CASRAI Dictionary

Tag: research governance

  • Governing the Sample: Biobanks, Consent and the Human Tissue Act

    A biobank is, at its simplest, an organised collection of biological samples and the data that describe them, held for use in research. But that simple description conceals a set of difficult responsibilities. The samples come from people, often donated in good faith for purposes that may not yet be fully defined. They may be stored and reused for many years, across many studies, by many researchers. Governing such collections responsibly, in a way that protects participants and maintains their trust while enabling valuable research, is one of the more demanding challenges in research compliance.

    The problem of consent over time

    Consent is the foundation of ethical research involving people, but biobanks complicate it. Traditional specific consent asks a participant to agree to a particular study with defined aims. That works when the use is known in advance. Biobank samples, however, are frequently collected for future research whose precise questions cannot be specified at the time of donation. Requiring fresh specific consent for every new study would be impractical and would waste valuable, sometimes irreplaceable, material. The field has therefore developed alternative consent models to bridge the gap between respecting participant autonomy and enabling reuse.

    Broad, dynamic and specific consent

    Three broad approaches are commonly discussed:

    • Specific consent ties the use of a sample to a defined study or narrow purpose. It maximises participant control over each use but is poorly suited to open-ended biobanking.
    • Broad consent asks participants to agree to their samples and data being used for a wide range of future research, typically within a described framework and subject to ongoing ethical oversight. It is the model many large biobanks rely upon, trading some specificity for the ability to support unforeseen studies, while keeping governance in place to set limits.
    • Dynamic consent uses ongoing, often digital, communication to let participants review and adjust their preferences over time, choosing which kinds of research their materials may support and staying informed about how they are used. It aims to restore some of the granularity of specific consent within a long-lived collection.

    None of these is a complete answer on its own. Each balances participant autonomy, practicality, and the public interest in research differently, and the right choice depends on the nature of the biobank and the expectations of its participants.

    The Human Tissue Act 2004 and the Human Tissue Authority

    In England, Wales, and Northern Ireland, the use and storage of human tissue is governed by the Human Tissue Act 2004, legislation introduced in the wake of serious failures in which organs and tissue were retained without proper consent. The Act made appropriate consent the fundamental principle governing the removal, storage, and use of human tissue, and it created the Human Tissue Authority (HTA) as the regulator responsible for licensing and overseeing organisations that store and use such material.

    For biobanks, this means operating within a statutory framework: holding the appropriate licences, meeting standards for consent and traceability, and remaining accountable to a regulator. Governance is therefore not merely a matter of good intentions but of legal compliance, with oversight of how samples are obtained, stored, tracked, and used.

    UK Biobank as a governance example

    UK Biobank is one of the largest and most studied research resources of its kind, holding biological samples and extensive health and lifestyle data from a very large cohort of volunteer participants, available to approved researchers. Its governance illustrates how the principles above are put into practice. Participants gave consent for their samples and data to be used in a broad programme of health-related research, and the resource operates under an ethics and governance structure designed to set the boundaries of acceptable use, oversee access by researchers, and maintain participant trust over the long term. Access is granted to bona fide researchers for approved purposes, rather than being open to all, reflecting the balance between enabling research and protecting participants.

    Trust as the underlying asset

    What ties these elements together is trust. A biobank can only function if participants believe their contributions will be handled responsibly, used for legitimate purposes, and protected from misuse. Robust consent models, statutory regulation under the Human Tissue Act, oversight by the HTA, and transparent governance structures all serve to sustain that trust. They also support the responsible reuse of data, including the careful application of FAIR data principles and appropriate safeguards, so that the scientific value of these collections can be realised without compromising the people who made them possible.

    Governance as an enabler

    It is tempting to see governance as a brake on research, a set of hurdles between a scientist and a sample. In the context of biobanks, the opposite is closer to the truth. Sound governance, clear consent, statutory oversight, and accountable management is what makes large-scale, long-term reuse of human tissue possible at all. The standards and vocabularies catalogued in the CASRAI data dictionary help describe the associated data consistently, supporting the traceability that responsible biobanking demands. Done well, governance is not the enemy of discovery but its precondition.

  • CRISPR-Cas9: How Gene Editing Works as a Research Tool

    CRISPR-Cas9 is a programmable gene-editing system that uses a short guide RNA to direct the Cas9 enzyme to a matching DNA sequence, where Cas9 makes a precise cut so the sequence can be altered. As a research tool, it lets laboratories target specific genes for study; the foundational work on harnessing it as a programmable system is associated with Jennifer Doudna and Emmanuelle Charpentier.

    This article describes the mechanism and its use as a research method. It makes no clinical or therapeutic claims; the framing throughout is how CRISPR works as a laboratory tool and how its use is documented and governed.

    The bacterial origin of CRISPR

    CRISPR originates as a natural defence system in bacteria. The acronym stands for clustered regularly interspaced short palindromic repeats — segments of DNA that, together with associated (Cas) proteins, help bacteria recognise and cut the DNA of invading viruses. Researchers adapted this natural recognise-and-cut machinery into a programmable laboratory tool by supplying a custom guide RNA.

    How the guide RNA and Cas9 work together

    The system has two essential parts. The guide RNA is a short RNA sequence designed to match a chosen DNA target. The Cas9 enzyme is the molecular scissors that binds the guide RNA, locates the matching DNA, and introduces a cut at that site.

    Component Role
    Guide RNA Programmable sequence that directs the system to a specific DNA target
    Cas9 enzyme Binds the guide RNA and cuts the DNA at the targeted site
    Target DNA The genomic sequence selected for study or modification

    Because the guide RNA can be reprogrammed simply by changing its sequence, the same Cas9 enzyme can be directed to many different targets. That programmability is what makes CRISPR a flexible research method, and the precise notation of target sequences relies on standard conventions like those in the CASRAI dictionary.

    CRISPR as a research method

    In the laboratory, CRISPR-Cas9 is used to investigate gene function — for example, by disabling a gene and observing the result. Treating CRISPR as a method places it firmly within the research lifecycle: it must be planned, documented, executed and reported like any other experimental technique. Recording the exact guide-RNA sequences, target sites and reagents used is essential for others to interpret the work.

    Reproducibility and governance considerations

    Reproducibility depends on complete reporting. Independent researchers can only repeat or build on a CRISPR experiment if the guide-RNA design, target sequence, delivery method and verification approach are fully described. This connects CRISPR reporting to the standards-led thinking across our reproducibility coverage and to method-reporting frameworks such as those discussed in our guide to gene-expression reporting standards.

    Governance is the second consideration. Research use of gene editing is subject to institutional oversight and ethical review, and provenance — what was edited, how and under what approvals — should be documented. The same governance discipline appears in our coverage of stem-cell research registries and governance, and stable identifiers help link methods to outputs as set out in our note on persistent identifiers in 2026. For documentation practice, see our guidance for authors.

    Frequently asked questions

    How does CRISPR-Cas9 work?

    A short guide RNA is designed to match a chosen DNA sequence. The Cas9 enzyme binds the guide RNA, finds the matching DNA, and cuts it at that site, allowing the targeted sequence to be studied or altered in the laboratory.

    Where does CRISPR come from?

    CRISPR originates as a natural defence system in bacteria that recognises and cuts the DNA of invading viruses. Researchers adapted this recognise-and-cut machinery into a programmable laboratory tool by supplying a custom guide RNA.

    Who is associated with developing CRISPR as a tool?

    The foundational work on harnessing CRISPR-Cas9 as a programmable gene-editing system is associated with Jennifer Doudna and Emmanuelle Charpentier.

    What needs to be reported for a CRISPR experiment to be reproducible?

    Complete reporting should include the guide-RNA design and sequence, the target site, the delivery and verification methods, and the reagents used, so that independent researchers can interpret and repeat the work.

  • Stem Cell Research Registries, Provenance and Reporting Governance

    Stem cells are cells capable of dividing to renew themselves and of giving rise to more specialised cell types, and in research they are tracked through cell-line registries that record provenance and reporting metadata. This article scopes stem cells strictly to research, registries and governance — it does not address therapies, treatments or clinical use.

    For research-data infrastructure, the key questions are definitional and administrative: what type of cell line is being used, where it came from, under what consent, and how its use is reported so that studies remain transparent and reproducible.

    Types of stem cells at a definitional level

    Stem cells are commonly grouped into three broad categories used in research. The distinctions matter for registries because provenance and governance requirements differ by type.

    Type Definitional description
    Embryonic stem cells Derived from early-stage embryos in a research setting; broad capacity to give rise to many cell types
    Induced pluripotent stem cells (iPSCs) Adult cells reprogrammed in the laboratory to a pluripotent-like state
    Adult (tissue) stem cells Found within tissues; more limited in the cell types they typically generate

    These are definitional categories rather than clinical claims. Recording the precise type — and the laboratory line identifier — is essential metadata, much like the controlled terms catalogued in the CASRAI dictionary.

    Cell-line registries and persistent identifiers

    A stem-cell registry is a curated database that records standardised information about research cell lines, including a stable identifier, the line’s origin and the conditions under which it was derived. The concept exemplified by resources such as a human pluripotent stem cell registry (the hPSCreg concept) is to give each line a persistent, citable identifier and a consistent metadata record.

    Persistent identifiers for cell lines play the same role they play across the research ecosystem: they disambiguate one line from another and link it to the studies that used it. This mirrors the wider identifier landscape described in our overview of persistent identifiers in 2026.

    Provenance: tracking where a line came from

    Provenance is the documented history of a cell line — its derivation, the consent under which source material was obtained, and any ethical approvals associated with its creation and use. Robust provenance is a compliance requirement as much as a scientific one, ensuring that the line’s permitted uses are clear and auditable.

    Because consent and ethical-approval terms govern how a line may be used and shared, this provenance metadata must accompany the line through the research lifecycle. The same governance logic underpins responsible data exchange in our guide to genomic data-sharing standards.

    Reporting and governance for reproducibility

    Transparent reporting of which cell line was used, with its registry identifier and provenance, lets independent researchers interpret and build on a study correctly. Misidentified or undocumented lines are a known source of irreproducibility, so registries and clear reporting requirements directly support the goals covered in our reproducibility news. For practical advice on documenting research resources, see our guidance for authors.

    Frequently asked questions

    What are the main types of stem cells used in research?

    At a definitional level, research commonly distinguishes embryonic stem cells, induced pluripotent stem cells reprogrammed from adult cells, and adult tissue stem cells. Each category carries different provenance and governance requirements.

    What is a stem-cell registry?

    A stem-cell registry is a curated database that gives each research cell line a persistent identifier and a standardised record of its origin, derivation conditions and consent, supporting transparent and citable reporting.

    Why does provenance matter for stem-cell lines?

    Provenance documents a line’s derivation, consent and ethical approvals, which together define how the line may be used and shared. Without it, permitted uses are unclear and studies are harder to reproduce or audit.

    Does this guide cover stem-cell therapies?

    No. This guide is scoped to research, registries, provenance and governance. It does not address therapies, treatments or clinical applications.

  • Clinical Trial Phases I to IV: Structure and Governance

    A clinical trial is a prospective study that evaluates the effects of a medical intervention — a medicine, device, procedure or behavioural change — in human participants under a pre-specified protocol. Trials are organised into phases, each answering a different question and building on the evidence of the last. This article describes the structure and governance of trials from a methodology and standards perspective; it is not clinical advice.

    The four phases

    Phase Primary question Typical scope
    Phase I Is it safe, and how is it handled by the body? First-in-human; small numbers; focus on safety, tolerability and dose-finding.
    Phase II Does it show signs of working, and at what dose? Larger groups; preliminary efficacy and further safety.
    Phase III Does it work better than current options? Large, often multi-centre randomised controlled trials supporting regulatory approval.
    Phase IV How does it perform in routine use? Post-marketing surveillance after approval; rare effects and long-term outcomes.

    How trials are designed

    The strongest designs use randomisation to allocate participants to groups, blinding to reduce expectation bias, and a control group — often a placebo or an existing standard of care — for comparison. A pre-registered protocol specifies the hypotheses, primary and secondary outcomes, sample size and analysis plan before data are collected, which guards against selective reporting. These ideas connect directly to our explainers on the placebo and placebo effect and randomised controlled trials.

    Registration and transparency

    Clinical trials are expected to be registered in a public registry — such as ClinicalTrials.gov or an ISRCTN registry — before they begin. The International Committee of Medical Journal Editors (ICMJE) requires prospective registration as a condition of publication, and the World Health Organization maintains a registry network and a minimum data set. Registration creates a public record of what a trial set out to do, so that its results can be checked against its original aims and so that unpublished trials do not vanish from the evidence base.

    Governance and ethics

    Trials are governed by independent research ethics committees (institutional review boards), by informed consent from participants, and by adherence to Good Clinical Practice. International principles trace back to the Declaration of Helsinki. Data are monitored, adverse events reported, and the conduct of the trial audited. Reporting is governed by the CONSORT statement for randomised trials, which specifies what must appear in the published account.

    Why this matters to the research record

    A registered protocol, a transparent results report and a persistent identifier together make a trial part of a citable, auditable record. The same contributor-attribution and identifier infrastructure that CASRAI works on — ORCID for people, DOIs for outputs, registries for studies — is what lets the scholarly and regulatory records stay connected.

    Frequently asked questions

    What are the four phases of a clinical trial?

    Phase I assesses safety and dose in small numbers; Phase II looks for preliminary efficacy; Phase III is a large comparison against existing options to support approval; and Phase IV monitors performance after a product is on the market.

    Why must clinical trials be registered?

    Prospective registration creates a public record of a trial’s aims and design before results are known. It deters selective reporting, reduces publication bias, and is required by the ICMJE as a condition of publishing the results.

    What is the difference between a clinical trial and clinical research?

    A clinical trial is one type of clinical research in which an intervention is tested under a protocol. Clinical research is the broader field, which also includes observational studies that do not assign an intervention.

    What governs the ethics of a clinical trial?

    Independent ethics committees, informed consent, the Declaration of Helsinki and Good Clinical Practice together govern trial ethics. See our Good Clinical Practice explainer.