Investigator Initiated Studies (ISS), What Are They and Their Value to Manufacturers 

What is an Investigator Initiated Study (IIS)?

An Investigator Initiated Study (IIS) is a clinical investigation conducted by a physician independently of the device industry. Under the sponsor's responsibility, as in a company-sponsored study.

In an IIS, the investigator assumes both roles defined in the regulation, Sponsor and Investigator, by initiating, implementing, and taking full responsibility for the clinical investigation. EU MDR 2017/745 defines an investigator as the individual responsible for conducting a clinical investigation at a site, and a Sponsor as the individual, company, institution, or organization responsible for the initiation, management, and financing of the study.

Why would a manufacturer fund an IIS?

Manufacturers fund Investigator Initiated Studies because they are a relatively low-cost, hands-off source of clinical data. The manufacturer carries none of the sponsor responsibilities and uses fewer resources to generate new data on its device, while the Sponsor-Investigator remains responsible for the research.

A true IIS begins with an unsolicited, spontaneous request for funding from the investigator, based on a research proposal. (To avoid confusion, this is described as funding, not sponsoring.) The manufacturer reviews the proposal and decides whether the proposed research meets its clinical needs and strategic goals, and judges the study's scientific merit, quality, and compliance. The manufacturer may then support the research with funding and/or free-of-charge devices, while the Sponsor-Investigator remains responsible throughout.

If the study succeeds, the investigator publishes the results, which the manufacturer can then use. Depending on the contract, the manufacturer may also obtain anonymized datasets, the original study protocol and reports, and may audit parts of the study.

What can IIS data be used for?

IIS data is well-suited to real-world evidence: post-market clinical data collection, marketing, and local projects such as reimbursement support. For regulatory purposes, its use is generally limited to supporting evidence only, because pre-market studies (MDR Art. 62) and PMCF studies outside the intended purpose (MDR Art. 74) require competent-authority approval and far more manufacturer involvement.

IIS can surface the issues practitioners face in the real world and answer questions grounded in day-to-day clinical use of the device. They can also be used exploratorily to investigate unmet clinical needs and new uses, though in such cases, additional regulatory approvals may be required. IIS also tends to carry a different profile of potential bias than company-sponsored studies.

What are the challenges of running an IIS?

The main challenges in an IIS are controlling deliverables, timelines, quality, and compliance, because the manufacturer does not hold sponsor control. A solid contract with the investigator is essential, covering roles, regulatory compliance, approvals, data ownership, monitoring, reporting, and milestone-based payments.

A robust contract should detail:

• Roles and responsibilities
• Adherence to applicable regulations
• Availability of the protocol and amendments
• Informed consent
• Ethics and regulatory approvals
• Registration in trial registries
• Data ownership and processing
• Review of manuscripts and dissemination of results
• Reporting obligations to the manufacturer
• Intellectual property and inventions
• A schedule of milestone-based payments

The manufacturer can reserve the right to audit certain elements, but source data verification (monitoring) and any activity requiring access to patient data will not be available to it. In an IIS, the Sponsor-Investigator must ensure adequate monitoring by an independent monitor (MDR Annex XV). Multicentre IIS adds coordination difficulty for the Principal Investigator across sites, and data collection can be demanding; electronic data capture (EDC) helps. Sites also tend to underestimate the resources required. Start-up, enrolment, and execution often run longer than expected, which can threaten milestones and trigger budget-extension requests.

How can a CRO help with an IIS?

A medical device CRO can take on activities a Sponsor-Investigator subcontracts: monitoring, medical writing, training, data management, auditing, and regulatory submission support. For a manufacturer funding an IIS, suggesting the research team engage a CRO helps ensure ISO 14155 / GCP compliance, ethical conduct, and the scientific validity of the data.

If you're funding an IIS or have questions about an existing IIS program or IIS data, get in touch to discuss how our CRO team can support you.