Every biosample or tissue sample used for medical research has a different journey. The journey starts when a person donates a biosample and it ends when a researcher analyses the same sample. In between, there are a wide variety of possible routes, events and timelines. It is important to realise that all of these have the potential to affect the sample quality. We need to record details of the sample journey for a variety of reasons. Firstly, there are scientific reasons relating to quality control, for example. Secondly, there are legal and ethical reasons, as explained below.
What Is Biospecimen Provenance?
According to the Merriam-Webster dictionary, ‘provenance’ means the origin or source of something.
For example in the world of antiques, provenance describes the history of ownership of a valued object or work of art.
According to the World Wide Web Consortium, provenance includes: ‘… information about entities, activities, and people involved in producing a piece of data or thing, which can be used to form assessments about its quality, reliability or trustworthiness.’
In medical research, the provenance of biospecimens includes four types of information about samples:
- Geographic origin
- Previous custodian(s)
- Sample processing history
- Donor information
Components Of Biospecimen Provenance
1. Geographic Origin
Knowing the country of origin is an essential component of biospecimen provenance. This is because it may provide information to help make sense of research findings. For example, it may provide information about environmental, socio-economic and genetic factors. Requesters also need to know if samples come from countries with export restrictions. Examples of such countries include China, India and Russia. In such cases, one must check compliance with national regulations (Hofman et al., 2017).
2. Previous Custodian(s)
Researchers need information about all previous custodians of the biosample. This information is required to ensure that the sample has been (a) obtained ethically and (b) processed reliably.
Ethical sourcing requires that sample donors have provided informed consent. Also, that sample collection has had ethical oversight and approval. These requirements are in line with the following regulations and guidelines:
- US revised Common Rule effective July 19, 2018
- European Recommendation Rec(2006)4 of the Committee of Ministers to member states on research on biological materials of human origin.
- UK Human Tissues Act (2004). https://www.hta.gov.uk/policies/human-tissue-act-2004
The source biorepository should provide researchers with evidence of compliance.
Certification, accreditation or licensing of the source biorepository gives confidence about reliability. For example:
- ISO 9001 certification, which sets out the criteria for a quality management system
- ISO 20387 certification, which specifies general requirements for the competence, impartiality and consistent operation of biobanks. It includes quality control requirements.
- CTRNet certification
- US CAP Accreditation for Biorepositories
- Licensing by the Human Tissue Authority in the UK.
The requester must know the identity of the source biorepository to be able to recontact to request extra samples or clinical information. Similarly, the requester must also know the identity to give credit to the source biorepository in publications.
Biobanks need to have a signed material transfer agreement (MTA) before supplying samples. Importantly, the MTA document includes information on usage restrictions, confidentiality requirements, and biosafety
3. Biorepository Tissue Sample Processing History
There is enormous potential for variation in tissue sample processing. Importantly, this variation can have significant effects on scientific results. So processing details are a vital part of biospecimen provenance.
Take, for example, the collection of samples at surgery. The warm ischaemia time affects sample quality. This is the time from clamping of blood vessels to surgical resection of tissue. Furthermore, the cold ischaemia time also affects quality. This is the time the sample is on wet ice until frozen. Both warm and cold ischaemia vary from case to case, so recording them is the best practice.
The collection and processing of blood samples provide another example. In this case there are many steps at which variations can occur and may affect quality. For example, the type of primary container. Also, the pre-centrifugation delay time and temperature. In addition, centrifugation parameters include temperature, speed, and the presence or absence of braking.
The Standard PREanalytical Code (SPREC) provides a systematic method for recording these variables. Betsou et al., 2010. Some professional biobanks offer this information to requesters.
4. Donor Information Is A Part Of Biospecimen Provenance
Demographic and clinical information about the donor is part of biospecimen provenance. The biobank must anonymise such information to protect donor confidentiality.
Sometimes researchers need to come back to the biobank for extra information on a patient. For example, they may need to know whether a disease recurs. In such cases, the researcher needs to know the identity of the source biobank.
Conclusion
Researchers need biospecimen provenance information to be confident of sample quality. Without such information, researchers are at risk of producing irreproducible results.
Freedman et al. (2015) analysed errors that contribute to irreproducibility in preclinical research. They concluded that unreliable biological reagents and reference materials are a major source. In summary, they concluded that:
‘ … the challenge of increasing reproducibility and addressing the costs associated with the lack of reproducibility in life science research is simply too important and costly to ignore. Lifesaving therapies are being delayed, research budgets face increasing pressure, and drug development and treatment costs are rising. Improving reproducibility remains a critical cornerstone to solving each of these challenges.’
It is important to realise that to improve reproducibility, researchers must have biospecimen provenance information.
This article is on the Biosample Hub blog. Other posts in this blog include:
- Why Academic / Hospital Biobanks Should Provide Biosamples to Industry
- Ensuring Public Support For Biobank Cooperation With Industry
- The Main Actors Providing Biosamples To Industry
- Biosample Needs of Different Industry Players
- The Dual Role of Academic Biobanks
- What is Commodification?
- Acceptable Transactions in Biobanking
- Why Biobank Access Policies Should Be Publicly Available
- Biospecimen Provenance: What Researchers Need To Know
The Biosample Hub platform https://biosamplehub.org/ encourages ethical sourcing of biosamples for the industry sector.