The King’s Health Partners Clinical Trials Office

Case Record Form Design

Policy Details
Document Type Standard Operating Procedure

KHP-CTO/CT/SOP8.0
Document name
Case Record Form Design

Version Final version 5.0 05/Feb/2021

Effective from 11th February 2021

Review date 5thth February 2024

Owner King’s Health Partners Clinical Trials Office

Originally Prepared by Helen Critchley, Senior Clinical Research Associate

Reviewed by Amy Holton, KHP-CTO Quality Manager

Approved by Jackie Pullen, Director, King’s Health Partners

Clinical Trials Office

Superseded documents Version 4.1 24/Oct/18

Relevant Statutory Instrument 2004 no 1031

regulations/legislation/guidelines
Statutory Instrument 2006 no 1928 (as amended from
time to time)

Change History
Date Version Change details Approved by
Number

28/Feb/2012 2.0 Administrative changes to formatting and Jackie Powell

change in the department name from
JCTO to KHP-CTO

14/Oct/2014 3.0 Administrative changes to formatting. Jackie Pullen

05/Feb/21 Final Version 5.0 Page 1 of 10

 17/Jan/2018 4.0 Update to the glossary and minor Jackie Pullen
amendments ti the table in section 4.1

24/Oct/2018 4.1 Minor amendment to include trials Jackie Pullen

managed by KHP-CTO

05/Feb/2021 5.0 Clarifications to sections 2.0, 4,1, 4.2, Jackie Pullen

4.7 and 4.8. Addition of section 4.9 -
Archiving. Administrative changes to
formatting.

05/Feb/21 Final Version 5.0 Page 2 of 10

 Table of Contents

1. 0 GLOSSARY .................................................................................... 4

2.0 BACKGROUND AND PURPOSE ................................................... 5

3.0 SCOPE ........................................................................................... 5

4.0 PROCEDURE ................................................................................. 6

4.1 General Forms ........................................................................................ ......6
4.2 General Principles ........................................................................................ 7
4.3 Format ........................................................................................................... 8
4.4 Layout ........................................................................................................... 8
4.5 Data Collection ............................................................................................. 8
4.6 Trial Specific CRF Completion Guidelines: ............................................... 9
4.7 CRF approval process: ................................................................................ 9
4.8 CRF amendment........................................................................................... 9

5.0 RELATED TEMPLATES............................................................... 10

5.1 CRF templates ............................................................................................ 10
5.2 CRF Approval Form ................................................................................... 10

6.0 RELATED DOCUMENTS ............................................................. 10

6.1 CRF Design and Approval Process Map .................................................. 10

6.2 CRF Design Manual ................................................................................... 10
6.3 Document Version Control Guidelines .................................................... 10
6.4 CRF Completion Guidelines ........................................................................... 10

7.0 APPROVAL and SIGNATURE ..................................................... 10

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1. 0 GLOSSARY
Case Record Form (CRF) – “a printed, optical, or electronic document designed to record all
of the protocol required information to be reported to the sponsor on each trial subject”.

Chief Investigator (CI) - A Registered Physician, Dentist, Pharmacist or Registered Nurse

who has overall responsibility for the conduct of the study.

Clinical Research Associates (CRAs) – Members of the KHP-CTO Quality Team who
monitor trials to ensure GCP compliance

Clinical Trial - Any investigation in human participants, other than a non-interventional trial
intended to discover or verify the clinical, pharmacological or other pharmacodynamic effects
of one or more medicinal product or to identify any adverse reactions to one or more such
products and to study absorption, distribution metabolism and excretion in one of more such
products with the object of ascertaining the safety or efficacy of those products

Electronic Data Capture (EDC) - a computerised system designed for the collection of
clinical data in electronic format for in clinical trials.

Good Clinical Practice (GCP) – As defined in Statutory Instrument 2006/1928.

King’s Health Partners (KHP) – Kings Health Partners Academic Health Science Center is
a pioneering collaboration between one of the King’s College London (University) and three
of Londond’s most successful NHS Foundation Trusts - Guy’s & St Thomas’ NHS
Foundation Trust, King’s College Hospital NHS Foundation Trust and South London &
Maudsley NHS Foundation Trust

The King’s Health Partners Clinical Trials Office (KHP-CTO) Established in 2006 by
Kings College London, Guy’s & St Thomas’ NHS Foundation Trust and King’s College
Hospital NHS Foundation Trust to provide a streamlined approach for all aspects of trial
administration.

KHP-CTO Standard Operating Procedure (SOP) – "detailed, written instructions to achieve

uniformity of the performance of a specific function," SOPs are the base on which Quality
Systems and Processes are conducted and monitored against.

The Medicines & Healthcare products Regulatory Agency (MHRA) - UK Competent

Authority responsible for regulation of clinical trials.

The Regulations - Medicines for Human Use (Clinical Trial) Regulations 2004 transposed
the EU Clinical Trials Directive into UK legislation, as Statutory Instrument 2004 no 1031.
This became effective on the 1st May 2004. An amendment to implement Directive
2005/28/EC was made to the Regulations as Statutory Instrument 2006 no 1928 (as
amended from time to time).

Quality Policy - Policy signed by the Medical Directors’ of the Partner Organisations and the
Vice Principal of the Health Schools of King’s College London. The Quality Policy binds all

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relevant clinical research activity conducted or managed by the Partner Organisations to the
Clinical Trial SOPs.

Remote Data Capture (RDC) - Remote data capture is the process of automatic collection
of data.

2.0 BACKGROUND AND PURPOSE

The purpose of this Standard Operating Procedure (SOP) is to describe the standard
procedures to be followed when designing and developing CRFs for use within a Clinical
Trial. The CRF is a data capturing tool used in all Clinical Trials to record eligibility of a
participant and to capture the required data as defined by the trial protocol for each individual
trial participant during the course of his/her participation in a trial. CRFs may be printed or
electronic documents. The type of CRF used for the trial will vary according to the
requirements of each individual study. The Chief Investigator and Quality Manager will
decide what CRF is most suitable for each trial however the principles outlined in this
document remain the same for both systems. The design of the CRF and its completion have
a direct impact on the quality of the Clinical Trial data. It is subject to quality assurance and
control during monitoring for GCP compliance on behalf of the Sponsor by the KHP-CTO (or
other organization from time to time), as well as during audits and inspections by the MHRA
and REC.
The CRF will be designed in an appropriate format in order to collect only trial data as set out
in the protocol for planned analyses. A well-designed CRF will ensure that no essential data
is missed and that data queries are kept to a minimum as well as aiding data management,
statistical analysis and reporting.
This SOP will ensure that CRF design enables trials sponsored or co-sponsored by the
Partner Organisations comply with the regulations encompassed in the UK and European
Law.
SI 2006/1928 Part 2 Conditions and Principles which apply to all Clinical Trials:
“9. All clinical information shall be recorded, handled and stored in such a way that it
can be accurately reported, interpreted and verified, while the confidentiality of
records of the trial subjects remains protected”

3.0 SCOPE
All Clinical Trials sponsored by one or more of King’s Health Partner Organisations, or
clinical trials where the sponsor responsibilities are managed by the KHP-CTO.. An
exception being when a Clinical Trial is co-sponsored with organisations other than the
Partner Organisations and the task of CRF design is delegated to the other organisation.
However, this SOP can be referred to if the other party does not have a CRF design SOP in
place.

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When EDC or RDC is planned to be used for capturing Clinical Trial data, the principles
defined in this SOP are applicable.

4.0 PROCEDURE

CRF design is the responsibility of the CI or delegate, but should involve other members of
the team, including but not limited to: researchers, trial coordinators or managers, research
nurses, data managers and statisticians.The final CRF will be available before the first
patient is enrolled in to the Clinical Trial.

4.1 General Forms

The CRF will be designed to ensure that all data required by the protocol and statistical
analysis are captured in an appropriate format; only data defined in the protocol will be
entered into the CRF.
The following forms are normally found in a standard CRF (see related template for
examples in section 5.1). However, this list is not exhaustive – mandatory forms are
highlighted as bold. Depending on individual trial requirements additional forms may/will be
added:-

Case Record Form

Unambiguous participant identity code and visit dates

Baseline data including:

Confirmation of consent & Demographics
Medical History, and if applicable, prior treatment
Screening History of diagnosis studied (if applicable)
Physical Examination
Inclusion / Exclusion criteria review
Initial Primary and Secondary Endpoint Data (if applicable)

Participant Eligibility Review

Randomisation / Registration
Confirmation of randomisation (if applicable)

Administration of Trial Medication

Data during treatment period Safety and/or Efficacy Assessments
Participant Status
Primary and Secondary Endpoint Data
Adverse Events Adverse Events Log

Concomitant Medication Form Concomitant Medication data on protocol-defined period of

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 recording

Trial Completion Trial Completion form

Follow-up Concomitant Medications, if applicable

Unscheduled Form (if applicable) Data for visits that are not protocol scheduled visits

CRF Final page Principal Investigator sign off

4.2 General Principles

When designing a CRF, the following general principles will be considered:-
• Adopt a standardised format to achieve consistency in data recording.
• Ensure that the data to be captured is entered into the CRF in a logical order –
take in to account, for example, the order of trial procedures during a trial visit,
order of entry in medical notes and laboratory reports.
• Collect raw data to minimise unnecessary calculations and conversions.
• Structure the layout in an organised manner to minimise transcription error where
data will be transcribed from source documents to CRF.
• A Comments Form can be included in the CRF where comments can be
recorded centrally. However free-text entry cannot be analysed and hence
should be kept to the minimum
• Separate the CRF into sections by visit to ease organisation, and include a
checklist at the front of each section as reminder of assessments required per
visit.
• Provide a CRF trial schedule, to indicate which CRF pages are applicable to
particular visits.
• Use questions, prompts and provide instructions, which must be clear and
concise and must not contradict other CRF pages or the protocol.
• Ensure that copyright permissions are obtained for the replication of any licensed
measures (i.e. questionnaires), where applicable

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4.3 Format
The CRF will:-
• Be clearly version controlled; by version number and date (see section 6 of the
Document Version Control Guidelines).
• Be page numbered in sequential order. In cases where multiple page insertions
are required, eg, Adverse Event Form and Concomitant Medication Form, the
use of sub-numbering may be appropriate. (The following numbering pattern can
be followed: the initial page as XXX.0, the suffix will increase sequentially with
each inserted page as XXX.1, XXX.2, XXX.3).
• Be in chronological order, clearly identifying the visit or data collection point, as
defined in the protocol.
• Have sufficient information in the header, to identify EVERY CRF page - for
example, trial name, protocol number, patient trial number and initials. Hospital
numbers are not acceptable as patient identifiers.
• Have an appropriate number of boxes for the digits required, for example, date,
laboratory results, and vital signs readings.
• Have pre-printed decimal points where applicable.
• Specify units if appropriate, ensuring units are the same as that in the protocol
and source documents.
• Have a designated area for sign-off at eligibility review and at the end of the CRF
by the investigator.

4.4 Layout
The layout of the CRF will:
• Be consistent throughout the entire CRF including alignment, page margins,
spacing and fonts.
• Have sufficient space in the page margin to accommodate hole punching/binding.
• Have text aligned with associating boxes where applicable.
• Not be overly cramped.

4.5 Data Collection

By specifying a required format for data entry, the responses received will be supplied in a
uniform manner.
• Data collected as “free text” should be limited as far as possible, as this
complicates data analysis, wherever possible use boxes to ensure consistency.

i) |_|_|-|_|_|_|-|_|_|_|_|
ii) Date:________________
DD - MMM - YYYY

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 • Listing definitive options with checkboxes will demand defined responses to
minimise ambiguity.

e.g.
Has the patient had any Adverse Events? No Yes

• Using a combination of definitive options, and option to enter “other” or “specify”

will allow for the collection of additional information if applicable.

e.g.
Origin: White / Caucasian
Black or African
Oriental
Other, specify: _______________________

• When assessing subjective variables e.g. pain, only use validated instruments.

4.6 Trial Specific CRF Completion Guidelines:

Trial specific CRF completion guidelines may be generated if required and can be a useful
training tool for accurate data entry and CRF completion.

4.7 CRF approval process:

CRF design is a multidisciplinary process, involving collaboration with the research team, the
trial statistician, data management (if applicable) and KHP-CTO CRA. An independent
review will ensure quality control is maintained (e.g. by Statistician, trial CRA)Documented
approval of the CRF by the Chief Investigator is mandatory (see section 5 for CRF approval
form template) and evidence of review must be retained in the Trial Master File. The CRF
should be finalised prior to the first patient being enrolled into the trial.

4.8 CRF amendment

Amendments to the CRF may be required from time to time due to, for example, a change of
trial design or a change in data requirements as specified in an amendment to the protocol
and /or statistical analysis plan. Amendments to the CRF should be made during the
amendment approval process, the current version of the CRF should be consistent with the
current version of the protocol. All CRF amendments will be tracked by the version number
and date and approval documented in the Trial Master File. Where paper CRFs are being
used updated versions should be provided to all sites and filed in the ISF. Superseded

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versions should be marked as such and retained in the TMF/ISF. eCRFs should be updated
and finalised before the amendment is implemented.

4.9 Archiving

CRFs shall be archived according to the requirements outlined in the Sponsor’s protocol.

5.0 RELATED TEMPLATES

5.1 CRF templates

5.2 CRF Approval Form

6.0 RELATED DOCUMENTS

6.1 CRF Design and Approval Process Map

6.2 CRF Design Manual

6.3 Document Version Control Guidelines

6.4 CRF Completion Guidelines

6.5 Data Management Plan Template

7.0 APPROVAL and SIGNATURE

11 February 2021
_________________________________ _________________
Jackie Pullen Date
Director
King’s Health Partners Clinical Trials Office

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