Research Gap Map
Where the evidence is thin — open questions across six research categories, framed as funding opportunities.
This map catalogues research gaps — places where the published evidence is thin, fragmented, or missing entirely — across the six categories of the ASH research library. Each row describes what is not yet known and why closing that gap would be valuable as a funded research project.
These entries are open questions for funders, grant programs, and investigators. They are not treatment recommendations, efficacy claims, or statements that any use is established. The American Society of Hirudotherapy is a research-infrastructure nonprofit; nothing here should be read as clinical advice or as a claim that leech therapy cures or treats any condition.
How to read this map
- Gap — the open question: what the literature does not yet answer.
- Current evidence level — the highest tier of evidence that exists today, using the same GRADE-aligned scale applied across the site. A low level signals a wider gap.
- Why it matters for funding — the research-infrastructure case for investing in this gap.
- On numbers: any count or quantity below is labeled illustrative and describes structure, not a verified tally of papers.
Illustrative framing. Counts such as “few RCTs” or “no systematic review” are illustrative characterizations of the evidence landscape used to structure a research agenda. They are not presented as exact, audited figures.
Salivary pharmacology
How individual salivary compounds behave — dosing, kinetics, and comparative potency.
Dose-response characterization for individual recombinant salivary compounds remains thin; few standardized pharmacokinetic models exist.
Why it matters for funding: Standardized PK/PD models would let later studies compare doses on a common scale — foundational infrastructure for any downstream program.
Comparative potency across leech species and across salivary fractions is rarely measured under harmonized assay conditions.
Why it matters for funding: A harmonized assay reference set is a reusable resource that reduces duplicated effort across labs.
Antimicrobial resistance
Activity of salivary antimicrobial peptides against contemporary resistant isolates.
Whether salivary antimicrobial peptides retain activity against contemporary resistant clinical isolates is largely uncharacterized.
Why it matters for funding: Resistance-panel screening is a discrete, fundable deliverable with clear go / no-go decision value for a research pipeline.
No systematic review currently aggregates the scattered in-vitro antimicrobial-peptide literature into a single evidence map.
Why it matters for funding: A systematic review is a low-cost, high-credibility output that defines where primary research is most needed.
Clinical trials
Trial design, statistical power, and agreed outcome measures across studied uses.
Several conditions in the literature rest on small or unblinded studies; adequately powered, blinded randomized controlled trials are sparse.
Why it matters for funding: Funding a single well-designed RCT in a defined indication is the clearest path from preliminary signal to interpretable evidence.
Standardized, validated outcome measures and core outcome sets are not yet agreed across the field, complicating cross-study comparison.
Why it matters for funding: A core-outcome-set consensus project is inexpensive and makes every future trial more comparable and poolable.
Drug development
Expression, purification, formulation, and stability of candidate compounds.
Scalable recombinant expression and purification routes for many candidate salivary proteins are not yet established or published.
Why it matters for funding: Process-development grants de-risk the supply bottleneck that otherwise blocks all later translational work.
Formulation and stability data for isolated compounds are limited, leaving open how candidates behave outside whole-saliva context.
Why it matters for funding: Stability and formulation studies are well-scoped, milestone-driven work suited to staged funding.
Genomics & proteomics
Functional annotation and shared reference resources for sequence and proteome data.
Functional annotation lags behind sequence data: many predicted salivary-gland gene products have no experimentally confirmed function.
Why it matters for funding: Functional-genomics annotation is a reusable database asset that compounds in value across the whole field.
Cross-species comparative proteomics is fragmented; no shared reference proteome ties findings across laboratories together.
Why it matters for funding: A shared reference proteome is classic research infrastructure with broad, long-lived utility.
Safety & infection control
Prospective surveillance, registries, and long-term adverse-event documentation.
Prospective surveillance data on Aeromonas and other infection rates under modern infection-control protocols are limited.
Why it matters for funding: A prospective safety registry generates the denominator data that every risk discussion currently lacks.
Long-term and rare adverse-event signals are under-documented; no standing registry aggregates them systematically.
Why it matters for funding: Registry infrastructure is fundable, durable, and directly improves the evidence base for safety domains.
Why safety gaps matter most
Safety-domain gaps — infection surveillance, registry coverage, and long-term adverse-event documentation — are listed alongside efficacy questions on purpose. Closing a safety gap does not depend on demonstrating benefit; it strengthens the evidence base regardless of outcome, which makes safety infrastructure an unusually robust target for research funding. None of this implies any use is recommended; the goal is honest characterization of what is and is not known.
Related pages
How Evidence Is Graded
The GRADE-aligned scale used to assign each gap its current evidence level.
See the framework →