Evaluating the Impact and Implementation of In Vitro Diagnostic Tests: Methods for Assessment, Adoption, and Optimal Use

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Executive Summary

Evaluating in vitro diagnostic tests (IVDs) requires balancing methodological rigor with practical applicability. By moving beyond accuracy metrics and focusing on real-world outcomes, the field can better demonstrate the value of diagnostics, drive adoption of effective tests, and support improvements in patient care and public health.

Complexity of Evaluating Diagnostics

Evaluating the clinical impact of IVDs for infectious diseases is inherently complex. Unlike pharmaceuticals, whose effectiveness can be measured directly by patient outcomes in controlled trials, the value of IVDs depends on how they are implemented, interpreted, and acted upon by healthcare providers. This complexity requires IVD clinical researchers to consider new frameworks and methodological approaches in addition to traditional study designs to capture the impact on patient care, antimicrobial stewardship, and public health.

From Test Accuracy to Real-World Value

The adoption of IVDs is often initially driven by test performance characteristics, such as sensitivity and specificity, rather than evidence of clinical outcomes. However, understanding their real-world value requires evaluating how results influence treatment decisions, provider behavior, and care pathways. Factors such as prescribing norms, healthcare settings, provider attitudes, and diagnostic stewardship play a critical role in whether an IVD improves outcomes. Therefore, methodological rigor paired with comprehensive methodologies, such as implementation science, are essential to design studies that reflect practical use and generate evidence that is relevant, generalizable, and supportive of policy and reimbursement decisions.

Key Methodological Considerations

Key methodological considerations include ensuring that a clinically meaningful opportunity for improvement exists before conducting a study and using baseline data to confirm that measurable changes are possible. The PICOTS framework (Population, Intervention, Comparator, Outcomes, Timing, Setting) should be applied to clearly define study parameters. Researchers are also encouraged to avoid subjective, adjudicated outcomes, which are prone to bias and unreliable agreement, and instead use objective, reproducible measures.

The study design approach should be based on what is feasible, pragmatic, and ethical. Performing randomized controlled trials (RCTs) for diagnostics can be particularly challenging given that the clinical impact of an IVD relies heavily on local context and RCT findings may not be generalizable across different healthcare systems or settings. The practice heterogeneity seen across settings highlights the need to evaluate center-level factors, which often requires resource-intensive, multicenter, mixed-methods designs. Additionally, diagnostic RCTs are costly and frequently face enrollment challenges, raising questions about their efficiency and value.

In many cases, well-designed observational studies can provide cost-effective and realistic insights into IVD performance. Tools like the target trial framework help structure observational studies to emulate RCTs and reduce common biases, such as immortal time bias. Analytical techniques such as directed acyclic graphs (DAGs) and careful clinical judgment should guide model selection to avoid spurious associations. Alternative approaches to analysis—such as intention-to-treat and per-protocol strategies—can further strengthen causal inference.

Emerging Frameworks

New frameworks, including BED-FRAME, DOOR-MAT, and DOOR, along with hybrid effectiveness-implementation designs, offer more holistic ways to assess the interplay between diagnostic performance, clinical outcomes, patient preferences, and resource utilization. These approaches integrate both clinical and implementation science perspectives, ensuring that evidence reflects the complexity of real-world practice.

	BED-FRAME	DOOR-MAT	DOOR	Hybrid Effectiveness
Full Name	Benefit-Risk Evaluation of Diagnostics: A Framework (BED-FRAME)	Desirability of Outcome Ranking Management of Antimicrobial Therapy (DOOR-MAT)	Desirability of Outcome Ranking (DOOR)	Hybrid Effectiveness-Implementation Study
Primary Objective	To guide the assessment of the trade-offs between multiple IVDs and their potential impact on clinical decision-making.	To optimize the management of antimicrobial therapy decisions based on organism resistance profiles.	To rank and evaluate the desirability of outcomes between treatment groups.	To simultaneously evaluate both the clinical effectiveness of an intervention and the strategies used to implement it in real-world settings.

Balancing Rigor and Practicality

Ultimately, evaluating IVDs requires balancing methodological rigor with practical applicability. Studies must account for contextual factors, engage stakeholders—including clinicians, laboratorians, policymakers, and payors—and generate evidence that informs guidelines, reimbursement, and market access. By moving beyond accuracy metrics and focusing on real-world outcomes, the field can better demonstrate the value of diagnostics, drive adoption of effective tests, and support improvements in patient care and public health.