Click here to open the filter panel
E
Explicit consent
F
Fairness and transparency
F
FDPIC (Swiss Federal Data Protection and Information Commissioner)
F
Federated learning
F
Filing system
F
First-in-class drugs
F
First-in-human (FIH) trial
F
Food and Drug Administration (FDA)
F
Fundamental rights impact assessment (FRIA)
G
General Data Protection Regulation (GDPR)
G
General-purpose AI model (GPAI)
G
Genetically modified organism (GMO)
G
Genetic data
G
Global public health security
G
Good clinical practice (GCP)
H
HDS certification (Hébergeur de Données de Santé)
H
Health data access body (HDAB)
H
Health data warehouse (HDW)
H
HHS Office for Civil Rights (OCR)
H
High-risk AI system
H
HIPAA (Health Insurance Portability and Accountability Act)
H
Homomorphic encryption
H
Human oversight (AI Act)
H
Human subjects protection review board
I
ICH E6(R3)
I
Incapacitated subject
I
Information Commissioner's Office (ICO)
I
Informed consent
I
Inspection
I
Institutional Review Board (IRB)
I
Interactive response technology (IRT)
I
Interactive voice response system (IVRS / IxRS)
I
Interactive web response system (IWRS)
I
International data transfer
I
Investigational Medicinal Product Dossier (IMPD)
I
Investigational medicinal product (IMP)
I
Investigational New Drug (IND) application
I
Investigator
I
Investigator's brochure (IB)
I
Investigator site file (ISF)
I
In Vitro Diagnostic Regulation (IVDR)
I
ISO/IEC 27001 (information security management)
I
ISO/IEC 42001 (AI management system)
J
Joint controllers
K
k-anonymity
K
Key-coded data (coded data)
K
Key (cryptographic key and pseudonymisation key)
K
Kinetics (pharmacokinetics and pharmacodynamics)
L
Large language model (LLM)
L
Lawfulness
L
Lay summary
L
Legal basis for processing
L
Legally designated representative
L
Legitimate interest
L
Legitimate interest assessment (LIA)
L
LGPD (Brazil's General Data Protection Law)
L
Limited data set (HIPAA)
L
Local site investigator
M
Main establishment
M
MedDRA
M
Medical Device Regulation (MDR)
M
Membership inference attack
M
Me-too drug
M
MHRA (Medicines and Healthcare products Regulatory Agency)
N
Natural history study
N
New drug application (NDA)
N
NIS2 Directive
N
Notified body
O
Observational study
O
Observer-reported outcome (ObsRO)
O
One-stop-shop mechanism and lead supervisory authority
O
Orphan drug designation (ODD)
P
Patient-reported outcome (PRO)
P
Performance outcome (PerfO)
P
Personal data
P
Personal data breach
P
Pharmacokinetics (PK)
P
Pharmacovigilance
P
Population pharmacokinetics (pop PK)
P
Post-market surveillance (PMS)
P
Predetermined change control plan (PCCP)
P
Principal investigator (PI)
P
Principles of data protection
P
Privacy
P
Privacy by design
P
Privacy-enhancing technologies (PETs)
P
Privacy notice (information notice)
P
Processing
P
Processor
P
Profiling
P
Protected health information (PHI)
P
Protocol
P
Provider and deployer (AI Act roles)
P
Pseudonymisation
P
Purpose limitation
Q
Qualified Person for Pharmacovigilance (QPPV)
Q
Quality management system (QMS)
Q
Quasi-identifier
Q
Query (clinical data query)
R
Randomisation and trial supply management (RTSM)
Click a letter to view all its definitions
Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.

Term of the Day

Natural history study

A natural history study is a preplanned observational study intended to track the course of a disease over time, identifying demographic, genetic, environmental and other variables that correlate with its development and outcomes in the absence of intervention, or under standard of care. Designs may be retrospective (chart review of existing records) or prospective (longitudinal follow-up of a cohort or registry).

Natural history data is particularly important in rare and paediatric diseases, where randomised placebo-controlled trials may be infeasible or unethical. The FDA (guidance on rare disease natural history studies, 2019) and the EMA accept well-designed natural history studies to define endpoints and biomarkers, identify patient subgroups, estimate sample sizes and, in some cases, serve as external or historical control arms for single-arm trials supporting orphan products.

Because they are non-interventional, natural history studies fall outside the CTR and are governed by national law (for example France's MR-003 or MR-004 reference methodologies) and by the GDPR. They typically involve secondary use of medical records, long-term follow-up, genetic data and small populations in which anonymisation is rarely achievable, so pseudonymisation, a DPIA and a robust research legal basis under Art. 9(2)(j) are essential. Registries maintained by patient organisations or academic consortia raise additional questions of joint controllership and data access governance.

A

ALCOA+

ALCOA+ is a set of principles used to describe trustworthy data throughout their lifecycle. The letters stand for attributable, legible, contemporaneous, original and accurate; the plus adds complete, consistent, enduring and available. In clinical research, these principles help teams assess whether records reliably show what happened, when and by whom.

Key takeaways

  • Integrity concerns the complete data lifecycle.
  • A readable export is not always a complete record.
  • Apply controls proportionately to data risk.

The Nine ALCOA+ Principles

The MHRA data integrity guidance explains the terminology. The TGA’s data integrity guidance also connects reliable records with the controls used to create, modify and retain them.

PrinciplePractical question
AttributableWho performed the activity?
LegibleCan the record be read?
ContemporaneousWas it recorded when it happened?
OriginalIs this the first record or a verified copy?
AccurateDoes it reflect the observation correctly?
CompleteAre relevant records and metadata retained?
ConsistentDo sequence and timing make sense?
EnduringWill the record remain usable?
AvailableCan authorised reviewers retrieve it?

Why It Matters for Data Protection

Our recommended approach is to assess integrity and confidentiality together. Preserve necessary audit information without granting every user access to identifiable participant records. Define account ownership, correction procedures and retrieval tests before deployment. ALCOA+ is a useful assessment vocabulary, not a substitute for evaluating applicable GCP requirements or electronic-record rules such as 21 CFR Part 11.

Hypothetical example: A site corrects an incorrectly entered visit date. Its process preserves the earlier value, records the person making the correction and explains the reason. The monitor can review that history without receiving unnecessary participant identifiers.

Frequently Asked Questions

Is ALCOA+ a certification?

It describes integrity principles, not a standalone product certification.

Does a PDF export prove integrity?

Not by itself. Consider context, metadata and the underlying record history.

How does it relate to ICH E6(R3)?

Use it alongside a study’s GCP data-governance assessment, rather than as a replacement checklist.

Related reading: source data verification, data quality, computerised system validation. For practical support, see quality assurance.

Updated: 27 October 2026