Serum Blood Clotting Changes During Blood Sampling Via Non-luer One-way Filter Valve Intravenous Needle: Implication on the Epidural Blood Patch Procedure
Phase: NA
Conditions: Post-Dural Puncture Headache, Low Pressure Headache
Sponsor: University Hospitals, Leicester

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Serum blood clotting changes during blood sampling via 
non-luer one-way filter valve intravenous needle:  
Implication on the epidural blood patch procedure 
 
Sponsor Reference No: This will be assigned by the Research Office on submission for initial 
Sponsor review  
Ethics Ref: Insert (NB only available once booked into Ethics – do not book into Ethics until 
authorised by the Sponsor) 
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Chief Investigator: 
Dr Paul Sharpe 
Investigators:  
Dr Asif Mahmood 
Sponsor:  
University Hospitals of Leicester NHS Trust 
Funder: 
Obstetric Anaesthetists’ Association Grant 
Signatures:  
The approved protocol should be signed by author(s) and/or 
person(s) authorised to sign the protocol 
 
 
 
  
Confidentiality Statement 
All information contained within this protocol is regarded as, and must be kept confidential.  No 
part of it may be disclosed by any Receiving Party to any Third Party, at any time, or in any form 
without the express written permission from the Chief Author/Investigator and / or Sponsor. 
 
 

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Authors 
 
Dr Asif Mahmood ST5 Anaesthesia Leicester Royal Infirmary 
Dr Paul Sharpe Consultant Anaesthesia Leicester Royal Infirmary 

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Signature Page 
 
Chief Investigator Name: 
Dr Paul Sharpe______________________ 
Chief Investigator signature: 
_________________________________ 
Date: 1/1/16____________________________________________ 
  
 
Sponsor Representative Name: 
Carolyn Maloney_________________ 
Sponsor Representative signature: _____________________________ 
Date: 
1/1/16____________________ 
  
 
Principal Investigator Name: Dr Asif Mahmood __________________ 
Principal Investigator signature: ________________________________ 
Date: 
1/1/16 __________________________________________ 
  
(In 
cases 
of 
Multi-centre 
studies, 
this 
must 
be 
replicated 
for 
each 
site)

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TABLE OF CONTENTS 
To update table of contents (TOC), hover cursor over the top left hand corner until the whole TOC 
highlights.  Press the ‘F9’ button.  Choose ‘update entire table’.   
1. 
AMENDMENT HISTORY ........................................................................................................... 7 
2. 
SYNOPSIS ................................................................................................................................. 8 
3. 
ABBREVIATIONS ...................................................................................................................... 9 
4. 
BACKGROUND AND RATIONALE .......................................................................................... 10 
5. 
OBJECTIVES ........................................................................................................................... 11 
5.1 
Primary Objectives ............................................................................................................. 11 
5.2 
Secondary Objectives ........................................................................................................ 11 
6. 
STUDY DESIGN ...................................................................................................................... 12 
6.1 
Summary of Trial Design ................................................................................................... 12 
6.2 
Primary and Secondary Endpoints/Outcome Measures .................................................... 12 
7. 
TRIAL PARTICIPANTS ............................................................................................................ 13 
7.1 
Overall Description of Trial Participants ............................................................................. 13 
7.2 
Inclusion Criteria ................................................................................................................ 13 
7.3 
Exclusion Criteria ............................................................................................................... 13 
8. 
STUDY PROCEDURES ........................................................................................................... 14 
8.1 
Informed Consent .............................................................................................................. 14 
8.2 
Screening and Eligibility Assessment ................................................................................ 14 
8.3 
Baseline Assessments ....................................................................................................... 14 
8.4 
Randomisation and Codebreaking (if applicable) .............................................................. 14 
8.5 
Subsequent Assessments ................................................................................................. 15 
8.6  
Definition of End of Trial ................................................................................................... 15 
8.7 
Discontinuation/Withdrawal of Participants from Study Treatment .................................... 15 
8.8 
Source Data ....................................................................................................................... 15 
9. 
TREATMENT OF TRIAL PARTICIPANTS ............................................................................... 16 
9.1 
Description of Study Treatment ......................................................................................... 16 

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9.2 
Storage of Study Equipment or Related apparatus ........................................................... 16 
10. SAFETY REPORTING ............................................................................................................. 17 
10.1 Definitions ......................................................................................................................... 17 
10.2 Reporting Procedures for All Adverse Events .................................................................. 18 
10.3 Reporting Procedures for Serious Adverse Events .......................................................... 18 
11. STATISTICS ............................................................................................................................. 19 
11.1 Description of Statistical Methods ..................................................................................... 19 
11.2 The Number of Participants .............................................................................................. 19 
11.3 The Level of Statistical Significance ................................................................................. 19 
11.4 Criteria for the Termination of the Trial. ............................................................................ 19 
11.5 Procedure for Accounting for Missing, Unused, and Spurious Data. ................................ 19 
11.6 Procedures for Reporting any Deviation(s) from the Original Statistical Plan .................. 19 
11.7 Inclusion in Analysis .......................................................................................................... 19 
12. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ........................................................... 20 
13. QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES ..................................... 21 
14. CODES OF PRACTICE AND REGULATIONS ........................................................................ 22 
14.1 Ethics ................................................................................................................................ 22 
14.2 Sponsor Standard Operating Procedures ......................................................................... 22 
14.3 Declaration of Helsinki ...................................................................................................... 22 
14.4 ICH Guidelines for Good Clinical Practice ........................................................................ 22 
14.5 Approvals .......................................................................................................................... 22 
14.6 Participant Confidentiality ................................................................................................. 22 
14.7  Other Ethical Considerations ............................................................................................ 22 
15. DATA HANDLING AND RECORD KEEPING .......................................................................... 23 
16. STUDY GOVERNANCE ........................................................................................................... 24 
16.1 Trial Steering Committee (TSC) ........................................................................................ 24 
16.2 Data Safety Monitoring Committee (DSMC) ..................................................................... 24 
17. FINANCING AND INSURANCE ............................................................................................... 25 

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18. PUBLICATION POLICY ........................................................................................................... 26 
19. REFERENCES ......................................................................................................................... 27 
20. APPENDIX A: STUDY FLOWCHART ...................................................................................... 28 
 
 
 

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1. 
AMENDMENT HISTORY 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes 
made 
1 
2 
1/1/17 
Paul Sharpe and Asif 
Mahmood 
APPENDIX A: STUDY 
FLOWCHART 
Time line edited to 
allow more time to 
recruit. 
 
List details of all protocol amendments here whenever a new version of the protocol is produced. 

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2. 
SYNOPSIS 
 
Study Title 
Serum blood clotting changes during blood sampling via non-luer 
one-way filter valve intravenous needle: Implication on the 
epidural blood patch procedure 
Internal ref. no. 
 
 
 
Trial Design 
Observational Study 
Trial Participants 
Healthy post natal and non-pregnant participants 
Planned Sample Size 
Total 50 participants 
Follow-up duration 
n/a 
Planned Trial Period 
12 months 
Primary Objective 
Investigate clotting profile changes due to the use of the new non-luer 
one-way valve filter needle compared to a standard hypodermic needle.  
Secondary 
Objectives 
n/a 
Primary Endpoint 
Analysis of blood via near patient TEG clotting analysis 

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3. 
ABBREVIATIONS 
AE 
Adverse event 
AR  
Adverse reaction 
CI 
Chief Investigator 
CRA 
Clinical Research Associate (Monitor) 
CRF 
 
Case Report Form 
CRO  
Contract Research Organisation 
CT 
 
Clinical Trials 
EC 
 
Ethics Committee (see REC) 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
GTAC 
Gene Therapy Advisory Committee 
ICF 
Informed Consent Form 
NHS 
National Health Service 
NRES 
National Research Ethics Service  
PI 
Principal Investigator 
PIL/S 
Participant/ Patient Information Leaflet/Sheet 
R&D / R&I 
NHS Trust Research &Development / Innovation Department 
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event 
SAR 
Serious Adverse Reaction 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TMF 
Trial Master File 
 
 

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4. 
BACKGROUND AND RATIONALE 
 
Patient safety agencies such as the National Patient Safety Agency (NPSA) and European Medicines 
Agency recommend adoption of equipment that prevents wrong route drug administration1.  For example 
medicine intended for the intravenous route should not be possible to be given via the epidural route, hence 
limiting potentially catastrophic complications associated with human error2. However,the epidural blood 
patch requires equipment that connects to the intravenous and epidural route, as blood is taken from a 
patient’s vein and then it is injected into the patient’s epidural space for therapeutic affect.  Hence equipment 
is required that allows blood aspiration from the patient but does not have the potential to inject into the 
patient hence complying with patient safety agency recommendations.  Aspirating blood from the patient via 
a non-Luer one-way filter valve has the theoretical potential of activating the clotting cascade.  If this 
occurred it could reduce the time the clinician has to utilise the blood before it clots in the syringe. Changes 
in clotting characteristics also has unknown implications when injected into the epidural space with regards 
to the therapeutic effect of the procedure. 
 
The epidural blood patch is mainly used in obstetric anaesthesia in the treatment of dural puncture 
headaches, however it is also used to treat conditions such as spontaneous intracranial hypotension, hence 
this study involves post natal and non-pregnant populations.  This study requires blood to be taken from the 
study participants via a venepuncture.  This will require 12mls of blood to be taken from the patent via a 
standard 21G hypodermic needle and also 2mls of blood via the new 21G non-Luer one-way filter valve 
needle.  The blood will undergo clotting profile testing.  The implications for study subjects would be two 
venepunctures and a total of 14mls of blood taken.  The post natal population would only require one 
additional venepuncture with the new one-way valve needle as they would already be having bloods taken 
for their day 2 post elective cesarean section bloods, an additional 9ml of blood only. 

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5. 
OBJECTIVES 
 
5.1 
Primary Objectives 
 
We aim to determine if there is a difference in the clotting profile values from blood extracted 
with a normal 21G hypodermic needle vs the new 21G non-Luer one-way filter valve needle. 
 
5.2 
Secondary Objectives 
 
Not Applicable 
 
 

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6. 
STUDY DESIGN 
6.1 
Summary of Trial Design 
 
This study will be an observational study.  The pregnant participants will be recruited from 
the elective pre-operative caesarean clinic and have their bloods taken on day 2 post natal 
after their elective caesarean section during their rountine full blood count testing.  
 
The healthy non-pregnant participants will be recruited via posters in the University Hospitals 
of Leicester. 
 
The blood taken via the two different needles will be analysed via near patient testing with 
Thromboelastography (TEG) analysis and this will be the end of their study participation.  
 
We will alternate between patients with regards to which needle will be used first during 
phlebotomy (ie hypodermic needle vs new non-Luer one-way valve filter needle).  The 
punctures will be from separate veins for each of the two needles. 
 
6.2 
Primary and Secondary Endpoints/Outcome Measures 
 
Blood taken by each needle from the participants will undergo near patient TEG analysis and 
we will be investigating the difference in R-Time, the time for a clot to form.  The blood will 
also be sent for laboratory full blood count and clotting profile testing.  
 
 

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7. 
TRIAL PARTICIPANTS 
7.1 
Overall Description of Trial Participants 
 
We will enrol pregnant participants who are due to have an elective caesarean section and 
have no medical condition.  Non-pregnant participants will be healthy volunteers.  
 
 
7.2 
Inclusion Criteria 
 
Participant is willing and able to give informed consent for participation in the study. 
Male (in the volunteer subgroup) or Female. 
Aged 18 years or above.   
Within first 2 days post natal for post natal arm of study 
Healthy participants must be in good health.  
Able (in the Investigators opinion) and willing to comply with all study requirements. 
Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of 
participation in the study. 
7.3 
Exclusion Criteria 
The participant may not enter the study if ANY of the following apply: 
Any medical condition 
Post natal women with haemorrhage greater than 1L 
Less than 12 hours post prophylactic dalteparin 
Any clotting abnormality 
On any medication including herbal medication (vitamins taken in pregnancy are acceptable) 
Age less than 18 years at recruitment 
Adults who are not capable of giving valid consent 
Adults with learning disabilities/ difficulties 
Adults in emergency situations 
Unable to speak or read English 
Prisoners 
Adults unable to consent for themselves 
Any person considered to have a particularly dependent relationship with investigators 
Any others deemed to belong to a vulnerable group. 
Any other significant disease or disorder which, in the opinion of the Investigator, may either 
put the participants at risk because of participation in the study, or may influence the result of 
the study, or the participant’s ability to participate in the study. 
Participants who have participated in another research study involving an investigational 
product in the past 12 weeks 
 

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8. 
STUDY PROCEDURES 
 
8.1 
Informed Consent 
The participant must personally sign and date the latest approved version of the informed 
consent form before any study specific procedures are performed. 
Written and verbal versions of the participant information and Informed consent will be 
presented to the participants detailing no less than: the exact nature of the study; the 
implications and constraints of the protocol; the known side effects and any risks involved in 
taking part.  It will be clearly stated that the participant is free to withdraw from the study at 
any time for any reason without prejudice to future care, and with no obligation to give the 
reason for withdrawal. 
 
The participant will be allowed as much time as wished to consider the information, and the 
opportunity to question the Investigator, their GP or other independent parties to decide 
whether they will participate in the study.  Written Informed Consent will then be obtained by 
means of participant dated signature and dated signature of the person who presented and 
obtained the informed consent. The person who obtained the consent must be suitably 
qualified and experienced, and have been authorised to do so by the Chief/Principal 
Investigator as detailed on the Delegation of Authority and Signature log for the study. The 
original signed form will be retained at the study site within the Trial Master File (TMF) or 
Investigator Site File (ISF). A copy of the signed Informed Consent will be given to 
participants and a copy retained in the participant medical notes.   
 
8.2 
Screening and Eligibility Assessment 
 
Pregnant participants will be identified in preoperative clinics for elective caesarean sections.  
Medical notes will be screened to recruit healthy volunteers. 
 
Non-pregnant healthy participnats will be recruited via poster advertisement placed within 
University Hospitals of Leicester.   
 
 
Demographics 
The age, gender, days post natal for pregnant women and blood loss will be recorded.  
 
 
Medical History 
 
We would only recruit participants who do not have any medical conditions. 
 
 
Concomitant Medication  
All over-the-counter or prescription medication, vitamins, and/or herbal supplements will be 
recorded on CRFs.  
  
 
 
 
 
 
8.3 
Baseline Assessments 
 
No baseline assessments are required for this research project. 
 
8.4 
Randomisation and Codebreaking (if applicable) 
 
All participants will have a paired set of bloods taken with a hypodermic needle and the new 
on way valve filter needle.  We will alternate which needle is used first between patients. 

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8.5 
Subsequent Assessments 
Each participant will have blood taken via a normal hypodermic needle and a new non luer 
one-way valve filter needle.  The blood taken with each needle will undergo near patient TEG 
testing.  This will represent the end of the participants research participation 
 
8.6  Definition of End of Trial 
The end of trial will be the completion of the 30th paired TEG test in the pregnant group and 
the 10th in the volunteer group. 
 
8.7 
Discontinuation/Withdrawal of Participants from Study Treatment 
Each participant has the right to withdraw from the study at any time.  In addition, the 
investigator may discontinue a participant from the study at any time if the investigator 
considers it necessary for any reason including:  
Ineligibility (either arising during the study or retrospective having been overlooked at 
screening) 
Significant protocol deviation 
Significant non-compliance with treatment regimen or study requirements 
An adverse event which requires discontinuation of the study or results in inability to 
continue to comply with study procedures 
Developing a medical condition 
Consent withdrawn 
Lost to follow up 
 
If participants are withdrawn from the study they will be replaced and data acquired from 
withdrawn participants will be destroyed.  The reason for withdrawal will be recorded in the 
CRF.   
If the participant is withdrawn due to an adverse event, the investigator will arrange for follow-
up visits or telephone calls until the adverse event has resolved or stabilised.   
 
8.8 
Source Data 
Source documents are original documents, data, and records from which participants’ CRF 
data are obtained.  These include, but are not limited to, hospital records (from which medical 
history and previous and concurrent medication may be summarised into the CRF), clinical 
and 
office 
charts, 
laboratory 
and 
pharmacy 
records, 
diaries, 
radiographs, 
and 
correspondence. 
CRF entries will be considered source data if the CRF is the site of the original recording 
(e.g., there is no other written or electronic record of data). In this study the CRF will be used 
as the source document to aid recruitment of participants from the preassessment elective 
caesarean section clinic. 
All documents will be stored safely in confidential conditions.  On all study-specific 
documents, other than the signed consent, the participant will be referred to by the study 
participant number/code, not by name. 
 
 

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9. 
TREATMENT OF TRIAL PARTICIPANTS 
9.1 
Description of Study Treatment  
Participant involvement in the study involves allowing phlebotomy to be taken with the two 
different needles. 
  
 
9.2 
Storage of Study Equipment or Related apparatus 
The new non-Luer one-way valve filter needles will be stored in the anesthetic office situated 
in the maternity unit at Leicester Royal Infirmary. 
 

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10. 
SAFETY REPORTING 
10.1 Definitions 
 
10.1.1 Adverse Event (AE) 
An AE or adverse experience is: 
Any untoward medical occurrence in a patient or clinical investigation participants, which 
does not necessarily have to have a causal relationship with this treatment. 
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom or disease temporally associated with the the study, whether or 
not considered related to the study. 
 
10.1.2 Adverse Reaction (AR) 
All untoward and unintended responses related to the study. 
All cases judged by either the reporting medically qualified professional or the sponsor as 
having a reasonable suspected causal relationship to the study qualify as adverse reactions.   
 
10.1.3 Severe Adverse Events 
To ensure no confusion or misunderstanding of the difference between the terms "serious" 
and "severe", which are not synonymous, the following note of clarification is provided: 
The term "severe" is often used to describe the intensity (severity) of a specific event (as in 
mild, moderate, or severe myocardial infarction); the event itself, however, may be of 
relatively minor medical significance (such as severe headache).  This is not the same as 
"serious," which is based on patient/event outcome or action criteria usually associated with 
events that pose a threat to a participant's life or functioning.  Seriousness (not severity) 
serves as a guide for defining regulatory reporting obligations. 
 
10.1.4 Serious Adverse Event or Serious Adverse Reaction 
A serious adverse event or reaction is any untoward medical occurrence that at any dose: 
• 
Results in death, 
• 
Is life-threatening, 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the 
participant was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. 
• 
Requires inpatient hospitalisation or prolongation of existing hospitalisation, 
• 
Results in persistent or significant disability/incapacity, or 
• 
Is a congenital anomaly/birth defect. 
• 
Other important medical events* 
*Other events that may not result in death, are not life threatening, or do not require 
hospitalisation, may be considered a serious adverse event when, based upon appropriate 
medical judgement, the event may jeopardise the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed above. 
 
10.1.5 Expected Serious Adverse Events/Reactions 
This study is not expected to cause any serious adverse events or reactions.  The main 
issues to note would be difficult phlebotomy which would be uncomfortable and phlebotomy 
can lead to brusing.  None of these would require reporting.   
 
10.1.6 Suspected Unexpected Serious Adverse Reactions 
A serious adverse reaction, the nature or severity of which is not consistent with the 
applicable product information  
 

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10.2 Reporting Procedures for All Adverse Events 
All AEs occurring during the study observed by the investigator or reported by the 
participant, whether or not attributed to study, will be recorded on the CRF.   
The following information will be recorded: description, date of onset and end date, severity, 
assessment of relatedness to study, other suspect device and action taken.  Follow-up 
information should be provided as necessary.  
AEs considered related to the study as judged by a medically qualified investigator or the 
sponsor will be followed until resolution or the event is considered stable.  All related AEs 
that result in a participant’s withdrawal from the study or are present at the end of the study, 
should be followed up until a satisfactory resolution occurs. 
Any abnormal results from the laboratory full blood count or clotting profile will be shared 
with the patient, the patients clinical team or GP in the case of the volunteer limb. 
It will be left to the investigator’s clinical judgment whether or not an AE is of sufficient 
severity to require the participant’s removal from treatment (see section 7.7).  A participant 
may also voluntarily withdraw from treatment due to what he or she perceives as an 
intolerable AE.  If either of these occurs, the participant must undergo an end of study 
assessment and be given appropriate care under medical supervision until symptoms cease 
or the condition becomes stable. 
The severity of events will be assessed on the following scale:  1 = mild, 2 = moderate, 3 = 
severe.   
The relationship of AEs to the study will be assessed by a medically qualified investigator.  
 
10.3 Reporting Procedures for Serious Adverse Events 
All SAEs, except those expected ones defined in section 10.1.5 that do not require 
immediate reporting (see 10.1.5), must be reported to the Sponsor within one working day of 
discovery or notification of the event.  The Sponsor will perform an initial check of the 
information and ensure that it is reviewed at the next R&I Management meeting.  All SAE 
information must be recorded on an SAE form and sent to the Sponsor using the appropriate 
reporting form and the contact details on there. Additional information received for a case 
(follow-up or corrections to the original case) needs to be detailed on a new SAE form which 
must be sent to the Sponsor using the appropriate reporting form and the contact details on 
there.  
The Sponsor will report all SUSARs to the Research Ethics Committee concerned. Fatal or 
life-threatening SUSARs must be reported within 7 days and all other SUSARs within 15 
days. The CI will inform all investigators concerned of relevant information about SUSARs 
that could adversely affect the safety of participants. 
In addition to the expedited reporting above, the CI shall submit once a year throughout the 
study or on request an Annual Report to the Ethics Committee which lists all SAEs / 
SUSARs that have occurred during the preceeding 12 months. 
 
 

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11. 
STATISTICS 
 
11.1 Description of Statistical Methods 
The primary outcome for this study is change in time to initiate clot formation, as measured by 
the R time using thromboelastography.  As subjects are to be exposed to both study limbs the 
data collected will be analysed using paired tests for statistical differences. The variation is 
different for non-pregnant and post natal subjects, therefore we have calculated sample size 
for each of the two study populations separately. As the sample size is small it is unlikely that 
the results will be normally distributed, therefore non-parametric test will be employed.  As the 
sample sizes are small we do not anticipate needing any interim analysis. There is no plan to 
compare non-pregnant and post natal groups, only the within group differnces. 
 
11.2 The Number of Participants 
We have used established reference ranges for TEG pqarameters in pregnant and non-
pregnant populations to allow us to calculate an estimated standard deviation of the difference 
in R times for paired data to inform our power calculation.  To see a 25% reduction in R time, 
with an alpha error of 5% and a beta error of 20% (power 80%) we require 10 non-pregnant 
subjects and 30 post natal participants. 
 
11.3 The Level of Statistical Significance 
 
 
Alpha error of 5%, beta error 20%, power 80% 
 
11.4 Criteria for the Termination of the Trial. 
The trial will be terminated when 10 non-pregnant volunteers and 30 post natal volunteers 
have completed the study protocol. 
 
11.5 Procedure for Accounting for Missing, Unused, and Spurious Data. 
The trial will be terminated once we have 40 complete data sets. There will be no unused 
data sets. Spurious data will be excluded from analysis and will require additional 
recruitment. 
 
11.6 Procedures for Reporting any Deviation(s) from the Original Statistical Plan 
We don’t anticipate any variation from our statistical plan, however this would be explained in 
the final report if required. 
 
11.7 Inclusion in Analysis 
All evaluable patient data will be analysed to a total of 10 non-pregnant and 30 post natal 
participants have completed the intervention arms of the study. 
 

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12. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
 
Direct access will be granted to authorised representatives from the sponsor, host institution and the 
regulatory authorities to permit trial-related monitoring, audits and inspections. 
 
 

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13. 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES 
 
The study will be conducted in accordance with the current approved protocol, ICH GCP, relevant 
regulations and standard operating procedures.  
 
Regular monitoring will be performed according to ICH GCP. Data will be evaluated for compliance 
with the protocol and accuracy in relation to source documents. Following written standard 
operating procedures, the monitors will verify that the clinical trial is conducted and data are 
generated, documented and reported in compliance with the protocol, GCP and the applicable 
regulatory requirements.  
 
 

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14. 
CODES OF PRACTICE AND REGULATIONS 
14.1 Ethics 
Describe ethical considerations relating to the trial. Include general and study specific ethics 
considerations. 
 
14.2 Sponsor Standard Operating Procedures 
All relevant Sponsor SOPs will be followed to ensure that this study complies with all 
relevant legislation and guidelines  
 
14.3 Declaration of Helsinki 
The Investigator will ensure that this study is conducted in full conformity with the current 
revision of the Declaration of Helsinki (last amended October 2000, with additional footnotes 
added 2002 and 2004). 
 
14.4 ICH Guidelines for Good Clinical Practice 
The Investigator will ensure that this study is conducted in full conformity with relevant 
regulations and with the ICH Guidelines for Good Clinical Practice (CPMP/ICH/135/95) July 
1996. 
 
14.5 Approvals  
Once Sponsor authorisation has been confirmed, the protocol, informed consent form, 
participant information sheet and any proposed advertising material will be submitted to an 
appropriate Research Ethics Committee (REC), regulatory authorities (MHRA in the UK), and 
host institution(s) for written approval.   
Once Sponsor authorisation has been confirmed, the Investigator will submit and, where 
necessary, obtain approval from the above parties for all substantial amendments to the 
original approved documents.    
 
14.6 Participant Confidentiality 
The trial staff will ensure that the participants’ anonymity is maintained.  The participants will 
be identified only by initials and a participants ID number on the CRF and any electronic 
database.  All documents will be stored securely and only accessible by trial staff and 
authorised personnel. The study will comply with the Data Protection Act which requires data 
to be anonymised as soon as it is practical to do so.   
 
14.7  Other Ethical Considerations 
Not Applicable 
 

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15. 
DATA HANDLING AND RECORD KEEPING 
Describe method of data entry/management 
 
All study data will be entered on to SPSS version22 for Mac OS. 
The participants will be identified by a study specific participants number in a database.  The name and any 
other identifying detail will NOT be included in any study data electronic file.  
 
 

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16. 
STUDY GOVERNANCE 
16.1 Trial Steering Committee (TSC) 
The Trial Steering Committee will include Dr Paul Sharpe and Dr Asif Mahmood.  They will 
meet on multiple occasions throughout the course of the study.  A minimum of once every 4 
months. 
 
16.2 Data Safety Monitoring Committee (DSMC) 
The Data Safety Monitoring Committee will include Dr Paul Sharpe and Dr Asif Mahmood.  
They will meet on multiple occasions throughout the course of the study.  A minimum of once 
every 4 months. 
 
 

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17. 
FINANCING AND INSURANCE 
 
 
Research Costs – We will be applying for a Obstetric Anaesthetists’ Association Grant 
Cost of single tests: FBC: £6.66, INR/APTT: £7.88, Fibrinogen: £7.94, Thromboelastography: £8.20 
TEG Quality Control Check: £16.50 max 4 required (Total cost £66) 
Administration fee for laboratory: £200 
Pregnant Participants: 38 INR/APTT (£299.44) and 38 fibrinogen: (£301.72) 
Post Natal Participants: 12 FBC (£79.92), 12 INR/APTT (£94.56), 12 fibrinogen (£95.28) 
Total 100 Thromboelastography (£820) 
Total Cost: £1956.92 
The equipment (one-way non-luer filter valve needle) will be provided free of charge by Intervene, 
the company that produces them.  
 
• 
NHS Treatment Costs – not applicable 
• 
NHS Support Costs – not applicable 
 

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18. 
PUBLICATION POLICY 
Any publication will include authors Dr Asif Mahmood and Dr Paul Sharpe.  We will acknowledge 
the funding acquired from an Obstetric Anaesthetists’ Association Grant.  The results of the study 
will be disseminated to publications aimed at obstetric anaesthesia.  The results will be presented 
to the manufacturers of the new non-Luer one-way filter needle, ‘Intervene’. 
 
 

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19. 
REFERENCES 
(1) Recommendations to prevent administration errors with Velcade (bortezomib). EMA ⁄ 34910 ⁄ 2012. 
European Medicines Agency. http://www.ema.europa.eu/docs/en_GB/docu- 
ment_library/Medicine_QA/2012/01/WC500120701.pdf (accessed 10 ⁄ 10 ⁄ 2015). 
(2) National Patient Safety Agency Patient Safety Alert. Safer spinal, epidural and regional anaesthesia 
devices – Part A. October 2009. http://www.nrls.npsa.nhs.uk/resources/patient-safety- topics/medical-
device-equipment/?entryid45=94529 (accessed 10⁄10⁄2015).  
 

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20. 
APPENDIX A: STUDY FLOWCHART 
 
 
Tasks 
Duration 
 Sept 2016 
to 
Dec 2017 
Jan 2017 
to 
August 
2017 
Jan 2017 
To 
August 2017 
September 
2017 
to 
October 2017 
 
Setting up project, ethics 
approval, liaising with recruiting 
centres 
 
4 months 
 
 
 
 
 
Identification and recruitment  
 
8 months 
 
 
 
 
 
Phlebotomy and TEG analysis, 
data collection and data 
analysis 
 
 
8 months 
 
 
 
 
 
Paper preparation and 
presentation of the findings 
 
2 months