Investigator-initiated trials (IITs) are clinical trials conceived and led by investigators rather than initiated by an industry sponsor. In many IITs, the investigator also serves as the sponsor-investigator, taking on responsibilities associated with both sponsoring and conducting the study.
This beginner’s guide explains what investigator-initiated trials are, who is responsible for them, which regulations may apply, and how INDs, IDEs, and IRB oversight can fit into an IIT.
What is an investigator-initiated trial (IIT)?
An investigator-initiated trial (IIT), sometimes called an investigator-initiated study (IIS) or investigator-initiated research (IIR), is a clinical trial in which an investigator develops the research concept and protocol and initiates the study. When that individual both initiates and conducts an FDA-regulated investigation, the FDA uses the term sponsor-investigator.
A sponsor-investigator carries the obligations of both a sponsor and an investigator. Depending on the study, those obligations can include regulatory submissions, study oversight, investigational product accountability, participant protection, monitoring, and reporting.
How are investigator-initiated trials different from industry-sponsored trials?
The central difference is who initiates and takes responsibility for the research. In an industry-sponsored trial, a pharmaceutical, biotechnology, medical device, or other organization typically acts as the sponsor and investigators conduct the study at participating sites.
In an IIT, the research concept originates with an investigator or academic research team, and an individual investigator may also assume sponsor responsibilities. Industry may still provide funding, drug supply, or other support without necessarily serving as the regulatory sponsor.
Who is involved in an investigator-initiated trial?
An IIT may involve a sponsor-investigator, collaborating investigators, study coordinators, regulatory staff, pharmacists, statisticians, data managers, an Institutional Review Board (IRB), and other research personnel. When one individual serves as sponsor-investigator, that person is accountable for the applicable responsibilities assigned to both roles, even when specific study tasks are delegated to qualified team members.
Sponsor responsibilities in an IIT
For an FDA-regulated IIT, sponsor responsibilities generally focus on initiating and overseeing the investigation. Depending on the trial, the sponsor or sponsor-investigator may need to select qualified investigators, provide investigators with the information needed to conduct the study, monitor study progress, maintain required records and reports, manage an investigational new drug application (IND) or investigational device exemption (IDE) when applicable, and control and document the disposition of investigational product.
Overview of sponsor responsibilities in an IIT:
- Selecting qualified investigators and participating sites, when applicable
- Collecting required investigator documentation, such as Form FDA 1572 and financial disclosures when applicable
- Helping to ensure the rights, safety, and welfare of research participants are protected
- Providing investigators with the information needed to conduct the investigation properly
- Monitoring the progress and conduct of the investigation
- Controling and document the receipt, use, and disposition of investigational product
- Maintaining required sponsor records and submit required safety or regulatory reports
Investigator responsibilities in an IIT
Investigator responsibilities in an IIT are similar to those in other clinical trials. Investigators are responsible for conducting the study according to the protocol, applicable regulations, IRB requirements, and the signed investigator commitments that apply to the research.
They must protect participants’ rights, safety, and welfare and maintain appropriate oversight of delegated study activities.
Overview of investigator responsibilities in an IIT:
- Conducting the investigation according to the approved investigational plan or protocol
- Maintaining accurate case histories and study records
- Submitting required progress, safety, final, and financial disclosure reports
- Protecting the rights, safety, and welfare of participants
- Obtaining and document informed consent as required
- Maintaining appropriate control of investigational drugs or devices
- Obtaining IRB review and comply with IRB requirements
- Permit FDA inspections when the investigation is subject to FDA oversight
- Maintain oversight of study staff and delegated responsibilities
Although sponsor-investigator responsibilities can be extensive, IITs are usually conducted by multidisciplinary research teams. Tasks may be delegated to qualified personnel, but delegation does not eliminate the investigator’s responsibility for appropriate supervision and oversight.
What regulations apply to investigator-initiated trials?
The rules that apply to an investigator-initiated trial depend on the study design, funding source, institution, and whether the research involves an FDA-regulated drug, biologic, or medical device. Drug and biologic studies may be subject to 21 CFR Part 312, while device studies may be subject to 21 CFR Part 812. Human subject protection and IRB requirements under FDA regulations may also apply.
Research conducted or supported by HHS may be subject to 45 CFR Part 46. Some IITs must comply with more than one regulatory framework.
Because the sponsor-investigator may be responsible for regulatory submissions and ongoing sponsor oversight, institutions should determine early whether an IND or IDE is required, which IRB and institutional requirements apply, and what operational infrastructure is needed to maintain compliance throughout the study.
Why are investigator-initiated trials important?
Investigator-initiated trials can address research questions that arise directly from clinical practice, scientific discovery, or unmet medical needs. They can support translational research by moving promising ideas from scientific investigation toward practical clinical application and can generate evidence about new uses, populations, combinations, dosing approaches, or care strategies that may not be the focus of an industry development program.
IITs can also be strategically important for academic medical centers and cancer centers because they demonstrate scientific leadership, cross-functional research capabilities, and the infrastructure needed to design and conduct complex clinical research.
For institutions pursuing or maintaining programs such as an NCI Cancer Center Support Grant (CCSG), a strong portfolio of investigator-driven research can help demonstrate research depth and organizational capability.
What are INDs and IDEs in investigator-initiated trials?
An investigational new drug application (IND) is the FDA mechanism that allows a sponsor to conduct a clinical investigation involving an investigational drug or biologic when an IND is required. An IND may also be required for certain studies of an approved product when the research involves a new indication, route of administration, dosage level, or other change that increases risk or otherwise does not meet the criteria for an IND exemption.
Once an IND is submitted, the sponsor generally must wait 30 calendar days before beginning the investigation unless FDA notifies the sponsor that the study may proceed sooner; a clinical hold can prevent the study from starting.
An investigational device exemption (IDE) permits an investigational device to be used in a clinical study when an IDE is required. The specific pathway depends in part on whether the device study presents significant risk or non-significant risk. Unlike an IND, an IDE should not be described simply as the device equivalent of an IND: device studies have distinct regulatory requirements, IRB roles, and approval pathways.
For sponsor-investigators, determining whether an IND or IDE is required is an early and important planning step. The answer affects regulatory submissions, study startup, monitoring, safety reporting, investigational product controls, and ongoing compliance.
Frequently asked questions about investigator-initiated trials
Who is the sponsor of an investigator-initiated trial?
The sponsor is the person or entity that initiates the clinical investigation. In many IITs, an individual investigator also serves as the sponsor-investigator and therefore assumes both sponsor and investigator responsibilities. The funding source does not automatically determine who the regulatory sponsor is.
Do all investigator-initiated trials require an IND or IDE?
No. Whether an IND or IDE is required depends on the product, study design, intended use, risk, and applicable FDA exemption criteria. The determination should be made early in study planning and documented appropriately.
Does an investigator-initiated trial need IRB review?
Human subjects research generally requires appropriate IRB review when required by applicable regulations, institutional policy, or funding terms. Sponsor-investigators should build IRB submission, continuing oversight, amendments, safety reporting, and study closure requirements into the study plan.
Can industry support an investigator-initiated trial?
Yes. A company may provide funding, investigational product, scientific input, or other support while the investigator or institution retains responsibility for initiating the study. The written agreement should clearly define roles, responsibilities, data rights, safety reporting expectations, and regulatory obligations.
Planning an IIT: key questions for sponsor-investigators
Before launching an investigator-initiated trial, sponsor-investigators should carefully assess whether they have the resources, expertise, and regulatory support needed to manage both sponsor and investigator responsibilities. Asking the right questions early can help identify operational gaps, clarify oversight requirements, and reduce delays as the study moves from concept to activation.
- Who is the regulatory sponsor, and who will hold the IND or IDE if one is required?
- Which FDA, HHS, state, institutional, and IRB requirements apply?
- What monitoring, safety reporting, data management, and investigational product controls are needed?
- Does the research team have sufficient staffing, funding, and regulatory expertise to fulfill sponsor obligations?
- Which responsibilities can be delegated, and how will oversight be documented?
- What agreements are needed with collaborators, participating sites, funders, or product manufacturers?
Careful planning can help sponsor-investigators identify compliance gaps before study activation and build an oversight model proportionate to the complexity and risk of the research.
For practical guidance on preparing for an IIT, explore Advarra’s resource, Setting Yourself Up for Success During Investigator-Initiated Trials, which outlines key considerations for navigating sponsor-investigator responsibilities and supporting study execution.
To learn more about investigator-initiated trials, including funding sources and operational challenges, read Advarra’s article “Meeting the Challenges of Investigator-Initiated Trials.”