Beginner’s Guide to Investigator-Initiated Trials

While many clinical trials are initiated by industry sponsors, such as pharmaceutical companies or contract research organizations (CROs), other trials originate within a research site. When an investigator has an idea for a study they’d like to conduct, they may begin what is known as an investigator-initiated trial, or IIT. This article aims to provide a basic understanding of IITs and how they fit into the clinical research landscape.

What is an IIT?

Also referred to as an investigator-initiated study (IIS) or investigator-initiated research (IIR), an IIT is a clinical trial in which the investigator conceives the research, develops the protocol, and serves as sponsor investigator. The sponsor investigator initiates and conducts a clinical trial – alone or with a team. It’s under the sponsor investigator’s immediate direction that the investigational product (if any) is administrated, dispensed to or used by a subject. As the name implies, the obligations of a sponsor investigator include both those of a sponsor and those of an investigator: both creating and coordinating the study and conducting it.

Who is involved in an IIT?

In addition to a sponsor investigator, the individual roles of investigator and sponsor are still present in an IIT. Since the investigator is assuming dual roles, the regulatory requirements for both roles are imposed upon him or her.

Sponsor

Similar to an investigator, the sponsor’s role is the same on an IIT as it would be on an industry-sponsored trial. The sponsor is the entity initiating the clinical trial and acting as the coordinating center. They select qualified investigators at other sites they believe are a good fit for the trial. Sponsors ensure investigation is conducted following the general investigational plan laid on in the protocol, and managing the investigational new drug (IND) or investigational device exemption (IDE) if applicable. Sponsors also provide information and training to investigators to properly conduct their IIT.

A sponsor’s responsibilities include:

• Select qualified investigators
• Include executed 1572 and financial disclosures from each PI
• Assure the protection of human subjects
• Provide the investigator with information to conduct the investigation properly
• Monitor progress of investigation
• Control and document disposition of investigational product

Investigator

The responsibilities of an investigator on an IIT are the same as any other clinical trial. Their main duties are ensuring the clinical trial is conducted according to the applicable regulations, including the Institutional Review Board (IRB) and Food & Drug Administration (FDA), protecting the rights, safety and welfare of subjects, and controlling the use of the investigational product.

An investigator’s responsibilities include:

• Ensure the investigation is conducted according to the investigational plan
• Maintain case histories
• Provide reports
• Submit progress, safety reports, final reports, financial disclosures
• Protect the rights and safety of subjects under the investigator’s care
• Obtain informed consent from each subject
• Control the drugs under investigation
• Assure review by a responsible IRB and comply with its requirements
• Permit FDA inspections

As daunting as these responsibilities appear, in most cases an investigator isn’t the only person conducting research; they rely on a team of research staff. In such cases, the investigator is responsible for any and all delegation of authority.

Whose Rules Must the Investigator/Sponsors Follow?

The funding agency as well as the products employed in the clinical study will determine what regulations to follow. For an FDA-regulated product, drugs (21 CFR 312) or devices (21 CFR 812) dictates the conduct of the study. If another federal agency funds the research, HHS rules may apply (45 CFR 46). If a study is federally funded by an agency other than HHS, but involves an FDA-regulated product, both sets of rules may apply. Due to the regulatory burden imposed when using FDA-regulated products, many sponsor-investigators hesitate to undertake a clinical study involving regulated drugs or devices. The FDA provides ample guidance for those willing to try.

Why are IITs important?

IITs drive translational research by taking information from clinical trials to address critical medical needs. Translational research takes basic science research and applies it to day-to-day, real-world practices. Oftentimes, it is described as taking a protocol from “bench to bedside.”

Additionally, IITs are especially important for cancer centers. IITs are required when an institution applies for and maintains the Cancer Center Support Grant (CCSG). IITs are key when a cancer center needs to demonstrate the six essential characteristics: cancer focus, center director, facilities, institutional commitment, organizational capacity, and trans-disciplinary collaboration and coordination.

Of these characteristics, IITs demonstrate collaboration, institutional commitment, and organizational capabilities. Traditional clinical trials typically work within one department, while IITs involve frequent cross-functional collaboration. Working with different departments in your institution is one way to show your organization’s capabilities in conducting and carrying out an IIT. IITs also show that your organization is financially capable. IITs are relatively expensive to run, so it’s important to show how you are using different funding or grants your institution has received. By keeping these things in mind, it will help your institution when it comes time to apply for or maintain your CCSG.

What are INDs and IDEs?

An IND is a request from an investigator for an authorization from the FDA to administer an investigational drug or biologic to humans. The FDA considers an investigational drug to be any substance which is not currently approved for marketing by the FDA or is approved but the study is to expand its use to a new indication, route of administration, or dose that significantly changes the risk profile. After an investigator applies for an IND, the clinical trial cannot start for another 30 days, ensuring the FDA has ample time to review the IND for the safety and wellbeing of research participants.

On the other hand, an IDE allows an investigational device to be used in a clinical study to collect safety and effectiveness data required to support a premarket approval application or a premarket notification submission to the FDA. IDEs are essentially the same as INDs – they require approval from the FDA prior to use, the only exception is it’s a device being reviewed as opposed to a drug.

Both INDs and IDEs can be important to IITs. If a sponsor-investigator is conducting research that requires an IND or IDE, they must also assure compliance with the regulations governing these products.

To learn more about IITs, including funding sources and challenges, read Advarra’s article “Meeting the Challenges of Investigator-Initiated Trials.”

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