MR1213 - Lung-SEARCH: A RANDOMISED CONTROLLED TRIAL OF SURVEILLANCE FOR THE EARLY DETECTION OF LUNG CANCER...

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Data controllers: − CANCER RESEARCH UK

Objective for processing

The Lung-SEARCH trial is a national screening study of >1700 individuals who smoke and have COPD are randomised to yearly sputum (and those who are positive have an annual bronchoscopy and CT scan) or no screening. All patients are followed up for 5 years, and the aim of the trial is to determine whether this screening policy can identify cancers at a lower stage at diagnosis. Because patients are free from cancer when they enrol in the study, we need to flag all patients with the national register to ensure that we find out about cancers in both trial groups, and also deaths and cause of death. The target sample size is about 80 lung cancers, so it is important that we can identify as many as possible, particularly those in the unscreened group. This Data Sharing Agreement permits University College London (UCL) to retain data which was supplied under a previous version of this Agreement for the purpose of the Lung-SEARCH trial. The Lung-SEARCH trial was a national screening study of >1700 individuals who smoked and had COPD and were randomised to yearly sputum (and those who were positive had an annual bronchoscopy and CT scan) or no screening. All patients were followed up for 5 years, and the aim of the trial was to determine whether this screening policy can identify lung cancers at a lower stage at diagnosis compared to no screening. Because patients were free from cancer when they enrolled in the study, they were flagged with the national register to ensure that we find out about cancers in both trial groups, and also deaths and cause of death. The target sample size was about 80 lung cancers, so it was important that we could identify as many as possible, particularly those in the unscreened group. There are no moral or ethical issues raised by the data dissemination because only summary data have been (or ever will) be published, so no individual can ever be identified. In accordance with article 9(2) of the GDPR, all Lung-SEARCH participants gave explicit consent to the processing of their personal data for the study objectives purposes, as all versions of the Participant Information Sheet contained the text: “We may also use information from the National Health Service Care Register, the Office of National Statistics and/or Cancer Registries to follow your progress.” Under this Agreement, the purpose is to retain datasets that have already been collected from the national cancer and death registries. These data consist of cancer notifications (type of cancer and date of diagnosis), and cause and date of death. This is one of only 2 randomised lung cancer screening trials conducted in the UK. The data are required for future analyses of existing data that could be pertinent to setting up the national screening programme in the UK for lung cancer, currently being considered. The Lung-SEARCH trial provides data on outcomes of the efficacy of low dose CT scanning specifically among high risk smokers and ex-smokers with COPD. The data are requested for another 5 years, by which time further analyses should have been completed. The data contain personal identifiers (name, date of birth, sex and NHS number), which participants had already consented to providing as part of the study. These identifiers are securely stored on a server in a folder that has very restricted access. The data are from 10 UK centres because screening uptake for lung cancer is known to vary substantially between geographical regions. Uptake was one of the main results of the trial. Given the duration of the study, and that people can move around the country, collecting cancer and death data via the registries minimises the number of missed events, compared to if the study investigators only relied on outcomes reported by the recruiting hospital. LungSEARCH was a national multicentre randomised trial. 1568 participants were randomised during 2007–2011 from 10 UK centres. These participants were current or ex-smokers with mild or moderate chronic obstructive pulmonary disease (COPD). They were randomised (1:1) to have either 5 years surveillance (screening) or standard of care management. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual low dose CT of their lung and also autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples, unless a sample became positive. The trial ended in 2016, which was when the last participant had their last protocol-specified assessment (an exit chest CT scan or X-ray). LungSEARCH is one of only 2 randomised trials of screening for lung cancer that was conducted in the UK. Whereas the other trial recruited smokers and ex-smokers, LungSEARCH focussed on a higher risk subset of this, i.e. smokers who also had COPD. The trial evaluated sequential testing as a screening approach, in which a cheap first screen (sputum) is used to select who is offered low dose CT and AFB. In accordance with article 6 of the GDPR, the basis for processing these data are: • all study participants had given explicit consent to the processing of his or her personal data, in relation to the study objectives of evaluating a lung cancer screening policy. • processing is necessary for the performance of a task carried out in the public interest, in relation to the UK’s forthcoming plans to roll out a national lung cancer screening programme. Patients signed the consent form after reading the Patient Information Sheet. This states that information from the National Health Service Care Register, the NHS Information Centre and/or Cancer Registries will be used to follow the patients’ progress. It also states these bodies had to be sent identifiable information to be able to provide information. This means the patient consented for their details (including name and date of birth) to be sent to the Cancer Research UK & UCL Cancer Trials Centre. With the participant’s permission, their GP were notified of their participant’s participation in the trial. The Data Controller is University College London. No other institution will have access to the data; including no other funders or commissioners.

Processing activities

Patients sign the consent form after reading the Patient Information Sheet. This states that information from the National Health Service Care Register, the NHS Information Centre and/or Cancer Registries will be used to follow the patients’ progress No new data will be supplied under this Agreement. It also states these bodies need to be sent names identifiable information to be able to provide information. This means the patient is happy for their details (including name and date of birth) to be sent to the Cancer Research UK & UCL Cancer Trials Centre. With the patient’s permission, their GP will be notified of their patient’s participation in the trial. Data provided under previous versions of this Agreement may be retained and reused as required for the purposes described in this Agreement only.

Expected output

The Ethics committee has been informed that this trial will be registered with the NHS Information Centre. Patients’ names are required for this and the ethics committee have approved this on the Patient Information Sheet and Consent Form. There have been a few publications so far including the main trial paper. Patel D, Akporobaro A, Chinyanganya N, Hackshaw A, Seale C, Spiro S, Griffiths C. Attitudes to participation in a lung cancer screening trial: a qualitative study. Thorax 2012; 67:5 418-425 Spiro SG, Hackshaw A; LungSEARCH Collaborative Group. Research in progress--LungSEARCH: a randomised controlled trial of surveillance for the early detection of lung cancer in a high-risk group. Thorax. 2016;71(1):91-3 Spiro SG, Shah PL, Rintoul RC, George J, Janes S, Callister M, Novelli M, Shaw P, Kocjan G, Griffiths C, Falzon M, Booton R, Magee N, Peake M, Dhillon P, Sridharan K, Nicholson AG, Padley S, Taylor MN, Ahmed A, Allen J, Ngai Y, Chinyanganya N, Ashford-Turner V, Lewis S, Oukrif D, Rabbitts P, Counsell N, Hackshaw A. Sequential screening for lung cancer in a high-risk group: randomised controlled trial: LungSEARCH: a randomised controlled trial of Surveillance using sputum and imaging for the EARly detection of lung Cancer in a High-risk group. Eur Respir J. 2019;54(4)

Expected measurable benefits

Not stated in the previous version; added here.

The trial did not show that the sequential screening approach was better at identifying low stage lung cancer, compared to no screening.

However, the trial has implications for future research and screening practice. First, it provides evidence from a large randomised trial that it is difficult to find ways of targeting low dose CT screening to make it more efficient (other than risk-based algorithms). LDCT should therefore be offered to all eligible individuals within planned screening programmes. Second, our study was based on particularly high-risk individuals (smokers with COPD) and many unscreened individuals (controls) were diagnosed at an early cancer stage, indicative of them seeking medical attention sooner. This probably means that this group is more receptive to screening and early detection than previously thought, such that the uptake of low dose CT within organised programmes could be high among these individuals. Third, low dose CT detected all lung cancers among COPD patients in our trial who were sputum positive, which is suggestive evidence that planned screening programmes should consider sufficient inclusion of COPD.

Benefits reported

Not stated in the previous version; added here.

The UK (Public Health England and NHS England) is currently considering and planning how to implement a national lung cancer screening programme. Research groups can undertake modelling and the findings from LungSEARCH can be used to help with this (e.g. that all smokers with COPD can be detected by low dose CT, so should be a key target group for screening invitations).