NHS Digital Data Release Register - reformatted

IQVIA Ltd

🚩 IQVIA Ltd received multiple files from the same dataset, in the same month, both with optouts respected and with optouts ignored. IQVIA Ltd may not have compared the two datasets, but the identifiers are consistent between datasets for the same recipient, and NHS Digital does not know what their recipients actually do.

Project 1 — DARS-NIC-373563-N8Z9J

Opt outs honoured: No - data flow is not identifiable (Does not include the flow of confidential data)

Sensitive: Non Sensitive, and Sensitive

When: 2016/09 — 2020/07.

Repeats: Ongoing

Legal basis: Health and Social Care Act 2012, Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii)

Categories: Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Outpatients
  • Hospital Episode Statistics Accident and Emergency
  • Hospital Episode Statistics Admitted Patient Care
  • Emergency Care Data Set (ECDS)
  • HES:Civil Registration (Deaths) bridge
  • Civil Registration - Deaths

Objectives:

IMS Health is a brand comprised of a number of legal entities which provide technology and services to healthcare. This application/agreement is a request for pseudonymised record-level HES data which will be controlled by two legal entities: • IMS Health TS • IMS Health UK ltd Hereafter, these two entities will be referred to collectively as IMS Health. IMS Health will use the HES data to perform two types of service: 1. Data visualisation and benchmarking tools which includes: i) Care Pathway Analyser (formerly visualise treatment pathways) ii) Hospital Feedback services iii) Visualise Healthcare Data 2) Advanced Statistical Analysis (formerly referred to as structured disease analysis) It should be noted that these services have been renamed from the previous application. 1) The data visualisation and benchmarking tools are described below: • Care Pathway Analyser (CPA). Presents users with simple views of aggregated care pathways. This allows investigation of the causes of variation in patient pathways and the subsequent impact on service delivery. • Hospital Feedback Services (HFS). A dashboard allowing chief pharmacists to optimise their use of medicines. It will also allow them to monitor their own performance against internal targets and benchmark against similar hospitals. This service is still in development. • Visualise Healthcare Data (VHD). A suite of tools/reports that allows users to perform queries on aggregated HES data then view graphs and tables. 2) Advanced Statistical Analysis includes: diagnostic algorithm development, epidemiology, health economics and outcomes research studies. Both services will only be provided to the following categories of types of organisation: - Providers of healthcare services • Clinical Commissioning Groups • Commissioning Support Units (CSU’s) • Hospital Trusts • Private secondary care providers • Mental Health trusts • Community Provider Trusts • Pharmacies • NHS England • Public Health England • Health and Wellbeing Boards - Universities - Life science industry • Pharmaceutical companies • Medical Device companies • Industry bodies – limited to the Association of the British Pharmaceutical Industry (ABPI), Ethical Medicines Industry Group (EMIG) and the Proprietary Associated of Great Britain (PAGB) Third parties will only see aggregated and small number suppressed data. The number of organisations to whom IMS Health provide products and services changes regularly. In the year to date IMS Health have worked on 31 Advanced Statistical Analysis projects and Data Visualisation and Benchmarking services using HES data held under this DSA. Of these projects, approximately half were for repeat customers (who had purchased at least one other tool or project from IMS Health within that period). When finalised, HFS will be given to all NHS Trusts. IMS Health understands the importance of data minimisation and outline IMS Health’s requirement for national, timely HES data in the following paragraphs. IMS Health requires national data to enable the end users of IMS Health’s tools to benchmark against organisations in their local area or with similar demographic characteristics. IMS Health also requires national data to inform economic analyses for inclusion in submissions to NICE, which makes decisions at a national level. HFS is intended for all chief pharmacists in NHS Trusts. The requirement for timely data is because the commissioners and providers to whom IMS Health provide IMS Health’s tools need to make decisions based on the most up-to-date information. IMS Health won an open tender to perform a medicines optimisation study for a group of cancer treatment providers. More detail on this project is given in later sections. Historic data is required to support Advanced Statistical Analysis projects, as historical data allows robust analysis of trends over time.

Yielded Benefits:

Examples of how previous projects have provided benefit to patient care are given below. Cancer Vanguard Medicines Optimisation Project IQVIA supported the NHS Cancer Vanguard (The Christie, UCLH and Royal Marsden NHS Foundation Trusts) to optimise the care and use of medicines for mCRC (Metastatic Colorectal Cancer) patients, whilst reducing the unnecessary variation in patient care. IQVIA used Advanced Statistical Analysis and the Care Pathway Analyser tools to deliver this project, involving a review of medicines usage at each centre and identification of avoidable variation in episodes of care. The output was a model to reduce the cost of treating cancer to ensure clarity around best practice processes. Patient reported outcomes also ensured that the relationship between best practice and improvement in patients’ quality of life is quantified. The analysis was developed alongside chief pharmacists and associated clinical teams with results shared with healthcare professionals in a way that allowed them to improve patients’ quality of life in a cost-effective manner. More information about the Cancer Vanguard can be found here - http://cancervanguard.nhs.uk/about/. Multi-Hospital Site DVT Treatment Variation Project Since their introduction novel oral anticoagulants (NOACS) have not experienced the uptake anticipated following their NICE recommendation. By utilising these new compounds, the NHS can alter the way Deep Vein Thrombosis (DVT) treatment pathways are delivered. The goals of this partnership project were: • Understand how DVT is currently treated (nationally utilising HES data assets) • Compare how individual Trusts treat patients with DVT Nationally and within Benchmark Trusts • Quantify the potential financial implications associated with a change in DVT treatment pathway • Outline potential change tactics and key messages that could be aligned to a shift in treatment approach The National analysis presented key observations associated with the current clinical management of DVT. DVT hospital treatment is resource intensive placing scarce hospital resources under further pressure with variation in current care pathways. Findings uncovered from the study identified key drivers that all impact on the financial sustainability of local DVT services. The choice of clinical pathway will impact on Trust financial performance, working with key stakeholders to implement alternative pathways can mitigate financial risk. A key outcome of the work presented to representatives from 90 UK Trusts was the need to understand how the clinical strategy adopted by a Trust can impact the level of financial risk the Hospital is exposed to. Greater Manchester Liver Disease Working with key NHS, academic and professional bodies from the Greater Manchester region IQVIA presented an overview of how liver disease, defined by a cohort of ICD.10 diagnosis codes, was currently being managed across the region. This overview of liver disease treatment pathways was delivered utilising National HES data assets with National Care Pathway Analytics technology deployed over the data. This provided IQVIA with treatment pathway visualisation at Clinical Commissioning Group level showing aggregated treatment pathway volumes, the cost associated with these pathways, the typical length of stay and the average number of treatment events per pathway. Isolating key performance indicators by each of the 12 Greater Manchester CCG’s highlighted the variation in both clinical management of the disease area, and the cost and capacity implications of that variation. A key outcome of the work will be the utilisation of the analysis to improve and standardise the management of patients’ within this disease cohort. Salford Royal Hospital – Unwarranted treatment pathway variation IQVIA presented the National Care Pathway Analytics solution (NCPA - based on care pathway technology applied to HES data assets) solution to Salford Royal NHSFT. However, when demonstrating the NCPA solution to the Trust, the Trust commented that; NCPA, provided an insight into the performance of Salford Royal NHSFT and allowed them to benchmark against other Trusts both nationally and within the Greater Manchester region and identified that there was an issue. In order to investigate further and allow for real change, deeper analysis on local Trust data, taking in additional datasets not available in HES was required. However without the initial NCPA analysis, these issues may have gone unnoticed. Instead of individual “APC – Admitted Patient Care Events” the Trust would ideally want to see more detailed event level granularity within the ‘hospital stay’ part of the treatment pathway, i.e. visualisation of a daily activity breakdown of the patients’ treatment The Trust have developed for 2017/18 a local programme between the ‘Better Care Lower Cost – BCLC’ team and ‘Quality Improvement - QI team’. The programme would utilise QI methodologies to be used on local projects which would benefit from this approach. The BCLC and QI teams are developing a 90-day cycle approach to service review with a view to identifying 10% gains in both quality and efficiency. Trust senior directors invited IQVIA to develop Care Pathway technology to support them in the delivery of this local improvement initiative. Because of the utilisation of National HES data delivered to the Trust in a unique and creative way has led to the development and delivery of a detailed local project that can enable the Trust to support the identification and reduction of unwarranted variation in patient treatment pathways. Outcome – Delivered to Client, Acute Care Pathway Analytics product that will enable and support the delivery of a reduction in clinical variation, improving Length of Stay (LOS), increase profitability and deliver improved operational efficiency UCLH – Trauma & Orthopaedics Clinical Productivity This Clinical Productivity Pilot aimed to understand the causes of clinical variation in the provision of T&O services at UCLH, using a combination of benchmarking (HES data), and “deep dive” analytical capabilities that IQVIA tested with Trust members including operational, financial and clinical stakeholders. From an overall analysis of clinical variation across the T&O speciality, knee replacement and hip replacement represented some of the biggest opportunities to reduce length of stay. To fully understand how actionable and feasible these opportunities were to the Trust, a detailed analysis around knee replacement elective procedures was completed. The results of the analysis into knee replacement indicated that: • Some of the LOS variation that could be reduced are patients that are currently being discharged on Thursdays and Fridays. Patients characteristics (including complexity measures) between key consultants is indicated to be comparable. Data highlighted that key consultants operate on a specific day from Wednesday to Friday, generating three types of “pathways” to compare against. • Further emphasis in ward rounds/discharges during Wednesdays could be worth investigating further (most of the capacity gaps were isolated to this day). • By targeting only 20% of the potential opportunity, a reduction of 107 Bed Days across a year could be achievable. The main purpose of this work was to provide actionable insights and support discussions that the Trust might undertake for further service transformation involving the provision of T&O services. Going further, the same data assets, methodologies and approaches used in this pilot study were suggested to be used to identify potential opportunities in other specific procedures, or specialties to inform wider a case for change and improve further operational and clinical performance. Greater Manchester breast cancer service analysis, a joint working project led by the Christie NHS FT, Novartis and IQVIA The principle of this joint working project is that the Greater Manchester (GM) secondary breast cancer service could be optimised and perceived variations in access to treatment addressed if an analytical approach to pathway optimisation was conducted. This can be achieved through the analysis of data generated by routine delivery of care, in particular Hospital Episode Statistics, for breast cancer services in GM involving The Christie. The project consists of two components, pathway analysis and patient pathway experience. The project, due to conclude summer 2018, will provide a visual representation of the secondary breast cancer service in order to understand the variation of access to breast cancer services that exist to the people of GM and build a case for change that can be shared with operational healthcare leaders in the GM region. This project is based around partnership working and the collaborative sharing of insights and expertise between the Christie/Greater Manchester and Novartis, with the support of IQVIA, in order to optimise the treatment of secondary breast cancer within Greater Manchester.

Expected Benefits:

IMS operates on a project by project basis. Each project using this data source must generate benefit to healthcare, for example by: • Providing detailed evidence based recommendations for how to improve care in specific organisations or therapy areas • Giving healthcare professionals (HCPs) the ability to understand their own organisation’s performance via dashboards and reports; enabling them to reduce cost whilst delivering best practice care • Providing analyses to decision making bodies such as the European Medicines Agency and the National Institute for Health and Care Excellence; in order to enable them to grant patients access to innovative medicines • Contributing to knowledge to the medical community in order to stimulate further research into improving patient care Examples of how previous projects have provided benefit to patient care are given below. Developing diagnostic pathways in Fabry Disease: IMS Health developed a diagnostic algorithm for patients with Fabry disease. In current ICD-10 coding the 4 characters code (E75.2 other sphingolipidosis) encompasses 5 different diseases: Gocher disease, Krabbe disease, Niemann-Pick disease and Metachromatic leukodystrophy. Despite the similarities in disease genesis the symptoms, treatment pathways, procedures and prognosis are different. By identifying the actual underlying disease patient would be put on the correct treatment pathway more quickly and better managed their condition. The project involved working with Lysosomal storage disorder (LSD) clinical experts to understand the different diseases, the epidemiology and the diagnosis and treatment pathway. Clinicians then worked with IMS to identify inclusion and exclusion criteria for Fabry disease based on the specialties visited by the patient, associated diagnosis codes (ICD-10 codes), procedures and treatments performed (OPCS codes), and LSD specialty centres visited (key specialist centres). The team also divided some of the variables by age of the patients to define patients for disease that typically affect certain age groups. The output was a logic-based algorithm which could be used to identify Fabry disease patients in routine clinical practice. This project was completed in March 2016, the expected benefit is an improvement in the speed and accuracy of Fabry disease diagnoses. Analysis and validation of musculoskeletal services for the NHS and Care UK: Working with Aylesbury Vale CCG, Chiltern CCG, Buckinghamshire NHS Trust & Care UK, IMS Health modelled the level of service in changing environments over the next five-year period in order to improve their long-term planning process. The analysis used HES data plus data supplied from 8 CCGs. The IMS Health team designed interventions to make the service more efficient and compiled forecasts to show the impact of these interventions on the forecast. The analysis was initially summarised in a presentation but subsequently delivered as dashboard that allowed the clients to model and understand the impact of pursuing different strategies for transformation and therefore inform decision making. For example, the model predicted that reducing the rate of inpatient spells with excess bed days had a low impact on overall MSK spend; however, reducing the rate of inpatient spells where the patient had complications or comorbidities or moving outpatient appointments to the community had a much greater potential to increase efficiency. The research proposal for this project was submitted in October 2014. The final analysis was delivered in February 2016. The expected benefit is that this tool will allow HCPs to understand how to deliver more effective cost saving programmes. Patient profiling and pathway analysis for University Hospital South Manchester: In response to a requirement from a senior clinician at the University Hospital of South Manchester (UHMS), IMS performed an exploratory analysis using VHD in pneumonia and cellulitis. In both diseases, the analysis showed that more than half of all admissions were in patients from the most deprived 20% of neighbourhoods. The analysis went on to benchmark UHSM against its peers and found it had the third highest readmissions ratio in the region. The UHSM project also included analysis of patient pathways. The analysis found that the average pneumonia pathway was 69% longer than the national average and cost the NHS 37% more. Further analysis showed 38% of pneumonia pathways in Manchester contained at least one COPD-related event; this was 10 percentage points more than the national average. On average, this group of pathways was more expensive and longer than the group without a recorded COPD event. The results of this work were presented to the Trust in February 2016. The Trust expects to reduce costs and improve patient outcomes by applying best practice from Trusts with a similar case mix. Analysis of cardiology pathways for the Heart of England NHS Foundation Trust: CPA and VHD were used to review the cardiology services in the Heart of England Foundation Trust. The analysis, combined with the Trust’s own data, aimed to improve the efficiency of care. The analysis was presented at various stages to a team from the Trust in early 2016. Following on from the analysis, IMS Health recommended providing care based on clusters of procedures as this would allow the Trust to monitor consistency more closely and improve demand forecasting. IMS Health expects that this analysis will allow the Trust to improve care by being better prepared for demand for cardiology services. Using CPA to streamline hip replacement pathways in Cambridge and Peterborough CCG: CPA in combination with HES and the CCG’s own local activity data was used to establish a gold standard pathway in Cambridgeshire and Peterborough for four providers in the region. Treatment pathway analysis and benchmarking against similar CCGs enabled them to envisage where the NHS’s Cost Improvement Programme (CIP) and the Quality, Innovation Productivity and Prevention (QIPP) programme could be delivered. In the words of the Local Chief Officer “IMS Health provided me the insight to see where CIP and QIPP could be delivered by commissioning shorter pathways in line with best practice” This work was presented in February 2016. The expected benefit is that this analysis will help HCPs deliver hip replacements safely and efficiently in line with best practice. Three further examples of projects under development and their expected benefits are: Cancer Vanguard Medicines Optimisation Project: IMS Health has won a tender with a group of NHS Trusts. The aim of the project is to optimise the use of cancer medicines and reduce the unnecessary variation in cancer care. IMS Health will use Advanced Statistical Analysis and the Care Pathway Analyser tool to deliver this project; it will involve a review of medicines usage in cancer, and identification of avoidable variation. The output will be a model to reduce the cost of treating cancer to ensure clarity around best practice processes. Patient reported outcomes will also ensure that the relationship between best practice and improvement in patients’ quality of life is quantified. This analysis is being developed alongside HCPs and the expected benefit is that the results will be presented back to HCPs in a way that will allow them to improve patients’ quality of life in a cost effective manner. Staffordshire CCGs and the Rightcare programme: IMS Health is working with the Director of Strategic Programmes for a group of CCGs including: Cannock and Chase CCG, Stafford and Surrounds CCG, South East Staffs and Seisdon Peninsula CCG. The Director would like to use CPA to support the implementation of the NHS Rightcare programme. The Director had the following to say about the initiative: “NHS Rightcare (http://www.rightcare.nhs.uk/) promotes the principle of eliminating unwarranted variation in healthcare. The IMS care pathway analysis tool allows commissioners and providers to see variation in care provided and benchmark compliance with best practice utilising national HES (Hospital Episode Statistics) data in conjunction with locally available data. It is therefore a potentially valuable tool in allowing commissioners and providers to redesign pathways to achieve high quality affordable care.” Hospital Feedback Services: IMS Health is committed to ensuring that the NHS chief pharmacists have accurate and up-to-date information in order to better manage their drug dispensing. The IMS medicines optimisation dashboard is designed to include IMS Health’s Hospital Pharmacy Audit data and National HES data. The ability to include HES data is a vital component in ensuring that the output accurately reflects the seasonal variation in hospital activity and medicines usage. For example, the antibiotic usage dashboard includes the following report: Ratio of Defined Daily Dose of all dispensed antibacterial (ATC J1) products per 1000 admissions. It is the HES data that ensures accuracy on the 1000 admissions and enables IMS Health to account for seasonal variation in the analysis. IMS Health will provide HFS to all hospital trusts. It is being designed in collaboration with the chief pharmacist community to ensure that it meets their needs. IMS Health expects HFS to benefit healthcare by allowing chief pharmacist to improve prescribing efficiency leading to a financial savings; it will also allow them to better forecast the amount of medicines required and therefore prevent waste:

Outputs:

For clarity services covered within this application only produce two types of output: • Dashboards • Aggregated tables In both cases outputs are aggregated and small numbers suppressed in line with the HES Analysis Guide. Details for each of the services are given below. Visualise Healthcare Data (VHD): VHD is an internet browser based application, an iPad application or a bespoke report. Users are given role based access to the applications. The applications allow users to produce graphical and tabular estimates of burden of disease, cost of care, common comorbidities and similar analyses. These analyses may be stratified by diagnosis, organisation and other similar parameters. Care Pathway Analyser (CPA): CPA is currently an internet browser based application and other delivery methods are in development. CPA will either be deployed directly to users or used to support consulting projects. In the former users are given role based access to the application which will allow them to analyse images of aggregated pathways. In the latter, outputs will be presentations and reports containing pathway images as well as IMS Health recommendations. Hospital Feedback Services (HFS): HFS will be delivered (expected in late 2016) as a browser-based application and other delivery methods are in development. Chief pharmacists will be given role-based access to a dashboard which will show them aggregated HES data, aggregated prescribing data and performance indicators. These data will be presented in graphs and tables. Advanced Statistical Analysis The data included in advanced statistical analysis are always aggregated and small number suppressed in line with the HES Analysis Guide. These outputs are produced to meet different objectives and delivered in different ways. A health economic analysis may require analysis of the data to estimate the cost of managing a given condition then used as an input in an economic model for a NICE submission. Developing a diagnostic algorithm will result in the production of a formula which may be presented to clinicians in an Excel based calculator with an explanatory report or presentation. Many of the outputs of advanced statistical analysis are reported in journal articles or conference presentations.

Processing:

IMS Health will receive the data from HSCIC and will apply derivations. No linkage is carried out to other datasets. In the context of this application/agreement applying derivations does not mean linking to other patient-level information. In this application/agreement, applying derivations means that IMS Health will use non-identifiable data to derive new information. For example, length of stay is approximated using the relationship between admission and discharge dates and the cost of an admission is approximated using the NHS payment by results tariff. For data visualisation and benchmarking services, further derivations are applied to allow benchmarking and the data is presented in dashboards alongside other IMS Health and publically available data sources e.g. Quality Outcomes Framework data. All data visualisation and benchmarking tools are hosted by IMS Health. All data seen by end users is aggregated, small number are suppressed and are compliant with the HES Analysis Guide. Usage of these tools is auditable and role based access controls are applied. Customers using these tools are contractually prevented from using the data for solely commercial purposes. For advanced scientific analysis, IMS Health produce bespoke analysis for external organisations on a project by project basis. All requests for bespoke analysis are subject to review by an independent scientific advisory committee (ISEAC – details in the following paragraph) who review the proposed study design. If ISEAC approves the study, it is logged on an access control register and the IMS Health researchers are allowed to access the relevant subset of HES data. The researchers will present the results of their analysis to external organisations in the form of aggregated, small number suppressed tables compliant with the HES Analysis Guide. These outputs may also take the form of counts, proportions or formulae. Anonymised abstracts will be published on the IMS Health global bibliography 6-12 months after completion of the study. ISEAC is a group of medical and scientific advisors who are independent of IMS Health. For studies based on the HES data held under this Data Sharing Agreement the role of the committee is to ensure that will ensure that any study performed is compliant with this Data Sharing Agreement and by extension the Care Act 2014. All ISEAC decisions are binding, and any studies not approved will not be performed unless revised and subsequently approved. ISEAC records of decisions can be made available to NHS Digital under the caveat that they remain commercial in confidence.


Project 2 — DARS-NIC-296034-T4Y4K

Opt outs honoured: Yes - patient objections upheld (Section 251 NHS Act 2006)

Sensitive: Non Sensitive

When: 2020/07 — 2020/07.

Repeats: One-Off

Legal basis: National Health Service Act 2006 - s251 - 'Control of patient information'.

Categories: Anonymised - ICO code compliant

Datasets:

  • Hospital Episode Statistics Admitted Patient Care
  • Hospital Episode Statistics Outpatients
  • Hospital Episode Statistics Accident and Emergency

Objectives:

Pulmonary Arterial Hypertension (PAH) (a type of Pulmonary Hypertension (PH)), is a progressive and rare disease caused by narrowing or tightening (constriction) of the pulmonary arteries. PAH primarily affects the small pulmonary arterioles through vascular proliferation and re-modelling, while resulting in a progressive rise in lung blood pressure and heart failure. PAH represents Group 1 (of 5) within the Pulmonary Hypertension World Health Organisation clinical classification system (Dana Point, 2008). In Europe, PAH prevalence and incidence are in the range of 15–60 subjects per million population and 5–10 cases per million per year, respectively. Furthermore, there are several types of PAH including Idiopathic PAH (iPAH) and Associated PAH related to a range of disease processes, including cirrhosis, connective tissue disease, congenital heart disease, HIV infection and sickle-cell disease In addition, there are other types of PH, including Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Sarcoidosis-Associated Pulmonary Hypertension (SAPH). CTEPH is caused by complications of acute Pulmonary embolism (PE), leading to an obstruction of the large pulmonary arteries and distal small-vessel arteriopathy, with an estimated incidence of 3-5 cases per 100,000 patients. Sarcoidosis is a multisystem immune-mediated inflammatory disorder categorised by the presence of granulomas in tissues and is highly associated with respiratory tissue. Sarcoid patients may develop SAPH, which can lead to significant complications. Due to the complexity, late diagnosis and absence of real world studies across all subtypes of PH (PAH, CTEPH and SAPH), there is currently a lack of understanding regarding the clinical pathway leading to diagnosis. In addition, there is also the need to further explore and study post-diagnosis pathways and patient related outcomes associated with these diseases in routine clinical practice. As a result, IQVIA Ltd and IQVIA Technology Services Ltd, are carrying out a retrospective real world data analysis of UK PAH, CTEPH and SAPH patients for Janssen-Cilage Limited. The study will focus on describing and comparing PAH, CTEPH and SAPH populations (and define sub-populations) in terms of characteristics of patients, clinical pathways pre-diagnosis and diagnostic procedures, treatment patterns post diagnosis, clinical outcomes and Healthcare Resource Utilisation (HCRU). This presents a great opportunity for both Janssen and the broader scientific/research community to improve the body of knowledge around these three sub-types and further enhance the possibility of developing better clinical pathways, improving treatment patterns and informing clinical guidelines to improve patient’s health and Quality of Life (QoL). The Pulmonary Hypertension Association UK (PHA UK) is the UKs largest and foremost patient advocacy group for those suffering from this life threatening and shortening condition; PHA UK has some 4,340 members representing the views of a large part of the UK patient population. The Pulmonary Hypertension Association UK, agree that the study “Pulmonary Hypertension (PH) population characterisation and epidemiological analysis” will benefit the broader scientific community by improving the body of knowledge around PH and its subtypes, while enhancing the possibility of developing better clinical pathways, advancing treatment patterns and informingclinical guidelines to improve patient’s health and Quality of Life (QoL). This research study represents for the members a crucial part of PHA UK's collective endeavours to find new and more efficacious therapies for those with PH. There is an additional purpose of this study for the patients involved, namely that the study could potentially support the development of future novel drugs in clinical trials. It was determined that the combined analysis of HES data and the enhanced diagnostic clinical data jointly held by STHFT and the University of Sheffield (UoS) could be very beneficial to this study, hence the joint involvement of each in the development of this study. IQVIA Ltd and IQVIA Technology Services Ltd. will be processing the data in line with their related to the research objectives, as part of their legitimate interests. IQVIA Ltd and IQVIA Technology Services Ltd are affiliated healthcare technology companies with interest in medical research which typically establishes relationships between pharma companies and healthcare providers to further this interest. IQVIA Ltd and IQVIA Technology Services Ltd considers this study will provide the healthcare community and academia with a better understanding of the diagnosis and treatment of PH patients in England, providing opportunities to identify areas to improve services, improve the patient journey, as well as opportunities to provide earlier treatment and to improve quality of life for patients. It is anticipated that patients and other healthcare stakeholders will have increased access to information about the disease given the planned production of publications of study findings. The evidence produced upon completion of the study could potentially help inform research direction for novel treatment in this severely under-served disease. Covered under the GDPR Article 6(1)(f) - This work is necessary for the purposes of the legitimate interests pursued by the controller except where such interests are overridden by the interests or fundamental rights and freedoms of the data subject which require protection of personal data, in particular where the data subject is a child. The data requested is to help achieve the following: pre- and post-diagnosis pathway analysis, health economics/burden of illness studies, treatment pathway analysis, diagnostic pathway assessment and improvement of clinical services as well as potential support for drug development. Janssen-Cilag Limited will be processing the data in line with their research objectives as part of their legitimate interests. Janssen-Cilag Limited is a pharmaceutical company with interest in the pulmonary hypertension therapy area. It is funding this study to further the body of knowledge of PAH, CTEPH and SAPH populations in terms of patient characteristics, clinical pathways pre-diagnosis, treatment patterns post diagnosis, clinical outcomes and HCRU. Janssen-Cilag Ltd. is particularly interested in understanding more about patient journeys through the secondary care system which can help identify ways of improving diagnosis and treatment, as well as potentially providing evidence to support applications for novel therapies in this highly under-served disease area. The reported results of this analysis may potentially assist in allowing patients to get access to new treatment options and provide health economic information to help design a more efficient care pathway for PH patients Reseacrh veung undertaken by is covered under the GDPR Article 6(1)(f) - This work is necessary for the purposes of the legitimate interests pursued by the controller except where such interests are overridden by the interests or fundamental rights and freedoms of the data subject which require protection of personal data, in particular where the data subject is a child. The data requested is to help achieve the following: pre- and post-diagnosis pathway analysis, health economics/burden of illness studies, treatment pathway analysis, diagnostic pathway assessment and improvement of clinical services as well as potential support for drug development. Sheffield Teaching Hospitals NHS Foundation Trust will be processing the data in line with its goals to carry out the task in the public interest. STHFT one of England’s leading PH diagnostic and treatment centres considers that this analysis may provide it with information to better support their patients through the full care pathway. They consider that their patients will benefit from the research by furthering their understanding of patient journeys outside of the Sheffield Pulmonary Vascular Disease Unit (SPVDU) – leading to a more coordinated approach to care - in addition to understanding the outcomes of its unique diagnosis process and allowing it to share its learning with other centres. Research being undertaken by Sheffield Teaching Hospitals NHS Foundation Trust is covered under the GDPR Article 6(1)(e) - Processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller. The data requested is to help achieve the following: pre- and post-diagnosis pathway analysis, health economics/burden of illness studies, treatment pathway analysis, diagnostic pathway assessment and improvement of clinical services as well as potential support for drug development. The use of this pseudonymised data will allow the data controllers and data processors to provide the research outputs to Sheffield Teaching Hospitals assist in enabling them to deliver better healthcare. This includes analysis and interpretation which provide understanding of care pathways, understanding use of medicines, and supporting healthcare commissioners and providers in achieving data quality, all these examples are with the aim of improving overall healthcare. The data processors also utilise this pseudonymised data to provide services to Janssen-Cilag Limited to improve healthcare and assist the efficiency of the National Health Service in the interest of public health. The service supports the development of innovative solutions and service improvement and helps to track outcomes and provide real-world evidence as required by the NHS, NICE, and NHS England with the aim of improving patient care and support enhanced access to improved services and innovative solutions. Individuals have got the right to opt out of the use of the HES data. All data removed from the storage location is small number suppressed as per HES Analytics guide. Research overview The goal of the research is to: • Generate real world evidence on the clinical and treatment management of patients diagnosed with PAH, CTEPH and SAPH • Analyse the characteristics of diagnosed patients at the time of confirmed diagnosis, and the clinical pathways leading up to diagnosis, diagnostic procedures and the post-diagnostic treatment patterns • Investigate various clinical outcomes associated with PH and its subtypes, and comparative outcomes analysis of PH treatments • To explore the healthcare resource use (HCRU) and the costs associated with the diagnosis of PAH, CTEPH and SAPH To achieve the above objectives, IQVIA Ltd and IQVIA Technology Services Ltd propose to build a joint dataset that has the required patient cohorts and clinical information. The database will comprise of non-identified patient data derived from the STHFT deep clinical databases which collect data on all patients attending the Sheffield Pulmonary Vascular Disease Unit (SPVDU) and national level hospital interactions from HES data. Parties involved in the research: Each party in the collaboration will have a different role during the research: 1. STHFT will take responsibility for ethics approval for the study, provide expert clinical insight on the research findings, support on datasets de-identification and linkage of data in addition to supporting the publication of research findings 2. IQVIA Ltd will support STHFT ethical approvals activities, co-develop the study protocol and SAP, conduct the transformation and data processing of non-identified data into analysable format and perform the analysis to meet the research objectives 3. Janssen- Clilag Ltd (Janssen) will be funding the research and willvsupport the development of the study protocol and SAP and provide expert clinical insight on the findings. 4. IQVIA Ltd and IQVIA Technology Services Ltd will each have access to non-identifiable record level data and create aggregate outputs which will be shared with both Janssen and STHFT. Janssen will not be permitted to access record level HES data and shall only ever have access to aggregated data with small number suppressed in line with the HES Analysis Guide. 5. STHFT and Janssen will provide clinical interpretation of the results. Janssen is funding the research to further the body of knowledge of PAH, CTEPH and SAPH populations in terms of patient characteristics, clinical pathways pre-diagnosis, treatment patterns post diagnosis, clinical outcomes and HCRU. STHFT as one of England’s leading PH diagnostic and treatment centres benefits from the research by furthering their understanding of patient journeys outside of the Sheffield Pulmonary Vascular Disease Unit (SPDVU), in addition to the verification that their unique diagnostic process is beneficial to patients, allowing them to share their learning with other centres. To ensure findings are published fairly and not suppressed there will be a clinical interpretation committee in place. This shall be comprised of two representatives of each ofSTHFT the UoS and Janssen and with IQVIA Ltd and IQVIA Technology Services Ltd having one representative who will chair the group. The committee will perform the following functions: 1) Provide clinical interpretation of the results to support refinements of the analysis within the bounds of the protocol 2) Agree the dissemination / publication routes for research findings (e.g. conference posters vs peer review papers etc.) based on the nature and strength of findings. (Please see output section for further information) No organisation on the clinical interpretation group or any of the data controllers will have the ability to suppress any of the findings or outputs of the analysis. The clinical interpretation group members do not have any access to record level data. The studies chief investigator from STHFT will oversee the research and offer clinical insight on the findings. The dissemination of findings has been pre-agreed with the committee and outlined in the outputs section. It is important when linking HES data with the STHFT dataset to utilise the confirmed and sub-typed (PAH, CTEPH and SAPH) patient diagnoses present in the STHFT dataset, where the patient PH classification has been confirmed by world leading clinical experts. This will allow IQVIA Ltd and IQVIA Technology Services Ltd to identify patients with confirmed PAH, CTEPH and SAPH diagnoses within the HES data for investigation and analysis with high certainty. Current ICD-10 coding available in HES (the International classification system for coding of disease types, maintained by the World Health Organisation) does not have a specific code for the different PH sub-types (PAH, CTEPH and SAPH), instead multiple different pulmonary diseases coded under the same ICD-10 4-level character code. In addition, coding is not consistently applied across centres, meaning that PH patients in HES are coded across many different ICD-10 codes and therefore confirmation of disease and subtype in HES alone is not possible with complete certainty. Access to STHFT data will be critical as it will provide great insight on all the patients who have attended SPDVU since 2012, to gain a better understanding of both the diagnostic pathway and process at SPDVU. Patients diagnosed with PAH, CTEPH or SAPH will be included. Furthermore, STHFT data will also provide information on in-depth patient clinical characteristics that will allow IQVIA Ltd and IQVIA Technology Services Ltd to characterise these patients at different points of the patient journey and develop matched cohorts for conducting comparative outcomes analysis across different PH treatments, and further investigate the variation in clinical outcomes of patients that have other comorbidities. Data from Hospital Episode Statistics Accident and Emergency, Hospital Episode Statistics Outpatients and Hospital Episode Statistics Admitted Patient Care is being requested in order to understand the complete patient pathway. Often, PAH patients may be admitted to A&E and may be taken as inpatients in relation to their PAH diagnosis, therefore this data will be crucial to understand the complete patient pathway. All 20 of the diagnosis codes are being requested in order to understand the comorbidities associated with PAH. The OPCS codes are also required in order to understand the procedures that a patient may have undergone as a results of their PAH diagnosis. Other data requests such as age, gender and ethnicity are needed in order to characterise the patients. This data will allow the aims discussed in previous sections of this application to be achieved. The study design is a non-interventional retrospective database analysis of data collected on patients with PH (including its subtypes; PAH, CTEPH and SAPH) based on data from the Pulmonary Vascular Disease Unit at Sheffield Teaching Hospitals NHS Foundation Trust (STHFT) and HES data from NHS Digital. To facilitate this project, IQVIA Ltd and IQVIA Technology Services Ltd are requesting the following patient cohort from NHS Digital; Cohort: Patients with PH who have been managed at the SPDVU since 2012, which will allow IQVIA Ltd and IQVIA Technology Services Ltd. to confirm the patient diagnosis (and subtype) in HES data and understand the diagnostic pathway before and at the SPDVU along with the post-diagnosis pathway. It is estimated that this cohort will be around 3000 patients. NHS numbers and dates of birth will be provided by STHFT to NHS Digital with the defined cohort of patients for linking to HES data. Due to the complicated disease area and goals of the research the patient pathway analysis requires a long period of data for the following reasons: • Having sufficient time to understand patient activity from onset of symptoms to diagnosis IQVIA Ltd and IQVIA Technology Services Ltd. are requesting ~12-year historical extract of data for the study to cover the requested cohort (patients with PH who have been managed at the SPDVU since 2012). The reason for the extended time period of the extract is that PH patient populations (especially at subtype level) are very small and the diagnosis pathway is a long multi-year processes and often complex. By analysing a longer period of data, it is more likely that IQVIA Ltd and IQVIA Technology Services Ltd will be able to create cohorts of patients with a higher number which will contribute to a more robust analysis and avoid some of the predicaments and biases of small patient number. In Europe, PAH prevalence and incidence are in the range of 15–60 subjects per million population and 5–10 cases per million per year, respectively. One of the most common forms, idiopathic PAH, has an annual incidence of 1-2 cases per million. The other subtypes of PH are equally rare, with CTEPH having estimated full incidence of 3-5 cases per 100,000, and SAPH having an estimated incidence of 10-35 cases per 100,000. Because these datasets have relatively small numbers of patients with a rare disease, this request is for a ~10-year historical extract to ensure that a sufficient number of patients in order to ensure the results show statistical significance.

Expected Benefits:

There are likely benefits from this research for patients, the NHS, academia and life sciences companies. Overall, there are large gaps of knowledge within PH especially when looking at a subtype level (e.g. PAH, CTEPH, SAPH). Understanding more about patient journeys through the secondary care system can help identify ways of improving diagnosis and treatment, as well as potentially providing evidence to support applications for novel therapies in this highly underserved disease area. This could potentially allow patients to get access to new treatment options and provide health economic information to help design a more efficient care pathway for PH patients. This more efficient care pathway could potentially lessen the burden on patients by reducing repeat visits during patient’s diagnostic pathways and supporting earlier diagnosis to improve patient treatment outcomes. In heritable forms of the disease benefits may well subsequently advantage patient’s family members. Patient pathway analysis: • The healthcare community & academia will gain a better understanding of the diagnosis and treatment of PH patients in England, providing opportunities to identify areas to improve services, improve the patient journey, provide earlier treatment and to improve quality of life for patients. • Participants and non-participants will have increased access to information about their disease from the production of publications of study findings, which will be made available through the listed IQVIA Ltd website (noted on the posters at the STHFT), and potentially other channels e.g. PHA UK who support this research. • The evidence produced will help inform research direction for novel treatment in this severely under-served disease. • There is also the additional purpose of this study for the patients involved, as the study could potentially support the development of future novel drugs in clinical trials. The outcomes from this study could help provide vital insights into the PH (and its subtypes) population, and potential novel treatments that could be useful in the drug development process from its early stages through to post-authorisation.

Outputs:

IQVIA Ltd and IQVIA Technology Services Ltd will conduct initial analysis of the clinical pathway leading up to diagnosis and the post-diagnostic treatment patterns of patients, including a comparative outcomes analysis of PH treatments that will aim to investigate different outcomes of interest such as, but not limited to, overall survival of the treated groups, liver toxicity, oedema/fluid retention, as well as the reason and number of hospitalisations. In addition, the study will explore both the HCRU and the costs associated with the diagnosis. An amendment of the Data Sharing Agreement will be required in the future to support any supplementary questions arising from publications, in addition to supporting further publications to contribute to the body of knowledge on PH. In addition to the publication, additional dissemination plans are as follows: • Published results will be shared with the Pulmonary Hypertension Association UKPHA UK (PAH UK) patient advocacy group at the beginning of the year 2021. • Furthermore, the abstracts and links to publications will be hosted on IQVIA Ltd's online bibliography that is publicly available. Results will be presented at the European Society of Cardiology in August 2021, and in other journals such as the International Journal of Cardiology, the European Journal of Health Economics and potential others. • Results will also be shared with other parties where appropriate. For example, sharing results with other NHS trusts that also manage PH patients or sharing with international centres that also diagnose and manage PH patients Note: All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Processing:

To ensure the minimum amount of patient identifiable data will be used and handled by the fewest people outside of the direct care team the following process is currently proposed 1. STHFT will share with NHS Digital team, via a secure file transfer protocol, the NHS numbers and dates of birth of patients that have attended the SDPVU clinic since 2012, aligned to a generated study ID. The total number of this cohort is about 3000 patients 2. NHS Digital will link the identifiable patient cohort to the following data sets; Admitted Patient Care, Outpatient and Accident & Emergency data. NHS Digital will remove the NHS numbers and dates of birth and returning the non-identified extract (including study ID) to the STHFT informatics team. 3. Patient data received from STHFT will be linked to the HES data via the generated study ID and will be done in compliance with all trust policies on patient data handling. This data will only be accessible by the patient management team. NHS Digital will supply STHFT with the HES Data with a non-identifiable ID linked to the Study ID, which will allow STHFT to link the HES data to the diagnostic clinical data held at STHFT. The linked non-identified data will then be loaded to a second logical environment also located within STHFT. 4. This environment will be remotely accessed within the STHFT “De-militarized Zone” (DMZ), which is a special local network configuration designed to improve security by segregating computers on each side of a firewall. This is an additional layer of security between the trusted internal network and an untrusted external network i.e. the internet. The research will be undertaken by trained researchers from IQVIA Ltd and IQVIA Technology Services Ltd and specific members from the University of Sheffield who are under honorary contracts or hold Research Passports at the STHFT. Access is granted using strong two factor authentication based on USB keys which produce one time use passwords (more information can be found at https://www.yubico.com/). The research conducted on this combined dataset will be for the agreed research questions and will be performed on non-identified patient information. The HES linked data will not leave STHFT. Only aggregated non-patient level outputs will be shared. The applicant expects to conduct the following analysis with the data, in order to generate real world evidence on the current clinical and treatment management of adult patients with a confirmed diagnosis of PAH, CTEPH or SAPH within the Sheffield EMR who have been treated with at least one PH-specific medical treatment. 1.Detailed analysis of the clinical characteristics (including diagnostic tests where available, functional class, presence of co-morbidities, previous pulmonary embolism for CTEPH patients) of diagnosed patients at the time of confirmed diagnosis between 2010 and 2019 2. Describe the pathways leading to diagnosis, including time to diagnosis from initial symptoms (PAH and CTEPH patients) or from sarcoidosis diagnosis (SAPH patients) 3.Describe the prescribed treatments after diagnosis and the treatment pathways, from the date of start of the first prescribed treatment, including use of co-medications (if available), persistence, discontinuation, switching and add-on therapy 4. Investigate various clinical outcomes associated with PAH, CTEPH and SAPH across different patient groups (e.g. categorised by comorbidity) as well as conducting comparative outcomes analysis of PH treatments. In addition, there is the aim to explore the healthcare resource use (HCRU) and the costs associated with the diagnosis. These analyses are expected to be completed 9 to 12 months after HES data has been provided. Researchers who will access the patient level HES data will be logged on an access control register, ensuring that it is possible to identify everyone with access to patient level information. Each researcher from IQVIA Ltd. and /or IQVIA Technology Services Ltd that will have access to record level data will sign an Intra-Company Agreement that will contain information on best practice and rules. These rules must be adhered to as stated in specific section of the contract, including the prevention of exporting any data from the Sheffield (STHFT) server that contravenes the HES small numbers protocol. All individuals with access to the record level data must be substantive employees of IQVIA Ltd, and/or IQVIA Technology Services Ltd, and or/STH save researchers from other parts of the IQVIA group, who may be required from time to time to provide expertise in analysis of the data. These individuals will work under an Intra-Company Agreement to IQVIA Ltd. All individuals accessing the data under an Intra-Company vAgreement issued by IQVIA Ltd will be a substantive employee of the IQVIA company group. IQVIA Limited is not permitted under this agreement to enter into an Intra-Company Agreement with any individual, who is not substantively employed by an IQVIA group company. During the analysis process of the pseudonymised and aggregated data, there will be regular sessions with Sheffield (STHFT) and Janssen clinical experts to provide clinical perspective and impact of the results generated. Janssen-Cilag Limited will not carry out any processing of data under this agreement. There will be not attempt to re-identify any individuals No data linkage will be undertaken with NHS Digital data provided under this agreement except for the linkage already noted in the agreement. All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by "Personnel" (as defined within the Data Sharing Framework Contract i.e. employees, agents and contractors of the Data Recipient who may have access to that data).