Success depends on more than conducting an effective IVD clinical trial program or even securing a favorable regulatory determination. It requires building an evidence-generation strategy that supports the claims a sponsor ultimately wants to make, the markets they intend to enter, and the reimbursement pathway they need to secure once the product reaches the market. Sponsors bringing a product to market must generate more than safety and efficacy data – they need evidence that supports adoption, differentiation, and payer acceptance.
Organizations that approach IVD clinical trials as isolated studies, designed to satisfy a regulator and nothing more, often discover late in development that the data does not support the coverage or coding position they need, requiring additional studies, real-world evidence, or health economic analyses after the fact. Sponsors that begin with a comprehensive understanding of their reimbursement end goals are typically better positioned to avoid costly delays and generate evidence that supports regulatory clearance, payer coverage, and commercial success together.
This guide outlines the key considerations sponsors should evaluate before initiating an IVD clinical trial program and explains how initial decisions and planning influence study design, evidence requirements, and reimbursement outcomes.
Start With the End in Mind: What Commercialization Strategy Are You Building Toward?
Before designing a study protocol, selecting sites, or estimating enrollment targets, sponsors should answer a fundamental question: What evidence will regulators ultimately expect to see to support the claims of the commercialization strategy? Define the specific claims you want, both clinical and commercial; Work backward from “what does marketing/sales need to say” and “what does the payer need to see” to a concrete list of claims (e.g., sensitivity/specificity thresholds, cutoffs, specific populations or comorbidities covered, turnaround time). Each claim becomes a testable hypothesis the study must be powered to support.
What markets are included and does the requirement for supportive evidence vary between markets? Many sponsors now pursue commercialization across multiple markets. As a result, study planning increasingly requires a global perspective. Rather than designing separate evidence-generation programs for each market, organizations often seek opportunities to generate evidence capable of supporting multiple submissions.
Key considerations include:
- Alignment between FDA, IVDR and ROW evidence expectations
- Population representativeness across regions
- Geographic disease prevalence differences
- Global specimen sourcing
- Bridging requirements
- Multi-region enrollment strategies
The objective is not simply expanding geographic reach. It is ensuring that evidence generated today remains useful across future commercialization opportunities.
Teams often focus on the immediate objective of launching a study without fully considering how that study fits within the broader evidence package required for market authorization. The specific requirements vary based on the anticipated submission pathway and target markets.
Sponsors pursuing FDA clearance or approval must understand how evidence expectations differ across regulatory pathways and product categories. Those pursuing commercialization in Europe must also consider IVDR requirements, including expectations related to scientific validity, analytical performance, and clinical performance. Increasingly, sponsors seek to generate evidence that can support both U.S. and European submissions simultaneously, making early alignment particularly important.
The most successful programs begin by defining commercialization objectives and then working backward to determine what evidence will be required to support those goals.
Beaufort Insight
One of the most common causes of supplemental studies is not poor study execution, it is a disconnect between the evidence being generated and the claims sponsors ultimately want to support. For example, one Beaufort sponsor significantly expanded the validation sample size in order to attempt to meet evolving objectives specific to competitor product sensitivity and specificity during a race to the market. The Sponsor also updated the product design, which created complexities to analyze a homogenous data set. Beaufort supported the sponsor by troubleshooting time-saving methods to accelerate enrollment and clean data to salvage the timeline. Commercial objectives often evolve during development, but study designs do not always evolve with them.
Defining Intended Use: The Decision That Shapes Everything Else
Among all development decisions, the product intended use has the greatest influence on study requirements. Everything downstream depends on a precise statement of what clinical question the test answers, the target population, specimen type, testing setting (e.g., central lab, POC, home), and intended users and how clinicians will view the results.
While the intended use may appear straightforward at the outset of development, it frequently evolves as programs mature. Diagnostic tests initially envisioned for diagnostic applications may later be expected to support treatment selection, disease monitoring, screening, or prognostic claims. Each expansion introduces new evidence expectations.
For example, a study designed to support use in symptomatic patients may not adequately support screening claims in asymptomatic populations. Likewise, evidence sufficient for disease detection may not support treatment selection claims where clinical consequences of incorrect results are substantially different.
Map the Competitive and Reimbursement Landscape
Identify predicate devices, competitor performance claims, existing CPT/PLA codes, and payer coverage precedents for similar tests. This tells you what performance bar the market actually requires (not just what is regulatorily sufficient) and often reveals claims you will need that are not obvious from the regulatory pathway alone.
Determine Regulatory Classification and Pathway
For FDA: Class I/II/III, 510(k) vs. De Novo vs. PMA, or CLIA waiver eligibility. For EU: IVDR risk class (A–D) and Notified Body involvement. This determines the evidentiary bar, timeline, and cost, and it needs to happen before study design, not in parallel with it, since the pathway dictates what kind of IVD clinical trial will even be accepted.
Generating data against a comparator that regulators will accept is critical. Comparator selection influences study design, statistical analysis, performance claims, and regulatory acceptance. Key considerations include:
- Whether an accepted reference method exists
- Whether a predicate device is appropriate
- Whether a composite reference method will be necessary
- How discordant results will be evaluated
- Whether clinical adjudication may be required
Novel diagnostics can be particularly challenging because no universally accepted comparator may exist, which accentuates the value of engaging with regulatory authorities to discuss, identify requirements and current thinking, and subsequently strategize.
Beaufort Insight
Beaufort supported a Sponsor that submitted multiple pre-submissions for a novel diagnostic (U.S. FDA De Novo Pathway) over a several-year period. Beaufort experts advise of the importance of determining the regulatory, commercial, reimbursement and comparator plan in advance of the pre-submission process. This sponsor experienced program delays due to evolving regulations, agency staff turnover and changes in agency thinking over time, resulting in an extended timeline and increased costs.
Engage Regulators Early
Request FDA Pre-Submission (Q-Sub) meetings or informal Notified Body consultations to confirm classification, predicate selection, acceptable reference/comparator method, and statistical approach. This is the point where you find out whether your planned IVD clinical trial design will actually be accepted and is far cheaper to learn this now than after enrollment.
Pre-Submission meetings and other regulatory interactions provide opportunities to obtain feedback on study designs, statistical approaches, comparator strategies, and evidence-generation plans before major investments have been made.
Beaufort Insight
One of our most successful partners mapped the Intended Use/Intended Use Population across two major patient groups within one under-represented treatment scenario, aligned the intended use to represent both treatment groups, and assured reimbursement potential for both patient groups/Intended Use populations. This sponsor then designed the evidence-generation plan, determined the regulatory pathway, and proceeded with a pre-submission to the US FDA. This approach resulted in a successful launch post-clearance and positive patient impact.
Building the Evidence Generation Plan
Explicitly map each claim to the analytical and clinical data needed to support it:
Analytical Validation (e.g., precision, accuracy, LoD/LoQ, interference, stability, matrix effects).
Analytical validation studies establish whether the assay performs consistently and reliably under defined conditions. For many diagnostics, analytical studies represent the largest portion of the overall evidence package.
Clinical Validation (sensitivity, specificity, PPV/NPV vs. an appropriate reference standard)
Clinical performance studies establish how the test performs within representative patient populations and intended use settings. These studies generate evidence supporting performance claims and clinical decision-making.
Health economic or outcomes data that payers will want for coverage decisions.
Usability and Human Factors: As testing expands beyond traditional laboratory settings, sponsors increasingly need evidence demonstrating that intended users can safely and effectively operate the device.
Real-World Evidence: Real-world evidence continues to play a growing role in diagnostics development. However, successful use of real-world data depends heavily on data quality, traceability, and the ability to demonstrate that the underlying patient population reflects the intended use population.
Post-Market Evidence
Regulatory review is increasingly viewed as part of a broader product lifecycle. Sponsors should evaluate how post-market performance monitoring and evidence generation will support long-term commercialization objectives.
Beaufort Insight
Sponsors often think about evidence generation on a study-by-study basis. Regulators review evidence holistically. Gaps between analytical, clinical, and usability evidence frequently become apparent only when the entire package is evaluated together. Examples include sensitivity and specificity comparisons, cross-reactivity with particular analytes, a lack of reproducible results between user groups, user inability to effectively utilize a system component and an inability to effectively utilize within the user workflow. Beaufort experts supported a sponsor that faced an inability of the user to effectively use a capillary collection device to obtain a required volume of sample. The downstream impacts included missed sample collection, missing results, and an impact on the overall data set for the specific sample matrix. Beaufort experts identified this user problem early in the study by real-time data review and tracking and implemented corrective actions in order for the data collection to remain on course and on timeline.
Design the Pivotal Study to Support Regulatory, Reimbursement, and Commercial Evidence Needs
Beaufort’s successful sponsors confirm the data being generated will also satisfy payer evidence requirements. Payers often want more than accuracy (e.g., clinical utility or outcomes impact), so it is far cheaper to build that into the pivotal study than to run a second one later. Considerations include:
- Inclusion/exclusion criteria that mirror the intended use population exactly.
- Reference standard/comparator selection that regulators and payers will both accept.
- Site selection representative of the real-world testing setting
- Sample size and statistical power calculated against the specific claims (not just a generic “prove it works”).
- Pre-specified endpoints and success criteria, agreed with regulators where possible.
Regulatory, clinical affairs, marketing, market access, quality, and R&D should formally confirm that the Intended Use/Intended Use population, regulatory strategy, evidence plan, and study protocol are all internally consistent. No claim in the commercial plan should exist without a corresponding endpoint in the study, and no study endpoint should exist that is not tied to either a regulatory requirement or a commercial claim. The pivotal study protocol should be finalized in conjunction with the statistical analysis plan (SAP) in accordance with quality system/GCP requirements before the first patient is enrolled and the first sample is collected.
Beaufort Insight
Beaufort successfully completed a multi-trial program for a cardiovascular biomarker IVD manufacturer on time and within budget, resulting in successful commercialization of the assay. Looking back on the multi-year and expansive sample collections, what stands out is the strong collaboration between Beaufort and the sponsor regulatory, clinical affairs, marketing, market access, quality, and R&D teams. The market access team assured reimbursement potential and guidance as well as clinic acceptability, and the clinical teams and R&D reviewed the data to assure clinical data within the acceptable measurement range with the end user in mind. Beaufort was on the front lines, assuring patient protections, appropriate and effective user workflows, trial compliance and data integrity.
Common Reasons IVD Clinical Trials Get Delayed
While technologies vary considerably, many delays stem from a familiar set of issues.
Common causes include:
- Unclear intended use claims
- Insufficient analytical validation planning
- Poor specimen acquisition strategies
- Inappropriate comparator selection
- Instrument output errors/system software design errors
- Lack of regulatory alignment
- Failure to anticipate global evidence requirements
- Unrealistic assumptions regarding placement of assay into user workflow
Organizations that invest in strategic alignment before launching clinical studies are often better positioned to maintain timelines and avoid costly redevelopment activities.
Conclusion: Evidence Strategy as the Foundation of Commercial Success
The sponsors who move fastest through IVD development are rarely the ones who ran the most efficient single study. They are the ones who never had to run a second one. Every theme in this guide traces back to the same principle stated at the outset: the challenge is not conducting a successful clinical trial or even securing a favorable regulatory determination. It is building an evidence-generation strategy that supports the claims a sponsor ultimately wants to make, the markets they intend to enter, and the reimbursement pathway they need to secure once the product reaches the market.
A precise intended use statement, a clearly mapped competitive and reimbursement landscape, an early and well-informed regulatory pathway decision, and a pivotal protocol built jointly with market access are not sequential checkboxes. They are interdependent pieces of a single strategy. Weakness in any one of them – a vague intended use, a comparator regulators will not accept, a study that proves accuracy but not clinical utility – tends to surface late when it is most expensive to fix. The sponsors profiled throughout this guide who avoided that outcome did so not because their science was better, but because their planning connected the dots between regulatory clearance, payer coverage, and commercial claims before the first patient was enrolled.
This is also, fundamentally, a cross-functional discipline. Regulatory, clinical affairs, market access, quality, R&D, and marketing each hold a piece of the answer to “what evidence do we actually need?” The programs that stay on timeline are the ones where those functions align early and stay aligned as commercial objectives evolve. Objectives will evolve; study designs need the flexibility and foresight to evolve with them.
Beaufort’s role across these engagements has consistently been to help sponsors close the gap between what a study can prove and what a market will require, troubleshooting enrollment and data challenges in flight, but more importantly, helping sponsors ask the right questions before the protocol is finalized. Organizations that start with a clear, evidence-anchored view of their regulatory, clinical, and reimbursement end goals are best positioned to reach the market with a product and a data package, built to succeed once it gets there.
Looking for guidance on an IVD clinical trial? Connect with one of our experts to discuss your needs.