As science rapidly accelerates to address COVID-19 and other disease indications, we can’t lose sight of the importance of regulatory guidelines and requirements that ensure the safe, ethical treatment of patients participating in research studies.
Regulations governing the protection of human research subjects are based on the ethical principles identified in the Belmont Report, the Nuremberg Code and the Declaration of Helsinki (1-3), with guidelines contributed by the Council for the International Organization of Medical Sciences, the Nuffield Council on Bioethics and Good Clinical Practice (4-6). Many of these ethical principles relate to patient consent. Informed consent is a written acceptance, directly from the donor, to participate in a research project based on an understanding of the study’s purpose, its risks and benefits and the planned collection of specimens and data.
Legal and ethical oversight is country/region-specific. In the US, institutional review boards (IRBs) are responsible for the regulatory oversight of research involving human subjects, with the Office of Human Research Protection (OHRP) governing the operation of IRBs (7). In the UK, consent or authorization is required for the collection of biospecimens for research from both living and deceased donors; other European countries have similar regulations. Some UK research studies also require approval from an independent ethics committee (IEC); that can be determined via an online tool provided by the Health Research Authority (8). In other countries, the Ministries of Health (MOH), their equivalent or authorized IECs may be responsible for oversight.
Types of Collections
Prospective collections include excess material collected from a procedure that the subject is already undergoing for standard care or extra samples collected specifically for research. In most countries, prospective collections for research use require the donor’s written informed consent.
Retrospective or remnant specimens are not collected specifically for research. Instead, they are left over after diagnostic tests and analyses have been conducted. Regulations regarding the use of these samples is also country/region-specific.
In the US, cadavers are not considered human research subjects according to existing regulations. For this reason, federal and state laws, including the Health Insurance Portability and Accountability Act of 1996, should be referenced when procuring post-mortem samples. In the UK and Europe, post-mortem samples are regarded as gifts, and their use in research is regulated in a similar manner to samples from living donors (9). In the UK, the Human Tissue Authority (HTA) licenses organizations involved in the removal of tissue from the deceased, which may only be retained for use in research if appropriate consent has been obtained from the donor or their next of kin. Tissue for research must also be stored on HTA-licensed premises.
Quality Considerations
Originally, biobanks were used to store archival specimens from in-house longitudinal studies, such as the Framingham Heart Study (10). As research focused on personalized medicine, scientists identified a need for high-quality, data-rich specimens. Due to differences in collection processes, sample storage, data capture and regulatory documentation, various research groups began to define processing standards to ensure reliable specimen quality.
The International Society for Biological and Environmental Repositories (ISBER) was established in 1999 to focus on identifying and harmonizing “quality standards, education, ethical principles and innovation in the science and management of biorepositories” (11).
The US National Cancer Institute (NCI) Biorepository Coordinating Committee was established in 2004-2005 to identify and resolve biospecimen resource issues (12).
The consensus of these two organizations — as well as the Biobanking and Biomolecular Resources Research Infrastructure, the UK HTA and the European, Middle Eastern and African Society for Biopreservation and Biobanking — provides the basis for current biorepository standards and principles that meet the global research needs for high quality biospecimens (13-15).
Research frequently requires large numbers of samples with adequate specimen size and volume. Consistent sample quality is expected, with a range of sample types that are representative of the condition(s) being studied. Additionally, researchers are looking for clinical data and demographics to accompany the samples and support their research. The reliability of data derived from human specimens depends on the quality and consistency of the analyzed samples. For additional insight, please read BioIVT’s Recommendations to Consider When Sourcing Human Biospecimens and Questions to Ask Your Human Biological Specimens Provider.
References
1. hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html
2. cirp.org/library/ethics/nuremberg/
3. wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/
4. cioms.ch
5. nuffieldbioethics.org/wp-content/uploads/2014/07/Human-tissue.pdf
6. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e6-r1-guideline-good-clinical-practice_en.pdf
7. hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html#46.102
8. hra-decisiontools.org.uk/research/index.html
9. www.dt-toolkit.ac.uk/pathology/usingdiagnosticarchiveswithoutconsent.cfm
10. framinghamheartstudy.org
11. isber.org/page/BPR
12. biospecimens.cancer.gov/bestpractices/2016-NCIBestPractices.pdf
13. bbmri-eric.eu
14. hta.gov.uk/sites/default/files/Code%20E.pdf
15. esbb.org
BioIVT, formerly BioreclamationIVT, is a leading global provider of research models and value-added research services for drug discovery and development. We specialize in control and disease-state biospecimens including human and animal tissues, cell products, blood, and other biofluids. Our unmatched portfolio of clinical specimens directly supports precision medicine research and the effort to improve patient outcomes by coupling comprehensive clinical data with donor samples. By combining our technical expertise, exceptional customer service, and unparalleled access to biological specimens, BioIVT serves the research community as a trusted partner in ELEVATING SCIENCE®.