Grant Proposal- Peer Review

Running Head: Grant Proposal Draft 1

Draft 6

Grant Proposal Draft

04

University

Professor

May 21, 2018

Specific Aims

I am proposing a grant that will support the current efforts of conducting research on early diagnosis of pediatric neurology concerns in youth ages birth to adolescence. “Pediatric brain injury is among the most common causes of death of permanent disability in children” (Akedemir & Kapucu, 2016. pg. 7). By offering screening and treatment for these children and their families there may be a way to gain enough insight for a preventative measure to be introduced. There also may be away to prevent long term effects. The child neurology community has become somewhat detached from their patients due to introductions of technology in patient/practitioner relationships (Sherbany & Paylakis, 2018) and I would like to remedy that. Bridging a gap for not only the clients and their families, but the general population and future child neurologist to be excited about the undiscovered avenue this research may provide.

Conventional medicine has had its run at treating and preventing our youth’s neurological diagnosis for some time. We need to adapt to the new with whole exome sequencing. Taking what we have already learned through single-photon emission computed tomography (SPECT) and positron emission tomography (PET) scans, computed tomography (CT), magnetic resonance imaging (MRI), complementary and alternative medicine (CAM) to gain an understanding of the inner workings of these conditions. Also, measures like the Family Environment Scale (FES) measures environment of the patient. Family Crisis- Oriented Personal Evaluation Scales (F-COPES) that measure problem solving within the family. Family Assessment Measure (FAM) that measures family functioning. McCaster Family Assessment

Device (FAD) that measures structure of the family. Family Adaptability and Cohesion Scale (FACES) that measure family cohesiveness (Ketelaar, Bigossian, & Saini, et. al., 2017) to gain environment data to assist in creating what is pediatric neurology are the foundation we can now build on and bring in the next levels.

Background

When addressing Pediatric Neurology, we need to focus on where we are, where we want to be, and where we can be. Child Neurology covers age ranges from birth to adolescence and treats all neurological issues. “Pediatric brain injury is the most common causes of death or permanent disability in children” (Akedemir & Kapacu, 2016. Pg. 7). Also, “6% to 9% of the general public suffering from neurodisabilities are children or young people” (Ketelaar, Bogossian, & Saini, et. all., 2017). Currently we can use conventional measures and medication to assist with treatment and rehabilitation. Several studies have been done to achieve more. Children that suffer from movement issues are increasing and being able to find the results needed before adulthood can benefit the child and his/her life in the long run.

First is diagnosis. To gain an understanding we need to be aware of some of the conditions. Some are pediatric movement disorders. Tremors, chores, tics, myoclonus, athetosis, and stereotypies are just a few. Each one of these are can be diagnoses by a computed tomography (CT) or magnetic resonance imaging (MRI) as well as observation that is caused by a frontotemporal brain atrophy (Badheka, Barad, & Sankhla, 2018) Next are studies that go a step further. Nuclear medicine imaging has been able to assist prior to surgery on some patients that suffer from brain tumors, brain trauma, and epilepsy. Testing that utilizes single photon

emission computed tomography (SPECT) and positron emission tomography (PET) scans assist in early detection (Akedemir & Kapacu, 2016). Not all methods are similar, some are complementary and chiropractic medicine (CAM) that involve things like massage, multi vitamins or chiropractic care (Galicia-Connolly, Adams, & Bateman, et. all., 2014). Complementary and alternative medicine (CAM) have been used by many individuals, especially in pediatric neurology patients. A study done by 206 surveys completed regarding opinions on CAM. Many surveyed to their openness and previous use of CAM (Galicia-Connolly, Adams, & et. all., 2014). If we focus on the alternatives to prescribed drugs we may be able to avoid over medicating individuals and allowing for more natural, less harmful remedies.

The most recent method and the one that needs more exposure and study is whole exome sequencing (WES). Combine with and MRI this testing can assist with diagnosing brain abnormalities. In study conducted 24 patients out of 53 tested positive (Nolan & Carlson, 2016). With these methods the most influential could be the education of parents and those in the environment of those children that have these conditions. Therefore, I suggest that further studies be done on this population to increase early detection as soon as possible. This in turn would allow our youth that suffer from neurological issues the best chance at obtaining the correct treatment they will need. I propose we add this method as a mandatory test when diagnosing any child with brain abnormalities.

Significance

By increasing studies in this field, we will be able to obtain accurate diagnosis in these children and be able to increase remedies as needed and explore corrective measures for the most

prevalent conditions. Once accurate diagnosis’ are obtained thru the WES we can begin to educate the caregivers of these children as well. Creating patient reported outcome measures (PROMs) can gain attention. “The International Society for Pharmacoeconomics and Outcomes Research has recommended good practices for developing PROMs for children and young people which are a valuable resource to guide research” (Morris, Janssens, & Shilling, et. all., 2015). Not many populations are aware of the need for pediatric neurology. These conditions affect our youth and we go unknowingly until all other labels are issued. Most special education youth go without help. One in four school-aged children with a disability has an unmet need and 16% unmet needs for health care (Ansari, Dhongade, & Lad, et. all., 2016). This is unacceptable not only personally, but as a society.

Many obstacles are faced when dealing with youth as far as obtaining studies. Mostly is the consent and ethics as not many parents are willing to have their child studied. However, this is a necessity for clinical staff to obtain a beneficial result in this area. “Clinical research is, indeed, “the neck of the scientific bottle.” It’s conduct, quantity, and quality are of critical importance to improve future health and well-being. At present, there are insufficient data on the distribution and character of clinical research efforts in specific disciplines. Improving training and funding opportunities, identifying funding partners, and finding mechanisms to bring research efforts into clinical practice” (Al-Futaisi, 2004). Pediatric neurology will not benefit by staying stagnant. We need to move forward if we expect our children to.

Proposed Study

Research Question:

Will creating early testing of infants and children allow us to gain the knowledge in Pediatric Neurology by expanding past traditional MRI scans?

Hypotheses:

By getting our children screened with a whole exome sequencing test (WES) as well as traditional methods we will be able to fully identify patterns and severity of those young patients showing signs of brain abnormalities. If the WES is combined with traditional screening methods, then we will have vital information that will aid in diagnosis and possible patterns in those with these conditions.

Hypothesis Analysis:

The independent variable will be the WES addition and the dependent variable will be the participants will show positive reactions from accurate early diagnosis and correctly administered treatments. By gathering information from our participants, we will be able to enter in any signs of a pattern, increase or decreases resulting in specific treatments allowing for a documented study to allow for WES implementation into standard testing.

Methodology:

The methodology being used for this study is a mixed method as both quantitative and qualitive methods are represented due to the age of the patients and the data needs.

Study Design:

After gathering information from patients diagnosed with brain abnormalities that are ages 6 months to 10 years old a selection process will be done on 200 families. Of those 200 only 100 will be chosen depending on family consent, participation availability, and severity of brain abnormality. After gaining parent authorization and an interview process completed on the all caretakers that the child will be exposed to selection process will begin. To gain a foundation only families with children that were born with a condition that has progressed will be selected. Those that have had the injury inflicted on them will be considered for a follow up study. Four different groups will be made up of the 100 and split 50/50 by male and female. Each group will be split by age 6 months to 2, 3 to 5, 6 to 8, and 9 to 10 years old. Most screening are non-invasive, but screening solutions will be administered to all children so that scans can be read accurately. All participants will be screened for allergies to any substances will result in non- eligibility. All standard screenings will be done with the addition of the whole exome sequencing tests. Treatments will be administered depending on diagnosis of brain abnormalities and screening results as well as monitored for a 6-month period for any significant changes. Follow up will also be requested in a two year. Other risks will be monitored by therapist to ensure that the children are not in distress due to testing. Resources will also be provided to the families for 24-hour support should they require it.

Procedures:

Once full consent is authorized full physicals will be completed on all participants and a therapist and neurologist assigned to the child depending on what age group the child is in. Two

therapists and two neurologists will be main contacts with children. They will process all reports and data entry with assistance from a research assistant assigned to their group. All records will be kept confidential to medical personnel. Bi- weekly meetings will be held to gather and chart all data collected. Monthly reports will be issued to all caretakers as progress in the study as it pertains to the patient’s wellbeing. Equipment needed will be provided by St, Joseph’s hospital in Tacoma, Washington. Financially backed by approval of grant funds. This will include all neurological scans and computers needed for data entry along with all materials for charting and reporting. Office and presentation materials will be purchased by RA’s.

Budget Justification

Funding is requesting for two neurologists and two therapists. Dr. Ann will oversee all result input and reporting at a 10% increase. Two groups will have one graduate student to input data, recruiting, monthly family reports, data entry, result presentation format, and charting. Office supplies will be purchased and itemized from RAs. Each participant’s family will be given a $50 stipend. Computer rental and conference room to the hospital for the duration will be $333 a month. Screening, treatments, and lab use will be $10000 due to the hospital research department.

See Appendix A: Budget for detailed budget figures.

Appendix A: Budget

SUMMARY PROPOSAL BUDGET	FOR INSTITUTION USE ONLY
ORGANIZATION Child Neurology Clinic	PROPOSAL NO.	DURATION (MONTHS)
PRINCIPAL INVESTIGATOR (PI)/PROJECT DIRECTOR Instructor J. Ann	AWARD NO.
A. PERSONNEL: PI/PD, Co-PIs, Faculty, Graduate Assistants, etc.	Funds
List each separately with name and title.	Requested By
	Proposer
1. Instructor J. Ann, PhD ($90,000/year) - 10% effort for 6 months	$4,500
2. K. Bend, PhD ($90,000/year) – 6 months	$3,500
3. Therapist L. Carr, MA ($90,000/year) - 6 months	$2,000
4. Therapist M. Dee, MA ($90,000/year) - 6 months	$2,000
5. Research Assistants (RA) - 50% effort for 6 months	$12,500
6. Research Assistants (RA) - 50% effort for 6 months	$12,500
TOTAL SALARIES		$37,000
B. EQUIPMENT (LIST ITEM AND DOLLAR AMOUNT FOR EACH ITEM EXCEEDING $5,000.)
None
TOTAL EQUIPMENT	$0
C. TRAVEL	1. DOMESTIC – Presentation prep of results to medical board	$500
	2. OTHER - Travel for medical personnel to hospital and monthly visits	$400
TOTALTRAVEL		$900
D. PARTICIPANT SUPPORT	$5,000
1. STIPENDS	$	50
2. TRAVEL
3. SUBSISTENCE
4. OTHER
TOTAL NUMBER OF PARTICIPANTS (100) TOTAL PARTICIPANT COSTS	$5000
E. OTHER DIRECT COSTS
1. MATERIALS AND SUPPLIES- Computer rental for patient results, data collection, and analysis.	$2000
2. OTHER Screening, treatments, and lab use	$10,000
3 OTHER Office supplies	$707
4. OTHER
TOTAL OTHER DIRECT COSTS	$12707
F. TOTAL DIRECT COSTS (A THROUGH E)	$55607
G. TOTAL INDIRECT COSTS (F&A) (Rate = 7.9%)	$4392
H. TOTAL DIRECT AND INDIRECT COSTS (F + G)	$60,000

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