When a pharmaceutical sponsor and a diagnostic sponsor come together in a combined drug-device study, organisational complexity increases rapidly. This is not simply a collaboration between two organisations. It is a network of contract research organisations (CROs), testing laboratories, clinical sites, ethics committees, and competent authorities — all operating under different frameworks, timelines, and responsibilities.
Without a clear governance structure established upfront, operational issues tend to emerge quickly. And in practice, this is where many combined studies encounter some of their most avoidable delays.
In this blog, we explore why governance and operational alignment must be established early in combined drug-diagnostic studies and how sponsors can reduce downstream regulatory and operational friction.
More Stakeholders Than You Expect
On paper, a combined study may appear relatively straightforward:
- A pharmaceutical sponsor
- An in vitro diagnostic (IVD) or companion diagnostic (CDx) sponsor
In practice, the reality is significantly more complex. The IVD sponsor may not be the actual manufacturer. Sponsorship responsibilities may be divided across multiple organisations. Meanwhile, the pharmaceutical sponsor often works with several CROs responsible for clinical monitoring, biostatistics, and safety reporting.
The IVD side may simultaneously involve its own CRO, dedicated clinical research associates (CRAs), and centralised or decentralised testing laboratories. Add clinical sites, principal investigators, national competent authorities, and ethics committees across multiple Member States — and the result becomes what Jules Petit aptly described during our webinar as "a spider web of interrelations."
Each relationship requires clear agreements covering responsibilities, communication flows, escalation pathways, timelines, and documentation ownership. When these responsibilities remain undefined until issues arise mid-study, delays and compliance gaps become almost inevitable.
We have seen situations where one sponsor assumed the other was managing a task, the other sponsor believed the same — and ultimately no one was handling it at all. These situations are entirely preventable with upfront alignment.
Define the Framework Before Submission
The right time to establish governance is before the first regulatory submission, not during the first request for information (RFI).
Key governance elements that should be aligned early include:
- Documentation ownership
- RFI response workflows
- Clinical site communication procedures
- Safety reporting responsibilities
- Regulatory amendment handling
RFIs deserve special attention. They often come with short response timelines, and answering them may require information from the other sponsor's domain. For example, a competent authority reviewing the IVD performance study application may request documentation from the pharma dossier, or a signed page from a local principal investigator. If it has not been agreed in advance which party contacts the clinical sites, who obtains signatures, and who compiles the responses, the result is confusion and delay during a period when time is already limited.
Regulatory amendments present another area of friction. A protocol amendment may be a straightforward notification on the pharma side, but the same change can constitute a substantial modification under the IVDR, with its own review timelines. If this asymmetry is not anticipated, it creates unexpected delays and confusion about who is responsible for the additional submission.
Shared Documents, Separate Obligations
Certain documents naturally overlap between the drug and device components of the study. The Informed Consent Form (ICF) is one of the clearest examples.
Many Member States now require, or at least strongly encourage, combined or closely aligned consent documentation covering both the clinical trial and the IVD performance study. While this improves the patient experience, it also introduces additional regulatory complexity.
If authorities reviewing the device study request modifications to the ICF, those changes may cascade into the pharmaceutical submission as well, potentially triggering additional amendments or substantial modifications across the broader study framework.
The ICF must also clearly explain that an investigational device is being used and the role of the device within the study. If these elements are insufficiently addressed, authorities frequently issue RFIs — something we continue to see regularly in practice.
The same principle applies to insurance documentation. Insurance coverage must explicitly reference the IVD study, not only the pharmaceutical trial. Incomplete or insufficiently aligned insurance documentation remains a recurring source of avoidable RFIs.
Safety reporting introduces a similar combination of overlap and separation. Not every pharmaceutical adverse event is relevant for the IVD sponsor, and not every adverse device effect is relevant for the pharmaceutical sponsor. In addition, adverse device events must follow IVD-specific safety reporting pathways.
A shared governance framework should therefore clearly define:
- Which events are relevant to each sponsor
- How information flows between parties
- Which reporting obligations apply under each regulatory framework
Study Startup and Conduct: Keeping Everything Aligned
Once approvals are secured, operational complexity continues during study startup. On the IVD side, activities may include:
- Completing laboratory certifications and accreditations
- Finalising analytical validation
- Performing site-specific verification
- Training operators
- Confirming laboratory proficiency
- Establishing data management agreements
The objective is to ensure reliable data flow between the IVD sponsor, testing laboratories, and the pharmaceutical sponsor.
Alignment remains equally important during study conduct. Questions that require clear ownership include:
- Who performs monitoring activities on each side?
- How are IVD protocol deviations communicated?
- Can testing continue during pending amendments?
- How do adverse events and adverse device effects flow into sponsor reporting obligations?
The ICF must also clearly explain that an investigational device is being used and the role of the device within the study. If these elements are insufficiently addressed, authorities frequently issue RFIs. Something we continue to see regularly in practice.
Practical Governance Approaches That Work
Several practical governance measures consistently improve operational efficiency:
- Shared submission and RFI trackers
- Version-controlled documentation management
- Defined communication channels
- Central coordination contacts between pharma and IVD teams
- Regular cross-functional governance meetings
The upfront investment in governance delivers benefits throughout the study lifecycle. It accelerates RFI response times, reduces role confusion, improves inspection readiness, protects data integrity, and minimises operational delays.
As we often advise: you do not want to be in the middle of an ongoing study asking, "I thought you were handling that."
Combined Studies Succeed When
- Roles are clearly defined
- Regulatory differences are respected
- Responsibilities are documented early
Discuss everything upfront. Respect each other's regulatory frameworks. And put the agreements in writing.
Watch the webinar: Grey Zones & Growing Pains in Drug-Diagnostic Co-Development
Watch nowAbout the Author
MSc Biomedical Sciences · Business Unit Manager RA IVD & Representative Services
With over 20 years of experience in the diagnostics industry, Kirsten leads the IVD Regulatory Affairs business unit at QbD Group, guiding regulatory strategy and compliance across all IVDs with a focus on companion diagnostics.
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