Natalizumab in Preventing Post-partum Relapses in Multiple Sclerosis
Phase: PHASE4
Conditions: Multiple Sclerosis
Sponsor: State University of New York at Buffalo

 
Official Title: 
NAtalizumab for Prevention of Post-partum Relapses in 
patients with Multiple Sclerosis (NAPPREMS) 
NCT number: 
NCT03046251 
Document Type: 
Study Protocol 
Date of the 
Document: 
05/15/2019 
 

 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
PROTOCOL TITLE: NAtalizumab for Prevention of Post-partum 
Relapses in patients with Multiple Sclerosis (NAPPREMS) 
Page 1 of 36 
 
 
INSTRUCTIONS: Complete Research Protocol (HRP-503) 
• Depending on the nature of what you are doing, some sections may 
not be applicable to your research.  If so, you must provide the 
reason why the section is not applicable for the response.  For 
example, most behavioral studies would answer all questions in 
section 30 with words to the effect of “drugs and medical devices 
are not used in this study.” 
• When you write a protocol, keep an electronic copy. You will need 
to modify this copy when making changes. 
• Do not remove the italics instructions or headings. 
• If you are pasting information from other documents be sure to use 
the “Merge Formatting” paste option so that the formatting of the 
response boxes is not lost.  If information is presented outside of 
the response boxes, it will not be accepted.  
• If this study involves multiple participant groups who participate 
in different research procedures, consent processes, etc., be 
certain to provide information in each applicable section for each 
participant group and clearly label each participant group within 
a section or subsection.  
 
PROTOCOL TITLE: 
Include the full protocol title. 
Response:  
NAtalizumab for Prevention of Post-partum Relapses in patients 
with Multiple Sclerosis (NAPPREMS) 
PRINCIPAL INVESTIGATOR: 
Name 
Department 
Telephone Number 
Email Address 
Response:  
Bianca Weinstock-Guttman 
UBMD Neurology 
716-829-5063 
bw8@buffalo.edu 

 
Page 2 of 36 
Revised: March 6, 2017 
VERSION NUMBER: 
Include the version number of this protocol. 
Response:  
Version 5 
DATE: 
Include the date of submission or revision. 
Response:  
05/15/2019 
Grant Applicability: 
Describe whether or not this protocol is funded by a grant or contract and if so, 
what portions of the grant this study covers. 
Response:  
Study specific procedures (Physical and neurological 
examinations, completion of QOL questionnaires) are covered 
by the grant.  Subjects may receive medication that is 
standard of care. Treatment related testing (that related to 
medication) required during the study is standard of care. 
 

 
Page 3 of 36 
Revised: March 6, 2017 
Table of Contents 
1.0 
Objectives ................................................................................................................ 4 
2.0 
Background .............................................................................................................. 4 
3.0 
Inclusion and Exclusion Criteria .............................................................................. 9 
4.0 
Study-Wide Number of Subjects (Multisite/Multicenter Only) ............................ 11 
5.0 
Study-Wide Recruitment Methods (Multisite/Multicenter Only).......................... 11 
6.0 
Multi-Site Research (Multisite/Multicenter Only)................................................. 11 
7.0 
Study Timelines ..................................................................................................... 12 
8.0 
Study Endpoints ..................................................................................................... 13 
9.0 
Procedures Involved................................................ Error! Bookmark not defined. 
10.0 Data and Specimen Banking .................................................................................. 16 
11.0 Data Management .................................................................................................. 17 
12.0 Provisions to Monitor the Data and Ensure the Safety of Subjects ....................... 20 
13.0 Withdrawal of Subjects .......................................................................................... 21 
14.0 Risks to Subjects .................................................................................................... 23 
15.0 Potential Benefits to Subjects ................................................................................ 23 
16.0 Vulnerable Populations .......................................................................................... 24 
17.0 Community-Based Participatory Research ............................................................ 24 
18.0 Sharing of Results with Subjects ........................................................................... 25 
19.0 Setting .................................................................................................................... 25 
20.0 Resources Available............................................................................................... 26 
21.0 Prior Approvals ...................................................................................................... 27 
22.0 Recruitment Methods ............................................................................................. 28 
23.0 Local Number of Subjects ..................................................................................... 29 
24.0 Confidentiality ....................................................................................................... 29 
25.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 30 
26.0 Compensation for Research-Related Injury ........................................................... 30 
27.0 Economic Burden to Subjects ................................................................................ 31 
28.0 Consent Process ..................................................................................................... 31 
29.0 Process to Document Consent in Writing .............................................................. 35 
30.0 Drugs or Devices.................................................................................................... 35 
 

 
Page 4 of 36 
Revised: March 6, 2017 
1.0 
Objectives 
1.1 Describe the purpose, specific aims, or objectives. 
Response:  
The primary objective of the trial is to assess the efficacy of IV 
administered natalizumab, monthly for 1 year, in preventing 
relapses during the postpartum period. 
The secondary objectives of the trial are to assess the efficacy 
of natalizumab in decreasing the risk for disability progression 
during the postpartum period and to prevent the appearance of 
new and/or enlarging brain MRI lesions as measured by 
qualitative MRI analysis. 
The tertiary objective is to assess the association of the clinical 
outcomes with subject evaluations including patient reported 
outcomes (QOL, satisfaction). 
1.2 State the hypotheses to be tested. 
Response:  
Natalizumab therapy instituted shortly after delivery will 
decrease the risk of relapses and /or MRI activity in the 
immediate postpartum period. 
2.0 
Background 
2.1 Describe the relevant prior experience and gaps in current 
knowledge. 
Response:  
Multiple sclerosis (MS) has a higher prevalence in women than 
men and recent literature suggests that the gender gap is 
widening .1 As the disease onset of MS is most likely to occur 
during child-bearing years, concerns about pregnancy and 
child rearing are frequently observed among MS patients. Even 
though there are no negative short-term effects of pregnancy 
on MS disease outcomes, and studies indicate there might even 
be beneficial long-term effects,2,3  a short rebound of disease 
activity is frequently observed after pregnancy. Recent studies 
have shown that relapse frequency during pregnancy 
decreased during the first three trimesters, after which a sharp 
increase can be observed three months postpartum.4 While not 
all women experience a rebound in relapse rates, there are 
indications that an increased relapse rate in the year prior to 
pregnancy, an increased relapse rate during pregnancy, and a 
higher Kurtzke’s Disability Status Scale at pregnancy onset are 
important indicators of an increased likelihood of postpartum 
exacerbations.5 Other results indicate that there are no effects 

 
Page 5 of 36 
Revised: March 6, 2017 
of epidural analgesia or breastfeeding on the risk of having 
postpartum relapses.6 
Several methods have been tried in order to prevent a rebound 
of relapses, which included treatment with IV steroids 
intravenous immunoglobulin (IVIg),7-9  sex hormones,10 and 
breast feeding.11 While some have been found to be beneficial 
in reducing the frequencies of relapses, none have been able to 
work consistently in preventing it. Studies investigating the 
therapeutic effect of IVIg on postpartum relapses have looked 
at both (re)starting treatment during the postpartum period, as 
well as continuing medication use throughout the pregnancy 
and postpartum period. Women who were treated throughout 
their pregnancy, and those who were treated postpartum 
showed significantly fewer relapses compared to women who 
did not receive treatment.12 While the effects of breastfeeding 
seemed notable when studies were first published, more recent 
literature suggests little to no benefit.13,14 Most recent data 
available from a retrospective assessment querying MSBase 
registry, a recent database including  24 months pre-conception 
and 2 years post- delivery information obtained from 674 
females with 893 pregnancies identified a raise in in ARR from 
0.32 pre-pregnancy level to 0.13 during the third trimester and 
0.61 in the first 3 months-postpartum.15 Pre-conception ARR 
and disease modifying therapy predicted early post-partum 
relapses. Interestingly pre-conception DMT use and low ARR 
were shown to be independently protective against postpartum 
relapses. 
Natalizumab has been found to be very successful in 
minimizing MS disease activity. No increase in negative birth 
outcomes after natalizumab exposure was found during 
pregnancy, and a trend towards a reduced number of relapses 
in women treated with natalizumab compared to women who 
were DMT naive was reported.16 While none of the above 
mentioned studies had patients that were treated with 
natalizumab during the whole gestational period, a recent case 
report showed no negative birth outcomes in a patient that was 
treated throughout her pregnancy with no signs of disease 
activity postpartum. 17 
It is generally advised to avoid exposure if possible to DMTs 
during pregnancy. There are currently no studies investigating 
the effects of natalizumab in preventing the anticipated 
postpartum increase in disease activity. Use of natalizumab, a 
high efficacy therapy for the 1 year post-partum, emerges as an 
appropriate intervention to control the high inflammatory milieu 
that characterize the post-partum period. The primary concern 

 
Page 6 of 36 
Revised: March 6, 2017 
related to the use of natalizumab is the risk to develop 
progressive multifocal encephalopathy (PML). The risk for 
development PML in patients treated with natalizumab is 
primarily linked to prolonged therapy (over 2 years), previous 
exposure to chemotherapy and being anti JCV antibody 
positive (STRATIFY JCV). As the risk for relapses in post-
partum period is in general limited to 1 year we propose to 
evaluate the efficacy of natalizumab therapy for this period. 
Continuing natalizumab vs. switching to another disease 
modifying therapy after 1 year should be re-assessed in case to 
case bases. 
2.2 Describe any relevant preliminary data.  
Response: 
A recent retrospective small French study18  reports the 
benefit of natalizumab use in postpartum period in 6 
previously very active MS patients. The annualized relapse 
rate (ARR) between natalizumab withdrawal and onset of 
pregnancy was 1.8 ±0.7. Six relapses occurred before onset of 
pregnancy and seven during pregnancy. Natalizumab was 
restarted 7.8 days after delivery (between day 2 and 8 for five 
patients and on day 23 for one). Only one patient, who had 
restarted natalizumab 2 days after delivery, had a relapse 2 
weeks later. The others five patients were relapse free after a 
mean of 14.2 ±9.1 months of follow-up. The conclusion of the 
study: “Despite a known high risk of post-partum relapses, 
early redosing of natalizumab led to a complete disappearance 
of disease activity in all but one patient. These data suggest 
that natalizumab could be a good candidate for preventing 
early post-partum relapses”. 
2.3 Provide the scientific or scholarly background for, rationale for, and 
significance of the research based on the existing literature and how 
will it add to existing knowledge. 
Response:  
As presented in the background section the post-partum period 
(especially the first 3 months) is characterized by an increased 
risk for relapses in MS patients. Although many disease-
modifying drugs (DMTs) have come to market in the past two 
decades, when used during pregnancy and lactation, their 
beneficial effects on the course of MS have to be balanced with 
fears concerning potential risks to the fetus or child. Therefore 
the general recommendation is to discontinue therapy during 
pregnancy and often even at the time of considering 
conception. As for the post-delivery period, breastfeeding and 
treatment options after delivery should be discussed to outline 

 
Page 7 of 36 
Revised: March 6, 2017 
the options for prevention of postpartum relapses, and the 
possible resumption of disease-modifying drugs Multiple 
interventions were considered in the postpartum period 
including: Immunoglobulins (IVIG), steroids9, estrogens10, none 
of which were able to show a significant positive effect in 
preventing the postpartum relapses as compared to no 
intervention. 
Based on the well-established natalizumab efficacy, especially 
seen in high risk patients, we expect that initiation of this 
therapy shortly after delivery can prevent relapses in a more 
effective manner than any other interventions. 
2.4 Include complete specific citations/references.  
Response:  
1. Orton S-M, Herrera BM, Yee IM, et al. Sex ratio of multiple 
sclerosis in Canada: a longitudinal study. Lancet neurology. 
2006;5:932-936. 
2. D'hooghe M. Long-term effects of childbirth in MS. Journal of 
Neurology, Neurosurgery& Psychiatry. 2010;81(1):38-41.  
3. Teter B, Kavak K, Kolb-Sobieraj C, Coyle P, Weinstock-Guttman 
B. Parity Associated with Long-Term Disease Progression in 
Women with Multiple Sclerosis. Journal of Multiple Sclerosis. 
2014;1(101):doi: 10.4172/jmso.1000101. 
4. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire 
P, Moreau T. Rate of pregnancy-related relapse in multiple 
sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J 
Med. 1998;339:285-291. 
5. Vukusic S, Hutchinson M, Hours M, et al. Pregnancy and 
multiple sclerosis (the PRIMS study): clinical predictors of 
post-partum relapse. Brain. 2004;127:1353-1360. 
6. Vukusic S, Confavreux C. Pregnancy and multiple sclerosis: the 
children of PRIMS. Clin Neurol Neurosurg. 2006;108:266-
270. 
7. Haas J, Hommes OR. A dose comparison study of IVIG in 
postpartum relapsing-remitting multiple sclerosis. Mult Scler. 
Aug 2007;13(7):900-908. 
8. Hellwig K, Beste C, Schimrigk S, Chan A. Immunomodulation 
and postpartum relapses in patients with multiple sclerosis. 
Ther Adv Neurol Disord. Jan 2009;2(1):7-11. 
9. de Seze J, Chapelotte M, Delalande S, Ferriby D, Stojkovic T, 
Vermersch P. Intravenous corticosteroids in the postpartum 

 
Page 8 of 36 
Revised: March 6, 2017 
period for reduction of acute exacerbations in multiple 
sclerosis. Mult Scler. Oct 2004;10(5):596-597. 
10. Vukusic S, Ionescu I, El-Etr M, et al. The Prevention of Post-
Partum Relapses with Progestin and Estradiol in Multiple 
Sclerosis (POPART'MUS) trial: rationale, objectives and 
state of advancement. J Neurol Sci. Nov 15 2009;286(1-
2):114-118. 
11. Langer-Gould A, Huang SM, Gupta R, et al. Exclusive 
breastfeeding and the risk of postpartum relapses in women 
with multiple sclerosis. Arch Neurol. Aug 2009;66(8):958-
963. 
12. Achiron A, Kishner I, Dolev M, et al. Effect of intravenous 
immunoglobulin treatment on pregnancy and postpartum-
related relapses in multiple sclerosis. J Neurol. 
2004;251:1133-1137. 
13. Airas L, Jalkanen A, Alanen A, Pirttila T, Marttila RJ. Breast-
feeding, postpartum and prepregnancy disease activity in 
multiple sclerosis. Neurology. Aug 3 2010;75(5):474-476. 
14. Portaccio E, Ghezzi A, Hakiki B, et al. Breastfeeding is not 
related to postpartum relapses in multiple sclerosis. 
Neurology. Jul 12 2011;77(2):145-150. 
15. Hughes SE, Spelman T, Gray OM, et al. Predictors and 
dynamics of postpartum relapses in women with multiple 
sclerosis. Mult Scler. May 2014;20(6):739-746. 
16. Hellwig, K., Haghikia, A. & Gold, R. Pregnancy and 
natalizumab: results of an observational study in 35 
accidental pregnancies during natalizumab treatment. Mult 
Scler 17, 958-963 (2011). 
17. Fagius, J. & Burman, J. Normal outcome of pregnancy with 
ongoing treatment with natalizumab. Acta Neurol Scand 129, 
e27-29 (2014). 
18. Vukusic, S., et al. Natalizumab for the prevention of post-
partum relapses in women with multiple sclerosis. Mult Scler 
21, 953-955 (2015). 
19. Horakova, D., et al. Environmental factors associated with 
disease progression after the first demyelinating event: 
results from the multi-center SET study. PLoS One 8, 
e53996 (2013). 
20. Weinstock-Guttman, B., et al. Lipid profiles are associated with 
lesion formation over 24 months in interferon-beta treated 
patients following the first demyelinating event. J Neurol 
Neurosurg Psychiatry 84, 1186-1191 (2013). 

 
Page 9 of 36 
Revised: March 6, 2017 
21. Browne, R.W., et al. Apolipoproteins are associated with new 
MRI lesions and deep grey matter atrophy in clinically 
isolated syndromes. J Neurol Neurosurg Psychiatry 85, 859-
864 (2014). 
22. Messina, S., et al. Increased leptin and A-FABP levels in 
relapsing and progressive forms of MS. BMC Neurol 13, 172 
(2013). 
3.0 
Inclusion and Exclusion Criteria 
3.1 Describe the criteria that define who will be included or excluded in 
your final study sample.  
Response:  
Subjects meeting all of the inclusion and none of the exclusion 
criteria provided below are eligible for enrollment in the 
natalizumab group. 
Inclusion Criteria: 
1. Female subjects postpartum, 0-30 days postpartum at the 
time of informed consent. 
2. Diagnosis of relapsing form of MS. 
3. Willing to initiating natalizumab and enroll in the TOUCH 
system. 
4. Willing and able to comply with the study procedures for the 
duration of the trial. 
5. Signed informed consent and HIPAA authorization. 
Exclusion Criteria: 
1. Diagnosis of primary progressive MS. 
2. Breastfeeding 
3. Use of IVIG in Tysabri treated subjects. 
4. Significant renal or hepatic impairment (in the opinion of the 
investigator) or other significant disease (e.g., cognitive 
impairment) that would compromise adherence and completion 
of the trial. 
5. History of hypersensitivity to previous exposure or presence 
of antibodies to natalizumab. 
6. Any other factor that, in the opinion of the investigator, would 
make the subject unsuitable for participation in this study. 
7. Patients that experience relapses and/or initiated DMT’s 
during pregnancy 

 
Page 10 of 36 
Revised: March 6, 2017 
The Control group will consist of relapsing MS patients post-
delivery who decline natalizumab therapy but open to enroll in 
the study. 
Similar Inclusion and Exclusion criteria as the Natalizumab 
group with the exception of requiring TOUCH enrollment 
program.  The Control group will be allowed to initiate any FDA 
approved DMT at any time post delivery or remain on no therapy 
while breastfeeding. 
3.2 Describe how individuals will be screened for eligibility. 
Response:  
During routine clinical visits patients who fulfill the inclusion 
criteria may be identified as potential candidates. 
Women are routinely seen in clinic for evaluation postpartum to 
discuss treatment options.  Clinic staff may identify potential 
candidates during routine clinic visits and offer the opportunity 
to enroll in this study. 
3.3 Indicate specifically whether you will include or exclude each of the 
following special populations: (You may not include members of 
these populations as subjects in your research unless you indicate 
this in your inclusion criteria.) 
• 
Adults unable to consent 
• 
Individuals who are not yet adults (infants, children, teenagers) 
• 
Pregnant women 
• 
Prisoners 
Response:  
Vulnerable populations (adults unable to consent, individuals 
who are not yet adults, pregnant women, and prisoners) will not 
participate in this research. 
3.4 Indicate whether you will include non-English speaking individuals.  
Provide justification if you will exclude non-English speaking 
individuals.  
(In order to meet one of the primary ethical principles of equitable 
selection of subjects, non-English speaking individuals may not be 
routinely excluded from research.  In cases where the research is of 
therapeutic intent or is designed to investigate areas that would 
necessarily require certain populations who may not speak English, 
the researcher is required to make efforts to recruit and include non-
English speaking individuals.  However, there are studies in which it 
would be reasonable to limit subjects to those who speak English: 
e.g., pilot studies, small unfunded studies with validated instruments 

 
Page 11 of 36 
Revised: March 6, 2017 
not available in other languages, numerous questionnaires, and 
some non-therapeutic studies which offer no direct benefit.)  
 
Response:  
As this study will require patient reported outcomes in the form 
of Quality of Life questionnaires that are in the English 
language, we will enroll only patients who are fluent in English. 
It is not feasible to have the patient reported outcomes tools 
translated for this small study. 
4.0 
Study-Wide Number of Subjects (Multisite/Multicenter Only) 
4.1 If this is a multicenter study, indicate the total number of subjects to 
be accrued across all sites. 
Response:  
30 subjects will be enrolled study wide. 
5.0 
Study-Wide Recruitment Methods (Multisite/Multicenter Only) 
If this is a multicenter study and subjects will be recruited by methods not under 
the control of the local site (e.g., call centers, national advertisements) describe 
those methods.  Local recruitment methods are described later in the protocol. 
5.1 Describe when, where, and how potential subjects will be recruited. 
Response:  
Patients will be identified during routine clinical visits. 
5.2 Describe the methods that will be used to identify potential subjects. 
Response:  
MS patients enrolled at one of the 2 participating centers.  
Women are routinely seen in clinic for evaluation postpartum to 
discuss treatment options.  Clinic staff will identify potential 
candidates during routine clinic visits and offer the opportunity 
to enroll in this study. 
5.3 Describe materials that will be used to recruit subjects. (Attach 
copies of these documents with the application. For advertisements, 
attach the final copy of printed advertisements. When advertisements 
are taped for broadcast, attach the final audio/video tape. You may 
submit the wording of the advertisement prior to taping to preclude 
re-taping because of inappropriate wording, provided the IRB 
reviews the final audio/video tape.) 
Response:  
No advertisement will be used for this study. 
6.0 
Multi-Site Research (Multisite/Multicenter Only) 

 
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Revised: March 6, 2017 
6.1 If this is a multi-site study where you are the lead investigator, 
describe the processes to ensure communication among sites, such 
as: 
• 
All sites have the most current version of the protocol, consent 
document, and HIPAA authorization. 
• 
All required approvals have been obtained at each site 
(including approval by the site’s IRB of record). 
• 
All modifications have been communicated to sites, and 
approved (including approval by the site’s IRB of record) 
before the modification is implemented. 
• 
All engaged participating sites will safeguard data as required 
by local information security policies. 
• 
All local site investigators conduct the study appropriately. 
• 
All non-compliance with the study protocol or applicable 
requirements will reported in accordance with local policy. 
Response:  
The coordinating center will provide the protocol (including 
source and questionnaires) to the participating sites.  Any 
amendments to the protocol will be communicated to the sites 
to be implemented appropriately.  The sites will provide proof 
of their local IRB approval prior to beginning research activity 
with subjects and any amendments will require approval prior 
to implementation.  IRB approvals for participating sites will be 
provided to the UBIRB as they are submitted to the coordinating 
center at UBMD Neurology. 
Each site will follow its own local regulatory requirements. 
6.2 Describe the method for communicating to engaged participating 
sites: 
• 
Problems. 
• 
Interim results. 
• 
The closure of a study 
Response:  
Site will receive status reports.  We do not anticipate problems 
with the conduct of the study, if any arise, communication with 
sites will be made as needed via email or telephone. 
If difficulty with enrollment within year 1 (less than 50% of 
expected enrollment) is encountered, consideration will be 
given to adding additional sites. 
7.0 
Study Timelines 

 
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Revised: March 6, 2017 
7.1 Describe the duration of an individual subject’s participation in the 
study. 
Response:  
Subjects will be followed for 1 year after enrollment. 
7.2 Describe the duration anticipated to enroll all study subjects. 
Response:  
Approximately 18 months after all sites are approved to begin 
enrollment. 
7.3 Describe the estimated date for the investigators to complete this 
study (complete primary analyses) 
Response:  
Approximately 18 months year for study completion after the 
last subject completes the study. 
8.0 
Study Endpoints 
8.1 Describe the primary and secondary study endpoints. 
Response: 
The primary endpoint is the proportion of patients who 
experience a relapse postpartum (proportion of patients 
relapsed, PPR) during 1 year post-delivery in patients treated 
with natalizumab. This will be compared to the PPR in the 
parallel control group. 
The secondary endpoints are: 
1. If appropriate, annualized relapse rate (ARR) between the 
natalizumab-treated group and the control group (who may 
remain off treatment or be on other DMTs). 
2. Confirmed (12 week) EDSS change of 1 point or more for a 
baseline EDSS > 1, or a confirmed increase of 1.5 points for an 
EDSS of 0-1, at Week 48 as compared to baseline between the 2 
groups. 
3. Change in MRI: MRI at Week 48 for: new or enlarging T2, and 
T1 gadolinium-enhancing (GdE) lesions counts compared to the 
change in MRI control group. 
4. Percent of patients that discontinued the primary therapy 
initiated post-partum (efficacy/tolerability) 
Tertiary endpoints: 
Change in QOL measures that will include: SF12v2, FSMC, and 
MSIS-29 v2 from baseline to week 24 and 48 as compared to the 
control group. 

 
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8.2 Describe any primary or secondary safety endpoints 
Response: All serious adverse events (SAEs), will be collected 
and summarized descriptively in the clinical study report 
and appropriate aggregate safety report. 
9.0 
Procedures Involved 
9.1 Describe and explain the study design. 
Response: 
This is a Phase IV, prospective, open-label, multicenter trial. 
Postpartum patients with a diagnosis of MS will be invited to 
enroll in this study that will evaluate the efficacy of IV 
natalizumab 
300 
mg 
to 
prevent 
postpartum 
relapses. 
Natalizumab, administered q 4 weeks, will be initiated 
postpartum (0-30) days post-delivery. Breastfeeding will be 
permitted up to 30 days postpartum in subjects opting to initiate 
Natalizumab 
(breastfeeding 
must 
be 
discontinued 
at 
natalizumab initiation). Patients who decline natalizumab 
treatment postpartum will be invited to enroll in the study in the 
control group. The control group will have similar inclusion, 
exclusion criteria, scheduled visit and study procedures as the 
active natalizumab treatment group. This group will be 
permitted to continue breastfeeding if they will remain off DMT. 
Approximately 30 subjects will be enrolled study wide. 
9.2 Provide a description of all research procedures being performed 
and when they are performed, including procedures being performed 
to monitor subjects for safety or minimize risks. 
Response: 
At Visit 1 (Screening/Baseline: 0-30 days post-delivery), 
patients provide informed consent/Health Insurance Portability 
and Accountability Act (HIPAA) then undergo evaluation of 
inclusion/exclusion eligibility criteria, provide a complete 
medical history including relapse history (1 year before 
pregnancy and during pregnancy), undergo full physical and 
neurological examinations (including EDSS). Recording of 
concomitant medications/procedures and laboratory testing 
will also be performed at screening/baseline (lab testing if 
applicable as part of standard of care). An MRI evaluation after 
delivery represents a routine clinical accepted requirement. 
Laboratory testing includes: CBC/diff, CMP, JCV antibody 
status (STRATIFY JCV), urinalysis with culture at screening and 
q 3 months as part of standard of care for those on natalizumab 
treatment.  

 
Page 15 of 36 
Revised: March 6, 2017 
The investigator will review the baseline lab results to confirm 
there are no abnormalities that prevent inclusion in the study, 
for those entering natalizumab treatment group. The first dose 
of natalizumab will be administered after the MRI and baseline 
lab testing are obtained.  Breastfeeding, if initiated, should be 
discontinued if patient is assigned to start natalizumab therapy.  
Subjects will visit the clinic for assessments on Visit 2 (Week 
12), Visit 3 (Week 24), Visit 4 (Week 36) and Visit 5 (week 48) for 
monitoring of their status, well-being, EDSS, and completion 
of PROs. SAEs will be monitored on an on-going basis 
throughout the study. An additional standard of care MRI will be 
performed at week 48, final visit of the study. Additional non-
scheduled visits during possible relapses will be scheduled 
within 72 hours from development of new symptoms 
suggesting of a relapse. 
The control group will be evaluated at same time points and can 
consider different intervention (including any FDA approved 
DMTs or breastfeeding only). 
Patients who experience relapses will be treated with 3-5 days 
IV Methylprednisolone. They will continue to be followed as per 
study visits schedule. Steroid therapy will be allowed if new 
symptoms or activity on baseline MRI will be identified before 
enrolling in the study. The control group patients will be 
maintained in the study while continuing on their same DMT 
initiated postpartum. As the treating physician and/or patient 
will consider a switch to any other DMT (including natalizumab). 
Patients who switched to rescue therapy will be discontinued 
from the study.  The percent of patient that require 
discontinuation (i.e. related to efficacy vs. tolerability) will be 
also assessed and compared between the groups.  
9.3 Describe procedures performed to lessen the probability or 
magnitude of risks. 
Response: 
This is not an interventional study. The risks associated with 
participation are limited to potential loss of confidentiality.  
The management of this risk is described in Section 11. 
9.4 Describe all drugs and devices used in the research and the purpose 
of their use, and their regulatory approval status. 
Response:  
There are no drugs or devices used for research purposes in 
this study. 
All treatments mentioned are FDA approved therapies that have 
been prescribed to the subjects as part of standard of care. 

 
Page 16 of 36 
Revised: March 6, 2017 
9.5 Describe the source records that will be used to collect data about 
subjects. (Attach all surveys, scripts, and data collection forms.) 
Response: 
Data will be collected on paper source documents. Subjects 
will complete hardcopy questionnaires. Source forms and 
Quality of Life questionnaires are provided as part of 
submission. 
9.6 What data will be collected including long-term follow-up? 
Response: 
An overview of the data that will be collected includes 
demographics, medical history, MS history, MS treatment 
history, physical exam, neurological exam, and vitals. Subjects 
also complete questionnaires.  The source documents with the 
exact data to be collected at study visits and the questionnaires 
are provided as part of submission. 
In addition, MRI data will be obtained for subjects and a 
counting of new and/or enlarging T2 lesions as well the number 
of T1 Gd enhancing lesions present at baseline and at the 1-year 
repeat brain MRI.  MRI data will be obtained electronically.  
Hardcopy MRI reports will be provided by the Investigator for 
data entry. 
9.7 For HUD uses provide a description of the device, a summary of 
how you propose to use the device, including a description of any 
screening procedures, the HUD procedure, and any patient follow-
up visits, tests or procedures. 
Response:  
No device will be evaluated and/or included in the study 
10.0 Data and Specimen Banking 
10.1 If data or specimens will be banked for future use, describe where 
the data/specimens will be stored, how long they will be stored, how 
the data/specimens will be accessed, and who will have access to the 
data/specimens. 
Response: 
No data or specimen will be banked for future use. 
10.2 List the data to be stored or associated with each specimen. 
Response: 
Not applicable 
10.3 Describe the procedures to release data or specimens, including: the 
process to request a release, approvals required for release, who 

 
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can obtain data or specimens, and the data to be provided with 
specimens. 
Response: 
Not applicable 
11.0 Data Management 
11.1 Describe the data analysis plan, including any statistical 
procedures. 
Response: 
General Methods 
All collected data will be displayed in patient data listings. 
Statistical analyses will be performed using SPSS for 
Windows. All analyses will be performed on the Full Analysis 
Set (FAS) defined as the set of all enrolled patients who 
received at least one dose of study drug. 
Descriptive statistics (n, mean, standard deviation [SD], 
median, Q1, Q3, minimum, maximum) will be calculated for all 
patients in the FAS. Frequencies and percentages will be 
presented for categorical and ordinal variables. Where 
appropriate, 95% confidence intervals (CIs) will be presented. 
As no randomization will be considered in this study the 
statistical analysis will control for demographic and clinical 
identified significant differences (see above the subanalysis 
metrics). Additional analysis will be considered using the 
propensity scores method. 
A block enrollment of 20 per group (natalizumab vs controls) 
will be required to provide an even enrollment between the 2 
groups and prevent a possible overenrollment in the control 
group before the natalizumab will be completed. 
Baseline Analyses 
Demographics and baseline characteristics will be analyzed 
descriptively. 
Baseline analyses will also include descriptive analyses of 
medical history, physical exam, neurological exam, baseline 
QoL assessment, and concomitant medications. 
11.2 Provide a power analysis. 
Response:  
A sample size of thirty (30) patients will be sufficient to provide 
evidence of a statistical trend in the difference in PPR between 

 
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participants who utilize natalizumab postpartum and the 
control group. 
11.3 Describe the steps that will be taken secure the data (e.g., training, 
authorization of access, password protection, encryption, physical 
controls, certificates of confidentiality, and separation of identifiers 
and data) during storage, use, and transmission. 
Response:  
All research staff is trained in proper data handle procedures.  
Files are maintained in locked cabinets in locked rooms in the 
offices of the department of Neurology (UBMB Neurology) 
located at 1010 Main Street, 2nd Floor, Buffalo, NY 14202.  Data 
is maintained in a password protected encrypted database. 
Access is limited to only those directly involved in the conduct 
of the research, including data entry and analysis. 
11.4 Describe any procedures that will be used for quality control of 
collected data. 
Response:  
Data is subjected to quality review by research staff at time of 
data entry. The data is cleaned using a logic check system to 
ensure accuracy. Data that does not pass logic check criteria is 
queried for clarification. 
11.5 Describe how data and specimens will be handled study-wide: 
Response:  
A unique subject number will be assigned to each subject at 
inclusion, immediately after informed consent has been 
obtained. This number will serve as the subject’s identifier in 
the trial as well as in the clinical trial database. The subject’s 
data collected in the trial will be stored under this number. Only 
the Site Investigator will be able to link the subject’s trial data 
to the subject via an identification list kept at the site. 
CRFs will be provided by the Coordinating Center (CC) that will 
be located in Buffalo at UBMD Neurology. The completed forms 
required for a visit will be sent to the CC via fax or email within 
7 days of each visit. The CC data coordinator assigned to this 
study will record receipt of the data transmittal on a log all the 
CRFs contained in that transmittal. CRFs will be reviewed for 
clarity and completeness. Incomplete or incorrectly completed 
forms will generate queries which will be faxed or e-mailed to 
the originating site on a Data Clarification Form (DCF). The DCF 
will identify the subject, visit number, and CRF in question, and 
the data elements that have been flagged for review. The 
originating site investigate the discrepancy. The DCF must be 

 
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completed showing what corrections need to be made (or 
indicating why no changes are necessary) and returned to the 
CC within 7 days of receipt. Data entry staff at the CC will make 
the appropriate changes to the database. The original DCF will 
be filed by the site coordinator with the CRF source documents 
for that visit. The CC will keep a copy of the corrected DCF as 
well, attached to the corresponding CRF. 
The data will be entered into a validated database. The CC will 
be responsible for data processing. Database lock will occur 
once quality control procedure, and quality assurance 
procedures (if applicable) have been completed. 
Files are maintained in locked cabinets in locked rooms in the 
offices of the department of Neurology (UBMB Neurology) 
located at 1010 Main Street, 2nd Floor, Buffalo, NY 14202.  Data 
is maintained in a password protected encrypted database. 
Access is limited to only those directly involved in the conduct 
of the research, including data entry and analysis. 
11.6 What information will be included in that data or associated with the 
specimens? 
Response:  
The data described in Sections 9.5 and 9.6 will be included in 
database.  
No specimens are being collected. 
11.7 Where and how data or specimens will be stored? 
Response:  
Files are maintained in locked cabinets in locked rooms in the 
offices of the department of Neurology (UBMB Neurology) 
located at 1010 Main Street, 2nd Floor, Buffalo, NY 14202.  Data 
is maintained in a password protected encrypted database. 
Access is limited to only those directly involved in the conduct 
of the research, including data entry and analysis. 
No specimens are being collected. 
11.8 How long the data or specimens will be stored? 
Response:  
Data may be stored for up to 10 years. 
No specimens are being collected. 
11.9 Who will have access to the data or specimens? 
Response:  

 
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The Principal Investigator and delegated research staff will have 
access to data as necessary for data entry, data clarification and 
analysis. 
No specimens are being collected. 
11.10Who is responsible for receipt or transmission of the data or 
specimens? 
Response:  
The Principal Investigator and delegated research staff at sites 
will be responsible for the transmission of the data for entry into 
the database. 
11.11How data and specimens will be transported? 
Response:  
Data will be transmitted from external sites via fax or email. 
No specimens are being collected.  
12.0 Provisions to Monitor the Data and Ensure the Safety of Subjects 
12.1 Describe the plan to periodically evaluate the data collected 
regarding both harms and benefits to determine whether subjects 
remain safe.   
Response:  
This is not an interventional study.  It is an observational study.  
Subject safety is not the primary outcome being evaluated.  The 
data being obtained is subjected to database logic check 
system to ensure accuracy. 
12.2 Describe what data are reviewed, including safety data, untoward 
events, and efficacy data. 
Response:  
This is not an interventional trial. The data will include patient 
reported quality of life as related to the ongoing use of therapy 
or no therapy. In addition clinical data including vitals, relapses, 
and disability score will be obtained. 
12.3 Describe how the safety information will be collected (e.g., with case 
report forms, at study visits, by telephone calls with participants). 
Response:  
Subject data will be collected at study visits.  Data will be 
recorded on case report forms by research staff.  Quality of 
Life questionnaires are completed by subjects.  If a subject 
experiences a relapse between regularly scheduled study 
visits she may contact the office by telephone to report 

 
Page 21 of 36 
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symptoms and the investigator will collect initial data and 
schedule and “unscheduled study visit” as necessary. 
12.4 Describe the frequency of data collection, including when safety 
data collection starts. 
Response:  
Subjects are evaluation at 5 visits.  After enrollment (baseline 
visit), all visits occur at 12 week intervals.  Relapse assessment 
is on-going throughout the study. SAEs will be reported after 
informed consent is obtained. 
Subjects enrolled in the Tysabri treated group are treated per 
standard of care every 4 weeks. 
12.5 Describe who will review the data. 
Response:  
Research staff will review data at the time of collection.  Data is 
subjected to quality review by research staff at time of data 
entry.  The investigator may review the subject data at any time 
throughout the subject’s participation as necessary. 
12.6 Describe the frequency or periodicity of review of cumulative data. 
Response:  
Data will be reviewed and analyzed at the end of the study.  No 
interim analysis is planned. 
12.7 Describe the statistical tests for analyzing the safety data to determine 
whether harm is occurring. 
Response:  
This study is not using new therapeutic intervention or non FDA 
approved drugs. The study will evaluate demographics, patient-
reported outcome and usual routine clinical measurements. 
12.8 Describe any conditions that trigger an immediate suspension of the 
research. 
Response:  
This is not an interventional study.  As such there are no 
anticipated safety concerns that would warrant an immediate 
suspension of the research. 
13.0 Withdrawal of Subjects 
13.1 Describe anticipated circumstances under which subjects will be 
withdrawn from the research without their consent. 
Response:  

 
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A subject must be withdrawn in the event of any of the 
following: 
• Participation in any other interventional trial during the 
duration of this trial 
• Occurrence of an exclusion criterion which is clinically 
relevant 
and 
affects 
the 
subject’s 
safety, 
if 
discontinuation 
is 
considered 
necessary 
by 
the 
Investigator 
• Occurrence of pregnancy 
• Non-compliance with study procedures (in the opinion of 
the investigator) 
• Discontinuation of the study drug for any reason 
(including but not limited: therapeutic failure requiring 
urgent additional drug, occurrence of adverse events 
(AEs), if discontinuation of trial drug is desired or 
considered necessary by the Investigator and/or the 
subject)*  
*Patients may opt to continue to be followed for the 
remainder of the 48 week study. 
Patients enrolled in the control group will be permitted to initiate 
any FDA approved DMT excluding natalizumab therapy. 
However the patients failing a first DMT will be considered 
treatment failure and will be discontinued from the study. A 
subanalysis will be performed based on the reason for DMT 
change related to efficacy vs. tolerability. 
13.2 Describe any procedures for orderly termination. 
Response:  
If a subject is to be withdrawn, either self-withdrawn or by an 
investigator, the subject may be immediately withdrawn, no 
procedures need to be performed other than to document the 
reason for withdrawal, if provided by the subject. 
13.3 Describe procedures that will be followed when subjects withdraw 
from the research, including partial withdrawal from procedures 
with continued data collection. 
Response:  
In 
case of premature withdrawal from the trial, 
the 
investigations scheduled for the last visit should be performed, 
if possible. In any case, the appropriate Case Report Form 
(CRF) section must be completed capturing the reason for 
discontinuation.   

 
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If for any reason patient is withdrawn from the study her data 
will not be removed from the dataset. 
14.0 Risks to Subjects 
14.1 List the reasonably foreseeable risks, discomforts, hazards, or 
inconveniences to the subjects related the subjects’ participation in 
the research. Include as may be useful for the IRB’s consideration, a 
description of the probability, magnitude, duration, and reversibility 
of the risks. Consider physical, psychological, social, legal, and 
economic risks. 
Response:  
No discomfort is expected as patients will have to complete only 
questionnaires and undergo examinations which are routine 
and noninvasive in nature. 
14.2 If applicable, indicate which procedures may have risks to the 
subjects that are currently unforeseeable. 
Response:  
No procedures should be unforeseeable. 
14.3 If applicable, indicate which procedures may have risks to an 
embryo or fetus should the subject be or become pregnant. 
Response:  
Not applicable 
14.4 If applicable, describe risks to others who are not subjects. 
Response:  
Not applicable 
15.0 Potential Benefits to Subjects 
15.1 Describe the potential benefits that individual subjects may 
experience from taking part in the research. Include as may be 
useful for the IRB’s consideration, the probability, magnitude, and 
duration of the potential benefits. 
Response: 
There is no clear immediate benefit to the individual patient. 
However, if the results of the study are positive, it will clearly 
provide significant general therapeutic information: To 
consider initiating natalizumab therapy immediately post-
partum. 
15.2 Indicate if there is no direct benefit. Do not include benefits to 
society or others. 
Response: 

 
Page 24 of 36 
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There is no clear immediate benefit to the individual patient. 
16.0 Vulnerable Populations 
16.1 If the research involves individuals who are vulnerable to coercion 
or undue influence, describe additional safeguards included to 
protect their rights and welfare. 
• 
If the research involves pregnant women, review 
“CHECKLIST: Pregnant Women (HRP-412)” to ensure that 
you have provided sufficient information. 
• 
If the research involves neonates of uncertain viability or non-
viable neonates, review “CHECKLIST: Neonates (HRP-413)” 
or “HRP-414 – CHECKLIST: Neonates of Uncertain Viability 
(HRP-414)” to ensure that you have provided sufficient 
information. 
• 
If the research involves prisoners, review “CHECKLIST: 
Prisoners (HRP-415)” to ensure that you have provided 
sufficient information. 
• 
If the research involves persons who have not attained the 
legal age for consent to treatments or procedures involved in 
the research (“children”), review the “CHECKLIST: Children 
(HRP-416)” to ensure that you have provided sufficient 
information. 
• 
If the research involves cognitively impaired adults, review 
“CHECKLIST: Cognitively Impaired Adults (HRP-417)” to 
ensure that you have provided sufficient information. 
• 
Consider if other specifically targeted populations such as 
students, employees of a specific firm or 
educationally/economically disadvantaged persons are 
vulnerable to coercion or undue influence.  The checklists 
listed above for other populations should be used as a guide to 
ensure that you have provided sufficient information.  
Response:  
Not applicable.  The study will not include vulnerable 
populations. 
17.0 Community-Based Participatory Research 
17.1 Describe involvement of the community in the design and conduct of 
the research. 
Response:  
This study will not involve community based participants in its 
design and conduct of the research 
Note: “Community-based Participatory Research” is a collaborative 
approach to research that equitably involves all partners in the 
research process and recognizes the unique strengths that each 

 
Page 25 of 36 
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brings. Community-based Participatory Research begins with a 
research topic of importance to the community, has the aim of 
combining knowledge with action and achieving social change to 
improve health outcomes and eliminate health disparities. 
18.0 Sharing of Results with Subjects 
18.1 Describe whether or not results (study results or individual subject 
results, such as results of investigational diagnostic tests, genetic 
tests, or incidental findings) will be shared with subjects or others 
(e.g., the subject’s primary care physicians) and if so, describe how 
it will be shared. 
Response: 
No genetic testing is performed. 
If abnormal findings are identified during testing (i.e. MRI) 
these will be communicated to the patient and PMD as 
applicable.  
19.0 Setting 
19.1 Describe the sites or locations where your research team will 
conduct the research.  
Response:  
The research will be conducted in the Conventus building (1001 
Main Street, Buffalo, NY 14203) at the Buffalo Niagara Medical 
Campus in the department of neurology outpatient offices 
(UBMD Neurology).  Study visits will occur in private exam 
rooms. 
19.2 Identify where your research team will identify and recruit potential 
subjects. 
Response:  
Recruitment will be performed during the routine clinical visits 
as described in Section 22.  
19.3 Identify where research procedures will be performed. 
Response:  
The research will be conducted in the Conventus building (1001 
Main Street, Buffalo, NY 14203) at the Buffalo Niagara Medical 
Campus in the department of neurology outpatient offices 
(UBMD Neurology).  Study visits will occur in private exam 
rooms. 
19.4 Describe the composition and involvement of any community 
advisory board. 
Response:  

 
Page 26 of 36 
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No community advisory board will be involved. 
19.5 For research conducted outside of the organization and its affiliates 
describe: 
• Site-specific regulations or customs affecting the research for 
research outside the organization. 
• Local scientific and ethical review structure outside the 
organization. 
Response:  
All centers will develop an updated protocol and consent form 
as per their local IRB requirements. 
20.0 Resources Available 
20.1 Describe the qualifications (e.g., training, experience, oversight) of 
you and your staff as required to perform their role. When 
applicable describe their knowledge of the local study sites, culture, 
and society. Provide enough information to convince the IRB that 
you have qualified staff for the proposed research. Note- If you 
specify a person by name, a change to that person will require prior 
approval by the IRB. If you specify people by role (e.g., coordinator, 
research assistant, co-investigator, or pharmacist), a change to that 
person will not usually require prior approval by the IRB, provided 
that person meets the qualifications described to fulfill their roles. 
Response:  
All local research staff has completed CITI training and the PI 
and research coordinators have completed CITI GCP training.  
All research staff has extensive experience conducting clinical 
trials.  The physicians conducting the research specialize in 
treating the disease under study. 
Describe other resources available to conduct the research: For example, 
as appropriate: 
20.2 Justify the feasibility of recruiting the required number of suitable 
subjects within the agreed recruitment period. For example, how 
many potential subjects do you have access to? What percentage of 
those potential subjects do you need to recruit? 
Response:  
It is estimated that the site may have approximately 40 patients 
who meet the eligibility criteria during the enrollment period.  Of 
those it is anticipated that 25-28 will be interested in 
participating. 
20.3 Describe the time that you will devote to conducting and completing 
the research. 

 
Page 27 of 36 
Revised: March 6, 2017 
Response:  
10% of PI effort 
20.4 Describe your facilities. 
Response:  
The department of neurology outpatient offices (UBMD 
Neurology) in the Conventus building (1001 Main Street, 
Buffalo, NY 14203) at the Buffalo Niagara Medical Campus 
consist of private exam rooms in which patients are seen for all 
procedures.  Study procedures are performed in private areas 
after subjects check in with at the reception area.  Study 
documents are maintained in a locked staff office that is only 
accessed by designated personnel. 
20.5 Describe the availability of medical or psychological resources that 
subjects might need as a result of an anticipated consequences of the 
human research. 
Response:  
No unexpected or anticipated consequences are foreseen 
during this study that require only questionnaire completion. 
In the event it becomes necessary, referrals to appropriate 
medical facilities and/or specialists will be provided in the event 
a subjects experiences an adverse event during participation 
the research. 
20.6 Describe your process to ensure that all persons assisting with the 
research are adequately informed about the protocol, the research 
procedures, and their duties and functions. 
Response:  
All study staff is trained on the study protocol by first reviewing 
the protocol itself in detail.  The PI conducts a training session 
to ensure research team understand the protocol and each 
individuals’ responsibility. A major focus of training for an 
observational study for is to ensure the confidentiality 
measures are in place and will be followed. 
21.0 Prior Approvals 
21.1 Describe any approvals that will be obtained prior to commencing 
the research. (E.g., school, external site. funding agency, laboratory, 
radiation safety, or biosafety approval.) 
Response:  
IRB approval and executed contract with funding agency.  Prior 
to other sites initiating research activity, proof of IRB approval 
must be provided. 

 
Page 28 of 36 
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22.0 Recruitment Methods 
22.1 Describe when, where, and how potential subjects will be recruited. 
Response:  
Subjects will be identified during routine clinic evaluation (the 
neurologists who see MS patients in the UBMD Neurology 
private practice are all investigators on the study therefore 
familiar with the requirements of the protocol) and approached 
for interest in participation in the study.  A neurologist will 
identify that a subject meets basic eligibility criteria 
(diagnosis, age, postpartum status) during routine clinical 
evaluation and inquire if the subject has interest in 
participating in research in general (if no interest, then no 
further action is taken). If the subject has interest, then the 
research coordinator is called and the potential subject is 
provided with an informed consent form as a means to provide 
her with additional information about the study.  If the subject 
is interested, a study visit is scheduled. 
The site is not utilized posters, flyers or any other site specific 
advertisement. 
22.2 Describe the source of subjects. 
Response:  
Subjects may be identified from the UBMD Neurology practice 
as described in 22.1. 
22.3 Describe the methods that will be used to identify potential subjects. 
Response:  
Subjects may be identified from the UBMD Neurology practice 
as described in 22.1. 
22.4 Describe materials that will be used to recruit subjects. (Attach 
copies of these documents with the application. For advertisements, 
attach the final copy of printed advertisements. When advertisements 
are taped for broadcast, attach the final audio/video tape. You may 
submit the wording of the advertisement prior to taping to preclude 
re-taping because of inappropriate wording, provided the IRB 
reviews the final audio/video tape.) 
Response:  
No advertisement will be necessary 
22.5 Describe the amount and timing of any payments to subjects. 
Response:  
Subjects will not be compensated for participation. 

 
Page 29 of 36 
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23.0 Local Number of Subjects 
23.1 Indicate the total number of subjects to be accrued locally. 
Response:  
Approximately 25-28 
23.2 If applicable, distinguish between the number of subjects who are 
expected to be enrolled and screened, and the number of subjects 
needed to complete the research procedures (i.e., numbers of 
subjects excluding screen failures.) 
Response:  
There are no screening procedures for the study.  It is expected 
that subjects who agree to participate will enroll in the study.  
24.0 Confidentiality 
Describe the local procedures for maintenance of confidentiality. 
24.1 Where and how data or specimens will be stored locally? 
Response:  
Files are maintained in locked cabinets in locked rooms in the 
offices of the department of Neurology (UBMB Neurology) 
located at 1010 Main Street, 2nd Floor, Buffalo, NY 14202.  Data 
is maintained in an encrypted database. Access is limited to 
only those directly involved in the conduct of the research, 
including data entry and analysis. 
No specimens are being collected. 
24.2 How long the data or specimens will be stored locally? 
Response: 
Data may be stored for up to 10 years. 
No specimens are being collected. 
24.3 Who will have access to the data or specimens locally? 
Response:  
The investigators and designated staff will have access to the 
data. 
No specimens are being collected. 
24.4 Who is responsible for receipt or transmission of the data or 
specimens locally? 
Response:  
The Principal Investigator and delegated research staff. 
24.5 How data and specimens will be transported locally? 

 
Page 30 of 36 
Revised: March 6, 2017 
Response:  
Completed forms are maintained internally, no transportation is 
required. 
25.0 Provisions to Protect the Privacy Interests of Subjects 
25.1 Describe the steps that will be taken to protect subjects’ privacy 
interests. “Privacy interest” refers to a person’s desire to place 
limits on whom they interact or whom they provide personal 
information. 
Response:  
Study procedures are performed in private exam areas. Study 
procedures are performed only by study staff.  Study 
documents are maintained in a locked staff office that is only 
accessed by designated personnel. 
25.2 Describe what steps you will take to make the subjects feel at ease 
with the research situation in terms of the questions being asked and 
the procedures being performed. “At ease” does not refer to 
physical discomfort, but the sense of intrusiveness a subject might 
experience in response to questions, examinations, and procedures. 
Response:  
Subjects are made to feel at ease by ensuring that they 
understand every aspect of the research process.  Study visits 
occur in a comfortable environment, with which subjects are 
familiar.  They are familiar with the research staff and are made 
to feel comfortable and confident in their situation. 
25.3 Indicate how the research team is permitted to access any sources of 
information about the subjects. 
Response:  
Study procedures are performed in private exam areas. Study 
procedures are performed only by study staff.  Study 
documents are maintained in a locked staff office that is only 
accessed by designated personnel. 
26.0 Compensation for Research-Related Injury 
26.1 If the research involves more than Minimal Risk to subjects, describe 
the available compensation in the event of research related injury. 
Response:  
The research does not involve any more than minimal risk 
procedure. 
26.2 Provide a copy of contract language, if any, relevant to 
compensation for research-related injury. 

 
Page 31 of 36 
Revised: March 6, 2017 
Response:  
No injury is foreseen during questionnaire completion or during 
the conduct of physical or neurological examinations. 
27.0 Economic Burden to Subjects 
27.1 Describe any costs that subjects may be responsible for because of 
participation in the research. 
Response:  
No additional cost for subjects is foreseen. The study is 
observational in nature, all procedures that are strictly study 
related are paid for by the study.  Other costs are standard of 
care that the subject would incur regardless of participation. 
28.0 Consent Process 
28.1 Indicate whether you will be obtaining consent 
Response:  
Informed consent will be obtained from subjects. 
28.2 Describe where  the consent process take place 
Response:  
Informed consent will be obtained in the Conventus building 
(1001 Main Street, Buffalo, NY 14203) at the Buffalo Niagara 
Medical Campus in the department of neurology outpatient 
offices (UBMD Neurology).  The process itself will occur in a 
private exam room. 
28.3 Describe any waiting period available between informing the 
prospective subject and obtaining the consent. 
Response:  
Subjects may take as much time as they wish to consider 
participation. 
28.4 Describe any process to ensure ongoing consent. 
Response:  
It is regularly reinforced with subjects that they are participating 
in a research study and that participation is voluntary and that 
they may ask questions at any time.  In addition, at any time new 
or updated information is available the informed consent form 
will be updated and subjects will be reconsented. 
28.5 Describe whether you will be following “SOP: Informed Consent 
Process for Research (HRP-090).” If not, describe: 

 
Page 32 of 36 
Revised: March 6, 2017 
• 
The role of the individuals listed in the application as being 
involved in the consent process. 
• 
The time that will be devoted to the consent discussion. 
• 
Steps that will be taken to minimize the possibility of coercion 
or undue influence. 
• 
Steps that will be taken to ensure the subjects’ understanding. 
Response:  
Informed consent will be obtained following SOP HRP-090. 
Non-English Speaking Subjects  
28.6 Indicate what language(s) other than English are likely to be 
spoken/understood by your prospective study population or their 
legally authorized representatives. 
Response:  
Only subjects who speak English will be enrolled in the study.  
The purpose of the study is patient reported outcomes which 
are in English and it is not feasible to have the study documents 
translated into other languages for this small study. Therefore 
we will not obtain consent from subject who do not speak 
English. 
28.7 If subjects who do not speak English will be enrolled, describe the 
process to ensure that the oral and written information provided to 
those subjects will be in that language. Indicate the language that 
will be used by those obtaining consent. 
Response:  
Not applicable 
Waiver or Alteration of Consent Process (consent will not be obtained, 
required information will not be disclosed, or the research involves 
deception) 
28.8 Review the “CHECKLIST: Waiver or Alteration of Consent Process 
(HRP-410)” to ensure you have provided sufficient information for 
the IRB to make these determinations. Provide any additional 
information necessary here: 
Response:  
Not applicable 
28.9 If the research involves a waiver the consent process for planned 
emergency research, please review the “CHECKLIST: Waiver of 
Consent for Emergency Research (HRP-419)” to ensure you have 
provided sufficient information for the IRB to make these 
determinations. Provide any additional information necessary here: 

 
Page 33 of 36 
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Response:  
Not applicable 
Subjects who are not yet adults (infants, children, teenagers) 
28.10Describe the criteria that will be used to determine whether a 
prospective subject has not attained the legal age for consent to 
treatments or procedures involved in the research under the 
applicable law of the jurisdiction in which the research will be 
conducted. (E.g., individuals under the age of 18 years.) For 
research conducted in NY state, review “SOP: Legally Authorized 
Representatives, Children, and Guardians (HRP-013)” to be aware 
of which individuals in the state meet the definition of “children.” 
Response:  
Not applicable 
28.11For research conducted outside of NY state, provide information that 
describes which persons have not attained the legal age for consent 
to treatments or procedures involved the research, under the 
applicable law of the jurisdiction in which research will be 
conducted. One method of obtaining this information is to have a 
legal counsel or authority review your protocol along the definition 
of “children” in “SOP: Legally Authorized Representatives, 
Children, and Guardians (HRP-013).” 
Response:  
Not applicable 
28.12Describe whether parental permission will be obtained from: 
• 
Both parents unless one parent is deceased, unknown, 
incompetent, or not reasonably available, or when only one 
parent has legal responsibility for the care and custody of the 
child. 
• 
One parent even if the other parent is alive, known, competent, 
reasonably available, and shares legal responsibility for the 
care and custody of the child. 
Response:  
Not applicable 
28.13Describe whether permission will be obtained from individuals other 
than parents, and if so, who will be allowed to provide permission. 
Describe the process used to determine these individuals’ authority 
to consent to each child’s general medical care. 
Response:  
Not applicable 

 
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28.14Indicate whether assent will be obtained from all, some, or none of 
the children. If assent will be obtained from some children, indicate 
which children will be required to assent. 
Response:  
Not applicable 
28.15When assent of children is obtained describe whether and how it will 
be documented. 
Response:  
Not applicable 
Cognitively Impaired Adults 
28.16Describe the process to determine whether an individual is capable 
of consent. The IRB sometimes allows the person obtaining assent to 
document assent on the consent document and does not 
automatically require assent documents to be used. 
Response:  
Not applicable 
Adults Unable to Consent 
When a person is not capable of consent due to cognitive impairment, a 
legally authorized representative should be used to provide consent and, 
where possible, assent of the individual should also be solicited. 
28.17List the individuals from whom permission will be obtained in order 
of priority. (e.g., durable power of attorney for health care, court 
appointed guardian for health care decisions, spouse, and adult 
child.)  For research conducted in NY state, review “SOP: Legally 
Authorized Representatives, Children, and Guardians (HRP-013)” 
to be aware of which individuals in the state meet the definition of 
“legally authorized representative.”  The list in the consent template 
signature section corresponds to the priority list for NYS.   
Response:  
Not applicable 
28.18For research conducted outside of NY state, provide information that 
describes which individuals are authorized under applicable law to 
consent on behalf of a prospective subject to their participation in 
the procedure(s) involved in this research. One method of obtaining 
this information is to have a legal counsel or authority review your 
protocol along the definition of “legally authorized representative” 
in “SOP: Legally Authorized Representatives, Children, and 
Guardians (HRP-013).” 
Response:  

 
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Revised: March 6, 2017 
Not applicable 
28.19Describe the process for assent of the subjects. Indicate whether: 
• 
Assent will be required of all, some, or none of the subjects. If 
some, indicated, which subjects will be required to assent and 
which will not. 
• 
If assent will not be obtained from some or all subjects, an 
explanation of why not. 
• 
Describe whether assent of the subjects will be documented 
and the process to document assent. The IRB allows the person 
obtaining assent to document assent on the consent document 
and does not routinely require assent documents and does not 
routinely require subjects to sign assent documents. 
Response:  
Not applicable 
28.20For HUD uses provide a description of how the patient will be 
informed of the potential risks and benefits of the HUD and any 
procedures associated with its use. 
Response:  
Not applicable 
29.0 Process to Document Consent in Writing 
 
If your research presents no more than minimal risk of harm to subjects and 
involves no procedures for which written documentation of consent is normally 
required outside of the research context, the IRB will generally waive the 
requirement to obtain written documentation of consent. 
(If you will document consent in writing, attach a consent document. If you will 
obtain consent, but not document consent in writing, attach a consent script. 
Review “CHECKLIST: Waiver of Written Documentation of Consent (HRP-411)” 
to ensure that you have provided sufficient information. You may use 
“TEMPLATE CONSENT DOCUMENT (HRP-502)”to create the consent 
document or script.) 
29.1 Describe whether you will be following “SOP: Written 
Documentation of Consent (HRP-091).” If not, describe whether and 
how consent of the subject will be obtained including whether or not 
it will be documented in writing. 
Response:  
Documentation of consent in writing will be performed 
following SOP HRP-091. 
30.0 Drugs or Devices 

 
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30.1 If the research involves drugs or device, describe your plans to store, 
handle, and administer those drugs or devices so that they will be 
used only on subjects and be used only by authorized investigators. 
Response:  
The study will not involve drugs or devices.  Subjects will be 
utilizing medications as part of standard of care. 
If the drug is investigational (has an IND) or the device has an IDE or a 
claim of abbreviated IDE (non-significant risk device), include the 
following information: 
30.2 Identify the holder of the IND/IDE/Abbreviated IDE. 
Response:  
The study will not use investigational drugs or devices  
30.3 Explain procedures followed to comply with FDA sponsor 
requirements for the following: 
 
Applicable to: 
FDA Regulation 
IND Studies 
IDE studies 
Abbreviated 
IDE studies 
21 CFR 11 
X 
X 
 
21 CFR 54 
X 
X 
 
21 CFR 210 
X 
 
 
21 CFR 211 
X 
 
 
21 CFR 312 
X 
 
 
21 CFR 812 
 
X 
X 
21 CFR 820 
 
X 
 
Response:  
Not applicable