NHSBT/MRC Clinical Studies Unit TRIGGER Trial: Transfusion in Gastrointestinal Bleeding Presented by Dr Vipul Jairath Research Fellow and Honorary SpR

NHSBT/MRC Clinical Studies Unit

TRIGGER Trial: Transfusion in Gastrointestinal Bleeding

Presented by

Dr Vipul Jairath

Research Fellow and Honorary SpR Gastroenterology

NHSBT and Oxford University Hospitals

Investigator MeetingNHSBT – Birmingham

August 29th 201211:00-16:30


TRIGGER Investigator Meeting• Welcome• Introductions• Apologies• Study Materials

– Site Folder– Screening Log and CRFs– Study Handbook


Overview of Policy Implementation, Screening and Consent Procedures

Vipul Jairath, Ana Mora, Sian Davies

11:30 – 12:15


Overview of trial recruitment processes

Follow the hospital’s allocated transfusion policy – Restrictive or Liberal

Participant admitted to hospital with suspected AUGIB Algorithm is followed for all patients except those where the clinician feels immediate transfusion is needed when the patient presents, regardless of or prior to obtaining the Hb result, due to severity of bleeding

Screen and Complete Screening Log Daily

Approach Eligible Patients to seek Consent

Complete CRFs for Consenting Patients

Collect data – discharge/death/D28

Telephone follow-up at Day 28

If participant declines consent for data use and follow-up, the algorithm is still followed


The Screening Log• Each site should develop their own methods of case-

ascertainment• Log should be completed daily Monday – Friday• Should record all new admissions with Acute Upper

Gastrointestinal Bleeding (AUGIB) defined by:- Haematemesis: vomiting of blood, blood clots or witnessed coffee grounds- Melaena: passage of dark tarry stools either on clinical history witnessed by medical or nursing staff, or discovered on rectal examination


The Screening Log• Screening Log (a): complete for ALL admission with AUGIB• Screening Log (b): only complete for patients considered

‘Ineligible due to severity of bleeding’• See Screening Log forms (a) and (b) and Study Handbook

pages 10 – 11• Send log through every Monday to CSU


Consent – for what?• Randomisation – from the cluster• Intervention – from the cluster• Data collection – from the participant• Follow-up – from the participant


Consent – what is capacity?• Mental Capacity Act 2005, Section 2 ‘... a person lacks capacity if at the material time he is unable to make a decision

for himself in relation to the matter because an impairment of, or disturbance in, the functioning of the mind or brain’

• The following factors have to considered when assessing if someone has capacity to make a decision, section 3 (1):- whether they are able to understand the information- whether they are able to retain the information related to the decision to be made- whether they are able to use or weigh that information as part of the process of making the decision- whether they are able to communicate that decision – by any means


Consent procedures• Spectrum of illness• Anticipate that most patients will be able to provide consent

for themselves• Patients who may lack capacity include:

- elderly patients with pre-existing cognitive impairment

• Patients who may have fluctuating capacity include:

- elderly patients with acute confusional state

- decompensated liver disease

- alcohol withdrawal – especially Delerium Tremens


When and How to approach patients• Suggested timeframe to approach eligible

patients/delegate:- on the same day for those who present in normal hours- the following day for those who present overnight- Monday for those who present over the weekend ... provided this is appropriate to their clinical condition

• Please use the suggested script as a guide which may help explain the transfusion policy – page 15 of Study Handbook

Remember – you cannot complete any paperwork other than the anonymised screening log until you have written patient consent


Definitions - England• Personal Consultee

- ‘... someone whom the person who lacks capacity would trust with important decisions about their welfare, but who is not acting in a professional or paid capacity, e.g you could consult a family member or close friend of the prospective trial participant, but not a paid carer or other professional such as social worker. Remuneration does not cover family members receiving some of the person’s pension or other benefits as a payment towards their share of the household expenses’

• Nominated Consultee- ‘... Someone who is prepared to be consulted by the researcher, but has no connection

with the research study, e.g this could be the consultant responsible for the patient’s care, provided they are not a named local PI, and should be of consultant (or equivalent) status. They must have received information about the research and a PIS is considered appropriate’


Definitions - Scotland• Relative/Welfare Attorney

- ‘... Someone who has been appointed by a court to make decisions on behalf of those lacking capacity’


Consent Procedures – England (p.13 SH) CRF Form 1b

Does the patient have mental capacity in relation to the study? Approach patient and use information sheet and consent form for participants with capacity

No

Does a personal consultee exist who can be approached in person?Approach personal consultee. Use personal consultee information sheet and declaration form

Approach nominated consultee. Use clinician agreement form

Yes

Does the patient regain mental capacity in relation to the study?

Use declaration provided by personal consultee

Use information sheet & consent form for participants regaining capacity and data preservation form

Yes No

Yes

No


Consent Procedures – Scotland (p.14 SH) CRF Form 1b

Does the patient have mental capacity in relation to the study? Approach patient and use information sheet and consent form for participants with capacity

No

Does a relative/welfare attorney exist who can be approached in person?

Approach relative/WA. Use relative/WA information sheet and declaration form

Patient is not enrolled into study

Yes

Does the patient regain mental capacity in relation to the study?

Use consent provided by relative/WA

Use information sheet & consent form for participants regaining capacity and data preservation form

Yes No

Yes

No


When is a Data Preservation form needed?• All patients who lacked capacity, and proxy consent

(consultee/relative/welfare guardian) was obtained, must be approached once they regain capacity

• Use Data Preservation form (DPF) if:- a patient who regains capacity (and was enrolled on the basis of proxy consent) then declines to take part further in the study. Use of a Data Preservation Form will allow use of data up to that point, provided the patient agrees to this

- a proxy initially provides consent and then decides to with draw this. Use of a Data Preservation Form will allow use of data up to that point, provided the proxy agrees to this


Special Considerations - Scotland• Any participant with a pre-existing condition which would

render them unable to provide consent would preclude them from participating in the study, e.g dementia

• Neither patients nor relatives/welfare guardians should be approached in this circumstance


Patients discharged prior to consent• Some centres are more pro-active at discharging lower risk

patients from the ED• Those will need to attempt to identify those patients and

indicate this option on the weekly screening log• In Scotland

- post a cover letter and PIS/Consent Form plus stamped return envelope

• In England – same approach applies but you will require R&D approval before

you can implement this and these are pending at this time


Patients who die prior to consent• We anticipate this in very few circumstances• Currently no approval process in place at this time and

under REC review• England – anticipate writing to relative >1 month after the

event; this is under review and will not be in place for the start of the trial

• Scotland – under review


Trial Participant Checklist (p.8 SH)• Screening Log• Consent – document in notes and 3 copies• Insert algorithm into medical and nursing notes and adjacent to blood prescription

chart• Inform member of the clinical team of enrolment• Inform Blood Bank if you have a flagging system• Record preferred contact number(s)• Post GP letter• Start completing CRFs 1 – 10b, 15 – 17• Contact GP surgery to check survival status – D28• Administer telephone follow-up (Forms 11a – 13f)• Complete End of Study form (Form 14)



Special considerations when consenting patients with AUGIB:

A first hand nursing perspective

Sian Davies – RN

11:30 – 12:15


Characteristics of patients who may present with AUGIB• Older patients• Patients with liver cirrhosis/alcoholic liver disease• Patients with gastrointestinal malignancy

(oesophageal/gastric/pancreatic)• Patients taking Antiplatelets/NSAIDS


Patients with liver cirrhosis• After a GI bleed, patient’s with cirrhosis can decompensate and

develop encephalopathy. This often resolves over 48-72 hours once treatment commenced

• In some situations encephalopathy is chronic, resulting in persistent fluctuating levels of confusion. Direct consent in this situation is often not achievable


Patients withdrawing from alcohol• Some patients (may or may not have cirrhosis) may be withdrawing

from alcohol• If withdrawal symptoms are adequately controlled, gaining consent

should be straightforward• If withdrawal symptoms are severe, e.g Delerium Tremens, consent

would need to be initially sought from a personal consultee/relative/welfare guardian

• Day 3-5 of admission is often the most challenging. It should be possible to re-approach the patient after this time


Patients with malignancy

• Under these circumstances there may be no issues with consenting the patient from a capacity perspective

• Patients may be taking high doses of Opioid medication which could effect their ability to consent

• Caution around time of approach would be advised after discussion

with medical/nursing team


Patients taking Antiplatelets/NSAIDS• Antiplatelets – likely to be older patient with co-morbidity. In this case

they could suffer with an acute confusional state. Consent would need to be sought from a personal consultee/relative/welfare guardian until confusion resolves

• NSAIDS – combination of younger and older patients. Most should be capable of consenting


Review of Case Report Forms

Vipul Jairath & Ana Mora

12:15 – 13:15


Review of CRFs• Tour through each CRF other than follow-up questionnaire

(11a – 13f) and SAE forms (16a&b & 17) which will be reviewed later in the day

• Open CRFs and Completion Guidance pages 16 – 42 of Study Handbook

• All CRFs are the same apart from the front page, page headers and the consent form 1b


Forms 1a&b, 2, 3 & 4 – ‘Batch 1’

These should be submitted together as the first batch

• Form 1a – Eligibility• Form 1b – Consent England and Scotland• Form 2 – Presenting Signs and Symptoms• Form 3 – First recorded Laboratory Data• Form 4 – Pre-existing Co-morbidities and Medication


Forms 5a – 10b, 15 – ‘Batch 2’These should be submitted together as the second batch

• Form 5a&b – Medication administered in Hospital• Form 6a&b – Hb Measurements and RBC Transfusion• Form 7 – Protocol Deviation Form• Form 8a&b – Endoscopy Record• Form 9 – Acute Transfusion Reactions• Form 10a&b – Clinical Outcomes during Hospital Admission• Form 15 – Additional Resource Use


Forms 11a – 14, 18 – ‘Batch 3’These should be submitted together as the third batch

• Forms 11a – 13f – Follow-up Questionnaire • Form 14 – End of Study Form• Form 18 – Investigator Declaration Form


Transmittal of CRFs• Order of transmittal

- Forms 1a – 4 at trial entry

- Forms 5a – 10b, 15 at Hospital Discharge

- Forms 11a – 14, 18 at end of study

• SAE transmittal forms

- 16a, 16b & 17 as they occur



Lunch

13:15-13:45


Alison Deary

Clinical Operations Manager

NHSBT

13:45-14:15

Investigator responsibilities and Safety reporting


Investigator Responsibilities

• These are divided into several areas:– Qualifications and agreements– Resources– Responsibilities to the Participant– Ethics and Governance– Record Keeping– Safety Reporting


Qualifications and Agreements

• GCP states that the investigator should be qualified by education, training and experience to assume responsibility for the proper conduct of the trial..– CV/GCP training certificate– Familiar with the protocol and the appropriate

use of the investigational product– Delegation of trial-related duties


Qualifications and Agreements

• Should be aware of, and comply with GCP and applicable regulatory requirements

• Should permit monitoring and audit by the sponsor and inspection by regulatory authority

• Should maintain a list of appropriately qualified persons to whom trial related duties are delegated


Resources

• Be able to demonstrate the potential to recruit the required number of suitable participants within the agreed recruitment period

• Have sufficient time• Have adequate number of qualified staff

and adequate facilities• Ensure all staff are adequately informed


Responsibilities to the Participant

• Medical care of the participants – make all trial related medical decisions

• Ensure adequate care for adverse events• Make a reasonable effort to ascertain reasons for

withdrawal from the trial• Ensure participant confidentiality respected at all

times• Ensure participant’s medical records reflects their

participation• Inform GP


Ethics and Governance

• Ensure have ethical and trust approval to conduct the study

• Conduct study according to current version of the protocol

• Document and explain any deviation from the protocol

• Not to implement any deviation from study without permission from sponsor (and REC) unless immediate safety concern


Ethics and Governance

• Obtain informed consent • Ensure using current version of information and

consent forms• Until consent obtained, no trial-related activity

may commence• Ensure a copy of information and consent form

are provided to participant/representative• Follow randomised trial treatment policy


Record keeping• Obtain informed consent and document this• Ensure data collected are consistent with source

documents• Collect, record and report all study data accurately ,

completely, legibly and in a timely manner• To sign the completed CRFs• To ensure all trial documentation is maintained

appropriately• To ensure essential documents are archived• To ensure annual reports are made to the R&D

department


Safety Reporting


Adverse Event Definitions

• An adverse event is defined as “Any untoward occurrence in a subject receiving treatment according to the protocol, including occurrences which are not necessarily caused by or related to administration of the research procedures”


Serious Adverse Events (SAE)

• Defined as any adverse event that– Results in death– Is life-threatening– Results in hospitalisation or prolongation of

existing hospitalisation– Results in persistent disability or incapacity

Do not confuse serious with severe


Expected or Unexpected?

• Section 9 of the protocol contains a list of “expected” SAEs

• Only unexpected SAEs – i.e. not on the list of “expected” SAEs - are subject to expedited notification to the CSU

• An unexpected related SAE is one that is judged to be possibly, probably or definitely related to the transfusion policy


Definitions of Imputability

Relationship Description

Possible There is some evidence to suggest a causal relationship, however the influence of other factors may have contributed to the event

Probable The evidence is clearly in favour of attributing the SAE to the transfusion policy

Definite There is conclusive evidence beyond reasonable doubt attributing the SAE to the transfusion policy


Expected SAEs which are clinical outcome measures

• Death• Further bleeding• Need for surgery or radiological intervention

to control bleeding• Any element of the composite endpoint of

thromboembolic and ischaemic events (MI, stroke, PE, DVT, acute kidney injury)

• Acute transfusion reaction


Other expected SAEs

• Multi-organ failure

• Congestive Cardiac Failure

• Respiratory complications

• Transient ischaemic attack

• Decompensated liver disease

• Need for paracentesis to drain ascites

• Gut infarction


Other expected SAEs

• Rise in serum Troponin I or E

• GI perforation or obstruction

• Post-operative complication

• Need for repeat endoscopy for any reason

• Non-acute transfusion reaction


Notification within one working day

• Any unexpected SAE

• Death

• Further bleeding

• Any element of the composite endpoint of thromboembolic and ischaemic events (MI, stoke, PE, DVT, acute kidney injury)


Reporting to IDMC

• When received at the CSU, the reports of the events listed will be sent to the IDMC and the CI

• Be prepared to answer any queries in a timely manner

• The IDMC will know which treatment regimen the site has been randomised to


When to collect SAEs

• Collect on all participants from enrolment to Study Day 28

• Include any that occur following discharge if before Day 28, in particular infection, further bleeding and thromboembolic/ischaemic events


Responsibilities -PI

• Ensure notification of all SAEs in the appropriate timeframe

• SAE forms must be completed by the PI, or, if a designate, counter-signed by the PI

• Initial report must contain at least patient identifier, name of event, date of occurrence and causality

• Further more detailed information can be provided later


Responsibilities - Sponsor

• The CI will review all reported SAEs and Clinical Outcomes.

• Any disagreement with regard to imputability will be recorded but the PI opinion cannot be over-ruled.

• Unexpected related SAEs will be reported to REC within 15 days


Form Completion

• Review of Forms 16a&b, 17

• SAE transmittal



Case-Study 1• 68 year old female admitted with UGIB and found to have a large

ulcer at endoscopy which is treated. Has further bleeding 72 hours later and a repeat endoscopy and therapy. Discharged home 5 days later uneventfully.

• How many SAEs in this scenario?• Are they expected or unexpected?• Within what timeframe should they be notified to the CSU?


Case-Study 1 Answer• 68 year old female admitted with UGIB and found to have a large

ulcer at endoscopy which is treated. Has further bleeding 72 hours later and a repeat endoscopy and therapy. Discharged home 5 days later uneventfully.

• How many SAEs in this scenario? - One• Are they expected or unexpected? Expected• Within what timeframe should they be notified to the CSU? Within

1 working day


Case-Study 2 • 45 year old female with alcoholic liver disease admitted with a

variceal bleed. Varices successfully banded at endoscopy but she was combative during the procedure and it was prolonged. She then developed an aspiration pneumonia requiring antibiotics. She was discharged without further complications

• How many SAE’s are there in this scenario?• Are they expected or unexpected?• Within what timeframe should they be notified to the CSU?


Case-Study 2 Answer • 45 year old female with alcoholic liver disease admitted with a

variceal bleed. Varices successfully banded at endoscopy but she was combative during the procedure and it was prolonged. She then developed an aspiration pneumonia requiring antibiotics. She was discharged without further complications

• How many SAE’s are there in this scenario? One• Are they expected or unexpected? Expected• Within what timeframe should they be notified to the CSU? Within

one week


Case-Study 3• 54 year old male has a successfully treated duodenal ulcer at

endoscopy. He has further bleeding and then goes straight to radiological embolisation. He has further bleeding and then has surgery. He is due for discharge 10 days later but develops a wound infection and is kept in for a further 4 days for antibiotics.



Case-Study 3 Answer• 54 year old male has a successfully treated duodenal ulcer at

endoscopy. He has further bleeding and then goes straight to radiological embolisation. He has further bleeding and then has surgery. He is due for discharge 10 days later but develops a wound infection and is kept in for a further 4 days for antibiotics.

• How many SAE’s are there in this scenario? Four• Are they expected or unexpected? All expected• Within what timeframe should they be notified to the CSU?

Further bleeding within one working day; Embolisation/surgery/wound infection within one week


Case-Study 4• 78 year old man previous heart attacks and “mini-strokes” taking

life-long aspirin and dypiridamole. Found to have a gastric cancer at endoscopy. Anti-platelets are withheld and he develops a stroke with a dense right hemi-paresis.



Case-Study 4 Answer• 78 year old man previous heart attacks and “mini-strokes” taking

life-long aspirin and dypiridamole. Found to have a gastric cancer at endoscopy. Anti-platelets are withheld and he develops a stroke with a dense right hemi-paresis.

• How many SAE’s are there in this scenario? One• Are they expected or unexpected? Expected• Within what timeframe should they be notified to the CSU? Within

one working day


Case-Study 5• A 32 year old alcoholic went on a binge and was vomiting for 24

hours. He was found to have a Mallory-Weiss tear at endoscopy. His alcohol withdrawal symptoms were severe and he fell on the ward whilst mobilising to the toilet, banged his head and required 4 stitches.

• How many SAE’s are there in this scenario? • Are they expected or unexpected?• Within what timeframe should they be notified to the CSU?


Case-Study 5 Answer• A 32 year old alcoholic went on a binge and was vomiting for 24

hours. He was found to have a Mallory-Weiss tear et endoscopy. His alcohol withdrawal symptoms were severe and he fell on the ward whilst mobilising to the toilet, banged his head and required 4 stitches.

• How many SAE’s are there in this scenario? None!• This is an adverse event, not a serious adverse event. Adverse

events do not need reporting.


Elizabeth Stokes

Researcher

Health Economics Research Centre-University of Oxford

14:15-14:40

Health Economics Evaluations: What are they and what will we do in TRIGGER


Overview of session

1. Introduction to health economic evaluation– Rationale for it– What it is– How it is conducted and results interpreted

2. Health economics in TRIGGER

3. Data collection forms in TRIGGER


What is health economic evaluation?

• Premise: scarce (health care) resources• Aim: to maximise health gain with the resources

available• Method: compare costs and outcomes of two or

more interventions• Definition: “The comparative analysis of alternative

courses of action in terms of both their costs and their consequences” (Drummond et al. 2005)

• Explicit way of making choices


Types of health economic evaluation

Type Costs Outcomes

Cost-effectiveness analysis

Monetary units

Natural units e.g. cases detected, life years gained, episode-free day

Cost-utility analysis Monetary units

Quality Adjusted Life Years (QALYs)

Cost-benefit analysis Monetary units

Monetary units


Quality Adjusted Life Years (QALYs)

• Composite endpoint combining:1. Quantity of life (survival)2. Health related quality of life (HRQoL) measured on a 0

(dead) to 1 (full health) scale

Patient 1 = 0.8 + 0.6 = 1.4 QALYs

Patient 2 = 0.4 + 0.15 = 0.55 QALYs

QALY difference = 0.85 QALYs

Hea

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rel

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qu

alit

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f lif

e

0

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Survival time (years)21

0.6

0.40.3

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Cost-effectiveness framework

Intervention 1

Cost 1

Effectiveness 1 Effectiveness 2

Incremental cost-effectiveness ratio (ICER) =

Cost 1 - Cost 2

Effect 1 – Effect 2

Cost 2

Intervention 2


Incremental Costs and Outcomes: Example – chronic low back pain

Surgery

£7,830

1.004 QALYs

Rehabilitation

£4,526

0.936 QALYs

£7,830 - £4,526

1.004 QALY - 0.936 QALY = £48,588 per QALY

Rivero-Arias et al. BMJ 2005; 330(7502): 1239


Health Economics in TRIGGER

• Feasibility trial• Feasibility of gathering data required in a cost-effectiveness

analysis to inform data collection for the phase III trial– Pilot resource use data collection forms– Assess feasibility of collecting inpatient data from routine

hospital information systems, post-discharge data from patients by telephone, and HRQoL data using the EQ-5D

• Feasibility of using these data within a cost-effectiveness model to identify parameters with the potential to be key drivers of cost-effectiveness– These will require detailed measurement in phase III trial


Costs I • Perspective of National Health Service, patients / their carers,

and employers• Data will be collected from each trial patient on inpatient

health care resource use, including:– RBCs and other blood products transfused– Endoscopies– Time spent in ICU, HDU, general wards– Adverse events– Discharge / transfer to another hospital / facility

• Data collection integrated into the CRFs


Costs II

• Primary and secondary health care resource use post discharge will be captured via a telephone contact with patients at 28 days

• Also in this questionnaire patients will be asked about– any unpaid care received from relatives or friends and any

costs they have incurred– and about return to paid employment

• Unit costs from a variety of sources will be used to cost this resource use data.


Effects I

• Measured using Quality Adjusted Life Years (QALYs)• EuroQol EQ-5D questionnaire used to classify a person’s

health state by telephone at day 28• EQ-5D asks respondents whether they have no problems,

some problems or extreme problems with

• Responses are converted into a single index value on the scale 0 to 1, dead to perfect health, using an accompanying scoring tariff

- Mobility - Self-care

- Usual activities - Pain / discomfort

- Anxiety / depression


Effects II

• Survival data available for each trial patient to 28 days

• HRQoL assessed at 28 days using the EQ-5D questionnaire

• No baseline values due to unplanned nature of the condition

• Quality and quantity of life combined and used as inputs into decision model


Key drivers of cost-effectiveness

• Trial data will allow exploration of mean costs and QALYs per patient for each trial arm to 28 days

• Feasibility trial, so the time horizon is short

• Model acute upper GI bleeding (AUGIB) patient pathway & associated costs and outcomes beyond 28 days to identify parameters with the potential to be key drivers of cost-effectiveness– Use trial data, and other sources such as audit of AUGIB


Summary

This feasibility trial will allow us to

• Determine workable data collection methods for resource use, unit costs and outcomes (quality of life) for the phase III trial

• Identify key parameters for focussed measurement in the phase III trial


Data Collection Forms in TRIGGER

• All data collection is integrated into the CRFs

• Form 15 - length of stay around various departments and wards of hospital

• Follow up telephone contact at day 28– Form 12a – EQ-5D– Forms 13a-f – resource use

• GP verification of patient reported events


Tania Reed

Clinical Data Manager

NHSBT

14:40-14:55

The Do’s and Dont’s of CRF Completion


All clinical trial information should be recorded, handled, and stored in a way

that allows its accurate reporting, interpretation, and verification.

(Principle 11 - Records, WHO Good Clinical Research Practice)


The Importance of Data Quality and Integrity in Clinical Trials

• Data quality refers to the extent to which data is accurate, legible, complete, original, and attributable to the person generating it

• Data integrity refers to the extent to which data is credible, consistent and verifiable

• It is important that we maximise data quality and integrity when recording information on CRFs and resolving data queries, in the TRIGGER trial


Objectives of Clinical Data Management

• To ensure the quality and integrity of clinical trial data

• To ensure that trial data is collected in accordance with the clinical trial protocol

• To provide a data set that is of sufficient quality for statistical analysis, interpretation and reporting

• To work in accordance with ICH-GCP principles


Things to remember when recording information on CRFs:

Write in black ink If you make an error put a make sure your original

entry is visible, write your correction alongside, sign and date

Do not scribble over your original entry Do not change numbers by writing over them Do not use correction fluid

Do not destroy CRFs if you make an error(s)



If you make an error effecting the whole CRF page, put a line across the page, write ‘In error’, sign and date. Make sure the original entry is visible. Keep the copy in the patients file

Write clearly, make sure it is legibleMake sure that your writing is readable on fax or

scanned copies



If data is unknown or not recorded write ‘UNK’ or ‘NR’ in boxes or write ‘UNKNOWN’ or ‘NOT RECORDED', alongside, sign and date

When transcribing from source documents e.g. patient records, laboratory records, double check what you have written

Include leading zeros e.g. write 8.23 as 08.23Complete decimal places if boxes are provided

for them, if no decimal place enter zero e.g. 4 should be 4.0



Use dd-mm-yyyy format for dates, if there are no boxes provided

Use hh:mm format for timesDouble check your calculations before recording

on CRF e.g. Blatchford score, Rockall score If you add any additional comments to CRFs

remember to sign and date each one If sending any additional pages or documents

with CRFs - include the patient’s trial no, date of birth and initials on each page


Sending CRFs to the CSU:Check that all questions on the CRF have been

completed Check that the patient’s trial no, initials and date of

birth are correct and the same on all CRF pages Check that you have printed your name, signed

and dated at the bottom of all CRF pagesDo not write any patient identifiable information on

any documents to be sent to the CSU


Sending CRFs to the CSU:Always use a CRF transmittal formSend copies of the Screening Log every MondaySend CRFs in 3 batches for each patient

(1) Trial entry (Forms 1a – 4) (2) Discharge or Day 28 (Forms 5a – 10b)(3) End of study/Follow up (Forms 11a – 14 & 18)

Always complete a safety event transmittal form when sending Serious Adverse Events and Serious Transfusion Related Adverse Event CRFs


Sending CRFs to the CSU:

The preferred method of sending the CRFs is by scanning and emailing or by post

Email or fax SAE forms

At the CSU the Trial data manager will send an email to confirm that the CRF pages or Screening log pages have been received


Resolving Data Queries:

Data Queries are usually raised due to:-

• Missing data

• Missing CRF pages

• Data anomalies

• The Trial Data Manager will send an email to site staff, with details of the query


Resolving Data Queries:• Data clarification forms are generated by the

database during data entry, and will be attached to the query email as a pdf

• Data clarification form specifies the site, patient, form, question and the actual query text

• Site staff should clarify the discrepancy, provide missing data or missing CRF(s)

• Record the amended or missing data on the CRF• Write the requested information in the ‘Answer’

section below the query text


Resolving Data Queries:

• If no data clarification form send an email back responding to the query and attach or send a copy of the amended CRF

• Print your name, sign and date each data clarification form

• Send a copy of the amended CRF and/or missing CRF pages to CSU

• Keep the original amended CRF(s), email and data clarification form in the site file


Summary• Discussed best practice when completing

CRFs and resolving data queries • The aim of following this best practice is to

maximise data quality and integrity during the TRIGGER trial

• Reduce the number of data queries sent to you - thereby reducing your workload!


Exercise in pairs

• How many discrepancies can you find on this CRF - Haemoglobin Measurements and RBC Transfusion Record – Form 6a?








Tea

14:55-15:10


Ana Mora

15:10-15:20

Trial Site File


Investigator Site File •An Investigator Site File (ISF) contains essential documents on the trial and forms/documents used by the individual site

• The responsibility to hold and maintain an up to date ISF, including all superseded documents, is with the Principal Investigator at each participating site

•When new or amended trial documents become available (e.g. protocols, PIS, reports, etc), it is the responsibility of the Trial coordinating team to provide copies to the Investigator Site together with relevant Ethics approvals






Site Initiation/Activation

Before enrolling patients each site must ensure they have:

An Investigator Site file

Written permission from the site R&D

A signed study site agreement

A signed delegation log.


Vipul Jairath, Ana Mora, Elizabeth Stokes, Tania Reed, Alison Deary

15:20-16:20

Open Forum for Q’s&A’s


Lower Gastrointestinal Bleeding• Pragmatic study – patient will have been included on the

basis of a suspected UGIB which later turns out to be a LGIB.

• Stop completing any further CRFs and proceed to end of study form (Form 14) and indicate the patient did NOT complete the study as planned with the reason.

• Do not complete Day 28 follow up questionnaire• Do return all completed CRFs and end of study form


Co-Enrolment Guidelines• The only competing study we are currently aware of is the

early TIPSS study in Edinburgh and Glasgow.• Patients can be co-enrolled to this study.• Any future competing studies will be considered on a case

by case level after discussion with each trial steering committee.


Vipul Jairath & Ana Mora

16:20-16:30

Trial Website and Close

http://www.nhsbt.nhs.uk/trigger/


Documents

NHSBT/MRC Clinical Studies Unit TRIGGER Trial: Transfusion in Gastrointestinal Bleeding Presented by Dr Vipul Jairath Research Fellow and Honorary SpR