Primary aims

1. To describe the HRQL (eg, physical, psychosocial) of men with prostate cancer using qualitative and quantitative methods;

2. To explore if and how their HRQL is associated with or is predicted by disease, treatment and/or patient characteristics with a view to inform development of healthcare policy and service delivery in ways that better meet the needs of such men and their families;

3. To describe the levels of patient empowerment and undertake preliminary exploration of the interaction between patient empowerment and HRQL.

4. To undertake a normative study of men without prostate cancer to determine community levels of symptoms for comparison.

Secondary aims

1. To undertake provider-level and health economic analyses, and explore methods for producing robust, meaningful comparisons of outcomes across the UK;

2. To explore the acceptability/options of electronic PROMs data collection;

3. To explore and check the psychometric properties (eg, reliability, validity) of the newer, less well-established questionnaire measures used in the study;

4. To investigate the possibility of developing an item-bank for HRQL assessment in men living with and beyond prostate cancer;

5. To identify ‘gaps’ within existing surveys that are of importance to patients and partners/spouses.

The study will achieve these aims through six interlinking work-streams centred round the collection of PROMs data and linkage with existing data sets (figure 1). The study will collect data from across all nations in the UK. While the survey questionnaire and analysis will be similar, the methodology differs in parts for each country in order to satisfy legal governance requirements; this is made clear throughout the protocol.

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Figure 1

Study overview.

A: survey development

A survey instrument has been developed which covers a range of generic and cancer-specific PROMs plus items covering treatments received, sociodemographic characteristics and the patient perspective on their disease, treatment and experiences. The survey content has been informed by a range of factors. These include the incorporation of questionnaire measures which will be used by international colleagues in similar surveys undertaken in their countries,35 three systematic reviews of questionnaires used in prostate cancer research36–38 and the International Consortium for Health Outcomes Measurement (ICHOM) recommendations for a minimum outcomes data set for men with localised prostate cancer.39 The experiences from other surveys undertaken by the coapplicants, including scope and response rates,40 the availability of routine demographic and health data (to avoid duplicate collection of information), questionnaire burden (length/number of items; suggested ≈100 acceptable), item duplication/ redundancy, costs and permission, and the priorities of different coapplicants and advisory group members, including service users were also considered. In addition to the survey items included, a free-text box is included at the end of each survey section for respondents to add further detail or to capture any other important relevant issues not covered in the section.

B: survey delivery

Men who are between 18 and 42 months postdiagnosis of prostate cancer will be eligible for inclusion in the study. Eligible men will be identified through cancer registration systems in England, Wales and Northern Ireland, and through hospital activity data in Scotland (with verification of a cancer diagnosis by cancer registration records). Two discrete cohorts of men will be surveyed in each UK nation (see table 1 and figure 2 for more information on the cohorts, timelines and expected numbers).

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Figure 2

Schematic outline of proposed patient-reported outcome measures data collection.

Methodology

The methods for delivering the survey and the subsequent data flows are outlined in figure 3. These vary within each nation due to differing legal and governance processes and guidelines. The methodology for England (the largest portion of the survey) is outlined here. Deviations from this methodology in the other nations are summarised below and in table 1.

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Figure 3

Study data flows.

England

The methodology follows that successfully used by the National Colorectal PROMs Survey, England 2013.32 Briefly, the National Cancer Registration and Analysis Service (NCRAS), study team and funder will write to the Chief Executive and prostate cancer MDT lead of each Trust to seek their permission to survey men treated by their Trust. Trusts will be offered the chance to verify the list of identified patients and filter any patients where contact would be inappropriate. For the Trusts that agree to take part, the NCRAS will extract a list of eligible men and send this securely to NHS Digital for up-to-date address tracing and death checks (48 hours prior to mailing). On completion of these checks, the information will be passed on to the appointed survey provider, Picker Institute Europe. The survey will be sent out with a covering letter from the treating NHS Trust's Chief Executive and MDT lead and a participant information sheet. All documents will indicate that the survey is only to be completed if the patient has received a diagnosis of prostate cancer. A double-windowed envelope method will be used to reduce the chances of someone other than the addressee opening the survey. A translation sheet will be included which, in the 20 most spoken minority languages in the UK, informs participants that if they have any questions, or would like to speak to an interpreter, they can call the study helpline and they can then complete the survey over the phone in their preferred language.

Patients who agree to participate will complete the questionnaire which will be returned in prepaid envelopes to Picker Institute Europe. The questionnaires will not contain any personal information (ie, no names or addresses) but will be assigned a unique reference number (URN). The URN can be linked back to the original patient list in order to keep track of which men have returned the survey or have opted out (by returning the survey blank or phoning the dedicated survey helpline). Two reminders will be sent (with additional death checks performed each time). Picker Institute Europe will scan the completed surveys, transcribe any written ‘free-text’ comments and clean the data, including removing any identifying information where patients may have named specific Trusts or clinicians. The cleaned electronic data will be sent back to NCRAS using a secure transfer mechanism where they will be linked back to the necessary patient, disease and treatment information. The data set of pseudonymised survey responses, disease and treatment information will be forwarded, alongside a study ID number, to the research teams for analysis.

Wales

In Wales, the methodology follows that for England with a few minor changes. Approval will be sought at the Health Board level rather than individual Trusts. Following approval, eligible men will be identified through the Welsh Cancer Intelligence and Surveillance Unit (WCISU). The letters and patient information sheet will be provided in Welsh and English. However, the first survey will only be available in English, as not all of the items and scales included have been validated in Welsh. Those participants that wish to complete the questionnaire in Welsh will be able to do so by telephoning the survey helpline and articulating their responses to a Welsh speaker. It is hoped that subsequent surveys will also be available in Welsh once translation and validation of the items has been undertaken.

Northern Ireland

The methods for undertaking the survey in Northern Ireland follow those used for the International Cancer Benchmarking Partnership Module 4.56 Northern Ireland Cancer Registry (NICR) staff will compile a list of eligible men and will confirm diagnosis of prostate cancer using ‘stage of cancer’. Where stage is missing and a prostate cancer diagnosis cannot be confirmed by the NICR, a list of unconfirmed patients will be sent to research nurses for a final check. The lists of patients will also be available for MDT leads to view on request.

As information from the NICR cannot be passed to an external survey provider, Picker Institute Europe will provide pre made-up packs, containing the survey and cover letter, each with the same URN. The cover letter will have the logo of the Trust of residence at the time of diagnosis and the signatures of all three Northern Ireland Urology MDT leads. The NICR staff will print labels with the names and addresses of the eligible men and these labels will be cross checked against the URN before being applied to the cover letter. A death check will be carried out by the NICR staff (via Northern Ireland Business Services Organisation (BSO)) 24 hours before the surveys are posted. Patients will return the questionnaires to Picker Institute Europe in the prepaid envelope provided. On a fortnightly basis, Picker Institute Europe will supply the NICR staff with a list of the URNs for the patients who have responded and will also provide the associated reminder letters/packs. The NICR staff will carry out further death checks and send up to two reminders to the non-responders.

Scotland

In Scotland, patients identified from the Scottish Cancer Registry can only be approached through their doctor. In previous studies, this has resulted in low response rates (∼30%) and placed a high administrative burden on NHS National Services Scotland and GP practices. As such, this study will follow the methodology approved for the 2015 Scottish Cancer Patient Experience Survey.

Information Services Division (ISD: part of NHS National Services Scotland, Public Health and Intelligence) will identify eligible participants using hospital activity data, with cross checking against the Scottish Cancer Registry to confirm a diagnosis of prostate cancer in the required timeframe. This method means that only around 65% of Scottish men diagnosed with prostate cancer in the required timeframe will be sampled. The sample will also include a higher rate of men who have had surgery to treat their prostate cancer than the full population of men with prostate cancer. The sample will therefore be adjusted by removing a small number of men who have had surgery, using stratification to ensure that the sample otherwise retains the same profile as the full population of Scottish men with prostate cancer. ISD will carry out initial death checks against National Records for Scotland (NRS) deaths data and request current name and address for sampled patients from the Community Health Index (CHI) database. ISD will coordinate further death checking with the Scottish NHS Central Register (NHSCR) and the CHI database, to be run overnight before the day of each mail-out. ISD will pass the mailing lists and results of death checking to Picker Institute Europe who will post survey packs to eligible participants using URNs to track responses. The covering letters will be signed by the Medical Director for the NHS Board in which the patient currently lives (which may not be where some of their treatment was received).

Picker Institute Europe will pass the response data to ISD for further linkage (eg, cancer type and stage, treatment information). These data will only be added where the responding patient has given their consent for linkage. ISD will also provide basic demographic and treatment data for the men who have not responded to the survey (at an aggregated level), so that the full cohort can be described and the potential for bias in response fully assessed. The pseudonymised Scottish data set will then be passed to the research team.

Normative study

Many of the symptoms experienced by patients with prostate cancer are common in the general population. Therefore, to understand and document health and quality of life deficits experienced by patients with prostate cancer, we need to develop an understanding of the background levels of these symptoms in the population. To this end, a normative study will be conducted in Northern Ireland. Using GP registration data, BSO will generate a reference group of 10 000 men matched by 5-year age band and deprivation quintile to patients with prostate cancer. BSO will issue questionnaires with participants responding anonymously directly to Picker Institute Europe. The normative study questionnaire has been adapted from the main prostate cancer questionnaire, with exclusion of questions relating specifically to the prostate cancer diagnosis. Validated instruments were not amended. The tool was reviewed by the study advisory groups and by a focus group of older men in NI. A pilot survey of 500 men will be used to test response rates, bias and acceptability of the survey to the general public.

Assuming a 33% response rate, the sample size will allow (at 80% power and 5% confidence level) observation of a 6% difference in the proportion of 190 patients with prostate cancer aged 80+ reporting severe difficulty or inability to perform usual activities compared with the normative population. This will allow hypothesis testing that significant differences in health in patients with prostate cancer exist compared with the general population.

Free-phone helpline/symptoms process

A 24 hour free-phone service will be provided during the times when surveys are live. Any queries relating to prostate cancer symptoms or disease management will be directed to the Prostate Cancer UK (PCUK) nurse-led telephone advice service. For other queries, for example, the patient wishes to report they do not have cancer or the patient does not wish to be contacted again, an escalation process has been developed (figure 4). Procedures to rapidly manage and report any symptoms/incidents arising from the survey have been established. It is not possible to foresee all possible queries that will be raised by the patients, but these processes have been developed to deal with the issues that have arisen in previous PROMs surveys.

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Figure 4

Patient query escalation process.

Cross-sectional telephone interviews (year 1)

Sampling, recruitment and interviews will start ∼4–6 weeks after survey opening (figure 5). Survey participants will be asked to tick a box indicating their interest in taking part in a telephone interview. Using a sampling framework, Picker Institute Europe will randomly select individuals who have agreed to be interviewed. Sample groups comprise the four main treatment groups: radical prostatectomy; radical radiotherapy; systemic therapy (hormone therapy); active monitoring (active surveillance and watchful waiting), and a group of black and minority ethnic (BME) men from across the treatments groups. Approximately 100 men will be interviewed in England and 50 men from across the 3 devolved nations (NI /Wales/Scotland). There may be subtle differences in the processes for contacting men across the different nations.

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Figure 5

Outline of qualitative data collection process.

Approximately five times, the required number of men will be identified by Picker for each group in order to meet the target of completed interviews. Picker will then send the names and addresses of the selected men to the research team. From this randomised sample, the research team will then purposively select men for interview to include a range of interviewees in terms of age, marital status, time since diagnosis, sexual orientation and prostate cancer-related problems.

The research team will send selected men an invitation pack containing a letter, participant information sheet, consent form and reply slip (for them to respond with their telephone number and email address, should they wish to take part in the interview). A reminder letter will be sent to non-responders after 2 weeks. Researchers will contact responders by phone/email and arrange a date/time for the telephone interview for approximately a week (but more than 48 hours) later. If there is no reply at the set interview time, the researcher will try to contact the participant by telephone/email to arrange another time on up to two separate occasions over the following 2 weeks, after which the researcher will stop trying to contact the individual.

A further sample group comprising partners/spouses of men with prostate cancer will be interviewed (n=20 in England and n=10 across the three devolved nations). The survey will ask men to indicate on a tick box whether their partner/spouse (should they have one) would be interested in being interviewed. Partners will be sampled by Picker according to treatment type and sociodemographic characteristics of the respondent (five times the required number). Contact details will be sent by Picker to the research team. The research team will then purposively select a small group to be invited to be interviewed.

The research team will then write to the respondent informing them that the researchers would like to interview their partner. The respondent will be asked to give the enclosed invitation letter, participant information sheet, consent form and reply slip to their partner. A reminder letter will be sent to non-responders after 2 weeks. Once a partner reply slip is received, a researcher will contact them by phone/email and arrange a date/time for the telephone interview to take place (procedure as outlined above for the participants).

The consent form will be read through with the individual (patient or partner) over the phone immediately prior to the interview taking place. Verbal consent to participate in the study and for audio-recording of the interview will be obtained. The interviewer will initial the tick boxes on the consent forms as they read them through, date and sign two copies and offer to send one copy to the patient/partner. Completed consent forms will be stored in a locked filing cabinet within a locked office in the University of Southampton or Oxford Brookes University.

Two separate recordings will be made, one for consent, the other for the interview. Audio files recording consent will be labelled and stored in the study's secure data repository. Researchers will ensure that interview recordings are anonymised by deleting any identifiable information that interviewees may have inadvertently disclosed. The recordings will then be transcribed verbatim by professional transcribers who have signed confidentiality agreements with either the University of Southampton or Oxford Brookes University.

Data collection and analysis will be synchronous, allowing the interview team to be aware of emerging themes while data collection continues. Three trained and experienced researchers will conduct the telephone interviews. Regular meetings will take place throughout the data collection process to review progress, interview techniques and discuss preliminary findings.

Longitudinal interviews (year 2)

At the completion of the first interview, the interviewer will ascertain whether the participant might be willing to take part in a second interview 12 months later. Those who agree to a second interview will be contacted by telephone 12 months later and willingness to be interviewed again confirmed. If so, a date/time will be set for the interview following the same methodology outlined for the year 1 interviews. Baseline interviews with each participant will be read by researchers prior to the second interview to ensure that issues of concern can be revisited to ascertain whether those issues have improved, worsened or been supplanted by other concerns during the intervening period. Owing to time constraints, the longitudinal interviews will take place in England only.

Topic guides

A literature review and meta-synthesis of qualitative studies exploring the experiences of men with prostate cancer and their partners has been undertaken.57 First-order, second-order and third-order constructs from this analysis have informed interview topic guides and ensure that data collected include important concerns previously identified while allowing further issues to emerge. The topic guides will be pilot tested with user representatives.

PhD substudy

As the basis of a PhD studentship, a substudy will aim to explore the experiences and needs of younger men with prostate cancer and their partners, in order to identify ways that couples can be better supported. The substudy will seek to recruit and interview 25 younger men with prostate cancer and their partners, and to conduct a second interview 9–12 months later with those who agree.

Free-text questions

At the end of each of the seven sections of the questionnaire, participants will be invited to provide free-text comments expanding on their responses to the closed questions. At the end of the survey, a final free-text question will ask participants whether there is anything else they would like to comment on regarding their life since diagnosis, which was not covered by the survey. The responses to these questions will be analysed using a variety of methods to identify insights and determine patterns in participant experiences (see the Data analysis and reporting section for more details).

Comparison across countries (benchmarking)

The HRQL and other health-related outcomes of the respondents will be compared, within the UK and internationally, where possible (eg, comparing with Ireland and Australia where similar PROMs work is being undertaken). In this study, information on generic health outcomes will be collected through EQ-5D and cancer-specific outcomes through EPIC-26. A common methodology of data collection would allow meaningful comparisons to be made. Such analyses will require robust adjustment for casemix (age, deprivation level of the population) and other confounding factors to ensure that fair comparisons are made. This will depend on the amount and quality of information across the different countries.

Comparison across providers (organisational performance)

Performing robust comparison across provider organisations, such as hospitals, throws up a number of methodological issues,60 including correct allocation of patients to the institution that provided their main treatment, ensuring a sufficient number of respondents per hospital to allow meaningful comparison, differing response rates by hospital and robust adjustment for casemix. The feasibility of comparison across organisations, taking into account these issues, will be explored. Members of the study team are experienced in analysing the results of large-scale surveys and in the robust assessment of cancer outcomes.32 ,61–63

Feedback of information to providers

Initial results will be reported at national and provider/organisational level after each data collection (within 6 months of completion of data collection). This will be performed using an electronic toolkit, already developed by the team for the colorectal PROMs work, providing a national overview and organisational-level data compared with national averages. This will allow providers to see the responses from their patients and to quickly identify any areas of concern. These results will not, however, be adjusted for differences in casemix. More detailed results taking into account the issues described above will be disseminated to providers through specific topic-focused reports, as well as presentations and academic papers.

User advisory group

The UAG comprises six service user members plus a limited number of (1) health professionals and (2) researchers, with commitment to, as well as detailed expertise and research knowledge and experience of, user concerns and priorities. This Group has adopted Terms of Reference and a modus operandi based on the NIHR ‘PPI Research Cycle Model’.64 The UAG will meet every 3 months and the Chair is a full member of the study team and named Coinvestigator.

Reference group

The UAG's work will be supported by a reference group consisting of prostate cancer service users, partners and family members who will be invited, as appropriate, to provide information and views on particular issues. Members of PCUK's ‘On-Line Community’ (an open forum of PCUK volunteers and bloggers) will be kept up to date about the study and will be appraised of opportunities to contribute to advising the project on specific matters, as and when topics requiring additional input are identified. Those service users who express an interest in offering views on the identified topic will then act, de facto, as a member of the reference group.

Quantitative data analysis

Descriptive statistics will be used to report the survey results and ‘describe’ the health outcomes of men with prostate cancer. The outcome variables, that is, EQ-5D, EPIC-26 and SDI, will be analysed according to stage/severity of disease (TNM and Gleason Score, where available), treatment type, comorbidity, age, ethnic and sociodemographic group (and other relevant variables). These descriptive analyses will identify potential relationships of interest which can be investigated further. Regression modelling will be used to investigate associations and to identify statistically and clinically significant risk factors and predictors of health outcomes. In order to be robust, analyses will require appropriate adjustment for casemix and other confounding factors and may require more complex techniques, such as the modelling of hierarchies within the data (multilevel modelling) and post hoc weighting to overcome response bias. Multiple imputation methods may be used to deal with missing data. A similar methodology would be used for international comparison of health outcomes, depending on the comparability of the survey instruments used.

Respondents from the first cohorts (Cohorts 1 and 2) will be resurveyed 12 months after the initial survey, which will allow measurement of any changes in their outcomes over time. For example, differences in EQ-5D scores could be calculated between the two time points and this would allow assessment of whether outcomes improve, decline or remain static. Interpretation is difficult, however, as there is no information regarding the individuals' health before their cancer diagnosis. Normative data from the general population will be used, where these are available, in order to compare the health of men with prostate cancer with those in the general population and to assess whether their health returns to a ‘normal’ level over time.

New instrument development is not being undertaken as part of this work. However, there is the opportunity to explore and check the psychometric properties of the newer, less well-established questionnaires and to determine the most fitting instruments for future prostate cancer PROMs work using the Rasch analysis.65

Qualitative data analysis