The Extended Salford Lung Study Data Access Project

Following completion of the research studies conducted using the Hospital Episodes Statistics (HES) data, GSK wish to retain HES data provided under a previous iteration of this Agreement until the findings of these studies are published as manuscripts in the peer reviewed literature. GSK anticipate some additional processing of the data in order to be able to satisfy peer review comments during the publication process for these studies. No additional data is requested.

BACKGROUND

The Extended-SLS is a follow-on study to the Salford Lung Studies (SLS), two landmark effectiveness trials of fluticasone furoate / vilanterol (an inhaled corticosteroid combined with a long-acting-b2-agonist [LABA] in a single inhaler device) in patients with Chronic Obstructive Pulmonary Disease (COPD) (NCT01551758) and asthma (NCT01706198) which ran from March 2012 to December 2016.

The SLS subjects represent patient cohorts that are extremely well-characterised over a short period of their COPD/asthma disease experience. The cohort comprises of 1121 extended Salford Lung Study participants and recruitment ended in May 2019. Subjects in the SLS originally consented for information relevant to the study to be shared with the sponsor, GSK, and these data were limited to three years prior to randomisation and the twelve-month interventional treatment period. This finite period of data coverage limits the potential to address scientific questions of clinical interest related to long-term COPD/asthma disease progression and associated outcomes (for example, mortality). Broadened access to patients’ data would allow SLS subjects’ entire disease journey to be researched, presenting a rare opportunity to use epidemiological research to improve scientific and clinical understanding of COPD/asthma disease risk, treatment and progression.

The Extended-SLS sought to broaden capture of SLS patients’ data through the collection of additional subject-level data encompassing past and periodic future (up to 10 years duration from the date of consent) demographic, COPD/asthma risk factors and healthcare-related information from both primary and secondary care, resulting in the creation of the Extended-SLS cohort. Additional patient reported data on early life exposures, impact of disease on sleep, smoking history and other information not typically available from electronic medical records (EMR) were captured using disease-specific questionnaires. Secondary care data on hospital admissions and attendances available in NHS Digital’s HES data were crucial to understanding and researching hospitalised exacerbations of COPD/asthma, comorbidity, long-term safety of COPD and asthma therapies, and healthcare resource utilisation.

Adelphi Group Limited trading as Adelphi Real World (for purpose of this application referred to as 'Adelphi'), had been contracted by GSK to carry out research on the Extended-SLS Data to help GSK answer some of the Asthma specific research questions detailed below:

• Burden of moderate exacerbations in asthma patients participating in the Ex-SLS

• Patient-initiated changes in the dose and frequency of their asthma maintenance therapy

• Asthma control and adherence in Ex-SLS patients prescribed ICS/LABA

The Extended-SLS involved four organisations throughout the wider study though only GSK, Ignite and Adelphi were involved in the processing of the HES data. Ignite have now completed their processing activities and are therefore no longer a data processor under this Agreement.

• GlaxoSmithKline (GSK): The sponsors of the original SLS and the Extended-SLS. GSK received the final pseudonymised cut of study data, including the HES data provided by NHS Digital. GSK are the data controller and also process the data in this study. GSK is an international pharmaceutical company and the relevant GSK party for this agreement is a company registered in England and Wales. GSK produces drugs directly relevant to the ailments being studied and holds the international patent to one of the drugs specifically referred to in this Agreement.

• Ignite Data (Ignite): The contracted research company were looking after site management, patient consent and data processing. Ignite had the explicit consent of Participants for bringing together multiple different data sources captured on each individual study volunteer, specifically including the consent of patients to process their HES and mortality data. Note: patients provided consent for use of mortality data, however, this Agreement does not cover the request of ONS mortality data. Ignite’s role as a processor has been completed and Ignite no longer have access to the data.

• Graphnet Health (Graphnet): were the general practitioner (GP) extract provider for the study. Graphnet had active Data Sharing Agreements with every GP who is participating in the study for direct care and hold Data Security and Protection (DSP) Toolkit. Study specific agreements existed with each individual GP giving Graphnet permission to extract consented participant data for this study only. Graphnet were not in receipt of any HES data provided to Ignite Data by NHS Digital. Graphnet were not directly involved with this Agreement but were a source of the main study data set.

• Adelphi Real World (Adelphi): are the contracted research company who have developed and are executing protocols, analysing data and developing reports on behalf of GSK researchers that will answer Asthma specific research questions using data from the Extended-SLS. Adelphi have received pseudonymised data for a subset of the Extended-SLS cohort, those with Asthma.

GSK had contracted to have this work carried out by Adelphi Real World, a trading name of Adelphi Group Limited (in Macclesfield: Adelphi Mill, Grimshaw Lane, Macclesfield, England, SK10 5JB). Adelphi Group Limited are wholly owned by DAS UK Investments Ltd (in London: Bankside 3, 90 - 100 Southwark Street, London, England, SE1 0SW) who are in turn wholly owned by Omnicom Group Inc. (in New York).

Omnicom Group inc / DAS UK Investments Ltd were not a Data Controller nor were any data seen by them, nor any data stored or processed outside of the UK.

GlaxoSmithKline (GSK), who sponsors and funds the Extended Salford Lung Study (Ex-SLS), is a manufacturer of treatments for asthma, including the treatment originally studied in the prior Salford Lung Studies. Processing of the HES secondary care data to address specific research questions relating to identified evidence gaps in asthma using the Extended SLS cohort will have broad public benefit. The intended benefits are advances in disease understanding of asthma and treatment which GSK anticipate will improve patient care by better informing clinicians on which asthma patients may benefit from a change in their inhaled maintenance therapy; and improve understanding of the burden of illness and unmet medical need in patients with asthma.

Hospital Episode Statistics were used to form a longitudinal patient record that GSK wished to build over the lifetime of the study. HES data supplied to GSK were essential to answer questions in the Extended-SLS related to:

• Healthcare resource utilisation and costs (HRG); primary care electronic medical records did not accurately and reliably capture complete information about hospital attendances and admissions and therefore could not inform the full spectrum of healthcare resource utilisation.

• Severe exacerbation's of COPD and asthma; these were defined, according to global standards, as exacerbation's requiring hospital admission (asthma and COPD) and exacerbation's requiring emergency care (asthma), validation studies demonstrated that severe exacerbation's were not adequately recorded in primary care EMR.

• Frailty and disease severity were defined based on prior hospitalisations (all-cause) and comorbidities not managed in primary care.

• Potential, treatment-related adverse events resulting in hospitalisation.

• Impact of treatments and/or disease severity/subtypes on all-cause or COPD- and asthma- related mortality; primary care.

(HRG is analysed using the latest publicly available National Cost Collection:

https://improvement.nhs.uk/resources/national-cost-collection/)

The number of study participants in England in the SLS who consented onto the study were 1,183, with those consenting for NHS Digital sharing their data being 1,121.

All participants were 18 years or older. Each study participant had a current diagnosis of COPD or asthma and were previously enrolled on to RCT (Randomised Controlled Trial) known as the Salford Lung Study. Each individual participant was recruited via the SLS study site, which in every case was their local GP. The GP Practices were selected from the Greater Manchester Region based on the fact they had participated in the original Randomised Control Trial (RCT).

GSK had many questions that were potentially answered as a result of learnings from the study. Within GSK’s COPD and Asthma disease areas, these data may help to identify other key areas for GSK to focus their medicines development.

By linking NHS Digital’s HES data to the data already held from the SLS study for patients in the Extended-SLS cohort (primary care EHR, disease-specific patient-completed questionnaires, and the SLS trial data), GSK addressed a range of research questions. Without access to HES data GSK would not have been able to answer any research questions where data on severe asthma or COPD exacerbations were required as these important adverse outcomes of asthma and COPD could only be reliably identified using discharge data from hospitals. Furthermore, GSK would not have been able to describe the full societal burden of these conditions without access to HES Admitted Patient Care (APC), Accident and Emergency (A&E) and Outpatient (OP) data as these were important sources of health-care resource utilization in asthma and COPD.

Research questions which GSK could not fully answer without access to the HES data include:

• Identifying which specific patient and disease traits could be used to guide clinician’s choice of treatment.

• Identifying what impact biomarkers (eosinophils, fibrinogen, etc.) had on (a) the risk of asthma and COPD exacerbations and (b) the risk of pneumonia.

• How patients progress from diagnosis to particular treatments, and if there were factors associated with this progression, e.g. potential clusters of comorbid conditions.

• Identifying if there was a relationship between events pre-COPD or pre-asthma diagnosis (respiratory infections, comorbidities, healthcare-resource utilisation patterns, smoking and body mass index [BMI] dynamic changes) and natural history of COPD and asthma disease progression?.

• Identifying how smoking status modulated or predicted disease trajectory in COPD.

• How healthcare resource utilisation differed in patients with and without exacerbations.

• Examining the effect of asthma onset (early vs late onset) on longitudinal healthcare utilisation and asthma management.

• Long term symptom control, adherence and outcomes (e.g. exacerbations) for asthma patients using specific treatments.

• Investigation of sentinel events (e.g. exacerbations, a prescription of antibiotics or prednisolone) triggering a change in management and investigating what the health care is after a sentinel event.

DATA MINIMISATION

GSK required HES Critical Care (CC) data to accurately ascertain the level of Healthcare Resource Utilisation (HRU) during hospitalisation. Although these were a subset of admitted patient care episodes, critical care was associated with a higher cost. These data were required for example, to ascertain the number of days of advanced respiratory support for patients ventilated in critical care during an admission for COPD exacerbation.

HES Accident and Emergency (A&E) data was required to understand any serious events which resulted in attendance at the emergency department but did not result in admission to hospital. Without these data the study team would not have been able to, for example, ascertain episodes of treatment associated with attendance at A&E for acute exacerbations of Chronic obstructive pulmonary disease (COPD), where the patient is seen in A&E without admission. HES Admitted Patient Care (APC) data was required to ascertain any serious events which resulted in admission to hospital – for example – severe COPD or Asthma exacerbations and other comorbidities; HRU/cost. HES Outpatients (OP) data was required to ascertain secondary care treatment and outcomes, for example, outpatient respiratory clinic appointments where the patient had been referred to the respiratory physician by their GP and the associated cost/HRU of this treatment.

The data provided had been linked against each consented participants’ Randomised Control Trial (RCT) data via their unique Study ID. Only this pseudonymised dataset was provided to GSK by Ignite Data Ltd for analysis. Ignite Data Ltd have since destroyed the data and no longer have access to any NHS Digital data. As this data was being linked to an RCT dataset and then viewed prospectively for the next few years, only the years relevant to the study period were being requested. If the number of years were reduced any further, it would not have been possible to complete any beneficial analysis as the dataset would no longer match the study timeline or provide the depth of information required to study the desired outcomes.

The data have been narrowed by geography due to the fact that the consented patient list only contained patients from specific English research sites. Due to the condition, all patients lived within a reasonable commute of each study site. As the study was a consented a recruited cohort, it was not possible to further minimise them by demographic information any further. The data could not be narrowed down by clinical factors as without data relating to events outside of the main study condition, GSK would not be able to understand all cause HRU.

Patient episodes were required to achieve the study purpose. The patients had consented to GSK having access to relevant data in their whole medical record, so the study team could truly get a picture of their disease history, its treatment and progression historically during the prospective period of the study. Elective episodes were also required because without data relating to events outside of the main study condition GSK would not be able to understand all cause HRU. Maternity episodes were not required for analysis.

There was a timeframe around the index event required because without the dates relating to events, GSK would not have been able to determine whether events occurred after the patient’s entry into the study and before study end, so during that individual patient’s follow up. The study team would not have been able to determine the pattern or treatment and relevant measures contributing to a developing picture of a patient’s disease progression or management. Further, although record identifiers can be used to link episodes of care into spells, associating spells into super-spells of care (when patients may receive care from more than one hospital or trust) it still requires dates of admission and discharge.

Not all the fields within the HES APC, A&E and CC dataset were required. Only the specific fields required, which have been reviewed by GSK epidemiologist had been selected.

For linkage, the data were only linked to the RCT cohort for the analysis set out in this application. As previously described the dataset was minimised by the recruited study cohort and all episodes on the patients were required to determine all cause HRU.

The data was being processed under General Data Protection Regulation Article 6 (1) (f) Legitimate interests as this was for the benefit of science and public health. Processing the NHS Digital data enabled specific research questions relating to asthma and COPD to be addressed, including advances in general knowledge of COPD and asthma disease risk and treatment that may alter how clinicians care for their patients and raise awareness of the burden of these on patients and the wider health system. Insight into the longer-term burden of COPD and Asthma (which were common chronic respiratory conditions which place a high burden on patients and society) would be beneficial to the wider medical science community including medicines developers and healthcare providers.

As special category data, the data was further processed under article 9(2)(j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). This is because the consented data was used to enhance the potential outcomes and improve care, which is in the public interest.

Within a year of data receipt, and during the lifetime of the study, there were multiple outputs. Some outputs for the Extended-SLS study had been completed before the availability of the HES data. The Extended-SLS cohort was further described using HES data and outputs included abstracts presented at the ISPOR US conference in May 2022. Other outputs to be completed in 2022 include oral and poster presentations at the CHEST congress in October 2022. Further outputs will include three published manuscripts in scientific peer-reviewed journals on asthma control, moderate exacerbations of asthma and the use of maintenance and reliever therapy in asthma patients from the Extended-SLS study and is expected to be completed in the first/second quarter of 2023. These completed studies are detailed below.

Study 1: Whilst numerous studies had described the clinical and economic burden of severe asthma exacerbations, very few studies had investigated the concept of moderate asthma exacerbations. Defining moderate asthma exacerbations in electronic medical records (EMR) and administrative claims databases was challenging. A consequence was that the information currently available on the burden posed on the patients and the healthcare system by moderate exacerbations was limited. The project quantified the frequency and burden of moderate exacerbations in asthma, using the bespoke research cohort which included patient-reported data on moderate exacerbation frequency.

Study 2: Despite awareness regarding asthma control and advances in treatment, asthma control remains sub-optimal worldwide. The aim was to describe the burden of uncontrolled asthma in patients using ICS/LABA. As such, a key target of the research was to generate real world data from the UK on the clinical and health system (healthcare-resource utilisation, HCRU) burden in patients inadequately controlled whilst treated with ICS/LABA.

Study 3: ICS/LABAs are typically prescribed in asthma as daily maintenance therapies. In the UK, two ICS/LABAs (budesonide/formoterol [Symbicort] and beclometasone/formoterol [Fostair]) are available as daily maintenance therapies but can also be prescribed as ‘maintenance and reliever therapy’ (MART) regimens. MART dosing or regimens are administered as a directed number of inhalations daily, plus additional as-needed reliever doses – additional reliever therapy with SABA is therefore unnecessary. A key aim of the study was to improve understanding of how patients are using their ICS/LABA therapy, correctly or incorrectly, whether as maintenance or ‘Maintenance and Reliever Therapy’ (MART), by describing how often patients are initiating changes in the dose or frequency of their maintenance therapy.

GSK is committed to sharing results of impactful research with the wider scientific community and all research evaluating a medicine, providing important scientific knowledge, and/or which has relevance for patient care is published externally (and on the GSK Study Register: https://www.gsk-clinicalstudyregister.com/) in line with GSK's policies.

The audiences for outputs of the wider Extended-SLS predominantly include researchers, scientists, and clinicians. GSK planned to disseminate information to Extended SLS participants throughout the lifecycle of the study via newsletters to GP sites. Information needed to be disseminated via GPs as GSK does not have access to participants names, addresses or email.

Any published results contain data which has been aggregated with small number suppression applied as per the HES Analysis Guide to ensure privacy is maintained. All data in outputs are published in-line with GSK policies.

In accordance with GSK’s internal policy, all trial results were shared, regardless of whether they reflect positively or negatively on GSK’s medicines. GSK posted information about the EX-SLS study on a publicly accessible register (ClinicalTrials.Gov) before it started and will update it with a result summary after the study is finished. GSK sought the publication of all results of all clinical trials in peer-reviewed scientific journals and the EX-SLS study and any relevant results found as part of the data processing activities in this application were no different.

The outputs of the studies aimed to support the below listed benefits by looking at the range of benefits for asthma patients and HCPs as below:

The abstract “Operationalising the 2019 GINA asthma treatment steps for application to real-world data from the UK” was presented via poster presentation to the International Society for Pharmacoeconomics and Outcomes (ISPOR) US 2022 in May 2022 where the study was disseminated to the community of healthcare providers, health economics and outcomes researchers and academicians and patient engagement organisations and contributed to pharmacoeconomics methodological research.

Two further manuscripts are currently in development for publication in a scientific peer reviewed journal in the first/second quarter of 2023 subject to peer review.

The abstract “Operationalising the 2019 GINA asthma treatment steps for application to real-world data from the UK” was presented via poster presentation to the International Society for Pharmacoeconomics and Outcomes (ISPOR) US 2022 in May 2022 where the study was disseminated to the community of healthcare providers, health economics and outcomes researchers and academicians and patient engagement organisations and contributed to pharmacoeconomics methodological research.

The moderate exacerbation study highlighted the need for disease management in ICS/LABA asthma patients. Firstly, it was found that a higher rate of moderate exacerbations was associated with poorer asthma control. This also increased the understanding of the unmet need in ICS/LABA groups which had at least one moderate exacerbation in patients with COPD and would benefit from increased disease management.

The asthma control and adherence study also highlighted the need for a review of prescribed therapy in ICS/LABA asthma patients. A substantial proportion of patients within the cohort experienced somewhat controlled and poorly controlled levels of asthma was observed. This was also seen in COPD patients' adherent to ICS-LABA and such patients would benefit from increased disease management.

It also demonstrates to clinicians, ACT and ACQ as objective measures of control and a useful tool to identify sub-optimally controlled patients in clinical practice and thereby improve patient outcomes.

Additionally, operational definitions were developed in conduct of the study which was used to classify patients into GINA treatment steps for use with real-world data. This would enable researchers to conduct better studies and generate more real -world evidence to understand the unmet need in the population.

BACKGROUND

The Extended-SLS is a follow-on study to the Salford Lung Studies (SLS), two landmark effectiveness trials of fluticasone furoate / vilanterol (an inhaled corticosteroid combined with a long-acting-b2-agonist [LABA] in a single inhaler device) in patients with Chronic Obstructive Pulmonary Disease (COPD) (NCT01551758) and asthma (NCT01706198) which ran from March 2012 to December 2016.

The SLS subjects represent patient cohorts that are extremely well-characterised over a short period of their COPD/asthma disease experience. Subjects in the SLS originally consented for information relevant to the study to be shared with the sponsor, GlaxosmithKline Research & Development Limited (referred to in this application as GlaxosmithKline or GSK), and these data were limited to three years prior to randomisation and the twelve-month interventional treatment period. This finite period of data coverage limits the potential to address scientific questions of clinical interest related to long-term COPD/asthma disease progression and associated outcomes (for example, mortality). Broadened access to patients’ data would allow SLS subjects’ entire disease journey to be researched, presenting a rare opportunity to use epidemiological research to improve scientific and clinical understanding of COPD/asthma disease risk, treatment and progression.

The Extended-SLS seeks to broaden capture of SLS patients’ data through the collection of additional subject-level data encompassing past and periodic future (up to 10 years duration from the date of consent) demographic, COPD/asthma risk factors and healthcare-related information from both primary and secondary care, resulting in the creation of the Extended-SLS cohort. Additional patient reported data on early life exposures, impact of disease on sleep, smoking history and other information not typically available from electronic medical records (EMR) will be captured using disease-specific questionnaires. Secondary care data on hospital admissions and attendances available in NHS Digital’s Hospital Episode Statistics (HES) data are crucial to understanding and researching hospitalised exacerbation's of COPD/asthma, comorbidity, long-term safety of COPD and asthma therapies, and healthcare resource utilisation.

**In this amendment GSK wishes to add a further Data Processor, Adelphi Group Limited trading as Adelphi Real World (for purpose of this application referred to as 'Adelphi'), who are contracted by GSK to carry out research on the Extended-SLS Data to help GSK answer some of the Asthma specific research questions detailed below:

• Burden of moderate exacerbations in asthma patients participating in the Ex-SLS

• Patient-initiated changes in the dose and frequency of their asthma maintenance therapy

• Asthma control and adherence in Ex-SLS patients prescribed ICS/LABA

The impact of adding Adelphi as a data processor to the current data flow is that they will be a recipient of pseudonymised data from GSK for Extended-SLS Asthma patients that comprised the HES data, GP medical records and Questionnaire data. **

**The Extended-SLS has four organisations involved in the work though only GSK, Ignite and Adelphi are involved in the processing of the HES data being requested in this application:**

• GlaxosmithKline (GSK): The sponsors of the original SLS and the Extended-SLS. GSK wish to receive the final pseudonymised cut of study data, including the HES data provided by NHS Digital. GSK are a data controller and a data processor in this study. GSK is an international pharmaceutical company and the relevant GSK party for this agreement is a company registered in England and Wales. GSK produces drugs directly relevant to the ailments being studied and holds the international patent to one of the drugs specifically referred to in this agreement.

• Ignite Data (Ignite): The contracted research company looking after site management, patient consent and data processing. Ignite will have the explicit consent of Participants for bringing together multiple different data sources captured on each individual study volunteer, specifically including the consent of patients to process their HES and mortality data. Note patients provided consent for use of mortality data; however, this application is not requesting ONS mortality data.

• Graphnet Health (Graphnet): The general practitioner (GP) extract provider for the study. Graphnet currently have active data sharing agreements with every GP who is participating in the study for direct care and hold Data Security and Protection (DSP) Toolkit. Study specific agreements exist with each individual GP giving Graphnet permission to extract consented Participant data for this study only. Graphnet will not be in receipt of any HES data provided to Ignite Data by NHS Digital. Graphnet are not directly involved with this application but are a source of the main study data set.

** • Adelphi are the contracted research company who will develop and execute protocols, analyse data and develop reports on behalf of GSK researchers that will answer Asthma specific research questions using data from the Extended-SLS. Adelphi will only receive pseudonymised data for a subset of the Extended-SLS cohort, those with Asthma.

GSK have contracted to have this work carried by Adelphi Real World, a trading name of Adelphi Group Limited (in Macclesfield: Adelphi Mill, Grimshaw Lane, Macclesfield, England, SK10 5JB). Adelphi Group Limited are wholly owned by DAS UK Investments Ltd (in London: Bankside 3, 90 - 100 Southwark Street, London, England, SE1 0SW) who are in turn wholly owned by Omnicom Group Inc. (in New York).

Omnicom Group inc / DAS UK Investments Ltd are not a Data Controller nor will any data be seen by them, nor any data stored or processed outside of the UK. **

Hospital Episode Statistics will be used to form a longitudinal patient record that GSK wish to build over the lifetime of the study. HES data supplied to Ignite Data and GSK are essential to answer questions in the Extended-SLS relating to:

• Healthcare resource utilisation and costs (HRG); primary care electronic medical records do not accurately and reliably capture complete information about hospital attendances and admissions and therefore cannot inform on the full spectrum of healthcare resource utilisation.

• Severe exacerbation's of COPD and asthma; these are defined, according to global standards, as exacerbation's requiring hospital admission (asthma and COPD) and exacerbation's requiring emergency care (asthma), validation studies demonstrate that severe exacerbation's are not adequately recorded in primary care EMR.

• Frailty and disease severity defined based on prior hospitalisations (all-cause) and comorbidities not managed in primary care.

• Potential, treatment-related adverse events resulting in hospitalisation.

• Impact of treatments and/or disease severity/subtypes on all-cause or COPD- and asthma- related mortality; primary care.

(HRG is analysed using the latest publicly available National Cost Collection:

https://improvement.nhs.uk/resources/national-cost-collection/)

The number of study participants in England in the SLS who have consented onto the study is currently 1,183, with those consenting for NHS Digital sharing their data being 1,121. This is an ongoing study and Ignite Data Limited estimate the cohort to be 1,300 individuals. All participants are 18 years or older. Each study participant has a current diagnosis of COPD or asthma and was previously enrolled on to RCT (Randomised Controlled Trial) known as the Salford Lung Study. Each individual participant was recruited via the SLS study site, which in every case was their local GP. The GP Practices were selected from the Greater Manchester Region based on the fact they had participated in the original Randomised Control Trial (RCT).

GSK and Ignite Data have many questions that can potentially be answered as a result of learnings from the study. Within GSK’s COPD and Asthma disease areas, these data may help to identify other key areas for GSK to focus their medicines development.

By linking NHS Digital’s HES data to the data already held from the SLS study for patients in the Extended-SLS cohort (primary care EHR, disease-specific patient-completed questionnaires, and the SLS trial data), GSK and Ignite Data hope to address a range of research questions. Without access to HES data GSK and Ignite Data will not be able to answer any research questions where data on severe asthma or COPD exacerbations are required as these important adverse outcomes of asthma and COPD can only be reliably identified using discharge data from hospitals. Furthermore, GSK and Ignite Data will not be able to describe the full societal burden of these conditions without access to HES Admitted Patient Care (APC), Accident and Emergency (A&E) and Outpatient (OP) data as these are important sources of health-care resource utilization in asthma and COPD.

Research questions which GSK and Ignite Data cannot fully answer without access to the HES data include:

• Identifying which specific patient and disease traits can be used to guide clinician’s choice of treatment.

• Identifying what impact biomarkers (eosinophils, fibrinogen, etc.) have on (a) the risk of asthma and COPD exacerbations and (b) the risk of pneumonia.

• How patients progress from diagnosis to particular treatments, and if there are factors associated with this progression, e.g. potential clusters of comorbid conditions.

• Identifying if there is a relationship between events pre-COPD or pre-asthma diagnosis (respiratory infections, comorbidities, healthcare-resource utilisation patterns, smoking and body mass index [BMI] dynamic changes) and natural history of COPD and asthma disease progression?.

• Identifying how smoking status modulate or predict disease trajectory in COPD.

• How healthcare resource utilisation differs in patients with and without exacerbations.

• Examining the effect of asthma onset (early vs late onset) on longitudinal healthcare utilisation and asthma management.

• Long term symptom control, adherence and outcomes (e.g. exacerbations) for asthma patients using specific treatments.

• Investigation of sentinel events (e.g. exacerbations, a prescription of antibiotics or prednisolone) trigger a change in management and investigate what the health care is after a sentinel event.

DATA MINIMISATION

Ignite Data Ltd requires HES Critical Care (CC) data to accurately ascertain the level of Healthcare Resource Utilisation (HRU) during hospitalisation. Although these are a subset of admitted patient care episodes, critical care is associated with a higher cost. These data are required for example, to ascertain the number of days of advanced respiratory support for patients ventilated in critical care during an admission for COPD exacerbation.

HES Accident and Emergency (A&E) data is required to understand any serious events which resulted in attendance at the emergency department but did not result in admission to hospital. Without these data the study team would not be able to, for example, ascertain episodes of treatment associated with attendance at A&E for acute exacerbations of Chronic obstructive pulmonary disease (COPD), where the patient is seen in A&E without admission. HES Admitted Patient Care (APC) data is required to ascertain any serious events which resulted in admission to hospital – for example – severe COPD or Asthma exacerbations and other comorbidities; HRU/cost. HES Out Patients (OP) data is required to ascertain secondary care treatment and outcomes, for example, outpatient respiratory clinic appointments where the patient has been referred to the respiratory physician by their GP and associated cost/HRU of this treatment.

The data provided has been linked against each consented participants’ Randomised Control Trial (RCT) data via their unique Study ID. Only this pseudonymised dataset will be provided to GSK by Ignite Data Ltd for analysis. Ignite Data Ltd will destroy the date they hold after processing has been completed. As this data is being linked to an RCT dataset and then viewed prospectively for the next few years, only the years relevant to the study period are being requested. If the number of years are reduced any further it will not be possible to complete any beneficial analysis as the dataset would no longer match the study timeline or provide the depth of information required to study the desired outcomes.

The data has been narrowed by geography due to the fact that the consented patient list only contains patients from specific English research sites. Due to the condition, all patients will live within a reasonable commute of each study site. As the study is a consented and recruited cohort it is not possible to further minimise by demographic information any further. The data cannot be narrow by clinical factors as without data relating to events outside of the main study condition, Ignite Data Ltd and GSK will not be able to understand all cause HRU.

Patient episodes are required to achieve the study purpose. The patients have consented to GSK having access to relevant data in their whole medical record, only then can the study team truly get a picture of their disease history, its treatment and progression historically and during the prospective period of the study. Elective episodes are also required as without data relating to events outside of the main study condition GSK will not be able to understand all cause HRU. Maternity episodes are not required for analysis.

There is a timeframe around the index event required because without the dates relating to events, GSK will not be able to determine whether events occur after the patient’s entry into the study and before study end, therefore during that individual patient’s follow up. The study team will also not be able to determine the pattern or treatment and relevant measures contributing to a developing picture of a patient’s disease progression or management. Further, although record identifiers can be used to link episodes of care into spells, associating spells into super-spells of care (when patients may receive care from more than one hospital or trust) requires dates of admission and discharge.

Not all the fields within the HES APC, A&E and CC dataset are required. Only the specific fields required, which have been reviewed by GSK epidemiologist have been selected.

For linkage, the data will only be linked to the RCT cohort for the analysis set out in this application. As previously described the dataset is minimised by the recruited study cohort and all episodes on the patients are required to determine all cause HRU.

The data is being processed under General Data Protection Regulation Article 6 (1) (f) Legitimate interests as this is for the benefit of science and public health. Processing the NHS Digital data will enable us to address specific research questions relating to asthma and COPD including advances in general knowledge of COPD and asthma disease risk and treatment that may alter how clinicians care for their patients and raise awareness of the burden of these on patients and the wider health system. Insight into the longer-term burden of COPD and Asthma (which are common chronic respiratory conditions which place a high burden on patients and society) would be beneficial to the wider medical science community including medicines developers and healthcare providers.

As special category data, the data is further being processed under article 9(2)(j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). This is because the consented data will be used to enhance the potential outcomes and improve care, which is in the public interest.

Outputs for the Extended-SLS will include a series of reports, conference abstracts (international and UK conferences including: European Respiratory Society, British Thoracic Society, ISPOR, etc) and published manuscripts in peer-reviewed journals on COPD/asthma disease risk, treatment and progression.

GSK is committed to sharing results of impactful research with the wider scientific community and all research evaluating a medicine, providing important scientific knowledge, and/or which has relevance for patient care is published externally (and on our GSK Study Register: https://www.gsk-clinicalstudyregister.com/) in line with their policies.

The first publication and piece of research they intend to conduct using the Extended-SLS cohort is a descriptive analysis , comparing participants in the Extended-SLS with those in the original SLS. The analysis using SLS trial data, Extended-SLS GP data and Extended-SLS data from the disease-specific questionnaires has been completed and is being developed as a manuscript. An abstract on the Extended-SLS study, including results from this initial analysis was presented at the European Respiratory Society congress in September 2020. Once HES data are available, the Extended-SLS cohort will be further described using HES data. Additional outputs of the Extended-SLS, including reports, presentations, manuscripts, etc. will be determined once recruitment into the Extended-SLS study has completed. Three studies that are proposed to begin from 2021 will explore specific questions relating to asthma control, moderate exacerbations of asthma, and use of ‘maintenance and reliever therapy’ regimens in asthma patients in Ext -SLS, with conference abstracts and publications planned.

**GSK have contracted with Adelphi Real World to address 3 research questions using the Extended-SLS data, in the form of 3 studies, the research is described briefly below:

Study 1: Whilst numerous studies have described the clinical and economic burden of severe asthma exacerbations, very few studies have investigated the concept of moderate asthma exacerbations. Defining moderate asthma exacerbations in electronic medical records (EMR) and administrative claims databases is challenging. A consequence is that the information currently available on the burden posed on the patients and the healthcare system by moderate exacerbations is limited. Our project intends to quantify the frequency and burden of moderate exacerbations in asthma, using our bespoke research cohort which includes patient-reported data on moderate exacerbation frequency.

Study 2: Despite awareness regarding asthma control and advances in treatment, asthma control remains sub-optimal worldwide. Aim is to describe the burden of uncontrolled asthma in patients using ICS/LABA. As such, a key target of our research is to generate real world data from the UK on the clinical and health system (healthcare-resource utilisation, HCRU) burden in patients inadequately controlled whilst treated with ICS/LABA.

Study 3: ICS/LABAs are typically prescribed in asthma as daily maintenance therapies. In the UK, two ICS/LABAs (budesonide/formoterol [Symbicort] and beclometasone/formoterol [Fostair]) are available as daily maintenance therapies, but can also be prescribed as ‘maintenance and reliever therapy’ (MART) regimens. MART dosing or regimens are administered as a directed number of inhalations daily, plus additional as-needed reliever doses – additional reliever therapy with SABA is unnecessary. A key aim of this project is to improve our understanding of how patients are using their ICS/LABA therapy, correctly or incorrectly, whether as maintenance or ‘Maintenance and Reliever Therapy’ (MART), by describing how often patients are initiating changes in the dose or frequency of their maintenance therapy. The outputs will be shared with the research community through presentation at scientific and medical congresses and via publication in scientific journals. **

The audiences for outputs of the wider Extended-SLS will predominantly include researchers, scientists, and clinicians. GSK plan to disseminate information to Extended SLS participants throughout the lifecycle of the study via newsletters to GP sites. Information will need to be disseminated via GPs as GSK does not have access to participants names, addresses or email.

Any published results would contain data which has been aggregated with small number suppression applied as per the HES Analysis Guide to ensure privacy is maintained. All data in outputs will be published in-line with GSK policies.

In accordance with GSK’s internal policy, all trial results will be shared, regardless of whether they reflect positively or negatively on GSK’s medicines. GSK posted information about the EX-SLS study on a publicly accessible register (ClinicalTrials.Gov) before it started and will update it with a result summary after the study is finished. GSK seek the publication of all results of all clinical trials in peer-reviewed scientific journals and the EX-SLS study and any relevant result found as part of the data processing activities in this application will be no different.

Within a year of data receipt, and during the lifetime of the study, there will be multiple outputs: GSK's aim is to provide updates to annual scientific conferences/congresses as the study progresses and to answer further disease specific questions generated by the research community inside and external to GSK.

The outputs of this study aim to support the below listed benefits by looking at the range of benefits for COPD and asthma patients and HCPs as below:

- Identifying what other factors are associated with diagnosis of early COPD. This will increase understanding of groups at higher risk for developing COPD and who may benefit from increased monitoring/ alternative treatment paradigm or disease management

- Identifying what triggers a COPD diagnosis, e.g. are there particular events that lead to a initial diagnosis of COPD? This will improve understanding of presenting events which often suggest a COPD diagnosis; improved patient diagnosis.

- To aim to describe patient progression from diagnosis to therapy with a long-acting bronchodilator (LABD) to triple therapy (comprising an ICS, a LABA and a long-acting muscarinic antagonist [LAMA]), and describe factors associated with this progression, including the role of potential clusters of comorbid conditions. This will mean patient treatment pathways can assist in identifying subgroups of patients which may be over/under treated based upon their symptoms and COPD profile.

None. GSK are waiting for the chosen analytics partner to be approved as a data processor to this agreement.

GSK took a decision to outsource the analysis to Adelphi Real World, a GSK trusted partner organisation, who will being helping GSK to answer 3 research questions:

Study 1: Whilst numerous studies have described the clinical and economic burden of severe asthma exacerbations, very few studies have investigated the concept of moderate asthma exacerbations. Defining moderate asthma exacerbations in electronic medical records (EMR) and administrative claims databases is challenging. A consequence is that the information currently available on the burden posed on the patients and the healthcare system by moderate exacerbations is limited. Our project intends to quantify the frequency and burden of moderate exacerbations in asthma, using our bespoke research cohort which includes patient-reported data on moderate exacerbation frequency.

Study 2: Despite awareness regarding asthma control and advances in treatment, asthma control remains sub-optimal worldwide. Aim is to describe the burden of uncontrolled asthma in patients using ICS/LABA. As such, a key target of our research is to generate real world data from the UK on the clinical and health system (healthcare-resource utilisation, HCRU) burden in patients inadequately controlled whilst treated with ICS/LABA.

Study 3: ICS/LABAs are typically prescribed in asthma as daily maintenance therapies. In the UK, two ICS/LABAs (budesonide/formoterol [Symbicort] and beclometasone/formoterol [Fostair]) are available as daily maintenance therapies, but can also be prescribed as ‘maintenance and reliever therapy’ (MART) regimens. MART dosing or regimens are administered as a directed number of inhalations daily, plus additional as-needed reliever doses – additional reliever therapy with SABA is unnecessary. A key aim of this project is to improve our understanding of how patients are using their ICS/LABA therapy, correctly or incorrectly, whether as maintenance or ‘Maintenance and Reliever Therapy’ (MART), by describing how often patients are initiating changes in the dose or frequency of their maintenance therapy.

Adelphi Real World are being added as a processor to this agreement to allow them to receive the relevant data for these analyses so this analysis cannot proceed until this process is completed.

BACKGROUND

The Extended-SLS is a follow-on study to the Salford Lung Studies (SLS), two landmark effectiveness trials of fluticasone furoate / vilanterol (an inhaled corticosteroid combined with a long-acting-b2-agonist [LABA] in a single inhaler device) in patients with Chronic Obstructive Pulmonary Disease (COPD) (NCT01551758) and asthma (NCT01706198) which ran from March 2012 to December 2016.

The SLS subjects represent patient cohorts that are extremely well-characterised over a short period of their COPD/asthma disease experience. Subjects in the SLS originally consented for information relevant to the study to be shared with the sponsor, GlaxosmithKline Research & Development Limited (referred to in this application as GlaxosmithKline or GSK), and these data were limited to three years prior to randomisation and the twelve-month interventional treatment period. This finite period of data coverage limits the potential to address scientific questions of clinical interest related to long-term COPD/asthma disease progression and associated outcomes (for example, mortality). Broadened access to patients’ data would allow SLS subjects’ entire disease journey to be researched, presenting a rare opportunity to use epidemiological research to improve scientific and clinical understanding of COPD/asthma disease risk, treatment and progression.

The Extended-SLS seeks to broaden capture of SLS patients’ data through the collection of additional subject-level data encompassing past and periodic future (up to 10 years duration from the date of consent) demographic, COPD/asthma risk factors and healthcare-related information from both primary and secondary care, resulting in the creation of the Extended-SLS cohort. Additional patient reported data on early life exposures, impact of disease on sleep, smoking history and other information not typically available from electronic medical records (EMR) will be captured using disease-specific questionnaires. Secondary care data on hospital admissions and attendances available in NHS Digital’s Hospital Episode Statistics (HES) data are crucial to understanding and researching hospitalised exacerbation's of COPD/asthma, comorbidity, long-term safety of COPD and asthma therapies, and healthcare resource utilisation.

The Extended-SLS has three organisations involved in the work but only GSK and Ignite are involved in the processing of the HES being requested in this application:

• GlaxosmithKline (GSK): The sponsors of the original SLS and the Extended-SLS. GSK wish to receive the final pseudonymised cut of study data, including the HES data provided by NHS Digital. GSK are a data controller and a data processor in this study. GSK is an international pharmaceutical company and the relevant GSK party for this agreement is a company registered in England and Wales. GSK produces drugs directly relevant to the ailments being studied and holds the international patent to one of the drugs specifically referred to in this agreement.

• Ignite Data (Ignite): The contracted research company looking after site management, patient consent and data processing. Ignite will have the explicit consent of Participants for bringing together multiple different data sources captured on each individual study volunteer, specifically including the consent of patients to process their HES and mortality data. Note patients provided consent for use of mortality data; however, this application is not requesting ONS mortality data.

• Graphnet Health (Graphnet): The general practitioner (GP) extract provider for the study. Graphnet currently have active data sharing agreements with every GP who is participating in the study for direct care and hold Data Security and Protection (DSP) Toolkit. Study specific agreements exist with each individual GP giving Graphnet permission to extract consented Participant data for this study only. Graphnet will not be in receipt of any HES data provided to Ignite Data by NHS Digital. Graphnet are not directly involved with this application but are a source of the main study data set.

Hospital Episode Statistics will be used to form a longitudinal patient record that GSK wish to build over the lifetime of the study. HES data supplied to Ignite Data and GSK are essential to answer questions in the Extended-SLS relating to:

• Healthcare resource utilisation and costs (HRG); primary care electronic medical records do not accurately and reliably capture complete information about hospital attendances and admissions and therefore cannot inform on the full spectrum of healthcare resource utilisation.

• Severe exacerbation's of COPD and asthma; these are defined, according to global standards, as exacerbation's requiring hospital admission (asthma and COPD) and exacerbation's requiring emergency care (asthma), validation studies demonstrate that severe exacerbation's are not adequately recorded in primary care EMR.

• Frailty and disease severity defined based on prior hospitalisations (all-cause) and comorbidities not managed in primary care.

• Potential, treatment-related adverse events resulting in hospitalisation.

• Impact of treatments and/or disease severity/subtypes on all-cause or COPD- and asthma- related mortality; primary care.

(HRG is analysed using the latest publicly available National Cost Collection:

https://improvement.nhs.uk/resources/national-cost-collection/)

The number of study participants in England in the SLS who have consented onto the study is currently 1,183, with those consenting for NHS Digital sharing their data being 1,121. This is an ongoing study and Ignite Data Limited estimate the cohort to be 1,300 individuals. All participants are 18 years or older. Each study participant has a current diagnosis of COPD or asthma and was previously enrolled on to RCT (Randomised Controlled Trial) known as the Salford Lung Study. Each individual participant was recruited via the SLS study site, which in every case was their local GP. The GP Practices were selected from the Greater Manchester Region based on the fact they had participated in the original Randomised Control Trial (RCT).

GSK and Ignite Data have many questions that can potentially be answered as a result of learnings from the study. Within GSK’s COPD and Asthma disease areas, these data may help to identify other key areas for GSK to focus their medicines development.

By linking NHS Digital’s HES data to the data already held from the SLS study for patients in the Extended-SLS cohort (primary care EHR, disease-specific patient-completed questionnaires, and the SLS trial data), GSK and Ignite Data hope to address a range of research questions. Without access to HES data GSK and Ignite Data will not be able to answer any research questions where data on severe asthma or COPD exacerbations are required as these important adverse outcomes of asthma and COPD can only be reliably identified using discharge data from hospitals. Furthermore, GSK and Ignite Data will not be able to describe the full societal burden of these conditions without access to HES Admitted Patient Care (APC), Accident and Emergency (A&E) and Outpatient (OP) data as these are important sources of health-care resource utilization in asthma and COPD.

Research questions which GSK and Ignite Data cannot fully answer without access to the HES data include:

• Identifying which specific patient and disease traits can be used to guide clinician’s choice of treatment.

• Identifying what impact biomarkers (eosinophils, fibrinogen, etc.) have on (a) the risk of asthma and COPD exacerbations and (b) the risk of pneumonia.

• How patients progress from diagnosis to particular treatments, and if there are factors associated with this progression, e.g. potential clusters of comorbid conditions.

• Identifying if there is a relationship between events pre-COPD or pre-asthma diagnosis (respiratory infections, comorbidities, healthcare-resource utilisation patterns, smoking and body mass index [BMI] dynamic changes) and natural history of COPD and asthma disease progression?.

• Identifying how smoking status modulate or predict disease trajectory in COPD.

• How healthcare resource utilisation differs in patients with and without exacerbations.

• Examining the effect of asthma onset (early vs late onset) on longitudinal healthcare utilisation and asthma management.

• Long term symptom control, adherence and outcomes (e.g. exacerbations) for asthma patients using specific treatments.

• Investigation of sentinel events (e.g. exacerbations, a prescription of antibiotics or prednisolone) trigger a change in management and investigate what the health care is after a sentinel event.

DATA MINIMISATION

Ignite Data Ltd requires HES Critical Care (CC) data to accurately ascertain the level of Healthcare Resource Utilisation (HRU) during hospitalisation. Although these are a subset of admitted patient care episodes, critical care is associated with a higher cost. These data are required for example, to ascertain the number of days of advanced respiratory support for patients ventilated in critical care during an admission for COPD exacerbation.

HES Accident and Emergency (A&E) data is required to understand any serious events which resulted in attendance at the emergency department but did not result in admission to hospital. Without these data the study team would not be able to, for example, ascertain episodes of treatment associated with attendance at A&E for acute exacerbations of Chronic obstructive pulmonary disease (COPD), where the patient is seen in A&E without admission. HES Admitted Patient Care (APC) data is required to ascertain any serious events which resulted in admission to hospital – for example – severe COPD or Asthma exacerbations and other comorbidities; HRU/cost. HES Out Patients (OP) data is required to ascertain secondary care treatment and outcomes, for example, outpatient respiratory clinic appointments where the patient has been referred to the respiratory physician by their GP and associated cost/HRU of this treatment.

The data provided has been linked against each consented participants’ Randomised Control Trial (RCT) data via their unique Study ID. Only this pseudonymised dataset will be provided to GSK by Ignite Data Ltd for analysis. Ignite Data Ltd will destroy the date they hold after processing has been completed. As this data is being linked to an RCT dataset and then viewed prospectively for the next few years, only the years relevant to the study period are being requested. If the number of years are reduced any further it will not be possible to complete any beneficial analysis as the dataset would no longer match the study timeline or provide the depth of information required to study the desired outcomes.

The data has been narrowed by geography due to the fact that the consented patient list only contains patients from specific English research sites. Due to the condition, all patients will live within a reasonable commute of each study site. As the study is a consented and recruited cohort it is not possible to further minimise by demographic information any further. The data cannot be narrow by clinical factors as without data relating to events outside of the main study condition, Ignite Data Ltd and GSK will not be able to understand all cause HRU.

Patient episodes are required to achieve the study purpose. The patients have consented to GSK having access to relevant data in their whole medical record, only then can the study team truly get a picture of their disease history, its treatment and progression historically and during the prospective period of the study. Elective episodes are also required as without data relating to events outside of the main study condition GSK will not be able to understand all cause HRU. Maternity episodes are not required for analysis.

There is a timeframe around the index event required because without the dates relating to events, GSK will not be able to determine whether events occur after the patient’s entry into the study and before study end, therefore during that individual patient’s follow up. The study team will also not be able to determine the pattern or treatment and relevant measures contributing to a developing picture of a patient’s disease progression or management. Further, although record identifiers can be used to link episodes of care into spells, associating spells into super-spells of care (when patients may receive care from more than one hospital or trust) requires dates of admission and discharge.

Not all the fields within the HES APC, A&E and CC dataset are required. Only the specific fields required, which have been reviewed by GSK epidemiologist have been selected.

For linkage, the data will only be linked to the RCT cohort for the analysis set out in this application. As previously described the dataset is minimised by the recruited study cohort and all episodes on the patients are required to determine all cause HRU.

The data is being processed under General Data Protection Regulation Article 6 (1) (f) Legitimate interests as this is for the benefit of science and public health. Processing the NHS Digital data will enable us to address specific research questions relating to asthma and COPD including advances in general knowledge of COPD and asthma disease risk and treatment that may alter how clinicians care for their patients and raise awareness of the burden of these on patients and the wider health system. Insight into the longer-term burden of COPD and Asthma (which are common chronic respiratory conditions which place a high burden on patients and society) would be beneficial to the wider medical science community including medicines developers and healthcare providers.

As special category data, the data is further being processed under article 9(2)(j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). This is because the consented data will be used to enhance the potential outcomes and improve care, which is in the public interest.

Outputs for the Extended-SLS will include a series of reports, conference abstracts (international and UK conferences including: European Respiratory Society, British Thoracic Society, ISPOR, etc) and published manuscripts in peer-reviewed journals on COPD/asthma disease risk, treatment and progression.

GSK is committed to sharing results of impactful research with the wider scientific community and all research evaluating a medicine, providing important scientific knowledge, and/or which has relevance for patient care is published externally (and on our GSK Study Register: https://www.gsk-clinicalstudyregister.com/) in line with their policies.

The first publication and piece of research they intend to conduct using the Extended-SLS cohort is a descriptive analysis , comparing participants in the Extended-SLS with those in the original SLS. The analysis using SLS trial data, Extended-SLS GP data and Extended-SLS data from the disease-specific questionnaires has been completed and is being developed as a manuscript. An abstract on the Extended-SLS study, including results from this initial analysis was presented at the European Respiratory Society congress in September 2020. Once HES data are available, the Extended-SLS cohort will be further described using HES data. Additional outputs of the Extended-SLS, including reports, presentations, manuscripts, etc. will be determined once recruitment into the Extended-SLS study has completed. Three studies that are proposed to begin from 2021 will explore specific questions relating to asthma control, moderate exacerbations of asthma, and use of ‘maintenance and reliever therapy’ regimens in asthma patients in Ext -SLS, with conference abstracts and publications planned.

The audiences for outputs of the wider Extended-SLS will predominantly include researchers, scientists, and clinicians. GSK plan to disseminate information to Extended SLS participants throughout the lifecycle of the study via newsletters to GP sites. Information will need to be disseminated via GPs as GSK does not have access to participants names, addresses or email.

Any published results would contain data which has been aggregated with small number suppression applied as per the HES Analysis Guide to ensure privacy is maintained. All data in outputs will be published in-line with GSK policies.

In accordance with GSK’s internal policy, all trial results will be shared, regardless of whether they reflect positively or negatively on GSK’s medicines. GSK posted information about the EX-SLS study on a publicly accessible register (ClinicalTrials.Gov) before it started and will update it with a result summary after the study is finished. GSK seek the publication of all results of all clinical trials in peer-reviewed scientific journals and the EX-SLS study and any relevant result found as part of the data processing activities in this application will be no different.

Within a year of data receipt, and during the lifetime of the study, there will be multiple outputs: GSK's aim is to provide updates to annual scientific conferences/congresses as the study progresses and to answer further disease specific questions generated by the research community inside and external to GSK.

The outputs of this study aim to support the below listed benefits by looking at the range of benefits for COPD and asthma patients and HCPs as below:

- Identifying what other factors are associated with diagnosis of early COPD. This will increase understanding of groups at higher risk for developing COPD and who may benefit from increased monitoring/ alternative treatment paradigm or disease management

- Identifying what triggers a COPD diagnosis, e.g. are there particular events that lead to a initial diagnosis of COPD? This will improve understanding of presenting events which often suggest a COPD diagnosis; improved patient diagnosis.

- To aim to describe patient progression from diagnosis to therapy with a long-acting bronchodilator (LABD ) to triple therapy (comprising an ICS, a LABA and a long-acting muscarinic antagonist [LAMA]), and describe factors associated with this progression, including the role of potential clusters of comorbid conditions. This will mean patient treatment pathways can assist in identifying subgroups of patients which may be over/under treated based upon their symptoms and COPD profile.

Yielded Benefits is not a requirement for new applications.