How to get R&D approval? LINDA POINTON RESEARCH PROJECT - - PDF document

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How to get R&D approval?

LINDA POINTON RESEARCH PROJECT MANAGER WELLCOME TRUST CONSORTIUM FOR NEUROIMMUNOLOGY OF MOOD DISORDERS AND ALZHEIMER’S DISEASE (NIMA)

Write your protocol Get ethics approval Get R&D approval

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The BIODEP study

Primary Clinical Cohort Adult MDD, 25-50 yrs, sampled from NHS services, N~200

Stratified by monoaminergic (MA) anti-depressant exposure and response

Secondary Clinical Cohort Adult MDD, sub-sampled from primary cohort plus new recruits, N~90

Stratified by peripheral blood level of C-reactive protein (CRP) MDD unresponsive to MA drugs N≈100 MDD responsive to MA drugs N≈50 MDD not treated by MA drugs N≈50 Healthy adults N≥50 All primary participants will complete the following assessments:

• Clinical interview including anti-depressant treatment history
• Clinical symptom questionnaires
• Venous blood sample for peripheral immunophenotyping and DNA
• Routine safety labs

High CRP > 3mg/L N≈45 Low CRP ≤ 3mg/L N≈45 All secondary participants will complete MRI plus 0, 1 or 2 below:

• [11C]-PK11195 positron emission tomography (PET)
• Lumbar puncture for cerebrospinal fluid (CSF) sampling

Healthy adults N≥45

Study design

 Adults with depression  Standardised clinical questionnaires  Routine safety bloods  Immunophenotyping  MRI scans  PET scans (PK11195)  Lumbar punctures

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Where do you start?

• What is the first thing to do?
• How do you write a protocol?
• Who do you need to contact in UoC, CUH, CPFT?
• What approvals do you need?
• What forms do you need to complete?
• What training do you/your team need
• Other considerations?

R&D Roadmap

LINDA POINTON RESEARCH PROJECT MANAGER WELLCOME TRUST CONSORTIUM FOR NEUROIMMUNOLOGY OF MOOD DISORDERS AND ALZHEIMER’S DISEASE (NIMA)

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What is the first thing to do? How do you write a protocol?

PROTOCOL PIS ICF

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Download a good protocol template (CCTU)

 Project summary  General information  Rationale & background

information

 References  Study goals and objectives  Study Design  Methodology  Safety Considerations  Follow-Up  Data Management and

Statistical Analysis

 Quality Assurance  Expected Outcomes of the

Study

 Dissemination of Results and

Publication Policy

 Duration of the Project  Problems Anticipated  Project Management  Ethics  Informed Consent Forms

Who do you need to contact?

PROTOCOL WBIC (MRI/PET) PIS ICF

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Wolfson Brain Imaging Centre (WBIC)

Contact: Daniel Barnes djb233@cam.ac.uk PROTOCOL WBIC (MRI/PET) Neurology (LPs) PIS ICF

Who do you need to contact?

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Neurology

PROTOCOL WBIC (MRI/PET) Neurology (LPs) Immunology PIS ICF

Who do you need to contact?

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Immunology

Dr Lori Turner

PROTOCOL WBIC (MRI/PET) Neurology (LPs) Immunology PIS ICF PPI (EBE)

Who do you need to contact?

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Patient & public involvement (PPI)

What time? Fasting?

PROTOCOL WBIC (MRI/PET) Statistician Neurology (LPs) Immunology PIS ICF PPI (EBE) External reviewer

Who do you need to contact?

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Who do you need to contact?

else

^

IDE (CenCom) Good draft of PROTOCOL PIS ICF

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IDE (CenCom)

Who do you need to contact?

else

^

CUH labs Good draft of PROTOCOL PIS ICF

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IDE (CenCom) CUH labs

Who do you need to contact?

else

^

CCRC/HSB Good draft of PROTOCOL PIS ICF

HSB Clinic

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IDE (CenCom) CUH labs CCRC/HSB

Who do you need to contact?

else

^

Insurance

• ffice

Good draft of PROTOCOL PIS ICF

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Complete the IRAS form & submit to REC

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IRAS

 Have a good draft protocol first  Look at other examples  Feels repetitive in places  Find out REC meeting dates  Need to factor in getting signatures  ARSAC – for ionising radiation  Don’t be afraid to call the helpdesk  Allow at least a month  Make all documents the same date and “Version 1”

Beware copy & paste!

After submission

 Study manual/SOPs  Training – GCP, EPIC  Get licences, vendor contracts, etc  Set up participant payments with finance  Get taxi coupons if needed  Set up data collection on the IDE

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Once REC approval comes through

 Get final insurance letter  Send all approved documents to WBIC,

CCRC

And finally...

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WBIC (MRI/PET) Statistician Neurology (LPs) Immunology PPI (EBE) External reviewer CUH labs CCRC/HSB IDE Insurance

• ffice

PROTOCOL PIS ICF

R&D Roadmap

IRAS/ REC REC approval R&D approval

Start study

• Study manual/SOPs
• Training – GCP, EPIC
• Get licences, vendor

contracts, etc

• Set up participant

payments with finance

• Get taxi coupons if

needed

• Set up data collection
• n the IDE
• Final insurance letter
• Send all approved

documents to WBIC, CCRC

Research passports 6-12 months

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Take-aways

 There is a lot to do!  Allow at least 6-12 months for set up/approvals  You are not alone – talk to other people  Keep in touch with the R&D Office  Contact the IDE early  Involve service users and carers at all stages

Any questions?

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The Human Tissue Act

How to Conduct Clinical Research - Training Event

Friday 20th May 2019 Dr Karen Ersche

Biological Safety

 What do we mean by human tissue?  What is the Human Tissue Act?  What do I need to know for my research?  Knowledge Quiz

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Human Tissue

 Any sample that consists of or includes

human cells:

 blood  urine  saliva

 Human tissue does not include:

 hair and nails  gametes  embryos  cell lines  DNA

The Human Tissue Act (HTA)

 Provides a legal framework for the removal, storage and use of human tissue.  Aimed to re-build public trust.

• 1. Consent
• 2. License
• 3. Transparency

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Relevance for Research

Am I allowed to use the samples?

 Informed consent must be obtained from the individual concerned to use and store relevant material for research or with the intent to analyse its DNA.

Am I allowed to store the samples?

 An HTA licence must be in place in order to store relevant material or exceptions apply.

• I. Consent: Permission to use Samples

 Honest information about the risks and the purpose for which the samples are needed.  Voluntary decision to provide a sample.  Promise to deliver expectations.

 Use samples only for what agreed.  Look after the samples (preserving integrity).  Look after the data that adds value to the samples.  Maintain link between data and samples.  Respect the donors’ confidentiality (anonymity). 41 42

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Specific versus Generic Consent

 Specific consent is required for tissue that is to be used just for a particular piece of research. Leftover material must be disposed of.

 “I understand that a blood sample will be taken and that DNA

will be extracted to determine variants of gene XYZ involved in brain functions that are being examined by this study.”

 Generic consent covers more general research including use of surplus samples for an unspecified use.

 “I have been informed that the laboratory may retain any

leftover samples to be used in future studies that have been ethically approved. I give consent for my DNA and related material to be stored for use in future studies.”

• II. Licence: Permission to Store Samples

 The Department of Psychiatry has no HTA licence.

 Samples can only be stored if they relate to a specific study that has been approved by an

NHS Research Ethics Committee.

 University REC approval is not acceptable!  When NHS REC approval expires, samples must be stored

• n licensed premises or renewed approval must be sought.

 Samples should only be stored in designated

freezers after an induction by the Biological

Safety Officer.

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• III. Transparency: Building Public Trust

 Demonstrating that you are working with the samples in line with the donor's expectations. 

purpose, quality, recordings, confidentiality/anonymity

 Clear processes in place (SOPs).

 e.g. sample labelling, storage, tracking, transportation, disposal

 Defined responsibilities.  Clear lines of accountability.

Standard Operating Procedures

 the responsibilities of researchers

 what to do when samples arrive

 how samples should be coded  where samples should be stored  how samples are disposed of Documented standard operating procedures (SOP) are required that describe:

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Storage in Psychiatry

 Location of Freezers:



Level 4 (Anaesthesia): 2 x -70C°



HSB (Clinical Suite): 1 x -70C°



Douglas House: 1 x -80C°, 1 x -20C°  Containers used must be suitable

for the required storage conditions.

 Samples should be kept upright.

Sample Labelling

 Relevant material must be labelled appropriately before they are put in the freezer.  All samples should have a unique and traceable sample code that should at least include the following information:

 Study ID  Subject ID  Date of collection

 The sample code should be written on the container using a permanent freezer-proof marker pen.

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Sample Tracking

 Study needs to be registered with the Biological Safety Officer.  Study-specific log sheets.  Logs must be completed in a timely manner. Sample tracking is necessary to provide a complete audit trail of the samples from collection to final analyses or disposal:

Study Resgistration I

 Researcher leading the study should provide the Biological Safety Officer with the details

about the study:

 Start date when you are planning to collect samples:  Study title:  Study ID (e.g. CRF number):  PI name:  Ethics (NREC) number:  Initial expiry date of ethical approval:  Type of specimen collected (serum/plasma, saliva, urine):  Overall sample size (numbers of participants):  Samples per participant:  Name & emails of researchers dealing with the samples:

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Study Resgistration II

 Researcher leading the study should also provide details about everyone in the team who needs access to the freezer:

 Copy of individual training record of handling biological samples  Copy of any equipment-specific training records (e.g. dry ice training, pressurised gas and cryogens course)  Confirmation that you will only access the psychiatry freezers  Badge number of your Addenbrooke’s NHS card

Log Sheets

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Removing Samples Sample Transport

When samples are transported within the university

• r to another destination, the samples must be

packaged appropriately ( preserving integrity!).

Examples of sample transport containers.

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Dry Ice

 Do not touch with bare hands – use gloves.  Do not eat or store in freezer designed for food storage.  Do not place in airtight container.  Store containers upright, in dry, well-ventilated areas.  When finished with dry ice, unwrap and leave it at room temperature in a well-ventilated area. It will sublimate from a solid to a gas.

Points to remember:

 Leading researcher of the study should liaise

with Biological Safety Officer on behalf of their team.

 Record everything that goes in / out of the freezer!  Wear gloves!  Do not move samples from other researchers

to a different freezer shelf!  Keep the time to open the freezer door to an absolute minimum.  Do not touch/move any other equipment in the room.

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Sending Samples

 The date of dispatch and destination must be filled out on the sample tracking log.  A copy of the sample tracking log must accompany the samples being sent.  Confirmation of receipt should be requested from the receiving site.  The Biological Safety Officer can recommend courier services to be used for the transport of samples.

When sending samples externally for storage or analysis:

Receiving Samples

 Verify that appropriate consent is in place before using the samples in your research.  Check that the expected number of samples and labelling matches the samples received.  All movements must be signed and dated to maintain a complete audit trail for all samples.

If you receive samples collected elsewhere and delivered to you by courier:

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Material Transfer Agreement (MTA)

 A contract that governs the transfer of research materials between two organisations when the recipient intends to use the material for their

• wn research.

 MTA defines the rights of the parties in respect to the extent of use, confidentiality, publication, and the ownership of intellectual property (IP).  The PI is responsible for making arrangements with the provider or recipient for transportation and delivery of the requested material.

Long-term Storage

 Once a study has closed, it is necessary for any remaining samples to be disposed of or transferred to long-term storage.  If consent has been given for further unrelated research, the samples must be transferred to a licensed tissue bank.

 It is illegal to hold human tissue in the Department

• f Psychiatry without valid ethical approval!

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Disposal of Biological Waste

Examples

 Human tissues must be disposed of with care.  Human samples should be double wrapped in two yellow, 300/500 gauge, plastic, clinical waste sacks.  Samples that had been collected at the Clinical Research Facility can be disposed of at this facility.

For More Information

 Human Tissue Act

 www.hta.gov.uk/guidance-professionals  www.hra.nhs.uk/  www.dt-toolkit.ac.uk/home.cfm

 Research Ethics

 www.byglearning.co.uk/mrcrsc-lms/course/category.php?id=1  www.ethicsguidebook.ac.uk/Human-Tissue-Act-119

 Biological Safety Issues

 Dr Karen Ersche: ke220@cam.ac.uk

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Take the Quiz Question 1

 I need to apply for a new HTA licence for every new project.

 

true false

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Question 1

 I need to apply for a new HTA licence for every new project.

 

true false

X

Question 2

 When I have biological samples, I can just put them straight in the freezer, if there is space.

 

true false

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Question 2

 When I have biological samples, I can just put them straight in the freezer, if there is space.

 

true false

X

Question 3

 If I ever need to dispose of human tissue, I should dispose of it in line with the SOPs that are described in the pink folder .

 

true false

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Question 3

 If I ever need to dispose of human tissue, I should dispose of it in line with the SOPs that are described in the pink folder .

 

true false

X

Question 4

 Samples only need to be labelled just with the subject ID and the date - no more information is needed .

 

true false

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Question 4

 Samples only need to be labelled just with the subject ID and the date - no more information is needed .

 

true false

X

Question 5

 When I take samples out of the freezer at the end of the study to send them away for analysis, I then don't need to do anything as long as I have arranged a courier to pick them up.

 

true false

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Question 5

 When I take samples out of the freezer at the end of the study to send them away for analysis, I then don't need to do anything as long as I have arranged a courier to pick them up.

 

true false

X

The End

Thank you!

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Infrastructure

James Rowe

People/organisations to help your Interventional study….

1. Funding agency 2. Research Ethics Committee 3. R&D office (CUHT, CPFT) 4. Research operations office (UoC) 5. Clinical research facility (CRF, HSB, other) 6. Clinical Trials Unit 7. The research facility eg WBIC 8. Trials pharmacy 9. University insurance office 10. Clinical research network/NIHR/Dendron 11. Clinical engineering 12. Head of department 13. Departmental H&S officer 14. MHRA/scope protocol review 15. The Director/Manager of each site 16. Human tissue authority and/or tissue bank 17. Legal services/Research services (Material transfer agreement) 18. Cambridge enterprise (IP) 19. HR letters of access/honorary contract (nb do you know where you are working?) 20. Gene Therapy Advisory Committee (GTAC) 21. Health research authority

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Infrastructure

• Addenbrooke’s Clinical Research Centre (WT-CRF)
• Herchel Smith Building
• Wolfson Brain Imaging Centre
• Windsor House
• Others
• Douglas House
• MRC-CBSU
• Adrian Building
• BCNI/Craik Marshall ….

Addenbrooke’s Clinical Research Centre (WT-CRF)

• .

Director: Professor Krishna Chatterjee Manager: Caroline Saunders Applications and Costing Manager: lindsay.carr@addenbrookes.nhs.uk Tel: 01223 254642

• inpatient beds, outpatient rooms, and investigation rooms
• Nurse supported biomarkers
• Nurse led CSF (lumbar puncture) for biomarkers
• Eating behaviour equipment
• Laboratory and tissue culture facilities
• Audiology soundproofed room
• Body composition measurement (DXA / Bod Pod)
• Ultrasonography and ophthalmology suite
• Exercise testing equipment
• Ideal for psychopharmacology and intensive biomarkers studies,

including mild to moderate risk groups Start up fee £1000 Renewal annually £500 Annual reporting

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Applicant Details Research Team (including trainees) Principal Investigator Project Details Project Type Project Funding Source Session Planning Session Request Facilities Required MRS (WBIC) Study Interventions Medical Cover Manager: Caroline Saunders Tel: 01223 596057 caroline.saunders@addenbrookes.nhs.uk Applications and Costing Manager: lindsay.carr@addenbrookes.nhs.uk 01223 254642 Information required? Just the basic and sensible information

Herchel Smith Building

Clinical Suite Committee

Graham Murray/Gloria Calderon (Psychiatry) Tim Rittman (CNS) Tim Dagleish (CBSU) TBA (BCNI) Sarah Ayerst (Nurse, Admin)

Contact : Sarah Ayerst (sa719@medschl.cam.ac.uk) Nurse, receptionist, study administration Facilities: interview rooms, clinical rooms, EEG, TMS Clean utility, ECG, phlebotomy, centrifuge, -70 freezer (own team to undertake)

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Herchel Smith Building

Clinical Suite Committee

Graham Murray/Gloria Calderon (Psychiatry) Tim Rittman (CNS) Tim Dagleish (CBSU) TBA (BCNI) Sarah Ayerst (Nurse, Admin)

Contact : Sarah Ayerst (sa719@medschl.cam.ac.uk) Nurse, receptionist, study administration Excellent for interviews, neuropsychology, combined-MRI/PET (WBIC close), Low-risk drug studies, simple biomarkers, EEG, TMS, Not for: intensive nursing needs, overnight, mod-risk drugs

.

Main HSB stakeholder group for study (one only please) CNS, Psych, BCNI, CBU Sponsoring organisation (please append proof of sponsorship) CUHT, UoC, CPFT Details of ethical approval, & approval number IRAS (or CPREC) Details of insurance, including number (append copy/provisional insurance) NHS , UoC , Medical Name, position and department of researchers who will use the HSB Non NHS SSI form attached. NON-NHS Type of research to be conducted at the HSB Drug Study, TMS Study, Non interventional study, EEG etc Number of participants Number of visits Summary of study activity and risk assessment Is medical/nursing other clinical cover required PI signature

No cost

Sarah Ayerst sa719@medschl.cam.ac.uk

Information required? Just the basic and sensible information

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Wolfson brain imaging centre

Director - Ed Bullmore Physics - Adrian Carpenter, Chris Rodgers (7T) PET - Franklin Aigbirhio IT – Guy Williams Business operations - Linda Morgan (grants) Contact Vicky Lupson

vcl21@wbic.cam.ac.uk

MRI-3T MRI-7T PET-MR PET

Awake, anesthetised, pharmaco-imaging

.

REC application REC approval letter Research Protocols ARSAC application ARSAC Licence Evidence of insurance for non-negligent harm R & D application R & D approval letter Consent forms Information sheet(s) Checklist of info to be included with an application

(Good news though - applications will be considered prior to final approval)

Contact ahead of REC submission recommended: Vicky Lupson vcl21@wbic.cam.ac.uk Procedures and application form for “the Resource Allocation Committee, RAC” Resources required Funding and costs Special MRI sequences or PET ligands (Adrian, Chris 7T, Guy, Franklin) Medical Cover ? And guidance on text for approvable Participant Information Sheets and Consent

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Windsor Research Unit (WRU)

www.cpft.nhs.uk/RandD/Windsor.htm

Fulbourn Hospital site

• comfortable reception and lounge
• venepuncture,
• ECG monitoring,
• centrifuge, fridge, -20 and -80 freezer.
• patient/carer interview room
• Access to patients

Director: Ben Underwood Manager: Dr Gloria Calderon wru@cpft.nhs.uk Gloria.Calderon@nhs.net 01223 219534

Windsor Research Unit (WRU)

www.cpft.nhs.uk/RandD/Windsor.htm

Excellent for low-intensity day- case or out-patient type studies, biomarkers, clinical assessment and non-invasive trials Director: Ben Underwood Manager: Dr Gloria Calderon wru@cpft.nhs.uk Gloria.Calderon@nhs.net 01223 219534

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Summary

• Contact the research facilities early
• Advice on PIS and consents forms – special requirements
• Advice on costs, feasibility, administration process
• Protocols, forms and committees are there to help
• Safety for you and your participants
• ACRC

lindsay.carr@addenbrookes.nhs.uk

• HSB

Sarah Ayerst sa719@medschl.cam.ac.uk

• WBIC

Vicky Lupson vcl21@wbic.cam.ac.uk

• Windsor

Gloria Calderon wru@cpft.nhs.uk

The Integrated Data Environment (IDE)

Barry Widmer

Database Operations Manager

Department of Psychiatry

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The challenge of modern research data management

• Large scale studies
• Multi-centre studies
• Turn over of Research Staff
• Data Protection/security
• Large data sets
• Complex data sets (MRI data, machine

generated raw data)

• Long-term archiving
• Access to clean data for analyses by

local, national and international collaborators

Integrated Data Environment (IDE)

Research data Study management

MRI scan data Longitudinal data capture

• Trial Manager
• Research Assistants
• Research Nurses
• Admin Assistants
• Data Manager
• Research Assistants
• Research Nurses
• MRI facility staff
• Data Entry Clerks
• Laboratory Staff
• Machine form reader
• Statisticians

Cohort Management System

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R-Studio / Shiny

Cohort Management System

MRI scans PET scans

Machine reader Behavioural tasks Data entry clerks Field workers Laboratory data Online data collection

Standardised exports for most Stats packages

Direct link

Integrated Data Environment (IDE) Server Infrastructure

Clinical School Safe Haven

Barry Widmer Joe Fryer Barry Widmer Junaid Bhatti Barry Widmer Naresh Subramaniam Barry Widmer Laura Villis Joe Fryer Server LTS

HPHI

Paul Browne Guy Williams

Server LTS

CenCom

Central Command Database

WBIC

R-Studio Server LTS Joe Kearney / Rudolf Cardinal

CamCOPS

Server LTS Shiny Visualisation

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Cohort Management System (CMS)

Standardised study model

SUBJECTS Rupert Bear Mickey Mouse Minnie Mouse Donald Duck Packs Questionnaire Saliva sample Assessments Clinical assess Blood sample MRI scan Pet scan Visits Baseline 1st follow up Baseline

• name
• address
• sex
• date of birth
• email
• phone
• carer details
• GP
• etc

Studies NSPN U-Change

Collecting clean, complete data

Validations:

• Duplicate names
• Age against study criteria
• Mandatory fields complete
• Carer details if < 16 years
• Existing family members

Mobile phone format for automated SMS

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Aims for “one click” access

xxxxxx xxxxxx xxxxxx

Cohort Management System (CMS)

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Online Research Electronic Data Capture

Demographic data Clinical measures

(height, weight etc)

Laptop task files Assessment CRF MRI scan Longitudinal events Questionnaires

Online Research Electronic Data Capture

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Online Research Electronic Data Capture Online Research Electronic Data Capture

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Laboratory results Data transfer via the IDE

xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx xx

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Data reporting and export Data export module

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MRI Data Management with XNAT XNAT MRI processing

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Built in image viewer The Integrated Data Environment (IDE)

Department of Psychiatry

• Ownership and access to your own data!
• Quickly and easily configurable for both

small/simple studies or large and complex studies

• Separation of identifiable and research data
• Streamlining of analyses and data distribution
• Effective long-term archiving

Please contact the IDE Team at an early stage in planning your project! Barry Widmer: bw215@cam.ac.uk

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www.ide-cam.org.uk

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