Biomedical research generates novel information about cancer every day. New scientific capabilities, such as next-generation sequencing, provide investigators new ways to study cancer biology, while growing numbers of clinical trials test advanced interventions, such as combination therapies and immunotherapies. These efforts have created increased demand and need for human tissue and blood samples in addition to standard-of-care tissue-based assessments.
Human tissue, however, can be difficult to procure; samples may be limited, scope of use may be limited based on previous consent, competition for available tissue may be fierce, and maintaining tissue for future patient care purposes is not only desirable but also mandated by standards of care in pathology and federal regulations. Although obtaining tissue from patients may have associated risk and discomfort, individual patients and patient advocacy organizations are often eager to participate as true partners in the clinical research enterprise. The prevailing belief among all stakeholders is that, first and foremost, the priority for use of human tissue should be for diagnostic/clinical purposes. It is only after clinical need is met that tissue should be made available for research purposes. Investigators desiring tissue for research may include the patient's treatment institution, other institutions, or companies that develop drugs, devices, or companion diagnostics. Uses of the tissue may range from screening for clinical trial enrollment, exploratory biomarker analyses, and biobanking for future research and biomarker development.
Tissue samples, whether for research or clinical diagnosis, are often housed in a biorepository or clinical archive, where biological materials are collected, processed, stored, and distributed in support of future scientific investigation. The biorepository assures the proper consent, clinical provenance, annotation, and quality of the biospecimens in its collection and manages the accessibility and distribution/ disposition of samples and data. Large cancer centers often have a shared resource that provides banked tissues to investigators while maintaining patient confidentiality. Pharmaceutical companies and other entities may also maintain their own biorepositories. In general, biorepositories are required to be overseen by a committee that governs how the tissue and other samples are allocated to investigators and reviews specific proposals to assure that tissue requests are appropriate for a proposed study and in line with patient consent. However, even though biorepositories can enable greater sharing of resources, there are not enough specimens to meet the demand. As a result, tissue allocation has become a growing issue for many clinical and translational investigators.
Biospecimens are vulnerable to environmental and biological stresses introduced by routine collection, processing, storage, and transport procedures prior to analysis.1 This preanalytical variation may transform the molecular composition of the biospecimen before it ever reaches the clinician or researcher. Preanalytic variables include medical or surgical interventions before the specimen is removed from the patient, processing methods, and specimen transport and storage. Without proper understanding of the impact of these sources of variability, molecular changes may be misinterpreted as disease-related or even disease-specific findings. Thus, optimum collection, processing, storage, tracking, and shipment of biospecimens are central to ensuring reproducible and valid outcomes of clinical studies. Clinically, there is a potential for incorrect diagnosis or treatment. In research, there is increased risk of irreproducible results and misinterpretation of artifacts as biomarkers when preanalytic variables are not controlled.
Additionally, tumor biology is complex. Mutations found in single biopsies may not be found in other regions of the same tumor, and “favorable” and “unfavorable” molecular profiles may be generated by analysis of different regions of the same tumor.2 Different parts of the same tumor can have different mutations in the very same genes, resulting in local heterogeneity, whereas treatment often creates evolutionary pressures that increase heterogeneity.
A multitude of stakeholders, including academic clinicians and researchers, pharmaceutical industry scientists, individual patients, and patient advocacy organizations, have a vested interest in the sharing of human biospecimens. These stakeholders share goals for these biospecimens, including high-quality samples to serve both diagnostic and research purposes, and sufficient quantity of biospecimen for all planned and consented uses. In order to achieve these goals, new practices must be agreed upon and adopted, including consistent and standard sample collection, processing, storage, and release, and adoption of guidelines on sample control and ownership and also guidelines covering best practices in length of sample retention and uses outside of specified trials.
There are several key challenges to optimizing the use and usefulness of biospecimens. High-quality biospecimens are needed by all stakeholders in order to generate scientifically accurate studies and results, but who will define the quality standards? How can consistent collection of high-quality samples be ensured? Several process issues must be addressed, including improvement of preanalytic processes and sample collection, documentation and sample collection attribution, and management of competing priorities for tissue use.
To identify and examine challenges in tissue collection, processing, storage, and allocation, NCCN convened the NCCN Tissue Allocation work group comprised of clinical research, pathology, and ethics thought leaders from NCCN Member Institutions, including clinicians, pathologists, clinical and translational investigators, and Institutional Review Board (IRB) representatives, as well as representatives from industry, professional organizations, and patient advocacy groups. The work group met on March 30, 2015, in Philadelphia. In addition, NCCN held the NCCN Policy Summit: Emerging Issues in Tissue Allocation on June 8, 2015, in Washington, DC. This summit included additional thought leaders representing the aforementioned groups and relevant stakeholders.
This article focuses on 3 topics identified as critical by the work group and discussed at the policy summit: informed consent, preanalytic standards, and tissue sharing between academia and industry.
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