A randomised SWAT assessing the impact of an enhanced patient information leaflet on recruitment in a trial of axillary treatment for early-stage breast cancer

Cydney Bruce; Shabina Sadiq; Clare Calvert; David Dodwell; Patricia Fairbrother; Lesley Fallowfield; Valerie Jenkins; Mickey Lewis; Amit Goyal; Alan Montgomery

doi:10.12688/f1000research.171727.1

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Research Article

A randomised SWAT assessing the impact of an enhanced patient information leaflet on recruitment in a trial of axillary treatment for early-stage breast cancer

[version 1; peer review: awaiting peer review]

Cydney Bruce ¹, Shabina Sadiq¹, Clare Calvert¹, [...] David Dodwell², Patricia Fairbrother³, Lesley Fallowfield⁴, Valerie Jenkins⁴, Mickey Lewis¹, Amit Goyal⁵, Alan Montgomery¹

Cydney Bruce ¹, Shabina Sadiq¹, [...] Clare Calvert¹, David Dodwell², Patricia Fairbrother³, Lesley Fallowfield⁴, Valerie Jenkins⁴, Mickey Lewis¹, Amit Goyal⁵, Alan Montgomery¹

PUBLISHED 21 Oct 2025

Author details Author details

¹ Nottingham Clinical Trials Unit, School of Medicine, University of Nottingham, Nottingham, UK
² Oxford Population Health, University of Oxford, Oxford, UK
³ Patient Advocate, Independent Cancer Patients' Voice, London, UK
⁴ Sussex Health Outcomes Research & Education in Cancer (SHORE-C), BSMS, University of Sussex, Brighton, UK
⁵ Department of Surgery, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK

Cydney Bruce
Roles: Formal Analysis, Writing – Original Draft Preparation

Shabina Sadiq
Roles: Conceptualization, Funding Acquisition, Project Administration, Writing – Review & Editing

Clare Calvert
Roles: Conceptualization, Funding Acquisition, Project Administration, Writing – Review & Editing

David Dodwell
Roles: Conceptualization, Writing – Review & Editing

Patricia Fairbrother
Roles: Conceptualization, Writing – Review & Editing

Lesley Fallowfield
Roles: Conceptualization, Writing – Review & Editing

Valerie Jenkins
Roles: Conceptualization, Writing – Review & Editing

Mickey Lewis
Roles: Conceptualization, Funding Acquisition, Project Administration, Writing – Review & Editing

Amit Goyal
Roles: Conceptualization, Funding Acquisition, Writing – Review & Editing

Alan Montgomery
Roles: Conceptualization, Funding Acquisition, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS AWAITING PEER REVIEW

This article is included in the Oncology gateway.

This article is included in the Studies Within A Trial (SWAT) collection.

Abstract

Background

A study within a trial (SWAT) can be used to compare the effectiveness of various recruitment aids. In this SWAT, we assessed the impact of incorporating a pictorial aid into an enhanced Patient Information Leaflet (PIL) versus utilising a standard PIL, nested within a trial comparing adjuvant therapy alone with adjuvant therapy plus axillary treatment for women with early-stage breast cancer with metastases in one or two sentinel nodes (the POSNOC trial).

Methods

The pictorial aid was designed to illustrate the treatment procedures in both arms of the POSNOC trial for potential participants. POSNOC recruiting sites were cluster randomised to provide potentially eligible women who were approached about taking part in the study with either the enhanced PIL or the standard PIL. Allocation was stratified by recruitment activity in the 12 months preceding the SWAT.

Results

Eighty sites participated in the SWAT, with 40 randomised to each arm. Between December 2019 and July 2021, 258 participants were recruited. The enhanced PIL group recruited 117 participants (mean = 2.9 per site) while the standard PIL sites recruited 141 participants (mean = 3.5 per site). There was no evidence of a between-group difference in recruitment (adjusted difference in mean in enhanced vs standard PIL = -0.68, 95% CI -1.99 to 0.63, p=0.31).

Conclusion

The study found no evidence that an enhanced PIL increased recruitment compared with the standard PIL. These data may contribute to future systematic reviews of randomised studies of recruitment interventions.

Keywords

SWAT, Study Within A Trial, recruitment methods, embedded randomised controlled trial

Corresponding author: Cydney Bruce

Competing interests: No competing interests were disclosed.

Grant information: This work was supported by the Medical Research Council (MRC) [PROMETHEUS study award reference MR/R013748/1] and the National Institute of Health Research (NIHR) Health Technology Assessment (HTA) Programme [POSNOC study award reference 12/35/17].
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2025 Bruce C et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Bruce C, Sadiq S, Calvert C et al. A randomised SWAT assessing the impact of an enhanced patient information leaflet on recruitment in a trial of axillary treatment for early-stage breast cancer [version 1; peer review: awaiting peer review]. F1000Research 2025, 14:1145 (https://doi.org/10.12688/f1000research.171727.1) First published: 21 Oct 2025, 14:1145 (https://doi.org/10.12688/f1000research.171727.1) Latest published: 21 Oct 2025, 14:1145 (https://doi.org/10.12688/f1000research.171727.1)

Introduction

In multi-centre randomised controlled trials, recruitment can often be challenging^1–3 and methods to improve recruitment are commonly employed.^4,5 Providing eligible patients with information about the trial in different formats is one such intervention that may affect recruitment, and a pictorial aid is an approach identified by the PROMETHEUS programme as a priority question.⁶ A Study Within A Trial (SWAT) allows researchers to embed a study within the main trial to obtain high quality evidence about the effectiveness of interventions that aim to improve trial recruitment or retention.⁷

POSNOC is a pragmatic, multicentre, non-inferiority, international, randomised controlled trial comparing adjuvant therapy alone with adjuvant therapy plus axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes.⁸ The primary outcome of the trial is axillary recurrence within 5 years post randomisation.

After being approached about POSNOC, potential participants were offered access to a 45-minute information video about the study in either DVD or online format. The film included an explanation of the different treatments being compared in POSNOC and a Q&A session. In addition, communication training was provided to health care professionals at recruiting sites to ensure equipoise in their communication about the trial.

Recruitment for POSNOC opened in Aug 2014 and was planned to close in March 2018. However, by July 2019, over a quarter of the target sample size of 1900 remained still to be recruited. Whilst recruitment was consistent, a new method to boost recruitment was required. Despite the information film for patients and communication training for site staff, eligible women who were not randomised commonly reported a preference for one of the two treatment groups as the main reason for not participating in the trial.

Based on the findings of a previous systematic review,⁹ we hypothesised that a pictorial representation of the two treatment pathways being compared in POSNOC in an enhanced patient information leaflet (PIL), could provide a simple and easily-accessible explanation of the trial and increase recruitment of eligible women.

The aim of this SWAT was to determine the effect of an enhanced PIL compared with a standard PIL on participant recruitment in the POSNOC trial.

Methods

Study design

The SWAT was a two arm, parallel group, cluster randomised trial embedded within the POSNOC trial. POSNOC recruiting sites in the UK were randomised with an allocation ratio of 1:1 to use either the standard PIL, or an enhanced PIL containing an additional pictorial aid, when introducing the study to patients.

Participants

The target patient group for POSNOC was women with unifocal or multifocal invasive breast cancer, largest primary lesion ≤5 cm, undergoing sentinel node biopsy (SNB) and with 1 or 2 nodes with macrometastases (>2 mm or defined as macrometastases on molecular assay). Participants in the SWAT were all women approached about potential participation in the POSNOC trial. These women were approached about POSNOC using the randomised recruitment information (either the standard PIL or enhanced PIL).

Interventions

Standard patient information leaflet (PIL):

The standard patient information leaflet was designed during trial site-up and approved as part of Research Ethics Committee approval prior to commencing recruitment. This 6-page document contained the following sections: (1) Why are we doing this study; (2) Why have I been invited to take part; (3) What will I have to do if I take part; (4) Possible disadvantages or risks; (5) Possible benefits; (6) What happens after the study; (7) How will my data be used; (8) What are my choices about how my information is used; (9) Results of the study; (10) What if there is a problem; (11) Tissue samples; (12) Who has reviewed the study; (13) Where can I find out more about how my information is used.

Enhanced PIL:

In addition to information contained in the standard PIL, the enhanced PIL included a flow diagram to represent pictorially what would happen in each of the treatment groups (Appendix file 1). The pictorial aid was embedded into the PIL to ensure that participants would receive it.

The pictorial aid was designed by members of the trial management group, including a patient member, before being submitted for ethical approval. Sites randomised to the enhanced PIL were provided with printed colour copies from the central trial team.

Randomisation

A cluster randomised design for the SWAT was the only practical method of implementing a fair test of the enhanced PIL compared with standard PIL. Allocation was stratified by recruitment to POSNOC in the previous 12 months (0, 1, 2, >2 participants randomised). The trial statistician generated the sequence and allocated site to the PIL used. Sites were then notified of their allocation by the trial management team and provided with the enhanced PIL where appropriate.

Outcomes

The planned primary outcome was the recruitment fraction, defined as the number of women randomised to the POSNOC trial at each site, as a proportion of all women identified as potentially eligible and approached about participation. However, due to concerns about the quality of screening data provided by some sites, we changed the primary outcome to the number of women randomised to the POSNOC trial during the SWAT, rather than the recruitment fraction. The decision to change the primary outcome was made during a blinded review of data from all participating sites together, that is, prior to viewing any data separately by SWAT allocation.

Statistical considerations

Since data regarding numbers of women approached and recruited for POSNOC are reported at site level, the number of observations in the analysis is equal to the number of sites in the SWAT i.e. one observation per site. Between opening the study to recruitment and implementing the SWAT, mean annual recruitment was 3.8 participants per site with standard deviation 2.6. With 90% power and 5% two-sided alpha an expected sample size of 45 sites per arm enables detection of a standardised difference of 0.69 SDs, equivalent to a between-group difference in mean recruitment of 1.8 participants per year.

We used appropriate descriptive statistics to describe sites randomised to each of the SWAT groups. We estimated the between-group difference in mean number of women randomised using analysis of covariance, adjusted for duration of time in months each site had been open, and number of women recruited in the 12 months prior to the SWAT. Since the SWAT duration was equal for all sites, and the number of sites allocated to each SWAT arm identical, we did not need to standardise for analysis the number of participants recruited during the SWAT.

Ethical approval

Approval for the SWAT was granted by NRES Committee East Midlands Nottingham-2 on 19 November 2019. Full details are provided in the Declarations section.

Results

Of the total 115 sites in POSNOC, 95 were in the UK, and of these, 80 participated in the SWAT (n = 40 allocated to each arm). Baseline data for SWAT sites are presented in Table 1. SWAT arms were well balanced in terms of duration since opening to recruitment, and number of participants recruited both overall and in the 12 months prior to the SWAT.

Table 1. Baseline data for recruiting sites.

		Standard PIL (n = 40)	Enhanced PIL (n = 40)	Total (n = 80)
Duration site open prior to SWAT (months)	Mean [sd]	52.6 [9.4]	50.3 [12.1]	51.5 [10.8]
Duration site open prior to SWAT (months)	Median [IQR]	56 [46, 59]	56 [44, 59]	56 [45, 59]
Site recruitment prior to SWAT: TOTAL (n)	Mean [sd]	16.9 [10.6]	16.3 [14.9]	16.6 [12.9]
Site recruitment prior to SWAT: TOTAL (n)	Median [IQR]	14.5 [8.5, 25]	14.5 [7, 22]	14.5 [7, 23.5]
Site recruitment prior to SWAT: 12 MONTHS (n)	Mean [sd]	4.3 [3.7]	4.3 [3.9]	4.3 [3.7]
Site recruitment prior to SWAT: 12 MONTHS (n)	Median [IQR]	4 [1, 6]	3 [1, 6.5]	4 [1, 6]

A total of 258 participants were recruited by these 80 sites during the 19-month SWAT ( Table 2). Ten sites in the standard PIL arm and 7 in the enhanced PIL arm did not recruit any participants, and over 60% of recruited participants came from a total of just 20 (25%) sites.

Table 2. Number of participants recruited by SWAT arm.

		Standard PIL (n = 40)	Enhanced PIL (n = 40)	Total (n = 80)
Total recruited		141	117	258
Number randomised per site	Mean [sd]	3.5 [3.5]	2.9 [3.2]	3.2 [3.3]
Number randomised per site	Median [IQR]	2.5 [0.5, 5]	2 [1, 4]	2 [1, 4.5]
Participant recruitment per site n(%)	0	10 (25)	7 (18)	17 (21)
	1	2 (5)	11 (28)	13 (16)
	2	8 (20)	5 (13)	13 (16)
	3	4 (10)	3 (8)	7 (9)
	4	4 (10)	6 (15)	10 (13)
	5+	12 (30)	8 (20)	20 (25)

Although more participants were recruited in sites allocated to the standard PIL arm, 95% confidence limits for the adjusted difference in means are wide and include the null ( Table 3).

Table 3. Adjusted difference in means between groups.

	Adjusted difference in mean recruitment per site¹	95% CI	p value
Enhanced PIL vs Standard PIL	-0.68	-1.99, 0.63	0.31

1 Adjusted for number of participants per site recruited in the 12 months prior to the SWAT (0, 1, 2, >2) and recruitment duration prior to SWAT implementation (months).

Discussion

Our study did not find evidence suggesting that adding a pictorial representation of the host trial to the PIL had an effect on recruitment. However, the confidence limits do not exclude important potential effects in either direction, particularly for large trials such as POSNOC with many recruiting sites. Although the data did not show an impact on recruitment, anecdotal feedback from recruiters indicated some perceived benefit in using the aid during patient discussions about the trial.

The SWAT was conducted in the context of all potential participants being offered an information video about POSNOC. One possible explanation for the lack of effect is that the standard PIL and video provided patients with sufficient information about POSNOC, and that citing a treatment preference as the main reason for declining participation was due to reasons other than lack of understanding about the trial.

The main strength of this study is the robust design and conduct of a cluster-randomised SWAT to evaluate an intervention that may aid trial recruitment. However, a key limitation is that due to unreliable screening data, we were unable to use recruitment fraction, with number of women approached about POSNOC as the denominator, for analysis. While recruitment overall and in the 12 months preceding the SWAT was well balanced between arms, recruitment fraction is a more informative outcome because it takes account of the number of women approached which may vary between and within sites over time. In addition, the SWAT was conducted relatively late in the recruitment phase of POSNOC, with 83% of the target participants already recruited. It is possible that a longer duration for the SWAT may have enabled a more precise estimate of between-group difference.

Our findings align with similar interventions reported in the literature, such as the provision of video clips or DVDs to aid recruitment, which also showed no discernible benefit.^10,11 We are aware of two other SWATs evaluating pictorial interventions, SWAT 187¹² and SWAT 205.¹³ Effects of such interventions are likely to be small, and thus synthesis of high-quality randomised studies will be essential to quantify small but important effects on clinical trial recruitment.

Ethical approval

The SWAT was included as part of substantial amendment 7 to the POSNOC protocol (REC reference 13/EM/0459) and submitted to NRES Committee East Midlands Nottingham-2 in October 2019. Following ethical and HRA approval on 19 November 2019, sites were notified of their SWAT random allocation on 4 December 2019. Sites allocated to use the enhanced PIL were provided with printed copies and instructed to use them from 10 December 2019 until POSNOC recruitment was completed on 13 July 2021. As the intervention consisted of a choice of two ethics-approved standard documents, consent was not required, and patients remained unaware that the patients allocated to the other SWAT arm will have received a slightly different PIL.

Reporting guidelines

The Trial Forge guideline for reporting the results of randomised Studies Within A Trial has been completed and is available as Appendix 2.

Study registration

This work was supported by the Medical Research Council (MRC) [PROMETHEUS study award reference MR/R013748/1] and the National Institute of Health Research (NIHR) Health Technology Assessment (HTA) Programme [POSNOC study award reference 12/35/17].

SWAT 102 is registered with the Northern Ireland Methodology Hub’s SWAT repository. The SWAT protocol 102 can be found at: https://www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,927252,en.pdf.

Data availability

The data used for this analysis is a summary of recruitment data for the POSNOC trial.

Data is available subject to the Nottingham Clinical Trials Units Data Sharing Policy.

To obtain this data, the steps are as follows:

1. Contact ctu@nottingham.ac.uk, to obtain the “Data Sharing and use request form”
2. Once this form is completed and returned, the Data sharing committee will meet within 3 months to review the application.
3. A decision will be reached and communicated to the applicant within 7 days.
4. If successful, a deidentified version of the data used for analysis will be available.

Extended data

Additional figures (Appendix 1, 2 & 3) are available at Nottingham Research Data Management Repository.

Repository name: (Supplementary data) - A randomised SWAT assessing the impact of an enhanced patient information leaflet on recruitment in a trial of axillary treatment for early-stage breast cancer. https://rdmc.nottingham.ac.uk/handle/internal/12085.¹⁴

This project contains the following extended data:

Appendix 1. Pictorial Aid.

Appendix 2. Trial Forge guideline for reporting the results of randomised Studies Within A Trial.

Appendix 3. The POSNOC Study Group.

Acknowledgements

On behalf of the POSNOC Trialists (listed in Appendix 3), thank you to everyone who has been involved in POSNOC, including the co-investigators, NCTU staff, recruiting site staff and the patients participating in the trial.

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