Dienogest for endometriosis
In a randomized trial of women with endometriosis, dienogest (2 mg/day) significantly improved endometriosis-associated pelvic pain (VAS mean difference 6.0, 95% CI 4.9-7.1) and HRQoL, comparable to a combined oral contraceptive.
Hypothesized mechanism
Mechanism not yet characterized in the substrate.
This is the model’s proposed mechanism from the sources on file, not a demonstrated causal pathway. How well the published record supports it is reflected in the rigor and plausibility dimensions of the score, and traced to the verbatim sources at the foot of the page.
How the score was reached, for this pair
The composite score is the sum of five dimensions, each scored 0 to 2 by the model from the evidence on file. Below is the sub-score this specific pair received on each, with what that dimension measures. It scored 5 of 10 overall, a emerging reading, from a direct rated emerging in strength.
The model’s overall reasoning for this pair is the summary at the top of the page, and the mechanism it proposed is in the section above.
Scored for women. Female representation not stated — applicability to women uncertain (flagged for full text). (band F4, ×0.75).
Corroboration
Only a single claim is provided, an Open Targets database entry stating DIENOGEST is an approved clinical candidate for endometriosis. No independent mechanistic lines are described, so there is no convergence to assess.
Rigor
The sole claim is a regulatory/database status entry from Open Targets, not a mechanistic model (human, animal, or in-vitro). No experimental data of any kind is cited.
Specificity
The claim identifies DIENOGEST as a small-molecule clinical candidate but provides no information about its molecular target or mode of action on endometriosis. No specificity of drug-target action can be evaluated.
Plausibility
DIENOGEST is noted as having reached maximum clinical stage APPROVAL for endometriosis, which implies an established target-phenotype fit, though no mechanism is described in the claim. The approval status lends partial plausibility without explicit mechanistic support.
Consistency
With only one claim and no described mechanistic signals, there is nothing to compare for directional agreement. Consistency cannot be established from a single database entry.
Scored for women. Evidence generated in women (female population, ~100% female). (band F1, ×1.00).
Corroboration
The substantive efficacy data come from a single RCT (claims 2-10). The 'Medical management of endometriosis' source (claims 11-12) merely references the same trial rather than providing independent corroboration. A single primary study scores 0.
Rigor
The evidence is a randomized clinical trial comparing dienogest to a combined oral contraceptive (claims 1-2), which qualifies as RCT-level design. Outcomes include VAS scores, EHP-30 HRQoL, and validated B&B severity profiles.
Specificity
Both the drug (dienogest, 2 mg/day) and the condition (endometriosis-associated pelvic pain) are named directly and repeatedly (claims 2, 4, 5).
Plausibility
No mechanism of action is described in any claim; the evidence is purely clinical-outcome based with no statement of how dienogest acts on endometriotic tissue or pain pathways.
Consistency
Results derive essentially from one trial, so cross-study consistency cannot be assessed; within the trial, dienogest consistently improved VAS and HRQoL and was comparable to COC across multiple measures (claims 2, 6, 7-10).
Regulatory & development status
Where this candidate sits in the US regulatory landscape: whether the drug is already FDA-approved for endometriosis (on-label) or approved for something else (off-label), whether the molecule is available as a generic or a single-source brand still under patent, and how far it has been studied as a therapy for this condition. Each fact is drawn from a public US source and reported beside the score; none of it is folded into the score.
This is descriptive context, not regulatory advice. It maps the landscape a 505(b)(2)route would build on (an already-approved active ingredient proposed for a new indication), but it is not a 505(b)(2) viability assessment, and says nothing about whether any particular development path is advisable. “Approved” means FDA-approved (US); approvals elsewhere are out of scope.
Approval relationship Off-label
Read from the drug’s FDA label via DailyMed, the US National Library of Medicine’s label repository. A label is only counted when it carries an FDA-approved marketing category (an NDA, ANDA, or biologic BLA); dietary supplements, homeopathics, and OTC-monograph products are not FDA-approved drugs and are excluded.
For this pair. The drug has an FDA-approved label, but for a different indication, so using it for this condition would be off-label.
Generic & patent supply Only in combination products
Read from the FDA Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations), using single-ingredient products only so that patents on novel branded combination formulations are never attributed to the base molecule.
For this molecule. Appears only inside combination products, not as a stand-alone single-ingredient product.
Clinical-trial stage, for this condition Phase 3
Read from ClinicalTrials.gov (US National Library of Medicine). A trial only counts when the drug appears as an experimental or active-comparator intervention in an interventional study of this condition; mechanistic, drug-interaction, post-marketing (Phase 4), and comparator-background uses are excluded, so this reflects the drug being tested as a therapy for endometriosis.
For this pair. Studied in 12 qualifying interventional trials · highest stage reached Phase 3 · active trial(s).
Layers not covered for this pair
Not covered for this pair. This layer holds documented sex-specific pharmacokinetics for a limited set of drugs, and this compound is not among them yet. A blank here means the drug is not covered by the layer, not that no sex difference exists.
More on the sex-specific pharmacokinetics layer and its sources →Not covered for this pair. The cycle-phase layer is seeded for the strongest-evidence cases so far (PMDD), and this pair is not among them yet. A blank here means the pair is not covered by the layer, not that the effect was found to be phase-independent.
More on the cycle-phase layer and its sources →Source evidence · what the pipeline ingested
These are the sources the pipeline ingested to detect and score this signal, the published literature the model actually read, each tagged by study type. Where the model combined findings the claim is marked as a synthesis (S), and where the literature disagrees the contradiction is shown (!).
Every source below belongs to this signal’s evidence arm, Direct research. Whel reads each drug-condition pair through four such arms, each held to its own inclusion bar; a signal is surfaced through one of them.
- 1Both treatments improved the mean VAS score for endometriosis-associated pelvic pain significantly: mean difference 6.0 [95% confidence interval (CI) 4.9-7.1; p < 0.0001] in the dienogest group and 4.54 (95% CI 3.1-5.9; p < 0.0001) in the COC group; the difference between them was not significant (p = 0.111). PubMed · PMID 34826668 ↗
- 2Both treatments improved the mean VAS score for endometriosis-associated pelvic pain significantly: mean difference 6.0 [95% confidence interval (CI) 4.9-7.1; p < 0.0001] in the dienogest group and 4.54 (95% CI 3.1-5.9; p < 0.0001) in the COC group; the difference between them was not significant (p = 0.111). PubMed · PMID 34826668 ↗
- 3Both treatments improved the mean VAS score for endometriosis-associated pelvic pain significantly: mean difference 6.0 [95% confidence interval (CI) 4.9-7.1; p < 0.0001] in the dienogest group and 4.54 (95% CI 3.1-5.9; p < 0.0001) in the COC group; the difference between them was not significant (p = 0.111). PubMed · PMID 34826668 ↗
- 4Dienogest (2 mg/day) is comparable to the COC Yasmin for the relief of endometriosis-associated pelvic pain PubMed · PMID 34826668 ↗
These are the verbatim sources the pipeline surfaced and read; they may not be the full published record for a pair, and the score reflects the strength and agreement of the evidence rather than its volume. The strength of these source types is what the rigor dimension of the score reads off. MATRIX, sex-specific pharmacokinetics, and cycle phase are separate layers the pipeline does not ingest, external cross-references reported beside the score, and they link to their own sources in their sections above.
The primary sources and pipelines this evidence is drawn from →