Recruitment patterns in a large international randomized controlled trial of perioperative care in cancer patients

Aaron Gazendam, Anthony Bozzo, Patricia Schneider, Victoria Giglio, David Wilson, Michelle Ghert, Aaron Gazendam, Anthony Bozzo, Patricia Schneider, Victoria Giglio, David Wilson, Michelle Ghert

Abstract

Introduction: The Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) randomized controlled trial (RCT) was the first study to prospectively enroll and randomize orthopedic oncology patients in multiple centers internationally. The objective of this study was to describe recruitment patterns, to examine the differences in enrollment across different PARITY sites, and to identify variables associated with differing levels of recruitment.

Methods: Data from this study was obtained from the PARITY trial Methods Center and records of correspondence between the Methods Center and recruiting sites. We performed descriptive statistics to report the recruitment patterns over time. We compared recruitment, time to set up, and time to enroll the first patient between North American and international sites, private and public healthcare models, and the presence or absence of research personnel. Two-tailed non-paired t tests were performed to test average monthly recruitment rates between groups.

Results: A total of 602 patients from 36 North American and 12 international sites were recruited from 2013 to 2019. North American sites were able to become fully enrollment-ready at an average of 19.5 months and international sites at an average of 27 months. Once enrolling, international sites were able to enroll 0.59 patients per/month whereas North American sites averaged a monthly recruitment rate of 0.2 patients/month once enrolling. Sites with research personnel reached enrollment-ready status at an average of 19.3 months and sites without research support at an average of 30.3 months. Once enrolling, the recruitment rate was 0.28 patients/month and 0.2 patients per month for sites with and without research support, respectively. Publicly funded sites had a monthly enrollment of 0.4 patients/month whereas privately funded sites had a monthly enrollment rate of 0.17 patients/month.

Conclusions: As a collaborative group, the PARITY investigators increased the pace of recruitment throughout the trial, likely by increasing the number of active sites. The longer time to start-up at international sites may be due to the complex governing regulations of pharmaceutical trials. Nevertheless, international sites should be considered essential as they recruited significantly more patients per month once active. The absence of research support personnel may lead to delays in the time to start-up. The results of the current study will provide guidance for choosing which sites to recruit for participation in future collaborative clinical trials in orthopedic oncology and other surgical specialties.

Trial registration: ClinicalTrials.gov NCT01479283 . Prospectively registered on November 24, 2011.

Keywords: Orthopedic oncology; Randomized controlled trial; Recruitment; Surgical.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Monthly enrollment and sites open for each month of the study period
Fig. 2
Fig. 2
TTSU vs enrollment rate. Sites with faster TTSU did not display higher enrollment rates. No significant correlation is observed between TTSU and average enrollment (Pearson R = .27, p = 0.069)

References

    1. Wright JG. A practical guide to assigning levels of evidence. J Bone Joint Surg Series A. 2007;89:1128–30.
    1. Farrokhyar F, Karanicolas PJ, Thoma A, Simunovic M, Bhandari M, Devereaux PJ, et al. Randomized controlled trials of surgical interventions. Ann Surg. 2010;251:409–16.
    1. Cook JA. The challenges faced in the design, conduct and analysis of surgical randomised controlled trials. Trials. 2009;10:1–9.
    1. Jeray KJ, Tanner S, Schemitsch EH, Bhandari M. Are large fracture trials possible? J Orthopaedic Trauma. 2010;24:S87–92.
    1. Sibai T, Carlisle H, Tornetta P. The darker side of randomized trials: recruitment challenges. J Bone Joint Surg Series A. 2012;94:49–55.
    1. Søreide K, Alderson D, Bergenfelz A, Beynon J, Connor S, Deckelbaum DL, et al. Strategies to improve clinical research in surgery through international collaboration. Lancet. 2013;382:1140–51.
    1. Kenyon GM, David Mendelow A, Gregson BA, Rowan E. Obtaining regulatory approval for multicentre randomised controlled trials: experiences in the STICH II trial. Br J Neurosurg. 2011;25:352–6.
    1. Charlson ME, Horwitz RI. Applying results of randomised trials to clinical practice: impact of losses before randomisation. Br Med J. 1984;289:1281–4.
    1. Easterbrook PJ, Matthews DR. Fate of research studies. J R Soc Med. 1992;85:2.
    1. Toerien M, Brookes ST, Metcalfe C, de Salis I, Tomlin Z, Peters TJ, et al. A review of reporting of participant recruitment and retention in RCTs in six major journals. Trials. 2009;85:71.
    1. Fletcher B, Gheorghe A, Moore D, Wilson S, Damery S. Improving the recruitment activity of clinicians in randomised controlled trials: a systematic review. BMJ Open. 2012;2:1.
    1. Schroen AT, Petroni GR, Wang H, Gray R, Wang XF, Cronin W, et al. Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials. Clin Trials. 2010;7:312–21.
    1. Dickson S, Logan J, Hagen S, Stark D, Glazener C, McDonald AM, et al. Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings. Trials. 2013;14:1–8.
    1. Fogel DB. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: a review. Contemp Clin Trials Commun. 2018;11:156–64.
    1. Kenyon G, Gregson B, Mendelow AD, Rowan E. What does it take to deliver an international neurosurgical trial? Experiences from STICH II. Br J Neurosurg. 2014;28:461–6.
    1. Csimma C, Swiontkowski MF. Large clinical trials in musculoskeletal trauma: are they possible? Lessons learned from the international study of the use of rhBMP-2 in open tibial fractures. J Bone Joint Surg Series A. 2005;87:218–22.
    1. Evaniew N, Nuttall J, Farrokhyar F, Bhandari M, Ghert M. What are the levels of evidence on which we base decisions for surgical management of lower extremity bone tumors? Tumor. Clin Orthopaedics Relat Res. 2014;472:8–15.
    1. Lerman DM, Cable MG, Thornley P, Evaniew N, Slobogean GP, Bhandari M, et al. Has the level of evidence of podium presentations at the musculoskeletal tumor society annual meeting changed over time? Clin Orthopaedics Relat Res. 2017;475:853–60.
    1. Ghert M, Deheshi B, Holt G, Randall RL, Ferguson P, Wunder J, et al. Prophylactic antibiotic regimens in tumour surgery (PARITY): protocol for a multicentre randomised controlled study. BMJ Open. 2012;2:6.
    1. Ghert M. Prophylactic antibiotic regimens in tumour surgery (PARITY): a pilot multicentre randomised controlled trial. Bone Joint Res. 2015;4:154–62.
    1. Metzger-Filho O, de Azambuja E, Bradbury I, Saini KS, Bines J, Simon SD, et al. Analysis of regional timelines to set up a global phase III clinical trial in breast cancer: the adjuvant lapatinib and/or trastuzumab treatment optimization experience. Oncologist. 2013.
    1. Aban IB, Wolfe GI, Cutter GR, Kaminski HJ, Jaretzki A, Minisman G, et al. The MGTX experience: challenges in planning and executing an international, multicenter clinical trial. J Neuroimmunol. 2008;18:134.
    1. Klamerus JF, Bruinooge SS, Ye X, Klamerus ML, Damron D, Lansey D, et al. The impact of insurance on access to cancer clinical trials at a comprehensive cancer center. Clin Cancer Res. 2010;16:5997–6003.
    1. Hamel LM, Penner LA, Albrecht TL, Heath E, Gwede CK, Eggly S. Barriers to clinical trial enrollment in racial and ethnic minority patients with cancer. Cancer Control. 2016;23:327–37.
    1. Minisman G, Bhanushali M, Conwit R, Wolfe GI, Aban I, Kaminski HJ, et al. Implementing clinical trials on an international platform: challenges and perspectives. J Neurol Sci. 2012;313:1–6.
    1. Furlan P, Mcfedries P. Excel 2010. compare a journal of comparative education. 2010.
    1. Rosenthal R, Kasenda B, Dell-Kuster S, Von Elm E, You J, Blümle A, et al. Completion and publication rates of randomized controlled trials in surgery: an empirical study. Ann Surg. 2015;262:68–73.
    1. Mouw TJ, Hong SW, Sarwar S, Fondaw AE, Walling AD, Al-Kasspooles M, et al. Discontinuation of surgical versus nonsurgical clinical trials: an analysis of 88,498 trials. J Surg Res. 2018;227:151–7.
    1. Kasenda B, Von Elm E, You J, Blümle A, Tomonaga Y, Saccilotto R, et al. Prevalence, characteristics, and publication of discontinued randomized trials. JAMA. 2014;311:1045–52.
    1. Abdullah L, Davis DE, Fabricant PD, Baldwin K, Namdari S. Is there truly “no significant difference”? Underpowered randomized controlled trials in the Orthopaedic literature. J Bone Joint Surg (Am Vol). 2014;97:2068–73.
    1. McDonald AM, Knight RC, Campbell MK, Entwistle VA, Grant AM, Cook JA, et al. What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies. Trials. 2006;7:9.
    1. Al-Shahi Salman R, Beller E, Kagan J, Hemminki E, Phillips RS, Savulescu J, et al. Increasing value and reducing waste in biomedical research regulation and management. Lancet. 2014;383:101–4.
    1. Gentry KR, Arnup SJ, Disma N, Dorris L, de Graaff JC, Hunyady A, et al. Enrollment challenges in multicenter, international studies: the example of the GAS trial. Paediatric Anaesthesia. 2019;29:51–8.
    1. Hemminki A, Kellokumpu-Lehtinen PL. Harmful impact of EU clinical trials directive. Br Med J. 2006;332:501–2.
    1. Crow RA, Hart KA, McDermott MP, Tawil R, Martens WB, Herr BE, et al. A checklist for clinical trials in rare disease: obstacles and anticipatory actions—lessons learned from the FOR-DMD trial. Trials. 2018;19:291.
    1. Yanagawa H, Akaishi A, Miyamoto T, Takai S, Nakanishi R, Irahara M. Role of clinical research coordinators in promoting clinical trials of drugs for surgical patients. Int Arch Med. 2008;1:1–4.
    1. Katz S, Dufficy H, John C. Keys to success with clinical trials. Gastroenterol Hepatol. 2011:7;100.
    1. Thoma A, Farrokhyar F, McKnight L, Bhandari M. Practical tips for surgical research: how to optimize patient recruitment. Can J Surg. 2010;53:205.
    1. Kadam R, Borde S, Madas S, Salvi S, Limaye S. Challenges in recruitment and retention of clinical trial subjects. Perspect Clin Res. 2016;7:137.

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