Sponsor Reference Number:
Date and Version No:
Information on Clinical Investigation Plan (CIP) Template
This template has been designed primarily for device clinical investigations in accordance with ISO 14155:2011 guidelines. It has been specifically adapted for non-commercially sponsored studies.
The template is available for use by all investigators who are carrying out device clinical investigations sponsored by NUH NHS
Trust.
All advisory text and quotations from ICH GCP are highlighted in yellow. These should all be deleted before finalising the document.
All sample text is in ‘basic text’ style. This text of course will be altered or deleted as required while you produce the draft.
Repetition of information throughout the CIP is not necessary; it may be useful to cross-reference other sections of the CIP to avoid repetition.
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insert full title including brief reference to the design, disease or condition being studied, and primary objective
Sponsor
Funder
Funding Reference
Number
Chief Investigator
Eudract Number
Nottingham University Hospitals NHS Trust
Insert name of funder
Insert funding reference
Insert name of CI
Insert Eudract number
ISRCTN Number Insert ISRCTN number
REC Reference Number Insert REC reference number
Insert R&I number Sponsor Reference
Number
Version Number and
Date
Insert version number and date
Confidentiality Statement
This document contains confidential information that must not be disclosed to anyone other than the Sponsor, the Investigator Team, host NHS Trust (s), regulatory authorities, and members of the
Research Ethics Committee.
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Chief Investigator
Name:
Title:
Signature:
Date:
Principal Investigator
Name:
Title:
Signature:
Date:
Site:
Sponsor
Name:
Title:
Signature:
Date:
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Insert
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Date and Version No:
Chief Investigator Co Investigators (may not be
Name:
Address:
Telephone:
Email:
Statistician
Name:
Address:
Telephone:
Email: applicable, insert additional sections as appropriate)
Name:
Address:
Telephone:
Email:
Clinical investigation Management
Name:
Address:
Telephone:
Email:
(may not be applicable)
For general queries, supply of clinical investigation documentation, and collection of data, please contact:
Clinical investigation
Coordinator:
Address:
Telephone:
Fax:
Email:
Clinical queries should be directed to xxx who will direct the query to the appropriate person
Nottingham University Hospitals NHS Trust is the main research sponsor for this clinical investigation. For further information regarding the sponsorship conditions, please contact the Head of
Regulatory Compliance at:
Nottingham University Hospitals NHS Trust
Research & Innovation, Nottingham Health Science Partners
C Floor, South Block
Queens Medical Centre
Derby Road
Nottingham
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NG7 2UH
Email: ResearchSponsor@nuh.nhs.uk
[Who is funding the clinical investigation]
This CIP describes the xxx clinical investigation and provides information about procedures for entering participants. Every care was taken in its drafting, but corrections or amendments may be necessary. These will be circulated to investigators in the clinical investigation. Problems relating to this clinical investigation should be referred, in the first instance, to the Chief
Investigator.
This clinical investigation will adhere to the principles outlined in the NHS Research Governance Framework for Health and Social Care
(2 nd edition). It will be conducted in compliance with the CIP, the
Data Protection Act and other regulatory requirements as appropriate.
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Amendment
No.
CIP
Version
No.
Date
Issued
Author(s) of
Changes
Details of Changes
List details of all clinical investigation plan amendments here whenever a new version of the clinical investigation plan is produced.
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Insert clinical investigation title:
______________________
______________
Chief Investigator
______________________
Signature Date
______________________
______________
______________________
Clinical investigation Statistician
Date
Signature
______________________
______________
Sponsor Representative
______________________
Signature Date
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AE
AR
CI
CIP
CRA
CRF
CRO
CT
CTA
EC
GCP
GP
GTAC
IB
ICF
ICH
IEC
IMP
IRB
MHRA
NHS
NRES
PI
PIL
R&I
REC
SAE
SAR
SmPC/SPC
SOP
SUSAR
TMF
Add or delete as appropriate.
Adverse Event
Adverse Reaction
Chief Investigator
Clinical Investigation Plan
Clinical Research Associate
Case Report Form
Clinical Research Organisation
Clinical Trial
Clinical Trial Authorisation
Ethics Committee (see REC)
Good Clinical Practise
General Practitioner
Gene Therapy Advisory Committee
Investigator Brochure
Informed Consent Form
International Conference of Harmonisation
Independent Ethics Committee
Investigational Medicinal Products
Independent Review Board
Medicinal Health Research Authority
National Health Service
National Research Ethics Service
Principle Investigator
Participant Information Sheet
Research & Innovation
Research Ethics Committee
Serious Adverse Event
Serious Adverse Reaction
Summary of Products Characteristics
Standard Operating Procedure
Suspected Unexpected Serious Adverse Reactions
Clinical investigation Master File
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Clinical
Investigation
Title
Sponsor Reference
Number
Clinical Phase
Clinical investigation
Design
Clinical investigation
Participants
Planned Sample
Size
Number of
Participants
Follow-up Duration
Planned Clinical investigation
Period
Primary Objective
Secondary
Objective
Primary End points
Secondary End points
Device Name
Manufacturer Name
Principle Intended
Use
Length of Time the
Device has been
Used
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Include the following
 Summary description of the investigational device and its intended purpose.
 Details concerning the manufacturer of the investigational device.
 Name or number of the model/type, including software version and accessories, if any, to permit full identification.
 Description as to how traceability shall be achieved during and after the clinical investigation, for example by assignment of lot numbers, batch numbers or serial numbers.
 Intended purpose of the investigational device in the proposed clinical investigation.
 The populations and indications for which the investigational device is intended.
 Description of the investigational device including any materials that will be in contact with tissues or body fluids.
(This shall include details of any medicinal products, human or animal tissues or their derivatives, or other biologically active substances.)
 Summary of the necessary training and experience needed to use the investigational device.
 Description of the specific medical or surgical procedures involved in the use of the investigational device.
 Justification for the design of the clinical investigation and an evaluation of clinical data that is relevant to the proposed clinical investigation.
 Anticipated clinical benefits and risks.
There is usually only one primary objective, the rest are secondary objectives.
The wording of the objectives should be clear, unambiguous and as specific as possible – the clinical investigation will be judged on how and how well the objectives were satisfied.
6.1.1 Primary objective
Detail primary objective.
6.1.2 Secondary objective
Detail secondary objective.
Describe the end-points/outcome measures and how/when they will be measured during the clinical investigation.
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Endpoints/outcome measures should reflect the objectives. It is important that only one primary endpoint/outcome measure is selected as it will be used to decide the overall results or ‘successes’ of the clinical investigation. The primary endpoint/outcome measure should be measurable, clinically relevant to participants and widely accepted by the scientific and medical community.
6.2.1 Primary endpoint
Detail Primary endpoint
6.2.2 Secondary endpoint
Detail secondary endpoint
Summary of clinical investigation design
 Describe the overall clinical investigation design e.g., double-blind, placebo-controlled, parallel design, open labelled.
 Description of the measures to be taken to minimise or avoid bias, including randomisation and blinding.
 Give the expected duration of participant participation, number of visits, and a description of the sequence and duration of all clinical investigation periods e.g. screening period, treatment period, post treatment follow up period, and possibly add a flow chart here or as an appendix.
 Points in the clinical investigation to measure the outcomes.
 Detail any stopping rules for the clinical investigation.
 Any procedures for the replacement of subjects.
Include
 Number of participants
 Number of sites
 Length of recruitment period
Example criteria (amend as appropriate):
 Participant is willing and able to give informed consent for participation in the clinical investigation.
 Male or Female, aged 18 years or above.
 Diagnosed with required disease/severity/symptoms, any specific assessment criteria for these), or, if healthy volunteer clinical investigation: be in good health.
 (alter as required) Stable dose of current regular medication
(specify type if needed) for at least 4 weeks prior to clinical
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Date and Version No: investigation entry. Or (delete one or other), if healthy volunteer clinical investigation: have had no course of medication, whether prescribed or over-the-counter, in the four weeks before first clinical investigation dose and no individual doses in the final two weeks other than mild analgesia, vitamins and mineral supplements or, for females, oral contraceptives.
 Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the clinical investigation and for 3 months thereafter.
 Participants has clinically acceptable laboratory and ECG
(specify any other additional assessments) within <insert duration> of enrolment.
 Able (in the Investigators opinion) and willing to comply with all clinical investigation requirements.
 Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the clinical investigation.
 Additional clinical investigation specific criteria as required.
Example criteria (amend as appropriate):
The participant may not enter the clinical investigation if ANY of the following apply:
 Female participants who is pregnant, lactating or planning pregnancy during the course of the clinical investigation.
 Significant renal or hepatic impairment.
 Scheduled elective surgery or other procedures requiring general anaesthesia during the clinical investigation.
 Participant who is terminally ill or is inappropriate for placebo medication.
 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 clinical investigation, or may influence the result of the clinical investigation, or the participant’s ability to participate in the clinical investigation.
 Donation of blood during the clinical investigation. or, if healthy volunteer PK clinical investigation within the past 12 weeks.
 Participants who have participated in another research clinical investigation involving an investigational product in the past 12 weeks.
 Additional clinical investigation specific criteria as required.
Include
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 How will participants be identified eg, in clinic, database, invitation letters and posters
 Who will be responsible for identifying participants
Specify who will take informed consent, how and when it will be taken. Informed consent should be obtained prior to any clinical investigation related procedures being undertaken. Describe the informed consent process in situations of lack of capacity or emergency situations.
Example:
The participant must personally sign and date the latest approved version of the informed consent form before any clinical investigation 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 clinical investigation; the implications and constraints of the clinical investigation plan; 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 clinical investigation 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 clinical investigation. 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. A copy of the signed
Informed Consent will be given to the participants. The original signed form will be retained at the clinical investigation site.
*can be substituted parent/guardian or legally authorised representative, as appropriate, make sure that the term is consistent throughout the document
 Detail how potential participants will be identified, approached, screened and recruited.
 If applicable, specify pre-screening procedures.
 What is the maximum duration allowed between screening and randomisation?
 Specify the recruitment procedures e.g. referral by GPs, screening medical notes, using advertisements.
Describe the screening procedures in detail.
These are some of the headings and texts you may want to include.
Alter or add as necessary:
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Demographics
The date of birth, gender, race, smoking and drinking habits (add as required)… will be recorded.
Medical History
Details of any history of disease or surgical interventions in the following systems will be recorded: Provide details as appropriate.
Concomitant Medication
All over-the-counter or prescription medication, vitamins, and/or herbal supplements will be recorded on CRFs. Describe what information will be recorded.
Physical Examination
Height, weight and oral temperature will be recorded.
Resting pulse and blood pressure (BP) measurements will be measured after the participant has sat for at least five minutes. Provide details as appropriate.
ECG Test
A 12-lead ECG will be taken for each participant. At least the following ECG parameters will be recorded: heart rate (HR), PR, QT and QRS intervals and QTC. The report will be signed by the
Investigator who will record in the CRF whether it is normal, abnormal but not clinically significant, or abnormal AND clinically significant. In the latter case the eligibility of the participants will be reviewed.
Laboratory Tests
Describe any laboratory tests e.g. biochemistry, urinalysis and pregnancy tests.
Sample text:
All laboratory results will be reviewed and the reports signed by the Investigator who will record in the CRF whether they are normal, abnormal but not clinically significant, or abnormal AND clinically significant. In the latter case the eligibility of the participants will be reviewed.
Describe how randomisation is going to be carried out, and who will provide the randomisation codes. Will randomisation be done at the same visit as the baseline visit, or must participants return for a randomisation visit? Will there be a run in period?
Who will design the randomisation schedule (statistician, CRO), and who will hold it (Pharmacy, independent organisation).
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If the clinical condition of a participant necessitates breaking the code, who will do this and how? Will individual envelopes per participant per period be supplied so that the code may be broken for a single participant without unblinding the whole clinical investigation? Or will the pharmacist access the randomisation schedule if required by the Investigator and supply the needed information? Please refer to NUH SOP 9 on Unblinding.
State that if randomisation of a participant is unblinded during the clinical investigation then data for that participants will not be admitted to analysis.
Example
Subject numbers will be assigned sequentially as each subject enters the clinical investigation. The subjects will be assigned clinical investigation drug through a randomisation schedule based on the randomisation plan. The clinical investigation drug will be labelled with the clinical investigation number and unique identification number. The two treatments x and y will be indistinguishable. In the event of an emergency, the investigator is to decide the necessity of unblinding the subject’s treatment assignment. The blinded treatment assignments will be accessible to the investigator should a subject need to be unblinded in an emergency using the unblinding envelopes provided to the hospital pharmacy and X Toxicology Service. If unblinding occurs, the investigator or clinical investigation pharmacist must record the reason for unblinding, as well as the date and time of the event.
Corresponding information will be recorded on the CRF by the investigator.
Or
A contract research organisation will be commissioned to implement the randomisation process and provide the medication packs. Both the clinical investigation drug X and placebo will be formulated and supplied in identical capsules sealed in identical medication packs.
The allocation to placebo/X will be randomly assigned and the medication packs will be consecutively numbered with the clinical investigation PIN. Sealed randomisation envelopes will be kept unopened and in a secure place by the pharmacy at Nottingham
University Hospitals and the Investigators. The medication packs will be kept in the hospital pharmacy which will dispense them to clinical investigation participants. Participants will be enrolled and assigned a PIN consecutively, and issued with the medication pack corresponding to the PIN. Both clinical investigation participants and investigators will be blinded to the nature of the clinical investigation medication dispensed and all image and spectroscopic analysis will be conducted while blinded to clinical investigation treatment. Once all collected data has been analysed, the randomisation code will be broken by the clinical investigation investigators and the medication data entered into the analysis.
Should urgent un-blinding of a clinical investigation participant’s medication be required (when requested by a clinician treating the participant), this will be provided by the pharmacy at the
Nottingham University Hospitals. This is normally a working-hours
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The clinical investigation investigators have reviewed the clinical safety of the clinical investigation and do not feel that a 24-hour un-blinding service would be required for the appropriate treatment of participants, either within the Nottingham University Hospitals or elsewhere.
Detail criteria for participant withdrawal, discontinuation or replacement, and subsequent follow up if they are withdrawn or the clinical investigation terminates prematurely.
Detail
 Full name, generic name and UK trade name
 Is it CE marked
 Any other device to be used in the clinical investigation.
Detail the name and address of the company that will supply the
Medical Device.
Detail the name, address and MA number of the company manufacturing the device.
Describe.
Describe the storage arrangement and any required storage conditions, for the device. If applicable describe how the device is cleaned/re-sterilise. Describe any maintenance issues for the device.
10.5.1 Permitted medications
Detail drugs that maybe taken during the clinical investigation.
10.5.2 Prohibited medication
Detail other drugs that are not allowed during the clinical investigation due to interaction with the medical device or an effect on the clinical investigation outcomes.
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Example:
Throughout the clinical investigation Investigators may prescribe any concomitant medications or treatments deemed necessary to provide adequate supportive care except for those listed in the exclusion criteria. If these are required, the participant will be withdrawn.
Any medication, other than the clinical investigation medication taken during the clinical investigation will be recorded in the CRF.
List any contraindicated medications and check that they correspond with the exclusion and withdrawal criteria.
Detail any specific safety assessment required for the clinical investigation
11.2 CLINICAL INVESTIGATION ASSESSMENTS
Detail specific clinical investigation assessments to be performed and split them into the visit names. Refer to a schedule of events table in the appendices.
Define what will comprise source documents.
Example:
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, microfiches, 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 clinical investigation the CRF will be used as the source document for …<<add as required>>
All documents will be stored safely in confidential conditions. On all clinical investigation-specific documents, other than the signed consent, the participant will be referred to by the clinical investigation participant number/code, not by name.
Where possible the statistician should write this section.
The sub-headings given below are suggestions. However, if a
Statistical Analysis Plan is to be produced separately, state this here and condense the most relevant information from the sub sections here. You should give justification for:
 statistical design, method and analytical procedures,
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 sample size,
 the level of significance and the power of the clinical investigation,
 expected drop-out rates,
 pass/fail criteria to be applied to the results of the clinical investigation,
 the provision for an interim analysis, where applicable,
 criteria for the termination of the clinical investigation on statistical grounds,
 procedures for reporting any deviation(s) from the original statistical plan,
 the specification of subgroups for analysis,
 procedures that take into account all the data,
 the treatment of missing, unused or spurious data, including drop-outs and withdrawals,
 the exclusion of particular information from the testing of the hypothesis, if relevant, and in multicentre clinical investigations,
 the minimum and maximum number of subjects to be included for each centre.
Special reasoning and sample size(s) may apply for the early clinical investigation(s), e.g. feasibility clinical investigation(s).
Describe the statistical methods to be employed, including timing of any planned interim analysis.
State the approximate number of participants required to complete
(commence). Justify choice of sample size, including reflections on
(or calculations of) the power of the clinical investigation and clinical justification.
State the level of significance to be used.
Describe.
Describe.
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Procedures for reporting any deviation(s) from the original statistical plan (any deviation(s) from the original statistical plan should be described and justified in clinical investigation plan and/or in the final report, as appropriate).
The selection of participants to be included in the analyses (e.g., all randomised participants, all dosed participants, all eligible participants, evaluable participants).
14.1.1 Adverse Event (AE)
An AE or adverse event is:
Any untoward medical occurrence in a patient or other clinical investigation participant taking part in a clinical investigation of a medical device, which does not necessarily have to have a causal relationship with the device under investigation.
An AE can therefore be any unfavourable and unintended sign
(including an abnormal laboratory finding), symptom or disease temporally associated with the use of the device, whether or not considered related to the device.
14.1.2 Adverse Device Effect (ADE)
All untoward and unintended responses to the medical device.
The phrase "responses to a medical device" means that a causal relationship between the device under investigation and an AE is at least a reasonable possibility, i.e., the relationship cannot be ruled out.
All cases judged by either the reporting medically qualified professional or the sponsor as having a reasonable suspected causal relationship to the device qualifies as a device effect.
This also includes any event resulting from insufficiencies or inadequacies in the instruction for use or deployment of the device and includes any event that is a result of a user error.
14.1.3 Serious Adverse Event (SAE)
SAE is an adverse event that
 Led to death
 Led to fetal distress, fetal death or congenital abnormality or birth defect.
 Led to serious deterioration in the health of the subject that
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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. o Resulted in a permanent impairment of a body structure or a body function o Required in-patient hospitalisation or prolongation of existing hospitalisation o Resulted in medical or surgical intervention to prevent permanent impairment to a body structure or a body function o 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
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.
14.1.4 Serious Adverse Device Effects (SADE)
A serious adverse device effect (SADE) is any untoward medical occurrence seen in a patient that can be attributed wholly or partly to the device which resulted in any of the characteristics or led to characteristics of a serious adverse event.
SADE is also any event that may have led to these consequences if suitable action had not been taken or intervention had not been made or if circumstances have been less opportune.
All cases judged by either the reporting medically qualified professional or the sponsor.
14.1.5 Unanticipated Serious Adverse Device Effect (USADE)
Any serious adverse device effect on health or safety or any lifethreatening problem or death caused by, or associated with a device,
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All AEs occurring during the clinical investigation observed by the investigator or reported by the participant, whether or not attributed to the device under investigation will be recorded on the
CRF as specified in the clinical investigation plan. All ADEs will be recorded in the CRF.
The following information will be recorded: description, date of onset and end date, severity, assessment of relatedness to device, other suspect drug or device and action taken. Follow-up information should be provided as necessary.
The relationship of AEs to the device will be assessed by a medically qualified investigator or the sponsor/manufacturer and will be followed up until resolution or the event is considered stable.
All ADE that result in a participant’s withdrawal from the clinical investigation or are present at the end of the clinical investigation, should be followed up until a satisfactory resolution occurs.
Where relevant, any pregnancy occurring during the clinical investigation and the outcome of the pregnancy should be recorded and followed up for congenital abnormality or birth defect.
(Please delete the section which is not relevant for your clinical investigation)
For Non CE marked device clinical investigation: All
SAE/SADE/USADEs need to be reported to the sponsor/legal representative and manufacture and NUH R&I immediately ; regardless of relationship to the device.
For studies of CE marked devices: All SAE/SADE/USADEs need to be reported to the sponsor/legal representative and manufacture and NUH
R&I within one working day of the investigator team becoming aware of them.
All SAEs, except those expected ones defined in section 14.1.4
(remove if not applicable) that do not require immediate reporting must be reported to R&I within one working day of discovery or notification of the event. As Sponsor R&I at NUH will report all
SUSARs to the Competent Authorities MHRA and 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
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Date and Version No: will inform all investigators concerned of relevant information about SUSARs that could adversely affect the safety of participants.
If the University of Nottingham Clinical Trials Unit (CTU) is responsible for the Clinical investigation, it is the CTUs responsibility to report to the MHRA, Ethics and then notify the
R&I.
Reporting to the MHRA will be done in liaison with the Chief
Investigator and the Manufacturer.
The Manufacturer has a legal obligation to report all events that need to be reported to the Nominated Competent Authority immediately
(without any unjustifiable delay) after a link is established between the event and the device, but no more than:
 2 days following the awareness of the event for Serious Public
Health Threat.
 10 days following awareness of the event for Death or unanticipated serious deterioration in health.
 30 days following the awareness of the event for all other event meeting the SAE criteria.
In addition to the expedited reporting above, the CI shall submit once a year throughout the clinical investigation or on request a
Safety Report to R&I, the Competent Authority MHRA and Ethics
Committee.
Detail who will form part of the clinical investigation management group what their role will be and what they will be responsible for.
Detail who will form part of the clinical investigation steering committee what their role will be and what they will be responsible for. If a TSC is not being set up then this will need to be justified in this section.
Detail who will form part of the data monitoring committee what their role will be and what they will be responsible for. If a DMC is not being set up then this will need to be justified in this section.
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Investigators and institutions involved in the clinical investigation will permit clinical investigation related monitoring and audits on behalf of the sponsor and regulatory inspection(s).
In the event of an audit or monitoring, the Investigator agrees to allow the representatives of the sponsor direct access to all clinical investigation records and source documentation. In the event of regulatory inspection, the Investigator agrees to allow inspectors direct access to all clinical investigation records and source documentation
A risk assessment will be performed by the Sponsor to determine if monitoring is required and if so, at what level.
A Research Project Manager will visit the Investigator site prior to the start of the clinical investigation and during the course of the clinical investigation if required, in accordance with the monitoring plan. Monitoring will be performed according to ICH GCP.
Data will be evaluated for compliance with the clinical investigation plan and accuracy in relation to source documents.
Following written standard operating procedures, the monitors will verify that the clinical investigation is conducted and data are generated, documented and reported in compliance with the clinical investigation plan, GCP and the applicable regulatory requirements.
Describe ethical considerations relating to the clinical investigation. Include general and clinical investigation specific ethical considerations.
The Investigator will ensure that this clinical investigation 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).
The Investigator will ensure that this clinical investigation is conducted in full conformity with relevant regulations and with the
ICH Guidelines for Good Clinical Practice (CPMP/ICH/135/95) July
1996.
Consider the following text:
The clinical investigation plan, informed consent form, participant information sheet and any proposed advertising material will be submitted to an appropriate Research Ethics Committee (REC),
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The Investigator will submit and, where necessary, obtain approval from the above parties for all substantial amendments to the original approved documents.
The clinical investigation 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 clinical investigation staff and authorised personnel.
The clinical investigation will comply with the Data Protection Act which requires data to be anonymised as soon as it is practical to do so.
Include any other ethical considerations specific to the clinical investigation e.g. use of placebo, involvement of vulnerable participants.
Describe method of data entry/management.
Describe how data will be reviewed, cleansed and data queries will be resolved.
Describe how data will be verified and validated.
Example:
All clinical investigation data will be entered on a << quote software and validation procedure >>. Note that ICH GCP (Section 5.5) requires that electronic data entry systems are validated and that Standard
Operating Procedures are maintained.
The participants will be identified by a clinical investigation specific participant number and/or code in any database. The name and any other identifying detail will NOT be included in any clinical investigation data electronic file.
Amendments to the clinical investigation plan must be submitted to the Sponsor for review before submitting to the appropriate REC,
Regulatory Authority and local R&D for approval.
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Sponsor Reference Number:
Date and Version No:
The CI will not implement any deviation from the clinical investigation plan without agreement from the Sponsor, except where necessary to eliminate an immediate hazard to clinical investigation participants.
In the event that the CI needs to deviate from the clinical investigation plan, the nature of and reasons for the deviation will be recorded in the CRF and notified to the Sponsor. If this necessitates a subsequent clinical investigation plan amendment, this will be submitted to the Sponsor for approval and then to the appropriate REC, Regulatory Authority and local NHS R&I for review and approvals as appropriate. It is Sponsor policy that waivers to the clinical investigation plan will not be approved.
In the event that a serious breach of GCP is suspected, this will be reported to the Sponsor immediately. Refer to SOP-RES-017 “Non-
Compliance and Serious Breach Reporting”.
All clinical investigation documentation will be kept for 10 years from the clinical investigation plan defined end of clinical investigation point. When the minimum retention period has elapsed, clinical investigation documentation will not be destroyed without permission from the sponsor.
The end of clinical investigation is defined as the last participant’s last visit.
The Investigators and/or the clinical investigation steering committee and/or the co-sponsor(s) have the right at any time to terminate the clinical investigation for clinical or administrative reasons.
The end of the clinical investigation will be reported to the REC and Regulatory Authority within 90 days, or 15 days if the clinical investigation is terminated prematurely. The Investigators will inform participants of the premature clinical investigation closure and ensure that the appropriate follow up is arranged for all participants involved.
A summary report of the clinical investigation will be provided to the REC and Regulatory Authority within 1 year of the end of the clinical investigation.
NHS bodies are legally liable for the negligent acts and omissions of their employees. If you are harmed whilst taking part in a clinical clinical investigation as a result of negligence on the part of a member of the clinical investigation team this liability cover would apply.
Non-negligent harm is not covered by the NHS indemnity scheme. The
Nottingham University Hospitals NHS Trust, therefore, cannot agree in advance to pay compensation in these circumstances. In exceptional circumstances an ex-gratia payment may be offered.
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Sponsor Reference Number:
Date and Version No:
Optional
Describe funding arrangements
Ownership of the data arising from this clinical investigation resides with the clinical investigation team. On completion of the clinical investigation, the clinical investigation data will be analysed and tabulated, and a clinical clinical investigation report will be prepared in accordance with ICH guidelines.
The publication policy should cover authorship, acknowledgements, and review procedures for scientific publications. If there is a department or institution policy, or agreement, the clinical investigation plan can refer to it.
Detail procedures for peer review – these may be funder specific or involve an internal department.
Insert references used in text.
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Sponsor Reference Number:
Date and Version No:
Optional Alter as required, delete if not wanted
Procedures
Screening
Visits (insert visit numbers as appropriate)
Baseline
Informed consent
Demographics
Medical history
Concomitant medications
Physical examination
ECG
Laboratory tests
Eligibility
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Sponsor Reference Number:
Date and Version No: assessment
Randomisation
Assessment 1
(describe)
Assessment 2
(describe)
Assessment 3
(describe)
Assessment 4
(describe)
Adverse event assessments
CONFIDENTIAL Page 30 of 30