A first-in-human arthroplasty study has to do more than show that a new implant can be placed successfully. It must resolve the main uncertainties around implant, procedure, fixation and early patient outcomes, while opening a clear route to pivotal evidence, PMCF and long-term follow-up.
CMO · Orthopedics & Spine
NHS orthopedic surgeon
in orthopedic surgery & Class III implant evidence
Chief Operating Officer · former TÜV SÜD Senior Reviewer · Senior Consultant Surgeon
in device evaluation & Notified Body review
Chief Data Officer · Biometrics & Data Systems
in clinical data management, EDC & biometrics
This page is written for manufacturers taking a new joint replacement technology into patients for the first time. If you are still shaping the overall evidence strategy rather than a single study, start at the parent hub and come back here once first-in-human work is clearly on the roadmap.
A new platform with no clinical history in patients.
Changes to shape or articulation that alter how the joint behaves.
Fixation concepts whose early behavior is not yet documented.
Surfaces intended to change osseointegration or long-term fixation.
Planning accuracy, fit and intraoperative modification become the question.
Instruments and workflow that change how the implant is delivered.
Planned versus achieved position, technical failure and the learning curve.
Design changes large enough that previous evidence no longer covers them.
→ Clinical evidence for arthroplasty medical devices, the parent hub, where the full evidence architecture is set out.
The decision should begin with the clinical evidence gap, not with the assumption that every new device needs the same study design. A focused review of novelty, existing data and residual risk usually shows whether a full first-in-human investigation is proportionate, or whether a bridging strategy or a more targeted study would answer the open questions.
A pre-CE-mark clinical investigation in patients.
Bridging strategy or focused clinical evidence.
Pilot or usability-focused investigation.
Early clinical study with targeted imaging or RSA.
Prospective PMCF investigation or indication-specific study.
Targeted early study scoped to the residual question.
The factors that shape the decision are the novelty of the implant, material, coating or fixation method; how far the device differs from existing or previous-generation products; the availability and relevance of existing clinical evidence; the strength of any equivalence or bridging argument; the intended purpose and clinical claims; the identified residual risks; the uncertainty remaining after bench, biomechanical and preclinical testing; and any feedback from authorities or the Notified Body.
The evidence plan depends on what has actually changed. A modest revision to a well-characterized platform raises very different questions from a new bearing couple or a cementless surface with no clinical history. Defining the novelty precisely is what makes the rest of the study design proportionate.
Positioning, stability, range of movement, alignment and the device-specific failure modes a new shape could introduce.
Biocompatibility, wear, debris generation, fixation and longer-term performance, questions that mature slowly and shape the follow-up plan.
Migration, subsidence, radiolucent lines, osseointegration and loosening, where early radiographic behavior is an important signal.
Planning accuracy, fit, intraoperative modification and imaging confirmation that the achieved result matches the plan.
Planned versus achieved position, workflow, technical failures, conversion to a manual technique and the learning curve.
Worked example. A new cementless porous coating introduces uncertainty about early fixation. That uncertainty defines the study question, the question determines the endpoint (migration measured by RSA at defined timepoints), and the endpoint has to generate evidence that still supports the conclusion the CER will eventually need to make.
The study should be large enough to generate interpretable early evidence, but focused enough to protect patients and allow each case to be reviewed closely. That balance, rather than a fixed sample size, is what defines a proportionate first-in-human design.
Is consistency more important than recruitment speed?
How will procedural variation and the learning curve be controlled?
Should enrollment begin with sentinel patients?
Is a historical, concurrent or no comparator justified?
Which early and later uncertainties must be addressed?
What evidence is required before expanding enrollment?
First-in-human recruitment should reduce avoidable variability without creating a population so narrow that the findings have little relevance to real use. The aim is a cohort that lets the device be assessed cleanly, while still resembling the patients it is ultimately intended for.
The first cohort is normally not the place for severe bone loss, highly complex revision cases, unusual anatomy, patients with multiple competing causes of poor function, or patients unlikely to complete follow-up. Complex cases can be added later, once the early signal is understood.
Selection criteria should connect directly to the intended-use population and the future clinical development pathway, so that the early evidence stays relevant to the eventual claims.
Selecting first-in-human sites is more than identifying well-known names. The priority is centers that can deliver consistent surgery, disciplined documentation and complete follow-up, with the infrastructure to review early cases in detail.
Each market brings its own context. Germany offers high-volume arthroplasty centers, including centers certified under EndoCert. Austria has established specialist centers and national referral patterns. Switzerland combines specialist arthroplasty centers with local language requirements and familiarity with SIRIS. Our feasibility and site selection team assesses each center individually before it is proposed.
Selecting first-in-human sites is more than identifying well-known names. Each center is assessed individually against surgical, study, data and follow-up criteria.
A single first-in-human study can span the three markets, provided the different regulatory routes, language requirements and registry opportunities are planned from the start.
Submission routes, language requirements and registry access differ by country and are assessed individually during feasibility.
Planning and measuring the learning curve, rather than explaining it retrospectively, is what keeps the early evidence interpretable.
Key message. The learning curve should be planned and measured, not explained after inconsistent outcomes appear.
Investigator and site training follows ISO 14155 requirements and is documented before the first case.
Early enrollment should be deliberately controlled, so that each of the first cases can be reviewed in detail before the study expands. A staged model gives the sponsor and the oversight group defined points to confirm that the device is behaving as expected before more patients are exposed.
The model chosen should reflect the risk and complexity of the technology, and is agreed with the clinical monitoring plan before first enrollment.
Sentinel patients, review gates and an oversight model proportionate to the technology are agreed with the clinical monitoring plan before the first enrollment.
The first study should establish a clear early safety and performance picture, using endpoints defined in advance that map onto the intended claims. This is the framework; the detailed logic sits on arthroplasty endpoints and PROMs.
Device- and procedure-related adverse events, infection, dislocation or instability, periprosthetic fracture, neurovascular injury, thromboembolic events, wound complications, reoperation, revision, device deficiency or malfunction.
Successful implantation, completion with the intended instruments, intraoperative complications, procedure duration, blood loss, conversion to an alternative device or technique, technical difficulty and unplanned instrumentation.
Implant position and alignment, stability, range of movement, pain, joint-specific function, early fixation or migration, ability to complete rehabilitation and, where appropriate, patient satisfaction.
Each endpoint should remain traceable to a conclusion the clinical evaluation report will eventually need to support, and is prespecified with our biostatistics team in the SAP.
A concise orientation rather than a substitute for arthroplasty endpoints and PROMs, which covers endpoint selection and responder logic in detail.
Fixation, stability, dislocation, periprosthetic fracture, migration and function.
Alignment, stability, stiffness, pain, range of movement and function.
Stability, glenoid fixation, notching, range of movement and rotator-cuff-related function.
Implant integrity, pain, joint-specific function, reoperation and radiographic performance.
Imaging is often where early fixation and migration questions are answered, so the approach should be agreed before the first patient is enrolled rather than assembled afterwards. An imaging charter that defines acquisition, projections and timepoints keeps images comparable across sites and supports reliable pooled analysis.
Marker placement, precision and migration thresholds are covered on imaging, core lab and RSA for arthroplasty studies.
Imaging is often where early fixation and migration questions are answered, so the charter is written up front rather than assembled afterwards.
The first-in-human study should capture early safety, but it should also open a pathway for evidence that matures over time. Setting the schedule at the design stage means the same cohort can carry short-term safety, functional recovery, fixation behavior and, later, survivorship signals.
The final schedule depends on the joint, the implant type, the fixation method, the recovery pathway, the intended claims and the known and theoretical risks. Illustrative timepoints are a starting point, not a template. The long tail is carried by orthopedic PMCF and device registries under EU MDR.
Orientation across the three markets. The full submission routes, document sets and timelines are maintained by our regulatory team for each study.
The EU MDR clinical investigation pathway, with ethics and competent authority planning, device documentation requirements and site contracting. High-volume centers, including those certified under EndoCert, matter here. EPRD may support future registry or long-term evidence planning.
Also the EU MDR clinical investigation pathway, with ethics review and BASG requirements as applicable, country-specific document preparation, German-language requirements and specialist center feasibility.
A separate national framework: Swissmedic and ethics review, ClinO-MD requirements, local representation where applicable, and SIRIS as a potential source of long-term registry evidence.
Country submissions, ethics files and site activation are handled by our regulatory affairs and study start-up teams.
A single first-in-human study can span Germany, Austria and Switzerland, provided the regulatory routes, language requirements and registry opportunities are planned from the start.
Once the design is agreed, delivery becomes a connected chain rather than a series of handovers. Keeping strategy, operations, data and reporting within one team is what maintains consistency across DACH sites.
Eclevar MedTech can provide a single work package or full study delivery: feasibility and site selection, study start-up, clinical monitoring, EDC and data management, biostatistics and clinical reporting, as part of the wider medical device CRO offer, backed by our operational infrastructure.
The initial study is the start of the evidence program, not its conclusion. Its value is greatest when its endpoints are chosen so the early data stay traceable to the conclusions the CER will eventually need to support.
Early safety, feasibility and initial performance.
Refine assumptions, procedures and endpoint estimates.
Support predefined safety and performance objectives, in a pre-market clinical trial.
Address remaining uncertainty in routine clinical use, through a proportionate orthopedic PMCF strategy.
Long-term survivorship, revision and rare outcomes, through device registries and real-world evidence.
Integrate all evidence into the benefit-risk conclusion.
This mirrors the evidence architecture set out in the arthroplasty hub: early endpoints stay traceable to the eventual CER conclusions, and no single study is expected to answer every short-term and long-term question. Where appropriate, the first cohort can continue into arthroplasty PMCF, registries and real-world evidence in DACH.
The program is led by Dr Nikhil Khadabadi, an NHS orthopedic surgeon and former TÜV SÜD Notified Body clinical reviewer.
Clinical strategy, protocol writing, operations, imaging, data management, biostatistics, PMCF and CER support planned together.
Country feasibility, submissions, activation, monitoring and site coordination across Germany, Austria and Switzerland.
Commission a protocol review, endpoint strategy, imaging package or a full clinical investigation.
Timelines follow the maturity of the device and evidence package, protocol readiness, country selection, the number of centers, availability of specialist investigators, imaging and RSA requirements, contracting and submissions, the cohort-staging model and follow-up duration. Costs follow countries and sites, procedural complexity, monitoring intensity, investigator training and proctoring, imaging frequency, core lab or RSA scope, independent safety oversight, EDC and imaging integration, statistical complexity and follow-up duration. We quote in defined work packages, using the same cost model as our European clinical trial cost benchmarking.
Related Eclevar pages across the orthopedic program.
A first-in-human study may be required when a device is sufficiently novel that existing clinical data and any equivalence argument leave meaningful uncertainty about safety or early performance. A focused evidence-gap review should confirm this before a protocol is commissioned.
There is no fixed number. The cohort should be large enough for interpretable early evidence and small enough for close case-by-case review, with the size justified by the device, the questions and the staging model.
It depends on whether consistency or recruitment speed matters more. A single center can reduce variability early, while a multicenter design supports faster recruitment and broader generalisability once the technique is stable.
Suitable endpoints usually combine safety, procedural and early performance measures selected for the specific joint and intended claims. Each endpoint should remain traceable to a later CER conclusion.
RSA may be appropriate when early fixation or migration is the central uncertainty (a cementless design, a new porous coating, modified geometry or a new fixation concept), and when specialist centers and a clear interpretation plan are available.
Yes. A single study can span the three markets, provided the different regulatory routes, language requirements and registry opportunities are planned from the start.
Around defined review gates, beginning with sentinel patients and expanding only after each safety review. Pause and stop criteria should be predefined, with oversight proportionate to the technology.
Yes. Where appropriate, the early cohort can continue into longer-term PMCF or registry follow-up. Designing that pathway from the start strengthens the long-term evidence base and supports future CER updates.
Share your device description, intended claims, existing preclinical evidence and target markets. We review the main clinical uncertainties and outline a proportionate first-in-human strategy covering patients, centers, endpoints, imaging, DACH delivery and the route into longer-term evidence.
Your documents are reviewed confidentially. An NDA can be put in place before we receive any technical or clinical information. You can also reach the team through the contact page.
