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.
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.
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
Basel, Departement Klinische Forschung, CTU, dkf.unibas.ch
Lugano, Clinical Trials Unit, CTU-EOC, www.ctueoc.ch
Bern, Clinical Trials Unit, CTU, www.ctu.unibe.ch
Geneva, Clinical Research Center, CRC, crc.hug.ch
Lausanne, Clinical Research Center, CRC, www.chuv.ch
St. Gallen, Clinical Trials Unit, CTU, www.kssg.ch
Zürich, Clinical Trials Center, CTC, www.usz.ch
Swissethics – see in particular
- Broad selection of protocol templates
ICH GCP E6(R2) – see in particular guidelines
- 1.44 Protocol definition
- 1.45 Protocol amendment definition
- 6 Clinical trial protocol and protocol amendment(s)
ISO 14155:2020 Medical devices (access liable to costs) - see in particular sections
- 6.4 Clinical Investigational Plan (CIP)
- Annex A CIP
Declaration of Helsinki – see in particular principles
- 21 – 22 Protocol requirements
ClinO – see in particular articles
- Art. 19, 20, 49, and 61 Categorisation
- Art. 29 Changes
HRO – see in particular article
- Art. 7 Categorisation
- Art. 18 Changes