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Trial registered on ANZCTR


Registration number
ACTRN12623000914662p
Ethics application status
Submitted, not yet approved
Date submitted
24/04/2023
Date registered
25/08/2023
Date last updated
25/08/2023
Date data sharing statement initially provided
25/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Lung cancer screening: Testing the accuracy of risk prediction for Maori
Scientific title
Determination of an Indigenous Maori ethnic weighting within the PCLOm2012 risk prediction model for lung cancer screening by comparison between Maori and European participants age 50-74 years in Aotearoa New Zealand
Secondary ID [1] 309515 0
None
Universal Trial Number (UTN)
U1111-1291-6982
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung cancer screening 329800 0
Condition category
Condition code
Public Health 326697 326697 0 0
Other public health
Cancer 326698 326698 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a cross-sectional study of people offered one round of lung cancer screening. This study aims to test how an international model for determining the risk of lung cancer (the ‘PLCOm2012’ model) performs in an Aotearoa New Zealand context, specifically with Maori and European populations, and to provide an appropriate ethnic weighting to optimise this model to use locally.
The most appropriate ethnic weighting within the PLCOm2012 risk prediction model for lung cancer risk will be determined by comparing risk and outcomes for Maori and European populations.
We will not be able to determine the absolute accuracy of the risk predictions from the PLCO model are in the NZ context in this study as we will not have 6 years follow-up. Instead we are using a prevalence outcome which will provide the relative risk associated with Maori ethnicity compared with European ethnicity so that for any given screening threshold (1.7% etc) the algorithm will not underestimate Maori risk.
In doing so, we will describe key outcomes that are required to inform a potential national lung cancer screening programme in NZ, and will examine whanau activation and how participants have experienced the lung cancer screening pathway. We will also test the effectiveness of a novel mechanism for inviting participants for lung screening, a voucher provided by friends/whanau.


We will be testing the PLCOm2012 model, hypothesising that the PLCOm2012 risk prediction model (used without an ethnic weighting) will under estimate risk for Maori participants.
The Prostate Lung Colorectal and Ovarian (PLCOm2012) model is a lung cancer risk prediction model which has been used and validated by multiple lung cancer screening projects internationally. The PLCOm2012 is a logistic regression model based on cancer incidence (over 6 years) that occurred in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). This model has higher sensitivity, specificity and positive predictive value when compared to the NLST risk prediction criteria (which defines a person as of “high risk” when they have a smoking history of greater than or equal to 30 pack years, have smoked within the past 15 years, and are aged between 55–74). The PLCOm2012 model was developed using U.S. data, and includes variables such as age, education, body mass index, personal history of cancer, family history of lung cancer, COPD, smoking status, tobacco consumption, smoking duration and time since quitting.
(ref Tammemagi MC, ten Haag K, Toumazis I, Kong CY, Han SS, Jeon J, et al. Development and validation of a multivariable lung cancer risk prediction model that includes low-dose computed tomography screening results: A secondary analysis of data from the National Lung Cancer Screening Trial. JAMA Netw Open [Internet]. 2019 [cited 2020 Nov 11]; 2(3): e190204)


Potentially eligible participants will receive a written invitation to participate in the study, and followed up with a phone call to confirm eligibility and consent to participate. The first stage of participation is to undergo the PLCO risk assessment. The risk assessment will be done by the project research nurse in-person, over the phone or by Zoom/digital technology, depending on participant preference, or self-completed online. Participants who meet risk threshold or criteria-based eligibility for LCS will be offered a Shared Decision-Making process. In this process, participants and the study nurse share the best available evidence when making decisions, and participants are supported to consider options to achieve informed choice.
After the shared decision making process, participants who consent will be offered a CT scan of the chest.
Results will be followed up and participants informed and offered appropriate follow up, either through their GP or through referral to respiratory / oncology services

Estimated time required by participants is as follows:
Risk assessment - 10 minutes
Shared decision making - 15 minutes
Low dose CT scan - 2 minutes (for the scan) plus consenting time and waiting time

The study research nurses will collect information during the risk assessment conversation
Some participant responses will be double checked at CT scan to audit fidelity
Study nurses will interact with the model and if identified as high risk, participants will be offered a CT scan at a community scanning facility. Results will be followed up and participants informed and offered appropriate follow up, either through their GP or through referral to respiratory / oncology services
Intervention code [1] 325947 0
Early detection / Screening
Comparator / control treatment
The control arm of the study comprises European participants (this includes NZ European and Other European but excludes people who identify as European and any other ethnicity), both men and women aged 50 to 74 years, who are not ‘never smokers’ and who live in the Northern Region of New Zealand - Northland, Waitemata, Auckland and Counties Manukau districts (formerly ‘DHB’ areas).

To clarify, both arms of the study will use the established PLCO model - one arm will assess European participants risk - this comparator arm will be assesssed against an arm of Maori participants to determine relative risk for Maori allowing us to calculate the appropriate ethinic weighting for Maori.
Control group
Active

Outcomes
Primary outcome [1] 334562 0
The primary outcome is the magnitude and significance (F test) of the Maori risk adjuster calculated from the new logistic regression model.
Timepoint [1] 334562 0
PLCOm2021 model determined at time of risk assessment (for the individual participant).
CT scan will be offered at time of postitive risk assessment - according to participant availability
CT results to be processed within 2 weeks of screening
Secondary outcome [1] 421190 0
Accuracy of the PLCOm2012 model when using NZDep information in diagnosing lung cancer when compared to a low dose CT scan
Timepoint [1] 421190 0
This secondary outcome requires analysis of all participant data, and cannot be determined on a per patient basis. Therefore the timepoint for this outcome is at the end of the three year study
Secondary outcome [2] 421191 0
Differences in screening uptake rates for Maori and for high deprivation populations (Chi squared test; t-test; Wilcoxon-Mann-Whitney test). Assessed by monitoring the rates of those people invited to participate vs those that accept the invitaiton, by self reported ethnicity and dep rate of their area of residence
Timepoint [2] 421191 0
This secondary outcome requires analysis of all participant data, and neche cannot be determined on a per patient basis. Therefore the timepoint for this outcome is at the end of the three year study
Secondary outcome [3] 421192 0
Rates of unnecesary invastive investigations in LCS particiapants by ethnicity
This will be asssessed from patient records and calculated using Chi squared test of rates of invasive investigation for benign disease
Timepoint [3] 421192 0
At the end of the three year study
Secondary outcome [4] 421193 0
Proportion of risk assessments undertaken online - assessed using website analysis and Redcap data merge
Timepoint [4] 421193 0
At the end of the three year study
Secondary outcome [5] 421201 0
Prevalence of nodules detected by LDCT lung cancer screening - assessed by CT scan analysis using PANCAN nodule scoring system
Timepoint [5] 421201 0
At the end of the three year study
Secondary outcome [6] 421202 0
Prevalence of incidental findings by type (composite outcome), assessed by review of the CT scan report and follow up medical referral
Timepoint [6] 421202 0
At the end of the three year study
Secondary outcome [7] 421203 0
Cancer detection rate as determined by CT scan report and subsequent medical records
Timepoint [7] 421203 0
Medical records will be reviewed every 3 months to determine outcomes and will be analysed at the end of the three year study
Secondary outcome [8] 421204 0
Prevalence of screening associated harms assessed by review of medical records.

Timepoint [8] 421204 0
Medical records will be reviewed every 3 months to determine outcomes and will be analysed at the end of the three year study
Secondary outcome [9] 423654 0
Proportion of operable cancers detected, determined by medical record review
Timepoint [9] 423654 0
At the end of the three year study
Secondary outcome [10] 425360 0
Rates of non-invasive diagnostic investigation of benign disease (screening associated harms) determined from medical record review, determined by Chi squared test of rates of non-invasive diagnostic investigation of benign disease
Timepoint [10] 425360 0
At the end of the three year study
Secondary outcome [11] 425361 0
CT scan positivity rate
Timepoint [11] 425361 0
At the end of the three year study
Secondary outcome [12] 425710 0
Proportion of nodules of each PANCAN type detected, assessed by review of radiology report
Timepoint [12] 425710 0
At the end of the three year study

Eligibility
Key inclusion criteria
Participants will be recorded or self-identified as Maori or European (NZ European or Other European) in the primary care enrolment register. Ethnicity will be checked on enrolment in line with the ethnicity data protocols,
Aged between 50 to 74,
Live in the Northland, Waitemata, Auckland and Counties Manukau regions of New Zealand,
Are enrolled in participating general practices (clinics) or Maori Health Provider clinics,
Recorded as an ‘ever smoker’ within GP records, (‘Ever smokers’ includes both current and ex-smokers, classified in the primary care data extract (coded in the practice management system) as anyone who is not a never-smoker.)
Able to provide informed consent and agree to participate.
Minimum age
50 Years
Maximum age
74 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Never smokers; those with clinical symptoms suspicious for lung cancer; previous diagnosis of lung cancer; have other non-curatively treated cancer outside the lung; have had curative treatment for non-lung cancers within the last five years; have received chemotherapy or cytotoxic drugs within the last six months; pneumonia or bronchitis requiring antibiotic treatment within the last 12 weeks; chest CT that images the full lung within 2 years; pregnancy; unable to provide informed consent due to cognitive problems; unwilling to provide consent; unwilling to have a Low Dose CT (LDCT) scan; any end-stage medical condition.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Cross-sectional study of people offered one round of lung cancer screening. The most appropriate ethnic weighting within the PLCOm2012 risk prediction model for lung cancer risk will be determined by comparing risk and outcomes for Maori and European populations.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Our primary hypothesis is that the PLCOm2012 model will underestimate Maori risk of lung cancer (compared to European) to a similar extent as it has been found to underestimate LC risk for American Indians / Native Alaskans compared to white non-Hispanic Americans (requiring a weighting of 2.7931 greater risk to be applied to thePLCOm2012 model for AINA)).
Assuming equivalence for the T0 prevalence this corresponds to a LC prevalence ratio of 2.65 at 3% prevalence among the European sample. We have conservatively assumed a LC prevalence of 3% in our study population based on the Manchester Lung Health Study39 which found that same prevalence at a lower PLCOm2012 risk threshold (1.5%) than we intend to use (1.7%). Although a higher threshold might be used in a national screening programme (e.g. 2%) having a lower one in this study will facilitate calculation of the Net Reclassification Index (NRI) with incorporation of the Maori risk adjuster. Note that we will not use the “no race” PLCOm2012 version of the model in our initial risk assessments as we are assuming that the European population has risk equivalent to the ‘white’ American population and not to the total population mix of ethnicities in the United States.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2023
Actual
Date of last participant enrolment
Anticipated
30/01/2026
Actual
Date of last data collection
Anticipated
30/04/2026
Actual
Sample size
Target
1200
Accrual to date
Final
Recruitment outside Australia
Country [1] 25415 0
New Zealand
State/province [1] 25415 0
Northern Region

Funding & Sponsors
Funding source category [1] 313709 0
Government body
Name [1] 313709 0
Health Research Council
Country [1] 313709 0
New Zealand
Primary sponsor type
Government body
Name
Te Whatu Ora Waitemata
Address
15 Shea Terrace
Takapuna
Auckland
0622
Country
New Zealand
Secondary sponsor category [1] 315518 0
None
Name [1] 315518 0
Address [1] 315518 0
Country [1] 315518 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 312882 0
Health and Disability Ethics Committee (Northern B)
Ethics committee address [1] 312882 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 312882 0
New Zealand
Date submitted for ethics approval [1] 312882 0
23/03/2023
Approval date [1] 312882 0
Ethics approval number [1] 312882 0

Summary
Brief summary
This study aims to test how an international model for determining the risk of lung cancer (the ‘PLCOm2012’ model) performs in an Aotearoa New Zealand context, specifically with Maori and European populations, and to provide an appropriate ethnic weighting to optimise this model to use locally.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126206 0
Prof Sue Crengle
Address 126206 0
18 Frederik St
University of Otago
North Dunedin
Dunedin
9016
Country 126206 0
New Zealand
Phone 126206 0
+64 21 832 346
Fax 126206 0
Email 126206 0
sue.crengle@otago.ac.nz
Contact person for public queries
Name 126207 0
Dr Kate Parker
Address 126207 0
Te Whatu Ora Waitemata
Level 2
Q4
Smales Farm
74 Tarahoto Road
Takapuna
6022
Country 126207 0
New Zealand
Phone 126207 0
+64 21 678 907
Fax 126207 0
Email 126207 0
kate.parker2@waitematadhb.govt.nz
Contact person for scientific queries
Name 126208 0
Prof Sue Crengle
Address 126208 0
18 Frederik St
University of Otago
North Dunedin
Dunedin
9016
Country 126208 0
New Zealand
Phone 126208 0
+64 21 832 346
Fax 126208 0
Email 126208 0
sue.crengle@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Due to Maori data sovereignty principles, no individual data will be made available to researchers outside of this study.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18980Study protocol  kate.parker2@waitematadhb.govt.nz
18981Informed consent form  kate.parker2@waitematadhb.govt.nz



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.