In this session, Dr. Shomik Sengupta led a presentation entitled “About an ANZUP Trial” highlighting his experience designing a trial and the role of input from ANZUP. (The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)). He began highlighting the definition of clinical trials, emphasizing that these investigations depend on patients to volunteer to test new treatments, interventions, or tests to prevent, detect, treat, or manage the various diseases.
He emphasized that clinical trials are critical in advancing medical care, in particular through the assessment of new interventions aimed at improving outcomes. Further, randomized controlled trials may allow the overturning of “conventional wisdom”.
To this end, he highlighted data from a systematic review from Herrera-Perez and colleagues demonstrating that, among 3017 randomized controlled trials, 415 led to reversals compared to existing practice. Notably, a large proportion of these (209) randomized controlled trials were supported by concordant systematic reviews in spite of prevailing treatment trends.
Dr. Sengupta then highlighted two “sources” of clinical trials, emphasizing differences in the generation of study ideas: industry-sponsored trials and investigator-initiated studies (which may be single center or multi-center). He highlighted funding-related advantages to industry-sponsored trials though there are concerns regarding these studies, including in particular publication bias with the suppression of negative studies that are not deemed favorable to the sponsoring company.
Many multi-center investigator-initiated trials may be undertaken in the context of cooperative groups, of which ANZUP is one of many worldwide. ANZUP was established in 2008 through the merger of two existing groups with the missing to conduct trials to improve the treatment of bladder, kidney, testicular, and prostate cancer.
ANZUP trials initially began with collaboration, as in the case of the SORCE trial which was recently published in the Journal of Clinical Oncology, as well as co-badging, as in the case of the TROG-led RAVES trial. However, the core of the ANZUP portfolio is through investigator-initiated trials including ENZAMET and ENZARAD.
Dr. Sengupta then highlighted his personal experience designing a developing a trial within the context of ANZUP. He initially began with an idea to assess the role of bladder irrigation following transurethral resection. He highlighted the importance of concept development workshops to refine the study question, through the input of a multi-disciplinary team. Further, ANZUP and other cooperative groups can offer seed funding to support early pilot studies. In his particular experience, he described the ongoing struggle for funding to support the scaling up of research endeavors.
In developing a trial, Dr. Sengupta highlighted a number of ways that a cooperative group may assist, including in trial development through concept development workshops and subcommittees and trial implementation. In particular, development workshops bring in multi-disciplinary expertise to allow for refining of trial ideas.
Dr. Sengupta then discussed particular issues in the design and conduct of surgical trials. Historically, these trials have been difficult to run and accrue and there have been many failed trials with the resulting surgical literature thus dominated by case series and observational comparisons. Notably, surgery, as an intervention, differs from medications or radiation in the importance of individual surgeon expertise and experience in delivering outcomes. Further, there are difficulties relating to randomization and blinding. Given issues with sham surgery, most of these trials are open-label and unblinded.
This session closed with questions from the audience with Dr. Sengupta highlighting the importance of deriving study questions for identified unmet clinical needs and the evolution of these prior to actual implementation, emphasizing that “the first idea is never the final one”.
Presented by: Professor Shomik Sengupta, MS, MD, FRACS, academic urologist, Waverley Private Hospital, Melbourne, Victoria, Australia.
Written by: Christopher J.D. Wallis, MD, Ph.D., Urologic Oncology Fellow, Vanderbilt University Medical Center, @WallisCJD on Twitter, during the 2020 Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Mini Annual Scientific Meeting (ASM), November 29 - 30, 2020
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