Oxford Radcliffe Hospitals
Research Protocol Amendments
Document Ref. No.: Version: Applicable to: RD004 Final Version 6.0 All Sites & Staff
Research Protocol Amendments Final Version 6.0
Category:
Governance
The Research Governance Framework for Health and Social Care (RGF)
and The Medicines for Human Use (Clinical Trials) Regulations 2004
and amendments require that an organisation taking on the role of
‘Sponsor’ must have proper arrangements in place to initiate, manage,
monitor and finance a study.
Summary:
Where the organisation is providing care to research participants within
studies with other Sponsors, the organisation must ensure that
legislation related to research is followed.
These requirements not only apply to the initial approval of a research
protocol, but throughout the conduct of the research, including where
the protocol is amended,
Equality Impact
Assessment
Undertaken:
17th June
Date of Review:
11th June 2010
Approval Date/ Via:
Distribution:
Related Documents:
· Medical Director
· Clinical Risk Management Committee
Via Research and Development to:
· Researchers within ORH Trust
· Research and Development Web Site
Sponsorship of Clinical Research Studies
Trust Management Approval Policy
Monitoring and Audit of Research Studies Integrity in Research Policy
Safety Reporting in Clinical Research Policy
Incident Reporting Policy
Heather House, Research and Development Lead
Author(s):
Further Information:
From Heather House : heather.house@orh.nhs.uk
This Document
replaces:
Research Protocol Amendments Policy Version 5.1 May 2007
Lead Director:
Dr James Morris
Issue Date:
11 June 2009
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Research Protocol Amendments
C O N T E N T S
Page
Introduction……………………………………………………………………………………....
3
Policy Statement……………………………………………………………………………….....
3
Aim……………………………………………………………………………………………....
3
Scope……………………………………………………………………………………………...
3
Definitions………………………………………………………………………………………..
3
Organisational Responsibilities……………………………………………………………….
5
Chief Investigator……………………………………………………………………………
5
Principal Investigator…...…………………………………………...
5
Research and Development Staff …………………………………………………………...
5
Research & Development Lead……………
5
Organisational Arrangements………………………………………………………………….
5
Education and Training………..……………………………………………………………
5
Implementation Guidance…………………………………………………………………...
5
Equality Impact Assessment………………………………………………………………..
5
Monitoring and Review……………………………….....…………………………….....
6
References……………………………………………………………………………………
6
Document History…………………………………………………………………………..
6
Appendix A: Implementation Plan……………………………………………………………
7
Urgent Safety Measures
7
Identification of Requirement for Protocol Amendment
7
Submission Timelines
7
Documents Required
7
Review Process
7
Non­substantial Amendments
7
Implementation
8
Monitoring the Progress of Research Studies
8
Appendix B: List of Abbreviations
9
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Oxford Radcliffe Hospitals
Research Protocol Amendments
Research Protocol Amendments
Introduction
1.
The Research Governance Framework for Health and Social Care (RGF) and The
Medicines for Human Use (Clinical Trials) Regulations 2004 and amendments require
that an organisation taking on the role of ‘Sponsor’ must have proper arrangements in
place to initiate, manage, monitor and finance a study.
2.
Where the organisation is providing care to research participants within studies with
other Sponsors, the organisation must ensure that legislation related to research is
followed. by the researchers.
3.
These requirements apply not only to the initial approval of a research protocol, but also
throughout the conduct of the research, including where the research protocol is
amended,
Policy Statement
4.
It is the policy of the Trust to:
4.1 Protect the safety, dignity, rights and well­being of all patients involved in clinical
research.
4.2 Ensure that arrangements are in place for the management and monitoring of
research studies, where the Trust has taken on the role of Sponsor, including
compliance with the relevant regulations.
Aim
5.
This policy sets out a consistent procedure for the review and authorising of
amendments to the protocol of research studies for which the Oxford Radcliffe Hospitals
NHS Trust (‘the Trust’) has been asked to take on the role of ‘Sponsor’ or host
institution. 6.
This procedure aims to ensure that the Trust takes responsibility for the ongoing quality
of research studies.
Scope
7.
This Policy applies to anyone conducting research within the Trust, whether such
research is sponsored or hosted by ORH.
Definitions
Sponsor
8.
The organisation taking responsibility for initiation, management and financing (or
arranging the financing) of a clinical trial of an investigational medicinal product
(CTIMP) or research study.
Substantial Protocol Amendment
9.
A protocol amendment is required if it is necessary to make changes to the research after
approvals from the Research Ethics Committee (REC), the Medicines and Healthcare
products Regulatory Agency (MHRA) (for CTIMPS) and Research and Development
(R&D) Department have been received. The REC, MHRA and relevant R&D department
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must approve substantial amendments, before they are implemented, unless the
amendment requires immediate implementation due to safety concerns, in which case,
a formal amendment must subsequently be submitted.
A substantial amendment is defined as an amendment to the terms of the protocol or
any other supporting documentation that is likely to affect to a significant degree:
§
the safety or physical or mental integrity of the subjects of the trial
§
the scientific value of the trial
§
the conduct or management of the trial
§
the quality or safety of any investigational medicinal product used in the
trial
Further guidance is available at:
www.nres.npsa.nhs.uk/applicants/after­ethical­review/amendments/#Examples
Non­substantial Protocol Amendment
10.
These can be defined as changes to the details of the study which have no significant
implications for the subjects, conduct, management, or the scientific value of the study.
Urgent Safety Measure
11.
An amendment which needs to be implemented as a matter of urgency, in order to
protect research participants against any immediate hazard to their health or safety.
Chief Investigator
12.
The individual, as identified in the ethics application, who takes overall
for the conduct of a clinical study.
responsibility
Principal Investigator 13. The individual who takes on responsibility for conduct of the study at a particular site.
Clinical Trial of Investigational Medicinal Product (CTIMP)
14.
Any investigation in human subjects, other than a non­interventional trial*, intended
a) To discover or verify the clinical, pharmacological or other pharmacodynamic effects
of one or more medicinal products,
b) To identify any adverse reactions to one or more medicinal products or
c) To study the absorption, distribution, metabolism and excretion of one or more such
products
With the object of ascertaining the safety or efficacy of those products
Such trials will be governed by the Medicines for Human Use (Clinical Trials)
Regulations 2004 and updates.
Clinical Research Study 15.
Any investigation in human subjects, which may involve an intervention to their normal
clinical care, or may be purely observational.
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Organisation Responsibilities
Chief Investigator (CI) 16.
Identify the need for an amendment.
Principal Investigator (or delegate)
17.
Communicate with R&D, providing all relevant documentation for approval of the
amendment.
Research and Development Staff
18.
Provide advice and information to investigators regarding the amendment process.
Collation of all relevant documentation. Appraisal of any impact the amendment may
have on the Trust.
Research & Development Lead
19.
Authorise ongoing Trust Management Approval with regard to the amendment.
Organisational Arrangements
Education & Training
20.
All staff involved in the conduct of clinical trials will undertake training in Good
Clinical Practice GCP) prior to beginning their involvement in a trial. The process of
submission of substantial amendments is covered within this training.
Implementation Guidance
21.
Attached as Appendix A is an Implementation Plan, which details the measures to be
undertaken to ensure that the requirements of this policy are fully integrated in day to
day operations.
Equality Impact Assessment
22.
In accordance with Equality & Diversity legislation, this Policy has had an
Equality Impact Assessment undertaken. It has been determined that this Policy
does not discriminate against any individual or group and a full copy of the
assessment can be viewed on the Research and Development intranet page.
Monitoring & Review
23.
Staff of the Trust R&D Department are responsible for auditing compliance with the
policy on an annual basis. The R&D Manager/Lead will be responsible for formulation
and implementation of remedial action, should this be required.
24.
The Trust R&D Department will monitor and update this policy to reflect changes in
legislation and examples of best practice.
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References
25.
The Medicines for Human Use (Clinical Trials) Regulations 2004 and Amendments
26.
The Department of Health Research Governance Framework for Health and Social Care
2005
27.
ICH Harmonised Tripartite Guideline for Good Clinical Practice.
Document History
Version
Date
Author
Status
Comment
5
Feb 2006
E Tucker/J
Allen
Superseded
Reviewed and updated
5.1
May 2007
J Allen
Superseded
Reviewed and updated
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Appendix A: Implementation Plan
Urgent Safety Measures
28.
If the amendment requires urgent safety measures to be taken, it should be implemented
immediately. A formal amendment must subsequently be submitted. For CTIMPS, any
urgent safety measures must be notified to the MHRA within three days.
Identification of Requirement for Protocol Amendment
29.
Researchers should view the guidance for submitting amendments at the following web
addresses:
National Research Ethics Service (NRES)
http://www.nres.npsa.nhs.uk/
Medicines and Healthcare products Regulatory Agency (MHRA)
http://www.mhra.gov.uk/Howweregulate/Medicines/Licensing/Licensingofmedicin
es/Clinicaltrials/index.htm
Gene Therapy Advisory Committee (GTAC)
http://www.advisorybodies.doh.gov.uk/genetics/gtac/
Submission Timelines
30.
Submission of a Substantial Amendment to the REC, MHRA (where applicable) and
R&D can be undertaken in parallel. R&D staff can process the amendment in
anticipation of the relevant approvals being granted, providing that the approval letters
are, ultimately provided.
Documents Required
31.
All documents submitted to the Research Ethics Committee, should also be provided to
R&D. Other than the approval letters, an amendment cannot be processed by R&D until
all documentation has been provided.
Review Process
32.
On receipt of the required documents, a member of the R&D Team will collate all
relevant documents and assess whether there is any impact on the Trust and whether
the amendment is compliant with the relevant legislation. Further information may be
requested, where anything is unclear.
33.
Once the final approval letters relating to the amendment have been provided, a letter,
confirming ongoing Trust Management Approval (TMA) will be prepared and will be
signed by the R&D Lead or other authorised signatory. The original copy will be
supplied to the Investigator.
Non­substantial Amendments
34.
Non­substantial amendments should be copied to R&D for information and to update
the R&D database.
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Implementation
35.
Other than urgent safety measures, protocol amendments should not be implemented
until TMA has been receeived.
Monitoring the Progress of Research Studies
36.
The progress of the study through the approvals process is monitored through on­going
contact with the investigator. Copies of correspondence between the ethics committee
and the investigator, and between the MHRA (for CTIMPS) and the investigator, may
also be forwarded to R&D. The R&D database will be promptly updated on receipt of
any information.
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Appendix B: List of Abbreviations
CTIMP
Clinical Trial of an Investigational Medicinal Product
GCP
Good Clinical Practice
GTAC
Gene Therapy Advisory Committee
MHRA
Medicines and Healthcare products Regulatory Agency
NRES
National Research Ethics Service
REC
Research Ethics Committee
R&D
Research and Development
RGF
The Research Governance Framework for Health and Social Care
TMA
Trust Management Approval
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