What is it? Why is it important?

The protocol is the core document that describes the background, rationale, objective(s), design, statistical method, and organisation including safety aspects of a study.

  • The protocol lays down the rules to ensure that all study team members, including any additional participating study sites, perform study tasks as defined.
  • Use of correct protocol template depends on study type (e.g. IMP/MD as compared to other- or non-clinical studies) and in each case category (A, B or C).
  • Sometimes during study conduct a protocol amendment might become necessary. The aim is to facilitate recruitment, make applicable adaptations to the study design and its processes or emerging address safety issues.

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The SP-INV and trial statistician approve the protocol version (dated DD.MM.YYYY; ensure it corresponds to the current protocol version and date in the footer).

By approving and signing the study protocol, the SP-INV confirms his/her commitment to conduct the study according to:

  • Specifications given in the study protocol
  • The Declaration of Helsinki and if applicable ICH-GCP guidelines
  • If applicable, ISO 14155 standard (for medical device studies)
  • Local applicable laws

A protocol amendment:

  • Should normally improve the conduct of the study, but in many cases, may also pose additional requirements and thus have unwanted consequences on the running of a study.
  • Has to be submitted and approved by the EC/RA prior to implementation. Exceptions are urgent safety measures that must be immediately implemented to protect study participants. Still, EC/RA should be informed as soon as possible.

A substantial amendment:

  • Must be EC/RA approved prior to implementation
  • Requires staff to be retrained
  • Can require patients to re-consent, which carries the risk of participant dropping out of the study

Requirements regarding EC/RA approval prior to implementing an amendment, including potential participant re-consent procedures might significantly delay the study.

What do I need to do?

Based on your study, select the applicable and current protocol template provided by swissethics.

  • If unsure what templates to use clarify with EC in order to avoid re-writing the protocol
  • It is advisable to invest sufficient time in the development of the study protocol.
  • A well thought through protocol will avoid unnecessary amendments as well as unexpected difficulties due to protocol inconsistencies during study conduct
  • Protocol development also requires the assistance of other professionals such as a statistician, quality-, project-, data manager, or experienced study nurses.

For more information refer to Protocol in this Study Guide.

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For the development of the study protocol:

  • Analyse the particular medical/public health problem and include a review of current existing knowledge
  • Decide on the best way to perform the study by selecting an appropriate study design
  • Define study question(s) that can and need to be answered
  • Decide on achievable and measurable study endpoints (outcome measures)
  • Define required statistical power including sample size calculation
  • Evaluate regarding the impact any study findings will have on public health (e.g. how will they contribute to disease prevention as well as contribute to any health improvement of your target population)

Where can I get help?

Your local CTU can support you with experienced staff regarding this topic

External Links

Swissethics – in particular see

  • Broad selection of protocol templates

References

ICH GCP E6(R2) – see in particular guidelines

  • 1.44 Protocol definition
  • 1.45 Protocol Amendment
  • 2.5, 2.6 Principles
  • 6. Clinical trial protocol and protocol amendment(s)

ISO 14155:2020 Medical devices - see in particular sections (access liable to cost)

  • 6.4 Clinical Investigational Plan (CIP)
  • Annex A CIP

Declaration of Helsinki – see in particular principles

  • 21 – 22 Protocol requirements

Swiss Law

ClinO – see in particular article

  • Art. 19, 20, 49, and 61 Categorisation
  • Art. 29. Changes

HRO – see in particular article

  • Art. 7 Categorisation
  • Art. 18. Changes
Abbreviations
  • CTU – Clinical Trials Unit
  • EC/RA - Ethics Committee / Regulatory Authorities
  • ICH-GCP – International Council for Harmonisation - Good Clinical Practice
  • ISO – International Organisation for Standardisation
  • IMP/MD – Investigational Medicinal Product/Medical Device
  • CIP – Clinical Investigational Plan
  • SP-INV – Sponsor-Investigator
Development ↦ Management ↦ Study Documents ↦ Protocol
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
Basic Statistics
Basic Monitoring
Basic Drug or Device
Basic Biobanking
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
Concept Statistics
Concept Drug or Device
Concept Biobanking
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Protocol
Development Statistics
Development Drug or Device
Development Biobanking
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
Set-Up Ethics and Laws
Set-Up Statistics
Set-Up Drug or Device
Set-Up Biobanking
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
Conduct Statistics
Conduct Drug or Device
Conduct Biobanking
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
Completion Statistics
Completion Drug or Device
Completion Biobanking
Current Path (click to copy): Development ↦ Management ↦ Study Documents ↦ Protocol

Please note: the Easy-GCS tool is currently under construction.