Appendix E : Ethics Template APPLICATION FORMAppendix E : Ethics Template APPLICATION FORM Checklist...
Transcript of Appendix E : Ethics Template APPLICATION FORMAppendix E : Ethics Template APPLICATION FORM Checklist...
Appendix E : Ethics Template
APPLICATION FORM
Checklist
Document
Number of copies
Included
Research Protocol with checklist
Five
Yes No
Supplementary information (if applicable)
One
Yes No
Informed consent (English)
Fourteen
Yes No
Informed consent (local language)
Fourteen
Yes No
Study questionnaire
Fourteen
Yes No
Soft copy of IRB Application form
One / Soft
Yes No
------------------------------------------ ---------------------- Signature: Principal Investigator Date ------------------------------------------ ----------------------- Signature of supervisor (if applicable) Date ------------------------------------------- ------------------------ Signature of Chairman of the Department Date Institutional Review Board Institution / Organisation name
How to complete this form and begin the IRB review process
1. This form must not be handwritten. 2. Fill out all of the questions on this form completely. 3. Fill out and attach the appropriate appendices required by responses in this application. 4. Attach supporting documentation: consent form(s), protocol, survey instruments, interview
schedules, advertisements, letters of permission, etc. Consent form and questionnaire should also be submitted in other languages where applicable.
5. Complete the checklist that accompanies this form to ensure all requirements for submission are completed so that review is not delayed.
6. Submit this application and appendices along with the supporting documentation to the Institutional Review Board.
Principal Investigator Information:
Title: Professor
Name: Timothy R Walsh
Job Title: Professor
Department or Unit: Medical Microbiology and Immunology
Postal address: Room 174, 6th Floor Cardiff University School of Medicine UHW Main Building Heath Park Cardiff CF14 4XN Phone: +44(0)2920744725
Email: [email protected]
Signature of PI:
Date: 01/04/15
If more than three authors, please write down only name and institution for other authors. Project Information
1. Title of Research Project: Burden of Antibiotic Resistance on Neonates from Developing Societies
2. Select one of the category for your research project:
a. Clinical trial on a medicine/drug
b. Clinical trial on a medical device
c. Experimental surgical procedures
d. Study administering questionnaires/interviews for quantitative or mixed
qualitative/quantitative methods.
e. Study involving qualitative methods only
f. Study limited to working with human tissue samples, other human biological samples and / or
data
g. Research data base (secondary data analysis only)
h. Research involving animal subjects
If any other category then please write down in the space given below
__________________________________________________________________________
__________________________________________________________________________
__________________________________________________________________________
Note: Please provide details if study is related to Experimental drug(s) or Non-approved use or non-
approved dose for approved drugs
Not applicable
3. Do you plan to include any participants who are children or pregnant women?
Yes
(If yes please justify why it is important to take this study population)
The study is focusing on the burden of antibiotic resistance in neonates from developing societies, swabs
will be taken from expectant mothers and babies <60 days who present with sepsis will also be recruited
into the study.
4. Lay Summary of the Project
This study focusses on the burden of antibiotic resistance in neonates from developing societies. The
level of antibiotic resistance in neonatal infections and its impact on mortality in low-middle income
countries is unacceptably high. This study will provide the means, support, network and tools to
understand the impact of antibiotic resistance on neonatal morbidity and mortality, as well as to identify
possible solutions to minimise its impact.
5. Objectives of the Proposed Research
This study will be the first of its kind in the world to blend clinical and molecular epidemiology from low–
middle income countries with respect to neonatal Gram-negative infections. The data generated will be
used to inform, local, national and international health bodies and provide the means, support, network
and tools to understand the impact of antibiotic resistance on neonatal morbidity and mortality, as well
as to identify possible solutions to minimize its impact.
6. What is the scientific justification for the research?
The level of antibiotic resistance in neonatal infections and its impact on mortality in low-middle income
countries is unacceptably high. This study will provide the means, support, network and tools to
understand the impact of antibiotic resistance on neonatal morbidity and mortality, as well as to identify
possible solutions to minimize its impact.
7. Please list the principal inclusion criteria
All pregnant mothers coming into the clinic and all mothers returning with a child <60 days old presenting
with sepsis.
8. Please list the principal exclusion criteria
• Mothers who are present with diarrhoea, therefore rectal swab is unable to be taken.
• Child older than >60 days old.
9. Methodology and procedures involved in this study.
The BARNARDS network is unique and will centre on monitoring and improving mother/infant wellbeing
including exploring the impact on infection control interventions. We will not only assess the burden of
antibiotic resistance but also determine the prevalence of multi-drug resistant Gram-negative bacteria
(MDRGNB) carried as normal flora and causing neonatal sepsis. BARNARDS questionnaires will identify
demographic indices such as population size, overcrowding, access to clean water, sanitation conditions,
family size, poverty level, antibiotic usage and their impact on MDRGNB. We will map dominant clones
in each centre and correlate mother’s normal flora and neonatal infections and also compare strains
between the 5 centres examining emergence of international domain MDR clones. During the period of
the study, the number and type of specimens will be able to monitor local outbreaks of bacterial clones
(see Appendix A). We have made provision to take surface (environmental) swabs and therefore can
identify risk factors for nosocomial outbreaks. Concordantly, we will also monitor hand-washing
practices and analyze differences between the five centres and their correlation with neonatal sepsis.
Rectal swabs will be collected from pregnant women prior to delivery, and will be sent to the UK to
screen for MDR (specifically ESBL and carbapenemase positive) GNB. Bacterial isolates from neonates
from these mothers who develop both early (<72 hours) and late onset bacterial sepsis (>72 hours) will
also be studied, and compared to isolates from the mother. Rectal samples taken from mothers whose
infants do not present with infection will be used as a control group. Moreover, we aim to implement an
infection control policy supported by an educational campaign to enhance local health awareness in
preventing neonatal sepsis.
The molecular platform is a dedicated genomic hub that will provide data on strain type,
virulence/pathogenic potential and novel genetic data / mechanisms of resistance. The genomic hub will
be run from the UK and visiting fellows from the five centers will travel to the UK to learn about
sequencing/molecular biology.
Figure 1: Flow of data pipeline. Activities in the blue sectors are what will take place in LMICs.
BARNARDS is unique in engaging LMICs with a comprehensive genomic platform – we aim to sequence
4000 isolates over the 36 months of the project and establish a comprehensive international neonatal
GN sepsis database – the first of its type worldwide (see figure above). BARNARDS will not only produce
unique and critical data but has a strong educational aspect – uniform and excellent microbiology
practice across the 5 centers and a world-class molecular/genomics education program to be based in
the UK (fellows from the 5 centers will attend workshops at Cambridge (SANGER) and have practicable
experience analyzing the genomes of their own strains in the UK. The genomics platform will also allow
a database depository as well as a strain depository – these will be open and accessible to all partners
with in BARNARDS and provide a unique research source for future national and international funding
opportunities. On publication of data, all data associated with that part of the study, or the study in
whole, will be released to the public. BARNARDS will establish and operate a website that will be made
accessible to all partners and allow limited access by the general public. Publicity events and ICAAC (USA)
and ECCMID (Europe) will also be encouraged exposing meeting delegates to aspects of MDR/XDR in
LMICs.
10. How long do you expect each participant to be in the study in total?
Dependent on potential required treatment, which will vary patient to patient. The maximum will be for
60 days.
11. Please complete the following for each intervention / procedure as follows:
a. Total number of interventions/procedures to be received by each participant as part of the research
protocol.
• Mother: 1-2 – rectal swab on enrolment, and again if she returns with her baby at a later date
(i.e. the baby presented with clinical signs of sepsis after returning home within the first 60 days
of life)
• Baby <72 hours: 0*-1 if baby presents with clinical signs of sepsis a blood culture is taken.
• Baby >72 hours: 2 if baby presents with clinical signs of sepsis a rectal swab and a blood sample
will be collected.
*none if the baby does not present with clinical signs of sepsis.
b. If this intervention/procedure would be routinely given to participants as part of their care outside
the research, how many of the total would be routine?
N/A
c. Details of who will conduct the intervention / procedure, and where it will take place.
Rectal swabs will be collected from pregnant women prior to delivery, and will be sent to the UK to
screen for MDR (specifically ESBL and carbapenemase positive) GNB by research nurses within the
healthcare facility / clinic. Bacterial isolates from neonates from these mothers who develop both early
(<72 hours) and late onset bacterial sepsis (>72 hours) will also be studied, and compared to isolates
from the mother. Rectal samples taken from mothers whose infants do not present with infection will
be used as a control group. Moreover, we aim to implement an infection control policy supported by an
educational campaign to enhance local health awareness in preventing neonatal sepsis.
12. What are the potential risks and burden for research participants and how will you minimise them?
(Describe any potential adverse effects, pain, discomfort, distress, intrusion, inconvenience or changes
to lifestyle. Only describe risks or burdens that could occur as a result of participation in the research.
Say what steps would be taken to minimize risks and burdens as far as possible)
There are no side effects of the study.
13. Will interviews / questionnaires or group discussions include topics that might be sensitive,
embarrassing or upsetting?
o Yes
o No
14. What are the potential benefits for the research participants?
There is no personal benefit.
15. How and by whom will potential participants first be approached?
Participants will be approached by research nurses in each local healthcare facility.
16. How long will you allow potential participants to decide whether or not to take part?
Approximately 20 minutes to go through the consent form. Sample collection will take approximately
****** please complete ****. Participants have the right to withdraw from the study.
17. What arrangements have been made for persons who might not understand verbal explanations or
written information given in local language/English, or who have special communication needs? (E.g.
translation, use of interpreters)
The research nurses will be able to translate to the local language, if the participant cannot communicate
in this language, they will not be able to provide informed consent and therefore cannot be recruited
onto the study.
18. Please describe the physical security arrangements for storage of personal data during the study.
The questionnaires and consent forms completed by nurses after will be given to the data entry operator
at institution name will then keep all the forms locked in a drawer until the data is electronically entered.
After data entry, the forms will be retained on site until collection by the UK team / postage arranged at
the end of the study.
19. How will you ensure the confidentiality of personal data? Please provide a general statement of the
policy and procedures for ensuring confidentiality, e.g. anonymisation or pseudonymisation of data.
To maintain confidentiality participant will be given a study ID and all data collected will be coded, name
of participant will not be displayed only study ID given will be used.
20. Who will have access to participants' personal data during the study?
Staff related to the study.
21. Laboratory and Radiological studies
a. Will any tests be performed which are not routinely included as part of the work-up for these types
of patients?
Yes rectal swabs will be taken from the mothers, and in many sites it’s not standard practice to take
blood cultures from the infant.
b. Who or what agency will pay for these tests?
This will be covered by the funding of the grant
c. Who or what agency will pay for these tests?
Bill and Melinda Gates Foundation. (via Cardiff University)
22. How do you intend to report and disseminate the results of the study?
The grant will cater for the visitation of the Senior Research Scientist from each center at the end of the
project (30-36 month) to visit the UK and work on the bacterial genomes from their own projects. They
will also be enrolled on courses on molecular genomics and antimicrobial resistance and provided with
teaching materials to disseminate these materials in their own centers. When full genome sequences
are compiled, data on strain ID, strain type and a full virulence and antimicrobial resistance profile will
be sent back to each clinical center so that they have access to their own data and use it effectively
towards improving quality of healthcare. A central database will be stored in the UK that will capture all
demographic data, clinical and molecular information. When appropriate data will be uploaded on the
BARNARDS website which will be made fully public.
Findings will be disseminated to all partners and the funder.
Findings will be presented in peer reviewed journals.
23. Will you inform participants of the results of the study?
Yes, on the participant’s request.
Please give details of how you will inform the participants or justify if not doing so.
After patient’s consent, we’ll ask her if she wants to be conveyed the results of the study. If the
participant wants to, we’ll record her contact no. After the paper has been accepted in a journal, we’ll
contact the participants and inform them of the outcomes.
24. What is the primary outcome measure for the study?
• Establish a neonatal (<60 days of age) network in Africa (Nigeria, Ethiopia and Rwanda) and
South Asia (Pakistan, India and Bangladesh) addressing the burden of antibiotic resistance.
• Determine the prevalence of GNMDROs colonising and / or causing infections in neonates and
compare this to the prevalence of these organisms in the mother (GNMDROs will be used as a
convenient resistant marker).
• Describe the dominant bacterial clones of those bacteria causing infections in neonates, and
compare this with the dominant clones carried by mothers (which likely reflect the dominant
clones in the community).
• Provide a comprehensive genomic platform of approximately 4000 isolates over the duration of
the 36 month (?) project and establish an informatics database.
• Provide microbiome data on neonate and mother's normal flora and map bacteria causing
sepsis to the microbiome database.
• Monitor local outbreaks especially caused by GNMDROs and correlate this with samples
obtained from NICU hospital equipment as noted in Appendix A.
• Monitor hand hygiene practices towards establishing risk factors for GNMDRO transfer using the
5 Moments of hand hygiene (WHO).
• Microbiology laboratory technical support and capacity building in LMICs.
• Establish training in molecular biology and implement workshops in genomics/informatics (UK
based workshop/training) for interested participants from this study
• Investigate and identify risk factors for carriage of GNMDROs and infections in neonates.
• Evaluate and record the human and financial burden of antimicrobial resistance associated
infections amongst neonates (hospital stays, clinical outcome etc.)
• Establish a publically owned centralised international neonatal antimicrobial resistance
database and international strain repository. Develop and maintain a website linking existing
networks in LMI countries and promote their research and clinical experiences.
• Monitor and report changes in GNMDRO genomic profiles associated with transmission in
neonatal units.
25. What is the sample size for the research? How many participants / samples / data records do you
plan to study in total?
• 400 CRO/Site/Year will be forwarded for sequencing
• 1700 swabs per site per year.
• We aim to sequence 4000 isolates over the 36 months of the project and establish a
comprehensive international neonatal GN sepsis database
Please refer to Figure 1: Flow of data pipeline. Activities in the blue sectors are what will take place in
LMICs.
26. How was the sample size decided upon? If a formal sample size calculation was used, indicate how
this was done, giving sufficient information to justify and reproduce the calculation.
There are absolutely no studies gauging the burden of antibiotic resistance in neonates from developing
societies internationally. A sample size of 4000 was chosen to appropriately answer our research
questions.
27. Has funding for the research been secured?
Funding secured from one or more funders
28. Has this or a similar application been previously rejected by a Research Ethics Committee in local
country?
o Yes
o No
29. How long do you expect the study to last in local country?
48 months
30. Is this study?
o Single centre
o Multicentre
30. Where will the research take place?
Detail the wards / hospitals
Declaration by Principal Investigator
1. The information in this form is accurate to the best of my knowledge and belief and I take full
responsibility for it.
2. I undertake to abide by the ethical principles underlying the Declaration of Helsinki and good practice
guidelines on the proper conduct of research.
3. If the research is approved I undertake to adhere to the study protocol, the terms of the full application
as approved and any conditions set out by review bodies in giving approval.
4. I undertake to notify review bodies of substantial amendments to the protocol or the terms of the
approved application, and to seek a favourable opinion from the Ethical Review Board before
implementing the amendment.
5. I undertake to submit annual progress reports setting out the progress of the research, as required by
review bodies.
6. I am aware of my responsibility to be up to date and comply with the requirements of the law and
relevant guidelines relating to security and confidentiality of patient or other personal data, including
the need to register when necessary with the appropriate Data Protection Officer. I understand that I
am not permitted to disclose identifiable data to third parties unless the disclosure has the consent of
the subjects’ data.
7. I understand that research records/data may be subject to inspection by review bodies for audit
purposes if required.
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Signature: Principal Investigator Date