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CENTRAL UNIVERSITY RESEARCH ETHICS COMMITTEE (CUREC)

CUREC 3 Protocol and Application Form

Pharmacological Studies in Healthy Volunteers

ONLY FULLY SIGNED TYPE-WRITTEN APPLICATIONS WILL BE ACCEPTED, BY EMAIL

Please complete this Protocol and application form if your study involves the administration of a licensed drug, herbal remedy, or food supplement to healthy volunteers AND is not a clinical trial.

All advisory text is highlighted in yellow and should be deleted before finalising the document.Should you require any assistance in completing this document, please contact CTRG in the first instance: http://www.admin.ox.ac.uk/researchsupport/ctrg/

STUDY DETAILS

Full Study Title Insert full title including brief reference to the design, product being studied, and primary objective

Internal Reference / Short title

This should be assigned by the investigator/department (entire row may be deleted if not required)

MS IDREC Reference To be completed when approved

Date and version number

Principal Investigator Insert title and name

Student (if applicable) Insert title, name and degree programme (e.g. DPhil, BA, MPhil, BSc, MSc)

University email contact

University telephone contact

Medically qualified collaborator (Licensed Doctor)

Insert name, medical qualification and contact details (including institutional affiliation). If the PI or student is medically qualified, then insert their details here.

Sponsor The University of Oxford

External Funding Insert details of organisation providing funding (If none, please state ‘none’)

Give funding reference number if applicable

Will you submit or have you submitted this study to another ethics committee? Yes No

If other relevant approvals for this research are required (e.g. from other universities’ ethics committees) please attach them and give more details below:

CUREC 3 Protocol and Application Form Version 1.0. Approved by CUREC 17 Nov 2016 Page

http://www.admin.ox.ac.uk/researchsupport/ctrg/

Declaration of any Conflicts of Interest

If none, please state ‘none’

Confidentiality Statement This document contains confidential information that must not be disclosed to anyone other than the authorised individuals from the University of Oxford, the Investigator Team and members of the Medical Sciences Interdisciplinary Research Ethics Committee (Medical Sciences IDREC), unless authorised to do so.

RESEARCH TEAM

Copy and paste the below 4 rows as necessary to complete for each member of the research team, including student(s) then delete this entire row

Investigator Title and name

Department / Institute name

Add affiliation if not from University of Oxford

Role in Study Please give role(s), qualifications and relevant experience

Training/Qualification in Research Ethics

Please indicate what training received with title and date completed (online training available) or state relevant experience in research


https://www.admin.ox.ac.uk/curec/training/

https://www.admin.ox.ac.uk/curec/training/

1. TABLE OF CONTENTS

1. TABLE OF CONTENTS........................................................................................................................................3

2. SYNOPSIS..........................................................................................................................................................3

3. ABBREVIATIONS................................................................................................................................................4

4. BACKGROUND AND RATIONALE.......................................................................................................................5

5. PARTICIPANTS...................................................................................................................................................5

6. STUDY PROCEDURES.........................................................................................................................................7

7. INTERVENTION(S).............................................................................................................................................9

a) Drug/Substance 1.........................................................................................................................................9

b) Drug/Substance 2 (or placebo)...................................................................................................................10

8. SAFETY............................................................................................................................................................10

a) Definitions..................................................................................................................................................10

b) Reporting Procedures for Serious Adverse Events or Reactions.................................................................11

c) Safety of Participants..................................................................................................................................11

d) Ethical Considerations................................................................................................................................12

9. STATISTICS AND ANALYSIS..............................................................................................................................13

10.DATA MANAGEMENT.....................................................................................................................................13

11.STUDY MONITORING AND OVERSIGHT...........................................................................................................14

12.ETHICAL AND REGULATORY CONSIDERATIONS..............................................................................................15

Declaration of Helsinki........................................................................................................................................15

Approvals............................................................................................................................................................15

Annual Progress Report......................................................................................................................................15

13. INSURANCE STATEMENT................................................................................................................................15

14.DISSEMINATION AND FEEDBACK OF STUDY OUTCOMES...............................................................................15

15.REFERENCES....................................................................................................................................................15

16.DECLARATIONS AND SIGNATURES..................................................................................................................17

17.AMENDMENT HISTORY...................................................................................................................................17


2. SYNOPSIS

N.B. Please state briefly the objectives of the study as clearly, and unambiguously as possible.

Please state why this study is not considered a Clinical Trial of an Investigative Medicinal Product

Note that, typically, Experimental Medicine (EM) studies are conducted on volunteers (not NHS patients) and will specify non-clinical end-points. If you are in any doubt consult a PI experienced in writing appropriate descriptions of EM studies. Note that, while an EM study may eventually inform clinical practice and appear to be justified by its potential to do so, the actual design will not directly support a particular clinical indication and should not be described as if it will.

If you have sought opinion from the MHRA include details here

List all sites where study will be conducted

Age Range of Study Participants

Planned Sample Size

Planned Study Duration months or years

Anticipated Start Date

Anticipated End Date

Objectives Outcome Measures

Primary What question(s) are you trying to answer? Your answers should be succinct, excluding methodology, and realistic.

Example: To investigate how drug X influences brain function during a working memory task.

Describe the outcome measures and how/when they will be measured during the study.

Outcome measures should be chosen in advance as part of a pre-specified analysis plan. It is often wise to specify outcomes/measures of primary and secondary interest

Name of drug/substance You will be asked for more details in section 7

Purpose of drug/substance use in this study

Adverse reactions and side effects posing a particular risk with this treatment

Brief description – full details covered in sections 4 and 7 below


3. ABBREVIATIONS

Define all unusual or ‘technical’ terms related to the study.

Add or delete as appropriate to your study.

Maintain alphabetical order for ease of reference.

CTRG Clinical Trials & Research Governance, University of Oxford

CUREC Central University Research Ethics Committee

GCP Good Clinical Practice

GP General Practitioner

ICF Informed Consent Form

MS IDREC Medical Sciences Inter-Divisional Research Ethics Committee

PI Principal Investigator

PIS Participant Information Sheet

SOP Standard Operating Procedure

4. BACKGROUND AND RATIONALE

Please be brief: this is an explanation not a justification. Include the following:

Brief background to the study, including scientific justification for the research.

Outline of the research question(s).

Brief description of the intervention. Note: details of drug to be administered will be requested in section 7: do not duplicate here.

Summary of the known and potential risks, if any, to human participants.

References to literature and data that are relevant to the study and that provide background for the study.

5. PARTICIPANTS

Description of Study Participants

e.g. x number of Healthy Volunteers aged between y and z years

Inclusion Criteria

Example criteria only (amend as appropriate):

Participant is willing and able to give informed consent for participation in the study


Not currently taking any medications (except the contraceptive pill)

Additional study specific criteria as required

Exclusion criteria

Example criteria only (amend as appropriate):

The participant may not enter the study if ANY of the following apply:

Specify any diseases/disorders/ conditions that would preclude entry into the study Pregnant or breast feeding History or current psychiatric illness History or current neurological condition (e.g. epilepsy)

Additional study specific criteria as required

Recruitment

Describe how potential participants will be identified, approached, screened and recruited.

Example: Participants will be recruited by word of mouth, emails to departmental mailing lists and posters located in University Departments.

Screening and Eligibility Assessment

Specify the maximum duration allowed between screening and recruitment (if applicable).

Describe the screening procedures in detail. If applicable, specify pre-screening procedures such as demographics, medical history and physical examination.

If any screening procedures (such as blood sampling) require prior informed consent, then this must be stated.

Information Provided to Participants and Informed Consent

You need to specify who will take informed consent, how and when it will be taken. Informed Consent must be obtained prior to any study related procedures being undertaken.

Informed consent is the foundation of ethical research and provision of accurate and proportionate information is critical. Accordingly, the Participant Information Sheet (PIS) is the most important document you will prepare.

Please provide a copy of the PIS the participant will receive separately (with the relevant institutional heading).

Example:Written and verbal versions of the Participant Information and Informed Consent will be presented to the participants. The PIS will detail the exact practical demands of the study, written from the participant’s perspective and in simple non-technical language. (What will it involve for the participant?; when and where will they be required to attend, what procedures are involved and for how long? Describe how data will be collected, and briefly why this method will be used (e.g. type of equipment, questionnaire, interview schedule, observation schedule).

It will be clearly stated that the participant is free to withdraw from the study at any time for any reason and with no obligation to give the reason for withdrawal.

The participant will be allowed adequate time to consider the information, and the opportunity to question the Investigator or other independent parties to decide whether they will participate in the study.

Written Informed Consent will require a dated signature by the participant and dated signature of the person


who presented and obtained the Informed Consent. The person who obtained the consent must be suitably informed, qualified and experienced, and have been authorised to do so by the Principal Investigator. A copy of the signed Informed Consent will be given to the participant. The original signed form will be retained at the study site.

Are there any known adverse effects or risks involved in taking part? Will it be uncomfortable?

Explain what will happen to the data you collect. Distinguish between personal information and the research data you collect. Indicate how long you will keep the data for. Write this section to be compatible with what you write in section 10 below.

If you wish to retain the personal details of a subject for further contact (e.g. the opportunity to participate in other research projects), explain why and preferably for how long.

Participant Confidentiality

Give details about how you will maintain confidentiality of participant’s personal and research data.

Example:

The study staff will ensure that the participants’ data are safeguarded. The study will comply with the Data Protection Act, which requires personal data to be anonymised as soon as it is practical to do so. Where possible, participants will be identified only by a participant ID number on study documents and on any electronic database. Documents (such as consent forms) that contain identifying data and/or information allowing this to be linked to the participant ID will be stored separately under strict access controls. All documents will be stored securely and only accessible by study staff and authorised personnel.

6. STUDY PROCEDURES

Baseline Assessments and Procedures

You will have specified and described all baseline assessments and procedures on the participant’s information sheet. This must align with the relevant section of the PIS, and add any further technical detail, if necessary, from the investigator’s perspective. Include duration of procedures/session.

In particular, confirm that you will perform:

An eligibility check

assessments of safety including general (e.g. physical examination), specific safety assessments (e.g. adverse event collection)

dispensing of study product

assessment of compliance with study product


recording of concomitant medications (if applicable)

Provide a description sufficient to demonstrate adequate compliance with study objectives. If you will be following an approved procedure, do not duplicate here, but cite the procedure.

If there will only be one study visit, this section should be renamed ‘Study Visit’ and the next section ‘Subsequent Visits’ can then be deleted.

Subsequent Visits

You will have specified and described all follow up visits and procedures on the participant’s information sheet. This must align with the relevant section of the PIS here, and add any further technical detail, if necessary, from the investigator’s perspective.

Number these visits clearly and state the visit duration for each.

For each visit (including baseline), consider inclusion of the following, where appropriate:

assessment of outcome measures

assessments of safety including general (e.g. physical examination), specific safety assessments (e.g. adverse event collection)

adherence to dosing of study product

recording of concomitant medications (if applicable)

Provide a description sufficient to demonstrate adequate compliance with study objectives. If you will be following an approved procedure, do not duplicate here, but cite the procedure.

Sample Handling

Describe any samples that will be taken from each participant (e.g. blood, urine, saliva), the volume of sample, and the frequency of sampling. Describe briefly how the sample will be processed and stored once taken, and confirm that it will be rendered into a form not relevant under the Human Tissue Act within 7 days (and before use in the study). Identify who will have access (i.e. study team only for use in this study), and whether it will be stored long-term for use in future ethically approved studies). Provide a brief overview of the laboratory analyses that will be performed and how the samples will be destroyed (if appropriate).

If no samples will be taken, please state this.

Discontinuation/Withdrawal of Participants from Study

Example:

Each participant has the right to withdraw from the study at any time. In addition, the Investigator may discontinue a participant from the study at any time if the Investigator considers it necessary for any reason including:


https://www.hta.gov.uk/policies/list-materials-considered-be-%E2%80%98relevant-material%E2%80%99-under-human-tissue-act-2004

Delete/add as appropriate

Pregnancy Ineligibility (either arising during the study or retrospectively having been overlooked at screening) Significant protocol deviation Significant non-compliance with treatment regimen or study requirements Withdrawal of Consent Loss to follow up

If (for example) a participant is withdrawn due to an adverse reaction, specify any procedures and/or observations that will continue to be required until resolution of the reaction or the end of the study. Why will this be necessary?

State whether withdrawal from the study will result in exclusion of the data for that participant from analysis.

State whether or not withdrawn participants will be replaced.

The reason for withdrawal will be recorded

Definition of End of Study

The definition of end of study (for participant involvement) should be provided. In most cases the end of study will be the date of the last visit of the last participant. Any exceptions should be justified.Example:

The end of participant involvement in the study is the date of the last visit / telephone follow up / home visit of the last participant.

Expenses and Benefits

Please detail all expenses or gifts (vouchers, certificates etc.) that will be afforded to participants for taking part.

Example: Participants will be paid < £X > for their participation in the research. Reasonable travel expenses for any visits additional to normal care will be reimbursed on production of receipts, or a mileage allowance provided as appropriate.

7. INTERVENTION(S)

a) Drug/Substance 1

Name of drug/substance to be used

Formulation and route of administration for study

Dose and route of administration for study

Duration of treatment for study


Licence status of this drug/substance

Usual Indication

Usual Dose

Usual duration of treatment

Where will drug/substance be sourced from? Give name and address of manufacturer and/or supplier

Where will drug/substance be stored? Give location (building/room) and storage facility/temperature (room temp, fridge etc). Ensure that storage is correct for this drug/substance

How will drug/substance be dispensed?

How will the drug/substance be prepared by the researchers for use in this study?

Give details of any preparation or modification (such as over-encapsulation)

If more than one drug or substance will be administered (e.g. additional placebo), please also complete the below table. Delete if not necessary, and duplicate further as needed

b) Drug/Substance 2 (or placebo)

Name of drug/substance to be used

Formulation and route of administration for study

Dose and route of administration for study

Duration of treatment for study

Licence status of this drug/substance

Usual Indication

Usual Dose

Usual duration of treatment

Where will drug/substance be sourced from? Give name and address of manufacturer and/or supplier

Where will drug/substance be stored? Give location (building/room) and storage facility/temperature (room temp, fridge etc). Ensure that storage is correct for this drug/substance

How will drug/substance be dispensed?

How will the drug/substance be prepared by the researchers for use in this study?

Give details of any preparation or modification (such as over-encapsulation)


8. SAFETY

a) Definitions

Adverse Event (AE) Any untoward medical occurrence in a participant to whom a substance has been administered, including occurrences which are not necessarily caused by or related to that substance.

Adverse Reaction (AR) An untoward and unintended response in a participant to a substance, which is related to any dose administered to that participant.A causal relationship between the administered substance and an AE is at least a reasonable possibility, i.e. the relationship cannot be ruled out.

All cases judged by either the reporting medically qualified professional or the Sponsor as having a reasonable suspected causal relationship to the study intervention qualify as adverse reactions.

Serious Adverse Event (SAE)

A serious adverse event is any untoward medical occurrence that:

results in death is life-threatening requires inpatient hospitalisation or prolongation of existing hospitalisation results in persistent or significant disability/incapacity consists of a congenital anomaly or birth defect.

Other ‘important medical events’ may also be considered serious if they jeopardise the participant or require an intervention to prevent one of the above consequences.NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe.

Serious Adverse Reaction (SAR)

An adverse event that is both serious and, in the opinion of the reporting Investigator, believed with reasonable probability to be due to one of the study treatments, based on the information provided.

Suspected Unexpected Serious Adverse Reaction (SUSAR)

A serious adverse reaction, the nature and severity of which is not consistent with the information about the medicinal product set out in its summary of product characteristics (SmPC).


b) Reporting Procedures for Serious Adverse Events or Reactions

A serious adverse event (SAE) occurring to a participant should be reported to CTRG and the Medical Sciences IDREC where, in the opinion of the Principal Investigator, the event was ‘related’ (resulted from administration of any of the research procedures) and ‘unexpected’ (the type of event is not listed in the protocol as an expected occurrence). Reports of related and unexpected SAEs should be submitted within 15 days of the Principal Investigator becoming aware of the event. For fatal and life-threatening SUSARs, this will be done no later than 7 calendar days after the Sponsor or delegate is first aware of the reaction. Any additional relevant information will be reported within 8 calendar days of the initial report.

c) Safety of Participants

What level of baseline screening will take place for this study?

Give details as to what needs to be checked to ensure that it is safe to administer the drug to the participant

Provide details about the safety monitoring of participants and the staff/researchers carrying this out

Specify whether any study procedures require observation of, or ongoing communication with, the participant. If they do, detail how this will be carried out

Give details on the medical cover required and who will provide this cover

Specify whether study procedures require specific observation/monitoring by a medically-qualified professional. If they do, detail how this will be carried out

Will the participants’ GP be informed about their participation in the study? In not, please justify

What is your planned procedure if an incidental finding is suspected?

(Incidental findings are previously undiagnosed medical or psychiatric conditions that are discovered unintentionally during the course of the study)

If an incidental finding has clinical implications, what action will you take?

Please give details of departmental SOPs (if any) that will be followed in the case of an incidental finding

d) Ethical Considerations

Some research always carries the risk of ethical challenge. If this is the case you need to demonstrate your awareness of the problem and your response to mitigate ethical objections.

For more guidance on ethical issues, please see www.admin.ox.ac.uk/curec/resources/ , however the following areas are often a cause for concern:


http://www.admin.ox.ac.uk/curec/resources/

Will you include any vulnerable participants (e.g. children, elderly)?

If yes, please describe how they are defined as vulnerable and detail any CUREC approved procedures or guidance that you feel apply.

Yes No

Will taking part in the research put participants under any particular burden and/or risk?

If yes, describe how this will be mitigated.

Yes No

Will the research involve deliberate *deception* of participants?

If yes, justify why deception is used, describe deception and debriefing process, and include debriefing documents in the application

Yes No

Will any procedures affect your own physical and/or psychological safety as a researcher?

If yes, describe how this will be mitigated.

Yes No

Does your research raise issues relevant to the Counter-Terrorism and Security Act (the Prevent Duty), which seeks to prevent people from being drawn into terrorism?

If yes, please say how you plan to address any related risks. Please see advice on this on our Best Practice Guidance Web Page.

Yes No

Please give details of any other ethical and/or safety considerations

Include any study-specific ethical/safety considerations.

9. STATISTICS AND ANALYSIS

Do you have a statistical plan?

If no, please justify.

Yes No

Number of Participants


https://www.admin.ox.ac.uk/curec/resources/bestpractice/

https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/445916/Prevent_Duty_Guidance_For_Higher_Education__England__Wales_.pdf

https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/445916/Prevent_Duty_Guidance_For_Higher_Education__England__Wales_.pdf

https://www.admin.ox.ac.uk/curec/faqs-glossary/glossary/#d.en.163297

Have you done a sample size calculation?

If yes, please give details below

If no, please give details to indicate you have considered the implications the selected sample size will have on the study outcome

Yes No

Analysis of Outcome Measures

It is recommended that you pre-specify how you will analyse your data. Please indicate briefly how far you have considered this: for example, with a statistician or with your supervisor and what principles will guide your analysis (e.g. whether you have a primary outcome, how you will limit the number of post hoc comparisons, etc.).

10. DATA MANAGEMENT

Who will have access to the research data? Give details of researchers and any wider data dissemination, such as availability of data for public use

The following statement must be included:

Direct access will be granted to authorised representatives from the University of Oxford and any host institution for monitoring and/or audit of the study to ensure compliance with regulations.

How will research data be stored?

How long will research data be stored for? Note that the University minimum retention period for research data and records is 3 years after publication or public release of the work of the research, but funders may have different longer requirements. Where the research involves children, data must be retained until 3 years after the youngest participant turns 21.

What will be done with the research data at the end of the storage period?

Who will have access to the participants’ personal data?

How will personal data be stored?

How long will personal data be stored for? To comply with the data protection act, personal data will be deleted as soon as possible after it is no longer needed for the study.

Note that if you would like to retain contact details in order to get in touch with participants for future studies, you must detail this on the PIS and obtain specific consent on the


consent form.

Describe method(s) of research data entry/management

Example:All study data will be entered on a <<quote software and validation procedure e.g. Excel spreadsheet >>. The participants will be identified by a unique study specific number and/or code in any database. The name and any other identifying detail will NOT be included in any study data electronic file. Any documentation with identifiable (personal) data will be stored securely and separate from the research data.

11. STUDY MONITORING AND OVERSIGHT

Who will be responsible for day-to-day supervision of the study?

Give information about frequency of meetings that will be held to discuss progress/problems. Who will be present at the meetings?

12. ETHICAL AND REGULATORY CONSIDERATIONS

Declaration of Helsinki

The Investigator will ensure that this study is conducted in accordance with the principles of the Declaration of Helsinki.

Approvals

Consider the following text:

The protocol, informed consent form, participant information sheet and any proposed advertising material will be submitted to the Medical Sciences IDREC, and host institution(s) for written approval.

The Investigator will submit and, where necessary, obtain approval from the Sponsor and the above parties for all amendments to the original approved documents.


Annual Progress Report

The CI shall submit an Annual Progress Report to the Medical Sciences IDREC with a copy to CTRG.

13. INSURANCE STATEMENT

The University has a specialist insurance policy in place which would operate in the event of any participant suffering harm as a result of their involvement in the research (Newline Underwriting Management Ltd, at Lloyd’s of London).

14. DISSEMINATION AND FEEDBACK OF STUDY OUTCOMES

Please describe your plans with respect to participants as well as public dissemination plans, e.g. in journals and conferences. If the study results form part of a Masters or DPhil dissertation, please refer to Departmental policy on publications.

Consider describing how study results may be disseminated to study participants.

15. REFERENCES

Insert references used in text (preferably numbered, or in alphabetical order of first author).


16. DECLARATIONS AND SIGNATURES

I/We, the researcher(s) agree:

To start this research study only after obtaining approval from MS IDREC/CUREC;

To carry out this research study only if funding is adequate to enable it to be carried out according to good research practice and in an ethical manner;

To provide additional information as requested by MS IDREC/CUREC before approval is secured and as research progresses;

To maintain the confidentiality of all data collected from or about study participants;

To notify CTRG and MS IDREC in writing immediately of any proposed change which would increase the risks that any participant is exposed to and await approval before proceeding with the proposed change;

To notify CTRG and MS IDREC if the principal researcher on the study changes and supply the name of the successor;

To notify CTRG and MS IDREC in writing within seven days if any serious *adverse event* occurs in the course of research;

To use data collected only for the study for which approval has been given;

To grant access to data only to authorised persons; and

To maintain security procedures for the protection of personal data, including (but not restricted to): removal of identifying information from data collection forms and computer files, storage of linkage codes in a locked cabinet and password control for access to identified data on computer files.

Principal Investigator (Name)

Principal Investigator (Signature)

Medically qualified collaborator (Name)

Medically qualified collaborator (Signature)

Student (Name)

Student (Signature)

17. AMENDMENT HISTORY

Amendment No.

Protocol Version No.

Date issued

Author(s) of changes Details of Changes made


List details of all protocol amendments here whenever a new version of the protocol is produced. This is not necessary prior to initial REC submission.
