For sponsors developing rapid infectious disease diagnostics, the landscape is shifting fast. Traditional lab tests take hours or days, but rapid diagnostics deliver results in minutes. This shift creates a significant challenge: clinical trial strategies designed for slow, centralized tests won’t work for fast, decentralized ones. This isn’t just a technology upgrade. It’s a fundamental shift that requires new clinical trial strategies tailored for rapid, decentralized diagnostics.

The Clinical Imperative: Why “Under 2 Hours” Matters

The World Health Organization’s (WHO) declaration of mpox as a public health emergency reinforced a now-familiar truth: conventional diagnostic infrastructure often fails under the demands of outbreak conditions. The COVID-19 pandemic exposed critical gaps in testing capacity, turnaround times, and real-time clinical decision support. In response, the infectious disease diagnostics landscape is shifting toward rapid, decentralized solutions that can deliver actionable results at or near the point of care.

Rapid diagnostic tests with turnaround times under two hours are not merely technological improvements—they represent a fundamental shift in clinical utility. These tools are designed to support decisions that must be made within tight windows, particularly in emergency departments, urgent care, and outbreak response settings. In many cases, the timing of a result directly impacts patient isolation protocols, treatment initiation, and antimicrobial stewardship efforts.

However, clinical trial methodologies have not always kept pace with this shift. Traditional trial designs emphasize analytical performance under controlled conditions, but rapid diagnostics require a broader validation approach. It is no longer sufficient to demonstrate sensitivity and specificity alone. Studies must also assess how diagnostic speed translates into clinical action: whether faster diagnosis leads to more timely treatment, earlier infection control measures, or reductions in unnecessary antibiotic use. Validating rapid diagnostics, therefore, requires trial designs that reflect the real-world settings in which these tools are deployed and the clinical decisions they are intended to support.

Overcoming Real-World Trial Challenges

Bridging the Infrastructure and Environment Gaps

Currently, most molecular assays for infectious disease testing remain confined to academic medical centers or commercial laboratories, where specialized equipment and trained personnel are readily available. The high cost of primary equipment for portable molecular platforms creates significant barriers to accessibility and widespread adoption, particularly in decentralized or resource-limited settings.

A notable example is the Dragonfly platform, a portable molecular diagnostic tool developed for mpox testing. This platform demonstrated impressive performance: 96.1% sensitivity and 100% specificity for orthopoxviruses using 164 clinical samples. Yet, its true innovation lies in its adaptability across diverse clinical environments. To address cost constraints, the researchers developed a simple isothermal heater manufacturable for under £100, eliminated the need for cold-chain storage, and incorporated a companion app to facilitate result interpretation.

This case exemplifies the critical need to bridge the implementation gap: clinical trials must demonstrate not only that a diagnostic performs well analytically, but also that it functions effectively in the hands of non-laboratory personnel, under suboptimal conditions, and with variable sample handling quality. To validate rapid diagnostics in real-world conditions, trial designs must go beyond analytical accuracy under ideal lab settings. They need to account for the following operational and environmental factors:

• Site capability: Not all healthcare facilities have experience with POC testing or the staff trained to administer rapid molecular diagnostics. Selecting trial sites that reflect the intended deployment environment, such as clinics with established decentralized testing protocols and flexible workflows, is critical.
• Environmental stressors: Temperature fluctuations, humidity, inconsistent storage, and variable sample handling quality can impact test performance. Trials must simulate these conditions to demonstrate robustness.
• Operational workflow: The test must fit into fast-paced clinical encounters, often within tight time windows. Usability and integration with existing processes are key to successful adoption.
• Training and competency: Many rapid diagnostics are administered by healthcare workers with minimal lab experience. Trials should evaluate whether users can perform the test correctly with the training provided and assess error rates under real-world conditions.

Combining these factors into a comprehensive validation strategy ensures that rapid diagnostics are not only analytically sound but also operationally feasible and scalable in the settings where they are most needed. By bridging this infrastructure and environment gap, clinical trials generate evidence that supports regulatory approval, payer acceptance, and, ultimately, patient benefit.

Usability and Human Factors: Evaluating the End-User Experience

In decentralized and point-of-care settings, diagnostic tests are often administered by individuals with minimal laboratory training, such as nurses, community health workers, or patients themselves. Even highly accurate tests can underperform in these environments if they are not intuitive or robust to user error.

To ensure success beyond analytical validation, clinical trials should include formal assessments of usability and human factors. Key considerations include:

• Instruction adherence: Whether intended users can follow test protocols without supervision.
• Result clarity: Whether results, visual or digital, are easy to interpret under varying conditions.
• Error identification and mitigation: Common failure modes during sample handling or result entry, and whether they can be reduced through better design or training.
• Workflow fit: Whether the test can be run and results acted upon without disrupting patient flow or care protocols.

These factors often determine whether a diagnostic can be adopted at scale. Usability data, particularly when gathered across diverse user profiles, strengthens both regulatory submissions and commercial readiness.

Tackling Multiplex Complexity in Trial Design

There are currently several molecular multiplex syndromic panels available in the U.S.: bloodstream infections, respiratory tract infections, gastrointestinal infections, and meningitis/encephalitis. These panels bring efficiency, but clinical complexity must also be considered when designing a clinical trial.

A respiratory panel might show simultaneous positives for influenza, RSV, and rhinovirus. When interpreting multiplex results, clinicians must consider prolonged shedding periods, multiple positive results or co-infections, detection of asymptomatic carriage, and variable accuracy for different agents on the panel.

This complexity has real implications for trial design. It's no longer enough to prove your test can detect multiple pathogens accurately. It must be demonstrated that results can guide clinical decisions. These clinical endpoints need to account for:

• Primary endpoints that handle multiple simultaneous positive results: Traditional binary positive/negative frameworks break down with multiplex testing
• Clinical utility assessments that evaluate decision-making with complex result patterns: How do clinicians interpret and act on multiplex results, and does that action lead to better outcomes?
• Post-market surveillance built into trial design from day one: Real-world complexity emerges after deployment

Demonstrating Value: Cost-Effectiveness and Regulatory Expectations

Closing the Cost-Effectiveness Evidence Gap

Demonstrating cost-effectiveness is essential for the adoption of rapid infectious disease diagnostics, particularly when these tools carry higher per-test costs or require changes to standard care pathways. Payers, health systems, and regulatory bodies increasingly expect evidence that a new diagnostic not only improves clinical outcomes but also delivers measurable value across the healthcare continuum.

To meet these expectations, health economic endpoints should be integrated into clinical trial design from the outset. Key evaluation areas include:

• Time to appropriate therapy: Measuring whether earlier diagnostic results translate into faster, more targeted treatment decisions.
• Healthcare resource use: Assessing impacts on emergency department throughput, hospital admissions, and length of stay.
• Antimicrobial stewardship: Evaluating the test’s ability to reduce unnecessary or inappropriate antibiotic prescriptions.
• Downstream utilization: Capturing broader effects on repeat visits, follow-up testing, or escalation of care.

These data help establish a diagnostic’s role not only in clinical decision-making but also in improving system-level efficiency. Embedding health economic measures in trial protocols ensures that performance claims are supported by real-world value evidence, which can accelerate both regulatory clearance and market access.

Evolving Regulatory Expectations for Rapid Infectious Disease Diagnostics

Regulatory agencies have demonstrated increasing flexibility and responsiveness in evaluating POC and rapid diagnostic technologies. Recent approvals reflect a growing recognition of the clinical value these tools provide, especially in addressing urgent public health needs.

In 2024, the U.S. Food and Drug Administration (FDA) approved the first point-of-care molecular diagnostic for hepatitis C, highlighting the agency’s willingness to work closely with developers of innovative platforms. The FDA has also supported clinical studies for rapid diagnostics targeting sexually transmitted infections. Visby Medical received 510(k) clearance and a CLIA waiver for its POC test targeting chlamydia, gonorrhea, and trichomoniasis, a rapid diagnostic administered at home, delivering results in under 30 minutes.

These authorizations reflect more than just approval of individual products. They signal a regulatory paradigm shift: the FDA is increasingly endorsing decentralized, POC, and even at-home testing models that maintain high accuracy while expanding access. For rapid infectious disease diagnostics sponsors, these developments underscore that innovative, real‑world clinical trial designs, including usability assessments, workflow integration, and clinical impact endpoints, are now recognized and accepted elements of the regulatory review process.

Adaptive and Strategic Trial Design for Rapid Infectious Disease Diagnostics

Traditional clinical trial designs can be too rigid to keep up with rapidly evolving pathogens and diagnostic technologies. They often evaluate one test at a time, under static conditions, which limits responsiveness and efficiency.

The Advantages of Platform Trials

Platform trials use a single master protocol to evaluate multiple diagnostic tests or multiple versions of the same test simultaneously. Regulatory agencies have increasingly embraced platform trials, especially following their success during the COVID-19 pandemic. This adaptive approach offers key benefits:

• Efficiency: Assess multiple pathogen panels or test variants together, saving time and resources.
• Responsiveness: Add emerging targets in real time to support outbreak response.
• Data sharing: Use shared control groups to reduce recruitment needs and speed up trials.
• Continuous evidence generation: Collect data continuously to enable staged regulatory submissions and quicker market access.

Core Principles for Trial Design

Designing clinical trials for rapid infectious disease diagnostics requires balancing rigorous validation with real-world practicality:

• Prioritize Clinical Utility Over Analytical Precision: Focus on endpoints that measure impact on patient care and antimicrobial stewardship.
• Ensure Operational Feasibility: Evaluate integration into real-world healthcare workflows and user training needs.
• Mitigate User-Related Errors: Assess variability due to user factors and develop strategies to reduce errors.
• Demonstrate Economic Value: Incorporate cost-effectiveness analyses relevant to payers and health systems.

Flexibility and Adaptability

To keep pace with the evolving infectious disease landscape and advances in technology, trial designs must be adaptable. This includes accommodating the addition of new pathogens or syndromic panels, incorporating technological improvements such as hardware or software upgrades, and responding to shifts in clinical care standards or treatment guidelines. Regulatory requirements may also change, necessitating flexible evidence generation strategies. By embedding adaptability and real-world implementation endpoints from the outset, sponsors can produce robust evidence that not only meets current regulatory demands but remains relevant as diagnostics and disease threats evolve.

Partnering for Success: Navigating Trials in Rapid Infectious Disease Diagnostics

The rapid diagnostics landscape is evolving quickly, and success depends on demonstrating how faster results can support improved patient care in real-world settings. The next advances will come from platforms delivering lab-quality results in minutes, validated through clinical trials designed to address today’s clinical complexities and timelines.

At Lindus Health, we help sponsors navigate these challenges with tailored trial strategies designed specifically for infectious disease research. Ready to design a clinical trial approach built for the future of infectious disease diagnostics? We’re here to support you every step of the way. Get started with our team today.