SOP 037: Amendments to Research
Documents of Papworth Sponsored Studies
post Trust Approval
Document Title: Amendments to Research Documents of
Papworth Sponsored studies post Trust Approval
Document Number:
Staff involved
Job titles only
in
SOP037
development: 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:
July 2016
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
a. This document sets out the procedures to be followed by all Papworth Staff who are responsible
for submitting amendments to research studies run at Papworth.
b. It aims to provide clear guidance on the procedure of seeking approval for amendments to
research studies that require Regulatory and Trust approval.
c. The SOP indicates when an amendment should be submitted, by whom and what is required.
Version 5.0 Review Date: July 2016
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SOP 037: Amendments to Research
Documents of Papworth Sponsored Studies
post Trust Approval
1
Purpose and Content
a. This document defines the Trust’s procedure for changes to research studies following Trust
approval.
b. The document clarifies the situation when an amendment is required and the approval and
implementation process so as to meet the standards described in Good Clinical Practice (GCP: ‘a
standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and
reporting of clinical trials that provides assurance that the data and reported results are credible
and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected’).
c. The document aims to provide clear guidance on the processes involved in making amendments to
research studies including the recording the requirement for change, classification of the
amendment and submission of the amendment for Trust, REC and the applicable regulatory
bodies’ approval as applicable.
d. This SOP does not cover NHS permission for implementation of amendments for non-Papworth
sponsored studies. For amendments to research documents for non-sponsored studies please refer
to SOP034.
2
Roles & Responsibilities
a. This Policy applies to all Papworth Sponsored research that is being conducted at the Trust.
b. Staff involved in amendment applications, both submission and review, must comply with the
requirements set out in section 4
c. The Chief Investigator of a research study is responsible for initiating any amendments to a study
and ensuring that all the relevant regulatory approvals have been obtained prior to its
implementation. The actual procedure of applying for and implementing amendments may be
delegated to a responsible member of the research team.
d. The Chief Investigator of a study is responsible for ensuring all participating sites receive revised
documentation and ensuring host sites grant NHS permission for substantial amendments prior to
implementation at the participating site. The revised documentation must be send to the Principal
Investigators and the R&D departments at the participating sites.
e. The sponsor is responsible for the classification and authorisation of the amendment prior to
submission to regulatory bodies. The responsibility of classification is delegated to the R&D
department.
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SOP 037: Amendments to Research
Documents of Papworth Sponsored Studies
post Trust Approval
3
Policy
a. This SOP is mandatory and, as per the Trust’s Information Governance and Records Management
framework, non-compliance with may result in disciplinary procedures.
4
Procedure
4.1 Definition and Classification of amendment
a. An amendment is any change that is made to the design, conduct and management of a study
following Ethical, Regulatory and Trust approval. It includes any amendments to the protocol or
study documentation that has been approved by ethics, regulatory bodies and Trust. In addition
changes to the management of the sutdy (ie change in Chief investigator or additional site, is
considered an amendment. Any changes must be appropriately reviewed and approved by the
relevant organisations and the change documented to ensure compliance with Good Clinical
Practice, national leglisation and guidelines.
b. An amendment broadly speaking is a change to any of the particulars of the design, management,
conduct, or documentation of a research study. Amendments are classified into 2 types:
substantial and non-substantial.
c. A substantial amendment is defined as amendment that is likely to affect to a significant degree
any of the following:
o
the safety or physical or mental integrity of the subjects of the trial,
o
the scientific value of the trial,
o
the conduct or management of the trial, or
o
The quality or safety of any investigational medicinal product used in the trial.
d. An urgent safety measure is taken by the sponsor or investigator in order to protect the subjects of
a clinical trial against any immediate hazard to their health or safety. These can be implemented
immediately
e. Non-substantial amendments are minor changes that are not considered substantial as described
above. Non-substantial amendments do not require submission to REC and /or MHRA but must be
documented in the TMF, including the rationale to why the amendment is not considered
substantial.
f.
Further details regarding the classification of substantial amendments are defined by the Research
Ethics Committees: http://www.nres.npsa.nhs.uk/applications/after-ethical-review/notification-ofamendments/examples-of-substantial-and-non-substantial-amendments/
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SOP 037: Amendments to Research
Documents of Papworth Sponsored Studies
post Trust Approval
g. Details concerning amendments to CTIMPs and non-CE marked devices can be found at:
http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Clinicaltrials/Managin
gyourCTA/Amendments/Generalinformation/index.htm
4.2 Process for applying for an amendment
a. Flow chart A provides an overall view of the process for review, classification and implementation
of an amendment.
b. With the exception of urgent safety measure, the sponsor of a clinical trial is required to obtain
authorisation from REC and / or MHRA and local Trust approval before implementing the
amendment. It is the Chief Investigators responsibility at Papworth to ensure the necessary
approvals have been sought before implementation of an amendment.
c. For all clinical trials rationale and justification for the proposed amendment must be documented
in the Trial Master File.
d. Consideration must be given to the overall impact of the change; finance and resource to ensure
the amendment is feasible. Any impact on other services must be discussed and agreed with the
services implicated.
e. For Papworth Sponsored studies the delegated member of the research team will coordinate the
amendment application process.
f.
The study team is responsible for the decision to make a change, proposed classification into
substantial / non-substantial amendment and revision of any documentation and submission to
the necessary bodies in accordance with the requirements of the regulatory bodies.
g. All proposed amendments must be submitted to R&D for ratification of the classification prior to
submission for authorisation by the Sponsor delegate (Clinical Lead for R&D or other authorised
delegate).
h. R&D will confirm if the amendment needs ethical approval, MHRA approval or ethical and MHRA
approval.
4.3 Procedure for Substantial Amendments
a. If the amendment is substantial a notice of substantial amendment is created in IRAS.
b. Any changes to study documentation should be recorded (i.e. using the ‘track-changes’
function in Word) and the new documents given a new version number and date. It is
likely that both the ‘track-change’ and clean form of the new version will be required for
review by the relevant regulatory bodies.
c. Documentation must be submitted to R&D for review and confirmation of classification
prior to seeking authorisation from the sponsor delegate.
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SOP 037: Amendments to Research
Documents of Papworth Sponsored Studies
post Trust Approval
d. Sponsor authorisation for substantial amendments is delegated to the clinical lead for R&D
or delegated deputy.
e. Submissions are made by the CI to the necessary bodies. A covering letter must
accompany the amendment, and a copy must be stored in the TMF.
4.4 Final sign off for Trust permission to proceed with Substantial Amendments
a. When all appropriate regulatory approvals for an amendment have been obtained, an e-mail
should be sent to the generic R&DEnquiries address box (R&[email protected])
supplying a copy of all correspondence with regulatory bodies; the notice of no objection,
favourable opinion, the notice of amendment and a copy of all the approved documents
submitted.
b. The amendment will be reviewed by the R&D Governance co-ordinator to ensure:
o
If applicable, a notice of no objection from the MHRA is in place.
o
If applicable, a favourable opinion from the appropriate REC is in place.
o
It is judged not to have any negative effect on the risk of the study, the contractual
obligations of Papworth, the resources required or the impact on clinical directorates.
c. If the above conditions are met the amendment will be approved by chairman’s action and
recorded for information at the next Research Governance Project Approval System Meeting
(RGPAS).
d. A letter confirming the approval of the amendment will be issued. Managers (8a and above) within
R&D are authorised to sign amendment approvals. A copy of the letter must be stored in the TMF.
Where applicable a copy will also be sent to the Pharmacy department.
e. Once permission has been granted by the Trust the amendment can be implemented at the Trust.
4.5 Implementation at participating sites
a. For substantial amendments, approval must be granted by the participating Trust prior to the
implementation. The permission letter must be stored in the TMF.
4.6 Procedure for Non-substantial amendments
a. For non-substantial amendments, a copy of all revised documentation must be submitted to
R&Denquiries.
b. R&D will confirm amendment is non-substantial.
c. Once confirmation is received the amendment may be implemented.
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SOP 037: Amendments to Research
Documents of Papworth Sponsored Studies
post Trust Approval
d. Non-substantial amendments do not require ethical or MHRA approval, although it is good practice
to notify the relevant bodies of any non-sustantial amendment in either annual reports, or when
submitting substantial amendments.
e. All non-substantial amendment must be notified to participating sites with confirmation of
sponsor’s decision on the classification.
4.7 Exceptions: Urgent Safety Measures
a. Amendments due to urgent safety measures can be implemented immediately with all subsequent
documentation forwarded to R&D.
b. MHRA and REC must be notified within 3 days that such a measure has been taken and why.
c. All decisions and rationale for the urgent safety measure must be documented in the Trial Master
File (TMF).
d. Urgent safety measures must follow MHRA and ethical process for follow-up of amendment.
5
Risk Management / Liability / Monitoring & Audit
a. The R&D department will ensure that this SOP and any future changes to this document are
adequately disseminated.
b. The R&D department 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).
c. In exceptional circumstances it might be necessary to deviate from this SOP for which the written
approval of a 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.
d. The Research and Development Directorate is responsible for the ratification of this procedure.
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SOP 037: Amendments to Research
Documents of Papworth Sponsored Studies
post Trust Approval
Flow Chart A
Consider justification and rationale for amendment,
Classification of amendment by study team
Urgent Safety
Measure
Substantial
Amendment
Non-substantial/
minor amendment
CI notify regulatory
bodies and send
any revised
documents to all
sites and
implement
immediately
Prepare revised
documentation and
application forms
Prepare revised
documentation
For multicentre
studies,
submit all revised
documentation and
approval letters, on
receipt to research
teams and host
R&D department.
Submit to R&D for
confirmation of
substantial
amendment and
sponsor
authorisation
Submit to REC and
/or MHRA or other
bodies
Submit all revised
documentation to
sites
Implement (no
approval required)
Submit all
correspondence
including cover
letters and approval
letters to R&D
Participating site
Trust approval issued
Trust approval issued
Implement at
participating site
Implement at
Papworth
Version 5.0 Review Date: July 2016
Submit to R&D for
confirmation of
non-substantial
amendment
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SOP 037: Amendments to Research
Documents of Papworth Sponsored Studies
post Trust Approval
Further Document Information
Approved by:
Management/Clinical Directorate Group
Research and Development Directorate
Approval date: (this version)
12th July 2013
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) Amended
Regulations 2006 and all associated amendments.
Research Governance Framework for Health and Social
Care (2005).
Key related documents:
Research and Development SOP entitled:
SOP034 Trust Approval and Research Governance
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
Yes/No:
NO
NO
NO
NO
NO
NO
& Other
NO
Positive/
Negative:
Review date:
July 2016
Version Control
Version
Date Effective
1.0
Approved by
Date of Approval
Sept 2009
RDD
4th Sept 2009
2.0
May 2010
RDD
14th May 2010
3.0
Sept 2010
Sept 2012
RDD
10th Sept 2010
4.0
13th April 2012
April 2015
RDD
13th April 2012
5.0
22nd August 2013
July 2016
RDD
12th July 2013
Version 5.0 Review Date: July 2016
Valid To
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