Institutional Conflict of Interest Risk Matrix for Human Subjects Research

Original Effective Date: May 17, 2024

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Additional examples of factors contributing to the risks for financial interests/relationships
  • Research Impact: Extent the research may impact the value of the financial interest as well as increasing perception of risks to the objectivity of the research
  • *Multiple relationships between WashU/Entity – e.g. gifts; facilities use, service, or sponsored research agreements; licenses for various
  • An Institutional Official’s COI and level of engagement in the research may impact the risk and management
  • Milestone payments for progress in human studies
  • WashU ownership of equity as a result of the license
  • High visibility and interest in the public domain
Additional examples of risk factors for the research
  • IP is the therapeutic under study or directly impacts clinical care decisions
  • Patient population is considered vulnerable or high risk
  • Research involves high risk procedures or toxicities/side effect profiles
  • Research is intended to meet major commercialization requirements (FDA approvals, post approval studies to obtain insurance reimbursement or establish as part of standard of care)

Risk Matrix Application of Compelling Circumstances

As part of the review process, the ICOIC will establish the degree of institutional risk (the appearance that the University’s significant financial interests in an entity could impact the integrity of the research or the safety/wellbeing of research participants). The ICOIC will consider the phase and design of the research while also taking into consideration the impact the financial interests have on the appearance of a conflict. As the ICOI risk increases, either by nature of the research or WashU’s relationship to the entity, the requirements for sufficient compelling circumstances mitigating said risk also increases (as outlined below). The committee will apply the risk matrix to facilitate the review to determine if there are sufficient compelling circumstances such that an ICOI can be effectively managed.

Compelling Circumstance Criteria based on Human Subject Research Phases/Categories:

  1. Sample Collection – Limited HS (e.g. sample collection only or using de-identified biobank samples)
    • The involvement of participants is minimal with little to no safety concerns and no impact to clinical care such that the research may be treated as non-human subject research.
    • WashU is uniquely qualified, by virtue of distinctive resources (e.g. special facilities or equipment, unique patient population)1
  2. Pre-Clinical HS Phase (e.g. IP are non-therapeutics – no impact to clinical care or decisions, correlative researchŦ, healthy subjects research)
    • The IP under study will have no impact on clinical care or decisions
    • WashU is uniquely qualified, by virtue of distinctive resources (e.g. special facilities or equipment, unique patient population)1
    • WashU investigators have unique experience and expertise essential to the safe or successful conduct of the research
  3. Early Phase HS – Low Risk (e.g. Phase 0-2, small scale efficacy studies, non-vulnerable population and research does not increase health risks to patients over clinical care, 510K clearance studies)
    • The research provides unique access to a therapeutic option that would otherwise be unavailable to patients (no other participating site within 50 miles)β
    • The research is being overseen by external organizations (IRB, DSMB, and/or CRO) independent of WashU2
    • The research endpoints are primarily based on quantitative measurements limiting opportunity for subjective interpretation
    • WashU investigators have unique experience and expertise essential to the safe or successful conduct of the research
    • WashU is uniquely qualified, by virtue of distinctive resources (e.g. special facilities or equipment, unique patient population)
  4. Early Phase HS – Higher Risk (e.g. Phase 0-2, small scale efficacy studies, in vulnerable populations or the research does create an increase in health risks to participants)
    • The research provides a therapeutic option for patients that have exhausted or have no existing conventional treatment options β
    • The research provides unique access to a therapeutic option that would otherwise be unavailable to patients (no other participating site within 50 miles) β
    • The research will not result in or directly lead to regulatory approval or commercialization (additional research or significant efforts remain prior to obtaining regulatory approval or a commercial product)
    • The research is being overseen by external organizations (IRB, DSMB, and/or CRO) independent of WashU.
    • WashU investigators have unique experience and expertise essential to the safe or successful conduct of the research
    • WashU is uniquely qualified, by virtue of distinctive resources (e.g. special facilities or equipment, unique patient population)
  5. Mid-Phase HS (e.g. Phase 3 studies, data essential for regulatory filings)
    • The research provides unique access to a therapeutic option that would otherwise be unavailable to patients (no other participating site within 50 miles)1
    • No member of the study team, nor their division/department leadership, has a financial or fiduciary/executive/managerial relationship with the organization sponsoring the research or owns/licenses the IP under study.
    • WashU’s role is as a participating site with no involvement in data coordination, analysis, or interpretation.
    • WashU’s participation in the research will not result in or contribute to meeting licensing milestones (financial or diligence). Any milestones achieved as a result of the research were accomplished prior to WashU’s participation in the research.
    • The research is being overseen by external organizations (IRB, DSMB, and/or CRO) independent of WashU.
    • The research endpoints are primarily based on quantitative measurements limiting opportunity for subjective interpretation
  6. Late Phase – Post Approval Research (e.g. Post-approval marketing studies or retrospective reviews, Phase IV long term follow up studies)
    • The research does not involve the IP licensed from WashU
    • WashU does not have additional contractual (SRA, Service, or Gifts) or financial relationships, including any ownership interests, with the entity sponsoring the research or owns/licenses the IP other than the license for the IP under study.

Ŧ Correlative Research conducted as part of higher phased research would be subject to the higher phased criteria for compelling circumstances.

β Research that does not evaluate for therapeutic efficacy does not meet this criteria (e.g. safety and tolerability or dose escalation only studies)

1 Criteria does not apply if the following compelling circumstance is applicable:

  • WashU does not have additional contractual (SRA, Service, or Gifts) or financial relationships, including any ownership interests, with the entity sponsoring the research or owns/licenses the IP other than the license for the IP under study.

2 Criteria does not apply if the following compelling circumstances are applicable:

  • WashU does not have additional contractual (SRA, Service, or Gifts) or financial relationships, including any ownership interests, with the entity sponsoring the research or owns/licenses the IP other than the license for the IP under study.
    AND
  • The research will not result in or directly lead to regulatory approval or commercialization (additional research or significant efforts remain prior to obtaining regulatory approval or a commercial product)

Typical Management based on risk level

Minimal Management

Full Disclosure of WashU Financial Interests (in all publications/presentations resulting from the research, the study team, and to research participants via the consent form).

Moderate Management

Full Disclosure of WashU Financial Interests

May also include (as determined by ICOIC based on risk/mitigating factors):

  • External IRB must serve as the IRB of record for the study
  • Safe Haven (mechanism for study team to report concerns on study conduct or inappropriate influence from institutional authorities)
  • Non-conflicted IND holder (If the IND holder is a WashU faculty member then he/she must be non-conflicted)
  • ICOIC approval required for modifications (any changes to study design, changes in PI, or increases to study enrollment must be pre-approved by the ICOIC)
  • Additional Oversight/Data Monitoring (periodic review of study progress and data to evaluate for any indication of bias in the research by non-conflicted individuals not affiliated with the study and reported back to the ICOIC)

If the research involves a conflicted Institutional Official the following strategies may be applied (direct research involvement is managed in coordination with the Conflicts of Interest Review Committee):

  • Limit role in the human study to treating physician or performing procedures
    • No involvement in consenting/enrollment processes, determining subject eligibility.
    • Limited or no involvement in the analysis, interpretation, or reporting of results.
  • Non-conflicted PI of the study that does not report to the conflicted IO
  • Transfer supervision of the study PI to a non-conflicted IO for the duration of the study, through publication
  • Recusal from contract negotiations or approvals for the research project

Significant Management

Full Disclosure

External IRB

Safe Haven (including Ombudsman Office and Non-WashU ICOIC members)

Non-conflicted IND Holder

ICOIC approval required for modifications (any changes to study design, changes in PI, or increases to study enrollment must be pre-approved by the ICOIC)

Also typically includes:

  • Additional Oversight/Data Monitoring (typically multiple reviewers and may require a Non-WashU reviewer)
  • Multi-center Requirement (study must be conducted at multiple sites with WashU enrolling a limited portion of the total enrollment, typically not more than 25%)
  • External member on DSMB/Safety Committee required (at least one member of the DSMB or equivalent safety review group must be from outside WashU)

If the research involves a conflicted Institutional Official the following strategies may be applied (direct research involvement is managed in coordination with the Conflicts of Interest Review Committee):

  • No role in the human study unless essential to performing procedures or patient care.
    • Cannot be involved in consenting/enrollment processes, determining subject eligibility
    • Typically no involvement in the analysis, interpretation, or reporting of results
  • Non-conflicted PI of the study that does not report to the conflicted IO
  • Transfer supervision of the study PI/key study team members to a non-conflicted IO for the duration of the study, through publication
  • Transfer the research to a non-conflicted division/department
  • Recusal from contract negotiations or approvals for the research project
  • University cannot serve as coordinating center
  • Reduction/elimination of the IO’s financial interest or IO role if not otherwise manageable.

Significant Management or May Not Be Permitted

Significant Management would apply if compelling circumstances criteria was met and it was deemed manageable. If not permitted, WashU would need to either discontinue (or not initiate) the research or alternatively the financial interest must be eliminated (or reduced to below thresholds) in order for the research to proceed.