drug/device protocol template - sydney children's hospital · study name: protocol number: ...

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 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

http://www.bmj.com/content/346/bmj.e7586.full?ijkey=QpAJnYI57zIwVr3&keytype=ref



http://www.creativecommons.org/licenses/by-nc-nd/3.0/

http://www.creativecommons.org/licenses/by-nc-nd/3.0/




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).




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




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




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




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


Trial identifier and registry name. If not yet registered, name of intended registry


2B DATA SET


All items from the World Health Organisation Trial Registration Data Set


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

http://www.spirit-statement.org/title/

http://www.spirit-statement.org/registry/

http://www.spirit-statement.org/data-set/




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


Date and version identifier


Issue Date:

Protocol amendment number:

Author(s):

Revision Chronology:

Date of change

Summary of changes

4. FUNDING


Sources and types of financial, material and other support


http://www.spirit-statement.org/protocol-version/

http://www.spirit-statement.org/funding/




5. ROLES AND RESPONSIBILITIES

5A CONTRIBUTORSHIP


Names, affiliations, and roles of protocol contributors.


Author Name

Summary of contribution

5B SPONSOR CONTACT INFORMATION


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)).


Study Sponsor

Sponsor’s Reference number (if applicable)

Contact name

Address

Telephone

Email

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.


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).


Example headings may include the following:

1. Principal Investigator and Research Staff

http://www.spirit-statement.org/contributorship/

http://www.spirit-statement.org/sponsor-contact-information/

http://www.spirit-statement.org/sponsor-and-funder/

http://www.spirit-statement.org/committees/




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.


6B EXPLANATION FOR CHOICE OF COMPARATORS What should be included in this section?

Explanation for choice of comparators.


7. OBJECTIVES What should be included in this section?

Specific objectives or hypotheses


Example headings 1. Research Hypothesis

2. Study Objectives

a. Primary Objectives

b. Secondary Objectives

c. Other Secondary Objectives

http://www.spirit-statement.org/background-and-rationale/

http://www.spirit-statement.org/choice-of-comparators/

http://www.spirit-statement.org/objectives/




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).


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.


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.


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).


http://www.spirit-statement.org/trial-design/

http://www.spirit-statement.org/study-setting/

http://www.spirit-statement.org/eligibility-criteria/

http://www.spirit-statement.org/interventions/

http://www.spirit-statement.org/modifications/




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).


11D CONCOMITANT CARE What should be included in this section?

Relevant concomitant care and interventions that are permitted or prohibited during the trial.


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.


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.


http://www.spirit-statement.org/adherence/

http://www.spirit-statement.org/adherence/

http://www.spirit-statement.org/outcomes-2/

http://www.spirit-statement.org/participant-timeline/




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.




Example Study Timeline (flow diagram)




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.


15. RECRUITMENT What should be included in this section?

Strategies for achieving adequate participant enrolment to reach target sample size.


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.


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

http://www.spirit-statement.org/sample-size/

http://www.spirit-statement.org/recruitment/

http://www.spirit-statement.org/sequence-generation/

http://www.spirit-statement.org/concealment-mechanism/




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.


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?


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

http://www.spirit-statement.org/implementation/

http://www.spirit-statement.org/blinding-masking/





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.


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.


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.


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.


20B ADDITIONAL ANALYSES What should be included in this section?

http://www.spirit-statement.org/emergency-unblinding/

http://www.spirit-statement.org/data-collection-methods/

http://www.spirit-statement.org/retention/

http://www.spirit-statement.org/data-management/

http://www.spirit-statement.org/outcomes/




Methods for any additional analyses (e.g., subgroup and adjusted analyses).


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).


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.


ETHICS AND DISSEMINATION

http://www.spirit-statement.org/additional-analyses/

http://www.spirit-statement.org/analysis-population-and-missing-data/

http://www.spirit-statement.org/formal-committee/

http://www.spirit-statement.org/interim-analysis/

http://www.spirit-statement.org/harms/

http://www.spirit-statement.org/auditing/




24. RESEARCH ETHICS APPROVAL What should be included in this section?

Plans for seeking research ethics approval.


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).


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.


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


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.


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.


http://www.spirit-statement.org/research-ethics-approval/

http://www.spirit-statement.org/protocol-amendments/

http://www.spirit-statement.org/concent-or-assent/

http://www.spirit-statement.org/concent-or-assent/

http://www.spirit-statement.org/confidentiality/

http://www.spirit-statement.org/declaration-of-interests/




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.


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.


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.


31B AUTHORSHIP What should be included in this section?

Authorship eligibility guidelines and any intended use of professional writers.


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.


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.

http://www.spirit-statement.org/declaration-of-interests/

http://www.spirit-statement.org/ancillary-and-post-trial-care/

http://www.spirit-statement.org/31a-trial-results/

http://www.spirit-statement.org/31b-authorship/

http://www.spirit-statement.org/31c-reproducible-research/





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).


http://www.spirit-statement.org/informed-consent-materials/

http://www.spirit-statement.org/biological-specimens/

drug/device protocol template - sydney children's hospital · study name: protocol number: ...

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