Clinical Risk Assessment and Management Plan
Study Acronym / Short Title
R&D Number
Protocol Version
Date
CRAMP version number
NB: Refer to Phase I Additional Information form for further details on phase I studies
NB: Refer to Risk Assessment for an Activity Involving Gene Therapy and Genetically Modified Micro-organisms form for all GMO studies
Risk category
Hazard identified
Unmitigated impact
(see tables below)
Risk Mitigation
Mitigated impact
(see tables below)
Study Team
Experience
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Training/supervision
required
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Starting dose selection
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Dose escalation plan
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Drug administration:
route and rate
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
IMP details
Pre-clinical Data, class,
novelty etc.
Refer to phase I additional
information form for phase I
study details
IMP dosing
ICRF-OR09 Form 3 v2 Clinical Risk Assessment and Management Plan March 2015
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Interval between
subjects
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Staffing level required
(during/after dosing &
other visits. State
requirement for 1st and
subsequent doses)
IMP/Pharmacy
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Storage
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Handling requirements
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Prescribing
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
AE/SAE reporting
system
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Independent
data/safety monitoring
committee
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Unblinding procedure
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Safety: general
IMP Safety: Adverse reactions
Add extra rows for all notable AEs
AR 1: name,
probability,
seriousness, potential
long term
consequences
ICRF-OR09 Form 3 v2 Clinical Risk Assessment and Management Plan March 2015
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AR 2: name,
probability,
seriousness, potential
long term
consequences
AR 3: name,
probability,
seriousness, potential
long term
consequences
AR 4: name,
probability,
seriousness, potential
long term
consequences
Invasive procedures/NIMPs adverse reactions
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Procedure/NIMP 1:
name, probability,
seriousness, potential
long term
consequences
Procedure/NIMP 2:
name, probability,
seriousness, potential
long term
consequences
Procedure/NIMP 3:
name, probability,
seriousness, potential
long term
consequences
Participants
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Patient/HV, special
requirements, GP
medical history, TOPS
etc.
CRF requirements
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Add extra rows for all notable ARs
ICRF-OR09 Form 3 v2 Clinical Risk Assessment and Management Plan March 2015
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Facilities: specified
rooms or other
requirements
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Staff: training etc.
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Consequence:
Likelihood:
Risk score:
Additional Risks
Overall risk (highest impact score if more than one field completed)
Completed by
Revised Risk Score (Post mitigation)
Principal Investigator
ICRF sign off
Post/role in study
Name (in capitals)
Date
Signature
Consequence Score
1. Insignificant - no obvious harm
2. Minor - non-permanent harm
3. Moderate – semi-permanent harm
4. Major – major permanent harm or death
5. Extreme – multiple deaths
Likelihood score
1. Rare- Not expected to occur for years
2. Unlikely- Expected to occur approx. annually
3. Possible- Expected to occur approx. monthly
4. Likely- Expected to occur approx. weekly
5. Almost certain- Expected to occur approx. daily
ICRF-OR09 Form 3 v2 Clinical Risk Assessment and Management Plan March 2015
Risk score
Consequence Score x Likelihood score
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Risk Matrix
Consequence
Likelihood
1 Insignificant
2 Minor
3 Moderate
4 Major
5 Extreme
1
2
3
4
5
5 (almost certain)
5 (M)
10 (H)
15 (E)
20 (E)
25 (E)
4 (likely)
4 (M)
8 (H)
12 (H)
16 (E)
20 (E)
3 (possible)
3 (L)
6 (M)
9 (H)
12 (E)
15 (E)
2 (unlikely)
2 (L)
4 (L)
6 (M)
8 (H)
10 (E)
1 (rare)
1 (L)
2 (L)
3 (M)
4 (H)
5 (H)
ICRF-OR09 Form 3 v2 Clinical Risk Assessment and Management Plan March 2015
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Guidance Notes for CRAMP
When completing the form please avoid copy and pasting from the protocol.
The Clinical Risk Assessment & Management Plan breaks the risk assessment up into specific groups, namely, Study
Team, IMP details, IMP dosing, Pharmacy, General Safety, Adverse Reactions, Invasive Procedures, Participants, CRF
and any additional risks.
These notes are to act as a guide to help improve completion and consistency.
Hazard Identified: It is impossible to identify every possible risk, the aim of the CRAMP is to identify the most likely
to occur and highest risks applicable to the particular research project. Below are some areas to consider. This is not
intended to be definitive.
 Study Team: Any experience working in early phase? Experience of being a Principal Investigator?
Number of studies conducted. Have received training on the protocol? Have received training on
ICRF SOP’s or study specific procedures?
 IMP Details: Pre clinical toxicology data – did it identify any particular concerns? Any downstream
cascade affects from the molecule? Is this a novel compound or has this been used and developed
before in previous trials?
 IMP Dosing: Is there a clear process and reason for dose selection based on pre-clinical or subject
safety data? IDMC and/or steering group over seeing dose escalation decisions. Is the drug
administered IV or aerosol? Will there be a staged dosing to allow for identification of any untoward
reaction? The number & skill of staff required should there be a reaction.
 Pharmacy: Temperature storage monitoring? Reconstitution process is this simple? Aseptic
preparation required? Dose the dose need to be calculated before admin or simple dosing
instructions?
 Safety General: Any specific safety reporting processes – is there a medical monitor? If blinded –
who, where and how accessible are the un-blinding codes? Are un-blinding procedures tested?
 Adverse Reactions/ Invasive Procedures: Anaphylaxis will be the most common and obvious, but are
there any specific areas of caution from previous safety data or pre-clinical data such as liver, kidney
or cardiac reactions? Venepuncture, cannulation are the most common – are there any study
specific procedures like central line insertion?
 Participants: How will past medical history be confirmed – from GP? Could participants have been
part or are part of another clinical trial? Is this a particular high risk group with respect to mobility,
capacity, vulnerability, cross infection?
 CRF Facilities: Is there a need for a specific room/nurse etc which could prevent bookings if not
available? Any equipment that if broken could delay procedure?
Risk Mitigation: Risks will vary across each project and it is impossible to remove risk entirely. Mitigations can take
the form of adhering to SOP’s for procedures to detailing specific staffing requirements or training that will be
undertaken before carrying out particular study procedures.
ICRF-OR09 Form 3 v2 Clinical Risk Assessment and Management Plan March 2015
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