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The glossary, random text
Glossary
21 CFR Part 11 is a U.S. FDA regulation that defines the criteria for determining when electronic records and electronic signatures are trustworthy, reliable, and equivalent to paper records and handwritten signatures, and establishes requirements for system validation, security, audit trails, and controlled access in FDA‑regulated environments.
21 CFR Part 11
FDA clearance pathway for devices that are "substantially equivalent" to a legally marketed predicate device. Less rigorous than PMA but still requires careful statistical planning.
510(k)
FDA determination that a device is substantially equivalent to a predicate.
510(k) Clearance
CDISC standard for analysis-ready datasets.
ADaM (Analysis Data Model)
Trial design that allows pre-planned modifications based on interim data analysis while maintaining trial integrity and statistical validity.
Adaptive Design
Modifying eligibility criteria during a trial to focus on patient populations most likely to benefit.
Adaptive Enrichment Design
Any unfavorable medical occurrence in a trial participant, regardless of whether it's related to the investigational treatment. AEs range from mild (headache, nausea) to life-threatening events and must be systematically collected, coded (using MedDRA), and reported per protocol and regulatory requirements. The key distinction: an AE is any bad outcome during the trial; causality is assessed separately. Comprehensive AE reporting is critical for FDA safety evaluations.
Adverse Event
Public meeting where independent experts advise FDA on approval decisions. High-stakes; BSC has extensive panel preparation experience.
Advisory Committee (Panel Meeting)
Method for controlling Type I error across multiple interim analyses (e.g., O'Brien-Fleming, Pocock).
Alpha-Spending Function
Case report form with annotations mapping fields to SDTM variables.
Annotated CRF
Historical term (now largely replaced by approval or CRL).
Approvable Letter
Chronological record of all changes to data, providing traceability.
Audit Trail
Statistical approach that incorporates prior information and expresses results as probability distributions. A BSC specialty, increasingly accepted by FDA.
Bayesian Methods
Evaluation weighing a treatment's benefits against its risks.
Benefit-Risk Assessment
Evaluators unaware of treatment assignment when assessing endpoints.
Blinded Assessment
Keeping participants, investigators, or assessors unaware of treatment assignment to reduce bias. "Single-blind" = participants blinded; "Double-blind" = participants and investigators blinded.
Blinding/Masking
FDA program providing intensive interaction and guidance for devices that offer significant advantages over existing treatments.
Breakthrough Device Designation
CE Marking is a mandatory conformity mark for many products sold within the European Economic Area (EEA), indicating that the manufacturer declares compliance with relevant EU health, safety, and environmental protection directives.
CE Marking
CBER (Center for Biologics Evaluation and Research) regulates biological products, including vaccines, blood and blood components, allergenics, tissues, and cellular and gene therapies, to ensure their safety, purity, potency, and effectiveness. Through this regulation, CBER works to protect and enhance public health, including addressing emerging infectious diseases and bioterrorism threats related to biologic products.
Center for Biologics Evaluation and Research (CBER)
CDRH (Center for Devices and Radiological Health) is responsible for protecting and promoting public health by ensuring that medical devices and radiation-emitting products used in the United States are safe, effective, and of high quality. It also provides science-based information about these products and supports innovation by advancing regulatory science and offering predictable, transparent regulatory pathways for device manufacturers.
Center for Devices and Radiological Health (CDRH)
CDER (Center for Drug Evaluation and Research) ensures that safe and effective drugs are available to improve the health of people in the United States, overseeing both prescription and over-the-counter drugs, including many biologic therapeutics and generics. It evaluates drugs before marketing to determine whether their health benefits outweigh known risks and monitors drug safety, quality, and labeling throughout the product lifecycle.
Center for Drug Evaluation and Research (CDER)
Organization developing data standards for clinical research.
Clinical Data Interchange Standards Consortium
Independent committee adjudicating whether clinical events meet endpoint definitions.
Clinical Events Committee
Comprehensive document describing a clinical trial's design, methods, results, and conclusions. Required for regulatory submissions.
Clinical Study Report
Multiple primary endpoints that must all achieve statistical significance for trial success.
Co-Primary Endpoints
Time-to-event analysis accounting for events that preclude the outcome of interest.
Competing Risks Analysis
FDA letter indicating that a submission cannot be approved in its current form. BSC helps clients navigate CRLs with creative re-analysis and redesigned studies.
Complete Response Letter
Single endpoint combining multiple outcomes (e.g., "death, MI, or stroke"). BSC has deep expertise in composite endpoint design.
Composite Endpoint
Probability of achieving statistical significance at the end of a trial, given interim data.
Conditional Power
Range of values within which the true treatment effect likely falls (typically 95% CI).
Confidence Interval
Centralized laboratory for consistent assessment of images, biomarkers, or other measurements.
Core Lab
Centralized, independent review of imaging to reduce variability and bias.
Core Lab Assessment
Trial where participants receive both treatment and control in sequence, serving as their own controls.
Crossover Design
Independent committee that reviews interim data and can recommend stopping a trial for safety, efficacy, or futility.
Data Safety Monitoring Board/Data Monitoring Committee
Technical documents defining dataset structures and derivations.
Data Specifications
Point when clinical trial database is finalized and no further changes are allowed.
Database Lock
The Database Lock Date is a critical milestone in clinical trials, marking the point at which data collection is finalized and the dataset is considered stable for analysis. This date is essential for ensuring the integrity of the trial results, as no further changes or additions to the data are permitted after it is locked. At BSC®, we understand the importance of this process in maintaining compliance and producing reliable outcomes for regulatory submissions.
Database Lock Date
FDA pathway for novel, low-to-moderate risk devices without a predicate. Establishes a new device classification.
De Novo
Machine-readable metadata file describing datasets in a regulatory submission.
Define.xml
Inadequacy of a medical device that could lead to an adverse event.
Device Deficiency
Visual acuity testing protocol used in ophthalmology trials.
Early Treatment Diabetic Retinopathy Study
Magnitude of the difference between treatment and control that the trial is designed to detect.
Effect Size
Measures of treatment benefit or effectiveness.
Efficacy Endpoints
Electronic form for collecting clinical trial data. eCRFs are now more common than paper-based CRFs.
Electronic Case Report Form
Standardized format for regulatory submissions accepted by FDA, EMA, and other agencies.
Electronic Common Technical Document
System for collecting clinical trial data electronically.
Electronic Data Capture
Process of recruiting and registering participants in a clinical trial.
Enrollment/Accrual
Trial designed to show that two treatments have similar effects.
Equivalence Design
The European Medicines Agency (EMA) is a decentralised agency of the European Union responsible for the scientific evaluation, supervision, and safety monitoring of medicines for human and veterinary use across the EU and European Economic Area. It aims to protect and promote public and animal health by assessing marketing authorisation applications, monitoring the safety of medicines throughout their lifecycle (pharmacovigilance), and providing scientific guidance to support the development of new therapies, including for rare diseases and paediatric populations.
European Medicines Agency
Hypothesis-generating measures not intended for confirmatory conclusions.
Exploratory Endpoint
An FDA guidance document is a formal public document that explains the Food and Drug Administration’s current thinking on a particular topic, such as product development, clinical studies, or submission content, and is meant to provide recommendations rather than legally binding requirements for industry and FDA staff.
FDA Guidance Document
An FDA Pre-Submission (often called a “Pre-Sub”) is a voluntary mechanism within the FDA’s Q-Submission program that allows a sponsor to request written feedback and/or a meeting with the FDA to obtain Agency input on planned studies or regulatory submissions (for example, IDE, 510(k), De Novo, PMA) before filing the formal application.
FDA Pre-Submission
For medical devices, a feasibility study is a clinical investigation, usually conducted under an IDE, designed to gather preliminary information on the safety and potential effectiveness of a near-final or final device design in order to plan an appropriate pivotal study. It typically enrolls a limited number of subjects and, by itself, is not intended to provide definitive evidence of safety and effectiveness for marketing authorization.
Feasibility Study
A first-in-human study is a type of early clinical study in which a device for a specific indication is evaluated in human subjects for the first time, often as part of an early feasibility study under an IDE. These studies focus on initial clinical safety and device functionality in a very small number of participants before larger feasibility or pivotal trials are undertaken.
First-in-Human Study
Follow-up is the period after a participant is enrolled or completes an intervention during which investigators continue to collect outcome and safety data, often at predefined visits or time points, to assess both short‑term and long‑term effects. It can also refer to the set of activities (such as visits, tests, and contacts) used to maintain contact with participants and obtain these data over time.
Follow-up
Frequentist methods are statistical approaches that interpret probability as the long‑run frequency of events under repeated sampling, and they base inference on the sampling distribution of estimators (for example, using p‑values, confidence intervals, and hypothesis tests). In clinical trials, frequentist methods typically control error rates such as type I and type II error using fixed decision rules, without assigning prior probabilities to parameters as in Bayesian methods.
Frequentist Methods
The Full Analysis Set is the primary analysis population defined in ICH E9 as being as complete and as close as possible to the intention‑to‑treat (ITT) ideal, typically including all randomized participants with minimal exclusions. Limited exclusions may be allowed for clear, pre‑specified reasons such as failure to meet major entry criteria, never receiving any study treatment, or having no post‑randomization data.
Full Analysis Set
A futility analysis is an interim evaluation in an ongoing clinical trial that assesses whether it is unlikely the study will achieve its primary objective if it continues as planned. If the accumulating data show a very low probability of ultimately demonstrating the targeted treatment effect (for example, low conditional or predictive power), the trial may be stopped early for futility to avoid exposing participants to an ineffectual intervention and to conserve resources.
Futility Analysis
Good Clinical Practice is an international ethical and scientific quality standard for the design, conduct, recording, and reporting of clinical trials and other research involving human subjects, ensuring that participants' rights, safety, and welfare are protected and that trial data are credible and reliable.
Good Clinical Practice
Good Laboratory Practice is a quality system for the organizational processes and conditions under which nonclinical health and environmental safety studies are planned, performed, monitored, recorded, reported, and archived, with the goal of ensuring the integrity, traceability, and reproducibility of laboratory data used for regulatory decision-making.
Good Laboratory Practice
Good Manufacturing Practice refers to regulations and guidelines that require pharmaceutical, biologic, and medical product manufacturers to have properly controlled facilities, equipment, procedures, and documentation so that products are consistently produced and controlled according to quality standards, thereby safeguarding patient and consumer safety.
Good Manufacturing Practice
Health Canada is the federal department of the Government of Canada responsible for helping Canadians maintain and improve their health by setting national health policy and regulating many aspects of the health system. It oversees the safety and efficacy of drugs, medical devices, and other health products; helps uphold national standards for universal health coverage; and works with provinces, territories, and other agencies such as the Public Health Agency of Canada to protect public health and ensure access to high‑quality health services.
Health Canada
Statistical model accounting for clustering or nesting (e.g., patients within sites, repeated measures within patients). BSC uses these to handle surgeon/site variability.
Hierarchical (Mixed-Effects) Model
Using data from previous studies as a comparison group (when concurrent controls aren't feasible).
Historical Controls
Pathway for devices intended to treat conditions affecting fewer than 8,000 patients per year.
Humanitarian Device Exemption
ICH E3 is the International Council for Harmonisation (ICH) guideline on the structure and content of clinical study reports, providing a standardized format and level of detail so that a single core report of an individual clinical trial is clear, complete, and acceptable to regulatory authorities in all ICH regions.
ICH E3
ICH E6 is the International Council for Harmonisation (ICH) guideline on Good Clinical Practice (GCP), setting the ethical and scientific quality standard for the design, conduct, monitoring, recording, and reporting of clinical trials involving human participants to protect their rights, safety, and well-being while ensuring reliable trial data.
ICH E6
ICH E9 is the International Council for Harmonisation (ICH) guideline on statistical principles for clinical trials, providing globally harmonized guidance on the design, conduct, analysis, and interpretation of clinical studies so that evidence on the efficacy and safety of investigational products is reliable, interpretable, and acceptable to regulators worldwide.
ICH E9
ICH E9(R1) is an addendum to the ICH E9 guideline that introduces the estimand framework, providing a structured way to define exactly what treatment effect a clinical trial aims to estimate and how events like treatment discontinuation or rescue medication use are handled in that definition.
ICH E9(R1)
Prior distribution incorporating meaningful prior knowledge (from historical data, literature, etc.).
Informative Prior
Document explaining trial procedures and risks that participants sign before enrolling.
Informed Consent Form
Independent body reviewing clinical trial ethics and participant protection.
Institutional Review Board/Ethics Committee
Compilation of efficacy data across multiple studies.
Integrated Summary of Effectiveness
Compilation of safety data across multiple studies for a product.
Integrated Summary of Safety
The ITT analysis set includes all randomized participants, analyzed according to the treatment group to which they were originally assigned, regardless of whether they received treatment, adhered to the protocol, or completed follow‑up. This approach preserves the benefits of randomization and aims to reflect real‑world effectiveness by avoiding bias introduced by excluding non‑adherent or withdrawn participants.
Intent-to-Treat Analysis Set
Event occurring after treatment initiation that affects interpretation of outcomes (e.g., treatment discontinuation, use of rescue therapy).
Intercurrent Event
Pre-specified analysis of accumulating data before study completion, typically to assess stopping for efficacy, harm, or futility. Interim analyses must be carefully planned: timing (information fraction), what will be analyzed, decision criteria, and who remains blinded. Key challenge: multiple looks at data inflate Type I error—requires alpha-spending function or Bayesian monitoring boundaries. Number and timing of IAs trade information vs. flexibility. DSMB typically reviews unblinded interim data while the sponsor remains blinded. BSC designs interim analysis strategies, balancing early stopping benefits against statistical and operational complexity.
Interim Analysis
Organization developing harmonized pharmaceutical guidelines (ICH E9 covers statistical principles).
International Council for Harmonisation
FDA approval required before conducting a clinical trial with a significant-risk investigational device in the U.S.
Investigational Device Exemption
Document summarizing clinical and non-clinical data about an investigational product.
Investigator's Brochure
Simple imputation method using the last observed value (often criticized, less preferred).
Last Observation Carried Forward
Participants who cannot be contacted or assessed during the trial.
Lost to Follow-up
Composite endpoint in cardiovascular trials, typically including death, MI, and stroke.
Major Adverse Cardiac Events
Standardized terminology for coding adverse events.
Medical Dictionary for Regulatory Activities
Statistical method for combining results across multiple studies.
Meta-Analysis
Development of novel statistical approaches for unprecedented challenges.
Methodological Innovation
Smallest treatment effect that would be meaningful to patients or clinicians.
Minimum Clinically Important Difference
The probability of a data point being missing is unrelated to any observed or unobserved values.
Missing Completely at Random (MCAR)
Observations not collected due to dropout, loss to follow-up, or incomplete forms.
Missing Data
Missing data mechanism where missingness depends on the unobserved values themselves (more problematic).
Missing Not at Random
Missing data mechanism where missingness depends on observed data but not unobserved outcomes.
Missing at Random
A Modified Intent‑to‑Treat (mITT) analysis set is a prespecified variation of the ITT principle in which some randomized participants are excluded based on additional criteria, such as not receiving any study medication or lacking key baseline or post‑baseline measurements. mITT sets are widely used but heterogeneous; they can introduce bias if exclusions are subjective or not clearly justified, so regulatory and methodological guidance recommends that any modifications be minimal, explicit, and scientifically defensible.
Modified Intent-to-Treat Analysis Set
Statistical technique that fills in missing values multiple times to account for uncertainty.
Multiple Imputation
The NHC is responsible for formulating and implementing national health laws, regulations, and policies, planning public health services, and coordinating disease prevention and control, including major outbreaks such as COVID‑19. Its duties also include supervising medical providers, managing basic public health services, guiding health system reforms, and overseeing family planning, food safety standards, and traditional Chinese medicine through subordinate agencies.
National Health Commission of the People’s Republic of China
The National Medical Products Administration (NMPA) is China’s central regulatory authority responsible for overseeing the safety, quality, and efficacy of drugs, medical devices, and cosmetics throughout their life cycle, from development and registration to post‑market surveillance. It operates under the State Administration for Market Regulation and performs functions similar to the U.S. Food and Drug Administration, including drafting and enforcing regulations, setting technical and quality standards (such as GMP, GCP, and device registration rules), inspecting manufacturing and R&D facilities, managing adverse event reporting, and coordinating international regulatory cooperation to protect public health and support innovation.
National Medical Products Administration
Questionnaire measuring neck pain-related disability.
Neck Disability Index
Trial designed to show that a new treatment is not meaningfully worse than an existing treatment (rather than proving superiority).
Non-Inferiority Design
Prior distribution expressing minimal prior knowledge, letting data drive conclusions.
Non-Informative (Vague) Prior
A notified body is an independent organization designated by an EU Member State (or certain associated countries) to assess whether specific products meet all applicable regulatory and safety requirements before they are placed on the market, often as part of the CE marking process. In medical devices and other regulated sectors, a notified body reviews technical documentation and quality systems, performs conformity assessments required by EU legislation, and issues certificates that allow manufacturers to affix the CE mark and market their products in the European Economic Area.
Notified Body
Assumption that there is no difference between treatment and control.
Null Hypothesis
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