Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) secondary care pathway analysis.

The purpose of this study is to understand the current treatment pathway and disease burden of patients suffering from nasal polyposis and who undergo a surgical treatment known as nasal polypectomy. Nasal polyps are common and affect up to four percent of the population. They are not usually serious, but they can keep growing and block the nose if not treated. Their aetiology remains unclear, but they are known to have associations with allergy, asthma, infection, cystic fibrosis, and aspirin sensitivity.

The Legal basis for processing of personal data relating to patient health is under Article 9(2)(j)of the GDPR - Processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. The data subjects’ interests and fundamental rights are protected through appropriate minimisation of fields; protection of the data in a secure environment and guaranteeing secure destruction at any stage at the request of NHS Digital or after a defined period on completion of the project.

IQVIA Ltd and IQVIA Technology Services Ltd are processing the data in line with their goals as part of their legitimate interests. This 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 use of this Pseudonymised /Anonymised data allows IQVIA to provide services to improve healthcare for citizen’s and provide support services to healthcare providers to enable them to deliver better healthcare. For this analysis specifically, this includes interpretation of data which will provide Sanofi Genzyme further insight into care pathways which will enable healthcare commissioners and providers in achieving a better understanding of the healthcare economy, with the aim of improving overall healthcare and patient outcomes. The reported results will inform further research into better and improved treatment options from patients who suffer from nasal polyposis and who undergo multiple revision surgeries over the course of their patient journey. In addition, the analysis provided to Sanofi Genzyme will provide insight to commissioners and providers on the burden of surgery, and how that differs across at-risk groups.

IQVIA also utilise this Pseudonymised data to provide services to commercial organisations 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. IQVIA have found no evidence that the use of this data negatively impacts the fundamental rights and freedoms of the data subjects.

All aggregated data and analysis is passed on to Sanofi Genzyme with small number suppressed in line with the HES Analysis Guide.

Patients with nasal polyposis often require multiple surgical revisions, as current treatment in the form of steroid nasal spray, as well as the surgery itself, is not curative. This results in the condition not only in the long-term having a burden on the secondary healthcare system but can also exacerbate the burden related to other respiratory conditions patients may suffer from e.g. asthma.

The primary objective of the study is to quantify the hospital-based burden of the condition related to chronic rhinosinusitis with nasal polyps (CRSwNP) and the surgical treatment patients undergo in the form of nasal polypectomy. The study will furthermore quantify the initial and subsequent treatment related to hospital attendances and admissions that include codes indicative of CRSwNP diagnosis, the co-morbidity and differential care profiles of patient subgroups based on risk groups, and the cost and wider burden of patient hospitalisations. Using the Hospital Episode Statistics Admitted Patient Care and Outpatients data, the analysis involves defining a CRSwNP patient cohort of interest based on a defined algorithm relating to nasal polyposis treatment, follow-up and associated costs to assess current disease burden to the NHS in England.

Patient level HES data is needed to establish and assess the total CRSwNP patient cohort, as well as relevant risk groups along with relevant case-mix adjusted negative control groups. These risk groups have been selected based upon clinical relevance, as well as potential patient need and include the following:

- All Nasal polyposis and/ or Nasal polypectomy patients

- Nasal polyposis and/ or Nasal polypectomy with asthma and/or aspirin sensitivity

- Nasal polyposis and/ or Nasal polypectomy with another related sinus procedure

- Nasal polyposis and/or Nasal polypectomy with cystic fibrosis

Control groups will be generated from the HES data provided to the data controllers by NHS Digital and will not require any further data to be extracted. The control group in this instance will be any patient who has a polypectomy and /or nasal polyps, with no associated co-morbidities i.e. asthma, aspirin sensitivity and/or cystic fibrosis.

This study will contribute to the benefits to health and social care as these objectives will provide:

• A better understanding of the natural history and epidemiology of the disease.

• The treatment patterns and pathway for patients diagnosed with CRSwNP in the real world. For example:

o The proportion of patients who underwent nasal polypectomy surgery and, of this patient population, how many patients went through multiple surgeries and what was the elapsed time between each surgical procedure?

o The associated secondary care impacts and healthcare utilisation burden of these pathways.

• Increased knowledge on the healthcare resource utilisation of CRSwNP treatment to support potential process improvement programmes.

A cumulative ten-year data period (including the most current five years already held by IQVIA Ltd and IQVIA Technology Services Ltd under Agreement DARS-NIC-373563 is required to allow for a more complete analysis of the patient pathway leading to repeat surgical interventions for CRSwNP patients, and to allow for more accurate insight to be drawn from any analysis performed. Given that patients may have multiple polypectomies, and these polyps may take more than five years to develop, the objective is to understand the pathways of patients undergoing polypectomies, in particular those with repeat polypectomies.

This project, sponsored by Sanofi Genzyme, intends to better understand the recent healthcare resource utilisation in order to report and publish on findings in peer reviewed journals and/or congresses, used in payer value and regulatory materials, and develop and instigate process improvements for and with the NHS. Sanofi Genzyme are not involved in any decision making on the direction of the analysis, data processing, or why and how the data itself is being used. The funder of this study, Sanofi Genzyme Ltd, will not have any influence on the outcomes of the study nor attempt to suppress subsequent publication of any research findings.

The study design has been solely led by IQVIA Ltd and IQVIA Technology Services Ltd. Sanofi Genzyme will receive an aggregated output of the final analysis, in PDF report format, with small numbers suppressed in line with the HES analysis guide.

In order to complete this, a dataset of adult patients in HES APC from the 5 years prior to data currently held by IQVIA Ltd and IQVIA Technology Services Ltd. (2009/10- 2013/14) to present), with diagnostic codes of J330 and/or J339 and/or relevant procedure E-codes will be required. To identify co-morbidities on interest and create relevant risk cohorts, both primary and secondary diagnostic and procedural coding will be required. Using the APC cohort definition, HES OP data from 2009/10 to 2013/14 will also be required to understand the additional contact burden that these patients, who meet the inpatient inclusion criteria, contribute to. A national coverage is needed to understand true burden and potential burden variation amongst the population and healthcare delivery. Data minimisation has been used, including limiting to specific conditions and treatments, age ranges, and data fields.

The project includes IQVIA Ltd and IQVIA Technology Services Ltd., as joint data controllers who also process data leading and directing analytical processing and output, with Sanofi Genzyme funding the study. The objective for processing is not new and has been previously agreed through NIC-373563. As per NIC 373563 the project has been reviewed by the internal Independent Ethics and Scientific Advisory Committee (ISEAC) which was set up as mandated by IGARD. In addition, analyses has already been conducted on a 5 year time period in order to begin understanding the burden these patients contribute to.

The current 5 year time period of data held and agreed under NIC 37363 is not sufficient to track the burden of surgical revision and how it relates to the NHS in terms of operational burden and patient outcomes. A cumulative ten-year data period i.e. the data requested from 2009/10 to 2013/14, plus the time period of 2014/15 to 2018/19 already held by IQVIA under NIC 373563, is required to allow for a more complete analysis of the patient pathway leading to repeat surgical interventions for CRSwNP patients, and to allow for more accurate insight to be drawn from any analysis performed. Given that patients may have multiple polypectomies, and these polyps may take more than five years to develop, the objective is to understand the pathways of patients undergoing polypectomies, in particular those with repeat polypectomies. The data will be linked in-house to provide a 10 year view of the patient pathway across the full time period of 2009/10 to 2018/19.

All data processed under this agreement would be restricted to England and Wales only.

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 ie: employees, agents and contractors of the Data Recipient who may have access to that data)”

Data processing and analysis is entirely under the purview of IQVIA Ltd and IQVIA Technology Services Ltd. This data will be processed at pseudonymised record level, with no attempt to re-identify individuals and small number suppression used for all outputs.

The data set is being requested is record level pseudonymised. It is not possible to create unique patient care pathways using aggregate level data.

Data will flow from NHS Digital to the N3 secure data warehouse IQVIA currently holds and uses for other NHS Digital data flows, including regular monthly HES extracts received under Agreement DARS-NIC-373563.

HES APC and HES OP 14/15 to 18/19 data held under DARS-NIC-373563 will also be accessed filtered to the same ICD10 diagnosis codes and or the OPCS4 procedures related to Chronic Rhinosinusitis with Nasal Polyps and processed for the same purpose as outlined in this agreement. NHS Digital will supply an encrypted HES ID field which will be consistent across both Agreements DARS NIC-315134 and DARS NIC-373563 to allow linkage of the data

There will be no data linkage undertaken with NHS Digital data provided under this agreement that is not already noted in the agreement.

Data will only be accessed and processed by substantive employees of IQVIA Ltd and IQVIA Technology Services Ltd. and will not be accessed or processed by any other third parties not mentioned in this agreement.

The 10 years of data being used for this study will be kept separate to other IQVIA datasets held by the organisation.

The analysis will be fed into a data analysis report. This report will then be written in PowerPoint, manuscript and poster formats for submission to peer review journals and international conferences/presentations, as well as payer value and regulatory materials. These outputs will include small number suppressed aggregate figures related to the risk groups under examination.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

IQVIA Ltd, IQVIA Technology Services Ltd. and Sanofi Genzyme have a documented history, independently and in collaboration, of scientific publication and dissemination. The current work will further this goal, including activities engaging research scientists, the public, and policy and regulatory bodies. The findings are intended to highlight previously unknown burdens to the healthcare system, and to highlight how benefits can be brought for a previously unmet need amongst a patient population. This will be a multi-channel dissemination strategy, including briefing documents, peer reviewing publications and events, care value materials, etc.

Furthermore, the evidence produced will better inform clinical decision makers as to how they can provide patients who already have limited treatment options, with more information as to how they can treat their condition, and will provide regulatory bodies, such as NICE, further real-word evidence as to the cost-effectiveness of Dupilumab in comparison to surgery and surgical revision, and less effective treatment for the CRSwNP patient group specifically. This will therefore support the NICE approval process.

A summary version of findings will be provided to clinicians and GPs to disseminate to patients in order to allow patients to inform themselves and determine the best treatment route. IQVIA Ltd and IQVIA Technology Services Ltd will also share and present this information via a patient government group (a public setting where the outcomes of select data projects are shared with patient groups) in order to share more widely with the public the outcomes of the study and translate the potential patient benefit.

In addition, all region-specific data analysis reports produced from these findings will support CCGs and providers in identifying specific areas where burden of polypectomy surgery is greatest for both patients and the secondary healthcare system, enabling them to undertake targeted service transformation actions which would in turn, improve patient outcomes.

Target dates of dissemination, communication, and application of findings, include completed analysis by early 2020, publication development spring 2020/early summer 2020, and subsequent application dependent on findings.

Measurable effects include CCG review of status as a procedure of low clinical value due to healthcare impact, or alternatively regulatory approval and subsequent uptake of alternative treatment strategies in the near term.

Intended journals for publication of any manuscript(s) produced as a result of this analysis are as follows:

- Journal of Otolaryngology

- Clinical Otolaryngology

- The Journal of Laryngology and Otology

- The Laryngoscope

- The Journal of Otolaryngology and Rhinology

As such, the conferences required for dissemination of findings will be as follows:

ENT UK: https://www.entuk.org/events/951

BACO 2020: https://www.baco2020.org/

Current prescribed treatments are steroid nasal drops followed by surgery. However, nasal polyps are a difficult condition to manage, tending to recur causing the patient to undergo repeated surgeries after continued recurrence. On top of the deleterious impact on patients, there is also an impact on the wider healthcare system with considerable resource utilisation expended in the treatment of these patients over time. Despite their prevalence and the recurring need for surgery in high risk patients, nasal polypectomy has been classified as a procedure of limited clinical value by a number of CCGs across England (1), and therefore it is likely that patient outcomes will continue to suffer due to the lack of appropriate treatment being readily available.

With this analysis, the aim is to identify and characterise the most severe patient population with the greatest burden on the secondary healthcare system.

The current requirement for moderate to severe patients with CRSwNP to undergo surgery to remove nasal polyps, and revision surgery should the polyps recur, results in both a high burden to patients but also to the healthcare system as a whole. Surgery is costly and involves downtime for the patient themselves. This study’s main aim therefore is to highlight the burden of surgery across the CRSwNP.

This study will contribute to the benefits to health and social care as these objectives will provide: - A better understanding of the natural history and epidemiology of the disease

- The treatment patterns and pathway for patients diagnosed with CRSwNP in the real world

- Increase knowledge on the healthcare resource utilisation of CRSwNP treatment to support potential process improvement programmes

- An understanding of the burden of repeat surgeries, as well as the indicative cost associated with surgical and repeat surgical intervention.

- Identification of possible ways to reduce the burden of repeat surgeries on local health economies as well as on the patient individually.

- Identification of more cost-effective ways to manage patients that may or may not involve surgical intervention.

Given that the condition effects up to four percent of the population, there is an impact to the health system. The dissemination strategy would work to support the NHS in understanding the burden of polypectomy surgery on both patients and the secondary healthcare system and enable them to undertake service transformation in line with overall NHS strategy and improve patient outcomes. This would be combined with the strategic relevance of Dupilumab for the treatment of CRSwNP in adult patients being likely to receive a license from the EMA in March 2020.

Dupilumab is currently used in the treatment of asthma and atopic dermatitis but has not yet been approved by NICE for the treatment of CRSwNP. The mechanism of action of the drug is favourable to the immunological nature of CRSwNP, where repeat surgical revisions for severe patients are likely, due to the fact the root cause of the condition cannot be treated with topical procedures or treatment. Studies have shown that it can be effective against key coprimary endpoints2 and support the view that patient outcomes will be improved by the drug itself, as well as overall burden on the healthcare system by reducing the need for surgery and/or less effective treatment that currently exists.

The stated benefits to the healthcare and social care system are achievable with the additional data being provided in the format required for correct linkage to the current five year data held under NIC-373563.

1. The Impact of Commissioning for Rhinosinusitis in England. Soni-Jaiswal, A, Philpott, C and Hopkins, C. 2015, Clin Otolaryngol, pp. 639-45.

2. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Bachert, C et al. 2019, The Lancet, pp. 1638-50

Yielded Benefits is not a requirement for new applications.