Analyses of the Rationale and Implementation of Research Biopsies in Oncology Clinical Trials at a Tertiary Cancer Center

Abstract

Background. Biomarkers in clinical trials have led to massive incorporation of research biopsies, with potentially risks and no direct benefit for patients. In 2018, ASCO has released an ethical framework to provide guidance on incorporating research biopsies in cancer clinical trials. Methods. We collected biopsy requirements of cancer clinical trials conducted at Institut Jules Bordet (IJB) between 2015 and 2019 to examine adherence with the ASCO Ethical Framework. We used logistic regression models to test the association between the request for biopsy, the request for tissue and the adherence to ASCO framework and some trials characteristics. Results. Between January 2015 and December 2019, 178 oncological studies were conducted at IJB. 138 (78%) were sponsored by industry, 132 (74%) were phase II and III studies and 141 (79%) concerned metastatic disease. Tissue was required for inclusion for 119 (67%) studies among which 59 required at least one new biopsy. Adherence to ASCO Ethical Framework was 67% for studies requiring tissue and went down to 39% for studies requiring at least one new biopsy.In multivariate analysis, the request for tissue or new biopsies was increased in early phase studies (p<0.001, p<0.001 respectively) and in studies investigating innovative treatments (immunotherapy or targeted therapies) (p<0.01, p=0.02). Compliance to ASCO framework significantly decreased with time (p<0.001) and in early phase studies (p<0.001). Conclusion.Numerous studies required tissue or new biopsies for exploratory objectives of unknown clinical utility. Request for tissue increases through years whereas compliance to ASCO's Framework decreases. The Oncologist 2021;9999:• • Implications for Practice: In 2019, the American Society for Clinical Oncology (ASCO) developed an Ethical Framework to provide guidance on incorporating research biopsies in clinical trials. We underline the growing request for tissue in clinical trials with potentially no impact on drug development and no benefit to actual or future patients. Adherence to ASCO Ethical Framework decreases through time.These results highlight the importance of improving the ethics of research biopsies. ASCO's Ethical Framework offers an opportunity to improve quality of care in clinical research by maximizing scientific utility and allowing for clinically meaningful correlative science and safe access to innovative treatments for a maximum number of patients.

Ethical Considerations for Phase I Trials in Oncology

“…In the era of targeted therapy, research procedures have increased in volume. 31,32 Research procedures that have no therapeutic rationale derive their ethical justification from their prospect of producing scientifically valuable information. This triggers obligations for transparent design, analytical integrity, and reporting in protocols and publications.…”

Ethical considerations about the collection of biological samples for genetic analysis in clinical trials

“…The solicitation of biological samples from therapeutic clinical trials participants is becoming very common (Olympios et al, 2021; Perez-Gracia et al, 2017). Consequently, we are confronted with the dilemma as to how to gather the required genetic information for clinical research without exposing the participants to serious risks of inappropriate use of their genetic data.…”

“…Results from exploratory studies are underreported, they might have no impact upon future drug development and consequently be of no benefit to current or future patients. Strong scientific rationale for exploratory studies is often lacking, they commonly fail to identify robust candidates for prediction of efficacy and toxicity, and solid biomarker identification programs are rare (Olympios et al, 2021; Perez-Gracia et al, 2017). The aforementioned risks associated with sequencing the whole genome may not be offset by the uncertain benefits of exploratory analysis.…”

An Expanded Role for IRBs in the Oversight of Research Biopsies

“…3 Additionally, re-search biopsies may be a condition of enrollment and/ or ongoing participation in a clinical trial; thus, patients are required to consent to the biopsies to enroll in a trial and to continue receiving an investigational treatment. 4 The American Society of Clinical Oncology (ASCO), 5 the Secretary's Advisory Committee on Human Research Protections of the U.S. Department of Health and Human Services (HHS), 6 and others 7 are increasingly examining the ethics of research biopsies, especially those that pose a substantial risk of harm, do not have any potential to benefit participants, and are a mandatory condition of trial participation. 8 Ethical concerns center on the limited scientific justification supporting some research biopsies, safety risks to research participants, and the potential for coercion and therapeutic misconception during the informed consent process.…”