ANZCTR - Registration

Registration number

ACTRN12623000236695

Ethics application status

Approved

Date submitted

17/02/2023

Date registered

6/03/2023

Date last updated

15/09/2024

Date data sharing statement initially provided

6/03/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

CogScreen: Validating cognitive screening in young people with first-episode psychosis

Scientific title

CogScreen: Validating cognitive screening in young people with first-episode psychosis

Secondary ID [1]

ORY-P04-22-39

Universal Trial Number (UTN)

Trial acronym

CogScreen

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Psychosis

Cognitive Impairment

Condition category

Condition code

Mental Health

Psychosis and personality disorders

Mental Health

Schizophrenia

Mental Health

Studies of normal psychology, cognitive function and behaviour

Intervention/exposure

Study type

Observational

Description of intervention(s) / exposure

The primary aim of this study is to validate a cognitive screening tool for young people with first-episode psychosis (FEP). We aim to evaluate the classification accuracy (relative to a neuropsychological assessment reference standard) and test-retest reliability of two cognitive screening tools in young people with FEP: the Screen for Cognitive Impairment in Psychiatry (SCIP) and Montreal Cognitive Assessment (MoCA).
All participants (N=350) will complete both cognitive screening measures (MoCA and SCIP), neurodevelopment assessment, psychiatric assessment, and other supplementary measures (e.g., other clinical measures and acceptability questionnaires). The assessments will be separated into two days: day 1) cognitive screening tests and psychiatric and developmental assessment, and day 2) full neuropsychological assessment. Day 1 is estimated to take 3 hours. The self-report measures will be split across both days to reduce participant burden, and will either be completed in person or the participant may choose to complete these measures at home.
The assessments on each day will be completed by separate members of the research team, ideally conducted within seven days of each other. The assessment will be completed by a trained research assistant and will be administered under the remote supervision of a clinical neuropsychologist. The cognitive screening measures, neurodevelopmental and psychiatric assessments, and full neuropsychological assessment will likely occur at each of the participating sites (e.g., Orygen Specialist Program, Headspace) or at a location in the community (e.g., local library). The self-report supplementary measures will be completed in person or the participant may choose to receive a link to complete these measures at home.

Test-retest assessment time-point (N=120)
The SCIP and MoCA will be re-administrated to a sample of 120 people who completed the classification accuracy component of the study after two weeks (T2). Version 1 of the MoCA and SCIP will be administered to 60 consecutive participants and Version 2 to 60 consecutive participants for the retest reliability part of this study to determine the role of practice effects in the test-retest analysis. Both Version 1 and Version 2 of the MoCA and SCIP are validated measures and follow the same structure and scoring (changes to the item content only).

A secondary aim of this study is to conduct a comprehensive implementation evaluation with key stakeholders during the recruitment period for the classification accuracy study using mixed methods. Following the administration of the MoCA and SCIP, all participants (N=350) will complete a brief self-report survey (i.e., two surveys per participant) which will collect data regarding the initial acceptability of the MoCA and SCIP (e.g., “Did you like/dislike the MoCA?”, “How much effort did it take to do the SCIP?”). To further explore the key perspectives about the acceptability, feasibility, and appropriateness of cognitive screening and identify the facilitators and barriers to implementation in FEP settings, a subset of young people with FEP (n=10-30) will be invited to participate in an interview or focus group to share their experiences of cognitive screening. This interview/focus group is likely to occur a within 3 months after completing the MoCA and SCIP. We will also invite other stakeholders in FEP treatment settings (i.e., clinicians, caregivers, service leaders) to participate in separate interview or focus groups as part of a comprehensive implementation evaluation.

Intervention code [1]

Early Detection / Screening

Intervention code [2]

Diagnosis / Prognosis

Comparator / control treatment

No control group will be used. Screening tests (index tests) for each participant will be compared to gold-standard neuropsychological tests (reference tests) for each participant to determine the accuracy of index tests in identifying cognitive difficulties in young people experiencing first episode psychosis. These gold-standard neuropsychological tests are a collection of computerised tests used to measure thinking and memory skills on iPads. These tests will take place on day two (a week after participants complete the screening tests) and is estimated to take approximately 2-3 hours, including breaks.

Reference standard neuropsychological tests include:
1. Core subtests of the Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V, for those aged 12-15) or Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV, for those aged 16-25). This is to obtain IQ and cognitive factor scores.
2. California Verbal Learning Test, Children’s Version (CVLT-C, for those aged 12-15) or California Verbal Learning Test, 3rd Edition (CVLT3 for those aged 16-25). This to measure verbal learning and memory for lists of information.
3. Logical Memory from the Wechsler Memory Scale-Fourth Edition (for those aged 16-25 only). This is to measure verbal learning and memory for stories. There is no equivalent measure for young people under 16 on Q-Interactive.
4. Verbal Fluency subtest from the Delis-Kaplan Executive Function System (D-KEFS). This is to measure verbal fluency.
5. Word Reading and Sentence Comprehension subtests from the Wide Range Achievement Test-Fifth Edition (WRAT5). This is to measure Reading Achievement Composite.

Control group

Active

Outcomes

Primary outcome [1]

To validate the classification and diagnostic accuracy of the MoCA against a gold-standard neuropsychological assessment battery that includes subtests from the following:
1.Core subtests of the Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V, for those aged 12-15) or Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV, for those aged 16-25). This is to obtain IQ and cognitive factor scores.
2.California Verbal Learning Test, Children’s Version (CVLT-C, for those aged 12-15) or California Verbal Learning Test, 3rd Edition (CVLT3 for those aged 16-25). This to measure verbal learning and memory for lists of information.
3.Logical Memory from the Wechsler Memory Scale-Fourth Edition (for those aged 16-25 only). This is to measure verbal learning and memory for stories. There is no equivalent measure for young people under 16 on Q-Interactive.
4. Verbal Fluency subtest from the Delis-Kaplan Executive Function System (D-KEFS). This is to measure verbal fluency.
5.Word Reading and Sentence Comprehension subtests from the Wide Range Achievement Test-Fifth Edition (WRAT5). This is to measure Reading Achievement Composite.
The neuropsychological battery will be used as a composite primary outcome to determine whether clinical cognitive impairment is evident, defined as either: (1) greater than or equal to 2 cognitive domain scores 1.5 SD below population mean on the reference test normative data, or (2) Full-Scale IQ <80 on the WISC/WAIS.

Timepoint [1]

All measures are administered cross-sectionally across two separate assessment days completed within 7 days of each other.

Primary outcome [2]

To validate the classification and diagnostic accuracy of the SCIP against a gold-standard neuropsychological assessment battery that includes subtests from the following:
1.Core subtests of the Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V, for those aged 12-15) or Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV, for those aged 16-25). This is to obtain IQ and cognitive factor scores.
2.California Verbal Learning Test, Children’s Version (CVLT-C, for those aged 12-15) or California Verbal Learning Test, 3rd Edition (CVLT3 for those aged 16-25). This to measure verbal learning and memory for lists of information.
3.Logical Memory from the Wechsler Memory Scale-Fourth Edition (for those aged 16-25 only). This is to measure verbal learning and memory for stories. There is no equivalent measure for young people under 16 on Q-Interactive.
4. Verbal Fluency subtest from the Delis-Kaplan Executive Function System (D-KEFS). This is to measure verbal fluency.
5.Word Reading and Sentence Comprehension subtests from the Wide Range Achievement Test-Fifth Edition (WRAT5). This is to measure Reading Achievement Composite.
The neuropsychological battery will be used as a composite primary outcome to determine whether clinical cognitive impairment is evident, defined as either: (1) greater than or equal to 2 cognitive domain scores 1.5 SD below population mean on the reference test normative data, or (2) Full-Scale IQ <80 on the WISC/WAIS.

Timepoint [2]

All measures are administered cross-sectionally across two separate assessment days completed within 7 days of each other.

Primary outcome [3]

Version 1 of the SCIP and MoCA will be re-administrated to a sub-sample of people (n = 60) two weeks after they completed the classification accuracy component of the study (T2). The test-retest reliability of Version 1 of the MoCA and SCIP will be determined by calculating the correlation between the results of the first round of testing and the results of testing repeated 2 weeks after the first round.

Timepoint [3]

Retest screening measures are re-administered two weeks after initial assessment.

Secondary outcome [1]

Primary Outcome 4:
Version 2 of the SCIP and MoCA will be administrated to a sub-sample of people (n = 60) two weeks after they completed the classification accuracy component of the study (T2). The test-retest reliability of Version 2 of the MoCA and SCIP will be determined by calculating the correlation between the results of the first round of testing and the results of testing repeated 2 weeks after the first round.

Timepoint [1]

Retest screening measures are re-administered two weeks after initial assessment.

Secondary outcome [2]

Implementation evaluation for young people with FEP – The aim is to explore the acceptability of the cognitive screening tools (i.e., MoCA and SCIP) for young people with FEP. All young people with FEP who complete the diagnostic accuracy component of the study (n= 350) will complete a brief self-report survey (Acceptability Questionnaire) which will collect data regarding the initial acceptability of the MoCA and SCIP. This questionnaire has been developed specifically for this study and contains several closed- and open-ended questions that aimed to explore a young person’s perspectives of completing cognitive screening. The items have been adapted from a published measure based on the Theoretical Framework of Acceptability (TFA) model and include likert-scales, multiple choice, and open text answer options. This measure will be administered immediately after cognitive screening has been completed with the young person.

Timepoint [2]

The self-report measure occurs immediately following completion of the MoCA/SCIP on day 1 of the assessment.

Secondary outcome [3]

To further explore the key perspectives about the acceptability, feasibility, and appropriateness of cognitive screening and identify the facilitators and barriers to implementation in FEP settings, key stakeholders in FEP treatment settings (i.e., clinicians, caregivers, service leaders) will be invited to participate in a separate interview or focus groups as part of a comprehensive implementation evaluation. Interviews will be semi-structured, facilitated by one member of the research team, and may occur face-to-face or online. Focus groups will be semi-structed, facilitated by two members of the research team, and may occur face-to-face or online.

Timepoint [3]

These interviews or focus groups will occur throughout the duration of the study. Based on established recommendations for reaching data saturation in theory-based studies, interviews will be conducted with a minimum n=10 and stopped after three consecutive interviews where no new findings emerge (Francis et al., 2010). Alternatively, will conduct 3 – 6 focus groups, which has been shown to identify 90% of all themes (Guest et al., 2017; Hennink et al., 2019).

Secondary outcome [4]

The Cognitive Strengths Scale (CSS) will be used to measure self-reported cognitive strengths.

Timepoint [4]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [5]

The Strengths Use Scale (SUS) is a self-report scale containing 14 items related to the general use of strengths in daily life.

Timepoint [5]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [6]

The Patient Health Questionnaire-9 (PHQ-9) is a 10-item self-report scale measuring the extent to which clinical symptoms of depression have been experienced over the past two weeks.

Timepoint [6]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [7]

The Generalised Anxiety Disorder-7 (GAD-7) is a 10-item self-report scale which measures the extent to which clinical symptoms of anxiety have been experienced over the past two weeks.

Timepoint [7]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [8]

The Rosenberg Self-Esteem (RSES) scale is a 10-item scale which will be used to measure how a person feels about themselves.

Timepoint [8]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [9]

The General Self-Efficacy (GSES) 10-item self-report will be used to measure an individual's self-confidence in their daily life.

Timepoint [9]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [10]

The frequency of a person's subjective cognitive difficulties over the past seven days will be measured using the Perceived Deficits Questionnaire (PDQ), a 20-item self-report measure.

Timepoint [10]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [11]

The World Health Organisation Disability Assessment Schedule 2.0 (WHODAS-2.0) is a self-report scale which measures a participant's general level of psychosocial disability over the past 30 days.

Timepoint [11]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [12]

The World Health Organisation Quality of Life - BREF (WHOQOL-BREF) is a self-report measure which will be used to measure a participant's quality of life over the past two weeks.

Timepoint [12]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [13]

The extent to which people feel satisfied with basic psychological needs in their lives in general will be measured using the Basic Psychological Need Satisfaction Scale.

Timepoint [13]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [14]

The Neuropsychological Symptom Self-Report - Frequency Version (NSSR-FV) is a self-report which will be used to measure the frequency of a person's subjective cognitive difficulties over the past two weeks.

Timepoint [14]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [15]

Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) is a clinician-rated scale with seven items which ask about a young person's substance use and potential indicators of problematic use of dependence (e.g., frequency, cravings, health impacts). The scales will be rated by a member of the research team.

Timepoint [15]

This assessment will occur at the end of Day 1 (following the cognitive screeners).

Secondary outcome [16]

The Social and Role Functioning Scales are 10-point scales that assess a person's interpersonal relationships and general vocational/household functioning. The scales will be measured by a member of the research team using standardised prompts to explore social and community participation over the last month.

Timepoint [16]

This scale will be administered at the end of Day 1 (following the cognitive screeners).

Secondary outcome [17]

The Adverse Childhood Experiences (ACE) Questionnaire is a 10-item self-report measure which will be used to identify childhood experiences of early life stress (e.g., parental divorce, abuse).

Timepoint [17]

Participants will complete this self-report measure at the end of Day 1 (following cognitive screening measures).

Secondary outcome [18]

The Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5) is a self-reported scale which will measure PTSD symptoms.

Timepoint [18]

Participants may choose to complete this self-report measure at the end of Day 1 (following cognitive screening measures), at the beginning of Day 2 (prior to the neuropsychological assessment), or they may choose to complete this measure at home between Day 1 and Day 2 to minimise participant fatigue.

Secondary outcome [19]

To further explore the acceptability of cognitive screening, a subset of young people with FEP (n=10-30) will be invited to participate in an interview or focus group to share their experiences of cognitive screening. This interview/focus group is likely to occur a within 3 months after completing the MoCA and SCIP. Interviews will be semi-structured, facilitated by one member of the research team, and may occur face-to-face or online. Focus groups will be semi-structed, facilitated by two members of the research team, and may occur face-to-face or online.

Timepoint [19]

The interview or focus group will occur within three months of participation in the diagnostic accuracy component of the study. Based on established recommendations for reaching data saturation in theory-based studies, interviews will be conducted with a minimum n=10 and stopped after three consecutive interviews where no new findings emerge (Francis et al., 2010). If young people opt to take part in focus groups rather than interviews, we will conduct 3 – 6 focus groups, which has been shown to identify 90% of all themes (Guest et al., 2017; Hennink et al., 2019).

Eligibility

Key inclusion criteria

Participants are eligible for the primary study if they are:
1. Aged 12-25 years inclusive
2. Diagnosed with FEP, defined as having a diagnosable psychotic disorder which is currently being treated at an early intervention service
2. Receiving public mental health treatment at one of the recruitment sites
3. Clinically stable as assessed by their treating team (e.g., no acute deterioration in mental health, risk issues, etc.).

Minimum age

12 Years

Maximum age

25 Years

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

The exclusion criteria for the study are:
1) inability to provide informed consent;
2) had a cognitive assessment in the past 12 months.

Study design

Statistical methods / analysis

Sample size:
The sample size needed for the diagnostic accuracy study has been calculated based on considerations for the expected rate of clinically significant cognitive impairment (i.e., approximately 70-75%), sensitivity and specificity of greater than or equal to 80%, and 95% confidence intervals (+/- 5%). A sample of 350 is needed to achieve these parameters (Malhotra & Indrayan, 2010).

Clinical cognitive impairment will be defined as either: (1) greater than or equal to 2 cognitive domain scores 1.5 SD below population mean on the reference test normative data, or (2) Full-Scale IQ <80 on the WISC/WAIS. This will be based on data collected from the standardised neuropsychological battery (i.e., STARD Reference Standard). The study will first examine the performance of the typical cut-off scores of the SCIP (<70) and MoCA (<26) (STARD Index measures) followed by exploration of the performance of other cut-scores using logistic regression analyses. Several indicators of classification accuracy will be calculated using logistic regression analysis (e.g., sensitivity and specificity, and LR+/-). LRs will be used to assist estimation of post-test probability across a relevant range of prevalence. Intra-class correlation coefficients for absolute agreement will used for the retest reliability analysis.

To test the hypotheses that both cognitive screeners will show accurate classification accuracy and retest reliability, a sensitivity and specificity of 80%, LR+ of greater than or equal to 5, LR- of <.1, and an intra-class correlation coefficient of 0.80 will be considered acceptable (Bowden et al., 2017).

To test the hypothesis that the classification accuracy of the SCIP will be superior to the MoCA, their relative positive and negative LRs will be compared using the formula in Hayen et al. (2010). If one of the screeners is not superior on both LR+/-, we will use the formula in Biggerstaff et al. (2000) to determine superiority.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

21/08/2023

Actual

4/09/2023

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

350

Accrual to date

50

Final

Recruitment in Australia

Recruitment state(s)

NSW,SA,VIC

Recruitment hospital [1]

Orygen Youth Health - Parkville - Parkville

Recruitment hospital [2]

The Alfred - Melbourne

Recruitment hospital [3]

Headspace Bentleigh - Bentleigh

Recruitment hospital [4]

Headspace Elsternwick - Elsternwick

Recruitment hospital [5]

Headspace Bondi Junction - Bondi Junction

Recruitment hospital [6]

Prevention Early Intervention & Recovery Service (PEIRS) - Parramatta

Recruitment hospital [7]

Northern Community Mental Health Service - Salisbury

Recruitment hospital [8]

Eastern Community Mental Health Service - Tranmere

Recruitment hospital [9]

Western Community Mental Health Service - Woodville

Recruitment hospital [10]

North East Community Mental Health Service - Modbury

Recruitment hospital [11]

headspace Early Psychosis (hEP) Service Parramatta - Parramatta

Recruitment hospital [12]

headspace Early Psychosis (hEP) Service Mount Druitt - Mount Druitt

Recruitment hospital [13]

headspace Early Psychosis (hEP) Service Adelaide - Adelaide

Recruitment postcode(s) [1]

3052 - Parkville

Recruitment postcode(s) [2]

3004 - Melbourne

Recruitment postcode(s) [3]

3204 - Bentleigh

Recruitment postcode(s) [4]

3185 - Elsternwick

Recruitment postcode(s) [5]

2022 - Bondi Junction

Recruitment postcode(s) [6]

2150 - Parramatta

Recruitment postcode(s) [7]

5108 - Salisbury

Recruitment postcode(s) [8]

5073 - Tranmere

Recruitment postcode(s) [9]

5011 - Woodville

Recruitment postcode(s) [10]

5092 - Modbury

Recruitment postcode(s) [11]

2270 - Mount Druitt

Recruitment postcode(s) [12]

5000 - Adelaide

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Department of Health and Aged Care, Medical Research Future Fund

Country [1]

Australia

Primary sponsor type

Charities/Societies/Foundations

Name

Orygen

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health Research Ethics Committee

Ethics committee address [1]

Office for Research
Royal Melbourne Hospital
CITY CAMPUS
Level 2
South West
300 Grattan Street
Parkville, Victoria, Australia 3052

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

29/11/2022

Approval date [1]

15/02/2023

Ethics approval number [1]

HREC/89942/MH-2022

Summary

Brief summary

To validate a brief cognitive screening tool for young people with FEP using established classification accuracy methodology and to explore the acceptability, feasibility and implementation barriers and facilitators of screening as part of an implementation evaluation.

Trial website

Public notes

Contacts

Principal investigator

Name

A/Prof Kelly Allott

Address

Orygen
35 Poplar Road
Parkville, Victoria, Australia, 3052

Country

Australia

Phone

+61 407 365 600

Email

[email protected]

Contact person for public queries

Name

Kelly Allott

Address

Orygen
35 Poplar Road
Parkville, Victoria, Australia, 3052

Country

Australia

Phone

+61 407 365 600

Email

[email protected]

Contact person for scientific queries

Name

Kelly Allott

Address

Orygen
35 Poplar Road
Parkville, Victoria, Australia, 3052

Country

Australia

Phone

+61 407 365 600

Email

[email protected]

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
18262	Study protocol			[email protected]
18377	Ethical approval			[email protected]		385291-(Uploaded-17-02-2023-14-29-04)-Study-related document.pdf

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