Strategies to address recruitment to a randomised trial of surgical and non-surgical treatment for cancer: results from a complex recruitment intervention within the Mesothelioma and Radical Surgery 2 (MARS 2) study

Our plain-English summary of Strategies to address recruitment to a randomised trial of surgical and non-surgical treatment for cancer: results from a complex recruitment intervention within the Mesothelioma and Radical Surgery 2 (MARS 2) study, by N. Mills, N. Farrar, B. Warnes, et al (BMJ Open, 2024).

The study

• Authors: N. Mills, N. Farrar, B. Warnes, K.E. Ashton, R. Harris, C.A. Rogers, E. Lim, D. Elliott
• Journal: BMJ Open
• Published: 2024;14(5):e079108
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Recruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised controlled trial (RCT) compared standard chemotherapy with or without (extended) pleurectomy decortication surgery for malignant pleural mesothelioma. Anticipating recruitment difficulties, a QuinteT Recruitment Intervention was embedded in the main trial phase to unearth and address barriers. The trial achieved recruitment to target with a 4-month COVID-19 pandemic-related extension. This paper presents the key recruitment challenges, and the strategies delivered to optimise recruitment and informed consent.

Design: A multifaceted, flexible, mixed-method approach to investigate recruitment obstacles drawing on data from staff/patient interviews, audio recorded study recruitment consultations and screening logs. Key findings were translated into strategies targeting identified issues. Data collection, analysis, feedback and strategy implementation continued cyclically throughout the recruitment period.

Setting: Secondary thoracic cancer care.

Results: Respiratory physicians, oncologists, surgeons and nursing specialists supported the trial, but recruitment challenges were evident. The study had to fit within a framework of a thoracic cancer service considered overstretched where patients encountered multiple healthcare professionals and treatment views, all of which challenged recruitment. Clinician treatment biases, shaped in part by the wider clinical and research context alongside experience, adversely impacted several aspects of the recruitment process by restricting referrals for study consideration, impacting eligibility decisions, affecting the neutrality in which the study and treatment was presented and shaping patient treatment expectations and preferences. Individual and group recruiter feedback and training raised awareness of key equipoise issues, offered support and shared good practice to safeguard informed consent and optimise recruitment.

Conclusions: With bespoke support to overcome identified issues, recruitment to a challenging RCT of surgery versus no surgery in a thoracic cancer setting with a complex recruitment pathway and multiple health professional involvement is possible.

Trial Registration Number: ISRCTN ISRCTN44351742, Clinical Trials.gov NCT02040272.

© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.

In plain English

This article described efforts to improve recruitment to MARS 2, a UK trial comparing chemotherapy with or without (extended) pleurectomy decortication surgery for malignant pleural mesothelioma. It did not study asbestos or report the trial's survival results. The authors' recruitment intervention, embedded in the trial's main phase, used staff and patient interviews, 55 recorded consultations and screening logs. Of 1030 patients assessed, 645 were eligible and 335 were randomised. The target of 328 was reached in November 2020, with a four-month extension after a COVID-19 pause. Staff felt that clinicians' doubts about surgery accounted for fewer referrals than expected. Older, less fit and sarcomatoid cell-type patients were less often put forward, despite meeting the criteria. Treatments were sometimes described in an unbalanced way. Average recruitment per site per month rose from 0.27 in September 2018, just before the intervention's second phase rolled out feedback and training, to 0.65 in March 2020. The authors concluded that recruitment to such a trial is possible with tailored support. They said they could not rule out other factors, such as new sites opening.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Mixed-methods recruitment study (QuinteT Recruitment Intervention) embedded in the main phase of a multicentre randomised controlled trial
• Who was studied: Staff and patients at MARS 2 sites in the UK. The data were 55 consultation recordings with 16 recruiters from 12 sites; 25 interviews with 24 study staff (of 39 invited) from 18 sites, December 2017 to March 2020; and 21 interviews with 20 patients from 5 sites. Overall, 1030 patients were assessed for trial eligibility.
• Exposure: No asbestos exposure was studied. What was studied was a recruitment intervention for trial staff: feedback, training, tips documents and newsletters. The trial itself compared chemotherapy with or without (extended) pleurectomy decortication.
• Main results:
  • Of patients assessed for the trial, 645 were eligible and 335 were randomised.
  • Of the 310 eligible patients who did not consent, 183 were not approached for consent, 74 did not consent, and 36 did not undergo two cycles of chemotherapy and a repeat CT scan.
  • The recruitment target of 328 patients was reached in November 2020.
  • Reaching the target required a 4-month extension related to the COVID-19 pandemic.
  • Staff felt that clinicians' doubts about surgery accounted for fewer study referrals than expected.
  • Older patients, less physically fit patients and those with sarcomatoid cell type were less likely to be put forward, even though they met the eligibility criteria.
  • A minority of clinicians offered patients surgery outside the trial.
  • Average recruitment per site per month was 0.27 in September 2018, just before the second phase of the intervention and its rollout of feedback and training, and 0.65 in March 2020. Some training had already been delivered earlier, from November 2017 to February 2018.
  • At one site where all three recruiters received feedback, no patients were randomised in the 17 months before feedback and six were randomised in the 5 months after.
  • At four sites the problems were considered insurmountable: two sites closed early and two recruited no patients.
• The authors' conclusion: The authors concluded that recruitment to a randomised trial with very different treatment options and a complex pathway is possible with tailored training and support addressing equipoise issues.
• Limitations the authors state:
  • Because the intervention ran throughout the main phase with study-wide actions, its impact on recruitment was difficult to evaluate.
  • Other factors, particularly the opening of new sites, could not be ruled out as causes of the increased recruitment.
  • The authors could not say whether the target would have been reached without the intervention.
  • Over a third of staff approached were not interviewed, and half of the sites had no consultation recordings.
  • Individual feedback was often sent as a written report with no confirmation that it was read.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Chemotherapy, Pleural Mesothelioma, Informed Consent, Clinical Trial.

Related studies

• Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma — E. Lim, L. Darlison, et al. (2020)
• Surgery in the treatment of malignant pleural mesothelioma: recruitment into trials should be the default position — A. Datta, R. Smith, et al. (2014)
• Patient experiences of participation in a radical thoracic surgical trial: findings from the Mesothelioma and Radical Surgery Trial 2 (MARS 2) — C. Warnock, K. Lord, et al. (2019)
• Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study — T. Treasure, L. Lang-Lazdunski, et al. (2011)
• Mailing strategies and costs of recruiting heavy smokers in CARET, a large chemoprevention trial — B. Valanis, J. Blank, et al. (1998)
• MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial — C. Matthews, C. Freeman, et al. (2019)

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