Training and Certification BCVA Examiner Training and Certification Lilly BDAD Clinical Trial © 2009 The EMMES Corporation

Training Objectives Review Examination Lane set up Train in protocol methods of performing the following tasks: ETDRS Refraction ETDRS Visual Acuity Completion of Worksheets related to the above tasks Review responsibilities Review certification requirements

Examination Lane

Exam Lane Requirements 4 meter space ETDRS light box ETDRS Charts R, 1, & 2 Trial lens set With – 0.37 lens Jackson Cross Cylinders 0.25, 0.50, 1.00 Trial frames Meter stick Primary & spare light tubes With fenestrated sleeves Burn-in & change documentation -0.37 Animation: ➙ Activates the first bullet Each ➙ activates the next bullet No fade – screen will have all needed equipment. NOTE: This is animated only in the BCVA PPT as you will not go through the detailed exam lane information given in the monitor PPT.

Examination Lane Established sites have the examination lane already configured Lane requirements are covered in the EMMES training manual Examination lane certification is granted by: EMMES certifier during EMMES site visit Grandfathering From Sponsor’s previous clinical trial From previous EMMES site visit

Refraction

Refraction Acceptable baselines: Phoropter Autorefractor Retinoscopy Lensometry Last visit Refraction in trial frames Sphere and Cylinder Final refinement must be done using trial lenses in trial frames and the Jackson Cross Cylinder (JCC) Animation: Phoropter appears soon after slide ➙ Autorefractor appears ➙ Retinoscope appears ➙ Lensometer appears, then glasses ➙ Woman appears ➙ Women appear, then JCC a few seconds later

Trial Lens Set Loose spherical and cylindrical lenses Used for ETDRS refraction and visual acuity measurement Plus and minus power spherical lenses Cylinders may be plus, minus, or both

-0.37 Sphere Additional lens needed in Lilly BDAD Study - 0.37 Additional lens needed in Lilly BDAD Study Not usually included in trial lens set and may need to be ordered separately Site must obtain this lens before start of study

Jackson Cross Cylinder Used to check for axis and power of cylinder Site must have JCC in three powers: 0.25 0.50 1.00

Trial Frames Must be comfortable for the subject to wear Must be in good repair with no broken or missing parts Several types are available Trial lenses are inserted into lens cells for refraction and visual acuity measurement

Technique

Refraction For visual acuity of 20/80 or better Start with +0.50 and -0.37 spherical lenses Start with +0.25 cylinder at axis 180o If using minus cylinder, begin with -0.25 at axis 90o For visual acuity worse than 20/80 Use higher diopter power spheres and cylinders Refer to BCVA Guidelines sheet for each step Step 1: Initial sphere power Step 2: Cylinder – axis and power Step 3: Final sphere power

Initial Sphere

Refraction Use Chart R Begin with right eye Refine: Chart R Initial sphere Cylinder (axis and power) Final sphere

Sphere Ask subject to read smallest line they are able to see on Chart R as a starting point Select beginning lens from BCVA Guidelines based on this reading As vision improves with addition of lenses, use lens appropriate for the vision at each point during testing

Refraction Ask subject if lens makes the letters Chart R Ask subject if lens makes the letters Better Worse No Different Do not say “Better 1 or 2”

Push Plus “Push Plus” – determine highest plus or least minus that produces minimal blur Offer +0.50 sphere and give +0.50 sphere as long as it is “Better” or “No Different” Once +0.50 sphere is “Worse” Ask subject to read smallest line they are able to read Necessary as when minus is offered, subject must earn minus by reading more letters on the chart

Offer Minus Offer -0.37 minus sphere - 0.37 Offer -0.37 minus sphere If “Better,” subject must earn minus by reading at least one more letter If earned, give -0.25 sphere Continue to offer -0.37 sphere until “Worse” or “No Different”

Offer Plus After minus has been offered, earned, and adjusted – that is, “worse” or “no different” Offer +0.50 again and ask if “Better, Worse, or No Different” Offer and give plus until plus is “Worse” Always end up offering plus

Refraction at 1 Meter Refract both eyes at 4 meters If fewer than 4 letters are read at 4 meters, move subject to 1 meter Carefully measure with 1 meter stick Add +0.75 sphere to distance refraction Remember to take this out when recording refraction worksheet Both eyes are refracted at 4 meters before moving subject to 1 meter

Cylinder

Cylinder Do not estimate the cylinder or use only the spherical refraction Use cylinder from autorefractor or retinoscopy as a starting point It must be refined and finalized using the Jackson Cross Cylinder Use JCC power according to BCVA Guidelines Refine cylinder axis and cylinder power Animation is automatic

JCC Flips and Rotates JCC with power dots JCC with power lines White & green are plus power Red is minus power

Axis Refinement

Instructions to Subject For axis refinement, instruct the subject to find the smallest line read comfortably and concentrate on a round letter one line above Smallest line read Instruct subject to concentrate here No animation

Axis Refinement When refining the cylinder axis, follow the handle of the JCC Offers plus and minus power 45o from beginning axis alignment - 1.00

Axis Refinement If working in minus cylinder, “chase” the minus line or dot Rotate the lens axis 5 – 15o - 1.00

Axis Refinement Now place the JCC with handle at the new axis and continue to flip, asking “Better 1 or 2, or about the same” Continue to chase the prefered line or dot - 1.00

Axis Refinement Continue to rotate the axis and the JCC according to the subject’s responses It may be necessary to use smaller degree changes as the end point gets closer or if there is high cylinder power - 1.00

Axis Refinement As long as the response is a number, continue to flip the JCC to refine the axis Correct axis has been determined when the subject’s response is “about the same” Cylinder axis must be determined before determining the correct cylinder power

Power Refinement

Instructions to Subject For power refinement, instruct the subject to find the smallest line read comfortably and concentrate on a round letter on that line Smallest line read Instruct subject to concentrate here No animation

Power Refinement When refining the cylinder power, follow the power dots or power lines Offers plus and minus power on the refined axis - 1.00

Power Refinement Continue to offer power and exchange trial lens until subject’s response is “about the same” Correct power has now been determined Animation is automatic - 1.25 - 1.50

Spherical Equivalent Once 0.50 diopter of cylinder has been added or subtracted, adjust the sphere by 0.25 of opposite power -0.50 cylinder added: give +0.25 sphere -0.50 cylinder taken away: give -0.25 sphere Adjust the sphere as you go – do not wait until the cylinder power is fully determined

Refraction – Cylinder If there is established cylinder from last Refraction: Refine axis using Jackson Cross Cylinder Follow the handle of the JCC Refine power using JCC When checking cylinder, the choices given the subject are: “Better 1 or 2 or about the same”

Cylinder If cylinder is unknown: Test for astigmatism by placing a +0.25 cylinder first at 180o and then at 90o if the first choice is not satisfactory (or -0.25 at 90o if working in minus cylinder) Refine the axis and power with Jackson Cross Cylinder (JCC) Follow the color line or dot of the cylinder you are working in Move the axis 5o – 15o or smaller increments as axis is refined

Final Sphere Refinement

Final Sphere Ask subject to read smallest line they are now able to see on Chart R Select refinement lens from BCVA Guidelines based on this reading As vision improves with addition of lenses, use lens appropriate for the vision at each point during testing Animation is automatic

Refraction – Final Sphere Offer +0.25 and ask if “Better, Worse, or No Different” Offer and give plus until plus is “Worse” Check visual acuity before offering minus Offer -0.37 sphere and give -0.25 if minus is better and more letters are read Offer +0.25 to finish Refraction If final sphere changes by ≥ 0.50 diopter, re-check the cylinder axis and power

Visual Acuity

Points of Note Always test the right eye first Use Chart 1 for the right eye Use Chart 2 for the left eye If < 20 letters are read correctly, the subject must be tested at 1 meter Add +0.75 sphere to distance refraction If the subject must be moved to 1 meter, both eyes should be tested at 4 meters before moving the subject to 1 meter Animation: ➙ Chart 1 expands (medium speed) ➙ Chart 2 expands (medium speed)

Points of Note Give the subject detailed instructions before testing begins Start at the upper left corner – read left to right There are no numbers – only letters Animation is automatic Read slowly – one letter per second It is acceptable and encouraged to guess letters Corrections should be made before going on to the next letter

ETDRS Charts 10 alphabet letters Sloan letters Random order Same degree of difficulty for each letter

Points of Note If subject loses their place on the chart Verbally orient place By row number from the top of the chart Do not ask for row lower than 3rd or 4th By horizontal lines on the chart Do not Repeat the last line read Point to the chart 1 2 3 Animation: ➙ Numbers 1, 2, 3 appear ➙ Arrows to horizontal lines appear

BCVA Examiner Responses Do not stop the subject if they give an incorrect response Do not comment as the subject responds “OK” or “yes” should not be said after each letter, nor should nods or other gestures be made Once the examiner does not respond, the subject knows they have given an incorrect response Testing must be completely unbiased on the part of the BCVA examiner

Subject Questions If the subjects asks if it is a certain letter, the BCVA examiner should ask them to choose the letter they think it is If the subject attempts to skip letters – “the third letter looks like...,” the BCVA examiner should immediately stop them and ask them to begin with the first letter on the left

Points of Note Encourage the subject to read as far as possible Do not allow subject to quit easily Ask subject to guess letters on next line Allow subject the opportunity to guess any letter they may confuse with a number or another letter Urge subject to pick one letter

Points of Note Corrections Subject may not go back and correct a letter once they have read the next letter Subject may correct before going to next letter Stop the subject immediately if they read letters too quickly or if they say a number This will give them the opportunity to correct before going to the next letter

Skipped Lines If it is obvious that the subject has skipped a line, the BCVA examiner should: Stop the testing Re-orient the subject to the correct line Ask the subject to read that line Continue with the testing as if the subject had not skipped a line (i.e. – this is the only time a subject is permitted to go back as it is technically not a correction but an omission)

Head Position The subject may be permitted to turn his or her head to fixate eccentrically, provided the fellow eye is adequately occluded The trial lens occluder may not be adequate for this A tissue or eye patch may be needed If patch used, it should be loose enough so that subject can keep both eyes open (even though one is occluded) Always use at 1 meter

When to Stop Visual acuity testing is stopped only when the subject convinces the examiner that they can read no more letters on the ETDRS chart It is not stopped when the subject misses two letters on a line as in some other clinical trials

Visual Acuity – Right Eye Chart 1 Tested at 4 meters Start with the right eye; occlude the left eye Place Chart 1 in light box Other charts should be out of view

Visual Acuity – Left Eye Chart 2 Tested at 4 meters Remove occluder lens from left eye; occlude right eye Remove Chart 1 Put it out of view Place Chart 2 in light box

Visual Acuity Testing Subjects unable to read at least 20 letters at 4 meters (either eye): Seat subject 1 meter from the chart and carefully measure the distance from the front of subject’s eye in a straight line to the front of the chart Add +0.75 sphere to Refraction Test again Both eyes should be tested at 4 meters before moving subject to 1 meter

Visual Acuity Testing Remove Chart 2 from view Testing is complete Chart R only may be displayed in the light box between screenings Testing is complete Score worksheets Check to ensure that worksheet is completely and accurately filled out Check addition for Visual Acuity score

Worksheet: Refraction Record the 4 meter (distance) refraction on the worksheet for each eye If any field has no power, insert zeros If refraction was performed at 1 meter, remember to take out the +0.75 sphere added for 1 meter testing when recording the refraction

VA Worksheet Completion All letters read correctly should be clearly and individually circled Letters read incorrectly or letters subject was unable to read should be left blank Lines the subject attempted to read but had no correct answers should have a “0” total No letters read on a line should have a “0” total Animation is automatic

Visual Acuity Worksheets Right Eye Left Eye Animation is automatic – does not fade.

Scoring Worksheet C Z R H S 5 O N 4 D K V 2

Worksheet Example

Worksheet Example

Worksheet Example

Worksheet Example

Snellen Equivalent To the left of the circled responses is the “Snellen Acuity Equivalent” Smallest line with one or fewer incorrectly read letters Line will have a score of 4 or 5 Enter this in the “Visual Acuity Score” section Animation: ➙ Vertical arrows will appear from top, followed by vertical ovals ➙ Vertical arrows and ovals fade. Arrow to smallest line with a score of 4 or 5, followed by horizontal oval – these do not fade ➙ Arrow to score line, followed by horizontal oval – these do not fade

Corrections All worksheet or CRF corrections should be uniform: Single line through error Correction inserted If necessary, use the margin for explanation or clarification Date Initials (or sign name) 5 4 Oct 30 2009 EK

Common Errors VA score ends in a line where all 5 letters were read correctly May indicate the subject was not encouraged to read more letters Crossing out letters not circled Not circling letters consistently or individually Not counting circled letters in individual rows correctly

Common Errors Not testing subject at 1 meter if fewer than 20 letters were correctly read at 4 meters Do not assume they would read all 30 letters at 1 meter Not adding +0.75 sphere when subject is moved to 1 meter Not testing both eyes at 4 meters before moving subject to 1 meter

Site Responsibilities

Site Equipment It is the site’s responsibility to obtain all required equipment and supplies before an EMMES site visit Equipment procurement information is given in the EMMES training manual sent to each site

Exam Lane Configuration The Study Coordinator (or other designated individual) at the site is responsible for setting up the exam lane prior to an EMMES site visit Exam lane cannot be fully certified until all equipment is obtained, in place, and required documentation is in place If site has “action items” – these must be satisfied e-mail documentation is acceptable

Exam Lane Changes Any changes to the exam lane should be reported to the monitor by the site New or changed lane must be certified before study subjects may be screened Changes include: Relocation of exam lane to another room or building Painting or color change which may affect lighting Newly-installed room lighting which may affect light measurement of charts

Examiner Certification

BCVA Examiner Certification Earned during an EMMES site visit or by being grandfathered from another active EMMES certification BCVA examiner may not screen study subjects until full certification is granted by EMMES A certification number is assigned by EMMES and will be effective throughout the study for that BCVA examiner Certification Letter issued by EMMES Should be kept in study binder

BCVA Examiner Certification It is the Study Coordinator’s responsibility to ensure sufficient number of BCVA examiners are certified at site If BCVA examiners need to be certified by EMMES, Study Coordinator should: Contact monitor – they will assess needs at the site and any other sites in the general area or country Site Visit Request will be sent to EMMES – EMMES will contact site to schedule site visit

Grandfathering It is the Study Coordinator’s responsibility to submit the Certification Affidavit required to grandfather a BCVA examiner into the Lilly BDAD study Grandfathering is not automatic – the required paperwork must be submitted to EMMES BCVA examiner may not screen study subjects until grandfathered

401 North Washington Street EMMES Contacts Eva Karlsson, COT: ekarlsson@emmes.com Ophthalmic Trainer/Certifier – Lead Point Lisa Motta: lmotta@emmes.com Lead Administrative Coordinator The EMMES Corporation 401 North Washington Street Rockville, MD 20850 U.S.A. Phone: 001-301-251-1161 Fax: 001-301-576-3695 www.emmescertification.com

Questions? T H A N K Y O U

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