Study no: Study Acronym:
Protocol Version:
Study Title:
FIH study? Yes No
Principal Investigator:
Researcher(s) conducting study:
Sponsor:
Documents submitted in support of application
Protocol version:
Study proposed start date:
Committee use only
Names of reviewers
Risk Assessment version: Date of committee review:
CRF Study ref number:
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Refer to guidance in ‘Guideline on Strategies to Identify and Mitigate Risks for First-In-Human Clinical Trials with
Investigational Medicinal Products’ EMEA 2007
The cv of the PI must clearly identify the qualifications, experience and key publications in support of the role as
PI for this study. Provide only concise, relevant information.
PI CV provided? Yes No
FIH studies: If the PI has no pharmacology qualification and/or no experience of conducting Phase I studies, the role must be with PRB oversight if at all. An appropriate Named Expert Advisor within the ICRF must be identified.
This approach is only acceptable for one-off/occasional FIH studies.
PIs with significant experience in Phase I patient trials and first time in patient studies may apply to the Faculty of
Pharmaceutical Medicine for exemption from the requirement for formal CP qualifications.
1.1.1 Clinical Pharmacology qualifications and experience of PI:
Clinical pharmacology qualification: CCT in clinical pharmacology & therapeutics Yes No Year
CCT in pharmaceutical medicine Yes No Year
PhD in clinical pharmacology Yes No Year
Clinical pharmacology experience: Industry experience Yes No No. Years
Academic experience Yes No No. Years
Faculty of Pharmaceutical Medicine Exemption: Yes No Year
1.1.2 Research experience of PI
Experience in Experimental Medicine studies or CTIMP studies in last 3 years? No. of studies and role:
Experience in Phase I trials: Yes No No. of trials and role:
Experience in FIH trials: Yes No No. of trials and role:
Experience in studies involving dose escalation: Yes No
Please provide details below of this Phase I/FIH/dose escalation experience, indicating the publications that have resulted from this work:
1.1.3 Role and competence of the PI
What clinical functions will the PI perform in this study (eg administration of drug, mentoring, clinical input etc)?:
1.1.4 PI clinical pharmacology advice for FIH studies (if required for role of PI)
What CP input does the PI require (eg review pre-clinical data, assess the pharmacology and subsequent aspects such as the proposed starting dose, dose escalation proposal/stopping criteria etc)?
Name of suggested Named Expert Advisor (if required):
1.1.5 Training status of PI
GCP trained Yes No Date of training: Click here to enter a date.
Training provider:
ALS trained Yes No Date of training: Click here to enter a date.
Training provider:
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Please provide details of other training/ skills essential for the PI for this study:
Please provide information for each researcher (other than PI)
Name of researcher:
1.2.1 Qualifications of researcher:
State relevant qualifications and training (including pharmacology):
1.2.2 Research experience of researcher:
State FIH, Phase I or relevant experience:
1.2.3 Supervision of researcher
Name of supervisor for the researcher(s) if not the PI:
What supervision will be provided?
1.2.4 Training status of researcher
GCP trained Yes No Date of training: Click here to enter a date.
Training provider:
ALS trained Yes No Date of training: Click here to enter a date.
Training provider:
Please provide details of other training/ skills essential for the PI for this study:
Section 1 - Committee use only:
1. Is the PI competent to conduct phase I trials?: Yes No With supervision
2. Is the PI competent to conduct phase I FIH trials? Yes No NA
3. Is the proposed Named Expert Advisor of the PI acceptable (if required)? Yes No NA
4. Is the proposed supervisor of the researcher acceptable? Yes No NA
5. Is the degree of supervision of the researcher(s) conducting the study acceptable? Yes No NA
6. Training needs identified for PI and researcher appropriately? Yes No NA
Comments/ Recommendations:
Provide key papers that detail the pre-clinical data of the study IMP(s)
2.1 Is there evidence of previous exposure of humans to compounds with related modes of action?
Yes No Provide details:
2.2 Is there evidence from animal models for potential risk of serious pharmacologically mediated toxicity?
Yes No Provide details:
2.3
What animal species have been studied? (see also 3.4)
2.4 Provide evidence of a risk analysis of the pre-clinical data for the IMP(s) including:
2.4.1 Identification of the on-target and off-target areas of the IMP(s).
2.4.2 The adverse events associated with the on-target and off-target areas.
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Section 2 – Committee use only
1. Is the risk analysis of the pre-clinical development data for the IMP(s) acceptable in terms of previous human exposure and animal models? Yes No
2. Have on-target and off-target areas been accurately identified and the possible associated adverse events?
Yes No
Comments/Recommendations:
Provide the full information available about the nature of the agent to be tested.
3.1 Mode of action:
Novel molecular structure: Yes No
Biological cascade/ cytokine release: Yes No
Multiple signalling pathways: Yes No
3.2 Nature of target:
Provide available knowledge on the nature of the target and variation between individuals:
3.3 Relevance of animal species and models:
Justify the use of the model used, ensuring evidence of comparison of available animal species to humans (in support of 2.3) :
3.4 CT(EAG) review:
Does this study have risk factors requiring review by the Expert Advisory Group (EAG) to the Committee on
Human Medicines (CHM)? Yes No
Section 3 Committee use only
1. Is there sufficient information provided on the nature of the agent(s) including mode of action, target and species model and justification for use in humans? Yes No
2. Does the Committee assess this study as requiring review by the CT(EAG)? Yes No
Comments/ Recommendations
Ensure that the trial design and protocol are clearly described and flow diagrams accompany the submission.
4.1 What is the route of administration?
4.2 What is the rate of administration?
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4.3 What is the estimation of first dose?
4.4 What method was used to calculate the dose?
4.5 Who will be responsible for checking the calculations at dosing time?
4.6 What is the expected total exposure of the associated drug and the anticipated plasma concentrations?
4.7 How do these values compare against the exposure and achieved concentrations in the animal models previously studied?
4.8 What is the dose escalation plan (if applicable)? include details of the number of subjects required to make a dose escalation decision (dose cohort) and the time interval required before proceeding to a new dose and / or new subject
4.9 What is the justification for the dose escalation plan adopted?
4.10 Who will administer the first dose? (eg PI/ researcher/nurse)
4.11 Which members of the study team will be present at the administration of first dose?
4.12 What is the time period between the first and subsequent doses in the first subject? (Justify this decision)
4.13 What is the time period between administration of IMP to subsequent subjects within the cohort? (Justify this decision)*
4.14 What medical cover will be in place on dosing days?* Include information on the process for the first subject and subsequent subjects. Provide information on who will be present, the duration of cover and the physical locality of the researcher for first dose and subsequent doses.
* To be completed with reference to the ICRF Phase I Staffing SOP
Section 4 Committee Use only
1. Trial design acceptable? Yes No
2. Route and rate of administration acceptable (each IMP)? Yes No
3. Estimation of first dose and method of calculation used acceptable? Yes No
4. Dosing calculation confirmed and provided by:
5. Expected exposure and plasma concentrations acceptable? Yes No
6. Comparison with exposure and achieved concentrations in animal model acceptable? Yes No
7. Dose escalation strategy acceptable? Yes No NA (if no, PRB must define a dose escalation plan for the study)
8. Period of observation of first subject prior to subsequent doses acceptable? Yes No
9. Interval between initial and subsequent subjects acceptable? Yes No
10. Level of subject supervision acceptable for first and subsequent doses? Yes No
Comments/ Recommendations
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Note: Please ensure that appropriate statistical advice has been sought. The Committee will review the statistical aspects of the study from the protocol and ethics form submitted. Provide any additional, relevant information below.
Section 5 Committee Use only
1.
Is the statistical analysis appropriate for the trial design? Yes No
2.
Is the sample size appropriate? Yes No
Comments/ Recommendations
6.1 Describe the measures in place to monitor key on-target and off-target areas as identified in 2.4.1, including the additional tests to be undertaken to monitor for possible off-target effects (eg bp, glucose, liver toxicity etc).
6.2 Describe the strategy to manage likely adverse events or adverse reactions as identified in 2.4.2.
6.3 Probability of event (categories) low med high
6.4 Seriousness of possible event:
6.5 Anticipated responses:
6.6 Potential long-term consequences:
6.7 Will an antidote be immediately available on site? : Yes No
If no, justify and detail contingency plan.
If yes, provide details of the antidote and plan for subject management:
6.8 Detail AE reporting system to be used:
6.9 Describe the procedures for emergency unblinding of study drugs:
Section 6 Committee use only
1.
Is the strategy to monitor and manage adverse events acceptable? Yes No
2.
Is the antidote or contingency plan acceptable? Yes No
3.
Is the AE reporting system acceptable? Yes No
Procedure for emergency unblinding of study drugs acceptable? Yes No NA
Comments/ Recommendations
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Note: It is a requirement that confirmation of subjects’ past medical history (PMH) for these trials is received via the subjects’ GP or other medic such as a hospital consultant for patient studies, to provide assurance that inclusion and exclusion criteria are met.
7.1 Describe how subjects’ past medical history will be obtained:
7.2 Justify choice of subjects for this study:
7.3 Give clear guidance on what constitutes a valid subject.
7.4 Do inclusion/ exclusion criteria take account of possible allergic response to planned antidotes or treatment of AEs? Yes No
Section 7 Committee use only
1. Is PMH check acceptable? Yes No
2. Is subject choice valid? Yes No
3. Are possible allergic responses to antidote or treatment of AEs adequately accounted for in inclusion/ exclusion criteria?
Comments/ Recommendations
Yes No
8.1Source of IMP(s)
Name of company providing IMP:
Is the company within the EU? Yes No
If not within EU please state where located and the company providing EU QP release:
Is availability guaranteed for the duration of the study?
Provide QP and TSE certification for manufacture and further manipulation or processing:
8.2 Dispensing/ Compounding
Does the IMP require further compounding and/or assembly by pharmacy, and if so what? Yes No
If yes, will doses be required to be ready outside of Mon-Fri 10.30am-5pm?
Is PK sampling required post-dose, and if so what?
8.3 Stability of the IMP(s)
What is the shelf life of the IMP(s)?
What is the stability of the IMP once in the form in which it will be administered to patients?
8.4 Storage of the IMP(s)
What are the storage requirements for the IMP(s) eg frozen?
8.5 Reliability of very small doses
Is there a need for demonstration that the intended formulation of the doses to be administered provides the intended dose?
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Section 8 Committee use only
1. Source of IMP, availability of IMP and QP certification acceptable? Yes No
2. Stability information relating to the IMP is sufficient and acceptable? Yes No
3. Storage requirements of the IMP are acceptable? Yes No
4. Information relating to the reliability of very small doses is acceptable? Yes No NA
Comments/ Recommendations
Please provide details of the contingency plans for the study within the CRF, include information relevant to
ICU.
To be included as a minimum:
9.1 The criteria and protocol for premature discontinuation of IMP in an individual? (This should include clear details on clinical parameters):
9.2 Specific instructions for antidote (if applicable):
9.3 Contingency plan for on- and off-target effects, including details of specific treatments that must be held on-site to manage expected adverse reactions:
9.4 Is it essential that ICU is aware? Yes No
9.5 Is it essential ICU have a bed available? Yes No
9.6 State if a relevant specialist is required to be available to support emergencies and adverse event management:
Please detail who is required and under what circumstances:
9.7 Time period between first, second and subsequent participants:
9.8 Plan for data and safety review following first dose and prior to subsequent dosing:
9.9 Plan for data and safety review prior to subsequent subject recruitment:
9.10 The criteria for stopping the trial:
9.11 Medical staff level of cover on first dose:
9.12 Medical staff level of cover for subsequent doses:
9.13 Duration of medical cover post dose (hrs) :
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9.14 CRF Nursing staff level requested per subject:
9.15 Identify proposed room allocation or specific requirements for participant observation for duration of CRF admission:
9.16 Maximum number of subjects on any given day (after review of initial dosing studies):
9.17 Need for overnight observation? Yes No
Additional comments:
Section 9 Committee Use Only
Please detail additional contingency recommendations, including information relevant to ICU.
Do t he Committee approve the study team contingency plan ?
Additional CRF recommendations and comments:
Yes No
The study has been risk assessed and deemed reasonable to proceed in the CRF: Yes No Click here to enter text.
Signature: Date of decision:
(CRF Director/Chair On behalf of the Protocol Review Board)
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