NERVES Trial

HES data are required for the purpose of the NErve Root Block VErsus Surgery (NERVES) trial.

Sciatica is a common condition; In 2010/2011 over 25,000 therapeutic epidural steroid injections (ESI) were administered in the UK and over 9,000 surgical procedures to remove herniated lumbar disc prolapses were performed for sciatica. Case values estimated for the UK NHS are £600 per ESI and approximately £4,000 for surgical microdiscectomy (which includes an average of two nights in hospital per patient).

Spinal injections are relatively cheap and low risk, compared to surgery, with a high success rate (estimated to be as high as 75%). They are delivered as a day case procedure by clinicians ranging from radiologists to surgeons or pain physicians. However, their true success rate is largely unknown. They may work well in the short term, but patients may have their pain return after some weeks. Spinal injections are also inappropriate for massive disc prolapses causing motor weakness or numbness in the leg.

Currently there is no evidence comparing steroid injections given via the nerve foramen to any other form of treatment i.e. surgical microdiscectomy and neither has a robust economic analysis been performed for this condition and these treatment paradigms.

The aim of this study is therefore, to assess the clinical and cost effectiveness of surgical microdiscectomy to transforaminal epidural steroid injection for treatment of sciatica caused by a prolapsed intervertebral disc. In order to fulfil the objective of the NERVES study relative to cost-effectiveness, Bangor University have conducted a health economic analysis that will adopt the perspective of the National Health Service (NHS) and Personal Social Services (PSS), and additionally consider indirect costs such as time off work (secondary analysis). The economics data was based on resource use using entries made in case report forms, patient questionnaire booklets, and Hospital Episode Statistics data sourced from NHS England.

There are three joint data controllers for this purpose: the Walton Centre NHS Foundation Trust, the University of Liverpool and Bangor University. Bangor University is the sole Data Processor. The day-to-day running of the trial is being coordinated by the Clinical Trials Centre (LCTC), University of Liverpool.

The legal basis for processing falls under GDPR Article 6(1)( e) and GDPR Article 9(2)(j). Processing and dissemination meet the public interest criteria as defined by the ICO for good decision-making by public bodies and securing the best use of public resources. The processing of data for this study is a task of public interest since it will inform the NHS, clinical commissioners and other healthcare decision makers on the most clinical and cost-effective treatment for this condition.

The NERVES trial is a randomised controlled trial funded by the National Institute for Health Research's Health Technology Assessment (NIHR HTA) Programme and is sponsored by The Walton Centre NHS Foundation Trust. NIHR HTA funds independent research on the effectiveness, costs and broader impact of healthcare treatments and tests for those who plan, provide or receive care in the NHS. This funded research serves a variety of key stakeholders including: decision-makers in local government, policy-makers including NICE, researchers, NHS health professionals, other NIHR stakeholders, and the general public.

NERVES opened for recruitment on 04/03/2015 at the Walton Centre; it recruited its first patient on 06/03/2015 and it's last patient on 21/12/2017 having exceeded its recruitment target, achieving a total of 163 recruited patients.

In order to undertake the cost-effectiveness analysis, data processing was necessary to cost the two treatment arms compared in the study, which comprises an evaluation of the resources used by patients in the NERVES trial. This includes an analysis of all NHS hospital visits, which can be quantified through the provision, by NHS England, of pseudonymised data on hospital visits for the NERVES clinical trial participants.

The primary and secondary objectives of the NERVES study was to compare the clinical and cost effectiveness of surgical microdiscectomy to transforaminal epidural steroid injection (TFESI) for treatment of sciatica caused by a prolapsed intervertebral disc (PID).

This was a one-off request for Bangor University to receive data on the number and duration of outpatient and admitted patient care episodes for NERVES trial patients, to cost the separate arms of the NERVES trial and to explore any difference in resource use between the two treatments.

Bangor University minimised the use of identifiable data for the purpose of this research by collecting HES Outpatients and Admitted Patient Care data only relevant to costing of NERVES trial patients. Data was pseudonymised by NHS England and forwarded to Bangor University, distinguished by patient clinical trial number only. Bangor University researchers did not have access to the “key” that allows for patient identification.

Eligible study participants were aged 16 to 65 years and had a diagnosis of lower extremity radiculopathy (sciatica) for between 6 weeks and 12 months, where their leg pain was unresponsive to conservative, non-invasive treatment.

The data required from NHS England was routine outpatient and admitted patient care data for NERVES trial participants commencing 3 months prior to their entry in the study, to the point of exit (54 weeks after randomisation). Specifically, the data required was the date of each outpatient visit according to Healthcare Resource Groups (HRG), and for admitted patient care, the date and duration of stay, according to HRG, within the specified timeframe.

The HES data was needed to record the number of hospitalisations experienced by members of each arm of the NERVES trial which investigated ways of treating patients with chronic radicular pain secondary to prolapsed intervertebral disc herniation. By measuring hospital resource use, researchers could estimate the overall cost for each patient then generate mean costs with confidence intervals for the trial arms. This information could then be used to inform future NHS treatments for patients with the condition by indicating which arm offers the best value for money. The data was handled by taking the sum of all inpatient and outpatient costs derived from the HRGs and doing a 10,000 replicant bootstrap to generate the confidence intervals for the costs. The results of the work and how it helps the health and social care sector will be published in an NIHR HTA report, peer reviewed journals such as the New England Journal of Medicine, if accepted, as well as being submitted to the International Society for Study of the Lumbar Spine (ISSLS) in Australia in April 2020 and a health economic conference. No patient-level data will be published.

The study required pseudonymised, patient level data so that an accurate costing of resource use per patient could be undertaken. Identifiable data was not required for the purposes of this task. Patients were identified by clinical trial number only. The researchers at Bangor University do not hold the “keys” to identifying individual patients based on clinical trial number. The hospitals involved in the NERVES study were restricted to England, therefore data relating only to NHS England was requested.

In order to provide an accurate estimation of patient NHS hospital resource use, the collection of NHS England data was considered the most appropriate route to obtain robust, reliable data on hospital visits. Patient questionnaires have also been completed but are reliant on patient completion as well as patient recall and may introduce biases into the cost-effectiveness analysis results.

Data was restricted to patients who have consented to participate in the NERVES trial and have agreed for their personal data to be shared with NHS England. Only data relevant to identifying the number and duration of admitted patient care and outpatient visits was required, and only for the trial duration.

The study is not aware of any moral or ethical issues raised by the dissemination of NHS England data to Bangor University, nor the dissemination of the aggregated study results to the wider public. The study is unaware of any risk of potential harm to the public by the dissemination. Data received from NHS England was pseudonymised at source prior to being sent to Bangor University. Bangor University researchers did have access to the “key” that allows patient identification. Any results from the study that are shared publicly will be aggregated.

LCTC extracted the following identifying information from their NERVES patient database and forwarded this to NHS England via secure file transfer:

- Study ID (patient randomisation study number)

- NHS Number

- Date of Birth

- Postcode

- Study start and end date

NHS England linked this information to HES Admitted Patient Care and Outpatient data. NHS England removed all identifying data items other than Study ID from this dataset and forwarded the pseudonymised data to Bangor University Centre for Health Economics and Medicines Evaluation Unit (CHEME).

HES data did not flow back to LCTC. There were no flows of patient-level data from Bangor University and no flow of data from LCTC to Bangor University which could have been used to reidentify participants.

Researchers at Bangor University were not in possession of any other data allowing the re-identification of patients in the dataset. No attempts were made by researchers in Bangor University to obtain the key linking the clinical trial number to any patient identifiers, removing any risk of re-identification. Pseudonymised data was processed in Bangor University to generate aggregated data pertaining to the cost effectiveness of the two arms in the clinical trial. Software used was R software and Excel 2016.

Patients were linked to their arm of the study via their randomisation number. The data was handled by taking the sum of all inpatient and outpatient costs derived from the Healthcare Resource Groups (HRGs) and doing a 10,000 replicant bootstrap to generate the confidence intervals for the costs in each arm of the study. It is anticipated that the results of the work and how it helps the health and social care sector will be made public during 2020. The results will be published in a NIHR HTA report, peer-reviewed journals such as the New England Journal of Medicine, if accepted, as well as being submitted to the International Society for Study of the Lumbar Spine (ISSLS) in Australia in April 2020 and a health economic conference No patient-level data will be published.

Bangor University conducted linkage via the HRG codes to obtain HRG costs from publicly available National Tariff registers and, via the patient randomisation study number, attached additional costs and Quality Adjusted Life Years (QALYs) to a consolidated working file. The multiple lines per patient inpatient and outpatient hospital visits in the pseudonymised HES datasets provided by NHS England were costed line-by-line by attaching HRG costs from the most up to date National Tariff to the corresponding HRG in each line of data. The dataset was compared with pseudonymised data obtained from patient questionnaires.

Any HRGs used in small numbers (in accordance with the HES analysis guide) were not identified and subsequently reported under miscellaneous HRGs.

Aggregated data was stored in Excel files, Word files, PowerPoint files and pdf files ready for publishing in peer-reviewed journals, presenting in symposia etc. Commonly used HRGs were included in the aggregated data. Seldom-used HRGs were not identified in the aggregated data mitigating any risk of re-identification.

Files holding pseudonymised data will be held securely on Bangor University servers in folders with access restricted to Bangor University analysts in CHEME.

Data will be moved to a secure server located at Bangor University and then archived where data will not be permitted to be viewed or processed under this 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).

No data will be shared with 3rd parties.

Analysis described in this Agreement is complete. HES data is considered source data under the Clinical Trials Regulations and needs to be archived for an extended period up to 15 years up to 2034. This Extension Agreement is for 10 years up to 2034 and permits the data to be retained for archiving purposes only. There will be no further processing in this archival period. There will be further publications using aggregated data collected from analysis already undertaken.

The plan is to share the results of the cost-effectiveness analysis with key stakeholders, including decision-makers in local government, policy-makers (e.g. NICE), researchers, NHS health professionals, other NIHR stakeholders, and the general public through journals, public reports, presenting at relevant conferences and symposium.

Bangor University has contributed to the NIHR HTA report underpinning the NERVES study, which will be a wider report on the entire NERVES study published on the NIHR website. One of the sections of this report has been dedicated to health economics and was due for publication within 18 months of the receipt of data from NHS England, anticipated to be Q3/Q4 2020.

A journal article based on the findings of the clinical and cost-effectiveness analysis will be published in a peer reviewed medical journal, that may be relevant to sciatica e.g. New England Journal of Medicine, if accepted, within 18 months of receipt of data from NHS England.

Presentations relating to the findings of the clinical and cost-effectiveness analysis will be given at local, national and international conferences as opportunities arise.

The dissemination activities undertaken concerning the NERVES study are two-fold; to enable the engagement with the scientific and policy-making communities and to ensure that knowledge developed by the research can benefit these communities.

The collaborative NERVES trial team will participate in active communication activities to ensure any information about the project and its results reaches interested groups and civil society and will involve knowledge sharing and dialogue. Planned communication channels to key stakeholders including decision-makers in local government, policy-makers including NICE, researchers, NHS health professionals, other NIHR stakeholders, and the general public will be made through the NERVES website and newsletters.

All outputs will be aggregated with small numbers suppressed in line with the HES Analysis Guide.

The aim of processing the HES data is to identify which of the two treatment arms of the trial is the most clinically and/or cost-effective method of treating sciatica.

Health care professionals and NHS commissioners will be better informed which of the expensive chronic radicular pain treatments will be the most clinically and cost-effective in terms of patient outcomes, need for hospitalisation or hospital visits, improved care and by extension, which offer the best value for money to the NHS healthcare system. This will be a health care benefit; not only to the NHS in terms of efficacy and best use of resources, but also to patients in terms of clinical outcomes and the global healthcare research community.

NHS England data will contribute to the NHS and wider clinical research communities (including decision-makers in local government, policy-makers including NICE, researchers, NHS health professionals, other NIHR stakeholders, and the general public) understanding of the most clinically and cost-effective means of treating sciatica. It would not be possible to undertake a robust economic evaluation without the NHS England HES data.

Sciatica is a common condition; in the UK (2010/2011) over 25,000 therapeutic epidural steroid injections were administered and over 9,000 surgical procedures to remove herniated lumbar disc prolapses were performed for sciatica. Case values estimated for the UK NHS are £600 per ESI and approximately £4,000 for surgical microdiscectomy (which includes an average two nights in hospital per patient). There is a potential saving of up to £30,000,000 per annum for the NHS.

Should ESI be shown to be clinically and/or economically beneficial compared to surgery, the patient will be subject to a less intensive regimen, avoiding hospital inpatient stay and potential for improved quality of life.

Benefits are also expected to the NHS through reduced resource use (fewer surgeries) and improved cost-efficiencies.

The benefits can be measured through changes in hospital annual submissions for ESI and sciatic surgery via the Patient Linked Information Costing System (PLICS).

Once the results of the study are published, it will up to local decision-makers such as clinical commissioning groups, health-care policy-makers including NICE, researchers, NHS health professionals, other NIHR stakeholders, and the general public to implement the changes.

Not stated in the register.