Use of Research Biopsies in Clinical Trials: Are Risks and Benefits Adequately Discussed?

Abstract

Background While the incorporation of research biopsies into clinical trials is increasing, limited information is available on how study protocols and informed consents integrate and describe their use. Methods All therapeutic clinical trials where image-guided research biopsies were performed from January 1, 2005 to October 1, 2010 were identified from an Interventional Radiology database. Data from study protocols and informed consents was extracted and analyzed. Procedural complications were recorded. Results A total of 57 clinical trials were identified, of which 38 (67%) contained at least one mandatory biopsy. Analysis of the research biopsy tumor tissue was a study endpoint in 95% of trials. The primary indication for research biopsy was for integral biomarker analysis in 32% and for correlative science in 68% of trials. A statistical analytic plan for the correlative science research biopsy tumor tissue was mentioned in 26%, described as exploratory in 51% and not mentioned in 23% of trials. For studies with mandatory biopsies, “biopsy” was an eligibility criterion in 71% of trials and a statistical justification for the research biopsy sample size was present in 50% of trials. 745 research biopsies were performed on 576 patients. The overall and major complication rates were 5.2% (39/745) and 0.8% (6/745), respectively. Complication rates for intra-thoracic and abdominal/pelvic solid organ biopsies were 17.1% (36/211) and 1.6% (3/189), respectively. Site stratified research biopsy-related risks were discussed in 5 consents. Conclusion A better representation of the risks and benefits of research biopsies in study protocols and informed consents is needed.

Variation in the Attitudes of Medical Oncologists Toward Research Biopsies in Patients With Metastatic Breast Cancer

“…This finding is concordant with data from patient surveys [15,16]. It is noteworthy, however, that most studies have suggested research biopsies are safe, with a 0.8%-1.4% major complication rate [4][5][6]17]. For example, of 61 patients who underwent a liver biopsy in a prospective tissue collection study at DFCI, only 1 grade 2 or higher adverse event (grade 2 pain) was noted [7].…”

Acquired Resistance to the TRK Inhibitor Entrectinib in Colorectal Cancer

“…However, tumor heterogeneity and tissue sampling limit the effectiveness of this strategy. In addition, tissue biopsies are not always feasible and are associated with nonnegligible risks ( 16 ). Most importantly, even when the biopsy reveals emergence of alleles that were not present before treatment, their functional role in driving resistance remains to be formally established using functional assays.…”

EGFR Mutations Status For Non-Small-Cell Lung Cancer Patients

“…Gene mutation analyses are the commonly used predictive biomarkers for selecting NSCLC patients to receive targeted agents. However, the current mutation analyses are often based on tumor tissues and have many limitations [18]. First, the accessibility of tumor tissues is not always satisfactory as most NSCLC patients are diagnosed with advanced stages and unsuitable to provide tissues through invasive surgery or biopsy.…”

“…Second, surgery and biopsy are not without clinical complications. The adverse events rate for thoracic biopsy was reported to be approximately 20% [18]. Furthermore, some percentages of NSCLC patients will develop resistance to molecular-targeted agents [20].…”