The challenge of equipoise: qualitative interviews exploring the views of health professionals and women with multiple ipsilateral breast cancer on recruitment to a surgical randomised controlled feasibility trial

Jenny Ingram, Lucy Beasant, John Benson, Adrian Murray Brunt, Anthony Maxwell, James Richard Harvey, Rosemary Greenwood, Nicholas Roberts, Norman Williams, Debbie Johnson, Zoe Winters, Jenny Ingram, Lucy Beasant, John Benson, Adrian Murray Brunt, Anthony Maxwell, James Richard Harvey, Rosemary Greenwood, Nicholas Roberts, Norman Williams, Debbie Johnson, Zoe Winters

Abstract

Background: A multicentre feasibility trial (MIAMI), comparing outcomes and quality of life of women with multiple ipsilateral breast cancer randomised to therapeutic mammoplasty or mastectomy, was conducted from September 2018 to March 2020. The MIAMI surgical trial aimed to investigate recruitment of sufficient numbers of women. Multidisciplinary teams at 10 breast care centres in the UK identified 190 with MIBC diagnosis; 20 were eligible for trial participation but after being approached only four patients were recruited. A nested qualitative study sought to understand the reasons for this lack of recruitment.

Methods: Interviews were conducted from November 2019 to September 2020 with 17 staff from eight hospital-based breast care centres that recruited and attempted to recruit to MIAMI; and seven patients from four centres, comprising all patients who were recruited to the trial and some who declined to take part. Interviews were audio-recorded, anonymised and analysed using thematic methods of building codes into themes and sub-themes using the process of constant comparison.

Results: Overarching themes of (1) influences on equipoise and recruitment and (2) effects of a lack of equipoise were generated. Within these themes, health professional themes described the barriers to recruitment as 'the treatment landscape has changed', 'staff preferences and beliefs' which influenced equipoise and patient advice; and how different the treatments were for patients. Patient themes of 'altruism and timing of trial approach', 'influences from consultants and others' and 'diagnostic journey doubts' all played a part in whether patients agreed to take part in the trial.

Conclusions: Barriers to recruiting to breast cancer surgical trials can be significant, especially where there are substantial differences between the treatments being offered and a lack of equipoise communicated by healthcare professionals to patients. Patients can become overwhelmed by numerous requests for participation in research trials and inappropriate timing of trial discussions. Alternative study designs to the gold standard randomised control trial for surgical interventions may be required to provide the high-quality evidence on which to base practice.

Trial registration: ISRCTN ( ISRCTN17987569 ) registered on April 20, 2018, and ClinicalTrials.gov ( NCT03514654 ).

Keywords: Equipoise; Mastectomy; Multiple ipsilateral breast cancer; Qualitative; Randomisation; Therapeutic mammoplasty.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
CONSORT diagram for MIAMI

References

    1. Winters ZE, Horsnell J, Elvers KT, Maxwell AJ, Jones LJ, Shaaban AM, et al. Systematic review of the impact of breast-conserving surgery on cancer outcomes of multiple ipsilateral breast cancers (MIBC) BJS Open. 2018;2:162–174. doi: 10.1002/bjs5.53.
    1. Winters ZE, Benson JR, on behalf of the MIAMI (Multiple Ipsilateral breast conserving surgery versus mastectomy) Trial Management Group Surgical treatment of multiple ipsilateral breast cancers. BJS. 2018;105:466–468. doi: 10.1002/bjs.10738.
    1. Boughey JC, Rosenkranz K, Nelson H. Multiple ipsilateral breast cancers: can the breast be preserved? Bull Am Coll Surg. 2012;97(12):43–45.
    1. Curigliano G, Burstein HJ, Winer EP, Gnant M, Dubsky P, Loibl S, et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer. Ann Oncol. 2017;28:1700–1712. doi: 10.1093/annonc/mdx308.
    1. Burstein HJ, Curigliano G, Loibl S, Dubsky P, Gnant M, Poortmans P, et al. Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer. Ann Oncol. 2019;30:1541–1557. doi: 10.1093/annonc/mdz235.
    1. Bellavance EC, Kesmodel SB. Decision-making in the surgical treatment of breast cancer: factors influencing women’s choices for mastectomy and breast conserving surgery. Front Oncol. 2016;6:74. doi: 10.3389/fonc.2016.00074.
    1. Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, et al. Twenty-year follow up of a randomized study comparing breast conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347:1227–1232. doi: 10.1056/NEJMoa020989.
    1. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Eng J Med. 2002;347:1233–1241. doi: 10.1056/NEJMoa022152.
    1. Early Breast Cancer Trialists Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomized trials. Lancet. 2005;366:2087–106.
    1. Litiere S, Werutsky G, Fentiman IS, Rutgers E, Christiaens MR, van Limbergen E, et al. Breast-conserving therapy versus mastectomy for stage I-II breast cancer: 20-year follow up of the EORTC 10801 phase 3 randomised trial. Lancet. 2012;13:412–419. doi: 10.1016/S1470-2045(12)70042-6.
    1. Benson JR. Long-term outcome of breast conserving surgery. Lancet Oncol. 2012;13:331–333. doi: 10.1016/S1470-2045(12)70074-8.
    1. Van Maaren M, de Munck L, de Bock GH, Jobsen JJ, van Dalen T, Linn SC, et al. 10-year survival after breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer in the Netherlands. A population-based study. Lancet Oncol. 2016;17:1158–1170. doi: 10.1016/S1470-2045(16)30067-5.
    1. Christiansen P, Carstensen SL, Ejlertsen B, Kroman N, Offersen B, Bodilsen A, Jensen MB. Breast conserving surgery versus mastectomy: overall and relative survival-a population based study by the Danish Breast Cancer Cooperative Group (DBCG) Acta Oncol. 2018;57(1):19–25. doi: 10.1080/0284186X.2017.1403042.
    1. de Boniface J, Frisell J, Bergkvist L, Andersson Y. Breast-conserving surgery followed by whole-breast irradiation offers survival benefits over mastectomy without irradiation. BJS. 2018;105(12):1607–1614. doi: 10.1002/bjs.10889.
    1. Sinnadurai S, Kwong A, Hartman M, Tan EY, Bhoo-Pathy NT, Dahlui M, et al. Breast-conserving surgery versus mastectomy in young women with breast cancer in Asian settings. BJS Open. 2018;3(1):48–55. doi: 10.1002/bjs5.50111.
    1. Gu J, Groot G, Boden C, Busch A, Holtslander L, Lim H. Review of factors influencing women’s choice of mastectomy versus breast conserving therapy in early stage breast cancer: a systematic review. Clin Breast Cancer. 2018;18(4):e539–e554. doi: 10.1016/j.clbc.2017.12.013.
    1. Morrow M, Harris JR, Schnitt SJ. Surgical margins in lumpectomy for breast cancer, bigger is not better. N Engl J Med. 2012;367:79–82. doi: 10.1056/NEJMsb1202521.
    1. Benson JR, Jatoi I, Toi M. Surgical management of multiple ipsilateral breast cancers. Future Oncol. 2019;15(11):1185–1191. doi: 10.2217/fon-2019-0028.
    1. Potter S, Trickey A, Rattay T, O’Connell RL, Dave R, Baker E, et al. Therapeutic mammaplasty is a safe and effective alternative to mastectomy with or without immediate breast reconstruction. BJS. 2020;107:832–844. doi: 10.1002/bjs.11468.
    1. Dicks E, Roome R, Chafe J, Powell E, McCrate F, Simmonds C, Etchegary H. Factors influencing surgical treatment decisions for breast cancer: a qualitative exploration of surgeon and patient perspectives. Curr Oncol. 2019;26(2):e216–e225. doi: 10.3747/co.26.4305.
    1. Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77–101. doi: 10.1191/1478088706qp063oa.
    1. Bidad N, MacDonald L, Winters ZE, Edwards SJL, Emson M, Griffin CL, et al. How informed is declared altruism in clinical trials? A qualitative interview study of patient decision-making about the QUEST trials (Quality of Life after Mastectomy and Breast Reconstruction) Trials. 2016;17:431. doi: 10.1186/s13063-016-1550-7.
    1. Kaur G, Hutchison I, Mehanna H, Williamson P, Shaw R, Tudur Smith C. Barriers to recruitment for surgical trials in head and neck oncology: a survey of trial investigators. BMJ Open. 2013;3. 10.1136/bmjopen-2013-002625.
    1. Winters ZE, Emson M, Griffin C, Mills J, Hopwood P, Bidad N, et al. on behalf of the QUEST Trial Management Group. Learning from the QUEST multicentre feasibility randomization trials in breast reconstruction after mastectomy. BJS. 2015;102:45–56. doi: 10.1002/bjs.9690.
    1. Harrop E, Kelly J, Griffiths G, Casbard A, Nelson A. Why do patients decline surgical trials? Findings from a qualitative interview study embedded in the Cancer Research UK BOLERO trial (Bladder cancer: Open versus Lapararoscopic or RObotic cystectomy) Trials. 2016;17:35. doi: 10.1186/s13063-016-1173-z.
    1. Cook JA, Ramsay CR, Norrie J. Recruitment to publicly funded trials—are surgical trials really different? Contemp Clin Trials. 2008;29:631–634. doi: 10.1016/j.cct.2008.02.005.
    1. Ergina PL, Cook JA, Blazeby JM, Boutron I, Clavien PA, Reeves BC, Seiler CM, for the Balliol Collaboration Challenges in evaluating surgical innovation. Lancet. 2009;374:1097–1104. doi: 10.1016/S0140-6736(09)61086-2.
    1. Donovan JL, Paramasivan S, de Salis I, Toerien M. Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled trials. Trials. 2014;15:5. doi: 10.1186/1745-6215-15-5.
    1. Paramasivan S, Huddart R, Hall E, Lewis R, Birtle A, Donovan JL. Key issues in recruitment to randomised controlled trials with very different interventions: a qualitative investigation of recruitment to the SPARE trial (CRUK/07/011) Trials. 2011;12:78. doi: 10.1186/1745-6215-12-78.
    1. Conefrey C, Donovan JL, Stein RC, Paramasivan S, Marshall A, Bartlett J, et al. OPTIMA Prelim Study Group. Strategies to improve recruitment to a de-escalation trial: a mixed-methods study of the OPTIMA Prelim Trial in Early Breast Cancer. Clin Oncol. 2020;32:382–389. doi: 10.1016/j.clon.2020.01.029.
    1. Wilson C, Rooshenas L, Daisy PS, Elliott MJ, Strong S, et al. Development of a framework to improve the process of recruitment to randomised controlled trials (RCTs): the SEAR (Screened, Eligible, Approached, Randomised) framework. Trials. 2018;19:50. doi: 10.1186/s13063-017-2413-6.
    1. Cutress RI, McIntosh SA, Potter S, Goyal A, Kirwan CC, Harvey J, et al. on behalf of the Association of Breast Surgery Surgical Gap Analysis Working Group. Opportunities and priorities for breast surgical research. Lancet Oncol. 2018;19:e521–e533. doi: 10.1016/S1470-2045(18)30511-4.
    1. Relton C, Torgerson D, O’Cathain A, Nichol J. Rethinking pragmatic randomised controlled trials: introducing the “cohort multiple randomised controlled trial” design. BMJ. 2010;340:c1066. doi: 10.1136/bmj.c1066.
    1. Relton C, Burbach M, Collett C, Flory J, Gerlich S, Holm S, et al. The ethics of ‘Trials within Cohorts’ (TwiCs): 2nd international symposium. Trials. 2017;18(Suppl 2):244. doi: 10.1186/s13063-017-1961-0.
    1. Young-Afat DA, van Gils CH, van den Bongard HJGD, Verkooijen HM, on behalf of the UMBRELLA Study Group The Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA): objectives, design, and baseline results. Breast Cancer Res Treat. 2017;2017(164):445–450. doi: 10.1007/s10549-017-4242-4.

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