A clinical data gap analysis under MDR is a GSPR-by-GSPR audit of what your current clinical evidence actually proves versus what Article 61 and Annex XIV Part A require. You list each relevant general safety and performance requirement, map the evidence you hold against it, mark where the evidence is thin or missing, and then choose one of four closure paths per gap: more literature, equivalence under MDCG 2020-5, a PMCF study under Annex XIV Part B, or a clinical investigation under Article 62 and Annex XV. This is how startups convert "our CER is not enough" into a concrete, costed plan.

By Tibor Zechmeister and Felix Lenhard. Last updated 10 April 2026.

TL;DR

  • A clinical data gap is any general safety and performance requirement (GSPR) relevant to your device that your current clinical evidence does not fully support. Gaps are identified GSPR by GSPR, not "in general."
  • The four closure options under MDR are: expand the literature search, claim equivalence per Article 61(4)-(6) and MDCG 2020-5, add a PMCF activity under Annex XIV Part B, or run a clinical investigation under Article 62 and Annex XV.
  • Gap analysis belongs in the clinical evaluation plan (CEP) required by Annex XIV Part A, Section 1(a) — not as a last-minute rescue when the Notified Body flags the CER.
  • The cheapest gap to close is almost always the one you close with a tighter intended purpose. Narrowing the claim shrinks the evidence burden before any new data is generated.
  • A clinical investigation under EN ISO 14155:2020+A11:2024 is the last option, not the default. Startups that default to investigations usually had a literature or PMCF route available and did not look for it.

Why gap analysis is the work most startups skip

Most first-time MDR startups do not fail clinical evaluation because they cannot find data. They fail because they never asked the prior question — "against what exact requirements am I measuring the data I have?" They write a clinical evaluation report that lists the evidence they happen to own, and they conclude the evidence is sufficient because nobody set an acceptance criterion that could prove otherwise. Then the Notified Body reviewer opens the CER, maps the evidence against Annex I, and finds the holes.

Gap analysis is the discipline of finding those holes before the reviewer does. It is uncomfortable because it forces the founder to name what is missing in writing, with specific article references, before they know how they are going to fix it. That is precisely why it works. A named gap is a gap you can cost, schedule, and close. An unnamed gap is a landmine.

This post walks through how to run a clinical data gap analysis that actually produces a plan — not a document that looks compliant.

What counts as a clinical data gap under MDR

A clinical data gap is not "we do not have enough studies." It is specific: a general safety and performance requirement relevant to your device that your current clinical evidence does not adequately support.

Article 61(1) requires the clinical evaluation to confirm conformity with the relevant general safety and performance requirements "under the normal conditions of the intended use of the device," and to evaluate undesirable side effects and the acceptability of the benefit-risk ratio referred to in Sections 1 and 8 of Annex I. (Regulation (EU) 2017/745, Article 61, paragraph 1.) That single sentence defines the scope of your gap analysis: every GSPR in Annex I that is relevant to your device, plus the benefit-risk ratio per Annex I GSPR 1 and GSPR 8, is a row in your gap analysis table.

A gap exists when one of the following is true for a given GSPR:

  • You have no clinical data addressing it.
  • You have data, but the data do not match your intended purpose (population, indication, site, duration, user).
  • You have matched data, but the methodological quality is too weak to support the claim.
  • You have adequate data for the claim today, but no plan to keep the evidence current under Article 61(11) as the device moves through its life cycle.

All four are gaps. All four have different closure paths. Lumping them together is the mistake that turns gap analysis into a rubber-stamp exercise.

The GSPR-by-GSPR method

Run the analysis as a single table, one row per relevant GSPR. The columns are fixed:

  1. GSPR reference — the exact Annex I section and subsection.
  2. Relevance — relevant, not relevant (justified), or partially relevant (scoped).
  3. Clinical claim being made — the specific claim your device makes that this GSPR covers.
  4. Current evidence — the specific data sources (literature, equivalence, prior PMS, bench testing with clinical correlation) that currently support the claim.
  5. Sufficiency assessment — sufficient, partial, or missing, against the acceptance criteria set in the CEP.
  6. Gap description — if not sufficient, a one-sentence statement of what is missing.
  7. Closure option — literature, equivalence, PMCF, clinical investigation, or narrowed intended purpose.
  8. Owner and deadline.

Annex XIV Part A, Section 1(a) requires the clinical evaluation plan to include an indication of the general safety and performance requirements that require support from relevant clinical data. (Regulation (EU) 2017/745, Annex XIV, Part A, Section 1(a).) The GSPR-by-GSPR table is the literal implementation of that requirement. If your CEP does not contain it, you are not running a gap analysis — you are writing prose around whatever evidence you already collected.

The table is also the single document a Notified Body reviewer will ask for when they want to understand your clinical strategy. Build it early and keep it current.

The four closure options

Every gap, once named, gets routed to one of four closure paths. The choice is not arbitrary — it follows from the gap type.

Appropriate when the gap is "we have not yet looked hard enough." The closure work is a refined literature search protocol — additional databases, broader or more targeted search strings, adjacent device categories, grey literature, or newer publications since the last search date. The cost is low. The time is days to weeks. Annex XIV Part A, Section 1(c) requires the literature review to be systematic, so any expansion is a protocol revision, not a fresh informal search.

Route a gap here when: the intended purpose is matched, the device class has an existing published evidence base, and your previous search was narrower than it needed to be.

Option 2: Equivalence under Article 61(4)-(6) and MDCG 2020-5

Appropriate when there is a well-documented comparator device with sufficient published or accessible clinical data, and your device genuinely meets all three pillars — technical, biological, and clinical — defined in Annex XIV Part A, Section 3 and in MDCG 2020-5, April 2020. For implantable and Class III devices, Article 61(5) additionally requires a contract giving the manufacturer ongoing access to the technical documentation of the equivalent device; MDCG 2023-7 (December 2023) clarifies what "sufficient levels of access" means.

Route a gap here only if all three pillars are genuinely met. Equivalence is the closure path startups reach for most often and qualify for least often. If any of the three pillars is weak, pick a different option. See our equivalence deep dive for the full pillar-by-pillar test.

Option 3: PMCF activity under Annex XIV Part B

Appropriate when the gap is in long-term performance, rare adverse events, real-world usability, or evolution of state of the art — things that can only be observed after the device is in use. Annex XIV Part B requires the PMCF plan to include general and specific methods and procedures, a rationale for their appropriateness, specific objectives, and reference to relevant parts of the CER and risk management. (Regulation (EU) 2017/745, Annex XIV, Part B.)

A PMCF study, a PMCF registry, a PMCF survey, or structured user feedback can close gaps that do not need to be closed before market access — provided the CEP justifies why it is safe and proportionate to launch with the gap open and close it post-market. Article 61(11) then requires the CER to be updated as PMCF data accrues. For implantable and Class III devices, the update must happen at least annually. Our PMCF guide for startups walks through what a real PMCF plan looks like.

Option 4: Clinical investigation under Article 62 and Annex XV

Appropriate when the first three options are genuinely exhausted. A clinical investigation is required under Article 61(4) for implantable and Class III devices unless one of the exemptions in Article 61(4)-(6) applies (MDCG 2023-7 covers the exemption cases). Article 62 governs the general requirements; Annex XV sets out documentation; EN ISO 14155:2020+A11:2024 is the good clinical practice standard. Costs for a first-time sponsor typically start in the mid-six figures and escalate from there.

Route a gap here when: the device is novel, the intended purpose cannot be narrowed further, no equivalence comparator meets all three pillars, and the gap is in a claim that cannot responsibly be closed post-market. Route it here with full knowledge of the cost — and with the prior check that none of the cheaper options was actually available.

The zero-th option: narrow the intended purpose

Before any of the four closure options, run the zero-th option: tighten the intended purpose. Most clinical data gaps exist because the intended purpose is wider than the available evidence. A population too broad, an indication too generic, a user group too loosely defined, a duration of use too long.

Narrowing the intended purpose shrinks the evidence burden without generating a single new data point. It is the cheapest closure path in the entire MDR, and it is available on almost every first-time CER we review. The constraint is honesty — the narrower intended purpose has to be the one you are actually willing to ship under, and it has to flow through labelling, IFU, and marketing consistently. Startups that narrow on paper but sell broadly end up with a vigilance problem, not a gap-closure win.

A worked startup case

A Class IIb wearable monitoring device — three founders, one regulatory consultant, a CER draft that listed fourteen papers and concluded the benefit-risk ratio was acceptable. The Notified Body flagged the CER with nine findings. The founders came to us convinced they needed a clinical investigation.

We built the gap analysis table. Twenty-three GSPRs were relevant. Fourteen were adequately supported. Nine had gaps. Of the nine:

  • Four were closed by a refined literature search — the original search had missed two databases and a relevant year range, and the refined search returned sixteen new matched papers. Two weeks of work.
  • Three were closed by narrowing the intended purpose. The original claim included a paediatric sub-population the evidence did not support. Removing paediatrics from the intended purpose eliminated the three gaps without any new data. The founders confirmed the adult-only market was still commercially viable.
  • Two were routed to a PMCF plan — long-term wear comfort and a rare skin reaction signal that could only be confirmed with post-market data. The PMCF plan was built against Annex XIV Part B as a literal checklist.
  • Zero needed a clinical investigation.

The cost of gap closure was under EUR 30,000 in consultant time and literature work, plus the ongoing cost of the PMCF plan. The founders had been budgeting for an EUR 500,000+ clinical investigation. The difference was entirely the result of running gap analysis GSPR by GSPR before deciding what to generate. This is the same discipline the Graz case in our biggest clinical evaluation mistakes post shows from a different angle: check the map before walking into the forest.

Ship — the gap analysis template

Use this as the header row of your gap analysis table. Drop it into the CEP, fill it per GSPR, keep it live through the life of the device.

| GSPR ref | Relevance | Clinical claim | Current evidence | Sufficiency | Gap description | Closure option | Owner | Deadline |
|----------|-----------|----------------|------------------|-------------|-----------------|----------------|-------|----------|
| Annex I, GSPR 1 | Relevant | [specific claim] | [sources] | Sufficient / Partial / Missing | [one sentence] | Literature / Equivalence / PMCF / CI / Narrow IP | [name] | [date] |

Rules for filling it in:

  1. Every GSPR judged "not relevant" gets a one-sentence justification in the relevance column. "Not relevant" is a defensible position only when it is written down and defended.
  2. Every "sufficiency = partial or missing" row gets exactly one closure option. If two options apply, split the row.
  3. Every closure option names an owner and a deadline. A gap without an owner is a gap that will not close.
  4. The table lives in the CEP and is updated whenever PMS, PMCF, vigilance, or state-of-the-art changes reveal a new gap. Article 61(11) requires the CER to be updated throughout the life cycle; the gap analysis table is the operational tool for meeting that requirement.

Reality Check — Where do you stand?

  1. Does your CEP contain a GSPR-by-GSPR gap analysis table, or does it summarise evidence in narrative form only?
  2. For every "not relevant" GSPR, do you have a written, defensible justification?
  3. For every relevant GSPR, have you named the specific clinical claim and mapped the specific evidence source?
  4. For every gap, have you picked exactly one closure option and named an owner and deadline?
  5. Have you run the zero-th option — checking whether a narrower intended purpose closes gaps before generating new data?
  6. If you are routing a gap to equivalence, can you defend all three pillars (technical, biological, clinical) in writing today, and do you hold the Article 61(5) contract if required?
  7. If you are routing a gap to a clinical investigation, have you documented why none of the other three options was available?
  8. Does your gap analysis table live inside the CEP, and does it update when PMS or PMCF data arrives?

If you answered "no" or "not sure" to three or more, the gap analysis is the next thing to fix — before you generate any new clinical evidence and before you touch the CER draft.

Frequently Asked Questions

What is a clinical data gap analysis under MDR? It is a GSPR-by-GSPR audit comparing the clinical evidence your device currently holds against the evidence Article 61 and Annex XIV Part A require for each relevant general safety and performance requirement. The output is a table of gaps, each with a named closure path, owner, and deadline. It belongs in the clinical evaluation plan, not in the CER.

When should a startup run a clinical data gap analysis? Before writing the CER, as part of building the clinical evaluation plan required by Annex XIV Part A, Section 1(a). Running gap analysis after the Notified Body flags the CER is possible but expensive — every week of delay costs cash, and rework is always more work than getting the plan right the first time.

Can I close a clinical data gap by narrowing the intended purpose? Yes, and this is usually the cheapest option. Narrowing the intended purpose shrinks the evidence burden without generating new data. The constraint is that the narrower claim must flow through labelling, IFU, and marketing consistently — a narrow intended purpose on paper with broad marketing creates a vigilance problem.

When is a clinical investigation actually required to close a gap? A clinical investigation under Article 62 and Annex XV is required when the first three closure options — literature, equivalence, PMCF — are genuinely not available, and for most implantable and Class III devices unless one of the Article 61(4)-(6) exemptions applies. MDCG 2023-7 clarifies the exemption cases. It should be the last option, not the default.

Can PMCF close a gap that exists before market launch? Only if the CEP justifies in writing that launching with the gap open is safe and proportionate, and the PMCF plan under Annex XIV Part B is structured to close it with defined objectives and methods. Article 61(11) then requires the CER to be updated as the PMCF data accrues. For implantable and Class III devices, the update must happen at least annually.

Sources

  1. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices: Article 61(1), 61(3), 61(4)-(6), 61(10), 61(11); Article 62; Annex I GSPR 1 and GSPR 8; Annex XIV Part A (clinical evaluation); Annex XIV Part B (PMCF); Annex XV (clinical investigations). Official Journal L 117, 5.5.2017.
  2. MDCG 2020-5 — Clinical Evaluation — Equivalence: A guide for manufacturers and notified bodies, April 2020.
  3. MDCG 2023-7 — Guidance on exemptions from the requirement to perform clinical investigations pursuant to Article 61(4)-(6) MDR and on "sufficient levels of access" to data needed to justify claims of equivalence, December 2023.
  4. EN ISO 14155:2020 + A11:2024 — Clinical investigation of medical devices for human subjects — Good clinical practice.
  5. EN ISO 14971:2019 + A11:2021 — Medical devices — Application of risk management to medical devices.

This post is part of the Clinical Evaluation & Clinical Investigations series in the Subtract to Ship: MDR blog. Authored by Felix Lenhard and Tibor Zechmeister. Gap analysis is the single highest-leverage move a first-time MDR startup can make on clinical evaluation — and it costs nothing except the discipline to name what is missing in writing.