Contents Page - A world-class university – a unique …/file/... · Web viewWomen in the intervention sites will express more positive illness representations (e.g. increased personal

Bridging the Age Gap in Breast Cancer:

Improving outcomes for older women.

Evaluation of a decision support intervention for older women with operable breast cancer.

A study nested within the Age Gap Cohort study.

Version 3 9th March 2016

Age Gap Supplemental Protocol Protocol Version 3 9th March 20161

Evaluation of a decision support intervention for older women with operable breast cancer. A study nested within the Age Gap Cohort

studyExecutive Summary

The Bridging the Age Gap in Breast Cancer study is a multicentre cohort study recruiting up to 3000 older women (>70) with operable breast cancer at up to 50 sites in the UK. Its aim is to collect detailed data about the personal and cancer characteristics of these women, the treatment they receive and what their short, medium and long term outcomes are. The data will be used to help to optimise the care of these older women so treatment can be better tailored to their health and fitness levels, reducing some of the wide practice variation that currently exists across the UK.

The second phase, which will be embedded within the existing study, will be to evaluate whether use of a package of decision support interventions (DESIs), given to 50% of existing sites and embedded as ‘standard of care’, helps to improve the quality of life, decision quality, decision regret, satisfaction and treatment understanding of older women entering the Age Gap study. These DESIs will be aimed at women facing a choice of surgery or primary endocrine therapy (PET) or, following surgery, for those with higher risk cancer facing a choice of chemotherapy or no chemotherapy. These are the two areas where clinical practice in older women differs most markedly from that in younger women and where there are high levels of variation between breast units.

A package of decision support interventions (DESIs) have been developed and will form a resource to be implemented in half of the Age Gap recruiting sites as part of standard care. These sites will be trained in their use which will become a routine part of the counselling they are able to offer all women, whether they are in the Age Gap study or not.

The DESIs comprise 2 patient facing booklets, incorporating 2 option grids and 2 web based algorithms which may be used by the clinical team to predict individual risk and benefit information that may be shared with an individual patient. These resources have been carefully developed using the best available evidence and have undergone extensive user testing, PPI input and field testing (with both patients and staff) to ensure they are accurate and tailored to the information needs of women of this age group. Sites will be allocated at random to utilise the DESIs or simply continue with normal best practice pre treatment counselling.

Data collection for the study will largely be unchanged with all of the current outcomes collected. In addition women will be asked to complete questionnaires about decision regret and feedback about their pre treatment counselling and decision making. Staff and patients in selected sites will be asked to give feedback about the resources as part of a formal process evaluation.

We expect that recruitment to the main study will have reached 2000 by the time we introduce the DESIs into 50% of our sites (based on a recruitment rate of about 70 per month). The study will continue to run for a further 24 months and recruit a further 1600 cases. Most of the data from these phase 2 patients will be co-analysed with the main cohort, but sub-group analysis will take place to compare outcomes in the intervention sites and non intervention sites. We expect recruitment rates to be similar in phases 1 and 2 as the study is largely unchanged other than that staff will have access to the DESIs to use alongside their routine counselling resources as part of normal practice.Age Gap Supplemental Protocol Protocol Version 3 9th March 2016

2

Study Funding and Sponsorship

Proposed start date: 1st September 2015

Proposed recruitment end date: 31th August 2017

Protocol version: Version 3

Funding

Title: Bridging the Age Gap in Breast Cancer

Funder: National Institute of Health Research

Funding Type: Programme Grant

Award Number RP-PG-1209-10071

Award Amount: £1,800, 000

Duration: 6 years (3.25 years remaining)

Date of Award: 20th March 2012

Programme Start date 1st July 2012

Sponsor Doncaster and Bassetlaw Hospitals NHS Foundation Trust


Contents Page

ContentsContents Page.......................................................................................................................................4

1 Study Team.........................................................................................................................................8

1.1 Project Leads...............................................................................................................................8

1.4 Process Evaluation Team.............................................................................................................8

1.5 Software and web tool design.....................................................................................................9

1.6 Consumer Representation:..........................................................................................................9

1.7 Trial Management Team..............................................................................................................9

1.8 DBH Trust NHS Foundation Trust Administration......................................................................10

2. Lay Summary..................................................................................................................................11

2.1 Introduction...............................................................................................................................11

2.2 Methods....................................................................................................................................12

2.3 Study schematic. (Figure 1)........................................................................................................13

3. Background and rationale................................................................................................................14

3.1. Breast cancer in Older Women.............................................................................................14

3.2. Primary Endocrine therapy...................................................................................................14

3.3. Adjuvant Chemotherapy.......................................................................................................15

3.4. Interim Update of the Age Gap Cohort study.......................................................................16

3.5. The information needs of older women facing treatment choices for breast cancer...........17

3.6 The Patient Facing Decision Support Tools............................................................................18

4. Objectives and hypothesis...............................................................................................................20

4.1 Aims:....................................................................................................................................20

4.2 Study Objectives...............................................................................................................20

4.3 Hypotheses.............................................................................................................................20

5. Trial design......................................................................................................................................21

6.1 Study setting.............................................................................................................................22

6.2 Eligibility criteria......................................................................................................................23

6.2.a Inclusion Criteria...............................................................................................................23

6.2.b. Exclusion Criteria...............................................................................................................24

6.3. Study Interventions..................................................................................................................24


6.3.a. Control Arm.......................................................................................................................24

6.3.b Intervention arm.................................................................................................................24

6.4. Outcomes.................................................................................................................................25

6.4.a Primary outcome measure............................................................................................25

6.4.b. Secondary outcomes.........................................................................................................25

6.4.d Process evaluation measures (see more detailed description in section 11).....................26

6.5 Study Timelines:..................................................................................................................27

6.5.a Table 2. Gantt Chart.........................................................................................................27

6.5.b. Ethics and R and D aapprovals (April 2015-June 2015)....................................................27

6.5.c. Training Phase (July to September 2015)...........................................................................27

6.5.d. Trial Recruitment, (October 2015-September 2017)........................................................27

6.5.e. Completion of minimum 6 weeks follow up of all participants.........................................28

6.5.f. Analysis of data, preparation of final report and publications (October 2017-June 2018).....................................................................................................................................................28

7. Sample size......................................................................................................................................29

7.1 Study population.......................................................................................................................29

7.2 Sample size calculation..............................................................................................................29

7.3 Cluster Randomisation...............................................................................................................30

8. Recruitment.....................................................................................................................................30

8.1 Identification and recruitment of patients.................................................................................30

9.0 Data collection and follow up........................................................................................................31

9.1 Table 3: Visit Schedule...............................................................................................................31

10. Study Questionnaires....................................................................................................................32

10.1 Decision Quality, Psychological and Process Evaluation Measures.......................................32

11. Process Evaluation.........................................................................................................................34

11.1 Process Evaluation overview...................................................................................................34

11.2 Aims.......................................................................................................................................34

11.3 Methods for process evaluation..............................................................................................34

11.4 Audio-recording clinical consultations.....................................................................................35

11.5 Questionnaires........................................................................................................................35

11.6 Interviews................................................................................................................................35

11.7 Recruitment for the process evaluation..................................................................................36

11.8. Data Collection for the process evaluation............................................................................37

11.9 Treatment Decision CRF...........................................................................................................37


11.10 Analysis of process evaluation.............................................................................................39

11.10.1 Consultations..................................................................................................................39

11.10.2. Interviews......................................................................................................................39

11.10.3. Questionnaires...............................................................................................................39

11.10.4. Integration of Analyses..................................................................................................39

12. Data management for the DESI sub-study.....................................................................................43

12.1 Security and storage...............................................................................................................43

13. Statistical methods........................................................................................................................43

13.1 Statistical analyis of primary and secondary outcomes..........................................................44

13.2 Methods for any additional analysis (e.g subgroup and adjusted analyses)...........................45

13.3 Monitoring of data completeness...........................................................................................45

14. Study Monitoring...........................................................................................................................45

15. Study Management.......................................................................................................................46

15.1 DMEC.......................................................................................................................................46

15.1.a Composition of DMEC......................................................................................................46

15.1.b. Summary of DMEC role and reporting structure............................................................46

15.1.c Description of any interim analyses and stopping guidelines...........................................46

15.1.d Harms...............................................................................................................................46

15.2 . Composition, roles, and responsibilities of the study team...................................................47

15.2.a. Chief Investigator (CI).......................................................................................................47

15.2.b Role of study sponsor......................................................................................................47

15.2.c Funder..............................................................................................................................47

15.2 d Trial Management Group (TMG).......................................................................................47

16. Ethics and dissemination...............................................................................................................48

16. 1 Research ethics approval-Plans for seeking REC/IRB approval...............................................48

16.2 Consent...................................................................................................................................48

17. Policy relating to non-English speaking participants......................................................................49

18. Confidentiality..............................................................................................................................49

19. Archiving........................................................................................................................................49

20. Declaration of interests.................................................................................................................49

21 Authorship eligibility guidelines......................................................................................................50

Appendix 1. PET versus Surgery Booklet.............................................................................................51

Appendix 2. PET versus Surgery On Line Algorithm Screen shots.......................................................52

Appendix 3. Chemotherapy versus no chemotherapy booklet...........................................................53


Appendix 4. Chemotherapy versus no chemotherapy On Line Algorithm Screen shots.....................54

Appendix 5 Decision regret scales......................................................................................................55

Surgery Versus Primary Endocrine Therapy.....................................................................................55

Chemotherapy versus no Chemotherapy........................................................................................55

Appendix 6 CollaboRATE Scale (patient and carer versions)...............................................................57

Appendix 7: Spielberger State-Trait Anxiety Inventory (STAI) 6 item..................................................59

Appendix 8 Knowledge and preference Q...........................................................................................60

Appendix 9 Brief Illness Perceptions Questionnaire............................................................................63

Appendix 10 Brief COPE.......................................................................................................................64

Appendix 11: Process evaluation questionnaires (for intervention and control arm patients respectively)........................................................................................................................................65

Appendix 12 Process evaluation interview schedules.........................................................................68

Appendix 13. Training Package.......................................................................................................72

1. Trial Initiation...............................................................................................................................72

2. Decision Support Intervention (DESI) Workshop – Intervention arm sites only..........................72

References...........................................................................................................................................73


1 Study Team

1.1 Project LeadsLynda Wyld, Senior Lecturer in Surgical Oncology, Academic Unit of Surgical Oncology, Room EU36, University of Sheffield Medical School, Beech Hill Road, Sheffield.

[email protected] Tel. 0114 2268640

Malcolm Reed, Dean Brighton and Sussex Medical School and Honorary Hospital Trust. Honorary Consultant Surgeon Brighton and Sussex University Hospital Trust

[email protected]

Karen Collins, Professor of Health Services Research, Centre for Health and Social Care Research, Sheffield Hallam University, Sheffield.


1.2 Qualitative data analysis, Quality of Life Expertise and Training Team.

Maria Burton, Principal Research Fellow, Centre for Health and Social Care Research Sheffield Hallam University, Sheffield.


Jenna Morgan, Clinical Research Fellow, Academic Unit of Surgical Oncology, University of Sheffield.

[email protected] Tel. 0114 271 2373

Fiona Armitage, Breast Clinical Nurse Specialist, Sheffield Teaching Hospitals NHS FT, Sheffield


1.3 Statistical Team

Stephen Walters, Professor of Medical Statistics and Clinical Trials, ScHARR, University of Sheffield.

[email protected], Tel. 0114 222 0730

Oscar Bortolami, Senior Medical Statistician, Clinical Trials Research Unit, ScHARR, University of Sheffield.


1.4 Process Evaluation TeamAdrian Edwards, Institute Director, Institute of Primary Care & Public Health, Cardiff University.

[email protected], Tel. 029 20687196

Kate Brain, Reader, Institute of Primary Care & Public Health, Cardiff University.



Kate Lifford, Research Associate, Institute of Primary Care & Public Health, Cardiff University


1.5 Software and web tool designChris Murray, Managing Director, epiGenesys, University of Sheffield.

Enterprise Zone, Portobello, Sheffield, S1 4DP, UK


Anthony Nettleship, Web Designer, EpiGenesys, University of Sheffield.

Enterprise Zone, Portobello, Sheffield, S1 4DP, UK

[email protected], Tel: 0114 2221888, extension 31832

Paul Richards, Research Fellow, Department of Health Economics and Decision Science, ScHARR, University of Sheffield.


Sue Ward, Senior Operational Research Analyst, Department of Health Economics and Decision Science, ScHARR, University of Sheffield.


1.6 Consumer Representation:Tracy Green, member of the North Trent Consumer Research Panel

[email protected]

Deirdre Revill, member of the North Trent Consumer Research Panel

[email protected]

Jacqui Gath, member of the North Trent Consumer Research Panel

[email protected]

1.7 Trial Management TeamCharlene Martin, Study Manager, University of Sheffield.


Tim Chater, Data Manager / Information Systems Co-ordinator, Clinical Trials Research Unit, University of Sheffield.



tel:%2B44%20(0)114%2022%2020876

tel:%2B44%20(0)114%20222%201888

Annaliza Todd, Age Gap Study Coordinator and Monitor, University of Sheffield.


Deborah Reid, Age Gap Administrator and Clerical Officer, University of Sheffield

[email protected] Tel: 0114 2713611

Kirsty Pemberton, Data Management Officer, Clinical Trials Research Unit, ScHARR, University of Sheffield

[email protected], 0114 22 20876

1.8 DBH Trust NHS Foundation Trust AdministrationAmy Bell, Clinical Research Development Manager, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust, Doncaster.


1.9 Oncology advisors:

Alistair Ring, Consultant Oncologist, Royal Marsden NHS Foundation Trust, London.


Robert Leonard, Professor of Oncology, Imperial College London.

[email protected]

1.10. Geriatrics Advisors:

Thompson Robinson, Professor of Ageing and Stroke Medicine, University of Leicester.

[email protected] Tel. 0116 252 3187

Riccardo Audisio, Honorary Professor of Surgical Oncology, University of Liverpool.


Kwok Leung Cheung, Professor of Breast Surgery, University of Nottingham.

[email protected]

1.11. Chemotherapy DESI Advisory Team

Helena Harder, Research Fellow, Sussex Health Outcomes Research & Education in Cancer

Brighton & Sussex Medical School, University of Sussex, Falmer, BN1 9RX

[email protected], Tel. (0)1273 873015


tel:%2B44%20(0)114%2022%2020876

2. Lay Summary.

2.1 Introduction.One third of all cases of breast cancer in the UK occur in women over the age of 70 years. Many of these women are fit, healthy and active and receive the same treatment as younger women, which may include different combinations of surgery, radiotherapy, chemotherapy, trastuzumab and anti-oestrogen treatment. However, for some older women with significant health problems, these treatments may not be as effective or well tolerated and their breast care team will have to balance the cancer therapy benefit against the risks of serious treatment side effects. Therefore in some cases a reduced treatment schedule may be used quite appropriately. Two of the key elements of breast cancer treatments which may cause serious side effects and may therefore be omitted under such circumstances are surgery and chemotherapy. For some women, there is a clear indication that they would not be able to tolerate these treatments and the breast care team will not offer them to patients in the first place. For other women, the benefits and risks will be less clear cut and the breast care team, the patient with their relatives and friends may weigh up the pros and cons to decide on their preferred treatment plan. These discussions and decisions are complex and until now, there has been very little research evidence on which to base these decisions in older women.

For the past few years our group has been undertaking a detailed study of how age, health status, fitness and frailty interact with cancer treatments in older women with breast cancer. This has given us a good understanding of the relative risks and benefits of these treatments in this age group. In addition we have also been assessing the information needs of older women when they make these decisions and how they would prefer to be supported in this decision making process. These findings have been used to develop decision support interventions (DESIs) specifically tailored to older women facing the choice between surgery or primary endocrine therapy (PET) or (for women with higher risk cancers), the choice between chemotherapy or no chemotherapy. These decision support interventions (DESIs) will be evaluated within the Age Gap cohort study which is already collecting data on quality of life and cancer outcomes in older women with breast cancer.

A package of DESIs have been developed and will be made available to half of the Age Gap recruiting sites to be adopted as their standard of care for all patients if indicated. The DESIs include:

1. A clinician facing web based algorithm which will permit calculation of the risks and benefits of different treatment strategies for an individual older woman, taking into account her age, frailty, other health problems (co-morbidities), cancer type and stage. The web tool has 2 sections: one to help clinicians with decision making between surgery or PET in older, frailer women with ER+ cancer and the other to help fitter women with higher risk cancers decide about whether they will benefit from chemotherapy or not. The web based clinical management algorithm is also able to generate a bespoke print out which is suitable for use during the clinical consultation where treatment decisions are discussed.

2. Two patient facing decision support booklets have been developed and piloted and will link to the individually tailored outputs from the clinician facing tool. One deals with the PET versus surgery choice and the other with chemotherapy decision making.


3. Two option grids dealing with these 2 clinical choices. These comprise a single sheet of A4 with a table format giving ‘at a glance’ information about the pros and cons of each choice based on frequently asked questions. Such option grids have been shown to be valuable in patient decision making by providing a rapid exposition of the key issues to start discussions.

In addition to collection of the standard data items and Quality of Life forms presently being used in the Age Gap study we will also evaluate the level of patient satisfaction with the decision making process using a range of simple measures and compare this between sites where these have or have not been used, both on an intention to treat and a per protocol basis.

2.2 Methods. This study is nested within the Age Gap Cohort Study which is recruiting well at 50 participating UK Breast Units. The current Age Gap protocol (Version 3) gives full details of the primary study methods.

Recruiting Breast Units will be cluster randomised to either continue usual Age Gap study practice (control) or to take part in staff training for and the optional use of the DESIs. Staff at all sites will be offered attendance at a training workshop to learn about the study but only staff from those sites using the DESIs will have additional training in the use of the tools. At all sites women with operable breast cancer over the age of 70 years will be invited to join the study using the current Age Gap recruitment protocol and eligibility criteria. The consent forms and PISs currently in use in the Age Gap study will be modified to give information about the assessment of decision making.For those in control sites, breast units will continue normal care and be asked to complete the standard Age Gap baseline and follow up questionnaires with the addition of several short questionnaires about how confident the patients were in making a decision about their treatment, (decision quality and whether they have any regrets about their treatment choice) at baseline, 6 weeks and 6 months after their treatment decision. Staff from the control sites will be invited to attend a study workshop to receive an update about the Age Gap study but this will not include training in the use of the DESIs.In the intervention arm, all staff associated with the participating breast units (surgeons, oncologists and breast care nurses) will be invited to attend a training workshop in the use of the DESIs in the run in phase of the study. Staff will be invited to attend a practical workshop consisting of presentations, demonstration and discussion. This will include an update about the study as well as training in DESI use and address any queries or concerns.

Staff and patients in the intervention arm breast units, (whether they have consented to take part in the study or not) will have access to the DESIs which may be used as part of normal care if the staff wish to use them. These tools may be offered, as part of the normal treatment decision making consultation, alongside usual resources, to help her and her clinical team decide on treatment during her discussions. Patient feedback about the tools as well as staff feedback will be collected. Usual Trust protocols for the approval of all patient leaflets will be followed before they are used.

Post treatment the standard Age Gap forms and questionnaires (plus the additional forms about decision making quality) will be applied as at control sites (see visit schedule). We will also seek


similar feedback from staff and patients at control sites about the information resources they use and how well they work (process evaluation).

2.3 Study schematic. (Figure 1)

The schematic diagram above shows normal clinical practice timelines for management of breast cancer patients (Row 1). Row 2 shows the current pathway for the Age Gap Cohort study with consent at the time of diagnosis or follow up counselling appointments followed by data collection via a range of questionnaires. Rows 3 and 4 show how this schema will be modified in the amended protocol with the addition of use of the optional DESIs by clinical staff in intervention sites and decision quality measures questionnaires to patients in all sites. This would only happen once per patient as it is unlikely that patients suitable for a choice of PET/surgery would be considered for chemotherapy.This amended study protocol will enable us to:

1. Evaluate the effectiveness of a package of DESIs (option grid, detailed information booklet and an individually tailored information sheet/web based algorithm) designed to support shared decision making in older women faced with the choice of PET versus surgery or chemotherapy versus no chemotherapy, respectively. Outcomes will include quality of life which is already collected in the main study (primary outcome), decision regret, decision quality, coping and illness perceptions (secondary).


2. Conduct a detailed process evaluation alongside the RCT which will assess DESI usage, acceptability, and utility , as well as facilitators and barriers to implementing and embedding the interventions into everyday clinical practice.

3. Finally, if effective, the tools will be made freely available to the wider clinical and academic communities to help improve treatment decision making for all older women.

4. The data collected from both arms will continue towards accrual for the main Age Gap cohort study whilst providing a valuable evidence base for optimal treatment in this group of older breast cancer patients.

3. Background and rationale

3.1. Breast cancer in Older WomenBreast cancer is the most common cancer affecting UK women with over 40 000 cases diagnosed per year (1). Of these one third are over the age of 70 at the time of diagnosis. Despite advances in the treatment and diagnosis of breast cancer enhancing cure rates to approaching 75%, less progress has been made in older women where breast cancer specific survival rates have not improved as they have in younger women (2). This relates to the fact that many of the advances in treatment (chemotherapy, trastuzumab, radiotherapy and surgery) are not always made available to older women (3) due to a lack of research to support their use and a perception that older women will not tolerate these treatments very well (4).

Older women are a very heterogeneous group in terms of their health and fitness and whilst for some older women, standard therapies will be well tolerated and beneficial, for others they will suffer unacceptable risks and side effects that do not justify their use.

At present there are no evidence based guidelines for clinicians to use to help them to decide which patients are likely to benefit from these different therapies. As a result there is a wide variation in treatment between UK breast units in terms of rates of surgery (5) and chemotherapy (4). The data collected in the Age Gap cohort study will help to define best practice and permit enhanced tailoring of treatment to the characteristics of the individual older woman and her cancer.

3.2. Primary Endocrine therapyA common treatment strategy for frailer older women with oestrogen sensitive breast cancer is to avoid surgery altogether and instead treat their cancer with anti-oestrogen tablets only. This is called primary endocrine therapy (PET). It is associated with high rates of patient satisfaction and low treatment morbidity but in the medium and long term some women may need a change of therapy once anti-oestrogen resistance develops (6). Randomised trials have shown that surgery (plus adjuvant anti-oestrogens) versus PET have equivalent overall survival rates (7, 8). For many healthy older women surgery has the benefit of achieving higher rates of local disease control and is therefore routinely recommended. For very frail women where surgery would be unsafe or poorly tolerated, PET is the clear choice. However for women at intermediate risk of surgery there are a complex series of trade-offs to be made for each patient. The decision must balance upfront surgical morbidity (pain, risks associated with hospitalisation, surgical complications) but with a greater certainty of local disease control against minimal morbidity with PET but a risk of later local disease


progression and the need for a change of treatment to either surgery or alternate anti-oestrogen therapy.

Currently there are no evidence based guidelines to establish the patient and cancer characteristics to guide patients and clinicians to one or other treatment for an individual patient. However preparatory work by our group has used detailed cancer registry outcome data linked to treatment related morbidity and patient and cancer characteristics to develop a web based tool which will provide this guidance to both the women themselves and their clinical teams. The data has been used to construct a web based clinical management algorithm which allows patient age, comorbidities, frailty and cancer characteristics to be considered in predicting survival and cancer outcomes. The tool may be used by the clinical team in helping to inform decisions about the risks and benefits of each treatment and it will also allow a bespoke patient facing leaflet to be printed off to help with the decision making process.

A screen shot from the tool is shown in Figure 2:

3.3. Adjuvant ChemotherapyIt is well established in younger age groups (<70 years) that adjuvant chemotherapy improves survival in women with high risk breast cancer phenotypes (high grade, node positive, Her-2 positive, triple negative). Whilst the majority (80%) of breast cancers in women over age 70 are biologically ER +ve and Her-2 negative (9), a proportion are large, high grade and node positive (10). However, chemotherapy utilisation is very low in women over 70 (14%) and non-existent in women over 80, even in those where high phenotypic risk is present. This reflects that fact that whilst there is ample evidence of benefit for chemotherapy in women under 70, most of the randomised trials have upper age cut offs at age 70 or recruit very poorly in this age group, meaning there is little evidence of whether it is effective or not. In addition rates of chemotherapy vary widely between UK breast units, between 6 and 60% in high risk women (4). This clearly suggests that guidelines for best practice are required. The primary tool used by oncologists to determine the likely benefit of


chemotherapy (Adjuvant On Line for example) has recently been shown to be inaccurate in older women (11).

Although, there are some data from meta-analyses suggesting a gradually reducing benefit with older age, there are very few specific trials (12) (13). The ACTION and CASA trials specifically set out to establish whether chemotherapy was effective in this age group but both closed early due to failure to recruit (14). This was largely due to a lack of equipoise by clinicians and a lack of enthusiasm for chemotherapy (in the absence of proven benefit) in the women themselves. Most of the information leaflets for chemotherapy relate to its use in younger women with none specifically developed for the over 70 age group. The risks for chemotherapy are higher and the benefits smaller (15) (16) and therefore the treatment decision is more complex both for the clinician and the patient herself. Our study group has also rigorously developed evidence based resources to help with this decision making process: a booklet incorporating an option grid for women to use in conjunction with face to face clinical consultation with their clinical team where treatment decisions are discussed and also the clinician facing web based management algorithm described above may also be used to assess the relative risks and benefits of chemotherapy or no chemotherapy according to the age, health and fitness of the women. Again a patient facing print out derived from the web based programme may be used to assist with patient decision making.

3.4. Interim Update of the Age Gap Cohort study.

Between 2013 and 2015 the Age Gap cohort study has been recruiting older women with operable breast cancer from 50 UK Breast Units. Recruitment is planned and funded to continue until 2017.

The study is a pragmatic cohort study with no change of management but simple data collection and questionnaire completion. Following written informed consent women are asked to complete a range of validated questionnaires including QoL (EQ5d, EORTC QLQ C30(17), BR23 (18) and ELD15 (19)), ADL (20) and IADL (frailty (21)), Charlson Index (co-morbidity(22)), MMSE (23)(cognition) as well as having data collection about cancer stage, type, treatments, adverse events and cancer outcomes (survival, recurrence etc). Direct follow up is 6 monthly for 2 years and then long term indirect follow up via cancer registry returns for up to 10 years.

Recruitment is excellent with a 50% uptake (women screened to women enrolled) which is very good for this age group of women and to date 68% of women have agreed to complete all QoL questionnaires suggesting that the protocol is tolerable and not too onerous. A reduced level of participation is also available and chosen by 28% of women where QoL questionnaires may be omitted but other data forms are completed. In addition, women with cognitive impairment who are judged incapable of consenting to take part themselves may be enrolled by proxy if their relatives agree to the study simply collecting their treatment and outcome data. Eight percent of study participants fall into this category providing a unique insight into the care of this most vulnerable group of older women with dementia.

Across the UK 3000 women will be recruited and the data used to develop evidence based guidelines on breast cancer treatment for women in this age group that are responsive to the age, cancer characteristics and the health and fitness of the patient.


3.5. The information needs of older women facing treatment choices for breast cancer

There is limited published research regarding the information needs of older women with breast cancer, or their preferences for engagement in breast cancer treatment decision making (24) (25). At the present time there are no information resources specifically tailored to the needs of older women or the breast cancer treatment choices they may face. There is therefore an important need to develop such tools and evaluate their effectiveness in the clinical environment. Previous researchers have shown that many older women do want to know about the likelihood of cure and the spread of the disease, breast cancer treatment information and age-specific prognostic information: very much in keeping with the needs of younger women (24, 26). However, there are some significant differences and challenges facing this age group. Presenting complex material to people who may have limited health literacy, reduced verbal fluency and numeracy and declining global cognitive function is a significant challenge. Older people may be more likely to have impaired hearing and eyesight (27) making access to printed materials problematic and internet literacy is low among the over 70s with only 14% of adults using it to seek health information (28). Several studies have reported that older women undergoing cancer treatment preferred information in the form of booklets with brief explanations of the risks and benefits of treatment, with examples from personal stories, clear diagrams and free of medical terminology (29).

Providing treatment choices to patients presents a considerable decision making challenge and there is limited evidence to assess the preferences for treatment decision making in older women with breast cancer. There is a trend for older patients to prefer the clinician to make the final treatment decision and this appears to be related to the severity of their illness. An American study of patients aged over 70 years with breast cancer concluded that whilst involvement does not vary significantly with age there is a trend for less involvement with increasing age (25).

We have previously investigated (30) the factors affecting the treatment decisions of older women (> 70) faced with a choice of surgery or PET for the treatment of breast cancer. This study indicated that older women relied heavily on the health care providers for information and that women reported listening for cues from the medical team to detect what treatment was being suggested rather than assessing the advantages and disadvantages of the treatment options. The main concerns for these women were disfigurement, the impact on their independence following surgery, and for some, a general fear of hospitals and operations. These women demonstrated complete trust in the health care professionals’ recommendations which is likely to be a product of the paternalistic view this generation have of the health service.

As part of the Age Gap research programme our group has been developing a series of decision support interventions (DESIs) for use with older women facing treatment choices in breast cancer. We have conducted interview and questionnaire studies regarding both the PET versus surgery treatment choice and chemotherapy versus no chemotherapy treatment choice. These have focused on the information wanted by older women when considering these choices. We have undertaken detailed literature reviews to ascertain the most accurate estimates of the risks and benefits of these treatments. We have consulted expert groups to refine the information and have then developed information resources based on best available evidence.


Based on this feedback older women had a strong preference for a written format which could be worked through with a health care professional (25). In response to the need for personalised risk and benefit information we have developed a clinician facing web based tool which will permit personal and cancer information about an individual women to be inserted and generate a printed, personalised leaflet which may be used alongside a pre-printed booklet.

The current version of the PET versus surgery and chemotherapy booklets are appended to this document. The documents are still undergoing some fine tuning and user evaluation. Both will be submitted for ethics review once finalised in the next few months and before the study commences.

Web based clinician facing breast cancer clinical outcomes management algorithm

This clinician facing breast cancer clinical outcomes management algorithm is a web based tool aimed at optimising the tailored breast cancer treatment and care of older women and which is responsive to patient age, cancer characteristics and co-morbidities. The web tool is available to view on line at:

https://agegap.shef.ac.uk/

It is designed to guide clinicians and their patients in the treatment of:

(1) Frailer older women with oestrogen receptor positive (ER+) breast cancer to optimise treatment with either surgery (+adjuvant endocrine therapy) or primary endocrine therapy (PET),

Or

(2) Fitter older women who have already had primary surgery and been found to have high risk cancer characteristics (for example ER negative, Her 2 positive or node positive breast cancer) to optimise treatment with either adjuvant chemotherapy or no adjuvant chemotherapy (note the term chemotherapy includes chemotherapy +/- trastuzumab if appropriate).

The algorithm is based on a computer model of predicted outcomes and variance caused by patient and disease parameters. Unlike existing web based algorithms for cancer treatment (PREDICT or Adjuvant OnLine (31)) which do not have the facility to specify frailty or comorbidity in detail (or at all), the Age Gap algorithm will permit these factors to be taken into account. These existing algorithms are known to be inaccurate in the assessment of older women. The Age Gap tool has been optimised for accuracy in this age group and has been based on analysis of data from over 20 000 UK women over the age of 70 derived from cancer registry data.

3.6 The Patient Facing Decision Support ToolsTwo Decision Support tools (Option Grid and generic and bespoke information booklet) have been developed, piloted and field tested among clinicians and patients in the earlier phases of the Age Gap Study.

3.6 a. PET Versus Surgery Decision Support Tools. 1. The Option Grid is a one page evidence-based summary of the treatment options alongside patients’ frequently asked questions, helping patients to differentiate the key features, risks and benefits of treatment options in relation to their personal values and preferences. The Option Grid Age Gap Supplemental Protocol Protocol Version 3 9th March 2016

18

has been designed to be sufficiently brief for use in clinical encounters and accessible enough to support a better dialogue between patients and clinicians (32). (Submitted as separate document)2. A generic booklet which gives information about both surgery and PET including diagrams to explain surgery to the breast and axilla, side effects of anti-oestrogen drugs and potential risks and benefits. It also includes a section to guide deliberation and encourage the patient to clarify their preferences. (Appendix 1)3. A bespoke or personalised section can also be printed off from the web based clinical algorithm to give a specific estimates of the risks and benefits of each treatment option for an individual woman based on her personal and cancer characteristics. This works in much the same way as the print outs from Adjuvant On Line or PREDICT and may be used to aid with patient decision making but in this case developed for the PET versus surgery decision and with more detailed data entry relating to the woman’s age and fitness level. A screen shot is included in Appendix 2.

3.6.b. Chemotherapy Versus No Chemotherapy Decision Support Tool1. The Option Grid is a one page evidence-based summary of the treatment options as above

but in this case developed to assist with the chemotherapy or no chemotherapy choice (Submitted as separate document).

2. A generic booklet which gives information about the risks and benefits of chemotherapy, including side effects of treatment, routes of administration and the practicalities of therapy and the possible benefits in helping reduce the risk of the cancer recurring (Appendix 3).

3. A bespoke or personalised section can also be printed off from the web based clinical algorithm to give a specific estimates of the risks and benefits of each treatment option for an individual woman based on her personal and cancer characteristics as above. This may be used to aid with patient decision making but in this case has been developed for the chemotherapy or no chemotherapy options and with more detailed data entry relating to the woman’s age and fitness level and specific information derived from the Age Gap Cohort study on the risk of side effects in this age group (screen shot in Appendix 4).


4. Objectives and hypothesis4.1 Aims:

1. To enhance the level of patient participation and decision quality in the treatment decision making process for older women with breast cancer. This will be achieved by making available bespoke and personalised patient facing decision support tools (comprising an option grid, longer information booklet and personalised risk information) focused on the following 2 choices:

a. Use of surgery versus PET in frailer less fit older women with ER positive cancers.

b. Use of adjuvant chemotherapy or no chemotherapy in older women with high risk cancers

2. To improve and standardise the management of breast cancer in older women by use of a specially developed, evidence based, clinician facing management algorithm.

4.2 Study Objectives

1. To assess the effectiveness of bespoke patient facing decision support tools (PET vs surgery/endocrine therapy and chemotherapy vs no chemotherapy) in clinical practice in terms of improving patient quality of life, decision quality (integrating knowledge, attitudes and decision made), coping and reducing decision regret, thus indicating better informed decision making.

2. To determine if, how, or to what extent, the interventions have an impact on clinical decision making among clinicians (change in PET/surgery rates and chemotherapy rates).

3. To determine whether the intervention improves patient knowledge and satisfaction with their preferred level of decision making.

4. To determine whether the intervention is effective in improving short, medium and long term, cancer outcomes in this age group of women, (treatment morbidity, QoL, overall and disease specific survival).

5. To assess the utility and uptake of the package of DESIs from the perspective of both clinicians and patients. To this end a detailed process evaluation to primarily assess the usage of the DESIs (fidelity to the trial protocol) their usefulness and acceptability and consider the facilitators and barriers to embedding them into everyday clinical practice.

4.3 Hypotheses1. Use of clinician and patient facing decision support tools will improve the Quality of Life in older women with operable breast cancer and ultimately improve cancer outcomes.


2. Older women faced with a choice of treatment decisions for their breast cancer will report an improved decision quality and shared decision-making experience and less decision regret using DESIs compared to older women who receive usual standard clinical decision making support.

3. Use of evidence based decision support instruments will improve short and longer term outcomes by improving adherence to evidence based guidance and thereby improving the quality of decision making, reducing the heterogeneity of practice across the UK.

4. Women in the intervention sites will express more positive illness representations (e.g. increased personal control, positive emotional consequences, less overall threat) and increased use of engagement coping strategies compared to women from the control sites.

5. Trial design

A multi-centre, parallel group, pragmatic cluster randomised controlled trial nested within the ongoing Age Gap Cohort Study.

Centres will be cluster randomised to one of 2 arms. Randomisation will be stratified according to PET rate and chemotherapy rate.

1. Control. Usual standard practice for older women (>70 years) diagnosed with breast cancer with no change to normal counselling and decision making practice.

2. Intervention. Usual standard practice for older women (>70 years) diagnosed with breast cancer plus optional clinician and patient access to the DESIs (option grid, detailed information booklet and clinical algorithm) which will have been made available to these units to adopt as their standard of care.

Both arms will collect data as per the standard protocol of the Age Gap Cohort Study.

In addition a range of simple decision quality and psychological measures will be used in both arms.

In the run in to the trial period, all centres will be expected to undergo staff training. For the control sites this will just be an update on the Age Gap study, recruitment tips and how the new questionnaires work. In the intervention sites there will be additional training in the use of the clinician and patient facing tools. This will include a practical workshop consisting of presentations, demonstration and discussion (further details below). Control sites will simply continue to recruit to the cohort study with standard data collection continuing but with the addition of a few additional simple questionnaires relating to decision making and an invitation to take part in the process evaluation at selected sites.


6. Methods

6.1 Study setting The study will require a minimum of 50 sites, 25 in each arm. A list of sites is shown below. The majority are already recruiting to the Age Gap Cohort Study, are in the process of opening or have expressed an interest in opening.Table 1. List of participating sites.

Site nameCurrently recruiting to cohort study

1 Sheffield Teaching Hospitals Yes2 Barnsley Hospital NHS Trust Yes3 Doncaster & Bassetlaw Hospitals NHS Trust Yes4 Milton Keynes Hospital NHS Trust Yes5 North Lincolnshire & Goole NHS Trust Yes7 University Hospitals of Leicester Yes8 East Lancashire Teaching Hospitals Yes10 Harrogate & District Foundation Trust Yes11 St Helens & Knowsley Teaching Hospitals Yes12 York Teaching Hospitals Yes14 Royal Liverpool University Hospital Yes15 Airedale NHS Foundation Trust Yes16 Leeds Teaching Hospitals NHS Trust Yes17 Bradford Teaching Hospitals NHS Trust Yes18 University Hospital Llandough Yes19 Aneurin Bevan Health Board Yes21 University Hospitals of Morecambe Bay NHS Trust Yes22 University Hospitals Coventry & Warwickshire NHS Trust Yes23 United Lincolnshire Hospitals NHS Trust Yes26 Hull and East Yorkshire Trust Yes27 Nottingham University Hospitals NHS Trust Yes28 Southport & Ormskirk Hospital NHS Trust Withdrawn29 Mid Cheshire Hospitals NHS Trust Yes30 Royal Marsden NHS Foundation Trust Yes32 Gloucestershire Hospitals NHS Trust Yes34 Guys and St Thomas NHS Foundation Trust Yes35 Dorset County Hospital NHS Foundation Trust Yes36 Mid Essex Hospital Services Trust Yes37 Mid Yorkshire Hospitals NHS Trust Yes38 North Bristol NHS Trust Yes39 Chesterfield Royal Hospital NHS Foundation Trust Yes40 Rotherham NHS Foundation Trust Yes41 Dartford and Gravesham Trust Yes42 Kingston Hospital NHS Trust Yes43 Colchester Hospital University NHS Foundation Trust Yes44 Yeovil District Hospital Foundation Trust Yes45 Croydon Health Services NHS Trust Yes46 North Tees and Hartlepool NHS Trust Yes


47 South Tees NHS Trust Yes48 Luton and Dunstable University Hospital Trust Yes49 Weston Area Health Trust Yes50 Tameside Hospital NHS Trust Yes51 East Cheshire NHS Trust Yes52 Wrightington, Wigan and Leigh NHS Trust Yes53 Sherwood Forest Hospitals NHS Trust Yes54 University Hospital of Manchester Yes55 Aintree University Hospital NHS Trust New Site56 Sandwell and West Birmingham Hospitals NHS Foundation Trust New Site55 Brighton and Sussex University Hospitals NHS Foundation Trust New Site

6.2 Eligibility criteria

6.2.a Inclusion Criteria These are identical to those of the Age Gap Cohort Study included in the primary protocol (V3).

(1) Female(2) Aged over 70 years of age at the time of diagnosis of cancer (3) Primary operable (TNM categories: T1, T2, T3, N0, N1, M0; please refer to appendix 3 for

further details) invasive breast cancer (core biopsy or diagnostic incision biopsy (4) Tumour ER and Her-2 status will be available (5) Ability to give informed consent if considering full or partial trial participation (see below).(6) Willing to complete the questionnaires for the additional trial evaluations if considering full

trial participation.(7) If suitable for data collection only, the patient does not need to give consent but participation

in the data collection exercise should be agreed and assented to by their next of kin, friend or carer.

In addition, for the amended protocol

(8) Willing to complete the additional questionnaires for the additional trial evaluations relating to decision making quality, regret and knowledge. All women in the Age Gap cohort study who are offered a choice of treatments will have the decision quality forms given/sent to them in both intervention and control sites at baseline, 6 week and 6 month after their treatment decision. The PIS has been slightly modified to include mention of these decision making quality questionnaires. The PET versus surgery DESI may be used for any woman who is considering this treatment choice. The chemotherapy versus no chemotherapy DESI may be used for any woman who is considering this treatment choice. For women who are not offered either choice neither DESI will be used and the study will just run as the normal Age Gap cohort study.

(9) Relating ONLY to women entered into the study by a proxy decision maker because they lack cognitive capacity: the proxy decision maker will be offered access to the DESIs as part of the normal counselling process in intervention sites (and normal counselling in control sites). These proxy decision makers will be invited to complete optional questionnaires and take part in an interview about the counselling process. A separate PIS and consent form will be


available for them to read and sign along-side the standard proxy consent and PIS. This will be of particular value for clinical practice as up to 10% of older patients have some degree of cognitive impairment and friends and relatives are often asked to comment on how they would like their relative to be treated. There are presently no resources to assist them and PET is much more likely to be used in the presence of dementia. These documents are submitted as separate documents.

6.2.b. Exclusion CriteriaAgain these are identical to the Age Gap study.

(1) Disease unsuitable for surgery e.g. inoperable, locally recurrent or metastatic disease.

(2) Previous invasive breast cancer within the last 5 years.

The following criterion is different to the current Age Gap cohort study:

(3) Must be able to speak and read English. For use of the DESIs designed for this study it will not be possible to translate the decision support instruments into multiple languages. However the DESIs may be used to aid counselling with the help of translators but these women will not be evaluated for decision making quality as the DESIs have not been optimised for non-English use. Non-English speakers will still be eligible for the standard Age Gap Cohort Study as per the main protocol.

6.3. Study Interventions

6.3.a. Control Arm

Usual standard practice for older women (>70 years) diagnosed with breast cancer with no change to normal planned treatment (control arm) with standard data collection, standard decision making counselling and follow up data collection and questionnaires as per the current Age gap study with the addition of several simple new questionnaires about decision quality, knowledge and regret.

6.3.b Intervention arm

As above but patients may be offered the use of either of the DESIs if they are felt to be of value by the treating team and the patient wishes to use them (option grid, booklet and/or clinical algorithm use). Clinical care and standard data collection as per the Age Gap Cohort Study and questionnaires as per the current Age gap study with the addition of several simple new questionnaires about decision quality, knowledge and regret.


6.4. Outcomes

6.4.a Primary outcome measure Global health status/quality of life score (questions 29+30 of EORTC QLQ-C30) at 6 months post-intervention

6.4.b. Secondary outcomes

Quality of life at 6 weeks and 6 months post treatment with the EORTC QLC-C30, BR23 and ELD15 at baseline, 6 weeks, 6 and 12 months. These are already collected as standard in the Age Gap study but will be the primary outcome of the amended study analysis.

These are all new to the amended protocol. All are brief scores.

Decision regret at 6 weeks and 6 months after the relevant treatment decision (Decision Regret Scale, (33) (Appendix 5)

Shared decision making using CollaboRATE, at baseline (after consent for those with a choice of PET/surgery and after consultation for chemotherapy/no chemotherapy choice) (34), www.collaboratescore.org/) (Appendix 6)

Patient anxiety levels using the Speilberger short-form State Anxiety Score at 6 weeks and 6 months after the relevant treatment decision (35) (Appendix 7)

Knowledge and treatment preference, measured using a non-validated questionnaire, at baseline (after consent for those with a choice of PET/surgery and after consultation for chemotherapy/no chemotherapy choice) (Appendix 8)

Illness perceptions at 6 weeks and 6 months after the relevant treatment decision (Brief Illness Perceptions Questionnaire, (36), www.uib.no/ipq/) (Appendix 9)

Coping at 6 weeks and 6 months after the relevant treatment decision (Brief COPE, (37) (Appendix 10)

6.4.c Other Outcomes

The study will also compare cancer outcomes, treatment outcomes and treatment types between control and intervention sites using data that is already collected via the normal cohort study protocol.


http://www.collaboratescore.org/

6.4.d Process evaluation measures (see more detailed description in section 11) DESI usage by trial staff and patients (staff and patient interviews, patient questionnaires and CRF) DESI acceptability (staff and patient interviews) DESI usefulness (staff and patient interviews and patient questionnaires) Barriers and facilitators to embedding the DESI into everyday routine clinical practice (staff interviews). Levels of shared decision making determined by scoring of audio-recordings of consultations, patient interviews and CollaboRATE.


6.5 Study Timelines:

6.5.a Table 2. Gantt Chart

Action Apr-Jun

15

Jul-Sep 15 Oct 15-Sep 17 Oct17-Dec

17

Jan 18-Jun

18

Ethics

Site R and D

Training/troubleshooting

Recruitment

Follow-up/data checking

Process evaluation

Data analysis/publication

6.5.b. Ethics and R and D aapprovals (April 2015-June 2015).

The protocol will be approved as a substantial amendment to the Age Gap Cohort Study. New sites will be opened to the main cohort study (although most are now open). The training packages will be developed. This will include a practical workshop and a DVD of

the workshop. Oncologist engagement will be secured at sites. The bulk of the present study is conducted

in surgical clinics but the chemotherapy DESI will largely be used by medical oncologists and oncology nurses.

Training dates and venues will be arranged. Final validation and piloting of the tools will be completed and sent for ethics approval.

6.5.c. Training Phase (July to September 2015)

Randomisation and Stratification of participating sites by PET rates/chemotherapy rates (50% control, 50% intervention).

Site visits to initiate centres and commence training will be scheduled and intervention sites will have a lead in period to gain confidence in the use of the tools for their first few cases (a learning curve phase) whose data will be collected and analysed but potentially excluded from the main analysis. Details of training is given in Appendix 13.

Feedback will be collected in this phase and any changes to optimise the study protocol will be incorporated in an amended final protocol.

6.5.d. Trial Recruitment, (October 2015-September 2017)


The intervention sites will start using the DESI as part of their normal practice for all women diagnosed if it is felt appropriate. Women recruited to the cohort study at both control and intervention sites will have the new questionnaires offered to them.

Process evaluation of the intervention will be conducted both during and shortly after this period using audio-recording of consultations, qualitative interviews and questionnaires (see detailed description in section 11)

The TMG will meet every 6 months, as at present, during this period to review progress and the DMEC every 3 months to monitor progress and safety.

Study monitoring will take place at all sites as per the current study protocol.

6.5.e. Completion of minimum 6 weeks follow up of all participants During this period the latest recruited cases will complete their 6 week follow up data

collection. Data monitoring will ensure all data returns are complete and commence study closure Data cleaning, checking and validation will be performed Site closure and secure data archiving.

6.5.f. Analysis of data, preparation of final report and publications (October 2017-June 2018) All data analysis will be completed Report to funder Publications and dissemination of findings Release of web based tool free to download from the internet.

6.5.g. Long term follow up.Cancer registry returns will be collected annually for up to 10 years and analysis of long term cancer outcomes (overall and disease free survival, cause of death: breast cancer or non-breast cancer related) as per the main Age Gap study protocol. The DESIs will be updated to reflect these outcomes and improve their validity and accuracy.


7. Sample size

7.1 Study populationRecruitment to the cohort study which has identical eligibility criteria has been excellent, recruiting up to 100 cases per month. Across these centres over the 24 months recruitment period we expect to recruit approximately 1800 women at an average of 75 per month.

In terms of women within the cohort study who may be considered for use of the DESIs, not all women will be considered for a choice of surgery or PET or chemotherapy of no chemotherapy. Two populations of women where these may be used will exist.

Chemotherapy choice population.

Based on data from the ACHEW study (Ring et al, 2013), in this over 70 age group 8% of older women receive chemotherapy so this would equate to 144 women. However 30% of women in the ACHEW study were classed as high risk and potentially eligible for chemotherapy, equating to 540 women. These women would therefore be suitable to use the clinician and patient DESIs relating to chemotherapy.

PET versus surgery choice population

Based on UK audit data 40% of women receive PET and others may be suitable for a choice of PET or surgery, therefore it is likely that approximately half of all the women may be suitable to be offered the PET versus surgery DESI, which would equate to approximately 900 women eligible to use the clinician and patient DESIs for PET versus surgery.

The remaining women may not be offered either tool but their data will simply continue to be collected as part of the main cohort study.

7.2 Sample size calculationThe primary endpoint will be the global health status/quality of life score (questions 29+30 of EORTC QLQ-C30) at 6 months post-intervention. Assuming 50 units are randomised to either the DESI intervention (25 units) or control (normal care- 25 units) then we can estimate a preliminary sample size assuming a fixed number of clusters (k=50) and try to recruit a set number of women per cluster (38). Data from the EORTC Reference Manual (39) suggests a mean Global health status/QoL score of 58.2 with a SD of 25.6 for women aged 70 or more with breast cancer. Cocks and colleagues (40) suggested the following guidelines for interpretation of the Global health status/QoL that estimates for trivial, small, and medium mean differences were 1, 7, and 13 points respectively.

Assuming a standard deviation of 26 points for the Global Health Status/QOL scale and a mean difference of 7 or more points Global Health Status/QOL scores between the groups is of clinical/practical importance (a “small” standardised effect size of 0.27). With no allowance for clustering; for the PET vs surgery DESI comparison with 291 eligible women per group we will have 90% power of detecting this difference or more as statistically significant between the groups at the 5% two-sided level. If we assume an intra-class correlation of 0.05 then allowing for the clustered RCT design we will need to recruit 25 women, eligible for the using the decision aids, per cluster (i.e.


50 clusters x 25 women), 1250 in total (this assumes a design effect of 2.2). With a 20% loss to follow-up by six months we need to recruit 34 women per cluster (50 clusters x 34) or 1700 in total (850 per group). Based on our site recruitment data the majority of sites will pass this number of cases after being open for 24 months.

7.3 Cluster Randomisation

Randomisation will be at breast unit level, stratified by high and low PET and chemotherapy rates. Data for this stratification will be derived from the cohort study which has collected accurate data on treatment rates for both PET versus surgery and chemotherapy versus no chemotherapy.

8. Recruitment

8.1 Identification and recruitment of patientsPotentially eligible women will be identified by clinicians and research nursing staff within MDTs as is happening currently for the Age Gap Cohort Study.

In non-intervention centres, practice will follow normal care plus continuance of the normal Age Gap questionnaires with only the minimal protocol change of the addition of the decision quality questionnaires.

In intervention sites, recruitment will continue as now for the Age Gap Cohort Study. Staff in the centres will have been given access to and training in the use of the DESIs and encouraged to use these as part of their normal practice if they wish, whether patients are part of the study or not.


9.0 Data collection and follow upThe Age Gap Cohort study is collecting follow up data at clinic visits at 6 weeks and then at 6 monthly intervals for 2 years. This schedule is unchanged but with the addition of several short additional questionnaires as per the visit schedule in table 9.1. In addition, following feedback from our study PPI team and site staff we have added a thank you letter to all patients who have completed the full 2 years on study and also to thank those who take part in the process evaluation.

9.1 Table 3: Visit ScheduleStandard Age Gap Questionnaires

Baseline 6 weeks 6 months 12 months

18/24 months

Long-term

IADL *ADL *MMSE *ECOG perf. status *Subjective Global Assessment

*

Co-morbidity *EQ5D * * * * *QoL (EORTC-QLQ C30; BR23 and ELD15)

* * * * *

Decision quality * *RECIST if PET * * * * *Registry data access *Tissue Access * *Tumour details *Treatment details * * * * *Adverse events * * * * *

New for DESI study (if offered choice of either PET/surgery, or chemotherapy/no chemotherapy)

Baseline (after consent for PET/surgery or after consultation for chemo/no chemo, as applicable)

6 weeks after relevant treatment choice

6 months after relevant treatment choice

Speilberger Anxiety * *Collaborate *Decision Regret * *Knowledge, readiness to decide and preference measure (either for PET/surgery or chemo/no chemo choice)

*

Brief IPQ * *Brief Cope * *Process evaluation (if taking part in process evaluation)Process evaluation questionnaire

*


Collaborate (for carers, partial trial involvement patients & those where only algorithm used)

*

†process evaluation questionnaire only for those recruited to take part in the process evaluation.

10. Study Questionnaires10.1 Decision Quality, Psychological and Process Evaluation MeasuresA number of decision quality, psychological and process evaluation measures will be used as part of the amended study protocol. These are:

Decision quality measures

Knowledge, readiness to decide and preference measure. Knowledge items have been developed in line with Option Grid Frequently Asked Questions (FAQs) (41) and field tested along with the DESIs. Knowledge items will be used to measure short-term decision quality (non-validated tool). Correct responses are given a score of 1 point whereas incorrect responses and ‘unsure’ responses are scored as a 0. The readiness and preference items have been adapted from a decision quality measure for lumpectomy vs. mastectomy decision, which itself was adapted from another decision quality measure (42, 43). (Appendix 8)

CollaboRATE Score. This is a shared decision making process measure within the consultation (partially validated tool)(e.g. CollaboRATE, (34). This 3 item measure is scored on a 10 point scale of 0 (no effort at all) to 9 (every effort was made). Scores are then summed and multiplied by 3.704 to be transformed to a scale of 0 to 100. (Appendix 6)

Decision regret (33) validated tool) (measured at 6 weeks and 6 months after the relevant treatment decision). Five items are rated from 1 (strongly agree) to 5 (strongly disagree), for example “It was the right decision”, “The choice did me a lot of harm”. The scale has good internal reliability (α>0.80) and has demonstrated convergent and discriminant validity (33). (Appendix 5).

Psychological and process evaluation measuresShort form Speilberger State Anxiety Inventory (STAI) (35) validated tool). The 6 item state version of the STAI will be included at baseline, 6 weeks and 6 months follow-up to assess emotional outcomes. The short state anxiety scale has good reliability (α=0.82) and correlates well with the full STAI (r>0.90) (35). (Appendix 7).

Brief Illness Perceptions Questionnaire (IPQ) (36). This is a 9 item questionnaire which will be used to measure women’s cognitive and emotional representations of breast cancer. (Appendix 9)

Brief Cope (37). This will be used to assess women’s coping strategies in response to being faced with breast cancer treatment options. (Appendix 10).

Process evaluation questionnaire. This is a brief questionnaire designed for the study to ascertain what information women received and how useful they found it. (non-validated tool). (Appendix 11).

The decision quality and psychological questionnaires will only be given to women who are offered a choice of treatment. Two of the decision quality measures (knowledge, readiness to decide and preferences and CollaboRATE) will be delivered at baseline (after consent for those with a choice of


PET/surgery and after consultation for chemotherapy/no chemotherapy choice) and the other decision quality and psychological outcome measures (STAI, decision regret, Brief IPQ and Brief COPE) will be delivered at 6 weeks and six months following the relevant treatment decision see visit schedule. The process evaluation questionnaire (and collaborate) will be given to those consenting to the process evaluation and may include some participants where only the clinical web-algorithm was used (and a treatment recommended, rather than a choice offered). The process evaluation questionnaire will be assessed at 6 week follow-up only. Relatives/friends/carers or partial trial participants who are taking part in the process evaluation will be asked to complete CollaboRATE at baseline (after consent for those with a choice of PET/surgery and after consultation for chemotherapy/no chemotherapy choice) as part of the process evaluation.


11. Process Evaluation

11.1 Process Evaluation overview Evaluation of the process of a complex intervention, such as the DESIs, can assist in further developing the intervention (e.g. fine-tuning the intervention itself or its delivery), identify how the intervention works (i.e. identifying the active ingredients), and aid interpretation of the trial effects in the light of knowledge gained about intervention fidelity in the trial (44). A process evaluation will therefore run alongside the main trial.

11.2 AimsThe primary aims of the evaluation are to assess the usage of the DESIs (what happened in practice and fidelity to the protocol), acceptability (ease of use, practicality) and usefulness, and consider the facilitators and barriers to embedding them into everyday clinical practice. A secondary aim is to compare the levels of shared decision making and information provision in the two trial allocation groups.

11.3 Methods for process evaluationThe intervention process will be evaluated using a mixed-methods approach (Fig 3) in a selection of breast units randomised to the intervention arm (8 units) and a selection of control arm breast units (8 units). These will be selected to be representative of the randomised units (e.g. geographical, socio-demographic, breast unit size, PET/surgery/chemo rates). Interviews with clinician will only be conducted within the intervention arm sites and consultations will only be recorded when the chemotherapy decision is being discussed. Where a relative/carer/friend is the proxy decision maker these will be included rather than the patient themselves. Only where there are differences in the procedure for proxy decision makers compared to patients are these specifically noted in the protocol.

Fig. 3 Schematic representation of the methods included in the process evaluation


11.4 Audio-recording clinical consultationsClinical consultations which use the chemotherapy DESI (i.e. consultations which discuss treatment options and in particular those during which the option grid and on line clinician algorithm are used) will be audio-recorded in order to assess the levels of information provision and shared decision making. They will also be used to assess how the DESIs are being used and whether the DESIs (in particular the option grid) are being implemented with fidelity to the protocol. Fifteen to 20 clinical consultations using the chemotherapy DESI within the intervention arm will be audio-recorded. Fifteen to 20 clinical consultations which discuss the chemotherapy treatment choice within the eight control units will be audio-recorded to assess the levels of information provision and shared decision making. Clinical consultations which use the PET vs. surgery DESI will not be audio-recorded. This is due to the fact that many women receive their diagnosis within the same consultation that they discuss the treatment options and sometimes make a decision about treatment. Asking women to consent for their consultation to be recorded would therefore be difficult as they would not have received a diagnosis (and not heard yet about the Age Gap study).

11.5 QuestionnairesOne of the decision quality measures used within the study protocol includes questions on the level of shared decision making (CollaboRATE, (34). (Proxy decision makers taking part in the process evaluation will be asked to complete an appropriate version of CollaboRATE. See appendix 6) Patients taking part in the process evaluation, will be sent on additional questionnaire at 6 week follow-up (6 weeks after the relevant treatment decision) to ask about any information provided to them regarding their treatment options using process measures of DESI usage, acceptability and utility developed in-house (Appendix 11). This measure will differ slightly for those in the trial vs. control arm, so those in the trial arm are specifically asked which of the DESI components were used. Age Gap Supplemental Protocol Protocol Version 3 9th March 2016

35

Audio-recording of consultations

(Chemotherapy decision only)

Patient interviews

Clinician interviews

Patient questionnaires

11.6 InterviewsQualitative interviews will be undertaken with approximately 15 to 20 patients in each treatment option group in the intervention arm of the trial (total 30-40 interviews from the 8 selected process evaluation units). We will ask about patterns of DESI usage within the patient pathway: were the DESIs used (did their clinician use the treatment algorithm/personalised risk assessment and/or option grid used in consultation, was the longer DESI offered to them); how were they used (in clinic/at home, with family/friends and other information sources); perceived usefulness (did the treatment algorithm output and/or option grid help or impede communication in clinic; did the longer DESI help/impede discussions with family/friends); perceptions of whether the DESIs influenced decision quality (level of shared decision making, deliberation and coping, perceived support, confidence in making the right decision) and if so, what aspects made a difference; possible improvements. The draft interview schedule can be found in Appendix 12a.

Interviews with control group patients will also be undertaken with approximately 15 to 20 patients in each treatment option group (total 30-40 interviews from 8 units) to assess normal practice and any possible changes to normal practice during trial duration, in particular whether there is evidence of direct contamination of interventions (e.g. using options grids etc.) or parallel information / decision support such as Adjuvant Online. Interviews will focus on what information they were given, how useful they found it and perceptions of shared decision making, support and coping (Appendix 12b).

Qualitative semi-structured interviews will be undertaken with approximately 6 to 10 clinicians per treatment option group working within the participating intervention group breast units (total 12 to 20 interviews from 8 units). Interviews with clinicians will ask about patterns of DESI usage and barriers/facilitators to implementation of the DESIs into routine clinical care: was the DESI used, and if so, which elements; how was the DESI used; perceived usefulness; perceptions of whether the DESI influenced decision quality; can they be delivered as planned; specific barriers and facilitators of implementation; possible improvements (see Appendix 12c for clinician interview schedule).

11.7 Recruitment for the process evaluationClinicians at the breast units selected for process evaluation will be written to about the process evaluation and invited to take part.At initial recruitment to the trial, patients will be asked to indicate whether they are happy to be contacted about other optional parts of the study (see PIS and consent form). A selection of these will then be invited to take part in the process evaluation study. At initial recruitment to the trial, a sub-set of proxy decision makers will also be invited to take part in the process evaluation study. Consecutive patients will be reviewed for inclusion in the process evaluation at the time of being reviewed for trial eligibility (by the clinicians and research nurses at MDT) based on:

the sixteen breast units involved in the process evaluation and their clinician (i.e. willingness of the clinician to be involved).

features of the purposive sampling frame (age, treatment option group (PET or surgery; chemotherapy or no chemotherapy), breast unit, time from start of trial).


Time from the start of the trial is included as a feature in the sample frame to ensure that the process of the trial is assessed throughout the course of the trial. It will examine whether the intervention becomes more ‘normalised’ as time progresses during trial, or whether fidelity wanes during study duration. At initial recruitment patients will be given the option of taking part in parts of the process evaluation (see PIS and consent form).Once a patient has indicated being happy to be contacted about other parts of the study, the details of this will be added to their notes and their contact details and relevant clinical details (such as age, treatment option, date of treatment decision) will be sent to the research staff. The research staff will then send an invitation pack (including process evaluation covering letter, PIS, study reply form and pre-paid envelope). Completion of the study reply form is logged in the study database (to trigger additional questionnaires to be sent to patients) and site staff informed (in order to arrange consent and recording of consultations). Consent forms will be completed at the start of the interview and just prior to the consultations (where appropriate). Completion of the questionnaires will be taken as consent for the questionnaire.

11.8. Data Collection for the process evaluationOnce a proxy decision makers has consented to take part in the process evaluation, the details of their consent to participate their contact details will be sent to the research staff.

Audio-recordings: For those with a choice of chemotherapy or no chemotherapy, their indication on the study reply form for audio-recording their consultation will be highlighted/flagged in their notes. Prior to the consultation, the local research nurse (or other appropriate person) will gain consent from the patient (proxy decision makers will have already consented, so this consent can be reviewed). Their consultation about treatment options (particularly that involving the option grid) will be audio-recorded by the clinician or research nurse (recording devices will be supplied to the breast units involved). This strategy is currently being adopted in the evaluation of the Making Good Decision in Collaboration (MAGIC) programme by the Cardiff University research team.

Questionnaires: CollaboRATE will be collected for the main trial at baseline (after the discussion of treatment options). For those not completing questionnaires for the main study but involved in the process evaluation, CollaboRATE will also be placed in their notes (or given to them directly by the local research nurse or clinician if a proxy decision maker, see appendix 6) so that the patient can be asked to complete a copy immediately following the consultation. Pre-paid envelopes will be provided for the return of the questionnaires (either to project leads at the centre or the researchers).

Interviews: Following their consultation(s) and at an appropriate time (to allow for potential surgery) the researcher will contact the patient (and intervention arm clinicians on some occasions) to arrange an interview. Interviews will be conducted shortly after completion of the main trial questionnaires to avoid contamination (i.e. between 6-8 weeks for PET versus surgery cases or later for chemotherapy cases) of the consultation. Consent for the interview will be gained from patients at the start of the interview (proxy decision makers and clinicians will have already consented, so


this consent will be reviewed at the start of the interview). Clinicians will only be interviewed once as part of the study to avoid over burdening them.

11.9 Treatment Decision CRFThe study set of case report forms will have an additional form added to include whether the patient was offered a choice of therapy, no choice was offered as the clinician felt one choice was overwhelmingly favourable and, if the latter whether the patient chose to disregard medical recommendation. This will be simple tick box form for the breast clinical nurse specialist of clinician to complete at the end of the consultation. All sites (process evaluation and non-process evaluation) will be asked to complete this CRF. A record of which components of the DESI will also be added to the CRF for clinicians from intervention sites to complete.


Fig. 4 Process evaluation involvement diagram


50 Age Gap Breast Units

Recruit 15 – 20 patients with choice of chemotherapy or

no chemotherapy

Treatment choice consultations recorded

25 intervention arm units

8 units selected for process evaluation

Recruit 15 – 20 patients with choice of

PET or surgery

Patients interviewed after treatment choice

consultation (30-40)

Patients complete CollaboRATE following choice consultation and information provision questionnaire at 6

week follow up

A sub-set of clinicians interviewed after treatment choice

consultation (6-10 per treatment option group, so 12-20 in total)

25 control arm units

8 units selected for process evaluation

Recruit 15 – 20 patients with choice of

PET or surgery

Recruit 15 – 20 patients with choice of chemotherapy or

no chemotherapy

Patients complete CollaboRATE following choice consultation and information provision questionnaire at 6

week follow up

Treatment choice consultations recorded

Patients interviewed after treatment choice

consultation (30-40)

11.10 Analysis of process evaluation

11.10.1 ConsultationsAudio recordings of the consultation will be analysed using the MAPPIN’SDM scale (45). The MAPPIN’SDM scale measures shared decision making behaviours of the patient, the clinician and the combination of the patient and clinician (the patient-clinician dyad).

11.10.2. InterviewsInterview recordings will be transcribed verbatim. Analysis of patient and clinician interviews will initially be conducted separately. Thematic analysis will then be used to identify key themes within the sample. These will be guided by, but not exclusive to, the topics areas covered within the interviews (such as use of the DESIs, shared decision making, coping, barriers and facilitators to the DESIs, possible improvements) using a framework approach (46). Analysis will be conducted by thorough reading of the transcripts and using both deductive (guided by the topic areas) and inductive (led by the data) key themes will be identified for coding. Within these codes, similarities and differences will be identified between transcripts in order to describe the content of each theme. Themes will also be examined according to high and low MAPPIN’SDM dyad scores (i.e. more/less shared decision making) for those in using the Chemotherapy DESI. Comparisons will also be made between the themes identified within the clinician and patient analyses.

11.10.3. QuestionnairesQuestionnaires will be analysed using SPSS. Descriptive statistics will be used to report DESI usage within each intervention arm (and possibly could split this by breast unit too). Descriptive statistics of CollaboRATE scores and MAPPIN’SDM scores (patient, clinician and dyad) will be calculated to give an indication of shared decision making. The associations between patient CollaboRATE scores and MAPPIN’SDM scores will be calculated. This will provide an assessment of agreement between actual and perceived levels of shared decision making.Patient CollaboRATE scores will be compared between trial allocation groups, followed by sub-group analysis within each treatment option group (PET or surgery and chemotherapy or no chemotherapy). Mean differences will be assessed using Mann Whitney-U tests.

11.10.4. Integration of AnalysesResults from the consultations, interviews and questionnaires will be integrated into one report to form the process evaluation (see Table 3). The Normalization Process Theory (47) will be used as a framework for the interpretation of how the DESIs have been implemented within the trial sites. Using the report, areas of improvement for the DESI will be identified (such as content and delivery of the DESIs and training needs) and then used to fine-tune the intervention and/or its implementation by making amendments. The results of the process evaluation will also be used alongside the overall trial results to try to identify which aspects of the DESIs did/did not work. Where differences between trial allocation groups are shown in the main trial, it may be possible to


use the process evaluation results to identify the potential active ingredient/s in the intervention. The knowledge gained from the process evaluation will also be used to help with the interpretation of the trial results. In particular, fidelity to the trial protocol, levels of information provision and levels of perceived vs. actual shared decision making in both trial arms will be important to consider alongside the effects (either significant or non-significant) of trial allocation on the main trial outcomes.


Table 4. Aligning process evaluation aims with methods, outcomes and analysis integration.Primary Aims Assessment method Outcome Analysis integrationUsage Recording of consultations†

Patient & clinician^ interviews

MAPPIN’SDM scores† Themes identified in patient

& clinician analysis frameworks

Comparison between themes identified in patient & clinician frameworks

Examination of themes (patient and clinician frameworks) identified within high & low MAPPIN’SDM dyad scorers†

Acceptability Patient & clinician^ interviews

Themes identified in patient & clinician analysis frameworks


Usefulness Patient & clinician^ interviews

Patient CollaboRATE questionnaire

Recording of consultations†


CollaboRATE scores MAPPIN’SDM scores†


Association between CollaboRATE & MAPPIN’SDM scores†.


Facilitators & barriers to implementation

Patient & clinician^ interviews




Secondary AimsShared decision making across trial arms

Patient CollaboRATE questionnaire

Recording of consultations†

CollaboRATE scores MAPPIN’SDM scores†

Association between CollaboRATE & MAPPIN’SDM scores†.

Comparison between CollaboRATE scores of intervention arm & control arm

Information provision across trial arms

Patient interviews, patient information questionnaire & CRF

Recordings of consultations†

Information from interviews, information provision questionnaire & CRF

Information from recorded consultations †

Descriptive comparison between control arm and trial arm

† chemotherapy DESI only^ clinician interviews in the intervention arm only

Table 5: Timetable for process evaluationAge Gap Supplemental Protocol Protocol Version 3 9th March 2016

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Task Description (Top level tasks and Sub-tasks

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Trial recruitment

Process evaluation

Preparation

Ethics and R&D

Engagement with recruiting centres

Data collection

Patient recruitment Recording of clinical consultations (30-40, chemotherapy DESI only) 3 per month

Questionnaire completion (patients)

Interviews with patients (60-80) 6 per month

Interviews with clinicians (12-20, intervention arm only) 1-2 per month

Interview transcription

Analysis and write up Develop interview analysis coding frame & preliminary analysis

Interview analysis

MAPPIN’SDM scoring Quantitative data cleaning & preliminary analysis

Questionnaire analysis

Integrated analysis

Report/paper writing


12. Data management for the DESI sub-study

12.1 Security and storage This is unchanged from that in the main protocol and is not detailed here.

13. Statistical methodsStatistical analysis is the responsibility of the study statistical team led by Professor Stephen Walters (Senior Study Statistician) with support from a junior statistician (Study Statistician). The analysis plan outlined in this section will be reviewed and a final statistical analysis plan (SAP) written before any analysis is undertaken. All analyses will be performed by the same junior statistician under the supervision of Professor Walters.

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13.1 Statistical analyis of primary and secondary outcomes As the trial is a parallel group cluster RCT data will be reported according to the CONSORT statement for cluster trials (48). The statistical analyses will be performed on an intention-to-treat basis comparing the DESI and control groups. All statistical exploratory tests will be two-tailed with = 0.05. Baseline demographic (e.g. age), physical measurements, and health-related quality of life data will be assessed for comparability between the treatment groups. The primary outcome will be the global health status/quality of life score global quality of life scale of the EORTC-QLQ-c30 questionnaire at 6 months following commencement of treatment.

A marginal Generalised Linear Model (GLM), with coefficients estimated using generalised estimating equations (GEE) with robust standard errors and an exchangeable auto correlation matrix in STATA v13 (Campbell and Walters 2014; StataCorp, 2013) will be used to analyse the outcomes and allow for the clustered nature of the data. The exchangeable correlation structure corresponds to an equal correlation model, meaning that the correlations of the outcomes with a cluster, i.e. breast centres, are the same.

For continuous outcomes, such as mean global health status/quality of life score (questions 29+30 of EORTC QLQ-C30) at 6 months post-intervention, knowledge score and preference for treatment score, an identity link with a Normal distribution for the outcome will be used. Estimates for the treatment group coefficient from this regression model will be reported along with their associated 95% confidence interval. In the event of differences between the Intervention and Control groups with respect to baseline demographic, physical, and health-related quality of life measurements, then these covariates will be used in the GLM to adjust the treatment effect for these variables. The adjusted regression coefficient estimate for the treatment group parameter along with its 95% confidence interval (CI) will then be reported.

For the other secondary outcomes, at 6 weeks and 6 months, such as the other dimensions of the EORTC QLQ C30, the EORTC QLQ-BR23 and EORTC QLQ-ELD14 the mean QoL dimension scores will be compared between the intervention and control groups, using similar models.

Missing primary outcome data

A sensitivity analysis using a variety of imputation methods, to impute any missing primary outcome data (6-month EORTC QLQ-C30 global health status/quality of life score will be performed. The imputation methods will include last observation carried forward (LOCF), regression and multiple imputation. The estimates of the treatment effect and its associated confidence interval, from the various imputation methods, will be graphically displayed alongside the results for the observed data.

Adverse events

These will be based on serious adverse events (SAE) from case report forms. The following summaries will be presented;

The number and percentages of patients reported as having Serious Adverse Events (SAE) in each treatment arm.

The number and percentages recorded as having all forms of Adverse Events (AE) in each arm; this will be presented as overall and stratified by AE classification.

Analysis of the decision quality questionnaires.Attrition analyses will first be conducted to examine the characteristics of questionnaire non-responders at each follow-up, using chi-square and independent t-tests as appropriate. The primary analysis will use a marginal GLM with robust standard errors to compare mean six-month post randomisation decision quality and decision regret

45

scores in women receiving the interventions versus usual care, controlling for baseline score (where appropriate) and other potential confounding variables. A 95 confidence interval for the treatment difference will also be reported.Secondary sub-group analyses will involve using regression techniques to examine the predictors (e.g. trial allocation, anxiety, illness perceptions and coping strategies) of decision quality and regret. The psychometric properties of the knowledge and collaborate components of decision quality will be examined using principal components analysis (underlying factor structure) and correlational analysis (convergence with other decision and coping measures).

13.2 Methods for any additional analysis (e.g subgroup and adjusted analyses) A series of exploratory sub group analyses using a marginal GLM with coefficients estimated using GEE with robust standard errors and an exchangeable auto correlation matrix, with the primary outcome the mean Global health status/quality of life score (questions 29+30 of EORTC QLQ-C30) at 6-month post-randomisation as the response will be carried out. We will use an interaction statistical test between the randomised intervention group and subgroup to directly examine the strength of evidence for the treatment difference between the treatment groups (Intervention versus Control) varying between subgroups. Age subgroup (75-79, 80-84, 85-89 and 90+ years) and co-morbidity levels (based on the modified Charlson co-morbidty score) will be the only a priori defined sub groups to be considered for interaction test. Sub group analysis will be performed regardless of the statistical significance on the overall intervention effect (Intervention versus control). The model below will be used to assess interaction:

Outcome = Randomised Group + Sub-group + randomised group*sub-group interaction

A graphical plot of mean profile subgroups with intervention group will be used to display the interaction.

13.3 Monitoring of data completenessReporting data completeness is an integral part of trial reporting. Hence a CONSORT style flow chart will be used to display data completeness and patient throughput from eligibility screening, invitation, study acceptance and final follow-up visit. This information will be made available to the TMG and DMEC on request and as regular reports. The statistical team will also report the number of:

Patients screened per month Patients recruited per month The number and percentage of patients who complete each follow up or are lost to follow up The number of patients who have complete data for each key variable.

To allow time for data entry, items will only be considered incomplete if they have not been entered within 30 days of the expected date.

14. Study MonitoringData will be monitored for quality and completeness by the Study Team. Missing data will be chased until it is received, confirmed as not available, or the trial is at analysis. The Study Team will conduct source data verification (SDV) on a minimum of 10% of patients. We have successfully monitored all 47 study sites during the cohort study.

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All sites have been adhering to GCP principles, data quality has been good with good levels of data completeness. There have been no safety concerns.

15. Study Management

15.1 DMEC

15.1.a Composition of DMECThe DMEC will be composed of the following independent members: a geriatrician, a medical oncologist and a breast surgeon. The DMEC for the Age Gap study is already well established and comprises Professor Alistair Thompson, Professor Margot Gosney and Dr Matthew Hatton. They meet every 6 months and review study progress and a full DMEC report is produced. So far there have been no issues related to study progress. The study will continue with the same monitoring arrangement.

15.1.b. Summary of DMEC role and reporting structure An independent Data Monitoring and Ethics Committee (DMEC) will be established to review the safety and ethics of the trial by reviewing interim data during recruitment. DMEC is independent from that of the study sponsor. The Committee will meet or communicate via teleconference 3-6-monthly. Detailed reports will be prepared by the Study Manager for these committees on a 3 monthly basis, and for the interim and final analyses.

15.1.c Description of any interim analyses and stopping guidelinesThere are no planned early stopping rules for this trial other than failure to recruit at a viable rate. This will be monitored by the TMG and DMEC. The study may be stopped after any interim review of recruitment after 12 months if the study is not meeting recruitment targets. This decision will be made by the TMG on the basis of advice from the DMEC. So far recruitment is proceeding at an acceptable rate and as the protocol for the amended study varied very little from the original we expect there to be no issues.

15.1.d HarmsThis study will monitor details of any Serious Adverse Events (SAEs) occurring to study participants during the study. The bulk of the research will involve completion of simple and well validated questionnaires, so there will be no physical pain, discomfort or distress. Questionnaires, however, take time to complete and so can be perceived as an inconvenience. Some of the questions refer to personal care (IADL, ADL) and mental health (MMSE), so they can also be perceived as being intrusive and it is possible in some participants the mere asking of these questions could give rise to a sense of distress, or could unmask distress about these issues. However, the Age Gap study has so far recruited over 1400 cases and 68% of women have completed all questionnaires, 8% have been data only recruits due to mental incapacity and only 24% have opted to not complete the QoL questionnaires which are optional. We have had very few withdrawals from the study due to study burden. Table 5 shows the data relating to study discontinuations for the Age Gap study showing a very small number where trial burden was cited as an issue (4 or 1400 6r 0.03%).

Table 5. Table of Age Gap Cohort Study Discontinuations after 18 months recruitment.

Number of patients Reason25 Death on Study 6 deaths due to breast cancer3 Lost to follow up1 Carer choice to withdraw pt15 Reason not specified12 Pt Choice to withdraw 3 for health reasons, 1 moved

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hospital, 4 found the questionnaires too time consuming or difficult.

Recruitment burdens will be minimised by the following approaches:

The recruitment process has been designed to avoid being overly onerous or time consuming. We have chosen assessments which are widely used and validated and have been found to be generally

acceptable in use. Experienced research nursing staff, used to dealing with patients with cancer, will be involved. In some cases women will be offered telephone/remote questionnaire completion to reduce time spent in

clinics. If a patient indicates that they have become tired or wish to stop during the application of the

questionnaires this will be respected and they will be offered an opportunity to continue them later, by telephone, by post or incomplete data returned.

15.2 . Composition, roles, and responsibilities of the study team

15.2.a. Chief Investigator (CI)Lynda Wyld will be the overall administrative lead with Malcolm Reed and Karen Collins leading on various aspects of the study such as site training, strategic development and writing committees. As a team, they will be responsible for the design, conduct, co-ordination and management of the trial.

15.2.b Role of study sponsor The trial will be sponsored by the Doncaster and Bassetlaw Hospitals NHS Foundation Trust (DBHNHSFT). This organisation will therefore be responsible for the initiation and management of the trial as defined in the principles of GCP according to the EU Directive 2005/28/EC (GCP Directive), which was implemented in The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006. The Trust will be liable for negligent harm caused by the design of the study. The NHS has a duty of care to patients treated, whether or not the patient is taking part in a clinical trial, and the NHS remains liable for clinical negligence and other negligent harm to patients under this duty of care. As this is a clinician-led study there are no arrangements for no-fault compensation.

15.2.c FunderThe study has been fully funded by a National Institute for Health Research Programme Grant.

15.2 d Trial Management Group (TMG) Objective

The Trial Management Group (TMG) is to manage and input into the running of the trial, including the clinical and practical aspects.

Roles and Responsibilities

Attend TMG meetings and provide advice on availability for future TMG meetings (non-attendance at three successive meetings may lead to removal from the TMG)

Input into and comment on the protocol and CRFs at the start of the trial Input into and comment on the protocol where amendments are required during the lifetime of the trial

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Input into the development of the statistical analysis plan Involvement in the day to day running of the trial, by supporting the Chief Investigators and Study manager

and researchers Respond to trial correspondence and any questions in a timely fashion Providing clinical or other expert guidance to the study researchers and participating sites on trial based

matters such as queries and interpretation of information recorded on CRFs Input into the monitoring and classification of serious adverse events (SAEs) Awareness of accumulating external evidence and assess its impact and relevance Providing responses to any issues or concerns raised by the Data Monitoring and Ethics Committee (DMEC) Consideration of the implications of any recommendations made by the DMEC Promotion of the trial Monitoring and encouraging recruitment Input into the interpretation and writing up of the trial results

Accountability

The TMG is responsible to the DMEC.

16. Ethics and dissemination

16. 1 Research ethics approval-Plans for seeking REC/IRB approvalThe trial will be performed in accordance with the recommendations guiding physicians in biomedical research involving human subjects, adopted by the 18th World Medical Association General Assembly, Helsinki, Finland, June 1964, amended at the World Medical Association General Assembly, Seoul, Korea, October 2008. Informed written consent will be obtained from the patients prior to participation in the study.

The right of a patient to refuse participation without giving reasons must be respected. The patient must remain free to withdraw at any time from the study without giving reasons and without prejudicing her further treatment. The study will be submitted to and approved by a National Research Ethics Committee and the appropriate locality site specific R&D approval prior to entering patients into the study. The Study will provide the main Research Ethics Committee with a copy of the final protocol, patient information sheets, consent forms and all other relevant study documentation. The trial will be conducted in accordance with the principles of GCP according to the EU Directive 2005/28/EC (GCP Directive), which was implemented in The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006.

16.2 Consent Written informed consent for entry into the trial must be obtained prior to participation. All staff involved in the consent process will be appropriately trained in the informed consent process. The right of the patient to refuse consent without giving reasons will be respected. Further, the patient will remain free to withdraw from the study at any time without giving reasons and without prejudicing any further treatment. A copy of the consent form will be given to the patient, a further filed in the hospital notes and a third will be held in the site file. Where appropriate, a fourth copy will be sent to the researchers working on the process evaluation. The patients will be asked if they wish for their GP to be notified of their participation in the study and if so, a standard letter will be sent out.

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17. Policy relating to non-English speaking participantsThe DESIs will not be applied to non-English speakers as its use would require high level language skills and the numbers will be small. However, if the DESIs are shown to be effective, the study team may arrange for translated versions to be made available for future use in a range of other languages.

18. ConfidentialityThe Study Team will collect patient data that includes some patient identifiers. The latter are required to allow back-identification of patients for the purpose of data clarification and clinical safety monitoring as well as to allow the researchers to contact patients to arrange an interview for the process evaluation. The Study Team will comply with all aspects of the Data Protection Act, 1998. Any information that would allow patients and clinicians to be identified will not be released into the public domain. If a patient withdraws consent from further study participation but not from collection of data, their data will remain on file and will be included in the final study analysis.

Trial data will be recorded by hospital staff (predominantly the NCRN funded locality research nurses) in the electronic or paper-based CRFs and signed off by appropriate trial personnel as detailed in the authorised signatories log completed for each participating site. It is anticipated that the majority of CRF completions will be electronic using a specially designed electronic web-based CRF designed for the study by the study Data Manager, (Tim Chater) and Chris Murray (EpiGenesys). The Study Manager, Study Monitor and Data Manager will collate all data from all study sites and will be responsible for verifying and checking the data.

All data will be handled, computerised and stored in accordance with the Data Protection Act 1998. Quality control will be maintained through adherence to departmental standard operating procedures (SOPs), and by following the principles of GCP according to the EU Directive 2005/28/EC (GCP Directive), which was implemented in The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006.

Participating hospitals will be expected to maintain a file of essential trial documentation (Investigator Site File), which will be provided by the Study team. It is the responsibility of each centre to retain copies of all completed CRFs for the trial and their study file on site or at their designated archive facility for a minimum of 15 years after study completion.

All centres will be asked to complete a log of all patients who are screened for eligibility who do not subsequently take part and the reason for non-participation.

19. ArchivingAt the end of the trial, data and the Trial Master File will be securely archived at the Academic Unit of Surgical Oncology and participating centres for a minimum of 15 years. Following authorisation from the sponsors arrangements for confidential destruction will then be made. If a patient withdraws consent for their data to be used, it will be confidentially destroyed.

20. Declaration of interestsNone of the study team have any conflict of interests to declare in this non-commercially sponsored and funded trial

21 Authorship eligibility guidelines The success of the trial depends upon the collaboration of all participants. For this reason, credit for the main results will be given to all those who have collaborated in the trial, through authorship and contributorship. Uniform

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requirements for authorship for manuscripts submitted to medical journals will guide authorship decisions. These state that authorship credit should be based only on substantial contribution to:

conception and design, or acquisition of data, or analysis and interpretation of data

drafting the article or revising it critically for important intellectual content

and final approval of the version to be published

and that all these conditions must be met (www.icmje.org ).

In light of this, the Chief Investigators will be named as authors in any publication. In addition, all collaborators will be listed as contributors for the main trial publications, giving details of roles in planning, conducting and reporting the trial. All publications will acknowledge the debt of gratitude to the women who have taken part in the study. Full acknowledgement will also be given to the PPI representatives in all publications and presentations.

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Appendix 1. PET versus Surgery Booklet (Front page only, full version sent as separate file)

52

Appendix 2. PET versus Surgery On Line Algorithm Screen shots.https://agegap.shef.ac.uk/

53

Appendix 3. Chemotherapy versus no chemotherapy booklet. Front page only: full version sent as separate file

54

Appendix 4. Chemotherapy versus no chemotherapy On Line Algorithm Screen shots.https://agegap.shef.ac.uk/

55

Appendix 5 Decision regret scales.

Surgery Versus Primary Endocrine TherapyPlease reflect on the decision that you made about your preferred treatment: to have surgery and hormone-blocking pills or hormone blocking pills only. Please show how strongly you agree or disagree with these statements by circling a number from 1 (strongly agree) to 5 (strongly disagree) which best fits your views about your decision.

Chemotherapy versus

no ChemotherapyPlease reflect on the decision that you made about your preferred treatment: to have chemotherapy or not to have chemotherapy after your surgery. Please show how strongly you agree or disagree with these statements by circling a number from 1 (strongly agree) to 5 (strongly disagree) which best fits your views about your decision.

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Strongly Agree

Agree Neither Agree Nor Disagree

Disagree Strongly Disagree

It was the right decision 1 2 3 4 5

I regret the choice that was made 1 2 3 4 5

I would go for the same choice if I had to do it over again

1 2 3 4 5

The choice did me a lot of harm 1 2 3 4 5

The decision was a wise one 1 2 3 4 5

Strongly Agree

Agree Neither Agree Nor Disagree

Disagree Strongly Disagree

It was the right decision 1 2 3 4 5

I regret the choice that was made 1 2 3 4 5

I would go for the same choice if I had to do it over again

1 2 3 4 5

The choice did me a lot of harm 1 2 3 4 5

The decision was a wise one 1 2 3 4 5

Appendix 6 CollaboRATE Scale (patient and carer versions)Patient version

These questions are about the appointment you had to talk about your breast cancer treatment

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Proxy version (for process evaluation)

These questions are about the appointment you had to talk about your relative’s/friend’s breast cancer treatment

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Appendix 7: Spielberger State-Trait Anxiety Inventory (STAI) 6 item.

Marteau TM, Bekker H. The development of a six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI). Br J Clin Psychol. 1992 Sep;31 (Pt 3):301-6.

A number of statements which people have used to describe themselves are given below. Read each statement and then circle the most appropriate number to the right of the statement to indicate how you feel right now, at this moment. There are no right or wrong answers. Do not spend too much time on any one statement but give the answer which seem to describe your present feelings best.

Not at all Somewhat Moderately Very much1. I feel calm 1 2 3 42. I am tense 1 2 3 43. I feel upset 1 2 3 44. I am relaxed 1 2 3 45. I feel content 1 2 3 46. I am worried 1 2 3 4

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Appendix 8 Knowledge and preference Q.Sections A1 are for women who had a decision to make about surgery or hormone blocking pills. Section A2 are for women who had to decide between chemotherapy and no chemotherapy.

Breast Cancer Treatment Choices

Completing the questionnaire

These questions are about what matters most to you and about your understanding of the treatments available to help to treat your breast cancer, such as surgery with hormone-blocking pills or hormone-blocking pills only.

Please tick the box to answer each item.

Section A1. Knowing your options (surgery and hormone-blocking pills or hormone-blocking pills only)

Some of these statements are true, some are false and we expect that you might be unsure sometimes. Please tick one box for each question.

1. Hormone-blocking pills are a type of chemotherapy. Unsure

False

True

2. Following surgery women do not need to take hormone-blocking pills. Unsure

False

True

3. Women who have hormone-blocking pills only (no surgery) will need hospital check-ups more often than women who have surgery. Unsure

False

True

4. Hormone-blocking pills can stop the cancer growing and may shrink it. Unsure

False

True

5. Women who have hormone-blocking pills only (no surgery) are likely to stay alive just as long as women who have the pills and surgery. Unsure

False

True

6. If the hormone-blocking pills stop working, women may need to have surgery or a change of pills later on. Unsure

False

True

7. Surgery to the underarm glands can cause arm swelling in some women. Unsure

False

True

8. Women usually need radiotherapy after having a mastectomy (surgery to remove the whole breast). Unsure

False

True

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Breast Cancer Treatment Choices

Completing the questionnaire

These questions are about what matters most to you and about your understanding of the treatments available to you to help treat your breast cancer, such as chemotherapy.

Please tick the box to answer each item.

Section A2. Knowing your options (Chemotherapy versus no chemotherapy)

Some of these statements are true, some are false and we expect that you might be unsure sometimes. Please tick one box for each question.

1.Chemotherapy may increase the chance of long term cure in some women with breast cancer but not all. Unsure

False

True

2.Chemotherapy can cause hair loss in some women. Unsure

False

True

3. Hair loss after chemotherapy almost always regrows.

Unsure

False

True

4. Herceptin is only used to treat women with a certain type of breast cancer.

Unsure

False

True

5. Chemotherapy is usually given into a vein Unsure

False

True

6. Chemotherapy can temporarily increase the risk of getting infections. Unsure

False

True

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Section B. Thinking about the decision you face

9. I know enough about the options available to me. I’m unsure if I know enough

No, I do not know enough

Yes, I know enough

10. I am aware of the advantages and disadvantages of each option. I’m unsure of the advantages and disadvantages

No, I’m not aware of the advantages and disadvantages

Yes, I’m aware of the advantages and disadvantages

11. I know which option I prefer. I’m unsure which option I prefer

No, I don’t know which option I prefer

Yes, I know which option I prefer

12. I am ready to make a decision. I’m unsure if I am ready to make a decision

No, I am not ready to make a decision

Yes, I am ready to make a decision

Section C. Choice of Treatment

13. At the moment I think that:Please tick only one box

I strongly prefer hormone-blocking pills only

I am leaning towards hormone-blocking pills only

I am not sure which option to choose

I am leaning towards surgery with hormone-blocking pills

I strongly prefer surgery with hormone-blocking pills

14. What influenced you most in making your decision?Please tick up to two boxes

I have not made a decision yet

Talking to family or friends

Reading the booklet “Deciding about your breast cancer treatment”

Reading other information (e.g. leaflets)

Using the Option Grid

Talking to a healthcare professional at the breast unit/hospital (specialist doctor or nurse)

Talking to family doctor/GP

Talking to other patients

Other

If ‘other’, please describe here: ………………………………………………………………………………………………………………………

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Appendix 9 Brief Illness Perceptions Questionnaire We’re interested to know your own personal views of your breast cancer.

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Appendix 10 Brief COPEThese items deal with ways you've been coping since you found out that you have breast cancer. Here is a list of things women might do to cope with their breast cancer. Different people deal with things in different ways, but we’re interested in how you've tried to deal with your breast cancer. We want to know how much you've been doing what each item says. Make your answers as true for you as you can.

I haven't been doing this at all

I've been doing this a

little bit

I've been doing this a medium

amount

I've been doing this a

lot1. I've been concentrating my efforts on doing something about the situation I'm in.

1 2 3 4

2. I've been saying to myself "this isn't real.". 1 2 3 43. I've been getting emotional support from others.

1 2 3 4

4. I've been giving up trying to deal with it. 1 2 3 45. I've been taking action to try to make the situation better.

1 2 3 4

6. I've been refusing to believe that it has happened.

1 2 3 4

7. I’ve been getting help and advice from other people.

1 2 3 4

8. I've been trying to see it in a different light, to make it seem more positive.

1 2 3 4

9. I've been trying to come up with a strategy about what to do.

1 2 3 4

10. I've been getting comfort and understanding from someone.

1 2 3 4

11. I've been giving up the attempt to cope. 1 2 3 412. I've been thinking hard about what steps to take.

1 2 3 4

13. I've been accepting the reality of the fact that it has happened.

1 2 3 4

14. I’ve been trying to get advice or help from other people about what to do.

1 2 3 4

15. I've been learning to live with it. 1 2 3 4

16. I've been looking for something good in what is happening.

1 2 3 4

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Appendix 11: Process evaluation questionnaires (for intervention and control arm patients respectively). Versions with appropriately adapted wording will be used for the chemotherapy/no chemotherapy decision and for patient or carers (see text in < > show variation).

A. Questionnaire for intervention arm patients onlyWe would like to ask you some questions about <your relative/friend> being given the treatment options of <surgery and hormone-blocking pills or hormone-blocking pills only> <chemotherapy or no chemotherapy>?

1. Who spoke to you about <your> <your relative’s/friend’s> treatment options? Please tick all that apply:

The doctor from the <breast unit> <hospital>

The nurse from the <breast unit> <hospital>

A doctor or nurse or similar on a telephone helpline

GP or practice nurse

other (please say who)………………………………………………………………………….

2. Were you provided with any booklets/leaflets about breast cancer and/or <your> <your relative’s/friend’s> breast cancer treatment options?

Yes NoIf yes, which of the following: (please tick all that apply)

Personalised risk information (print out from the doctor/nurse’s computer)

Option grid

Information booklet called “Deciding about your breast cancer treatment”

other (please give details)………………………………………………………………………….

3. If you were given information to take away how did you use it? Please tick all that apply:

I read it all

I read some of it

I did not read it

I filled in some/or all of the blank sections in the booklet

I showed it to friends or family


4. Overall, how useful did you find the information about <your> <your friend’s/relative’s> treatment options in thinking about and making <your> <your friend’s/relative’s> decision (if <you> <they> had a choice)?

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<Snapshot of relevant booklet>

<Snapshot of relevant option grid>

<Snapshot of relevant personalised risk info>

Not at all useful

Somewhat useful

Moderately useful

Very useful

5. How useful did you find the different parts of the information about <your> <your friend’s/relative’s> treatment options in thinking about and making <your> <your friend’s/relative’s> decision (if <you> <they > had a choice)?

a) Personalised risk information (print out from the doctor/nurse’s computer)I did not receive this or did not read or use it Not at all useful

Somewhat useful

Moderately useful Very useful

b) Option grid (or “options at a glance”)

I did not receive this or did not read or use it Not at all useful

Somewhat useful


c) “Deciding about your breast cancer treatment” booklet information sections (e.g. about breast cancer, <surgery, hormone blocking pills> <chemotherapy, Herceptin> )


Somewhat useful


d) “Deciding about your breast cancer treatment” booklet “My Decision” section (e.g. my questions, weighing up my options)


Somewhat useful


6. What did you think about the amount of information you were given?

Not enough

About right

Too much

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B. Questionnaire for control arm patients onlyWe would like to ask you some questions about <your relative/friend> being given the treatment options of <surgery and hormone-blocking pills or hormone-blocking pills only> <chemotherapy or no chemotherapy>?

1. Who spoke to you about <your> <your relative’s/friend’s> treatment options? Please tick all that apply:

The doctor from the <breast unit> <hospital>

The nurse from the <breast unit> <hospital>

A doctor or nurse or similar on a telephone helpline

GP or practice nurse

other (please say who)………………………………………………………………………….

2. Were you provided with any booklets/leaflets about breast cancer and/or <your> <your relative’s/friend’s> breast cancer treatment options?

Yes NoIf yes, can you tell us the name of the leaflets/booklets?............................................................

......................................................................................................................................................

3. If you were given information to take away how did you use it? Please tick all that apply:

I read it all

I read some of it

I did not read it

I showed it to friends or family


4. How useful did you find the information about <your> <your relative’s/friend’s> treatment options in thinking about and making <your> <your relative’s/friend’s> decision (if <you> <they > had a choice)??

Not at all useful

Somewhat useful

Moderately useful

Very useful

5. What did you think about the amount of information you were given?

Not enough

About right

Too much

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Appendix 12 Process evaluation interview schedulesVersions with appropriately adapted wording for carers will be used.

A. Process Evaluation Patient Interview Schedule – Intervention ArmWere you given a choice of treatment for your breast cancer?

If yes, what were the options?If no, what treatment did you have?

Which sources of information were used when discussing your treatment options? Did your clinician use the treatment algorithm/personalised risk assessment?Did your clinician use the option grid used in consultationDid your clinician offer you the booklet?

How were these information sources used? To what extent were they used in clinic/at home, with family/friends? What other information sources were used alongside them?

How useful do you think the information was?Which were the most/least useful component of information (treatment algorithm/ booklet/ option grid)?To what extent do you think the treatment algorithm output helped or hindered your conversation about treatment options in clinic?To what extent do you think the option grid helped or hindered your conversation about treatment options with your clinician?To what extent did the booklet help or hinder discussions about your treatment options with family/friends? Which sections were particularly useful/not useful? Which sections (if any) did you complete?

How do you feel now about your treatment decision?Would you make the same decision again?What impact has the decision had on you?

How do you feel about the way the decision about your treatment was made?How involved did you feel you feel in the decision about your treatment? How much effort was made to involve you?How much effort was made by the clinician to understand what matters most to you?To what extent do you feel that you knew enough to make a decision?To what extent did you feel ready to make a decision?

To what extent do you think the information sources (and discussion?)….

…helped you think about your treatment choice (pros and cons, your preferences, making the decision)?…helped you understand what the options were?/ knowledge of the treatments?…. influenced how you coped with the decision? ….influenced how much support you felt you had in making the decision?…influenced how much confidence you had in making the right/best decision?

Which aspects made a difference? How did the information sources make you feel about your decision?

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To what extent did having different figures in the generic and personalised information impact your decision?

(initial chemotherapy interviews only)Is the Option Grid/ booklet easy to use and understand?What do you think about the questions listed on the left (Option Grid only)?What do you think about the different sections of the booklet (booklet only)?

What improvements could be made to the information sources and how they were used? Are there pieces of information missing?Could they have been used in a more helpful way?Any disadvantages?

B. Process Evaluation Patient Interview Schedule – Control Arm Were you given a choice of treatment for your breast cancer?

If yes, what were the options?If no, what treatment did you have?

Which sources of information were used when discussing your treatment options? Did your clinician use a computer package to look at what treatment would be best for you (anything like adjuvant online)?Did your clinician use a list of FAQs about the treatments (anything resembling an option grid)?

How were these information sources used? To what extent were they used in clinic/at home, with family/friends? What other information sources were used alongside them?

How useful do you think the information was?Which were the most/least useful component of information?To what extent do you think the information you received helped or hindered your conversation about treatment options in clinic?To what extent did the information you were given help or hinder discussions about your treatment options with family/friends? In what way?

How do you feel now about your treatment decision? Would you make the same decision again?

What impact has the decision had on you?

How do you feel about the way the decision about your treatment was made?How involved did you feel you feel in the decision about your treatment? How much effort was made to involve you?How much effort was made by the clinician to understand what matters most to you?To what extent do you feel that you knew enough to make a decision?To what extent did you feel ready to make a decision?

To what extent do you think the information sources (and discussion?)….…helped you think about your treatment choice (pros and cons, your preferences, making the decision)?

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…helped you understand what the options were?/ knowledge of the treatments?…. influenced how you coped with the decision? ….influenced how much support you felt you had in making the decision?…influenced how much confidence you had in making the right/best decision?

Which aspects made a difference? How did the information sources make you feel about your decision?

C. Process Evaluation Clinician Interview Schedule - Clinicians

Which components of the DESI have you used when discussing treatment options with your patients? The treatment algorithm/personalised risk assessment?The option grid?The booklet?

How were the components of the DESI used? To what extent were they used in clinic/given to take away?

Discuss/show the patient their personalised risk?How was the option grid used? Did you go through any of the booklet? / offer it to take away?

What other information sources were used alongside them?

How useful do you think the DESI was?How useful was the treatment algorithm for your clinical decision making about what to offer the patient?To what extent do you think the treatment algorithm output helped or hindered your decisions about treatment options and the discussion with patients?To what extent do you think the option grid helped or hindered your discussions in clinic?To what extent did the booklet help or hinder discussions?To what extent and in what way do you think the DESI has changed your practice?

What has contributed to this? Which components? To what extent do you feel you shared the decision about treatment with your patients?

To what extent do you feel you involved your patients in the decision about their treatment?

To what extent do you think the DESI (and discussion?)….…helped patients think about their treatment choice (pros and cons, their preferences, making the decision)?…helped patients understand what the options were?/ knowledge of the treatments? ….helped you to understand what mattered most to your patients about the options?…facilitated the discussion between you and your patients about their treatment?… influenced how patients coped with the decision? …influenced how much support patients had in making the decision?…influenced how much confidence patients had in making the right/best decision? ...influenced how engaged/involved patients were in decision making?

Which aspects made a difference? What impact do you think the DESI might have on how patients feel about their decision?

What improvements could be made to the DESI and how it is used? 70

(Specific to each component: treatment algorithm, option grid, booklet)

To what extent do you think the components of the DESI can be delivered as planned? As part of the trial?As part of routine clinical practice in the future?

What do you think the barriers and facilitators to implementation of the DESI are? (Specific to each component: treatment algorithm, option grid, booklet)

Is there enough time in clinic to use the treatment algorithm and option grid?Is there a better place in the care pathway for them to fit in?Do you perceive a need for decision support?What (if any) system level changes been made or are needed to accommodate DESI use?Do you envisage any particular training needs (such as use of the option grid, or more broadly shared

decision making or communication skills)?

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Appendix 13. Training PackageThere are two sections to the workshop. Sites randomised to the control arm will only receive the Trial Initiation, whereas sites randomised to the intervention arm will receive the Trial Initiation and DESI workshop. The following outlines what will be covered during these sessions.

1. Trial Initiation Background/rationale (include update on cohort study & scientific evidence about PET or surgery and

chemotherapy or no chemotherapy in this age group) Aims/objectives/outputs Study Design (include brief description of intervention and process evaluation) Study Team contacts Open discussion of other issues as required

For sites taking part in the process evaluation only (6 control, 6 intervention): Eligibility Criteria, aims and components of the process evaluation Recruitment Data Collection (changes to patient materials/ additional questionnaires/ updated CRF forms) Monitoring Troubleshooting/what to do if things go wrong/frequently asked questions

2. Decision Support Intervention (DESI) Workshop – Intervention arm sites onlyThe DESI workshop will include presentations, a demonstration of the clinical algorithm and discussion. The session will be video and audio recorded and made available for new starter staff or staff who were unable to attend in person. The following will be covered:

Computer algorithmo Development and validation of the data: limitations, validity, accuracy. o Demonstration of the web based tool with several scenarios with discussion of the results and

question and answer sessionso Small group workshops for centre staff to try out the tool with trial staff on hand to trouble shoot.o Frequently asked questions and open discussion session

Patient option grid and bookleto Lecture on shared decision making: its value, evidence of benefit and techniques to facilitate. o The patient decision support intervention will be presented and each component discussed in detailso The development and rationale of the option grids. o Option grid use (include option grid cartoon: www.optiongrid.org)o The development of the booklets and the evidence base of their content

Discussion of clinical pathways and DESI use Small group break-out sessions to discuss use with team members. DESI team contacts

Materials from the workshop (as appropriate depending on trial allocation) will be made available to the PI/local study teams along with a DVD recording of the workshop (this will be of one of the initial workshops). This will allow for dissemination of the information to member of staff unable to attend.

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http://www.optiongrid.org/

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Contents Page - A world-class university – a unique …/file/... · Web viewWomen in the intervention sites will express more positive illness representations (e.g. increased personal