Open Research Questions
Forty-plus unresolved scientific and clinical questions in hirudotherapy — the intellectual honesty that grounds an evidence-based medical society
Last updated: June 18, 2026
Where open questions intersect the evidence registries
The questions below are scoped against the ASH RCT library (169+ trials catalogued) and the condition atlas (199+ entries spanning Tier A FDA-cleared, Tier B off-label evidence, and Tier C investigational). Each open question identifies a specific gap in trial design, dosing standardization, patient stratification, or mechanism attribution.
Why a Medical Society Should Say 'We Don't Know'
The most-cited papers in medicine often include explicit statements of uncertainty. Cochrane reviews routinely conclude 'low-certainty evidence' or 'insufficient data for firm conclusions.' GRADE working group methodology requires explicit confidence ratings. The willingness to acknowledge gaps is the marker of a serious evidence-based discipline — not the marker of weakness, but of intellectual maturity.
This page catalogues 40+ unresolved questions in hirudotherapy research, organized by category (clinical effectiveness, mechanism, dosing, biomarkers, regulatory, patient stratification). Each question identifies (a) why it matters clinically or scientifically, (b) what evidence currently exists, (c) what's missing, and (d) the research design that would resolve it. This list is a living document — updated as questions are resolved and new ones emerge.
Important: Open Research Questions on this page are NOT clinical recommendations. They identify gaps in evidence that the field acknowledges. Patient-care decisions should be based on existing best-available evidence (see Clinical Evidence Hub) and individual clinical judgment, not on speculation about unresolved questions.
42 open research questions across 12 categories
Comparative Effectiveness
How does hirudotherapy compare to standard-of-care alternatives?
What is the comparative effectiveness of hirudotherapy versus intra-articular corticosteroid injection for knee OA at 12-month follow-up?
Why It Matters
Knee osteoarthritis is the largest off-label hirudotherapy application with the strongest published evidence (6 RCTs, Cohen's d = 0.82). Corticosteroid injection is current standard-of-care first-line therapy. Direct comparison would inform clinical decision-making.
Current Evidence
Michalsen 2003 RCT compared leech to topical diclofenac (not corticosteroid). Andereya 2008 compared to hyaluronic acid. No head-to-head with intra-articular corticosteroid.
What's Missing
Direct comparison RCT, n≥200, 12-month primary endpoint, WOMAC pain + function, KOOS quality of life.
Design Proposal
Multicenter randomized open-label superiority trial; primary endpoint WOMAC pain at 12 months; secondary endpoints function, QoL, opioid use, durability of effect.
Does hirudotherapy reduce knee replacement progression rates over 5-year follow-up?
Why It Matters
Knee replacement is performed in ~700,000 U.S. patients/year. Therapies delaying replacement have major economic and quality-of-life value.
Current Evidence
No RCT addresses replacement progression. Cost-effectiveness analyses comparing replacement-delay therapies typically exclude hirudotherapy due to evidence gap.
What's Missing
Long-term (5-10 year) follow-up data from current OA cohorts; pragmatic effectiveness trial with replacement as endpoint.
Design Proposal
Open-label pragmatic effectiveness trial, n≥500, 5-year follow-up; primary endpoint time to knee replacement; analyzed by Kellgren-Lawrence baseline grade.
Is dual-agent prophylaxis (cipro + TMP-SMX) superior to TMP-SMX monotherapy for Aeromonas prevention in microsurgical leech therapy?
Why It Matters
43% environmental ciprofloxacin resistance in A. hydrophila isolates (FCM 2022) raised concerns about cipro monotherapy. Herlin 2017 advocated dual-agent prophylaxis but did not RCT it.
Current Evidence
Observational data favors dual-agent; no RCT.
What's Missing
Non-inferiority RCT or pragmatic effectiveness trial with infection rate as primary endpoint.
Design Proposal
Multicenter cluster-randomized trial across microsurgery centers; primary endpoint Aeromonas infection rate at 4 weeks post-leech therapy.
What is the comparative effectiveness of leech therapy versus standard supportive care for established flap venous congestion that has failed initial salvage attempts?
Why It Matters
Treatment for failed-salvage flap venous congestion is poorly studied — most data is from leech therapy applied early. The role for late-presenting cases is unclear.
Current Evidence
Whitaker 2012 systematic review n=277 mixes early and late applications.
What's Missing
Time-stratified analysis of salvage rates by hours post-anastomosis; comparative outcomes vs. alternative late-rescue interventions (re-anastomosis, alternative thrombolytics).
Design Proposal
Multicenter registry study with stratified time analysis; not feasible as RCT due to ethical constraints.
Does hirudotherapy improve outcomes in chronic venous insufficiency (CVI) versus standard compression therapy?
Why It Matters
CVI affects 25 million U.S. patients; compression is standard of care but adherence is poor. Hirudotherapy is investigationally used for severe cases.
Current Evidence
Case series document anecdotal benefit; no RCT.
What's Missing
RCT of leech-assisted intervention vs. compression alone for VCSS-defined severe CVI.
Design Proposal
Pragmatic effectiveness trial, n≥200, primary endpoint VCSS change at 6 months.
Mechanistic Uncertainties
Which of the 440+ salivary proteins are actually responsible for clinical effects?
What is the relative contribution of mechanical bleeding versus salivary pharmacology to clinical outcomes in microsurgical flap salvage?
Why It Matters
Therapeutic mechanism remains contested. Some clinicians attribute most benefit to mechanical blood-volume removal; others emphasize SGS-mediated anticoagulation and anti-inflammatory effects.
Current Evidence
Mechanical and salivary effects co-occur; cannot be isolated in vivo with leech application.
What's Missing
Comparative studies of mechanical-only bleeding (controlled-suction, scarification) vs. live leech application for flap salvage outcomes.
Design Proposal
Animal model comparing mechanical-bleeding-only vs. leech application; outcome biomarkers tissue oxygenation, perfusion parameters, inflammation markers.
Which 5-10 proteins from the 440+ identified salivary proteome account for ≥80% of clinical pharmacological activity?
Why It Matters
Biotech bioprospecting requires understanding which compounds matter most. Without this knowledge, recombinant 'leech cocktail' development is empirical rather than rational.
Current Evidence
Hirudin, calin, destabilase, eglin family well-characterized; saratin, hirustasin moderately; remaining ~430 proteins largely uncharacterized functionally.
What's Missing
Systematic high-throughput functional screening of recombinant SGS proteins for anticoagulant, antiplatelet, anti-inflammatory, fibrinolytic, antimicrobial activities.
Design Proposal
Multi-omics approach: proteomics + transcriptomics + functional assays; collaboration with academic pharmacology programs.
What is the immunogenicity profile of long-term repeated leech therapy in OA patients receiving 4+ sessions over 1-2 years?
Why It Matters
Repeated exposure to leech salivary antigens has theoretical risk of sensitization. Anaphylaxis to leech SGS is documented but incidence is unclear.
Current Evidence
Mild histamine-mediated local reactions in 37-75% of patients (not allergy). True IgE-mediated anaphylaxis rare but documented.
What's Missing
Prospective immunologic surveillance in multi-session protocols; specific IgE titers, basophil activation tests; identification of major allergens.
Design Proposal
Prospective immunologic cohort study, n=100, immune marker monitoring at baseline + post each session + 12 months.
How does destabilase isopeptidase activity compare to t-PA and tenecteplase in dissolving aged organized thrombi?
Why It Matters
Kurdyumov 2021 demonstrated destabilase dissolves aged human clots in vitro. The clinical translation question is whether the activity matches or exceeds current thrombolytics in clinically-relevant aged-clot models.
Current Evidence
In vitro proof-of-concept (Kurdyumov 2021); no animal model studies; no comparison head-to-head with FDA-approved thrombolytics.
What's Missing
Comparative in vitro plus animal model studies; rabbit/canine thrombosis models with aged clot induction.
Design Proposal
Standard preclinical thrombolytic development pathway: in vitro → ex vivo → small animal → large animal → IND.
What is the in vivo pharmacokinetic profile of leech-derived compounds across the application site to systemic circulation?
Why It Matters
Most clinical models assume primarily local effect, but documented systemic effects (blood viscosity, complement modulation) suggest absorption is non-trivial.
Current Evidence
Hirudin pharmacokinetics characterized through recombinant drug development; native-SGS absorption from leech bite poorly studied.
What's Missing
Pharmacokinetic studies measuring plasma levels of major SGS components after live-leech application in humans.
Design Proposal
Pharmacokinetic substudy nested within OA RCT; serial blood sampling for hirudin, calin, destabilase plasma concentrations.
Optimal Dosing & Application Parameters
How many leeches, how often, for how long?
What is the optimal leech-application frequency for free-flap salvage — every 2 hours, every 4 hours, every 6-8 hours?
Why It Matters
Application frequency directly affects nursing burden, patient comfort, infection risk, and total blood loss. Current protocols vary widely between institutions.
Current Evidence
Whitaker 2012 review notes variation; most protocols apply 'as needed' based on tissue color assessment.
What's Missing
RCT comparing standardized frequencies; surrogate outcomes (tissue oxygenation, flap salvage rate) vs. operational metrics (nursing time, transfusion requirements).
Design Proposal
Multicenter trial randomizing to fixed-frequency protocols vs. as-needed protocols; primary outcome flap salvage at 7 days.
Is a single leech session sufficient for chronic OA, or do repeated sessions provide additive benefit?
Why It Matters
Michalsen 2003 RCT used single-session protocol with sustained benefit at 3 months. Some clinics offer repeat sessions every 6-12 months. Evidence for repeat protocols is weak.
Current Evidence
Single-session data robust; repeat-session efficacy unstudied in RCT.
What's Missing
RCT of single vs. repeat-at-3-months vs. repeat-at-6-months protocols.
Design Proposal
3-arm RCT, n≥150, primary endpoint sustained pain reduction at 12 months.
What is the optimal number of leeches per session for knee OA — 4, 6, 8, or based on joint volume?
Why It Matters
Michalsen 2003 used 4 leeches; Andereya 2008 used 4 leeches; Lauche 2014 used variable. The dose-response relationship is unstudied.
Current Evidence
Convergent on 4-6 leeches; no dose-response RCT.
What's Missing
Dose-finding study before pivotal effectiveness RCT.
Design Proposal
Sequential dose-finding study (2-4-6-8 leeches per session) with WOMAC as response.
What is the optimal duration of leech attachment — until full engorgement (45-90 min) or fixed duration?
Why It Matters
Attachment duration affects blood removal volume, salivary delivery, nursing time, and patient tolerance.
Current Evidence
'Until full engorgement' is convention; physiologic basis is unclear.
What's Missing
Comparative outcomes of fixed-duration (30 min, 60 min) vs. full-engorgement protocols.
Design Proposal
Nested within larger RCT; randomize attachment duration.
Biomarker Development
How do we know it's working — and for whom?
Are there pre-treatment biomarkers that predict response to hirudotherapy in OA?
Why It Matters
Heterogeneous response is common in OA therapies. Predictive biomarkers would enable personalized treatment selection.
Current Evidence
Limited candidate biomarker research (synovial fluid inflammatory markers, structural MRI predictors); no predictive biomarker validated for hirudotherapy.
What's Missing
Biomarker discovery substudy nested within OA RCT.
Design Proposal
Pre-treatment synovial fluid + blood biomarker panel; correlation with WOMAC response at 3 months.
What real-time intra-treatment biomarkers predict successful flap salvage?
Why It Matters
Currently flap salvage decisions are based on tissue color and bleeding-on-pinprick. Real-time perfusion biomarkers could improve decision-making.
Current Evidence
Tissue oxygenation monitoring used in research settings (Rothenberger 2016). Not standard clinical practice.
What's Missing
Validation studies of real-time biomarkers as predictors of 7-day flap salvage.
Design Proposal
Prospective cohort study, real-time biomarker monitoring during leech therapy, primary outcome 7-day flap salvage.
What inflammatory biomarkers (CRP, IL-6, TNF-α) change after leech therapy for OA?
Why It Matters
Mechanism studies require biological readouts. Inflammatory markers would document anti-inflammatory mechanism.
Current Evidence
Limited individual case reports. No systematic biomarker substudy in completed RCTs.
What's Missing
Standardized biomarker substudy with baseline + 1 day + 1 week + 1 month sampling.
Design Proposal
Biomarker substudy nested in next OA RCT.
Regulatory Pathway Questions
How do we expand evidence-supported indications?
What 510(k) pathway exists for expanding the cleared indication beyond 'venous congestion in flaps/grafts/replants'?
Why It Matters
Knee OA has 6 RCTs (Cohen's d = 0.82). The evidence base is stronger than many FDA-cleared devices. The regulatory pathway for indication expansion is not well-defined for biological devices.
Current Evidence
All three medicinal leech 510(k) clearances (K040187/K132958/K140907) cite identical indication language. No precedent for indication expansion via Special 510(k).
What's Missing
FDA Pre-Submission (Q-Sub) consultation on indication expansion pathway; precedent legal/regulatory analysis.
Design Proposal
Engage FDA Pre-Submission program to map the indication-expansion pathway; coordinate with academic medical centers for sponsorship.
What is the impact of CDRH→CBER jurisdiction transfer (December 30, 2024) on future hirudotherapy 510(k) clearances?
Why It Matters
Center jurisdiction affects review standards, post-market surveillance, and labeling conventions. The transfer is recent and its operational implications unclear.
Current Evidence
Transfer announced; new BK tracking numbers issued. Operational impact on future submissions unclear.
What's Missing
FDA Q-Sub consultation to clarify CBER review standards for medicinal leech devices.
Design Proposal
Engage CBER directly through pre-submission consultation.
Does hirudotherapy qualify for FDA Breakthrough Device Designation in any specific clinical context?
Why It Matters
Breakthrough Designation provides accelerated FDA review for devices addressing serious or life-threatening conditions with unmet need.
Current Evidence
Application has not been attempted. Microsurgical flap salvage may qualify (life-altering condition; documented unmet need).
What's Missing
FDA pre-submission analysis; identification of strongest candidate indication.
Design Proposal
FDA Pre-Submission Q-Sub with specific Breakthrough Designation question.
What is the appropriate ICD-10 / CPT / HCPCS coding for hirudotherapy procedures?
Why It Matters
Reimbursement clarity drives clinical adoption. Without clear codes, insurance coverage is inconsistent.
Current Evidence
No specific CPT code; HCPCS C-codes may apply in hospital outpatient settings. Significant institutional variation.
What's Missing
AMA CPT Editorial Panel proposal for hirudotherapy-specific code; CMS-AMA dialogue on coverage.
Design Proposal
ASH coordinate with ASRM and ACS to propose CPT code; advocate via specialty society channels.
Patient Stratification
Which patients benefit most, and which should avoid treatment?
Should hirudotherapy be contraindicated in patients with concomitant DOAC therapy, or is bleeding risk manageable with coordinated dose adjustment?
Why It Matters
Safety-protocols.json currently lists active anticoagulation as absolute contraindication outside microsurgical context. Real-world practice often involves concomitant antiplatelets and DOACs in surgical patients.
Current Evidence
Whitaker 2012 documents 54% of microsurgical protocols use concomitant anticoagulation. Outpatient OA protocols are stricter.
What's Missing
Bleeding-risk dose-coordination protocols; pharmacologic interaction studies.
Design Proposal
Observational registry with DOAC + hirudotherapy bleeding outcomes; specialty pharmacist consultation protocols.
Is hirudotherapy safe in pregnancy for non-cleared indications when maternal benefit may outweigh fetal risk?
Why It Matters
Pregnancy is currently treated as a relative contraindication due to absent data. Maternal conditions like severe leg edema, varicose veins, or post-traumatic conditions may benefit.
Current Evidence
No controlled studies in pregnancy. Theoretical concerns: hirudin placental transfer (MW 7 kDa < 500 Da threshold suggests possible), bleeding risk, infection risk to fetus.
What's Missing
Animal placental transfer studies; voluntary registry of pregnancy exposures.
Design Proposal
Voluntary pregnancy exposure registry coordinated with OB/MFM specialists.
Should pediatric hirudotherapy protocols differ from adult protocols beyond weight-based antimicrobial dosing?
Why It Matters
Pediatric microsurgical reconstruction (replantation, syndactyly correction) sometimes requires leech therapy. Protocols are typically adapted from adult experience.
Current Evidence
No pediatric-specific RCT or protocol. Anesthesia/sedation requirements complicate procedure.
What's Missing
Pediatric microsurgery center consensus protocols; case-series outcomes.
Design Proposal
Multicenter pediatric microsurgery case registry.
Should immunosuppressed patients (transplant recipients, biologics, chemotherapy) receive modified prophylaxis beyond extended-duration antibiotics?
Why It Matters
Immunosuppression elevates infection risk. Current protocols extend antibiotic duration to 10-14 days but do not modify other elements.
Current Evidence
Mumcuoglu 2014 recommends extended prophylaxis. Other modifications not standardized.
What's Missing
ID specialist consensus on immunosuppression-specific protocols.
Design Proposal
Working group with IDSA/transplant infectious-disease society.
Operational & Implementation Questions
How do hospitals integrate hirudotherapy effectively?
What are the minimum institutional requirements (staffing, training, supply chain, infection control) for safe hirudotherapy program operation?
Why It Matters
Variability in institutional readiness leads to variable outcomes. Standardized minimum-requirement framework would support quality improvement.
Current Evidence
No published consensus minimum requirements. ASH practice guides synthesize current best practice.
What's Missing
Joint Commission or ASPS practice standards explicitly addressing hirudotherapy programs.
Design Proposal
ASH coordinate with ASPS, ASRM, Joint Commission to develop standards.
What is the optimal training-and-credentialing pathway for surgeons, nurses, and pharmacists involved in hirudotherapy programs?
Why It Matters
Without standardized training, safety and effectiveness are variable. Credentialing pathways are institution-specific.
Current Evidence
ASH offers educational resources; no formal credentialing exists.
What's Missing
ACS/ASPS-endorsed training standard; specialty board involvement.
Design Proposal
Develop ASH-endorsed training curriculum; pursue specialty board endorsement.
What is the cost-effectiveness of hirudotherapy program implementation in U.S. tertiary care centers?
Why It Matters
Hospital administrators require ROI analysis. Existing cost-effectiveness data is largely European and dated.
Current Evidence
Cost-effectiveness modeling exists for European protocols. U.S. implementation costs unclear.
What's Missing
U.S.-specific cost-effectiveness analysis from hospital administrator perspective.
Design Proposal
Health economics analysis from sponsor academic medical center.
Aquaculture & Supply-Chain Questions
How do we ensure quality, sustainability, and U.S. domestic capacity?
What is the minimum batch-traceability and quality-control protocol required for FDA-cleared medicinal leech supply?
Why It Matters
Three FDA-cleared suppliers worldwide; supply chain resilience is operationally important.
Current Evidence
FDA Quality Management System Regulation (21 CFR Part 820 → QMSR) applies. Specific protocols at each supplier are proprietary.
What's Missing
Public benchmarking of QC parameters across suppliers; consensus best practices.
Design Proposal
ASH-coordinated benchmarking study with supplier cooperation.
What is the appropriate Aeromonas surveillance protocol for medicinal leech aquaculture facilities?
Why It Matters
Documented 43% environmental ciprofloxacin resistance in A. hydrophila isolates raises concern about supplier surveillance.
Current Evidence
Each supplier maintains internal surveillance. Public reporting is limited.
What's Missing
Standardized surveillance protocol; periodic public reporting; antibiotic susceptibility trend data.
Design Proposal
FDA-CDC dialogue on standardized AMR surveillance for medicinal leech suppliers.
Can U.S. domestic medicinal leech aquaculture meet 30%+ of national supply by 2030?
Why It Matters
Supply chain resilience, biosecurity, and economic considerations support domestic production capacity.
Current Evidence
Two non-FDA-cleared U.S. producers; Carolina Biological is the only FDA-cleared U.S. supplier.
What's Missing
Comprehensive domestic capacity assessment; FDA pathway for new suppliers.
Global Health & Equity Questions
How should hirudotherapy be deployed in low-resource settings?
What is the safety and effectiveness of hirudotherapy programs in LMIC microsurgical reconstruction settings without standard intensive care infrastructure?
Why It Matters
LMIC reconstructive surgery programs face resource constraints. Hirudotherapy is cost-effective and low-technology — but requires monitoring infrastructure.
Current Evidence
Anecdotal LMIC use documented. No systematic outcomes data.
What's Missing
LMIC outcomes registry; WHO essential medicines framework analysis.
Design Proposal
Multicenter LMIC microsurgery registry with hirudotherapy substudy.
Does WHO Essential Medicines/Devices framework apply to medicinal leeches as a low-cost essential intervention?
Why It Matters
WHO Essential Medicines designation drives global availability.
Current Evidence
Medicinal leech is not currently on WHO Essential Medicines or Essential Devices lists.
What's Missing
Formal WHO designation analysis and proposal.
Design Proposal
ASH coordinate with WHO Pharmacopoeia Committee on designation proposal.
Long-Term Outcomes Research
What happens 5, 10, 20 years after hirudotherapy?
What is the long-term (5-10 year) durability of pain reduction in single-session knee OA hirudotherapy?
Why It Matters
Michalsen 2003 showed 3-month sustained pain reduction. Long-term durability informs cost-effectiveness analysis.
Current Evidence
Andereya 2008 reported 2-year follow-up. No 5+ year studies.
What's Missing
Long-term cohort follow-up; retrospective contact of historical RCT participants.
Design Proposal
Retrospective registry with Michalsen/Andereya cohort retracement.
What is the cumulative bleeding risk and scarring profile of patients receiving 4+ leech sessions over a decade for chronic OA?
Why It Matters
Repeat-session protocols (e.g., annual leech therapy for OA) require long-term safety data.
Current Evidence
No prospective long-term safety surveillance.
What's Missing
Long-term safety registry.
Design Proposal
Prospective registry of repeat-session patients.
What is the late-onset (>30 day) Aeromonas infection rate in microsurgical leech therapy patients?
Why It Matters
Most surveillance studies use 14-30 day windows. Late-onset infections may be underreported.
Current Evidence
Documented late-onset infections up to 26 days. Unclear if rare cases occur later.
What's Missing
Extended surveillance protocols.
Design Proposal
Extended 90-day post-treatment surveillance in next prospective study.
Ethics & Policy Questions
How should informed consent, off-label disclosure, and patient autonomy be balanced?
What is the appropriate informed-consent framework for off-label hirudotherapy applications?
Why It Matters
21% of all U.S. prescriptions are off-label (JAMA IM 2008). Yet patient understanding of off-label status is poor.
Current Evidence
ASH consent template includes off-label disclosure. Practice variation is wide.
What's Missing
Cognitive testing of consent comprehension; ABMS/AMA guidance.
Design Proposal
Consent-comprehension study with cognitive testing.
Should hirudotherapy programs require IRB oversight beyond the standard 510(k)-cleared device threshold?
Why It Matters
Standard device clinical use does not require IRB oversight. Off-label investigational use may.
Current Evidence
Practice variation: some institutions require IRB for off-label use, others do not.
What's Missing
AAMC/AAHRPP guidance on hirudotherapy IRB requirements.
Design Proposal
AAMC working group dialogue.
How should ASH balance evidence-discipline with the long-standing patient advocacy community supporting hirudotherapy for non-evidenced indications?
Why It Matters
Patient communities have strong belief in benefits for which RCT evidence is absent. Balancing intellectual rigor with respect for patient experience is a core editorial challenge.
Current Evidence
ASH editorial policy: cite historical and traditional uses as documentary evidence; do not assert efficacy for non-RCT-evidenced indications. Some patient communities consider this dismissive.
What's Missing
Patient-community engagement framework; stakeholder dialogue protocols.
Design Proposal
Patient-community advisory panel established; transparent dialogue on editorial standards.
Future Research Infrastructure
What infrastructure does the field need to answer these questions?
Should a hirudotherapy patient registry be established to support real-world evidence generation?
Why It Matters
Most clinical questions above could be answered with adequate registry infrastructure. No comprehensive registry exists.
Current Evidence
Institution-specific data only; no national or international registry.
What's Missing
Multicenter prospective registry with standardized outcome capture.
Design Proposal
ASH-coordinated multicenter registry; partnership with ASRM and academic medical centers.
Should a hirudotherapy clinical trial network be established analogous to NIH StrokeNet or NICHD Pediatric Trial Network?
Why It Matters
Standalone trials face logistical and statistical limitations. Networks enable efficient multicenter trials.
Current Evidence
No coordinated trial network exists.
What's Missing
NIH NCCIH or NIAMS-sponsored network proposal.
Design Proposal
Develop trial network proposal in coordination with academic medical centers.
Should a hirudotherapy comparative effectiveness research center be established?
Why It Matters
Comparative effectiveness research (CER) requires sustained infrastructure beyond individual trials.
Current Evidence
PCORI-funded CER programs do not include hirudotherapy.
What's Missing
PCORI methodology center proposal; integration with existing CER infrastructure.
Design Proposal
PCORI methodology center grant proposal.
Engaging with Open Questions
Researchers, clinicians, regulators, and funders who can contribute to resolving any of these open questions are invited to engage with ASH through several pathways:
Propose a Study
Have study design ideas? Contact us for collaboration opportunities and letter-of-support partnerships.
Volunteer Reviewer
Help ASH evaluate emerging evidence by joining the editorial review team.
Suggest New Open Questions
Identified an unanswered question we've missed? Submit it for inclusion.
Funder Partnership
Foundations and federal agencies funding research on any of these questions: ASH can connect you with qualified investigators.