Why Literature Reviews Should Start In R&D, Not Regulatory

How early-stage evidence analysis drives better devices and smoother approvals

During AKRA TEAM’s Medical Literature Review webinar, Ulla Gertig expressed this perspective:

“A proper literature review during your R&D can prevent you from redoing clinical investigations or from performing additional PMCF activities just to address those missing endpoints of relevance.”

- Ulla Gertig, Senior Consultant, AKRA TEAM

This viewpoint challenges conventional thinking about literature reviews as regulatory deliverables. Instead of compliance exercises conducted after device development, early literature reviews become strategic tools that inform fundamental design decisions, clinical strategies, and risk management approaches.

[Download the Guide to Medical Literature Review]

For manufacturers navigating MDR's expanded clinical evidence requirements, this upstream shift represents the difference between reactive compliance and proactive regulatory strategy—with profound implications for development timelines, costs, and market success.

The Strategic Shift: From Compliance to Foundation

Traditional approaches treat literature reviews as documentation requirements triggered by regulatory submission deadlines. However, mounting evidence suggests this reactive timing creates unnecessary risks and costs.

When initiated in the design phase, literature reviews inform not just regulatory strategy but the fundamental blueprint of the device itself.

Early literature reviews deliver practical advantages that extend far beyond compliance. They clarify competitive landscapes, establish current standards of care, and expose treatment gaps that new devices could address. These insights directly influence business strategy, target product profiles, and technical specifications that later become foundations for clinical claims and benefit-risk justifications.

Most critically, early engagement with clinical literature prevents misalignment between device capabilities and clinical measurement standards. Devices developed without understanding how safety and performance are assessed in existing literature often face evidence gaps that retrospective searches cannot fill—forcing costly additional studies and delayed timelines.

Integration with Design Controls: Building Evidence into Development

Under MDR's rigorous planning requirements, literature reviews become essential design control inputs. Evidence-based approaches to defining user needs, establishing performance benchmarks, and identifying foreseeable risks strengthen documentation and regulatory defensibility.

One of the key contributions of early literature review to design control is its role in defining the intended purpose and identifying key risk factors.

Literature analysis enables manufacturers to position devices relative to existing technologies and determine clinical challenges requiring solutions. This foundation supports target population definition, expected benefit articulation, and acceptable risk determination—all critical design inputs that guide engineering development and performance validation.

Literature reviews also strengthen risk management processes. Safety data from existing devices, adverse event reports, and published failure analyses contribute to hazard identification and mitigation planning. Integrating these insights into risk files demonstrates compliance with MDR's General Safety and Performance Requirements while improving hazard identification quality and relevance.

Additionally, literature evidence supports clinical study design decisions. Well-executed reviews reveal standard outcome measures, acceptable comparators, and clinically meaningful endpoints.

Early planning with literature review as a foundation can prevent costly missteps such as selecting non-standard endpoints or omitting key safety metrics.

Avoiding the Clinical Study Multiplication Trap

MDR's expanded clinical evidence requirements create particular challenges for manufacturers accustomed to 510(k) pathways with limited clinical study demands. EU requirements for clinical data across virtually all device categories increase evidence generation burdens significantly.

Early literature reviews offer strategic mitigation. By establishing state-of-the-art expectations and identifying comparable devices during development, manufacturers can design evidence generation strategies that satisfy both US and EU requirements simultaneously.

When clinical data are collected with both jurisdictions in mind, duplication of effort is minimized and costly follow-up studies may be avoided.

Literature-based evidence can sometimes substitute for or supplement new clinical data, particularly when high-quality published studies already exist. For legacy devices transitioning under MDR, literature reviews may support continued validity of earlier investigations or reinforce equivalence arguments.

Success requires robust, reproducible, and defensible methodology: defined protocols, documented search strategies, and transparent inclusion/exclusion records. Reviews must synthesize findings into clear arguments about safety, performance, and clinical relevance—not merely summarize study outcomes.

Early planning ensures these expectations are met without deadline-driven compromises.

Scaling Through Templates and Strategic Alignment

Implementing early-stage literature reviews across diverse product portfolios presents logistical challenges. The webinar panel emphasized standardized templates and reusable protocols as solutions for scaling review processes while maintaining compliance and quality.

Templates ensure consistency in how data sources, search strategies, inclusion criteria, and appraisal methods are documented.

Standardized frameworks facilitate cross-functional alignment. Clinical, regulatory, engineering, and quality teams operate from shared methodologies, promoting common understanding and reducing development friction. Embedding literature review planning into design control templates establishes traceability linking design inputs, risk mitigation measures, and performance claims to literature-derived evidence.

This foundation streamlines future technical documentation preparation. When CER, PMCF plan, or clinical development planning begins, much groundwork already exists.

Standardized processes lend themselves to automation.

Software platforms like DistillerSR, reference managers, and automation tools further streamline execution. Combined with structured templates, these technologies allow teams to focus on synthesis and interpretation rather than administrative tasks.

The Competitive Advantage of Early Integration

Medical device success requires more than engineering innovation—it demands comprehensive strategies aligning design, safety, and performance with clinical needs and regulatory expectations.

Literature reviews, when initiated early and integrated into development planning, offer a critical bridge between innovation and compliance.

Early literature reviews define clinical problems, validate proposed solutions, and guide evidence generation. They identify risks, support design decisions, and reduce costly revision likelihood later in development. In regulatory environments with increasing data requirements and tightening timelines, manufacturers embedding literature reviews into earliest development stages position themselves for greater efficiency and regulatory success.

The strategic value extends beyond compliance. Well-executed early literature reviews inform market positioning, competitive differentiation, and clinical value propositions that drive commercial success. They identify unmet needs, validate market opportunities, and guide feature prioritization based on clinical evidence rather than assumptions. 

With thoughtful planning, cross-functional collaboration, and appropriate tools, manufacturers can transform literature reviews from compliance obligations into competitive advantages—starting long before prototyping and enduring long after market launch.