review HB ferritin results)
Visit 4: Concomitant Medications•Iron treatment name, dose, unit and frequency are captured following assessments:
Iron Treatment & Excel Spreadsheet.
•Record all other prescribed medications on CRF Concomitant Medication page : Generic nameConcomitant medication taken after Visit 1 and before Visit 4 are not recorded, e.g. antibiotics.Over-the-counter medications are not recordedIngredients of combined medications should be listed separately Abbreviations should not be used.
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Presentation Notes
Iron treatment name, dose, unit and frequency are captured at Visit 4 (following assessments) on separate pages of the CRF. All other prescribed medications are recorded using the generic name, Visit 4, on the Concomitant Medication page of the CRF: Concomitant Medication taken after Visit 1 and before Visit 4 are not recorded, e.g. antibiotics. Over-the-counter medications are not recorded Ingredients of combined medications should be listed separately e.g. for Co-dydramol list codeine and paracetamol. Abbreviations should not be used.
V4:Medical Notes & DataoDate and time of visitoDetails of any notable events at the visit and any action taken.
oConfirmation that the visit was carried out as per protocol.
oName and Signature of RN completing the visit.
CRF
Recruitment TrackerQuarantined DataIron Treatment excel spreadsheetOral Iron Use excel spreadsheetParticipant experience questionnarie
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Worksheet for medical notes
SYSTEMS
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Presentation Notes
And SOPS
Monthly Logs & Essential Site Activities
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Monthly Email Logs: Screening Enrolment & RandomisationData Verification (Visual Verification)Deviations Delegation (if any team changes)
Recruitment Tracker – live tool and event capture
OpenClinica data entry – within 2 weeks of study visit
Lab Key Completed CRF pagesData queries / cleaningQuarantined Data Uploads: Oral Iron Use Iron Treatment Data Pt Experience Questionnaire
ISF filing – printed documents; correspondence.
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Presentation Notes
RN will receive monthly request to email the following RAINDroP Logs to BB Screening Enrolment & Randomisation Deviations Data Verification – VV tool provided Delegation (if any team changes) RN is responsible for providing data via OpenClinica, Recruitment Tracker and Lab Key: Completed CRF pages upload via LabKey Data queries / cleaning Quarantined Data Uploads: Oral iron Use and Iron Treatment Data Excel Spreadsheets Participant Experience Questionnaire Data entry is required within 2 weeks of a study visit. Where this is exceeded a deviation should be recorded on the Deviation Log. The RN, or delegate, is responsible for Investigator Site File maintenance. Printed documents, including correspondence with TM and RAINDroP Trial Coordinator will be filed according to the ISF index. ata queries – ongoing – 2 week turnaround
Monthly RN Meetings
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Research Nurse Meeting
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Presentation Notes
RN will receive monthly request to email the following RAINDroP Logs to BB Screening Enrolment & Randomisation Deviations Data Verification – VV tool provided Delegation (if any team changes) RN is responsible for providing data via OpenClinica, Recruitment Tracker and Lab Key: Completed CRF pages upload via LabKey Data queries / cleaning Quarantined Data Uploads: Oral iron Use and Iron Treatment Data Excel Spreadsheets Participant Experience Questionnaire Data entry is required within 2 weeks of a study visit. Where this is exceeded a deviation should be recorded on the Deviation Log. The RN, or delegate, is responsible for Investigator Site File maintenance. Printed documents, including correspondence with TM and RAINDroP Trial Coordinator will be filed according to the ISF index. ata queries – ongoing – 2 week turnaround
WebsitePublic information / Potential Participants
Staff Portal◦ Recruitment Tracker◦ TRuST◦ OpenClinica◦ LabKey◦ Trial Documents – generic and site specific◦ Recruitment / Accrual Numbers◦ Trial Announcements◦ Events Calendar
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Secure webpage / user account
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Recruitment Tracker•Password Protected Training Site
•RAINDroP Recruitment Tracker User Guide
•Dummy Data•Password Protected Live Account
oHIC DATA LINKAGE SERVICE - NHS FIFE
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Go to training site
TRuST: Randomisation•Unblinded RN•RAINDRoP TRuST User Guide•Password Protected Account
Randomisation NotificationUnblinded RN print and file in medical notesNo formal unblinding requiredEmergency RandomisationIf no web-access at site telephone TCTU 01382 383581 Treatment allocation notified by telephone & email (print and file when access resumes)
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Presentation Notes
Where possible blinded RN not to review notes until completion of V4 assessments Show screens if possible – go to test site
OpenClinica•Web-based Database
•Web-based training to follow
•RAINDroP OpenClinica User Guide•Dummy data
•Training Certificate
•Password Protected Account
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Quarantined Data Maintain statistician & health economist blinding
Data held at site until post-database lock TCTU will request upload via LabKey◦ Oral Iron Use Scale responses are entered on the Oral Iron Use Excel spreadsheet (to maintain blinding).◦ Iron Treatment Data will be entered on the Iron Treatment Data excel spreadsheet.◦ Patient Experience Questionnaire
Excel Spreadsheet SOP◦ System backups◦ Naming format
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LabKeyPassword Protected AccountRAINDroP User Guide – Folder Structure & Document Naming ConventionWeb-based Data Repository
Excel Spreadsheets: Oral Iron Use & Iron Treatment DataParticipant Experience QuestionnaireCompleted CRFsData Query Resolutions
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Case Report Form: Review
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REview
Investigator Site File: Review
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ISF
Next StepsRAINDroP training
GP invitations
Recruitment Tracker
Medical Notes Pre-screening / Clinician invitations
FPFV
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