The Vasoconstrictor Assay ( <scp>VCA</scp> ): Then and Now
Bibliographic record
Abstract
The US FDA introduced a Guidance in 1995 which described the application of the vasoconstrictor assay (VCA), also known as the human skin blanching assay (HSBA), as a surrogate measure to assess the bioequivalence (BE) of topical corticosteroid products. This procedure has proved valuable to Sponsors and Regulatory authorities, enabling the approval of generic topical corticosteroid products in global markets around the world whereby clinical trials in patients have been successfully circumvented. Since its introduction, the required procedures, applications, implementations, and data processing have remained largely unchanged. However, over the years, various issues have arisen, and which have remained largely unresolved. These include, among others, the use of visual or instrumental assessment of the blanching response, fitting of the pharmacodynamic response data, influence of circadian rhythm, use of occlusion to enhance the blanching response, and the appearance of erythema at application sites. A further aspect of the VCA is included in this chapter to describe its use to determine the potency of topical corticosteroid products and that the E max is a more appropriate parameter which correlates with product potency ranking as opposed to the ED 50 . Intriguingly, a European regulatory agency allowing the use of the VCA for BE of topical corticosteroid products has stipulated that in addition to the comparator reference product, two additional comparators be included, one to be more potent and another less potent than the innovator product.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.014 | 0.012 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".