Racial/Ethnic Differences in Comprehension of Biospecimen Collection: a Nationwide University of Rochester Cancer Center NCI Community Oncology Research Program Study.

To examine whether (a) non-minority participants differed from racial minority participants in the understanding of biospecimens collected for research purposes, (b) patients differed from comparison group in their understanding of the ways their biospecimens could be used by researchers, and (c) participants received adequate information before consenting to donate blood for research studies. We analyzed cross-sectional data from female breast cancer patients scheduled to receive chemotherapy at the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) clinical sites and a healthy comparison group. After reading a consent form related to biospecimens and consenting to participate in a clinical trial, participants' understanding of biospecimen collection was evaluated. Linear models were used to compare scores between non-minority and racial minority participants as well as cancer and non-cancer comparisons adjusting for possible confounding factors. A total of 650 participants provided evaluable data; 592 were non-minority (Caucasian) and 58 participants were a racial minority (71% Black and 29% other). There were 427 cancer patients and 223 comparisons. Non-minority participants scored higher than racial minorities on relevance-to-care items (diff. = 0.48, CI 0.13-0.80, p = 0.001). Comparison group scored higher than cancer patients on relevance-to-care items (diff. = 0.58, CI 0.37-0.78). A moderate number of the participants exhibited a poor understanding of biospecimen collection across all racial/ethnic backgrounds, but racial minority participants' scores remained lower in the relevance-to-care subscale even after adjusting for education and reading level. Differences were also noted among the patients and comparison group. Researchers should facilitate comprehension of biospecimen collection for all study participants, especially racial minority participants.

Development of a consensus approach for return of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project.

The active debate about the return of incidental or secondary findings in research has primarily focused on return to research participants, or in some cases, family members. Particular attention has been paid to return of genomic findings. Yet, research may generate other types of findings that warrant consideration for return, including findings related to the pathology of donated biospecimens. In the case of deceased biospecimen donors who are also organ and/or tissue transplant donors, pathology incidental findings may be relevant not to family members, but to potential organ or tissue transplant recipients. This paper will describe the ethical implications of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project, the process for developing a consensus approach as to if/when such findings should be returned, possible implications for other research projects collecting postmortem tissues and how the scenario encountered in GTEx fits into the larger return of results/incidental findings debate.

Primary care physicians and laypersons' perceptions of multicancer detection clinical trial designs.

BACKGROUND: The National Cancer Institute Cancer Screening Research Network is launching a pilot study (Vanguard) to determine feasibility of successful completion of a clinical trial of multicancer detection tests. This focus group study reports perceptions of primary care physicians and laypersons of different clinical trial designs and willingness to participate in a multicancer detection clinical trial. METHODS: We undertook 14 focus groups with 88 laypersons and 6 focus groups with 45 primary care physicians. Participants were shown graphics of clinical trial designs and asked for their reactions. Focus group recordings were transcribed verbatim, and thematic analysis of the transcripts were conducted to identify emergent themes. RESULTS: Primary care physician and layperson participants recognized the importance of conducting clinical trials to determine the clinical utility of multicancer detection tests. Primary care physicians expressed reluctance to participate in trials because of workload burden, and laypersons expressed hesitancy about enrolling in the control group. Primary care physicians and laypersons expressed concern about a study design in which multicancer detection test results would not be returned to the control group (intended effect), but they respectively indicated a willingness to refer patients to, or participate in, a multicancer detection test clinical trial given transparent and clear communication on collection and use of biospecimens and data, particularly if a multicancer detection test would eventually be run and results eventually returned. CONCLUSION: This study yielded important insights to guide trial design in planning prospective evaluation of multicancer detection testing. Maintaining transparency and trust while possibly withholding multicancer detection test results to maximize trial feasibility and efficiency is of particular concern.

Perceptions of Multicancer Detection Tests Among Primary Care Physicians and Laypersons: A Qualitative Study.

INTRODUCTION: Multicancer detection tests (MCDs) are blood-based tests designed to detect multiple cancer types. It is currently unclear whether these cancer screening tests improve mortality. To understand awareness of MCDs among providers and patients, as well as explore how they perceive the benefits, harms, and acceptability of MCDs, we have undertaken a focus group study in primary care physicians (PCPs) and laypersons to explore knowledge, attitudes, and expectations of cancer screening using MCDs. METHODS: We conducted six focus groups with 45 PCP participants and 12 focus groups with 80 layperson participants. Participants were identified via a consumer research firm and found eligible following the completion of a screener survey. Moderators used a semi-structured guide containing open-ended questions and prompts to facilitate the discussion. Recordings were transcribed and coded line by line using a codebook developed based on questions and emerging discussion concepts, and emergent themes were identified. RESULTS: Both PCP and layperson participants felt the that benefits of MCDs included ease of use and potential ability to detect cancers early. However, they felt that additional data is needed to overcome some of the concerns related to MCDs. PCP participants expressed concerns related to lack of practice guidelines, cost of diagnostic follow-ups, privacy and insurance issues, fear/anxiety related to confirmation of MCD results, and malpractice liability related to perceived false negative test results. Layperson participants expressed concerns related to costs, insurance coverage, and privacy, as well as anxiety over the confirmation of a positive test result. CONCLUSIONS: There is a major need for more rigorous data regarding MCDs to inform the development of guidelines for use as cancer screening tools.

NCI think tank concerning the identifiability of biospecimens and "omic" data.

PURPOSE: On 11 and 12 June 2012, the National Cancer Institute hosted a think tank concerning the identifiability of biospecimens and "omic" data in order to explore challenges surrounding this complex and multifaceted topic. METHODS: The think tank brought together 46 leaders from several fields, including cancer genomics, bioinformatics, human subject protection, patient advocacy, and commercial genetics. RESULTS: The first day involved presentations regarding the state of the science of reidentification; current and proposed regulatory frameworks for assessing identifiability; developments in law, industry, and biotechnology; and the expectations of patients and research participants. The second day was spent by think tank participants in small breakout groups designed to address specific subtopics under the umbrella issue of identifiability, including considerations for the development of best practices for data sharing and consent, and targeted opportunities for further empirical research. CONCLUSION: We describe the outcomes of this 2-day meeting, including two complementary themes that emerged from moderated discussions following the presentations on day 1, and ideas presented for further empirical research to discern the preferences and concerns of research participants about data sharing and individual identifiability.

Ethical, Legal, and Policy Issues Surrounding Biospecimen Research Conducted or Supported in the USA.

Rapid and dramatic advances in molecular sequencing technology, as well as medical discoveries from genome-wide association and other precision medicine studies, have highlighted the longstanding ethical and legal challenges research biobanks consistently face. Whose authority is needed to conduct research with excised tissue, and how that authority may be exercised with respect and transparency, are central questions. This review article explores how scholars have addressed ethical and legal controversies such as the proper breadth and scope of consent for collection and future research use of biological specimens and data, the importance of disclosing individual research results and secondary findings, and collecting cadaver tissue from deceased persons. This article focuses on the legal and regulatory environment for conducting and/or supporting biospecimen research in the United States of America. It takes the position that proper biobank governance strategies, which ensure accountability and model respect toward biospecimen contributors, as well as transparency in communications between participants and researchers, reduce the likelihood of downstream legal disputes.

Study design considerations for trials to evaluate multicancer early detection assays for clinical utility.

Blood-based assays using various technologies and biomarkers are in commercial development for the purpose of detecting multiple cancer types concurrently at an early stage of disease. These multicancer early detection (MCED) assays have the potential to improve the detection of cancers, particularly those for which no current screening modality exists. However, the unknown clinical benefits and harms of using MCED assays for cancer screening necessitate the development and implementation of a randomized controlled trial (RCT) to ascertain their clinical effectiveness. This was the consensus of experts at a National Cancer Institute-hosted workshop to discuss initial design concepts for such a trial. Using these assays to screen simultaneously for multiple cancers poses novel uncertainties for patient care compared with conventional screening tests for single cancers, such as establishing the diagnostic workup to confirm the presence of cancer at any organ site; clarifying appropriate follow-up for a positive assay for which there is no definitive diagnosis; identifying potential harms such as overdiagnosis of indolent disease; determining clinically effective and efficient strategies for disseminating MCED screening in real-world practice; and understanding the ethical implications, such as potentially alleviating or exacerbating existing health disparities. These assays present new and complex challenges for designing an RCT. Issues that emerged from the meeting centered around the need for a flexibly designed, clinical utility RCT to rigorously capture the evidence required to fully understand the net benefit of this promising technology. Specific topic areas were endpoints, screening protocols, recruitment, diagnostic pathway, pilot phase, data elements, specimen collection, and ethical considerations.

Intersection of biobanking and clinical care: should discrepant diagnoses and pathological findings be returned to research participants?

Diagnostic discrepancies occur when the diagnosis made on a biospecimen during the course of review at a biobank differs from the original clinical diagnosis. These diagnostic discrepancies detected during biobanking present unique challenges that are distinct from other types of research results or incidental findings. The proposed process for reporting diagnostic discrepancies or pathological incidental findings identified through a quality assurance evaluation at the biobank includes verification of the biospecimen identity, verification of the diagnosis within the biobank, and re-review of the case by the pathologist at the biospecimen collection site. If the pathologist at the biobank and the original pathologist do not reach agreement, an impartial and knowledgeable third party is consulted. The decision as to whether and how to notify research participants of any confirmed changes in diagnosis would be determined by institutional procedures. Implementation of this proposed process will require clear delineation of the roles and responsibilities of all involved parties in order to promote excellence in patient care and ensure that researchers have access to biospecimens of requisite quality.Genet Med 2012:14(4):417-423.

Broad Consent for Research on Biospecimens: The Views of Actual Donors at Four U.S. Medical Centers.

Commentators are concerned that broad consent may not provide biospecimen donors with sufficient information regarding possible future research uses of their tissue. We surveyed with interviews 302 cancer patients who had recently provided broad consent at four diverse academic medical centers. The majority of donors believed that the consent form provided them with sufficient information regarding future possible uses of their biospecimens. Donors expressed very positive views regarding tissue donation in general and endorsed the use of their biospecimens in future research across a wide range of contexts. Concerns regarding future uses were limited to for-profit research and research by investigators in other countries. These results support the use of broad consent to store and use biological samples in future research.