/ ImPACT QT / QT-PV Clinical Study Protocol
Development of a Neurocognitive Screening Test / QPR-15-44
Version: 03
APPROVALS
Date:
REVISION HISTORY
Version / Description of Change / Author
00 / Initial Release / Zagorski, Gyurke, Lovell
01 / Modified Indications to narrow age range of QT-PV to 6-11. The team determined that 5 year olds are too young to perform the QT-PV screening test.
Updated QT-PV sample matrix based on the change to age.
Expanded Investigators guide to include additional detail describing the use of the test application.
Minor formatting edits of the headers and footers.
This document includes the consent form that was approved by Quorum Review IRB / Zagorski, Gyurke
02 / Replaced Automated Working Memory Test in the non-reference standards with Color Trails for QT Validity study. The team decided the Color Trail test was better suited for the study design.
Modified time frame for test/re-test from 1-24 hours to 7 days minimum, but not more than 30 days from initial test, to better facilitate subject participation. / Gyurke, Luce
03 / Addition of ImPACT Pediatric Version to the Test-Re-Test. This change was instituted to increase the power of the reliability analysis. / Gyurke, Luce
TABLE OF CONTENTS

1Purpose

2Scope

3Definitions

4References and Applicable Documents

5Attachments

6Study Protocol

6.1Study objective.

6.2Clinical Study Design.

6.3Study goals/endpoints:

6.4Study population.

6.5Test protocol:

6.6Eligibility criteria:

Appendix A: Sampling Matrices

1Purpose

This document describes the study protocol and materials for the clinical investigation of two versions of ImPACT Quick Test neurocognitive screening test: ImPACT Quick Test(“ImPACT QT”) and Quick Test Pediatric Version (“ImPACT QT-PV”).

ImPACTQT is a neurocognitive screening test that provideshealthcare professionals with objective measure ofneurocognitive functioning forscreening ofconcussion in individuals ages 12-75

ImPACTQT-PV is a neurocognitive screening test that provideshealthcare professionals with objective measure ofneurocognitive functioning forscreening ofconcussion in individuals ages 6-11.

2Scope

This protocol applies to the study of ImPACT QT and ImPACT QT-PV.

3Definitions

Clinical Investigation / Clinical investigation or research involving one or more subjects to determine the safety or effectiveness of a device.
Investigational Device / A device, including a transitional device that is the object of an investigation.
Investigator / An individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team.
Significant risk device / An investigational device that:
(1) Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
(2) Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;
(3) Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or
(4) Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.
Sponsor / Sponsormeans a person who initiates, but who does not actually conduct, the investigation, that is, the investigational device is administered, dispensed, or used under the immediate direction of another individual. A person other than an individual that uses one or more of its own employees to conduct an investigation that it has initiated is a sponsor, not a sponsor-investigator, and the employees are investigators.
Sponsor-investigator / Sponsor-investigator means an individual who both initiates and actually conducts, alone or with others, an investigation, that is, under whose immediate direction the investigational device is administered, dispensed, or used. The term does not include any person other than an individual. The obligations of a sponsor-investigator under this part include those of an investigator and those of a sponsor.
Unanticipated adverse device effect / Any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

4References and Applicable Documents

QPR-15-38 / Quick Test R&D Plan
QPR-15-42 / Quick Test Pediatric Version R&D Plan
QPR-15-40 / Quick Test SRS
21 CFR 812 / Code of Federal Regulations Title 21 Part 812 Investigational Device Exemptions

5Attachments

Attachment 1: Investigators Guide(78 pages).

Attachment 2: Information and Consent Form (5 pages)

6Study Protocol

6.1Study objective.

The objective of this study is to norm and validateImPACTQT and ImPACT QT-PV, eachas intended for use as a computer-based neurocognitive screening test.

6.2Clinical Study Design.

6.2.1Standardization:

The standardization sample of 900 subjects for ImPACT QT and 700 for ImPACT QT-PV will be collected according to the Sampling Matrix contained in the Appendix A.

6.2.2Reliability and Validity

In addition to the standardization sample there are a number of clinical studies that will be conducted to establish the veracity of the results and clinical utility of ImPACT QT. The following studies will be conducted:

6.2.2.1Reliability – ImPACT QT

Test-Retest: A study on 75- 100 cases where the interest interval is 7 days minimum, but not more than 30 days from the initial test. Cases should be sampled 20 -25 from 3-4 age bands.

6.2.2.2Validity- ImPACT QT

1) Concurrent Validity: A 200 – 300 person case study with ImPACT Online where the two tests are administered in counterbalanced fashion. The cases should come from 3-4 age bands.

2) Discriminant Validity: 100 cases of concussed versus non-concussed cases. Concussion diagnosis performed by a healthcare professional.

3) Construct Validity: Validity studies with 100-200 subjects to determine agreement with each of the following non-reference standards:

  • Brief Visuospatial Memory Test, BVMT-R
  • Symbol Digit Modalities Test
  • Color Trails
6.2.2.3Reliability –ImPACT QT-PV

Test-Retest: A study on 75- 100 cases where the inter-test interval is 7 days minimum, but not more than 30 days from initial test. Cases should be sampled 20 -25 from 3-4 age bands. ImPACT Pediatric will be administered with QT-PV.

6.2.2.4Validity – ImPACT QT-PV

1) Concurrent Validity: A 100 case study with ImPACT Pediatric where the two tests are administered in counterbalanced fashion. The cases should come from 3-4 age bands.

2) Discriminant Validity: 50-100 cases of concussed versus non-concussed cases. Concussion diagnosis performed by a healthcare professional.

3) Construct Validity: Validity studies with approximately 50-60 cases to determine agreement with each of the following non-reference standards:

  • Children’s Memory Scale Study,
  • NEPSY Shapes;
  • Children’s Color Trails.

6.3Study goals/endpoints:

1)To collect data to establish normative performance of individuals.

2)To collect data to establish reliability and validity of the neurocognitive tasks:

  1. Test-retest reliability
  2. Concurrent Validity
  3. Discriminant Validity
  4. Construct Validity

6.4Study population.

The standardization sample of 900 subjects for ImPACT QT and 700 for ImPACT QT-PV will be collected according to the Sampling Matrix contained in the Appendix A.

Additional subjects will be recruited for reliability and validity studies described in section 5.2.2.

6.5Test protocol:

1)Review study materials and execution of the research agreement

2)Recruitment of subjects satisfying eligibility criteria.

3)Signing the consent form by each study participant.

4)Single administration of ImPACT (for normative, and reliability and validity);

5)Second administration of ImPACT Quick Test

6.6Eligibility criteria:

6.6.1Inclusion criteria:

1)Age:

  1. ImPACT QT: 12-75
  2. ImPACT QT-PV: 6-11

2)Primary English speaking or fluent in English.

3)No known special education diagnosis excluding a 504 designation.

4)Currently not suffering from a concussion or being treated for a concussion.

5)No known physical or psychological impairment that would affect their ability to perform the test.

6.6.2Exclusion Criteria

Unless specifically required by the particular study (i.e., a discriminant validity study differentiating concussed versus non-concussed individuals) the following exclusion criteria apply:

1)Documentation of a known special education diagnosis other than a 504 designation.

2)English is not their primary language nor are they proficient in the English language.

3)Currently suffering from a concussion or being treated for a concussion.

4)Any known physical or psychological impairment that would affect their ability to perform the test.

Confidential ImPACT Applications, Inc. | 2000 Technology Dr., Ste. 150 | Pittsburgh, PA 15219Page 1 of 6

/ ImPACT QT/QT-PV Clinical Study Protocol
Appendix A – Study Sampling Matrix / QPR-15-44
Version: 00

Appendix A: Sampling Matrices

Table 1. Quick Time Pediatric Version Sampling Matrix
Race
White / Black / Hispanic / Other / Subjects
Age/Gender
6-0 to 6-11
Male / 33 / 13 / 12 / 4 / 62
Female / 34 / 13 / 11 / 5 / 63
67 / 26 / 23 / 9
7-0 to 7-11
Male / 33 / 13 / 11 / 5 / 62
Female / 34 / 13 / 12 / 4 / 63
67 / 26 / 23 / 9
8-0 to 8-11
Male / 34 / 12 / 12 / 5 / 63
Female / 33 / 14 / 11 / 4 / 62
67 / 26 / 23 / 9
9-0 to 9-11
Male / 33 / 13 / 11 / 5 / 62
Female / 34 / 13 / 12 / 4 / 63
67 / 26 / 23 / 9
10-0 to 10-11
Male / 34 / 12 / 12 / 5 / 63
Female / 33 / 14 / 11 / 4 / 62
67 / 26 / 23 / 9
11-0 -11-11
Male / 34 / 13 / 11 / 4 / 62
Female / 33 / 13 / 12 / 5 / 63
67 / 26 / 23 / 9
700
Table 2. Quick Time Sampling Matrix
Race
White / Black / Hispanic / Other / Total
Age/Gender
12 to 15
Male / 30 / 6 / 8 / 2 / 46
Female / 33 / 8 / 10 / 3 / 54
63 / 14 / 18 / 5
16 to 18
Male / 30 / 6 / 8 / 2 / 46
Female / 33 / 8 / 10 / 3 / 54
63 / 14 / 18 / 5
21 to 25
Male / 30 / 6 / 8 / 2 / 46
Female / 33 / 8 / 10 / 3 / 54
63 / 14 / 18 / 5
31 to 40
Male / 30 / 5 / 7 / 2 / 44
Female / 34 / 8 / 10 / 4 / 56
64 / 13 / 17 / 6
41 to 50
Male / 32 / 4 / 6 / 3 / 44
Female / 36 / 7 / 8 / 5 / 56
68 / 11 / 13 / 6
51 to 60
Male / 32 / 4 / 5 / 2 / 43
Female / 38 / 7 / 8 / 4 / 57
70 / 11 / 13 / 6
61 to 65
Male / 33 / 3 / 4 / 2 / 42
Female / 39 / 7 / 8 / 4 / 58
72 / 10 / 12 / 6
66 to 70
Male / 33 / 3 / 3 / 2 / 41
Female / 41 / 6 / 9 / 3 / 59
74 / 9 / 12 / 5
71 to 75
Male / 32 / 2 / 3 / 2 / 39
Female / 45 / 6 / 7 / 3 / 61
77 / 8 / 10 / 5
Grand Total / 900

Confidential ImPACT Applications, Inc. | 2000 Technology Dr., Ste. 150 | Pittsburgh, PA 15219Page 1 of 6

/ ImPACT QT/QT-PV Clinical Study Protocol
Investigators Guide / QPR-15-44
Version 00

Investigators Guide for ImPACT Quick Test and QT-PV

Investigators Guide for ImPACT Quick Test and QT-PV...... 1

1Introduction to ImPACT and Research Philosophy...... 1

2Description of Project...... 1

2.1Test being normed...... 2

2.2Additional Tests in Use...... 2

3Contact Information for key personnel...... 2

4Required study documentation and tools...... 3

4.1Required Participation Documents...... 3

4.2Study materials and tools...... 3

5Overview of the testing application...... 3

5.1Neurocognitive Test Modules...... 3

6FAQ’s...... 6

7QT- PV ADMINISTRATION GUIDE...... 7

8QT ADMINISTRATION GUIDE...... 43

1Introduction to ImPACT and Research Philosophy

ImPACT Applications, Inc. is a Pittsburgh based software company founded by clinical experts who pioneered the field. Best known for its award winning computerized neurocognitive product, ImPACT® (Immediate Post-Concussion Assessment and Cognitive Testing), the company’s products are the most-widely used and most scientifically validated in the world.ImPACT provides trained clinicians with neurocognitive assessment tools and services that have been medically accepted as state-of-the-art best practices as informing a clinical decision to return a patient to activity.

ImPACT has the largestdatabase of clinical research(more than 250 peer reviewed) on concussion management, which validates ImPACT's model. ImPACT has received numerous accolades and endorsements from many of the world's leading sports authorities, governing bodies, teams and athletes. Currently, more than 10,000 medical professionals have been trained by ImPACT on concussion management and ImPACT software. ImPACT is in use by the majority of teams in MLB, NHL, NFL and WWE. More than 10,000+ high schools, 1,000+ colleges and universities, 900+ clinical centers, 475+ Credentialed ImPACT Consultants, 200+ professional teams and select military units use ImPACT. Cirque du Soleil, Irish and South African rugby teams, among many other organizations around the globe also use ImPACT.

ImPACT and its products continue to evolve by incorporating the latest advancements in neurocognitive science and in technology for portability and ease of use. In addition, ImPACT is constantly expanding educational resources and tools to raise awareness regarding the importance of proper concussion management. Proof of ImPACT's clinical value can be found in more than a thousand clinics and hospitals throughout the United States and elsewhere.

Research Philosophy

ImPACT is committed to conducting the highest quality research in accordance with the standards set forth by a wide variety of national and international regulatory agencies. We work diligently to use the most up-to-date technologies to ensure the safety and security of the research subject’s data. ImPACT highly values the time and commitment of both our research partners and the subjects who willingly participate to aid us in the development of high quality assessment tools

2Description of Project

This guide describes research plan for two tests:

-ImPACT Quick Test (“ImPACT QT”) indicated for individuals ages 12-75; and

-ImPACT Quick Test – Pediatric Version (“ImPACT QT-PV”) indicated for pediatric population ages 6-11.

ImPACT QTand ImPACT QT-PV are designed to be a 5-minute iPad based (computerized) test to aid medical personnel and first responders in determining if an athlete/individual is in need of further evaluation or is able to immediately return to activity. This “screening test” is not a substitute for a full neuropsychological evaluation or a more comprehensive computerized neurocognitive test.

2.1Test being normed

The standardization sample 900 subjects for ImPACT QT and 700 for ImPACT QT-PV will be collected according to the Sampling Matrix contained in the Appendix A.

2.2Additional Tests in Use

In addition to the standardization sample there are a number of clinical studies that will be conducted to establish the veracity of the results and clinical utility of ImPACT QT. The following studies will be conducted:

2.2.1Reliability – ImPACT QT

Test-Retest: A study on 75- 100 cases where the interest interval is a minimum of 7 days, but not more than 30 days from initial test. Cases should be sampled 20 -25 from 3-4 age bands.

2.2.2Validity- ImPACT QT

1) Concurrent Validity: A 200 – 300 person case study with ImPACT Online where the two tests are administered in counterbalanced fashion. The cases should come from 3-4 age bands.

2) Discriminant Validity: 100 cases of concussed versus non-concussed cases. Concussion diagnosis performed by a healthcare professional.

3) Construct Validity: Validity studies with 100-200 subjects to determine agreement with each of the following non-reference standards:

  • Brief Visuospatial Memory Test, BVMT-R
  • Symbol Digit Modalities Test
  • Color Trails

2.2.3Reliability –ImPACT QT-PV

Test-Retest: A study on 75- 100 cases where the inter-test interval is a minimum of 7 days, but not more than 30 days from initial test. Cases should be sampled 20 -25 from 3-4 age bands. ImPACT Pediatric will be administered with QT-PV.

2.2.4Validity – ImPACT QT-PV

1) Concurrent Validity: A 100 case study with ImPACT Pediatric where the two tests are administered in counterbalanced fashion. The cases should come from 3-4 age bands.

2) Discriminant Validity: 50-100 cases of concussed versus non-concussed cases. Concussion diagnosis performed by a healthcare professional

3) Construct Validity: Validity studies with approximately 50-60 cases to determine agreement with each of the following non-reference standards:

  • Children’s Memory Scale Study,
  • NEPSY Shapes;
  • Children’s Color Trails.

3Contact Information for key personnel

For inquiries related to the administration of the study or study materials, contact:

Michael Zagorski

Director of Regulatory Affairs

ImPACT Applications, Inc

E:

T: 412-345-3525

For information on protocol and/or safety issues, please contact:

Jim Gyurke, Ph. D.

Chief Operating Officer

E:

T: 813-326-0004

Dr. Mark Lovell

Chief Science Officer

T: 412-235-2802

E:

4Required study documentationand tools

4.1Required Participation Documents

  • Signed Research Agreement(required prior to participation)
  • Quorum Review IRB Site Information Questionnaire(required prior to participation)

4.2Study materials and tools

  • Investigators Guide (this document);
  • ImPACT-Approved consent form, required for each test subject;
  • Study Sampling Matrix, to be used to determine subjects needed to meet the study goal. Direct links are below; access requires a password, which will be provided in an email prior to study commencement.
  • QT, accessible at
  • QT-PV, accessible at

5Overview of the testing application

1)The first section of the test is a brief demographics questionnaire. Please complete this entire section. If there is a question you are unsure of (i.e., race) please ask the test taker or his or her legal guardian.

2)Following the demographics section, the examiner fills out the signs (observed) and symptoms (reported) section via touch screen. The symptoms section is designed to be administered by the examiner based on observations of the test subject. The symptoms section is to be administered by asking the test taker about the listed symptoms and recording the test takers responses.

3)Following the administration of the demographics and signs and symptoms sections, the neurocognitive test modules are administered.

5.1Neurocognitive Test Modules

5.1.1Symbol Match: Speed (Reaction Time) Component

Symbol Match is designed to measure neurocognitive speed (reaction time) and memory (recall of symbol number pairs). The test requires the test taker to match a series of symbols with specific numbers (9 pairs for the QT, and 5 pairs for the QT-PV). Reaction time is recorded and averaged across all trials. The memory component involves the recall of the number-symbol pairs at the end of the test, when the test taker is asked to recall which number goes with which symbol.

Figure 1 below shows the screen for the reaction time component of Symbol match. For each administration of the test, the stimuli are randomized to minimize practice effects. In other words, in the example in Figure 1, the triangle is paired with the number 6. If the test is re-administered, the computer will automatically randomize the shape-number pairs. For ImPACT QT-PV, there are 5 stimuli that should be familiar to younger children (circle, triangle, square, arrow and plus sign).

Figure 1: Symbol Match Speed Component (ImPACT Quick Test)

5.1.2Symbol match-Memory Component

This task requires the test taker to recall the number-letter pairs when the symbols disappear. The resulting score is the percent correct (the number correct divided by 9 and multiplied by 100). Figure 2 displays the compnent of the test.

For the memory component, the test taker is asked to recall the shape-number pairing. For the example below, the test taker would click on the number 4.

Figure 2. The memory component of the Symbol Match test.

5.1.3Three Letter Memory:

Three Letter Memory also measures both speed and memory. For the speed component, the test taker clicks a grid of computer-randomized numbers backwards (1 to 16 in forward order for QT-PV and 25 to 1 in backward order for QT). In addition to providing a measure of speed, this part of the test also serves as an interference task in between the presentation and recall trials of the 3 letters.