{"text_format":"1","workbook":"xlsx","n_sheets":5,"sheets":["Risk Assessment Matrix V4.0","LOW Risk V4.0","MED Risk V4.0","HIGH Risk V4.0","Dose Esc. Procedure V4.0"],"not_rendered":{"charts":0,"images":4,"macros":1,"external_links":0,"defined_names":5,"comments":0,"pivot_tables":0},"unopened":[],"bounds":{"document_bytes":16777216,"sheet_cells":100000,"rows_first":2000,"rows_last":500,"rows_between":2000,"halvings":0,"cell_chars":16384,"cell_head_chars":4096},"cells_cut":0,"cells_raw":0,"read":"whole","date_system":"1900"}

{"sheet":"Risk Assessment Matrix V4.0","index":0,"n_rows":38,"n_cols":10,"rows_kept":38,"cut":false,"hidden":false,"merged":[[37,8,37,9],[20,7,23,8],[24,7,26,8],[27,7,29,8],[30,7,32,8],[24,9,26,9],[20,6,23,6],[20,9,23,9],[34,0,34,2],[35,8,35,9],[36,8,36,9],[19,4,19,5],[20,4,23,5],[24,4,26,5],[27,4,29,5],[37,0,37,2],[20,3,23,3],[30,3,32,3],[27,3,29,3],[35,3,35,4],[36,3,36,4],[37,3,37,4],[0,0,0,9],[1,0,1,9],[2,0,2,9],[18,0,18,9],[4,0,17,9],[19,7,19,8],[39,0,42,9],[20,0,23,2],[24,0,26,2],[24,3,26,3],[19,0,19,2],[24,6,26,6],[27,6,29,6],[27,9,29,9],[30,6,32,6],[30,9,32,9],[30,4,32,5],[35,0,35,2],[36,0,36,2],[27,0,29,2],[30,0,32,2]]}
[]
["Risk Stratification Matrix and Contigency Plans"]
["Version 1.0, November 2020"]
[]
["The Risk Matrix has been developed as a tool to risk asssess a Phase I classified study and allow pragmatic and risk-adapted approach to manage hazards associated with the trial.\nThe risk outcome is a combination of the score from the status of the intervention and the trial design, and additional factors (i.e. study team experience).  \nIt is the responsibility of the PI to make these assessment, and where necessary, peer reviewed to ensure the outcome is a reflection of the study conducted at their site.\nFor studies with a Low or Medium risk outcome, the corresponding pre-set contingency plan will be used. For studies with a high risk, addition risk assessment will be required to identify the risk and the mitigation plan.\nThe potient risks should be balanced against the level of risk that a trial subject would be exposed to outside the trial as follows:\nType A = no higher than the risk of standard medical care\nType B = somewhat higher than the risk of standard medical care\nType C = markedly higher than the risk of standard medical care\n   \n"]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
["Intervention Status"]
["Study Design",null,null,"Used as per licence / off-label use is establised practice and supported by publised evidence and/or guideline","licenced and used in new formulation/ new delivery",null,"licenced but used in new age group/ disease","Unlicenced, used in healthy volunteers but first in patient group",null,"Unlicenced and never been used in humans (Healthy Volunteers or Patient group)"]
["Dose escalation - multiple/ complex cohorts, SAD/MAD\n"]
[]
[]
[]
["Single Ascending Dose escalation \nSingle dosage\n"]
[]
[]
["Dose expansion / dose ecalation with known/ tested doses\n"]
[]
[]
["Dosage used as per authorisation"]
[]
[]
[]
["Additional Risk"]
["Study team experience",null,null,"Research experienced",null,null,null,null,"No/lack of experience"]
["Experience with type of intervention",null,null,"Experienced",null,null,null,null,"Unfamiliar/not used before"]
["Number of intervention",null,null,"Single intervention",null,null,null,null,"Multiple interventions"]

{"sheet":"LOW Risk V4.0","index":1,"n_rows":112,"n_cols":5,"rows_kept":112,"cut":false,"hidden":false,"merged":[[0,0,0,2],[4,0,5,0],[7,0,8,0],[1,0,1,4],[25,1,25,4],[26,1,26,4],[17,0,18,0],[17,1,18,1],[21,2,21,3],[22,2,22,3],[23,2,23,3],[20,0,20,4],[10,0,11,0],[13,0,14,0],[13,1,14,1],[15,0,16,0],[15,1,16,1],[39,1,39,4],[40,1,40,4],[41,1,41,4],[32,0,32,1],[33,0,33,1],[36,0,36,4],[37,1,37,4],[38,1,38,4],[28,0,28,3],[29,0,29,1],[30,0,30,1],[31,0,31,1],[55,0,55,1],[56,0,56,1],[47,2,47,3],[51,0,51,1],[53,0,53,1],[50,0,50,4],[51,2,51,4],[52,0,52,4],[44,0,44,3],[45,2,45,3],[46,2,46,3],[75,0,75,1],[76,0,76,1],[69,0,69,1],[71,0,71,1],[72,0,72,1],[69,2,69,4],[70,0,70,4],[71,2,71,4],[65,0,65,1],[66,0,66,1],[67,0,67,1],[68,0,68,1],[68,2,68,4],[67,2,67,4],[90,0,90,1],[91,0,91,1],[92,0,92,1],[93,0,93,1],[90,2,90,4],[91,2,91,4],[92,2,92,4],[87,0,87,1],[88,0,88,1],[87,2,87,4],[88,2,88,4],[89,0,89,4],[93,2,93,4],[110,0,110,1],[110,2,110,4],[111,0,111,4],[112,0,112,4],[106,0,106,1],[107,0,107,1],[102,0,102,1],[103,0,103,1],[104,0,104,1],[102,2,102,4],[103,2,103,4],[104,2,104,4],[105,0,105,4],[106,2,106,4],[107,2,107,4],[108,0,108,4],[109,2,109,4],[64,2,64,4],[65,2,65,4],[4,1,5,4],[7,1,8,4],[10,1,11,4],[66,2,66,4],[53,2,53,4],[54,2,54,4],[55,2,55,4],[56,2,56,4],[57,2,57,4],[58,0,58,4],[62,0,62,1],[63,0,63,1],[64,0,64,1],[61,0,61,4],[62,2,62,4],[63,2,63,4],[57,0,57,1],[59,0,59,1],[60,0,60,1],[59,2,59,4],[60,2,60,4],[54,0,54,1],[81,2,81,4],[82,0,82,4],[83,2,83,4],[84,2,84,4],[85,2,85,4],[86,0,86,4],[72,2,72,4],[73,0,73,4],[74,2,74,4],[75,2,75,4],[76,2,76,4],[77,2,77,4],[83,0,83,1],[84,0,84,1],[85,0,85,1],[77,0,77,1],[78,0,78,1],[79,0,79,1],[80,0,80,1],[81,0,81,1],[78,2,78,4],[79,2,79,4],[80,2,80,4],[74,0,74,1],[94,2,94,4],[95,2,95,4],[96,2,96,4],[97,2,97,4],[98,2,98,4],[109,0,109,1],[101,0,101,4],[97,0,97,1],[98,0,98,1],[99,0,99,1],[100,0,100,1],[99,2,99,4],[100,2,100,4],[94,0,94,1],[95,0,95,1],[96,0,96,1]]}
[]
["LOW RISK CONTINGENCY PLAN"]
[]
[]
["Full Project Title"]
[]
[]
["Principle Investigator (PI):"]
[]
[]
["Lead Nurse"]
[]
[]
["Risk Assessment Number"]
[]
["Protocol used for assessment"]
[]
["IB used for assessment"]
[]
[]
["Revision History"]
["Protocol/ IB/ Notifications","Date of Assessment","Assessment outcome",null,"Contingency plan Version number"]
[]
[]
[]
["IMP","Target"]
[]
[]
["PI Phase I training and experiences"]
["Has clinical pharmacology experience?"]
["Received MHRA acceptance to serve as PI for FIH studies?"]
["Has experience in Phase I studies?"]
["Has experience in FIH studies?"]
["Has experience with dose escalation?"]
[]
[]
["Data from completed or ongoing trials"]
["How many completed trials? Please include the phase, dosage used and number of subjects."]
["How many on-going trails? Please include the phase, dosage used and number of subjects."]
["Are the previous trials involves same/ similar subjects as this trial? "]
["List grade 3 and 4 AEs from the above trials"]
["Potential long-term consequences"]
[]
[]
["Additional Informatin/ Regularly reviews/ additional requirements"]
["Does this study have risk factors requiring review by the Expert Advisory Group (EEAG) to the committee on Human Medicines (CHM)?"]
["Have the MHRA or REC imposed any approval conditions on the study?"]
["Has the study sponsor provided any SOPs for this study?"]
[]
[]
[]
["Item",null,"Required?"]
["Staffing and training"]
["Emergency scenario training required for all study staff ",null,"No "]
["Medic cover per dosing visit",null,1]
["Nursing staff level requested per subject per dosing visit",null,1]
["Level of Resuscitation training for medic required",null,"BLS+AED"]
["Level of Resuscitation training for nurses required",null,"BLS+AED "]
["First dose: pre-dosing"]
["Is any pre-medication required prior to dosing? Please specify:"]
["ICU Notification  required",null,"Not applicable"]
["First dose: Post dose Observation period "]
["Observation period"]
["Medic cover required",null,1]
["Please state the length of time of the medical cover will be physically present during dosing and observation, and length of time medical cover onsite (on-call) if applicable."]
["Nursing staff required",null,2]
["PI cover required? "]
["If no, please state how the PI will support the dosing day."]
["Is it suitable to substitute clinical staff resus training from what is outlined above to in the observation period?"]
["If yes, please outline the minimum resus level required, when in the observation period and the justification.  i.e. in a 24hour observation period, 8th hour after the dosing can be staffed by 1 ILS/PILS and 1 BLS_AED trained staff."]
["Subsequent doses: pre-dosing "]
["Is any pre-medication required prior to dosing? Please specify:"]
["ICU Notification  required",null,"Not applicable"]
["subsequent doses: Post dose Observation period for "]
["Observation period"]
["Medic cover required",null,1]
["Please state the length of time of the medical cover will be physically present during dosing and observation, and length of time medical cover onsite (on-call) if applicable."]
["Nursing staff required",null,2]
["PI cover required? "]
["If no, please state how the PI will support the dosing day."]
["Is it suitable to substitute clinical staff resus training from what is outlined above to in the observation period?"]
["If yes, please outline the minimum resus level required, when in the observation period and the justification.  i.e. in a 24hour observation period, 8th hour after the dosing can be staffed by 1 ILS/PILS and 1 BLS_AED trained staff."]
["AE management"]
["Is there a safety review within a cohort?"]
["Maximum number of subjects on any given day (after review of initial dosing studies)."]
["List the adverse events associated with off-target areas in this study",null,"\n"]
["List the Probability of event in accordance to the categories below:"]
["High"]
["Medium"]
["List of serious of possible event in accordance to the catergies below (refer to ctcae definitions):"]
["Grade 4"]
["Grade 3"]
["Specific Antidote required"]
["If yes, add details including management of antidote"]
["If no, what is required to manage AE"]
["Describe the measures in place to monitor key off-target areas including the additional tests to be understaken to monitor for off-target effects (eg. Bp, glucose, liver toxicity etc) or details of specific treatments that must be held on-site to manage expected adverse reactions"]
["Specialist, beyond the immediate study team, required to be available to support emergencies and adverse event management?",null,"Not required/ as identified by PI"]
["Is there a possibility the dosing and/or observation period takes place outside core hours?"]
["If yes, are addition measure/ process required?"]
["24/7 Emergency contact test",null,"Yes"]
["Un-blinding system test",null,"Not applicable/ Yes"]
["Dosing"]
["First Dose level per cohort must be reviewed by EPSC",null,"Not applicable/ Yes"]
["Data and safety submitted for EPSC review following first dose and prior to subsequent dosing.",null,"Not applicable/ Yes"]
["Data and safety submitted for EPSC review prior to subsequent subject recruitment.",null,"Not applicable/ Yes"]
["Facility and Equipment"]
["Proposed room allocation or specific requirements for participant observation for the duration of the CRF visit.",null,"Not required/ as identified by PI"]
["Specialist equipment required for dosing visit.",null,"Not required/ as identified by PI"]
["Subject Identification"]
["The Over Volunteering Prevention System (TOPS) and the associated photographic identification of subjects be utilised for this study?",null,"Not applicable/ Yes"]
["Confirmation of subject’s medical history required?",null,"Not applicable/ Yes"]
["Additional comments / Special consideration"]

{"sheet":"MED Risk V4.0","index":2,"n_rows":112,"n_cols":5,"rows_kept":112,"cut":false,"hidden":false,"merged":[[1,0,1,4],[0,0,0,2],[10,0,11,0],[10,1,11,4],[13,0,14,0],[13,1,14,1],[15,0,16,0],[15,1,16,1],[4,0,5,0],[4,1,5,4],[7,0,8,0],[7,1,8,4],[25,1,25,4],[26,1,26,4],[28,0,28,3],[29,0,29,1],[30,0,30,1],[31,0,31,1],[17,0,18,0],[17,1,18,1],[20,0,20,4],[21,2,21,3],[22,2,22,3],[23,2,23,3],[40,1,40,4],[41,1,41,4],[44,0,44,3],[45,2,45,3],[46,2,46,3],[47,2,47,3],[32,0,32,1],[33,0,33,1],[36,0,36,4],[37,1,37,4],[38,1,38,4],[39,1,39,4],[54,0,54,1],[54,2,54,4],[55,0,55,1],[55,2,55,4],[56,0,56,1],[56,2,56,4],[50,0,50,4],[51,0,51,1],[51,2,51,4],[52,0,52,4],[53,0,53,1],[53,2,53,4],[61,0,61,4],[62,0,62,1],[62,2,62,4],[63,0,63,1],[63,2,63,4],[64,0,64,1],[64,2,64,4],[57,0,57,1],[57,2,57,4],[58,0,58,4],[59,0,59,1],[59,2,59,4],[60,0,60,1],[60,2,60,4],[68,0,68,1],[68,2,68,4],[69,0,69,1],[69,2,69,4],[70,0,70,4],[71,0,71,1],[71,2,71,4],[65,0,65,1],[65,2,65,4],[66,0,66,1],[66,2,66,4],[67,0,67,1],[67,2,67,4],[76,0,76,1],[76,2,76,4],[77,0,77,1],[77,2,77,4],[78,0,78,1],[78,2,78,4],[72,0,72,1],[72,2,72,4],[73,0,73,4],[74,0,74,1],[74,2,74,4],[75,0,75,1],[75,2,75,4],[82,0,82,4],[83,0,83,1],[83,2,83,4],[84,0,84,1],[84,2,84,4],[85,0,85,1],[85,2,85,4],[79,0,79,1],[79,2,79,4],[80,0,80,1],[80,2,80,4],[81,0,81,1],[81,2,81,4],[90,0,90,1],[90,2,90,4],[91,0,91,1],[91,2,91,4],[92,0,92,1],[92,2,92,4],[86,0,86,4],[87,0,87,1],[87,2,87,4],[88,0,88,1],[88,2,88,4],[89,0,89,4],[96,0,96,1],[96,2,96,4],[97,0,97,1],[97,2,97,4],[98,0,98,1],[98,2,98,4],[93,0,93,1],[93,2,93,4],[94,0,94,1],[94,2,94,4],[95,0,95,1],[95,2,95,4],[103,0,103,1],[103,2,103,4],[104,0,104,1],[104,2,104,4],[105,0,105,4],[106,0,106,1],[106,2,106,4],[99,0,99,1],[99,2,99,4],[100,0,100,1],[100,2,100,4],[101,0,101,4],[102,0,102,1],[102,2,102,4],[111,0,111,4],[112,0,112,4],[107,0,107,1],[107,2,107,4],[108,0,108,4],[109,0,109,1],[109,2,109,4],[110,0,110,1],[110,2,110,4]]}
[]
["MED RISK CONTINGENCY PLAN"]
[]
[]
["Full Project Title"]
[]
[]
["Principle Investigator (PI):"]
[]
[]
["Lead Nurse"]
[]
[]
["Risk Assessment Number"]
[]
["Protocol used for assessment"]
[]
["IB used for assessment"]
[]
[]
["Revision History"]
["Protocol/ IB/ Notifications","Date of Assessment","Assessment outcome",null,"Contingency plan Version number"]
[]
[]
[]
["IMP","Target"]
[]
[]
["PI Phase I training and experiences"]
["Has clinical pharmacology experience?"]
["Received MHRA acceptance to serve as PI for FIH studies?"]
["Has experience in Phase I studies?"]
["Has experience in FIH studies?"]
["Has experience with dose escalation?"]
[]
[]
["Data from completed or ongoing trials"]
["How many completed trials? Please include the phase, dosage used and number of subjects."]
["How many on-going trails? Please include the phase, dosage used and number of subjects."]
["Are the previous trials involves same/ similar subjects as this trial? "]
["List grade 3 and 4 AEs from the above trials"]
["Potential long-term consequences"]
[]
[]
["Additional Informatin/ Regularly reviews/ additional requirements"]
["Does this study have risk factors requiring review by the Expert Advisory Group (EEAG) to the committee on Human Medicines (CHM)?"]
["Have the MHRA or REC imposed any approval conditions on the study?"]
["Has the study sponsor provided any SOPs for this study?"]
[]
[]
[]
["Item",null,"Required?"]
["Staffing and training"]
["Emergency scenario training required for all study staff ",null,"No / Yes"]
["Medic cover per dosing visit",null,1]
["Nursing staff level requested per subject per dosing visit",null,2]
["Level of Resuscitation training for medic required",null,"BLS+AED / ALS / APLS_EPLS"]
["Level of Resuscitation training for nurses required",null,"BLS+AED / ILS/ PILS"]
["First dose: pre-dosing"]
["Is any pre-medication required prior to dosing? Please specify:"]
["ICU Notification  required",null,"Not applicable / Yes"]
["First dose: Post dose Observation period "]
["Observation period"]
["Medic cover required",null,1]
["Please state the length of time of the medical cover will be physically present during dosing and observation, and length of time medical cover onsite (on-call) if applicable."]
["Nursing staff required",null,2]
["PI cover required? "]
["If no, please state how the PI will support the dosing day."]
["Is it suitable to substitute clinical staff resus training from what is outlined above to in the observation period?"]
["If yes, please outline the minimum resus level required, when in the observation period and the justification.  i.e. in a 24hour observation period, 8th hour after the dosing can be staffed by 1 ILS/PILS and 1 BLS_AED trained staff."]
["Subsequent doses: pre-dosing "]
["Is any pre-medication required prior to dosing? Please specify:"]
["ICU Notification  required",null,"Not applicable / Yes"]
["Subsequent doses: Post dose Observation period "]
["Observation period"]
["Medic cover required",null,1]
["Please state the length of time of the medical cover will be physically present during dosing and observation, and length of time medical cover onsite (on-call) if applicable."]
["Nursing staff required",null,2]
["PI cover required? "]
["If no, please state how the PI will support the dosing day."]
["Is it suitable to substitute clinical staff resus training from what is outlined above to in the observation period?"]
["If yes, please outline the minimum resus level required, when in the observation period and the justification.  i.e. in a 24hour observation period, 8th hour after the dosing can be staffed by 1 ILS/PILS and 1 BLS_AED trained staff."]
["AE management"]
["Is there a safety review within a cohort?"]
["Maximum number of subjects on any given day (after review of initial dosing studies)."]
["List the adverse events associated with off-target areas in this study",null,"\n"]
["List the Probability of event in accordance to the categories below:"]
["High"]
["Medium"]
["List of serious of possible event in accordance to the catergies below (refer to ctcae definitions):"]
["Grade 4"]
["Grade 3"]
["Specific Antidote required"]
["If yes, add details including management of antidote"]
["If no, what is required to manage AE"]
["Describe the measures in place to monitor key off-target areas including the additional tests to be understaken to monitor for off-target effects (eg. Bp, glucose, liver toxicity etc) or details of specific treatments that must be held on-site to manage expected adverse reactions"]
["Specialist, beyond the immediate study team, required to be available to support emergencies and adverse event management?",null,"Not required/ as identified by PI"]
["Is there a possibility the dosing and/or observation period takes place outside core hours?"]
["If yes, are addition measure/ process required?"]
["24/7 Emergency contact test",null,"Yes"]
["Un-blinding system test",null,"Not applicable/ Yes"]
["Dosing"]
["First Dose level per cohort must be reviewed by EPSC",null,"Not applicable/ Yes"]
["Data and safety submitted for EPSC review following first dose and prior to subsequent dosing.",null,"Not applicable/ Yes"]
["Data and safety submitted for EPSC review prior to subsequent subject recruitment.",null,"Not applicable/ Yes"]
["Facility and Equipment"]
["Proposed room allocation or specific requirements for participant observation for the duration of the CRF visit.",null,"Not required/ as identified by PI"]
["Specialist equipment required for dosing visit.",null,"Not required/ as identified by PI"]
["Subject Identification"]
["The Over Volunteering Prevention System (TOPS) and the associated photographic identification of subjects be utilised for this study?",null,"Not applicable/ Yes"]
["Confirmation of subject’s medical history required?",null,"Not applicable/ Yes"]
["Additional comments / Special consideration"]

{"sheet":"HIGH Risk V4.0","index":3,"n_rows":122,"n_cols":5,"rows_kept":122,"cut":false,"hidden":false,"merged":[[0,0,0,2],[10,0,11,0],[10,1,11,4],[13,0,14,0],[13,1,14,1],[15,0,16,0],[15,1,16,1],[4,0,5,0],[4,1,5,4],[7,0,8,0],[7,1,8,4],[1,0,1,4],[25,1,25,4],[26,1,26,4],[28,0,28,3],[29,0,29,1],[30,0,30,1],[31,0,31,1],[17,0,18,0],[17,1,18,1],[20,0,20,4],[21,2,21,3],[22,2,22,3],[23,2,23,3],[50,1,50,4],[51,1,51,4],[54,0,54,3],[55,2,55,3],[56,2,56,3],[57,2,57,3],[32,0,32,1],[33,0,33,1],[46,0,46,4],[47,1,47,4],[48,1,48,4],[49,1,49,4],[41,0,41,3],[43,0,43,1],[44,0,44,1],[35,0,35,4],[36,1,36,4],[37,1,37,4],[38,1,38,4],[39,1,39,4],[64,0,64,1],[64,2,64,4],[65,0,65,1],[65,2,65,4],[66,0,66,1],[66,2,66,4],[60,0,60,4],[61,0,61,1],[61,2,61,4],[62,0,62,4],[63,0,63,1],[63,2,63,4],[71,0,71,4],[72,0,72,1],[72,2,72,4],[73,0,73,1],[73,2,73,4],[74,0,74,1],[74,2,74,4],[67,0,67,1],[67,2,67,4],[68,0,68,4],[69,0,69,1],[69,2,69,4],[70,0,70,1],[70,2,70,4],[78,0,78,1],[78,2,78,4],[79,0,79,1],[79,2,79,4],[80,0,80,4],[81,0,81,1],[81,2,81,4],[75,0,75,1],[75,2,75,4],[76,0,76,1],[76,2,76,4],[77,0,77,1],[77,2,77,4],[86,0,86,1],[86,2,86,4],[87,0,87,1],[87,2,87,4],[88,0,88,1],[88,2,88,4],[82,0,82,1],[82,2,82,4],[83,0,83,4],[84,0,84,1],[84,2,84,4],[85,0,85,1],[85,2,85,4],[92,0,92,4],[93,0,93,1],[93,2,93,4],[94,0,94,1],[94,2,94,4],[95,0,95,1],[95,2,95,4],[89,0,89,1],[89,2,89,4],[90,0,90,1],[90,2,90,4],[91,0,91,1],[91,2,91,4],[100,0,100,1],[100,2,100,4],[101,0,101,1],[101,2,101,4],[102,0,102,1],[102,2,102,4],[96,0,96,4],[97,0,97,1],[97,2,97,4],[98,0,98,1],[98,2,98,4],[99,0,99,4],[106,0,106,1],[106,2,106,4],[107,0,107,1],[107,2,107,4],[108,0,108,1],[108,2,108,4],[103,0,103,1],[103,2,103,4],[104,0,104,1],[104,2,104,4],[105,0,105,1],[105,2,105,4],[121,0,121,4],[122,0,122,4],[117,0,117,1],[117,2,117,4],[118,0,118,4],[119,0,119,1],[119,2,119,4],[120,0,120,1],[120,2,120,4],[113,0,113,1],[113,2,113,4],[114,0,114,1],[114,2,114,4],[115,0,115,4],[116,0,116,1],[116,2,116,4],[109,0,109,1],[109,2,109,4],[110,0,110,1],[110,2,110,4],[111,0,111,4],[112,0,112,1],[112,2,112,4]]}
[]
["HIGH RISK CONTINGENCY PLAN"]
[]
[]
["Full Project Title"]
[]
[]
["Principle Investigator (PI):"]
[]
[]
["Lead Nurse"]
[]
[]
["Risk Assessment Number"]
[]
["Protocol used for assessment"]
[]
["IB used for assessment"]
[]
[]
["Revision History"]
["Protocol/ IB/ Notifications","Date of Assessment","Assessment outcome",null,"Contingency plan Version number"]
[]
[]
[]
["IMP","Target"]
[]
[]
["PI Phase I training and experiences"]
["Has clinical pharmacology experience?"]
["Received MHRA acceptance to serve as PI for FIH studies?"]
["Has experience in Phase I studies?"]
["Has experience in FIH studies?"]
["Has experience with dose escalation?"]
[]
["Pre-clinical development data"]
["Is there evidence of previous exposure of humans to compounds in related modes of action? Does this compound pose a risk?"]
["Please list the potential risk of serious pharmacologically mediated toxicity from animal models or state why not available."]
["What is the expected total exposure of the associated drug and the anticipated plasma concentrations?"]
["How do these values compare against the exposure and achieved concentrations in the animal models previously studied?"]
[]
["Mode of Action"]
["Novel molecular structure?"]
["Biological cascade / cytokine release?"]
["multiple signalling pathways?"]
[]
["Data from completed or ongoing trials"]
["How many completed trials? Please include the phase, dosage used and number of subjects."]
["How many on-going trails? Please include the phase, dosage used and number of subjects."]
["Are the previous trials involves same/ similar subjects as this trial? "]
["List grade 3 and 4 AEs from the above trials"]
["Potential long-term consequences"]
[]
[]
["Additional Informatin/ Regularly reviews/ additional requirements"]
["Does this study have risk factors requiring review by the Expert Advisory Group (EEAG) to the committee on Human Medicines (CHM)?"]
["Have the MHRA or REC imposed any approval conditions on the study?"]
["Has the study sponsor provided any SOPs for this study?"]
[]
[]
[]
["Item",null,"Required?"]
["Staffing and training"]
["Emergency scenario training required for all study staff ",null," Yes"]
["Medic cover per dosing visit",null,1]
["Nursing staff level requested per subject per dosing visit",null,2]
["Level of Resuscitation training for medic required",null,"ALS / APLS_EPLS"]
["Level of Resuscitation training for nurses required",null," ILS/ PILS"]
["First dose: pre-dosing"]
["Is any pre-medication required prior to dosing? Please specify:"]
["ICU Notification  required",null,"Not applicable / Yes"]
["First dose: Post dose Observation period "]
["Observation period"]
["Medic cover required",null,1]
["Please state the length of time of the medical cover will be physically present during dosing and observation, and length of time medical cover onsite (on-call) if applicable."]
["Nursing staff required",null,2]
["PI cover required? "]
["If no, please state how the PI will support the dosing day."]
["Is it suitable to substitute clinical staff resus training from what is outlined above to in the observation period?"]
["If yes, please outline the minimum resus level required, when in the observation period and the justification.  i.e. in a 24hour observation period, 8th hour after the dosing can be staffed by 1 ILS/PILS and 1 BLS_AED trained staff."]
["Subsequent doses: pre-dosing "]
["Is any pre-medication required prior to dosing? Please specify:"]
["ICU Notification  required",null,"Not applicable / Yes"]
["Subsequent doses: Post dose Observation period "]
["Observation period"]
["Medic cover required",null,1]
["Please state the length of time of the medical cover will be physically present during dosing and observation, and length of time medical cover onsite (on-call) if applicable."]
["Nursing staff required",null,2]
["PI cover required? "]
["If no, please state how the PI will support the dosing day."]
["Is it suitable to substitute clinical staff resus training from what is outlined above to in the observation period?"]
["If yes, please outline the minimum resus level required, when in the observation period and the justification.  i.e. in a 24hour observation period, 8th hour after the dosing can be staffed by 1 ILS/PILS and 1 BLS_AED trained staff."]
["AE management"]
["Is there a safety review within a cohort?"]
["Maximum number of subjects on any given day (after review of initial dosing studies)."]
["List the adverse events associated with off-target areas in this study",null,"\n"]
["List the Probability of event in accordance to the categories below:"]
["High"]
["Medium"]
["List of serious of possible event in accordance to the catergies below (refer to ctcae definitions):"]
["Grade 4"]
["Grade 3"]
["Specific Antidote required"]
["If yes, add details including management of antidote"]
["If no, what is required to manage AE"]
["Describe the measures in place to monitor key off-target areas including the additional tests to be understaken to monitor for off-target effects (eg. Bp, glucose, liver toxicity etc) or details of specific treatments that must be held on-site to manage expected adverse reactions"]
["Specialist, beyond the immediate study team, required to be available to support emergencies and adverse event management?",null,"Not required/ as identified by PI"]
["Is there a possibility the dosing and/or observation period takes place outside core hours?"]
["If yes, are addition measure/ process required?"]
["24/7 Emergency contact test",null,"Yes"]
["Un-blinding system test",null,"Not applicable/ Yes"]
["Dosing"]
["First Dose level per cohort must be reviewed by EPSC",null,"Not applicable/ Yes"]
["Data and safety submitted for EPSC review following first dose and prior to subsequent dosing.",null,"Not applicable/ Yes"]
["Data and safety submitted for EPSC review prior to subsequent subject recruitment.",null,"Not applicable/ Yes"]
["Facility and Equipment"]
["Proposed room allocation or specific requirements for participant observation for the duration of the CRF visit.",null,"Not required/ as identified by PI"]
["Specialist equipment required for dosing visit.",null,"Not required/ as identified by PI"]
["Subject Identification"]
["The Over Volunteering Prevention System (TOPS) and the associated photographic identification of subjects be utilised for this study?",null,"Not applicable/ Yes"]
["Confirmation of subject’s medical history required?",null,"Not applicable/ Yes"]
["Additional comments / Special consideration"]

{"sheet":"Dose Esc. Procedure V4.0","index":4,"n_rows":42,"n_cols":4,"rows_kept":42,"cut":false,"hidden":false,"merged":[[0,0,0,2],[1,0,1,3],[13,1,13,3],[24,0,24,3],[3,1,3,3],[5,1,5,3],[7,1,7,3],[9,1,9,3],[11,1,11,3],[15,0,15,1],[41,2,41,3],[35,2,35,3],[36,2,36,3],[37,2,37,3],[38,2,38,3],[39,2,39,3],[40,2,40,3]]}
[]
["Dose Escalation Procedure Form"]
[]
["What is the dose escalation design?"]
[]
["Are dose leaders to be used in this study? This is also known as sentinal. If yes, what is the process to ensure that all dose leaders are not assigned a placebo?"]
[]
["Is this study multi centre?\nIf yes, will Pls be given data from other sites in order to assist with the dose escalation decision? If not, then please justify this?"]
[]
["What process is in place to ensure site cannot issue a dose that's not within the cohort or when there's a study pause?"]
[]
["The study PI is responsible for authorising the dose escalation decision. Please state if this is formally delegated to another investigator by the PI, and in what capacity."]
[]
["If additional information which contradicts the dose escalation decision after the dissemination of the dose escalation package, what process is in place to notify the PI/Study team?"]
[]
["List the cohorts/arms and number of subjects"]
["Group/ cohort/ arms","number of subjects"]
[]
[]
[]
[]
[]
[]
[]
["List the data used for making the dose escalation decision and minimum  % Source Data Verification or QC and how it's conducted."]
["Data","minimum  % ","SDV/QC","how it's conducted"]
[]
[]
[]
[]
[]
[]
[]
[]
[]
["Does the document confirming the dose escalation decision contain:","Please delete as appropriate.","If no, how will the information be communicated to the PI?"]
["the cohort was completed"]
["the data used "]
["the % of SDV or QC of the data reviewed"]
["who was at the meeting and that it was quorate"]
["Confirmation that the stopping criteria had not met"]
["The data listing used in the dose escalation meeting"]