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 39thMarch2016

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

Executive 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 resourceto 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 DESIsto use alongside their routine counselling resources as part of normal practice.

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 NumberRP-PG-1209-10071

Award Amount:£1,800, 000

Duration:6 years (3.25 years remaining)

Date of Award:20th March 2012

Programme Start date1st July 2012

SponsorDoncaster and Bassetlaw Hospitals NHS FoundationTrust

Contents Page

Contents

Contents Page

1 Study Team

1.1 Project Leads

1.4 Process Evaluation Team

1.5 Software and web tool design

1.6 Consumer Representation:

1.7 Trial Management Team

1.8 DBH Trust NHS Foundation Trust Administration

2. Lay Summary.

2.1 Introduction.

2.2 Methods.

2.3 Study schematic. (Figure 1)

3. Background and rationale

3.1. Breast cancer in Older Women

3.2. Primary Endocrine therapy

3.3. Adjuvant Chemotherapy

3.4. Interim Update of the Age Gap Cohort study.

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

3.6 The Patient Facing Decision Support Tools

4. Objectives and hypothesis

4.1Aims:

4.2Study Objectives

4.3 Hypotheses

5. Trial design

6.1 Study setting

6.2 Eligibility criteria

6.2.a Inclusion Criteria

6.2.b. Exclusion Criteria

6.3. Study Interventions

6.3.a. Control Arm

6.3.b Intervention arm

6.4. Outcomes

6.4.a Primary outcome measure

6.4.b. Secondary outcomes

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

6.5Study Timelines:

6.5.a Table 2. Gantt Chart

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

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

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

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

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

7. Sample size

7.1 Study population

7.2 Sample size calculation

7.3 Cluster Randomisation

8. Recruitment

8.1 Identification and recruitment of patients

9.0 Data collection and follow up

9.1 Table 3: Visit Schedule

10. Study Questionnaires

10.1 Decision Quality, Psychological and Process Evaluation Measures

11. Process Evaluation

11.1 Process Evaluation overview

11.2 Aims

11.3 Methods for process evaluation

11.4 Audio-recording clinical consultations

11.5 Questionnaires

11.6 Interviews

11.7 Recruitment for the process evaluation

11.8. Data Collection for the process evaluation

11.9 Treatment Decision CRF

11.10 Analysis of process evaluation

11.10.1 Consultations

11.10.2. Interviews

11.10.3. Questionnaires

11.10.4. Integration of Analyses

12. Data management for the DESI sub-study

12.1 Security and storage

13. Statistical methods

13.1 Statistical analyis of primary and secondary outcomes

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

13.3 Monitoring of data completeness

14. Study Monitoring

15. Study Management

15.1 DMEC

15.1.a Composition of DMEC

15.1.b. Summary of DMEC role and reporting structure

15.1.c Description of any interim analyses and stopping guidelines

15.1.d Harms

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

15.2.a. Chief Investigator (CI)

15.2.b Role of study sponsor

15.2.c Funder

15.2 d Trial Management Group (TMG)

16. Ethics and dissemination

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

16.2 Consent

17. Policy relating to non-English speaking participants

18. Confidentiality

19. Archiving

20. Declaration of interests

21 Authorship eligibility guidelines

Appendix 1. PET versus Surgery Booklet

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

Appendix 3. Chemotherapy versus no chemotherapy booklet.

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

Appendix 5 Decision regret scales.

Surgery Versus Primary Endocrine Therapy

Chemotherapy versus no Chemotherapy

Appendix 6 CollaboRATE Scale (patient and carer versions)

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

Appendix 8 Knowledge and preference Q.

Appendix 9 Brief Illness Perceptions Questionnaire

Appendix 10 Brief COPE

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

Appendix 12 Process evaluation interview schedules

Appendix 13. Training Package

1. Trial Initiation

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

References.

1 Study Team

1.1 Project Leads

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

Tel. 0114 2268640

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

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

Tel. 0114 2255732

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.

Tel. 0114 2255498

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

l. 0114 271 2373

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

Tel. 0114 2711988

1.3 Statistical Team

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

, Tel. 0114 222 0730

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

, Tel. 0114 222 5450

1.4Process Evaluation Team

Adrian Edwards, Institute Director, Institute of Primary Care & Public Health, Cardiff University.

, Tel. 029 20687196

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

, Tel. 02920687194

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

, Tel. 029 20687809

1.5Software and web tool design

Chris Murray, Managing Director, epiGenesys, University of Sheffield.

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

, Tel. 0114 222 1888

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

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

, Tel: 0114 2221888, extension 31832

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

, Tel. 0114 2222989

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

, Tel. 0114 2220816

1.6 Consumer Representation:

Tracy Green, member of the North Trent Consumer Research Panel

Deirdre Revill, member of the North Trent Consumer Research Panel

Jacqui Gath, member of the North Trent Consumer Research Panel

1.7 Trial Management Team

Charlene Martin, Study Manager, University of Sheffield.

Tel. 0114 2713611

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

, Tel. 0114 22 20876

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

Tel. 0114 2713611

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

Tel: 0114 2713611

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

, 0114 22 20876

1.8DBH Trust NHS Foundation Trust Administration

Amy Bell, Clinical Research Development Manager,Doncaster and BassetlawTeaching Hospitals NHS Foundation Trust, Doncaster.

, Tel. 01302 366666

1.9Oncology advisors:

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

, Tel. 020 7352 8171

Robert Leonard, Professor of Oncology, Imperial College London.

1.10. Geriatrics Advisors:

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

Tel. 0116 252 3187

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

, Tel. 0151 4301679

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

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

, Tel.(0)1273 873015

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 theywould 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 basedclinical management algorithm is also able to generate a bespoke print out which is suitable for use during the clinical consultation where treatment decisionsare discussed.
  1. Two patient facing decision support booklets have been developed and pilotedand 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 isnested within the Age Gap Cohort Study which is recruiting well at50participating UK Breast Units. The current Age Gap protocol (Version 3) gives full details of the primary study methods.

Recruiting Breast Unitswill 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 sitesusing the DESIswill 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 formsand 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 continuenormal care and be asked to complete the standardAge 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 attenda 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 workshopconsisting 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 theDESIs 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 formsand 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).