Cancer survivorship

Improvements in cancer screening, early detection, and treatments mean there are an estimated 2.5 million people living with and beyond cancer in the United Kingdom, which is expected to rise to 4 million by 2030 [1]. Cancer is increasingly viewed as a chronic condition [2, 3], with median overall survival in cancer patients increasing since the 1970s [4]. Though improvements in treatments are reducing mortality and extending life, cancer continues to impact upon people’s lives long after treatment is over. Cancer survivorship refers to the time of diagnosis until the end of life and focuses on aspects of life such as physical, mental, emotional, social, and financial implications that occur from diagnosis, throughout treatment, and beyond [5]. Cancer survivors can face profound and lasting, physical, social, financial and psychological complications secondary to cancer diagnosis and treatment, with an estimated 25% of cancer survivors facing poor health or disability [6, 7].

Cancer survivorship has moved from being marginal to being mainstream on the health agenda [8–10], with survivorship care now perceived as a societal, third sector, and government priority [11]. Aftercare is increasingly provided through risk-stratified pathways, as hospital follow-up is being reduced and more care is being delivered within primary care [8, 10]. A primary care electronic health record (EHR) study reported an increased incidence of chronic illnesses, such as heart failure, coronary artery disease, dementia and diabetes mellitus were identified among survivors of different types of cancers, as compared to matched controls [12]. However, there is currently little evidence concerning: (i) the magnitude and variability between patients in terms of late morbidity, (ii) the costs for primary care, hospitals and patients associated with life after primary cancer treatment, (iii) the cost effectiveness of aftercare services, or (iv) the requirements of users of these services [11].

Patient Reported Outcome Measures (PROMs)

Healthcare providers strongly focus on the clinical outcomes and tend to give limited consideration to symptom intensity, particularly with subjective symptoms such as fatigue and dyspnoea [13–15]. The importance of capturing the patients’ own perspectives is becoming recognised and incorporated into clinical practice and research [16–18]. PROMs (Patient Reported Outcome Measures) are validated questionnaires completed directly by patients on their health and symptoms. In the UK, the National Health Service (NHS) White Paper, Equity and Excellence [19], recommends the wider use of PROMs and patient experience data to place patients at the heart of the health service. PROMs studies have revealed the significant unmet needs of cancer survivors, for example: for breast cancer, studies have shown deficits in physical and social functioning, arm and/or shoulder pain, fatigue, sexual difficulties, insomnia and financial issues [20–25]; for colorectal cancer survivors, studies have indicated bowel and/or urinary control issues, constipation, diarrhoea, sexual difficulties, fatigue, pain [26–28]; and within ovarian cancer, sexual dysfunction and psychosocial issues such as distress depression and anxiety [29–31].

Conversely, some studies have found that for certain cancers, survivors score similarly to the general population for some aspects of quality of life [22, 28, 31–33]. However, there remains a lack of high-quality large-scale studies comparing the quality of life (QoL) for long-term cancer survivors with age and gender matched controls and larger sample sizes. The department of Health recommended the introduction of an innovative quality of life metric to track and respond to the long-term impact of cancer. The Independent Cancer Taskforce in their strategy for England 2015–2020 [9] and NHS Long Term Plan [34] have recommended the introduction and implementation of Quality of Life data collection for cancer survivors in England. Pilot projects are underway looking at electronic methods of patient self-reported questionnaires. Therefore, this paper proposes a protocol to test the feasibility of integrating PROMs data into NHS systems in order to link with PROMs and healthcare records, and to gain a broader picture of life following a cancer diagnosis compared to matched controls.

Comprehensive Patient Records (CPR)

The study outlined in this paper is part of a larger programme of work called Comprehensive Patient Records for Cancer Outcomes (known as CPR) [35, 36]. CPR aims to develop a clearer picture of what happens to people living with and beyond cancer, and the costs to individuals and the healthcare system associated with their care, by securely linking de-identified information from patient questionnaires, electronic primary care and hospital records. The analysis is based upon data drawn from the records of 100,000 cancer patients and 500,000 matched controls. The CPR study comprises five workstreams: (1) data linkage, (2) co-morbidity and late effects of cancer, (3) identifying and predicting recurrence, (4) a health economic analysis of the long term costs of cancer to individuals and the healthcare system, and (5) patient reported costs of living with and beyond cancer (known as the Patient Reported Outcome Measures (PROMs) workstream). The PROMs workstream is the focus of this paper.

CPR PROMs involves collecting PROMs data directly from a subset of the main study population, and integrating it with an identical duplicate of the data collected from Electronic Health Records (EHR) in the main CPR study for this subset of patients. In doing so, CPR PROMs will test the feasibility of collecting PROMs from patients, and linking the PROMs data to patient records. This will enable a truly ‘comprehensive patient record’ to provide a broad picture of what happens to cancer patients across their cancer pathway, and the long-term impact of cancer treatment. Comparisons can be made between the cases and controls, to identify the aspects of life that has had the greatest impact following a cancer diagnosis.

Aim

The primary aim of this CPR PROMs study is to examine the long-term QoL, personal finances, psychological health, physical health, and social impacts of people living with and beyond a cancer diagnosis. The secondary aim of the study is to test the feasibility of the collection of PROMs data and the linkage procedures of the PROMs data to routine data, to investigate the full impact of cancer on individuals across a wide range of domains. Linkage of the PROMs data to routine data could enable a truly ‘comprehensive patient record’ to be created showing the long-term effects of cancer on factors such as quality of life, health, co-morbidities, and well-being.

Objectives

1. To collect PROMs data from a cohort of cancer survivors in breast, colorectal and ovarian cancer, and compare these with PROMs data collected from matched individuals without cancer. Data will include: long-term QoL, personal finances, psychological, and social impacts.
2. To integrate PROMs data with de-identified routinely collected primary care and hospital records data using the secure systems for data linkage approved for our wider programme of work [35, 36].
3. To test the feasibility of the PROMs collection and data linkage procedures for use in other research studies and patient care.

An overview of the data collection procedures and pseudonymisation is displayed in Fig 1.

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Fig 1. Diagram illustrating a brief over view of CPR PROMs data collection and pseudonymisation.

Note. PPM (Patient Pathway Management) is an electronic patient record to record and deliver patient records across the Leeds Teaching Hospital Trust NHS Spine supports the IT infrastructure for health and social care in England and enables information to be exchanged across local and national computer systems Clinical Research Facility conducts early stage and experimental trials in a range of disease specialities.

https://doi.org/10.1371/journal.pone.0266804.g001

Study design

The study uses a cross-section of matched-control PROMs survey with data linkage to de-identified hospital data (via Leeds Teaching Hospitals NHS Trust, LTHT) and primary care (via The Phoenix Partnership, TPP).

Study setting

Patients will be recruited from LTHT, one of the largest teaching hospitals in Europe. The hospital provides local and specialist services for the immediate population of 770,000 and regional specialist cancer care for up to 5.4 million people. TPP provide ResearchOne as a primary care research database containing de-identified data extracted from consenting SystmOne GP practices. Some primary care practices using SystmOne have agreed for their practice data to be included in a de-identified format on ResearchOne (a health and care research database which contains linked data from primary and secondary health care), which is also provided by TPP. Full details of the health records linkage is provided in the protocol for our wider programme of work [35, 36].

Participants

Patients will be eligible for this study if they are registered on the LTHT electronic patient record and listed as using a Leeds Clinical Commissioning Group primary care practice. Specific inclusion and exclusion criteria for the cases and matched controls are specified below.

Inclusion criteria for cancer cohort

1. A diagnosis of colorectal cancer (ICD-10 C18—C20), breast cancer (ICD-10 C50) or ovarian cancer (ICD-10 C56)
2. Approximately five years beyond their first cancer diagnosis (e.g., index date = 2013 ± 4 years). Date. Index date was the patient’s clinic appointment date. The year band is expanded incrementally until the full cancer cohort is obtained.
3. 18–100 years old on date of diagnosis

Inclusion criteria for control cohort

1. Reviewed by LTHT dermatology services on a two week wait for potential skin cancer, but were not diagnosed with cancer
2. No cancer diagnosis recorded within LTHT records at any time.
3. One dermatology appointment within 12 month of the matched case’s cancer diagnosis (their index date).
4. Age 18–100 on appointment date.
5. No further dermatology appointment in the 12 months following their index date.
6. Could be matched to cases by age, sex and primary care practice.

Sample size

The survey will be sent out to around 6,000 potential respondents. The estimated consent rate for cases is around 60% which is based on similar postal PROMs surveys recruitment rates of: 63% [37], 68% [38], 49.1% [39]. The anticipated consent rate for controls is lower and estimated at between 23.9% [39] and 30% based on recent returns from a control study matched to cases of men with prostate cancer [40]. Based on expected consent rates, this should result in a sample size of around 1,000 to 1,200 in each group (cases, controls). A power sample size calculation was undertaken using the study’s main measure the QLACS (Quality of Life in Adult Cancer Survivors), and this number exceeds the number of respondents required for 90% power for all the data analysis subsets.

Exclusion criteria cases and controls

All patients must have a valid NHS number. Patients will be excluded if they are on the national opt out register, are identified by LTHT clinicians as not meeting the eligibility criteria (e.g., at risk of lacking decision-making capacity), or if patients have informed LTHT they want to opt out of research. The primary care data available from the main CPR study may not be available for all patients within the CPR PROMs cohort. This is due to some patients who have opted out of R1 (an electronic database which stores non-identifiable patient records that have ethical approval to be used in research) being excluded from the main study dataset and some patients not attending a practice that uses R1.Thus, primary care data will only be linked where it is eligible and available.

Identification

Potential participants will be identified from LTHT’s internal computer patient management system, Patient Pathway Manager using a computerised search query created from the inclusion and exclusion criteria. If the query search produces too many results, potential participants will be randomly selected using a randomisation process. We will check the NHS Spine immediately prior to the mail out to ensure surveys are not mailed out to patients who have been recorded as deceased, and that ‘up to date’ names and addresses are retrieved.

Survey and invitation letter design

The survey content comprises psychometrically sound questionnaires relevant to the cancer survivor groups under investigation. The content was informed by the results of extensive engagement with patients and clinical staff. This included: clinical shadowing in consultant-led and nurse-led follow-up clinics for breast, colorectal and ovarian cancer; conversations with cancer clinicians and specialists; a ‘word wall’ activity in patient clinics to allow cancer patients to rank and discuss issues of importance to them (the ‘word wall’ is a novel visual method which allows participants to rank items by moving them around a board); and an electronic online ‘word wall’ activity undertaken by active service users from the websites Macmillan ‘Cancer Voices’ [41] and ‘use MY data’ [42, 43]. The survey was limited to be less than 120 items as a recent PROMs survey of cancer survivors had a response rate of 60% with 120 items [37]. A final review by patients and staff was undertaken to ensure the full scope of topics was included without being too burdensome. The survey takes around 30 minutes to complete. Patient and public involvement was also utilised to inform the letter that was sent out with the survey to invite people to participate in the study. People who have not been diagnosed with cancer provided feedback on receiving a letter about an oncology study and minimising anxiety.

Survey measures

The survey comprises four sections with 108 items for cases and 100 items for controls (see Table 1 for overview of survey). The same questions will be used for cancer survivors and the controls unless specific item changes are required for the control group.

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Table 1. An overview of the PROMs included in the survey.

https://doi.org/10.1371/journal.pone.0266804.t001

Section 1: Questions about you

Patients will be asked to provide basic background information about ethnicity, height and weight, relationship status (at the time of the survey, and at the time of their cancer diagnosis/or 5 years ago for controls), highest level of education, co-morbidities.

Section 2: Questions about your health

Section 3: Questions about your lifestyle

Section 4: Questions about your healthcare and finances

Survey administration

The survey may be completed on paper (delivered by post) or online.

Paper completion

A paper survey with a unique Participant Identification number (PID) and a freepost envelope for return to the research team will be mailed to each potential participant.

Online completion

The invitation letter will provide a website address for the survey and a unique participant log in (based on the PID) and password. The web-based system (QTool) is hosted securely by the Integrated Research Campus (IRC) at the University of Leeds [71].

Pilot study

A pilot study of 5% of total research population will be undertaken using the processes detailed below. Should negative responses be received, the study methods and processes will be reviewed and amendments undertaken if required.

Recruitment

Participant identification and recruitment are undertaken entirely within LTHT, the research team have no access to patient identifiable data (approved by the UK’s Health Research Authority (HRA) Confidentiality Advisory Group (CAG) (Reference: 18/CAG/0119)). The stages are summarised in Fig 1 and outlined in more detail below.

LTHT data analysts will generate a list of potential respondents by creating and running a query on the internal electronic patient management system derived from the eligibility and exclusion criteria. A list of identifiable data (name, address and NHS number) will be extracted and sent to LTHT IT Services using secure LTHT computer systems. A member of the LTHT IT Services team will check the list of potential respondents on the NHS Digital Spine (https://digital.nhs.uk/spine) for name, address and death. The updated list will be sent to the LTHT Clinical Research Facility who will manage the lists. The LTHT Clinical Research Facility conducts early stage and experimental trials in a range of disease specialities.

The clinical Research Facility will allocate PIDs using an automated process and will be the ‘key-holder’ for linking the PID to the individual patient within the secure LTHT systems. An automated ‘mail merge’ process will be used to merge the list of patients’ names and addresses with an invitation letter and survey. The completed ‘mail merge’ templates will be sent to LTHT medical secretaries for printing. Printed letters, signed by a consultant on behalf of the relevant treating Multi-Disciplinary Team (MDT), and containing the Participant Information Sheet will be mailed via the LTHT post room. Following a second NHS Digital spine check, a reminder letter will be sent after four weeks to those who have not responded at all and who have not contacted the research team requesting study withdrawal.

Consent

Informed consent (ticking or dating the front page of the paper survey or clicking the first page of the online survey) will be sought from participants for taking part in the PROMs survey and for the data linkage to de-identified data from hospital and primary care records, in accordance with the Data Protection Act 2018. The invitation letter and Participant Information Sheet will provide detail of the study aims, methods and processes for participation and withdrawal.

PROMs data

All collected PROMs data is non-identifiable and participants are asked not to include any identifiable data on their survey return. Each PROMs survey has a research participant ID. LTHT, who send the invitation and survey, retain a link between the research ID and the patient record (i.e. the PROMs data is reversibly pseudonymous from the perspective of LTHT).

Pseudonymisation and data linkage

LTHT will derive a project-specific pseudonym (called a “digest”) for each patient involved in the project and retain a link from this to the patient record ID. Participants consent to be part of the PROMs study and have their data linked by returning a completed survey. A list of research IDs is derived from the completed surveys and provided to the LTHT data analysts who use this to determine the pseudonymous digest for the PROMs participants. The digests are linked to the non-identifiable PROMs survey data. This is then transferred to a NHS and University of Leeds approved physical or cloud computing environment and linked with hospital data from LTHT and de-identified primary care data from ResearchOne via project specific digests (where the data is available and eligible). The process of linkage, with the linkage field subsequently being destroyed, will mirror the procedure of the main study, so that the research dataset cannot be linked back to data sources. A full explanation of the data linkage and pseudonymisation methodology has been previously published [35, 36]. This process uses the open source software OpenPseudonymiser [74]. The computing systems have advanced computational highly secure infrastructure with accredited certification to the international standard for information security management, ISO/IEC 27001:2013 and Level 2 NHS Information governance (IG) Toolkit.

Data on non-responders

Invited participants who do not respond to the survey are defined as ‘non-responders’. De-identified double-pseudonymised data will be requested on non-responders for the purpose of testing the response bias of the sample. This will be collected by the process described above, though necessarily without any PROMs data. The Research ID of non-responders is linked with the project-specific digest under the LTHT Fair Processing Notice. The data handling is similarly in accordance with the common law duty of confidentiality because the data is rendered anonymous through de-identification processes. The data providers (LTHT and TPP) have reviewed the data processing (as advised by the Health Research Authority Confidentiality Advisory Group) as part of the main study: Comprehensive Patient Records (CPR) for Cancer Outcomes, Research Ethics Committee reference: 16/NE/0155), and deemed the data to be de-identified. It is under the data providers’ approval that this data is used.

Data input

For those participants choosing to complete online, the weblink provided will allow participants to input their data directly onto QTool. For those choosing to return the paper survey, the surveys will be input onto QTool by LTHT medical and university secretarial staff.

Data storage

Compliance and approvals

This study will be conducted in accordance with both the Data Protection Act (2018) and the General Data Protection Regulation 2018. All clinical staff and research staff involved in the study have NHS (or honorary NHS) contracts and work to NHS codes of practice concerning confidentiality, information security management and records management (NHS Code of Confidentiality, 2003). This project was approved by the HRA (04/10/2018 IRAS Reference: 233983); HRA NHS Research Ethics Committee (10/09/2018 Research Ethics Committee Reference: 18/LO/1043); HRA NHS Confidentiality Advisory Group (CAG) approval (02/08/2018 CAG Reference: 18/CAG/0119); LTHT Capability and Capacity approval (14/03/2018); and received NIHR Portfolio study (12/09/2018 Reference: CPMS 39154).

Primary outcome

The QLACS is the primary outcome measure. The generic summary scores of the cancer survivor’s cohort will be compared to those of the matched controls to identify statistically and clinically significant differences. Comparisons will also be made on the individual domains of the QLACS, excluding those where comparative data is not available for controls (distress-recurrence and benefits of cancer). Subgroup analysis will be undertaken by cancer type.

Secondary outcomes

Secondary measures will be used to further explore the differences between the cancer survivors and the matched controls using the PROMs measure and the linked primary and secondary data, on the topics of:

• Health and quality of life using the EQ-5D-3L and VAS, and items from the EORTC bank.
• Difficulties navigating the healthcare system, using the PROMs measure CCCQ (Cancer Care Coordination Questionnaire) and de-identified healthcare appointment and co-morbidities data from primary and secondary care;
• Exercise, using the PROMs measures EBBS (Exercise Barriers and Benefits Scale) and GLTEQ (Godin Leisure-Time Exercise Questionnaire);
• Cancer survivor identity, using the included question on identity;
• Financial costs of cancer and personal financial impact, using the data collected in the questionnaire

Feasibility assessment