In today’s evidence-driven healthcare landscape, it is no longer enough to present the data you do have. Increasingly, regulators, payers, clinicians, and patients are asking: “What’s missing, and why?”
That’s where Evidence Gap Analysis (EGA) becomes a strategic tool. Instead of focusing solely on the strength of available data, EGA systematically highlights the blind spots in the evidence base — the areas that could delay approval, weaken payer confidence, or reduce clinical adoption if left unaddressed.
In this blog, we’ll explore:
- What Evidence Gap Analysis is and why it matters
- The key domains where evidence gaps occur
- How EGA supports regulatory submissions, health technology assessments (HTAs), and market access
- A real-world case study: using EGA to strengthen a Clinical Evaluation Report (CER) for a Class III device
- Best practices to integrate EGA into your evidence strategy
What Is Evidence Gap Analysis?
Evidence Gap Analysis is the structured identification and evaluation of areas where critical evidence is missing, insufficient, or inconsistent.
It goes beyond traditional literature reviews by not only cataloguing what is published but also spotlighting what is unknown — and determining whether those gaps are strategically important.
Unlike a systematic review, which answers a defined question, EGA serves a broader purpose:
- Mapping the evidence landscape
- Highlighting areas of strength and weakness
- Prioritizing what further research is needed
- Documenting gaps transparently for regulators and payers
In high-stakes contexts like Class III medical device evaluations, oncology therapies, or orphan drug submissions, evidence gap analysis can make the difference between a smooth regulatory review and a major deficiency letter.
Why Evidence Gaps Matter
Healthcare stakeholders know that perfect evidence rarely exists. Clinical trials often have limitations — narrow populations, short follow-up periods, or limited comparator data. Payers and regulators expect this. What they want to see is whether companies are aware of these gaps and proactively managing them.
Failing to identify gaps can lead to:
- HTA delays or rejections when inputs are deemed insufficient
- Regulatory deficiencies in CERs, NDAs, or HTA dossiers
- Payer skepticism due to lack of long-term outcomes, real-world data, or comparator evidence
- Strategic missteps in evidence generation planning, leading to higher costs and slower access
By contrast, acknowledging gaps demonstrates scientific integrity and builds trust.
Common Domains Where Evidence Gaps Emerge
Through our work in HEOR, regulatory writing, and scientific communication, we frequently see evidence gaps in the following areas:
1. Long-Term Safety and Effectiveness
Particularly in medical devices and oncology, trials often provide only 12–24 months of follow-up, while regulators and payers want durability of effect and long-term safety data.
2. Comparative Effectiveness
RCTs may lack active comparators relevant to clinical practice. This leaves payers asking, “How does this product compare to today’s standard of care?”
3. Real-World Evidence (RWE)
Trials typically exclude patients with comorbidities, older age groups, or diverse geographies. RWE is needed to show how products perform in practice.
4. Patient-Reported Outcomes (PROs) and Quality of Life
Increasingly, HTA bodies and regulators expect patient-centric outcomes, not just clinical endpoints. Missing PRO data can weaken value arguments.
5. Epidemiology and Burden of Illness
Lack of robust prevalence, incidence, and economic burden data makes it harder to justify unmet need and cost-effectiveness models.
6. Health Economics Inputs
Utility values, resource use, and cost data are often fragmented or absent, undermining the credibility of economic models.
How Evidence Gap Analysis Supports Regulatory and HTA Success
- Strengthening Clinical Evaluation Reports (CERs)
Under the EU Medical Device Regulation (MDR), CERs must include a systematic appraisal of clinical evidence and a transparent discussion of limitations. A gap analysis makes this explicit.
- Supporting HTA Submissions
Agencies like NICE, CADTH, and PBAC expect companies to acknowledge limitations in their evidence packages. Transparent gap documentation reduces the risk of rejection.
- Guiding Post-Market Evidence Generation
Gap analysis feeds into post-market clinical follow-up (PMCF) plans for devices or RWE strategies for drugs, ensuring targeted, efficient evidence generation.
- Enhancing Value Communication
By clearly showing both strengths and limitations, companies can preempt payer objections and strengthen credibility.
Case Study: Evidence Gap Analysis for a Class III Cardiovascular Device CER
Background
A global MedTech company developing a Class III implantable cardiovascular device was preparing a Clinical Evaluation Report (CER) to comply with the EU MDR. While their literature review identified multiple clinical studies, key gaps threatened the robustness of the CER.
The Challenges Identified:
- No head-to-head comparative studies against the leading competitor device
- Limited long-term outcome data (>24 months)
- Absence of patient-reported outcome measures (PROs)
- Geographic bias, with most studies conducted in one region outside the EU
If left unaddressed, these gaps risked major deficiencies during Notified Body review, potentially delaying CE marking and market access.
Our Approach: Structured Evidence Gap Analysis
Mapping the Evidence
We created an evidence matrix aligned to PICO parameters and MDR Annex XIV requirements, categorizing available data across safety, performance, and patient outcomes.
Identifying and Classifying Gaps
- Lack of direct comparator evidence
- Insufficient duration of follow-up
- Missing HRQoL data
- Limited generalizability to EU populations
Stakeholder Validation
Workshops with regulatory, clinical, and post-market teams prioritized gaps based on risk to CER acceptance.
Action Plan Development
- Integrated real-world registry data to strengthen safety/long-term outcomes
- Recommended a Post-Market Clinical Follow-Up (PMCF) study focused on HRQoL
- Clearly documented gaps and mitigation plans in the CER’s “Limitations” section
Key Outcomes
- CER was accepted with only minor clarifications; no major deficiencies raised
- Accelerated approval timeline by an estimated 4–6 months
- Built regulator trust through transparent acknowledgment of gaps
- Delivered a 3-year PMCF roadmap, aligning evidence generation with MDR requirements
Takeaways from the Case
- Gap analysis is not a weakness; it is a strength when managed proactively
- Regulators value transparency and mitigation planning over silence
- Embedding gap analysis into CER preparation ensures compliance and accelerates approval
Best Practices for Evidence Gap Analysis
Based on our experience, here are practical steps for conducting robust EGAs:
- Start Early – Don’t wait until submission drafting. Integrate gap analysis during evidence planning.
- Use a Framework – Apply PICO, GRADE, or HTA-relevant frameworks to map strengths and weaknesses.
- Document Transparently – Include detailed gap sections in CERs, GVDs, and HTA submissions.
- Link to Action – Every gap identified should lead to a mitigation plan: new studies, RWE collection, or PMCF.
- Collaborate Cross-Functionally – Involve HEOR, regulatory, medical, and clinical teams to ensure alignment.
Final Thoughts
In the evolving world of healthcare evaluation, what you don’t know is just as important as what you do know. Evidence Gap Analysis provides the strategic lens to identify, prioritize, and address these unknowns.
By making evidence gaps visible — and demonstrating clear plans to close them — companies not only strengthen regulatory and HTA submissions but also build trust with payers, regulators, and patients.
For high-risk products like Class III devices, oncology drugs, or rare disease therapies, EGA is not just a “nice-to-have” — it is a regulatory and strategic imperative.
Ready to strengthen your CERs, HTA submissions, or global dossiers with proactive evidence gap analysis?
At Vedara-IQ, an i-Qode company, our expert medical writing and HEOR team delivers structured EGAs that align with MDR, HTA, and payer expectations — turning gaps into opportunities.
👉 Contact us at info@i-qode.com to learn more our capabilities
