On-Eye Optical Quality of Lotrafilcon B Lenses Over 12 Hours
Phase: PHASE4
Conditions: Hyperopia, Myopia
Sponsor: Indiana University

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 1 of 14
 
 
 
On-Eye Optical Quality of Lotrafilcon B Lenses Over 12 Hours 
 
NCT03881670 
Unique Protocol ID: Kollbaum002 
 
 
 
 
 
 
 
 
 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 2 of 14
 
 
 
 
 
 
TITLE:  ON-EYE OPTICAL QUALITY OF LOTRAFILCON B LENSES OVER 12 HOURS   
 
 
INVESTIGATORS:  Pete Kollbaum, OD, PhD; Dawn Meyer, OD; Arthur Bradley, PhD; Matt 
Jaskulski, PhD; Neeraj K. Singh, MPhil; Martin Rickert, PhD 
 
 
INVESTIGATION SITE:  Indiana University  
 
STUDY OVERVIEW 
The optical aberrations and resultant visual quality of a contact lens wearer is influenced by several factors 
such as the optics of the eye, pre- and post-contact lens tear film, contact lens material, water content, 
and the lens design. Previous studies have evaluated the optical quality of soft contact lenses off of the 
eye (e.g. Kollbaum 2004) and on the eye (e.g. Kollbaum 2007).  A previous study by Montes-Mico (Montes-
Mico 2012) also evaluated the optical quality of soft contact lenses, focusing on the change in on-eye 
optical contact lens aberrations throughout the day.  They found that some lenses had relatively little 
change across the day, whereas other lenses had greater changes, presumed due to contact lens surface 
and lens bulk dehydration. This study, however, had limited published details making modeling and 
predictions based on the results not possible.  The study also used an incomplete set of lenes compared 
to what is currently in the marketplace.  The current study aims to systematically investigate the diurnal 
variation in the optical quality of soft contact lenses on eye throughout the day.  Subject reported quality 
of vision will also be evaluated. 
 
 
 
 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 3 of 14
PROTOCOL SYNOPSIS 
KEY OBJECTIVE 
1. Diurnal variation within lens in the on-eye optical quality of 
soft lenses over time (12 hours) 
2. Subject reported within-lens vision stability over time (0-100 
scale) 
KEY ENDPOINTS 
/OUTCOME MEASURES 
Key endpoints are the monocular (OD only) responses of: 
1. RMS.  RMS (total and higher-order) only, will be compared 
across time and between lenses.  From these measures of 
RMS, change over time can be quantified as a magnitude and 
percentage. 
2. Root Mean Square (RMS) Fit Error.  For each optical 
measurement, the wavefront will be reconstructed using both 
a ‘typical’ modal (Zernike) reconstruction and zonal (local 
integration) reconstruction.  The difference between these two 
reconstructed wavefronts constitutes an estimate of the RMS 
fit error (how much error is introduced from the “real 
wavefront” (local is closest approximation) relative to the 
Zernike modally fit wavefront.  
3. Subject reported within-lens vision stability over time (0-100 
scale, viewing distant target) 
 
 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 4 of 14
STUDY DESIGN 
The study is a monocular (only OD measured, matching type of 
correction for OS), subject masked, 2 x 2 randomized, crossover (with 
an additional non-randomized baseline reference (3 arms in all)) 
comparing the within-lens difference in diurnal (AM to PM) change in 
optical quality with different soft lenses relative to the diurnal change 
at baseline (no lens).  
 
Subjects will be tested for and must meet all inclusion criteria and not 
meet any exclusion criteria prior to beginning lens testing. 
 
Lens wearing protocol: 
1. Subjects will first have measurements acquired every 2±0.5 
hours for 12 hours without any lenses (no lens, baseline).  The 
subject will wear their habitual spectacles between 
measurement periods. 
2. Following a day of washout with spectacle wear only each type 
of lens will be used in both eyes for a period of 2±1 days.  Early 
the following morning, the subject will present to the clinic 
wearing spectacles.  A lens of the same type they have been 
wearing for the previous 2±1 days will be insterted while a 
masked examiner then performs measurements every 2±0.5 
hours for 12±1 hours.  Measurements will include monocular 
aberrometry (minimum 5mm analysis diameter), Medmont 
topography, and subjective measures. (0-100 scale). 
3. Subjects will then be dispensed the next randomized lens pair 
and told to not wear the lens that day or the following 
(washout) day, but the next 2±1 days.  As previous, the subject 
will present to the clinic on the third day not wearing the 
lenses.  Lenses will be inserted, and then measures will be 
taken throughout the day. 
 
Measurement protocol: 
1. At the beginning of each testing day, measures of the subject’s 
eye alone will be captured.  This will serve as ‘baseline’ for 
each day. 
2. The study lenses will then be inserted acrording to the lens 
randomization schedule. 
4. Following 10-20 minutes of lens settling, eye+lens aberrometry 
(minimum 5mm analysis diameter) and subjective measures 
(0-100 scale) will be acquired. 
3. This cycle will be repeated every 2±0.5 hours up to 12±1 hours. 
4. At the end of 12±1 hours, the subject will return all lenses of 
that set, and be given the next set of lenses to repeat the 
washout, wearing, and measurement cycle. 
 
Dilation Protocol:  
No pharmacological dilation will be used in this study.  Subjects 
will be in a dark room aiming to achieve a natural pupil 
diameter of at least 5 mm.  Upon inclusion, if a subject cannot 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 5 of 14
achieve a non-dilated pupil diameter of at least 5 mm, they will 
be excluded from the study.  If a subject meets a 5 mm pupil 
on most time points of both sets of lenses, but not all, inclusion 
of data acquired smaller than 5 mm will be scaled to 5 mm and 
considered on an individual basis. 
 
Equipment: 
1. An aberrometer (e.g. COAS-HD, CSO Osiris) will be used for 
all optical measures.  The aberration data will be obtained 
for central 3- and 5-mm diameter areas.  Wavefront data 
will be recontstructed by both modal (up to 6th order 
Zernike polynomials) and zonal (local slope) methods. 
Sample size Complete N=21, enroll up to N=24 
Hypothesis 
1. The Air Optix plus Hydraglyde lens will have levels of variation 
in aberration throughout the day not significantly different 
than the naked eye. 
2. The Air Optix Aqua lens will have levels of variation in 
aberration throughout the day not significantly different than 
the naked eye. 
3. The Air Optix plus Hydraglyde lens will have lower variation in 
aberration throughout the day relative to the Air Optix Aqua 
lenses. 
TEST COMPARATOR 
PRODUCTS 
Baseline = Naked eye  
Lenses: Set of soft lenses  
1. Air Optix plus Hydraglyde on daily disposable basis 
2. Air Optix Aqua on daily disposable basis 
(ALCON will provide lenses) 
INCLUSION/EXCLUSION 
CRITERIA 
1. Habitual prescription within the range of +5.00 D to -6.00 D  
2. 18-35 years of age 
3. No history of issues of eye alignment or binocularity by self-
report 
4. No doctor diagnosed, self-reported accommodative or 
binocular vision issues 
5. No doctor diagnosed, self-reported ocular surface disease or 
dry eye requiring regular, ongoing treatment 
6. The subject must appear able and willing to adhere to the 
instructions set forth in this clinical protocol. 
7. Vertex corrected refractive cylinder must be -0.75 or less.   
8. Visual acuity best correctable to 20/25 or better for each eye 
9. The subject must read and sign the Informed Consent form. 
10. No active conditions that may prevent soft contact lens wear. 
11. Mesopic pupil size >5.00 mm.    
OFF LABEL 
No. 
CLINICAL SUPPLIES 
REQUESTED FROM 
ALCON 
Trial set of soft contact lenses for each of the following 
1. Air Optix plus Hydraglyde on daily disposable basis 
2. Air Optix Aqua on daily disposable basis  
(ALCON will provide all lenses) 
RESULTS 
DISSEMINATION 
Work will be presented at least one international meeting, such as 
Global Specialty Lens Symposium, ISCLR, or ARVO.  Trade or peer-

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 6 of 14
reviewed publications will be prepared at Sponsor’s request and 
expense. 
CONFLICT OF 
INTEREST 
None. 
 
PROPOSAL SUMMARY 
STUDY DURATION 
Contract approval: unknown, estimate 1 month 
Human subjects approval:  1 month, concurrent to above 
Project setup: 1 month, concurrent to above 
Recruitment: 1 month, concurrent to above 
Data collection: 2 months 
Data analysis: 1 month 
Report writing: 1 month  
  
Contract for 1 year to account for any delays or necessary subsequent 
analyses. 
 
DURATION OF IRB  
1 year 
GCP TRAINING 
Received; 2015-03-14 
TYPE OF STUDY 
Single center 
OTHER FUNDING 
None 
 
 
 
 
 
 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 7 of 14
RATIONALE AND SIGNIFICANCE:   
The optical aberrations and resultant visual quality of a contact lens wearer is influenced by 
several factors such as the optics of the eye, pre- and post-contact lens tear film, contact lens 
material, water content, and the lens design. Previous studies have evaluated the optical quality 
of soft contact lenses off of the eye (e.g. Kollbaum 2004) and on the eye (e.g. Kollbaum 2007).  
A previous study by Montes-Mico (Montes-Mico 2012) also evaluated the optical quality of soft 
contact lenses, focusing on the change in on-eye optical contact lens aberrations throughout the 
day.  They found that some lenses had relatively little change across the day, whereas other 
lenses had greater changes, presumed due to contact lens surface and lens bulk dehydration.  
This study, however, had limited published details making modeling and predictions based on 
the results not possible.  The study also used an incomplete set of lenes compared to what is 
currently in the marketplace.   
 
 
AIM: The current study aims to systematically investigate the diurnal variation in the optical quality 
of soft contact lenses on eye throughout the day.  Subject reported quality of vision will also be 
evaluated. 
 
 
STUDY DESIGN 
The study is a monocular (OD only), subject masked, 2 x 2 randomized, crossover (with an 
additional non-randomized baseline reference (3 arms in all)) comparing the difference in 
diurnal change in optical quality with different soft lenses relative to baseline (no lens).  
 
Lens wearing protocol: 
1. Subjects will first have measurements acquired every 2±0.5 hours for 12±1 hours 
without any lenses (no lens, baseline).  The subject will wear their habitual spectacles 
between measurement periods. 
2. Following a day of washout with spectacle wear only, each type of lens will be used in 
both eyes for a period of 2±1 days.  Early the following morning, the subject will present 
to the clinic wearing spectacles.  A lens of the same type they have been wearing for the 
previous few days will be insterted while a masked examiner then performs 
measurements every 2±0.5 hours for 12±1 hours. 
3. Subjects will then be dispensed the next randomized lens pair and told to not wear the 
lens that day or the following (washout) day, but the next two days.  As previous, the 
subject will present to the clinic on the third day not wearing the lenses.  Lenses will be 
inserted, and then measures will be taken throughout the day. 
 
Measurement protocol: 
1. At the beginning of each testing day, aberrometry, Medmont topography (non-invasive 
tear break-up), and subjective quality measures of the subject’s OD eye alone will be 
captured.  This will serve as ‘baseline’ for each day. 
2. The study lenses will then be inserted acrording to the randomization schedule. 
3. Following 10-20 minutes of lens settling, eye+lens aberrometry (minimum 5 mm analysis 
diameter, Medmont corneal topography, and subjective (0-100 scale) measures will be 
acquired on the OD.  Measures of contact lens position (through recorded imaging) will also 
be performed. Measures at this time point will serve as “time 0” for each lens wearing 
day. 
4. This cycle will be repeated every 2±0.5 hours up to 12±1 hours. 
5. At the end of 12±1 hours, the subject will return all lenses of that set, and be given the 
next set of lenses to repeat the washout, wearing and measurement cycle. 
 
 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 8 of 14
Dilation Protocol:  
No pharmacological dilation will be used in this study.  Subjects will be in a dark room 
aiming to achieve a natural pupil diameter of at least 5 mm.  Upon inclusion, if a subject 
cannot achieve a non-dilated pupil diameter of at least 5 mm, they will be excluded from 
the study.  If a subject meets a 5 mm pupil on most time points/lenses, but not all, 
inclusion of data acquired smaller than 5 mm will be scaled to 5 mm and considered on 
an individual basis. 
 
 
Equipment: 
1. An aberrometer (e.g. COAS-HD or CSO Osiris) will be used for all optical measures.  
The aberration data will be obtained for central 3- and 5-mm diameter areas.  
Wavefront data will be recontstructed by both modal (up to 6th order Zernike 
polynomials) and zonal (local slope) methods. 
2. A Medmont corneal topographer will be used following each set of aberration 
measures to also monitor the tear film upon the eye/contact lens. 
 
SUBJECTS 
 
Sample Size: 
This section describes the rationale and approach used to establish the minimum sample 
size (N) needed to achieve 80% power at a nominal significance level α=0.05 for detecting a 
mean difference between percentage change in RMS of higher-order wavefront aberrations 
measured over a 12-hr period for the test lenses and the percentage change observed without a 
contact lens (no-CL).  For each subject and lens, a series of five RMS measurements will be 
obtained at 0 hours (baseline) and at six, 2-hr intervals within each period.  Technically, the 
statistical power for testing the contact lens main effect will depend not only on the structure of 
the covariance matrix but also on how the baseline measurements recorded at time=0 hours are 
incorporated into the statistical model(s).  But, given the degree of uncertainty about the input 
parameter values required to estimate sample size, we believe it reasonable to base initial 
calculations on a dependent sample t-test on a mean difference score under the assumption of 
no differential carryover effect.  Thus, the target parameter of interest for our primary analysis 
corresponds to the true difference in the mean post-baseline percentage change over 12 hours 
between each of the test contact lenses and no-CL for N subjects.  Note that this test would be 
equivalent to testing the interaction of “lens” and “hours of use” factors in a two-way repeated 
measurements ANOVA.   
 
Data was not available on the two test lenses, so we used previously published data on an 
ALCON lens expected to provide similar responses.  Specifically, we approximated parameter 
values for [1] effect size, [2] within-subject variance, and [3] within-subject correlation from the 
data reported in two previous studies.  Specifically, Montes-Mico, et al (2013) measured 
wavefront aberrations in 15 myopic eyes before and at 2-hr intervals after contact lens fitting 
over a 12-hr period.  Using the 5-mm pupil diameter data presented in Figure 2 of the 
referenced paper, we estimated that the group-averaged percentage change between the 
baseline (i.e., 2-hr after lens fitting) and the final measurement (i.e., after 12-hr wearing time) of 
~3% and ~5% for no-CL and DAILIES TOTAL ONE (DT1) lens, respectively.  Note that this 
difference between no-CL and DT1 was smaller than any of the other lenses under test, but 
mirrors the expectation for the current test lenses.  To allow for mean differences larger than the 
observed 2% mean difference between each of the test lenses and no-CL in the current study, 
we added a 1.5% non-inferiority margin; thus, our sample size calculation assumes a ‘null 
difference’ of 3.5%.  
 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 9 of 14
Our within-subject variability and correlation estimates were taken from Cheng, et al (2004) who 
reported on the stability of clinical monochromatic aberrometry measurements over a wide 
range of time scales.  First, temporal variability of wavefront root mean square (RMS) error, 
excluding defocus and astigmatism, was tracked across five repeated measurements for 4 
subjects at four different time scales.  The averaged variance estimates for different time scales 
ranged from 8.10 x 10-5 μm2 (t < 1 second) to 9.73 x 10-4 μm2 (t < 1 year).   For our calculations, 
we used their reported value of 4.41 x 10-4 μm2 (t < 1 week) as our variance estimate, which 
translates to a standard deviation of 2.1%.  We expect that this is a worst-case scenario 
because the value was derived by calculating the between-day variances for individual trials 
across five days for each subject and then calculating the average across the four subjects and 
five trials on each day.  Our data will be multiple measurements taken within a 12-hr period on 
the same day.  Second, Cheng, et al (2004) reported a within-subject correlation estimate of 
r=0.799 that was based on a linear regression analysis of the higher-order RMS error 
measurements over a one-year time scale for subject AB.  Again, because the time-scale in the 
current study proposal is only 12 hours (i.e., is much shorter than 1 year), we expect that the 
magnitude of the within-subject correlation in our sample is likely to be 0.80 higher. For 
purposes of the sample size calculation, we used three values for the correlation parameter, i.e., 
r = {0.70, 0.75, and 0.80}.  The input parameters for this sample size calculation scenario are 
shown in Table 1(a).  The actual power and number of paired observations for this scenario are 
presented in Table 1(b) and were obtained using SAS 9.4 by varying both the mean difference 
and the correlation parameters.   
 
Table 1 (a)  
Fixed Scenario 
  
 
Distribution Normal 
 
Method 
Exact 
 
Number of 
L 
 
Null 
3.50 % 
Alpha 
0.05 
 
Standard 
2.10 % 
Nominal 
0.80 
 
 
Table 1 (b)  
Index Mean Diff Corr Actual Power N Pairs 
1 
2.00 
0.70 
0.810 
9 
2 
 
0.75 
0.822 
8 
3 
 
0.80 
0.838 
7 
4 
2.25 
0.70 
0.802 
12 
5 
 
0.75 
0.829 
11 
6 
 
0.80 
0.824 
9 
7 
2.50 
0.70 
0.804 
18 
8 
 
0.75 
0.822 
16 
9 
 
0.80 
0.819 
13 
10 
2.75 
0.70 
0.806 
31 
11 
 
0.75 
0.805 
26 
12 
 
0.80 
0.803 
21 
13 
3.00 
0.70 
0.801 
67 
14 
 
0.75 
0.801 
56 
15 
 
0.80 
0.808 
46 
 
 
 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 10 of 14 
Note that the paired-sample t test assumes normally distributed data and requires N ≥ 2. The 
test statistics are 
𝑡𝑡= 𝑁𝑁1/2 ቀ
𝑑𝑑ത−𝜇𝜇0
𝑠𝑠𝑑𝑑ቁ ~ 𝑡𝑡(𝑁𝑁−1, 𝛿𝛿)  or, equivalently, 𝑡𝑡2~𝐹𝐹(1, 𝑁𝑁−1, 𝛿𝛿2) 
where 𝑑𝑑̅ and 𝑠𝑠𝑑𝑑 are the sample mean and standard deviation of the differences, and  
𝛿𝛿= 𝑁𝑁1/2 ൬
𝜇𝜇𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑−𝜇𝜇0
𝜎𝜎𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑൰  and  𝜎𝜎𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑= (𝜎𝜎1
2 + 𝜎𝜎1
2 −2𝜌𝜌𝜎𝜎1𝜎𝜎2)1/2  
represent the non-centrality parameter and standard deviation of the paired difference scores, 
respectively.  In order to compensate for potential data loss due to subject attrition, we propose 
increasing the targeted sample size of N=21 to 24 which is based on a post-
consent/randomization attrition rate between 5 and 10% observed in 50+ studies in our 
laboratory that have required multiple (>1) daytime visits.   
 
Inclusion Criteria: 
1. Habitual prescription +5.00 D to -6.00 D  
2. 18-35 years of age 
3. No history of issues of eye alignment or binocularity by self-report 
4. No doctor diagnosed, self-reported accommodative or binocular vision issues 
5. No doctor diagnosed, self-reported ocular surface disease or dry eye requiring regular, 
ongoing treatment 
6. The subject must appear able and willing to adhere to the instructions set forth in this 
clinical protocol. 
7. Vertex corrected refractive cylinder must be -0.75 or less.   
8. Visual acuity best correctable to 20/25 or better for each eye 
9. The subject must read and sign the Informed Consent form. 
10. No active conditions that may prevent soft contact lens wear. 
11. Mesopic pupil size >5.00 mm.    
 
 
LENSES 
Lens powers are based on vertexed (15 mm) spherical equivalent refraction (performed upon 
study entry) and matched between all lens types. 
1. Baseline no lens 
2. Air Optix plus Hydraglyde on daily disposable basis 
3. Air Optix Aqua on daily disposable basis  
(*ALCON supplies all lenses) 
 
 
 
 
 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 11 of 14 
OUTCOME MEASURES 
Primary: 
The primary outcome measure in this study will be a derived variable indexing the percentage 
change in the RMS of higher-order wavefront aberrations (microns) at a 3 and 5 mm pupil from 
baseline to 12 hours.  For each participant, we will convert the data from microns into the 
percentage change in RMS, %Δi(12-0)k = 100 x (RMSi12k –RMSi0k)/RMSi0k where i=1,2,..,N 
participant, j represents time (hrs) Є (0 (BL) , 2, …, 12), and k denotes lens.  Our initial analysis 
will compare the mean %Δ∙(12-0)test computed across N participants for each of the Air Optix plus 
Hydraglyde and Air Optix Aqua lenses independently with the mean %Δ∙(12-0)NCL with no contact 
lens. 
 
Secondary: 
1. Subject-reported vision-stability (0-100 scale, while viewing at distance) 
2. Root Mean Square Fit Error.  For each optical measurement, the wavefront will be 
reconstructed using both a ‘typical’ modal (Zernike) reconstruction and zonal (local 
integration) reconstruction.  The difference between these two reconstructed wavefronts 
will be evaluated. 
 
 
TESTING PROCEDURES:  
In office testing will be done at study entry, and following 2±1 days of lens wear for each of the 
follow up visits. 
 
Testing Day 1, Visit 1 Baseline/Inclusion: 
1. Demographics 
2. Ocular history 
3. Entrance Snellen visual acuity 
4. Entrance ocular health (with conjunctival and corneal staining) 
5. Habitual lens information (type, power) 
6. Habitual lens use (wearing schedule, replacement schedule, hours per day, insertion 
time, removal time) 
7. Subjective refraction (best objective with an additional -0.25 D for subjective 
improvement) 
8. Fit evaluation of all lens pairs.  If all lens pairs do not fit adequately enough per 
investigator clinical determination for dispensing, subject will be exited from the study. 
9. Snellen acuity of each eye for all lens pairs. 
 
Testing Day 2, Visit 1-7 Naked eye diurnal measures: 
1. Subjects will first have aberrometry, Medmont topography, and subjective quality 
measurements acquired every 2±0.5 hours for 12±1 hours without any lenses (no lens, 
baseline).  The subject will wear their habitual spectacles between measurement 
periods. 
 
 
 
Testing Day 3, Visit 1-7 and Testing Day 4, Visit 1-7 (each separated by a day of washout and 
2±1 days of study lens wear):   
1. At the beginning of each measurement day, aberrometry, Medmont topography, and 
subjective quality measures of the subject’s eyes alone (COAS and Medmont) will be 
captured.  This will serve as ‘baseline’ for each day (for the spectacle day, this will also 
be “time 0”). 
2. The study lenses (or no lens for spectacle day) will then be inserted acrording to the 
randomization schedule. 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 12 of 14 
3. Following 10-20 minutes of lens settling, the eye+lens aberrometry (minimum 5 mm 
analysis), Medmont topography, and subjective quality (0-100 scale) measures will be 
acquired for each eye.  This will serve as “time 0” for each lens wearing day. 
4. This cycle will be repeated every 2±0.5 hours up to 12±1 hours. 
5. At the end of 12 hours, the subject will return all lenses of that set, and be given the next 
set with a schedule of washout and wear days. 
 
Testing Day 4, Visit 7 = Exit: 
1. Exit ocular health (with conjunctival and corneal staining) 
2. Exit Snellen visual acuity 
 
 
STATISTICAL ANALYSIS 
Separate tables with descriptive statistics will be provided for all baseline, outcome/endpoint 
and safety variables, as appropriate.  Continuous variables will be summarized with location and 
dispersion parameter estimates while categorical data will be summarized using frequency 
counts, percentages and margin tables where appropriate.  Visualizations and related graphs 
will be provided in support of these data summaries.    
 
Statistical analyses will be performed only after all data have been collected, transcribed into the 
electronic database, and error checked and corrected if needed.   We will first test for a 
differential carryover effect of lens using a linear (ANOVA) model.  For a crossover design, the 
model can be expressed as   
𝑦𝑦𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖= 𝜇𝜇+ 𝛼𝛼𝑖𝑖+ 𝜌𝜌𝑗𝑗(𝑖𝑖) + 𝛾𝛾𝑘𝑘+ 𝜏𝜏𝑙𝑙+ 𝜆𝜆𝑚𝑚+ 𝛾𝛾𝜏𝜏𝑘𝑘𝑘𝑘+ 𝑒𝑒𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 
where μ is the overall mean, 𝛼𝛼𝑖𝑖 is the effect for the ith sequence, 𝜌𝜌𝑗𝑗(𝑖𝑖) is the random effect for the 
of the jth individual within the ith sequence (i.e. 𝜌𝜌𝑗𝑗(𝑖𝑖)  ∼𝑁𝑁(0, 𝜎𝜎𝜌𝜌2) , 𝛾𝛾𝑘𝑘is the effect of the kth period, 
𝜏𝜏𝑙𝑙 is the effect of the lth lens effect and 𝜆𝜆𝑚𝑚 is the effect of the mth carryover effect with  𝑒𝑒𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 being 
the NIID residual term (i.e., 𝑒𝑒𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 ~𝑁𝑁(0, 𝜎𝜎𝑒𝑒2).  Assuming that there is no statistical evidence of a 
period x lens interaction (𝛾𝛾𝜏𝜏𝑘𝑘𝑘𝑘), we will use a one-sided equivalence (i.e., non-inferiority) test to 
determine whether the average percentage increase in higher-order RMS induced by Dailies1 
Lens is no worse than the average increase without a contact lens.  In practice we can use a 
single directional paired-sample t-test to test the null hypotheses. If we reject Ho we should 
conclude that the percentage increase over a 12-hour period in higher-order RMS induced by 
each of the test lenses is no worse than the increase measured without a contact lens.  In this 
context, smaller differences in the mean difference in higher-order RMS are “better.”  Thus, the 
statistical hypotheses are arranged so that rejecting the null hypothesis for the specified null 
difference implies that, the observed mean change over 12 hours for each of the test lenses is 
not significantly worse than the mean change with no-CL. i.e., 
 
𝐻𝐻𝑜𝑜: 𝜇𝜇𝐷𝐷−𝜇𝜇𝑁𝑁𝑁𝑁≥𝑀𝑀𝐼𝐼𝐼𝐼 versus 𝐻𝐻𝑎𝑎: 𝜇𝜇𝐷𝐷−𝜇𝜇𝑁𝑁𝑁𝑁< 𝑀𝑀𝐼𝐼𝐼𝐼 
 
 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 13 of 14 
 
Second, a comparison of the statistic %Δi(12-0)test for one test lens with %Δi(12-0)k-1  the other test 
lens in the study will be performed by fitting a linear mixed effects regression model with 
restricted maximum likelihood (REML) estimation.  The effect of lens will be parameterized in 
this model with (0,1) GLM dummy coding using Air Optix with Hydraglide as the reference lens; 
thus, a separate parameter estimate will be obtained for the other test lens. The initial model will 
include a single random effect for subject.  We will also perform sensitivity analyses by adding 
covariates and refitting the model with ML to obtain ‘adjusted’ parameter estimates for the fixed 
effect of lens to account for potential confounding due to measured covariates. 
 
 
PUBLICATION PLAN:   
Work will be presented at least one international meeting, such as American Academy of 
Optometry, Global Specialty Lens Symposium, ISCLR, BCLA, American Optometric 
Association, or ARVO.  The work will also be prepared for submission for peer-reviewed or 
trade publication (e.g. Optometry and Vision Science) at Sponsor’s request and if results merit. 
 
 
𝑀𝑀𝐼𝐼𝐼𝐼 
𝑀𝑀𝐼𝐼𝐼𝐼 
3.50% 

CONFIDENTIAL STUDY PROPOSAL (v. 2018-09-05) 
 
Pete Kollbaum, OD, PhD; Indiana University 
 
Page 14 of 14 
TIMELINE:  (estimated) 
Contract approval: unknown, estimate 1 month 
Human subjects approval:  1 month, concurrent to above 
Project setup: 1 month, concurrent to above 
Recruitment: 1 month, concurrent to above 
Data collection: 2 months 
Data analysis: 1 month 
Report writing: 1 month1  
  
Contract for 1 year to account for any delays or necessary subsequent analyses.