The Terminus Notes

Methods · how to read this resource

How to read this resource

A short guide to the evidence grades, the kinds of study behind them, and the vocabulary — so the monographs are useful whether or not you arrived already fluent.

Two kinds of page

Everything here is one of two things, and the page tells you which at the top. Evidence pages (monographs) are neutral, graded, and sourced — they report what the literature shows, in no particular person's voice. Opinion is clearly labelled, visually distinct, and may argue a position about the evidence — but never advocates using, dosing, or obtaining anything.

If you are ever unsure which you are reading, look for the label. The two never share a header.

The evidence grades

Each monograph grades every claim separately, by how much trustworthy human evidence stands behind it. The indicator is monochrome on purpose: it measures certainty, not whether a compound is good or worth using. More filled cells mean more human evidence — not a stronger recommendation.

Robust human. Multiple controlled human trials, consistent, published in full.
Limited human. A single RCT, or small / short / open-label trials.
Topical/local only. Human evidence for a local route; systemic claims unsupported.
Preclinical only. Animal and/or in-vitro data; no human trials.
Mechanistic. A plausible mechanism, no direct outcome data.
Contested / negative. Off the ladder: tested, and mixed or negative — not untested.
(topline). Hatched: announced but not yet peer-reviewed; held at the Limited human cap.

Two things to read off the meter: how many cells are filled (how much evidence) and their texture (solid = published; hatched = announced but unverified). The written reason beside every grade always carries the full meaning.

Study types, ranked by what they can show

Not all evidence is equal. As a rough hierarchy, from strongest to weakest for establishing that an effect is real:

  1. 1Randomised controlled trial — randomly assigns treatment vs control; the strongest common design. Stronger still when double-blind and placebo-controlled.
  2. 2Open-label trial — everyone knows who got what; useful but more prone to bias.
  3. 3Preclinical — cells (in vitro) or animals; does not automatically transfer to humans.
  4. 4Mechanism — a reason to expect an effect, which is not the same as observing one.

A systematic review or meta-analysis sits above individual trials when it pools good ones — and below them when it pools weak ones. Quality of the inputs decides.

Why "topline" matters

A topline result is a headline number a sponsor releases before the full data are peer-reviewed. It can be genuinely promising and still be unverifiable: the analysis population, the handling of dropouts, the confidence intervals, and the adverse-event tables are exactly what a press release omits and what review exists to check.

A result you cannot yet inspect is a result you cannot yet rely on, however large the effect looks. That is why topline evidence is flagged and capped at Limited human until it is published in full — the grade is allowed to lag the news.

Absence of evidence

When a monograph says "no human trials exist," that is a finding, not an oversight. For many popular compounds the honest answer is that the human evidence simply isn't there yet — and a resource that reports this plainly is more useful than one that fills the silence with mechanism or anecdote.

"No evidence of harm" and "evidence of no harm" are not the same statement. The first often just means no one has looked.

Glossary

Plain definitions of the terms used across the monographs. Definitional only — defining a term is not instruction in using a compound.

Adverse eventClinical
Any unfavourable medical occurrence in a study participant, whether or not it is judged to be caused by the treatment.
BioavailabilityPharmacology
The fraction of an administered dose that reaches the bloodstream in active form.
Certificate of Analysis (COA)Analytics
A lab document reporting a sample's measured identity and purity against stated methods. Its worth depends on which tests were run, by whom, and on which sample — a COA is only as good as its provenance.
Clinical trial phasesClinical
Phase 1 tests safety and pharmacokinetics in a small group; Phase 2 explores efficacy and dose; Phase 3 confirms efficacy and safety in large controlled trials intended to support approval.
ContraindicationClinical
A situation or condition in which a compound should not be used because the risk outweighs any benefit.
Dose–responsePharmacology
The relationship between dose size and effect size. A dose-dependent effect changes predictably as the dose changes.
Double-blindClinical
A design in which neither participants nor investigators know who received the active treatment versus placebo, which reduces bias.
EndpointClinical
A predefined outcome a trial measures. The primary endpoint is the main question; secondary and exploratory endpoints are supporting measures with progressively weaker standing.
EstimandClinical
A precise statement of what a trial is trying to estimate — including how events like dropouts are handled — fixed before analysis so a result cannot be quietly reframed afterward.
Half-life (t½)Pharmacology
The time for the amount of a compound in the body to fall by half. It shapes how often something is dosed and how long it lingers.
HPLCAnalytics
High-performance liquid chromatography: a technique that separates a mixture's components to assess purity and quantify what is present.
HRMSAnalytics
High-resolution mass spectrometry: measures molecular mass very precisely, used to confirm a compound's identity.
In vitro / in vivoResearch
In vitro means in an artificial system such as cells in a dish; in vivo means in a living organism. In-vitro findings do not automatically transfer to living systems.
InvestigationalRegulatory
A compound under study in trials that has not received marketing authorisation for the use in question.
LyophilisedAnalytics
Freeze-dried into a dry powder for stability. Such material is later dissolved — reconstituted — before analysis.
Marketing authorisationRegulatory
Formal approval by a regulator (e.g. FDA, EMA, MHRA) permitting a medicine to be marketed for a defined use.
Mechanism of actionPharmacology
How a compound is understood to produce its effect biologically. A plausible mechanism is not, by itself, evidence of a clinical outcome.
Meta-analysisClinical
A statistical method that combines results from several studies to estimate an overall effect.
Open-labelClinical
A trial in which participants and investigators know which treatment is given. Useful, but more prone to bias than blinded designs.
Pharmacodynamics (PD)Pharmacology
What a compound does to the body — its effects, and the mechanisms behind them.
Pharmacokinetics (PK)Pharmacology
What the body does to a compound — how it is absorbed, distributed, metabolised, and eliminated.
Placebo-controlledClinical
A trial that compares the active compound against an inert placebo, isolating the compound's effect from expectation and natural change.
PreclinicalResearch
Research done before human trials, in cells or animals.
Purity vs identityAnalytics
Identity is whether a sample is the compound it claims to be; purity is how much of it is that compound versus impurities. A sample can be correctly identified yet impure, or pure yet misidentified.
Randomised controlled trial (RCT)Clinical
A study that randomly assigns participants to treatment or control — the strongest common design for establishing whether an effect is real.
Receptor agonist / antagonistPharmacology
An agonist activates a receptor to produce a response; an antagonist binds without activating it, blocking the response.
ReconstitutionAnalytics
Dissolving a lyophilised (freeze-dried) powder in a solvent to form a solution. This resource defines the term but does not provide reconstitution instructions.
Scheduling / controlled substanceRegulatory
Legal classification of a substance under drug-control law. It varies by country and determines how the substance may lawfully be handled.
Systematic reviewClinical
A structured review that gathers and appraises all relevant studies on a question using predefined methods.
Topline resultClinical
An early headline summary of a trial's outcome, released before the full data are peer-reviewed and published. A claim pending verification, not a settled finding.