IoPPN/SLaM Sponsorship Guidance v14
APPENDIX A – PROTOCOL GUIDANCE
A research protocol is a detailed set of instructions that outline the procedures for conducting a
research study and collecting data. It should contain detailed information about the study design and
methodology. The protocol is also a manual for the research team to ensure they adhere to the
methods outlined. Generally, your protocol should include sufficient detail so that someone unfamiliar
with the study would be able to use it to conduct the study in your absence, should they need to do so.
A research protocol is a mandatory document for submission to the research ethics committee.
It is important that your study design is classified correctly, and it is particularly important to identify
whether or not your study is a clinical trial. Clinical trials are managed in particular ways as mandated
by the Department of Health: - clinical trials now must be registered on a public trials database and NHS
trusts are monitored on their recruitment performance to clinical trials.
Please see Section A for guidance on classifying your study
Please see Section B for clinical trial protocol guidance and standards
Protocol templates
Researchers within King’s Health Partners are asked to use a good quality protocol template appropriate
for their study type. There are a range of protocol templates available as follows:
Clinical Trial of an Investigational Medicinal Product (CTIMP)
If you are conducting a Clinical Trial of an Investigational Medicinal Product (CTIMP) please use the KHP
CTO protocol template. This is downloadable on the KHP CTO website along with their SOP on writing a
GCP compliant protocol: http://www.khpcto.co.uk/SOP/gcpProtocolSOP.html
Other clinical trial (non-CTIMP)
If you are conducting a non-CTIMP clinical trial (for example a therapy randomised controlled trial)
please use the King’s College London CTU clinical trial protocol template available from the IoPPN/SLaM
R&D office or from the King’s Clinical Trials Unit directly
Basic science study
If you are conducting a basic science study, please use the GCP non-CTIMP protocol template available
from the IoPPN/SLaM R&D office
Other research
For other research where a clinical trial or basic science protocol template is not be appropriate, please
see below for details of good practice protocols which might be helpful.
https://drupal02.floridahospital.org/researchadmin/content/protocol-development-0
http://www.rch.org.au/emplibrary/cebu/Guidelines_for_writing_a_protocol.pdf
Additional guidance: for non-clinical research study designs, such as observational studies, the STROBE
guidance is a useful resource: http://www.strobe-statement.org/
PRISMA statement deals with systematic reviews and meta-analysis: http://www.prismastatement.org/
All Study Types: It would greatly benefit your protocol if you could include details of quality assurance
of the conduct of your study using Good Clinical Practice standards and the SPIRIT statement. Although
these standards relate primarily to clinical trials, where appropriate they should be used as a reference
for basic science and other study types.
Details of Good Clinical Practice can be found here:
- MRC guidelines www.mrc.ac.uk/documents/pdf/good-clinical-practice-in-clinical-trials/
- KHP CTO: GCP training: http://www.khpcto.co.uk/SOP/trainingSOP.html
- MHRA (CTIMPs only)
ttp://www.mhra.gov.uk/Howweregulate/Medicines/Inspectionandstandards/GoodClinicalPracti
ce/
The SPIRIT statement is at the end of this guidance document
Please also see the World Health Organisation recommended format for a research protocol:
http://www.who.int/rpc/research_ethics/format_rp/en/
The following points which should be included in your protocol where applicable:

The source of study funding on the protocol, and whether anything is being provided (for
example if a company is providing the study drug at no cost). For externally funded studies
please include details of the funder(s). Where studies have not been awarded external funding
please contact the R&D office for an R&D costings form and return this to us with your protocol.

Where a protocol has not been scientifically reviewed by an external funder, the R&D office will
organize an independent peer review. This will be done in parallel with risk assessment review.
Please provide the R&D office with the names and contact details of three potential reviewers
who have expertise in the area but are independent of the study. We will organise the peer
review and forward the comments to you.

Where participants will be recruited from (for example whether from the NHS, advertisement,
existing registries).

Where the consent and screening visit and subsequent study visits (post consent) will take
place.

For studies involving a drug, whether consent is taken by a medic, if not how the consent
process will be properly delegated.

For studies involving a drug, where the drug/placebo is sourced, and which pharmacy is storing
and dispensing.

An outline of risks and burdens (and a description of side effects of the study drug if applicable,
including contraindications).

Safety reporting as per NRES guidelines (http://www.hra.nhs.uk/resources/during-and-afteryour-study/progress-and-safety-reporting/ or contact the R&D office for a copy of current NRES
guidelines). Any safety reporting to NRES must also be copied to the sponsor via the
SLaM/IoPPN R&D office.

If you are randomizing, include the process of randomization and blinding, procedures and
conditions for unblinding. (please see the Emergency out of hours code break Flow Diagram
document)

If you are taking tissue samples, include details of storage and analysis of all tissue samples
(including urine, saliva, hair samples) - where they are stored and analysed and for how long,
whether they are stored under an organizational Human Tissue Authority licence, who will have
access to the samples in the future (including any other organisations/commercial companies).

Details of data management – how data will be managed appropriate to the study type,
including data handling and coding for computer analysis, monitoring and verification and
assuring the quality of the data. Include a description of the statistical methods to be used for
the data analysis, reasons for selection of the sample size and power of the study.

For clinical trials - details of the Data and Ethics Monitoring Committee (DMEC) and Trial
Steering Committee (TSC) arrangements, or the reasons if these are not being set up. For all
other study types such as basic science please include an explanation of appropriate oversight
arrangements.

It would also be helpful if you could include details of quality assurance of the conduct of the
study using Good Clinical Practice standards and SPIRIT statement. Although these standards
relate primarily to clinical trials, where appropriate they should be used as a reference for basic
science and other study types. Details of GCP and SPIRIT are on the R&D office protocol
guidance.
Appendix A Classification of studies
1. Classification of clinical trials
A. Is the study potentially a Clinical trial of an investigational medicinal product (CTIMP)
If your study involves administering or analysing a drug or other substance it is essential that we
determine whether or not it is a CTIMP. As a rule of thumb, this will apply if you are administering any
drug or substance, or if the protocol includes anything that looks as if you are trying to find out more
information about a study drug, whether or not you are administering this yourself (this includes a drug
that is being used already in routine clinical care).
The MHRA provide an algorithm to assist investigators and sponsors determine whether a study is a
clinical medicinal trial. Often a research study can be classified straightforwardly into CTIMP or non
CTIMP. There are a small number of studies however where it this is not clear and in these cases the
algorithm can be of limited use. Whether a study is a CTIMP or not is not always related to whether a
drug is administered as a part of the research. The MHRA have in the past classified studies as CTIMPs
where the drug involved has been administered to patients as part of their clinical care rather than
being administered by the research team for the purposes of the trial. In other studies where a drug is
administered by the research team but is being used as a probe in a scanning study for example, such
studies have been classified as non-CTIMPs.
Where there is uncertainty about how to classify a study the R&D office consults with the KHP Clinical
Trials Office, and will take their view as to whether there is a need to refer the protocol to the MHRA for
a decision. It is important that we do this, as if we make the decision ourselves to classify a study as a
non-CTIMP and were then to be inspected by the MHRA, it is possible that inspectors would take a
different view.
Where a referral to the KHP CTO and/or MHRA is required, this can take up to 3-4 weeks. Investigators
are advised to contact R&D at the earliest stage if their study might potentially be classified as a CTIMP.
B. Classification of clinical trials other than trials of medicines or devices (in line with the Health
Research Authority)
The Department of Health definition of a clinical trial is as follows: A set of medical research procedures
conducted on human participants to allow safety and adverse effects of interventions, their efficacy, or
their effectiveness to be established often by comparison with alternative or placebo/sham
interventions. Interventions may be drugs, diagnostics, prophylactics, surgery, devices, non-invasive
therapies, screening or other healthcare procedures or technologies.
Clinical trials are managed in a specific way and so it is important that they are correctly classified at the
outset. The HRA require clinical trials to be registered on a public trials database and for trials being
conducted in the NHS their recruitment is measured against Department of Health benchmarks. This
applies to trials of medicines and devices as well as other clinical trials which this section covers.
Both the HRA and the Department of Health classify clinical trials as those selecting one of the first four
options on the IRAS project filter section 2:




Clinical trial of an investigational medicinal product
Clinical investigation or other study of a medical device
Combined trial of an investigational medicinal product and an investigational medical device
Other clinical trial to study a novel intervention or randomised clinical trial to compare
interventions in clinical practice
This guidance covers the fourth option (Other clinical trial). The IRAS project filter guidance states that
this option should be selected for clinical research not involving investigational medicinal products or
medical devices. For example, this option would be appropriate for research involving:
 Surgery; Radiotherapy; Imaging investigations; Mental health investigations or therapies;
Physiological investigations; Trials of products not defined as medicines or medical devices (e.g.
nutritional); Complementary or alternative therapies
This option should be selected where a study is studying a novel intervention or randomised clinical trial
to compare interventions in clinical practice and has an impact on patient clinical care. Where a study
has clinical elements and doesn’t have an impact on clinical care, the next option on the IRAS project
filter will be more appropriate:

Basic science study involving procedures with human participants
This option may involve patients or healthy volunteers as participants, but the study does not affect any
clinical care that the participant may be receiving. It is appropriate for scientific investigations involving
procedures with participants that are additional to any clinical care, but not studying a novel clinical
intervention or involving randomisation between treatment groups or any other change in existing
clinical care. For example, it would be suitable for studies involving:
 Imaging investigations (MRI, ultrasound etc); Physical examinations; Physical tests; computer
tests; Filming or photography; Sample-taking.
There are some cases where a study will have an impact on clinical care but is not studying a novel
clinical intervention. In these cases it might be more appropriate to select the following IRAS project
filter option:

Other study:
This option is selected only if the research does not appear to fit any other category but might be
relevant where a study does impact on clinical care but where it is not studying a novel intervention or
randomised clinical trial to compare interventions in clinical practice.
Where a study impacts on patient clinical care and/or involves randomization and the investigator has
classified it as a non-clinical trial, the R&D office will need to record the reasons for this, and will ask you
to provide details of the rationale. Where the IRAS project filter option ‘other clinical trial’ has been
selected and a decision is made to not register the study on a clinical trials database, the sponsor/CI is
required to write to the HRA providing the reason for non-registration. If this is not done the study will
be deemed by the HRA to be in breach of its ethics approval. Full details are on the HRA website:
http://www.hra.nhs.uk/news/2013/09/10/trial-registration-to-be-condition-of-the-favourable-recopinion-from-30-september/
Appendix B Clinical trial protocol development and standards
The following guidance and standards apply to clinical trials and you are advised to refer to these when
developing your clinical trial protocol.
SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) is an international initiative
that aims to improve the quality of clinical trial protocols by defining an evidence-based set of items to
address in a protocol. For details including the SPIRIT checklist of protocol items please see:
http://www.spirit-statement.org/ and http://www.bmj.com/content/346/bmj.e7586 for an
explanation and elaboration of the SPIRIT guidelines.
Please see the SPIRIT checklist below.
CONSORT (Consolidated Standards of Reporting Trials) are a set of initiatives developed by the
CONSORT Group to alleviate the problems arising from inadequate reporting of randomised controlled
trials. Details of the CONSORT statement, 25 item checklist for reporting trials and links to the initiatives
can be found here: http://www.consort-statement.org/
There are currently nine extensions to the CONSORT statement that cover various trial designs,
interventions and data (including reporting ‘harms’) which can be found here: http://www.consortstatement.org/extensions. Please also see the following article on CONSORT extensions
http://annals.org/article.aspx?articleid=739590
TIDieR (template for intervention description and replication) is 12 point checklist and guide for better
reporting of interventions. Details can be found here: http://www.bmj.com/content/348/bmj.g1687
The Equator Network provides details and links to the above and additional initiatives:
http://www.equator-network.org/
The following toolkits might be helpful:
Experimental medicine toolkit http://www.em-toolkit.ac.uk/home.cfm is designed to assist with
assessing the risks involved in experimental medicine studies
Clinical Trials toolkit: http://www.ct-toolkit.ac.uk/ provides practical advice to researchers in designing
and conducting publicly funded clinical trials in the UK
SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related
documents*
Section/item
ItemN Description
o
Administrative information
Title
1
Descriptive title identifying the study design, population, interventions, and, if
applicable, trial acronym
Trial registration
2a
Trial identifier and registry name. If not yet registered, name of intended
registry
2b
All items from the World Health Organization Trial Registration Data Set
Protocol version
3
Date and version identifier
Funding
4
Sources and types of financial, material, and other support
Roles and
responsibilities
5a
Names, affiliations, and roles of protocol contributors
5b
Name and contact information for the trial sponsor
5c
Role of study sponsor and funders, if any, in study design; collection,
management, analysis, and interpretation of data; writing of the report; and
the decision to submit the report for publication, including whether they will
have ultimate authority over any of these activities
5d
Composition, roles, and responsibilities of the coordinating centre, steering
committee, endpoint adjudication committee, data management team, and
other individuals or groups overseeing the trial, if applicable (see Item 21a for
data monitoring committee)
6a
Description of research question and justification for undertaking the trial,
including summary of relevant studies (published and unpublished) examining
benefits and harms for each intervention
6b
Explanation for choice of comparators
Objectives
7
Specific objectives or hypotheses
Trial design
8
Description of trial design including type of trial (eg, parallel group, crossover,
factorial, single group), allocation ratio, and framework (eg, superiority,
equivalence, noninferiority, exploratory)
Introduction
Background and
rationale
Methods: Participants, interventions, and outcomes
Study setting
9
Description of study settings (eg, community clinic, academic hospital) and list
of countries where data will be collected. Reference to where list of study sites
can be obtained
Eligibility criteria
10
Inclusion and exclusion criteria for participants. If applicable, eligibility criteria
for study centres and individuals who will perform the interventions (eg,
surgeons, psychotherapists)
Interventions
11a
Interventions for each group with sufficient detail to allow replication,
including how and when they will be administered
11b
Criteria for discontinuing or modifying allocated interventions for a given trial
participant (eg, drug dose change in response to harms, participant request, or
improving/worsening disease)
11c
Strategies to improve adherence to intervention protocols, and any procedures
for monitoring adherence (eg, drug tablet return, laboratory tests)
11d
Relevant concomitant care and interventions that are permitted or prohibited
during the trial
12
Primary, secondary, and other outcomes, including the specific measurement
variable (eg, systolic blood pressure), analysis metric (eg, change from baseline,
final value, time to event), method of aggregation (eg, median, proportion),
and time point for each outcome. Explanation of the clinical relevance of
chosen efficacy and harm outcomes is strongly recommended
Outcomes
Participant timeline 13
Time schedule of enrolment, interventions (including any run-ins and
washouts), assessments, and visits for participants. A schematic diagram is
highly recommended (see Figure)
Sample size
14
Estimated number of participants needed to achieve study objectives and how
it was determined, including clinical and statistical assumptions supporting any
sample size calculations
Recruitment
15
Strategies for achieving adequate participant enrolment to reach target sample
size
Methods: Assignment of interventions (for controlled trials)
Allocation:
Sequence
generation
16a
Method of generating the allocation sequence (eg, computer-generated
random numbers), and list of any factors for stratification. To reduce
predictability of a random sequence, details of any planned restriction (eg,
blocking) should be provided in a separate document that is unavailable to
those who enrol participants or assign interventions
Allocation
concealment
mechanism
16b
Mechanism of implementing the allocation sequence (eg, central telephone;
sequentially numbered, opaque, sealed envelopes), describing any steps to
conceal the sequence until interventions are assigned
Implementation
16c
Who will generate the allocation sequence, who will enrol participants, and
who will assign participants to interventions
17a
Who will be blinded after assignment to interventions (eg, trial participants,
care providers, outcome assessors, data analysts), and how
17b
If blinded, circumstances under which unblinding is permissible, and procedure
for revealing a participant’s allocated intervention during the trial
Blinding (masking)
Methods: Data collection, management, and analysis
Data collection
methods
18a
Plans for assessment and collection of outcome, baseline, and other trial data,
including any related processes to promote data quality (eg, duplicate
measurements, training of assessors) and a description of study instruments
(eg, questionnaires, laboratory tests) along with their reliability and validity, if
known. Reference to where data collection forms can be found, if not in the
protocol
18b
Plans to promote participant retention and complete follow-up, including list of
any outcome data to be collected for participants who discontinue or deviate
from intervention protocols
Data management
19
Plans for data entry, coding, security, and storage, including any related
processes to promote data quality (eg, double data entry; range checks for
data values). Reference to where details of data management procedures can
be found, if not in the protocol
Statistical methods
20a
Statistical methods for analysing primary and secondary outcomes. Reference
to where other details of the statistical analysis plan can be found, if not in the
protocol
20b
Methods for any additional analyses (eg, subgroup and adjusted analyses)
20c
Definition of analysis population relating to protocol non-adherence (eg, as
randomised analysis), and any statistical methods to handle missing data (eg,
multiple imputation)
21a
Composition of data monitoring committee (DMC); summary of its role and
reporting structure; statement of whether it is independent from the sponsor
and competing interests; and reference to where further details about its
charter can be found, if not in the protocol. Alternatively, an explanation of
why a DMC is not needed
21b
Description of any interim analyses and stopping guidelines, including who will
have access to these interim results and make the final decision to terminate
the trial
Harms
22
Plans for collecting, assessing, reporting, and managing solicited and
spontaneously reported adverse events and other unintended effects of trial
interventions or trial conduct
Auditing
23
Frequency and procedures for auditing trial conduct, if any, and whether the
process will be independent from investigators and the sponsor
Methods: Monitoring
Data monitoring
Ethics and dissemination
Research ethics
approval
24
Plans for seeking research ethics committee/institutional review board
(REC/IRB) approval
Protocol
amendments
25
Plans for communicating important protocol modifications (eg, changes to
eligibility criteria, outcomes, analyses) to relevant parties (eg, investigators,
REC/IRBs, trial participants, trial registries, journals, regulators)
Consent or assent
26a
Who will obtain informed consent or assent from potential trial participants or
authorised surrogates, and how (see Item 32)
26b
Additional consent provisions for collection and use of participant data and
biological specimens in ancillary studies, if applicable
Confidentiality
27
How personal information about potential and enrolled participants will be
collected, shared, and maintained in order to protect confidentiality before,
during, and after the trial
Declaration of
interests
28
Financial and other competing interests for principal investigators for the
overall trial and each study site
Access to data
29
Statement of who will have access to the final trial dataset, and disclosure of
contractual agreements that limit such access for investigators
Ancillary and posttrial care
30
Provisions, if any, for ancillary and post-trial care, and for compensation to
those who suffer harm from trial participation
Dissemination policy 31a
Plans for investigators and sponsor to communicate trial results to participants,
healthcare professionals, the public, and other relevant groups (eg, via
publication, reporting in results databases, or other data sharing
arrangements), including any publication restrictions
31b
Authorship eligibility guidelines and any intended use of professional writers
31c
Plans, if any, for granting public access to the full protocol, participant-level
dataset, and statistical code
32
Model consent form and other related documentation given to participants
and authorised surrogates
Appendices
Informed consent
materials
Biological specimens 33
Plans for collection, laboratory evaluation, and storage of biological specimens
for genetic or molecular analysis in the current trial and for future use in
ancillary studies, if applicable
*It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation
& Elaboration for important clarification on the items. Amendments to the protocol should be tracked
and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons
“Attribution-NonCommercial-NoDerivs 3.0 Unported” license.