Linking and Evaluation of SABR CTE Patients

Stereotactic Ablative Radiotherapy (SABR) is an emerging novel radiation technology. SABR is a specialised radiotherapy treatment planning technique resulting in a high dose to the target with steep dose gradients resulting in rapid dose fall off outside the target area. This results in high biologically effective dose (BED) while minimising the dose received by the normal tissues, and could potentially minimise the radiotherapy treatment toxicity and side effects.

The technique requires specialist positioning equipment and/or imaging (stereotaxis) to confirm correct targeting (accuracy) and it can be delivered using either standard linear accelerators or specially designed devices which are dedicated to delivering stereotactic treatments. Using a small number of fractions provides the opportunity for cost savings compared with conventional fractionation or surgical alternatives, and may free up capacity within NHS radiotherapy departments.

The current SABR indications for which evidence is rapidly accumulating are:

• oligometastatic cancer (3 or fewer sites of metastatic disease)

• cancer that has recurred in a site treated previously treated with radiotherapy (re-irradiation)

• patients with hepatocellular carcinoma

These 3 groups of patients should receive SABR within this Commissioning through Evaluation (CtE) project, which will serve to improve access to SABR within the UK and enable data collection to further expand the current evidence base. It is possible that additional indications will be added to the program in due course, including benign spinal conditions and renal cancer.

This study has been commissioned by the National Institute for Health and Care Excellence (NICE) to support NHS England’s Commissioning through Evaluation (CtE) programme. As part of this CtE project the centres delivering SABR treatment will be collecting routine clinical data and data on quality of life, pain symptoms and patient experience using the interim access tool developed by King’s Technology Evaluation Centre (KiTEC - part of King's College London). KiTEC will be undertaking the analysis of this data in order to answer the NHS England evaluation question whether the treatment offers to these patients improved clinical outcomes in combination with less side effects and improved quality of life.

The evaluation scheme is being run for three years in a total of fifteen specialised centres in England, although not all centres are offering SABR to all three sets of patients. The first patient was recruited in June of 2015, and it is currently anticipated that patients will be enrolled up until September-2018, with patients being followed up for two years. As of September 2018, the number of patients recruited across all seventeen participating centres is approximately 1,700.

This CtE project has HRA ethics approval for the analysis of these patient data already recorded by the NHS Trusts delivering SABR in a pseudonymised format by KiTEC. This is, therefore, a low-risk observational data analysis.

The research is non-interventional as it deals with the collation of routine outcome data already collected after patients provide informed consent as part of their clinical management to undergo SABR. Consent to undergo SABR has been undertaken by the individual NHS Trusts.

The patients have consented for their data to be analysed by KiTEC. This consent is separate to their treatment consent.

This project seeks to identify the impact in secondary care health settings taking into consideration all contacts with hospitals. KiTEC are requesting data from NHS Digital to add to the commissioning through evaluation database that is currently being populated, as patients may see other healthcare professionals outside of the trial, or their participating centre. All of the work will take place within the UK.

KiTEC are acting as the sole Data Controller in relation to this study, and have engaged University Hospitals Birmingham (UHB) for the data management element of the study (managing and administering the database), acting under instruction from KiTEC. Additionally, KITEC are responsible for undertaking any analyses, therefore pseudonymised patient-level data will need to be shared between UHB and KiTEC.

A report that describes the evidence for the clinical and cost-effectiveness of SABR will be presented to the UK SABR consortium, NHS England, and NICE and will be used to inform future commissioning. Following review by the project's stakeholders, this report will be then submitted for publication in peer review journals. Outputs from the project will contain only data that is aggregated (with small numbers suppressed in line with the HES Analysis Guide).

The evaluation should show that there is an improvement in patient outcomes and a reduced burden on the NHS for subsequent treatment of complications and recurrence.

The aggregated SABR procedures numbers by centre, is required on a quarterly basis. This number will be compared with the number of procedures included in the database. Should there be a discrepancy, the data lead or data processor for that centre will need to be contacted. For the avoidance of doubt, this will not require HES data to be shared with the participating centres.

KiTEC are acting as the sole Data Controller in relation to this study, and have engaged University Hospitals Birmingham (UHB) for the data management element of the study (managing and administering the database), acting under instruction from KiTEC. KITEC are responsible for undertaking any analyses, therefore pseudonymised patient-level data will need to be shared between UHB and KiTEC.

UHB will create a pseudonymised extraction of data on a bi-monthly basis which will be sent to KiTEC for them to complete their analyses. All data shared from UHB to KCL will be pseudonymised.

In addition, identifiable data captured in the SABR database will need to be linked to relevant HES/Mortality records. This will enable accurate mortality data to be captured, as well as data on other diagnoses or procedures patients may have had at other departments (internal or external to the treating hospital), thus increasing the accuracy of the recording of both adverse event and mortality in the database. This process will require the collection of identifiable patient data (NHS number as a minimum), as well obtaining access to equivalently identifiable HES/Mortality patient records. UHB will receive and process the data.

In order to answer the evaluation question whether the treatment offers to these patients improved clinical outcomes in combination with less side effects and improved quality of life descriptive statistics will be presented to characterise the patient populations. This will include demographic and clinical factors.

Estimates of the rates of overall survival and progression-free survival (local control) at 1 year and 2 years following treatment with SABR will be calculated using the Kaplan-Meier method, for each of the three included indications (oligometastatic disease, re-irradiation of pelvis/spine, and hepatocellular carcinoma). A measure of the precision of each estimate will be provided by 95% confidence intervals. Kaplan-Meier graphs will be presented for key outcomes.

Survival estimates will be compared narratively with the ‘target outcomes’ for each condition (i.e. not using statistical tests), since the target outcomes were informed by a mixture of relevant literature and expert opinion, and therefore, there is no appropriate ‘sampling error’ which can be attributed to these outcomes (a requirement of statistical tests).

The number and percentage of adverse events following treatment with SABR will be presented with 95% confidence intervals, for each of the three indications.

The cost-effectiveness of providing SABR in cohorts of patients included in the CtE scheme (oligometastases, re-irradiation and hepatocellular carcinoma (HCC)) will be evaluated using a commonly applied Markov model of cancer. The model will include three states: progression free; progression; and death. Progression will be defined as the failure of local control. Patients accrue costs and quality-adjusted life expectancy for each period or time cycle they spend in either progression-free or progression states. Patients transit in the direction of the arrows with a given probability at the end of each time cycle and the model is run over a defined number of cycles (periods of time) allowing an estimate of total costs and quality-adjusted life expectancy for the cohort over the specified time period.

The following describes the flow of data for the SABR Study without data from NHS Digital:

1) Treatment centres collect data about the patients

2) Treatment centres submit the data (routine clinical data, quality of life, pain symptoms, etc.) to UHB.

3) UHB store the data on their servers

4) UHB send bi-monthly extracts of the pseudonymised data to KiTEC for analysis

The following describes the flow of data for the SABR Study including a supply of data from NHS Digital:

1) Treatment centres collect data about the patients

2) Treatment centres submit the data (routine clinical data, quality of life, pain symptoms, etc.) to UHB.

3) UHB store the data on their servers

4) UHB provide patient identifiers to NHS Digital which NHS Digital will use to identify relevant HES and mortality data

5) NHS Digital supplies hospital and mortality data to UHB

6) UHB stores the data on their servers

7) UHB send bi-monthly extracts of the pseudonymised data to KiTEC for analysis

The only data linkage permitted with NHS Digital data is the link with the data submitted by NHS treatment centres.

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).

Outputs from the project will contain only data that is aggregated (with small numbers suppressed in line with the HES Analysis Guide).

A final report on the analyses will be generated by KiTEC for NHS England and NICE that will answer the questions below:

- What is the 1-year and 2-year survival following treatment with SABR for the indications covered by the Commissioning through Evaluation (CtE) scheme (presented as estimates with confidence intervals)? How do these survival estimates compare with the target outcomes (see section 4), in terms of superiority or non-inferiority?

- Does treatment with SABR for the clinical indications covered within the CtE scheme increase LC?

- What Adverse Events occur as a result of SABR in the CtE cohort of patients?

- What is the patient experience of treatment with SABR for the clinical indications covered within the CtE programme?

- What is the cost-effectiveness of providing SABR in three subgroups of patients covered within the CtE scheme (oligometastases (liver), HCC, and pelvis re-irradiation)?

- What are the outcomes by indication in the CtE cohort of patients?

- Are there any factors from the experience of centres participating in the scheme that should be taken into account in terms of future service provision?

- Are there any research findings that have become available during the course of the CtE scheme that should be considered alongside the evaluative findings of the CtE scheme?

The final report will follow the NHS England and NICE guidelines for the production of such a report.

As well as the final report for NHE England and NICE, peer-review papers will be produced by both UHB and KiTEC, these reports will be on aggregate analyses, and will only include supplementary information from HES/ONS which will have the small numbers suppressed. The information may also be presented at relevant national and international conferences.

No outputs are planned specifically for any charities or patient groups [because the focus of the study is to influence commissioning policy (through NICE and NHS England), and it is at the point of any decision to change policy that the findings of the study will be addressed to the public], however, the report containing the results of KiTEC’s analysis for the Commissioning through Evaluation (CtE)” programme, when finalised, will be made publicly available. KiTEC will also produce a publication that will be made available to the public through open access; a direct link will be displayed on the KiTEC website.

This project is evaluating the effectiveness of Stereotactic Ablative Radiotherapy (SABR), an emerging novel radiation therapy technology in three specific areas outlined. The three areas include: oligometastatic cancer, cancer recurred in a site treated previously with radiotherapy, and patients with hepatocellular carcinoma. SABR is a specialized radiotherapy technique that delivers a high dose of radiation to the tumour while minimising the dose received by normal tissues, potentially minimising radiotherapy treatment toxicity and side effects. This project will look at both the impact on the patients as well as the financial impact to the NHS. This project will determine whether the treatment under investigation has both a positive benefit for patients and the NHS, or whether it has any disadvantages that have not previously been identified. If the findings are positive then this treatment may mean that patients end up undergoing fewer unsuccessful treatments and that the patient experience and survival are improved.

Not stated in the register.