Drug/Device Protocol Template
© Copyright SPIRIT Group 2013
Published date: March 2013
Review Date: August 2014
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 2 of 21
NOTE TO USERS Who should use this
template?
Anyone conducting clinical research which involves an intervention,
that may include drugs and/or devices and/or any other prospective
interventions (e.g., surgery)
Why do you need a
protocol?
The protocol is essential for study conduct, review, reporting, and
interpretation.
Why use this template? SPRIRIT (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.
Reference: Chan et al., (2013) SPIRIT 2013 Explanation and
Elaboration: Guidance for protocols of clinical trials. BMJ 2013;
346:e7586
How do I use this template? There is a brief explanation under each heading stating the
information that should be contained in that section. A detailed
explanation and example can be accessed via clicking on the
hyperlink titled “Explanation & Example”.
You will need to input your study specific information under each
heading and remove explanatory information.
As this is a template, users are remaindered that not all examples
may be applicable to their study. Please contact your institution to
discuss specific protocol questions.
Do I still need to complete
the National Ethics
Application Form (NEAF)
Yes – you must finalise your protocol prior to completing the NEAF.
The NEAF is a form used by ethics committees to conduct standard
review of all projects. While you need to refer to your protocol to
answer most questions in the NEAF, it does not replace the need for
a detailed protocol.
Copyright This template is licensed under the Creative Commons Attribution
NonCommercial-NoDerivs 3.0 Unported License
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 3 of 21
PROTOCOL
[Insert Full study Title] Protocol Number (if applicable):
Version: # Date: DD/MM/YYYY
CONFIDENTIAL
This document is confidential and the property of <<Insert Name of Institution/s>>. No part of it may be transmitted, reproduced, published, or used without prior written authorisation from the
institution.
Statement of Compliance
This document is a protocol for a research project. This study will be conducted in compliance with all stipulation of this protocol, the conditions of the ethics committee approval, the NHMRC National Statement on ethical Conduct in Human Research (2007) and the Note for Guidance on Good Clinical
Practice (CPMP/ICH-135/95).
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 4 of 21
TABLE OF CONTENTS
CONTENTS Notes to Users ............................................................................................................................. 1
Table of Contents ......................................................................................................................... 4
Administrative Information .......................................................................................................... 7
1. Title ............................................................................................................................................. 7
2. Trial Registration ......................................................................................................................... 7
2a Registry ....................................................................................................................................... 7
2b data set ...................................................................................................................................... 7
3. Protocol Version .......................................................................................................................... 8
4. Funding ....................................................................................................................................... 8
5. Roles and Responsibilities ........................................................................................................... 9
5a Contributorship .......................................................................................................................... 9
5b Sponsor Contact Information ..................................................................................................... 9
5c Sponsor and Funder ................................................................................................................... 9
5d Committees ................................................................................................................................ 9
Introduction .............................................................................................................................. 10
6. Background and Rationale ........................................................................................................ 10
6a Choice of Comparators............................................................................................................. 10
6b Explanation for Choice of Comparators ................................................................................... 10
7. Objectives.................................................................................................................................. 10
8. Study Design.............................................................................................................................. 11
Methods: Participants, Interventions, Outcomes ........................................................................ 11
9. Study Setting ............................................................................................................................. 11
10. Eligibility Criteria ................................................................................................................... 11
11. Interventions ......................................................................................................................... 11
11a Interventions .......................................................................................................................... 11
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 5 of 21
11b Modifications ......................................................................................................................... 11
11c Adherence .............................................................................................................................. 12
11d Concomitant Care .................................................................................................................. 12
12. Outcomes .............................................................................................................................. 12
13. Participant Timeline .............................................................................................................. 12
14. Sample Size ........................................................................................................................... 15
15. Recruitment .......................................................................................................................... 15
16. Allocation .............................................................................................................................. 15
16a Sequence Generation ............................................................................................................. 15
16b Concealment Mechanism ...................................................................................................... 15
16c Implementation ...................................................................................................................... 16
17. Blinding (masking) ................................................................................................................. 16
17a Blinding (masking) .................................................................................................................. 16
17B Emergency Unblinding ........................................................................................................... 16
Methods: Data Collection, Management, Analysis ...................................................................... 17
18. Data Collection Methods ...................................................................................................... 17
18a Data Collection Methods ....................................................................................................... 17
18b Retention ............................................................................................................................... 17
19. Data Management ................................................................................................................ 17
20. Statistical Methods ............................................................................................................... 17
20a Outcome ................................................................................................................................. 17
20b Additional Analyses ................................................................................................................ 17
20c analysis Population and Missing Data .................................................................................... 18
Methods: Monitoring ................................................................................................................. 18
21. Data Monitoring .................................................................................................................... 18
21A Formal Committee ................................................................................................................. 18
21b Interim Analysis ...................................................................................................................... 18
22. Harms .................................................................................................................................... 18
23. Auditing ................................................................................................................................. 18
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 6 of 21
ethics and Dissemination ........................................................................................................... 18
24. Research Ethics Approval ...................................................................................................... 19
25. Protocol Amendments .......................................................................................................... 19
26. Consent ................................................................................................................................. 19
26a Consent .................................................................................................................................. 19
26b Ancillary Studies ..................................................................................................................... 19
27. Confidentiality ....................................................................................................................... 19
28. Declaration of Interests ........................................................................................................ 19
29. Access to Data ....................................................................................................................... 20
30. Ancillary and Post-Trail Care ................................................................................................. 20
31. Dissemination Policy ............................................................................................................. 20
31a Trial Results ............................................................................................................................ 20
31b Authorship ............................................................................................................................. 20
31c Reproducible Research ........................................................................................................... 20
Appendices ................................................................................................................................ 20
32. Informed consent Materials ................................................................................................. 20
33. Biological Specimens ............................................................................................................. 21
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 7 of 21
ADMINISTRATIVE INFORMATION
1. TITLE
What should be included in this section?
Descriptive title identifying the study design, population, interventions. If applicable, include your
study acronym.
Explanation & Example
2. TRIAL REGISTRATION
2A REGISTRY
What should be included in this section?
Trial identifier and registry name. If not yet registered, name of intended registry
Explanation & Example
2B DATA SET
What should be included in this section?
All items from the World Health Organisation Trial Registration Data Set
Explanation & Example
Data Category Information
Primary registry and study indentifying number
Date of registration in primary registry
Secondary identifying numbers
Source(s) of monetary or material support
Primary sponsor
Secondary sponsor(s)
Contact for public queries
Contact for scientific queries
Public title
Scientific title
Countries of recruitment
Health condition(s) or problem(s) studied
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 8 of 21
Data Category Information
Intervention(s)
Key inclusion and exclusion criteria
Study type
Date of first enrolment
Target sample size
Primary outcome(s)
Key secondary outcomes
3. PROTOCOL VERSION
What should be included in this section?
Date and version identifier
Explanation & Example
Issue Date:
Protocol amendment number:
Author(s):
Revision Chronology:
Date of change
Summary of changes
4. FUNDING
What should be included in this section?
Sources and types of financial, material and other support
Explanation & Example
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 9 of 21
5. ROLES AND RESPONSIBILITIES
5A CONTRIBUTORSHIP
What should be included in this section?
Names, affiliations, and roles of protocol contributors.
Explanation & Example
Author Name
Summary of contribution
5B SPONSOR CONTACT INFORMATION
What should be included in this section?
Name and contact information for the study sponsor (note the sponsor may be a funding body such
as the National Health and Medical Research Council (NHMRC)).
Explanation & Example
Study Sponsor
Sponsor’s Reference number (if applicable)
Contact name
Address
Telephone
5C SPONSOR AND FUNDER What should be included in this section?
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.
Explanation & Example
5D COMMITTEES What should be included in this section?
Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint
adjudication committee, data management team, and other individuals or groups overseeing the
study, if application see item 21a for Data Monitoring Committee).
Explanation & Example
Example headings may include the following:
1. Principal Investigator and Research Staff
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 10 of 21
2. Steering Committee
3. Study management Committee
4. Data manager
5. Lead investigators
INTRODUCTION
6. BACKGROUND AND RATIONALE
6A CHOICE OF COMPARATORS What should be included in this section?
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.
Explanation & Example
6B EXPLANATION FOR CHOICE OF COMPARATORS What should be included in this section?
Explanation for choice of comparators.
Explanation & Example
7. OBJECTIVES What should be included in this section?
Specific objectives or hypotheses
Explanation & Example
Example headings 1. Research Hypothesis
2. Study Objectives
a. Primary Objectives
b. Secondary Objectives
c. Other Secondary Objectives
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 11 of 21
8. STUDY DESIGN What should be included in this section?
Description of study design including type of trial (e.g., parallel group, crossover, factorial, single
group), allocation ratio, and framework (e.g., superiority, equivalence, non-inferiority, exploratory).
Explanation & Example
METHODS: PARTICIPANTS, INTERVENTIONS, OUTCOMES
9. STUDY SETTING What should be included in this section?
Description of study settings (e.g., community clinic, academic hospital) and list of countries where
data will be collected. Reference to where list of study sites can be obtained.
Explanation & Example
10. ELIGIBILITY CRITERIA What should be included in this section?
Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centre and
individuals who will perform the interventions (e.g., surgeons, psychotherapists).
Explanation & Example Example headings 10.1 Inclusion Criteria
10.2 Exclusion Criteria
11. INTERVENTIONS
11A INTERVENTIONS What should be included in this section?
Interventions for each group with sufficient detail to allow replication, including how and when they
will be administered.
Explanation & Example
11B MODIFICATIONS What should be included in this section?
Criteria for discontinuing or modifying allocated interventions for a given study participants (e.g.,
drug dose change in response to harms, participant request, or improving/worsening disease).
Explanation & Example
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 12 of 21
11C ADHERENCE What should be included in this section?
Strategies to improve adherence to intervention protocols, and any procedures for monitoring
adherence (e.g., drug tablet return; laboratory tests).
Explanation & Example
11D CONCOMITANT CARE What should be included in this section?
Relevant concomitant care and interventions that are permitted or prohibited during the trial.
Explanation & Example
12. OUTCOMES What should be included in this section?
Primary, secondary, and other outcomes, including the specific measurement variable (e.g., systolic
blood pressure), analysis metric (e.g., change from baseline, final value, time to event), method of
aggregation (e.g., medical, proportion), and time point for each outcome. Explanation of the clinical
relevance of chosen efficacy and harm outcomes is strongly recommended.
Explanation & Example
13. PARTICIPANT TIMELINE What should be included in this section?
Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and
visits for participants. A schematic diagram is highly recommended.
Explanation & Example
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 13 of 21
Figure. Example template of recommended content for the schedule of enrolment, interventions, and assessments.*
STUDY PERIOD
Enrolment Allocation Post-allocation Close-out
TIMEPOINT** -t1 0 t1 t2 t3 t4 etc. tx
ENROLMENT:
Eligibility screen X
Informed consent X
[List other
procedures] X
Allocation X
INTERVENTIONS:
[Intervention A]
[Intervention B] X X
[List other study
groups]
ASSESSMENTS:
[List baseline
variables] X X
[List outcome
variables] X X etc. X
[List other data
variables] X X X X etc. X
*Recommended content can be displayed using various schematic formats. See SPIRIT 2013 Explanation and Elaboration for examples from protocols.
**List specific timepoints in this row.
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 14 of 21
Example Study Timeline (flow diagram)
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 15 of 21
14. SAMPLE SIZE What should be included in this section?
Estimated number of participants needed to achieve study objectives and how it was determined,
including clinical and statistical assumptions supporting any sample size calculations.
Explanation & Example
15. RECRUITMENT What should be included in this section?
Strategies for achieving adequate participant enrolment to reach target sample size.
Explanation & Example
16. ALLOCATION
16A SEQUENCE GENERATION What should be included in this section?
Method of generating the allocation sequence (e.g., computer-generated random numbers), and list
of any factors for stratification. To reduce predictability of a random sequence, details of any
planned restriction (e.g., blocking) should be provided in a separate document that is unavailable to
those who enrol participants or assign interventions. Explanation & Example
16B CONCEALMENT MECHANISM What should be included in this section?
Mechanism of implementing the allocation sequence (e.g., central telephone; sequentially
numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until
interventions are assigned.
Explanation & Example
Table 3. Differences between allocation concealment and blinding (masking) for trials with
individual randomisation.
Allocation concealment Blinding (masking)
Definition Unawareness of the next study
group assignment in the
allocation sequence
Unawareness of the study
group to which trial
participants have already been
assigned
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 16 of 21
Allocation concealment Blinding (masking)
Purpose Prevent selection bias by
facilitating enrolment of
comparable participants in each
study group
Prevent ascertainment,
performance, and attrition
biases by facilitating
comparable concomitant care
(aside from trial interventions)
and evaluation of participants
in each study group
Timing of implementation Before study group assignment Upon study group assignment
and beyond
Who is kept unaware Trial participants and
individuals enrolling them
One or more of the following:
Trial participants, investigators,
care providers, outcome
assessors.
Other groups: Endpoint
adjudication committee, data
handlers, data analysts
Always possible to implement? Yes No
16C IMPLEMENTATION What should be included in this section?
Who will generate the allocation sequence, who will enrol participants, and who will assign
participants to interventions.
Explanation & Example
17. BLINDING (MASKING)
17A BLINDING (MASKING) What should be included in this section?
Who will be blinded after assignment to interventions (e.g., trial participants, care providers,
outcome assessors, data analysts), and how?
Explanation & Example
17B EMERGENCY UNBLINDING What should be included in this section?
If blinded, circumstances under which unblinding is permissible, and procedure for revealing a
participant’s allocated intervention during the trial
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 17 of 21
Explanation & Example
METHODS: DATA COLLECTION, MANAGEMENT, ANALYSIS
18. DATA COLLECTION METHODS
18A DATA COLLECTION METHODS What should be included in this section?
Plans for assessment and collection of outcome, baseline, and other study data, including any
related processes to promote data quality (e.g., duplicate measurements, training of assessors) and
a description of study instruments (e.g., 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.
Explanation & Example
18B RETENTION What should be included in this section?
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.
Explanation & Example
19. DATA MANAGEMENT What should be included in this section?
Plans for data entry, coding, security, and storage, including any related processes to promote data
quality (e.g., double data entry; range checks for data values). Reference to where details of data
management procedures can be found, if not in the protocol.
Explanation & Example
20. STATISTICAL METHODS
20A OUTCOME What should be included in this section?
Statistical methods for analysing primary and secondary outcomes. Reference to where other details
of statistical analysis plan can be found, if not in the protocol.
Explanation & Example
20B ADDITIONAL ANALYSES What should be included in this section?
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 18 of 21
Methods for any additional analyses (e.g., subgroup and adjusted analyses).
Explanation & Example
20C ANALYSIS POPULATION AND MISSING DATA What should be included in this section?
Definition of analysis population relating to protocol non-adherence (e.g., as randomised analysis),
and any statistical methods to handle missing data (e.g., multiple imputation).
Explanation & Example
METHODS: MONITORING
21. DATA MONITORING
21A FORMAL COMMITTEE What should be included in this section? 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. Example & Explanation
21B INTERIM ANALYSIS What should be included in this section? 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. Example & Explanation
22. HARMS What should be included in this section?
Plans for collecting, assessing, reporting and managing solicited and spontaneously reported adverse
events and other unintended effects of trial interventions or trial conduct.
Example & Explanation
23. AUDITING What should be included in this section?
Frequency and procedures for auditing trial conduct, if any, and whether the process will be
independent from investigators and the sponsor.
Explanation & Example
ETHICS AND DISSEMINATION
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 19 of 21
24. RESEARCH ETHICS APPROVAL What should be included in this section?
Plans for seeking research ethics approval.
Explanation & Example
25. PROTOCOL AMENDMENTS What should be included in this section?
Plans for communicating important protocol modifications (e.g., changes to eligibility criteria,
outcomes analyses) to relevant parties (e.g., investigators, HRECs, trial participants, trial registries,
journals, regulators).
Explanation & Example
26. CONSENT
26A CONSENT What should be included in this section?
Who will obtain informed consent from potential trial participants for appropriate consent
procedures for persons under the age of 18.
Explanation & Example
26B ANCILLARY STUDIES What should be included in this section?
Additional consent provisions for collection and use of participant data and biological specimens in
ancillary studies, if applicable
Explanation & Example
27. CONFIDENTIALITY What should be included in this section?
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.
Explanation & Example
28. DECLARATION OF INTERESTS What should be included in this section?
Financial and other competing interests for principal investigators for the overall trial and each study
site.
Explanation & Example
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 20 of 21
29. ACCESS TO DATA What should be included in this section?
Statement of who will have access to the final trial dataset, and disclosure of contractual agreement
that limit such access for investigators.
Explanation & Example
30. ANCILLARY AND POST-TRAIL CARE What should be included in this section?
Provisions, if an, for ancillary and post-trial care, and for compensation to those who suffer harm
from trial participation.
Explanation & Example
31. DISSEMINATION POLICY
31A TRIAL RESULTS What should be included in this section?
Plans for investigators and sponsor to communicate trial results to participants, healthcare
professionals, the public, and other relevant groups (e.g., via publication, reporting in results
databases, or other data sharing arrangements), including any publication restrictions.
Explanation & Example
31B AUTHORSHIP What should be included in this section?
Authorship eligibility guidelines and any intended use of professional writers.
Explanation & Example
31C REPRODUCIBLE RESEARCH What should be included in this section?
Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical
code.
Explanation & Example
APPENDICES
32. INFORMED CONSENT MATERIALS What should be included in this section?
Model consent form and other related documentation given to participants and authorised
surrogates.
Study Name: <<insert study name>>
Protocol Number: <<insert protocol number>>
Version: Day Month Year Page 21 of 21
Explanation & Example
33. BIOLOGICAL SPECIMENS What should be included in this section?
Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or
molecular analysis in current trial and for future use in ancillary studies. (if applicable).
Explanation & Example