Lessons learned from a failed multi-institutional randomized controlled study.

Abstract

BACKGROUND/PURPOSE: In 1996, the Surgical Sections of the Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG) received National Cancer Institute funding to conduct a prospective, randomized, controlled, surgeon-directed study to evaluate the role of minimally invasive surgery (MIS) in children with cancer. Because of lack of patient accrual, the study was closed in 1998. The purpose of this study is to evaluate and describe those factors that impacted on study failure to ensure future successful clinical trials. METHODS: One hundred forty surgeons representing the surgical membership of CCG and POG as well as 111 institutions within CCG and POG were asked to complete a questionnaire about the failed clinical trial. The questionnaire focused on study objectives, organization, and institutional review board (IRB) submission. It also examined the surgeon's ability to perform the minimal access operation, the influence of the pediatric oncologist, and the existence of preconceived biases by surgeons, oncologists, and families. Statistical analysis was performed as appropriate. RESULTS: Eighty-six of 140 (62%) surgeons responded to the questionnaire. Only 23% of the potential protocols were submitted for IRB approval. Of responding surgeons, 39% were not actively performing MIS when the study opened. A surgeon's support of the study was directly related to when the surgeon received the protocols (P <.001) and whether the participating surgeon was actively participating in MIS (P <.016). The oncologist's knowledge and support of the study affected IRB submission and approval (P <.02) and was influenced by whether MIS was practiced at the institution (P <.05). The majority of responding surgeons believed the experimental question was relevant (P <.05). However, responding surgeons believed that a preconceived bias existed within both their local surgical and oncology communities favoring a particular surgical approach (P <.001), but this bias did not extend to the families (P >.05). CONCLUSION: The study failed because of lack of accrual for a variety of reasons: failure to submit to the institution's IRB, lack of surgical expertise with MIS procedures, and preconceived surgeon bias toward either an endoscopic or traditional open approach.