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Jo Steele x4147
Document Title:Case Report Form SOP
Document Number:SOP054
Staff involved in development:Job titles only / RM&G Manager, R&D Administration Manager, Research Officers
Document author/owner: / R&D Administration Manager
Directorate: / Research and Development
Department: / Research and Development
For use by: / NHS Staff Trust-Wide
Review due: / November 2015
THIS IS A CONTROLLED DOCUMENT
Whilst this document may be printed, the electronic version maintained on the Trust’s Intranet is the controlled copy. Any printed copies of this document are not controlled. ©Papworth Hospital NHS Foundation Trust. Not to be reproduced without written permission.
Key Points of this Document
- This document sets out the procedures to be followed by all Papworth Staff who are involved in research.
- It aims to provide clear guidance on the design of Case Report Forms.
1Purpose and Content
1.1This document defines the Trust’s procedures to be followed when designing and developing Case Report Forms (CRF’s) for use within a Clinical Trial. The CRF is a data capturing tool used in all Clinical Trials to record eligibility of a subject and to capture the required data as defined by the trial protocol for each individual trial subject during the course of his/her participation in a trial.
1.2The CRF design and 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 R&D (or other organization from time to time), as well as during audits and inspections by the external bodies.
1.3The CRF will be designed 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.
1.4This Standard Operating Procedure (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”
2Roles & Responsibilities
2.1This Policy applies to research that is conducted at the Trust.
2.2Staff recording study data must comply with the requirements set out in section 4.
2.3All Clinical Trials sponsored or co-sponsored by Papworth Hospital NHS Foundation Trust are bound by this SOP. An exception being when a Clinical Trial is co-sponsored with organisations other than Papworth Hospital NHS Foundation Trustand 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.
2.4When it is planned to use an Electronic Data Capture (EDC) or Remote Data Capture (RDC) for capturing Clinical Trial data, the principles defined in this SOP are applicable.
2.5CRF design is the responsibility of the CI or their 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. For medicinal trials, the CI must sign off the CRF validation form to show that they approve the final version of the CRF.
2.6The final CRF will be available before the first patient is enrolled in to the Clinical Trial.
3Policy
3.1This SOP is mandatory and, as per the Trust’s Information Governance and Records Management framework, non-compliance with may result in disciplinary procedures.
4Procedure
4.1General Forms
4.1.1CRF design will be based on the requirements of the protocol and the statistical analysis of the trial data; this principle remains the same whether the CRF is in paper or electronic format.
4.1.2The following forms are normally found in a standard CRF, 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 FormScreening / Baseline data including:
Confirmation of consent & Demographics
Medical History, and if applicable, prior treatment
History of diagnosis studied (if applicable)
Physical Examination
Inclusion / Exclusion criteria review
Randomisation / Registration / Participant Eligibility Review
Data during treatment period / Administration of Trial Medication (for CTIMPs)
Safety and/or Efficacy Assessments
Participant Status
CRF Comments Log (Advisable but not mandatory)
Adverse Events / Adverse Events Log
SAE form
Concomitant Medication Form / Concomitant Medication data on protocol-defined period of recording
Withdrawal Form / Information on the reason(s) for earlytermination
Follow-up / Concomitant Medications, if applicable
Unscheduled Form (if applicable) / Data for visits that are not protocol scheduled visits
Trial Completion / To indicate whether the study was completed which includes date and signed off by the Principal Investigator
4.1.3CRF design is a multidisciplinary process, involving the research team, the trial statistician, data manager(if applicable) and suitably qualified R&D staff. An independent review will ensure quality control is maintained (e.g. by Statistician, trial CRA).
4.1.4For CTIMPs, documented approval of the CRF by the Chief Investigator is mandatory. This will be recorded by signing-off of the CRF Validation Forms once the data collection system has been validated by the Data Manager for the trial. CRF documents may only be used in the trial once they have been finalised and approved for that study.
4.2General Principles
4.2.1The CRF must be finalised prior to the start of the trial.
4.2.2After finalisation of the CRF any changes deemed necessary must be discussed with the Principal Investigator, Statistician and the Database Manager.
4.2.3Patients should be allocated a study number and should be identified by their initials only.
4.2.4Each page of the CRF should have the following information as standard, so that in the event of the page being separated from the rest of the CRF, it will be possible to reunite them: Patient Study Number, Patient Initials and Date.
4.2.5Adopt a standardised format to achieve consistency in data recording.
4.2.6Ensure that the data to be captured are 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.
4.2.7Collect data in prescribed format to minimise unnecessary calculations and conversions.
4.2.8Structure 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.
4.2.9Separate 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.
4.2.10Provide a CRF trial schedule, to indicate which CRF pages are applicable to particular visits.
4.2.11Use questions, prompts and provide instructions, which must be clear and concise and must not contradict other CRF pages or the protocol.
4.3Format
4.3.1 The CRF will:-
4.3.2Be clearly version controlled; by version number and date (see SOP060: Version Control of Study Documents).
4.3.3Be 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 canbe followed: the initial page as XXX.0, the suffix will increase sequentially witheach inserted page as XXX.1, XXX.2, XXX.3).
4.3.4Be in chronological order, clearly identifying the visit or data collection point, as defined in the protocol.
4.3.5Have an appropriate number of boxes for the digits required, for example, date, laboratory results, and vital signs readings.
4.3.6Have pre-printed decimal points where applicable.
4.3.7Specify units if appropriate, ensuring units are the same as that in the protocol and source documents.
4.3.8Have a designated area for sign-off at eligibility review and at the end of the CRF by the investigator.
4.4Layout
4.4.1The layout of the CRF will:
4.4.2Be consistent throughout the entire CRF, including alignment, page margins, spacing and fonts.
4.4.3Have sufficient space in the page margin to accommodate hole punching/binding.
4.4.4Have text aligned with associating boxes where applicable.
4.4.5Not be overly cramped.
4.5Data Collection
4.5.1By specifying a required format for data entry, the responses received will be supplied in a uniform manner.
4.5.2Data collected as a “numeric value” and “free text” should be limited as far as possible, as this complicates data analysis, wherever possible use boxes to ensure consistency.
i)dd / mm / yyyy01 /10 / 2012 / ii) Date: ______
Date: 2ndOctober 2012
4.5.3Listing definitive options with checkboxes will demand defined responses to minimise ambiguity.
Has the patient had any adverse events Yes Noe.g.
4.5.4Using a combination of definitive options, and option to enter “other” or “specify” will allow for the collection of additional information if applicable.
Origin: / White / Caucasian Black or African
Oriental
Other, specify ______
e.g.
4.5.5When assessing subjective variables e.g pain, only use validated instruments.
4.6Corrections
4.6.1Cross out the incorrect entry with a single line so that the incorrect entry is still legible.
4.6.2Enter the correct data.
4.6.3Initial and date the correction.
4.6.4Give an explanation of the correction if it is not obvious why the change was made.
4.6.5If any changes are made on an eCRF system an electronic audit trail is to be maintained.
4.7Trial Specific CRF Completion Guidelines:
4.7.1Trial specific CRF completion guidelines may be generated if required and can be a useful tool for accurate data entry and CRF completion.
4.8CRF amendment
4.8.1Amendment 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. All CRF amendments will be tracked by theversion number and date and approval documented in the Trial Master File.
5Risk Management / Liability / Monitoring & Audit
5.1The R&D Department will ensure that this SOP, and any future changes to this document, are adequately disseminated.
5.2The Unit will monitor adherence to this SOP via the routine audit and monitoring of individual clinical trials and the Trust’s auditors will monitor this SOP as part of their audit of Research Governance. From time to time, the SOP may also be inspected by external regulator agencies (e.g. Care Quality Commission, Medicines and Healthcare Regulatory Agency).
5.3In exceptional circumstances it might be necessary to deviate from this SOP for which the written approval of the Senior R&D Manager should be gained before any action is taken. SOP deviations should be recorded including details of alternative procedures followed and filed in the Investigator and Sponsor Master File.
5.4The Research and Development Directorate is responsible for the ratification of this procedure.
Further Document Information
Approved by:Management/Clinical Directorate Group / Research and Development Directorate
Approval date:(this version) / 9th November 2012
Ratified by Board of Directors/ Committee of the Board of Directors / STET
Date: / N/A
This document supports:
Standards and legislation / Medicines for Human Use (Clinical Trials) Regulations 2004 and all associated amendments.
Research Governance Framework for Health and Social Care (2005)
Key related documents: / Trust Research Policy
Research and Development Standard Operating Procedures entitled:
Research Protocol SOP 019
Study Data (CRF & Source Data) SOP 047
Trust Policy DN48 Case Note Retention & Disposal of Patient Records
Equality Impact Assessment: Does this document impact on any of the following groups? If YES, state positive or negative, complete Equality Impact Assessment Form available in Disability Equality Scheme document DN192 and attach.
Groups: / Disability / Race / Gender / Age / Sexual orientation / Religious & belief / OtherYes/No: / NO / NO / NO / NO / NO / NO / NO
Positive/ Negative:
Review date: / November 2015
Version Control
Version / Date Effective / Valid To / Approved by / Date of Approval1.0 / 28th Dec 2012 / Nov 2015 / RDD / 9th Nov 2012
SOP 054: Case Report Form
Version 1.0Review Date: November 2015 / Page 1 of 8