A clause-by-clause interpretation of the "MDCG 2024-3 Guidance on content of the Clinical Investigation Plan for clinical investigations of medical devices" (March 2024)

Statement: All key points in this article are drawn directly from the MDCG 2024-3 document itself, with the corresponding sections/page numbers cited in each part for verification against the source text. This article does not introduce any additional requirements or "industry folklore" beyond the wording of the guidance.

I. First, what exactly is a "CIP"? It is your EU clinical investigation "field operations manual"

MDCG 2024-3 defines the CIP very clearly: it must describe the rationale for the clinical investigation, its objectives, design and methodology, monitoring, conduct, record retention, and methods of analysis; and it must be detailed enough to function as an operational manual so that investigators at different sites and at different times can implement the study consistently. It must also enable the Competent Authority/Ethics Committee to assess whether, after risk minimisation, the risks are reasonably outweighed by the expected benefits, and whether the reliability and robustness of the data justify exposing subjects to the device and procedures involved. (MDCG 2024-3, Section 2, p6)

Plain-language takeaway: when the CIP is well written, site execution is far less likely to derail; when it is vague, running the study is like driving fast in fog—you may think you are in control, but it is mostly luck.

II. General principle for drafting a CIP: include as much information as possible in the CIP itself; if information is placed in appendices, provide a summary + cross-reference + submit it together

The guidance explicitly prefers that all necessary information be included in the CIP itself. If certain content must be placed in separate documents (for example, the monitoring plan or site list), the CIP must still summarise and reference those documents, and the referenced documents must be submitted as part of the initial application package. (MDCG 2024-3, Section 3, p6; Section 3.6.6, p14)

Practical reminder: appendices are not a dumping ground. If the CIP does not state things clearly, reviewers will very likely ask follow-up questions; follow-up questions mean more time, more cost, and more wear and tear on your team.

III. A clause-by-clause breakdown of the CIP content corresponding to MDR Annex XV Chapter II Section 3: how to write it, how much detail is needed, and common pitfalls

MDCG 2024-3 presents the content according to the numbering in MDR Annex XV Chapter II Section 3 (which makes regulatory cross-referencing easier), but it also makes clear that you are not required to use the same layout order, as long as all statutory elements are covered and any "Not applicable" items are justified. (MDCG 2024-3, Introduction, p5)

3.1 General: get the "identity information" complete first, or the review may stall at the door

It should include: the title, CIP number, version/date, summary of revision history, abbreviations, and an overall synopsis (a flowchart may also be helpful). The information in the synopsis must also be fully elaborated in the main body and remain consistent throughout. In addition, the synopsis must be provided in the EU official language required by the Member State; corresponding language versions should therefore be prepared according to national requirements. (MDCG 2024-3, Section 3.1, p6)

Practical checklist highlights (perfectly acceptable to use as-is):

Write the version number, date, and revision history as clearly as a software release log, to avoid sites using the wrong version. (3.1, p6)
Do not let the synopsis become mere marketing copy; every point in it must be expanded in the body text, operationalised, and executable in practice. (3.1, p6)
For multilingual synopses, confirm Member State requirements early rather than discovering at the last minute that translation is still needed. (3.1, p6)

The CIP should also clearly identify, with contact details: the Sponsor, legal representative (if applicable), Principal/Coordinating Investigator, each investigational site, third parties such as the CRO and central laboratory, and the device manufacturer; it should also describe the roles, responsibilities, and qualifications of the different investigator levels. (MDCG 2024-3, Section 3.1, p7)

If the site and PI list is maintained in a separate document, the CIP must describe a mechanism that ensures all investigators can access the current list throughout the investigation, especially for emergency communications. (MDCG 2024-3, Section 3.1, p7)

In addition, the CIP should briefly describe the source of funding, the Sponsor-site agreement, and, where applicable, the Sponsor-manufacturer agreement. These agreements may cover matters such as device supply arrangements, proprietary information, and publication arrangements. (MDCG 2024-3, Section 3.1, p7)

Plain-language reminder: a site list is more than an Excel attachment—when something urgent happens, not being able to reach the right person can be even more alarming than an AE.

3.2 Device identification and description: do not leave reviewers unsure which exact version of the device is being studied

The guidance requires, where applicable, the following: a device summary (including the intended purpose under investigation and the target population/indication); any differences from the intended purpose for future market placement must be stated clearly; if the device is already CE marked, the CIP should explain whether the intended purpose in the investigation is different or is being further evaluated within the existing scope; manufacturer information; model/model number, software version, and accessories; traceability details (such as batch number/serial number); a list of materials contacting tissue/body fluids; definitions for implantable devices, devices incorporating a medicinal substance, or those containing human/animal tissues or biologically active substances (if applicable); training and experience requirements based on risk assessment; relevant medical/surgical procedures; and a background literature review. (MDCG 2024-3, Section 3.2, p7-8)

The guidance also recommends incorporating Section 3.18 (technical and functional characteristics and their relationship to the expected clinical outcomes) into the device description, in particular by explicitly identifying which characteristics are covered by the present investigation. (MDCG 2024-3, Section 3.2, p8; Section 3.18, p20)

Three practical ways to avoid common pitfalls:

Simply writing "a certain system" or "a certain catheter" is not enough—if the model, software version, accessories, or contact materials are missing, follow-up questions will continue throughout the review. (3.2, p7-8)
Investigational intended purpose vs future marketed intended purpose: if the difference is not clearly explained, you will repeatedly be asked what exactly you are trying to demonstrate. (3.2, p8)
Do not reduce training requirements to a single sentence such as "trained personnel only"—the guidance explicitly requires a summary of the necessary training/experience based on risk assessment. (3.2, p8)

3.3 Benefits and risks: the more "quantifiable" your description is, the more credible—and the easier the review becomes

For benefits: describe the direct benefits to subjects, and benefits to others may also be included (caregivers, family members, healthcare professionals, public health, etc.). For both direct and indirect benefits, the guidance recommends considering item by item: the type and estimated magnitude of benefit; the probability that subjects will benefit (or subgroups more likely to benefit); the duration of benefit; and the medical need addressed (i.e., whether the need is unmet by other devices/therapies). The availability of alternative devices/therapies and their accessibility should also be assessed, including regional differences. In addition, where available, patient preference information (PPI) may be used as background information. (MDCG 2024-3, Section 3.3.1, p8-9)

For risks: identify all risks arising from participation in the investigation, whether device-related or procedure-related, and consider interactions with concomitant treatments. Risk characterisation should cover the type of risk, likelihood of occurrence, duration, and severity of harm; risks to healthcare professionals, family members, and caregivers should also be considered. The guidance also specifically highlights the need to consider "data interpretation risk," for example the risk of drawing incorrect conclusions from the data or the risk created by data uncertainty or difficulty of interpretation. (MDCG 2024-3, Section 3.3.2, p9)

Priority for risk mitigation: first eliminate or reduce risks through inherently safe design and manufacture (with emphasis that design verification and validation should be completed before clinical submission); second, implement protective measures (such as physical protection or alarms); third, communicate safety information (labelling, informed consent, training, information transfer between sites, and communication with Ethics Committees/Competent Authorities, etc.). (MDCG 2024-3, Section 3.3.2, p9)

At the same time, the risk list must remain consistent with the foreseeable AE/ADE/SADE/DD described in Section 3.14; for CE-marked devices (including comparators), a brief summary of available PMS data should be provided; and the CIP should describe how risk thresholds and the degree of subject suffering will be defined and continuously monitored. (MDCG 2024-3, Section 3.3.2, p10)

Benefit-risk ratio: provide the rationale and consider the conditions set out in MDR Article 62(3) and 62(4)(e); the study design should minimise pain, discomfort, fear, and other foreseeable risks as far as possible. The guidance also recommends supporting the justification with available non-clinical data and the conclusions of the clinical evaluation. (MDCG 2024-3, Section 3.3.3, p10)

Plain-language summary: if benefits are described as "it should feel good" and risks as "it should probably be fine," that is not a CIP—it is a wish list.

3.4 Relevance of the investigation: you need to explain why this investigation is necessary

The investigation should be placed in the context of current clinical practice (State of the Art) to explain its relevance; the justification for the study design should also be based on the conclusions of the clinical evaluation: summarise relevant non-clinical tests/assessments and previous clinical investigations (where applicable) to demonstrate why the device can be used in humans, and evaluate the clinical data relevant to this investigation. The CIP should also explain which stage of clinical development the investigation belongs to: pilot, pivotal, or post-market. (MDCG 2024-3, Section 3.4, p10-11)

3.5 Objectives and hypotheses: do not treat endpoints as decoration—they determine the statistics, the sample size, and whether the study can ultimately support your regulatory objectives

The guidance requires a description of: the purpose of the investigation; the performance/effectiveness/safety claims to be verified; objectives classified as primary/secondary/exploratory; whether superiority/non-inferiority/equivalence is to be demonstrated, where applicable; the scientific justification and clinical relevance of the effect size, non-inferiority margin, or equivalence margin; the primary/secondary hypotheses, where applicable; and the risks and expected ADE to be assessed. (MDCG 2024-3, Section 3.5, p11)

Endpoint requirements: they should cover the intended purpose, clinical benefit, performance, and safety; they must be determined and assessed using scientifically valid methods; and the primary endpoint should be appropriate for the device, clinically relevant, and assessable. (MDCG 2024-3, Section 3.5, p11)

3.6 Investigation design: describe "how it will be done" clearly enough that sites do not need to call you for clarification

The guidance emphasises that the design must be sufficiently detailed and must demonstrate scientific robustness and validity. (MDCG 2024-3, Section 3.6, p11)

3.6.1 Type/endpoints/variables (consistent with the Clinical Evaluation Plan): fully explain the rationale for each choice

The CIP should specify the type of investigation (exploratory/confirmatory, etc.); define the primary/secondary endpoints and explain why they were selected and how they will be measured, with emphasis on endpoints covering safety, performance, and clinical benefit; composite endpoints, where used, should also be justified. For early-stage investigations, especially with new/high-risk devices, the guidance recommends considering additional safety measures such as closer Sponsor oversight, independent safety monitoring, and limits on the enrolment rate (for example, evaluating the first subject before treating the next subject, staged enrolment, or a run-in phase). The expected duration of the investigation should also be described, including both individual subject participation time and overall study duration. (MDCG 2024-3, Section 3.6.1, p11-12)

3.6.2 Study groups and controls: having no control may be acceptable, but the rationale must be clearly explained

The study groups should be presented, such as device vs control (another device, medicinal product, treatment modality, sham procedure, etc.), together with the justification for the selected control or for the absence of a control. For implantable devices, an implant card must also be provided to subjects, and the CIP should describe the content of the card and when/how it will be provided, taking into account the relevant aspects of MDR Article 18. (MDCG 2024-3, Section 3.6.2, p12)

3.6.3 Subjects and inclusion/exclusion criteria/sample size/representativeness/vulnerable populations: do not define the "target population" as vaguely as "whoever seems suitable"

The CIP should state: the total sample size and, where applicable, the allocation across groups; whether vulnerable populations are included (children, pregnant or breastfeeding women, persons lacking capacity, immunocompromised subjects, older adults, etc.); the inclusion/exclusion criteria and who is responsible for determining eligibility (including role and qualifications); the recruitment process (including when a subject is considered enrolled and, if different, the timing of randomisation); and compliance with the requirement that the investigation setting should represent the normal conditions of use for the target population. This means discussing the representativeness of the sample relative to the target population (aetiology, disease severity, sex, age, etc.) and why the investigational site environment is appropriate; in multicentre/multinational investigations, differences in standard of care and the impact of local adaptation should also be considered. The CIP may also describe whether patients were involved in setting objectives, assessing burden, or disseminating results. (MDCG 2024-3, Section 3.6.3, p12-13)

3.6.4 Reducing bias and confounding: if this is not clearly described, your "effectiveness" claims may be treated as speculative

The CIP should describe randomisation, allocation concealment, blinding/unblinding, and management of confounding factors; single-arm design, control selection, historical controls, open-label design, and similar elements should all be addressed with justification. If a sham procedure is invasive or burdensome, it must be fully justified, otherwise the ethical basis may not hold. Potential conflicts of interest and their management should be transparently disclosed, especially where the inventor is deeply involved, including how undue influence on subjects and endpoint assessment will be prevented; independent committees may be used for eligibility confirmation, event classification, endpoint adjudication, etc. The guidance also recommends considering a DSMB/DMC to provide ongoing oversight and recommend continuation, termination, or modification of the investigation; if blinding is used, the CIP should specify who may be unblinded and under what triggering conditions. (MDCG 2024-3, Section 3.6.4, p13)

3.6.5 Clinical procedures and diagnostic methods: a schedule of events is helpful, but a table alone is not enough

All investigation-related procedures and diagnostic methods should be described, with particular emphasis on what deviates from routine clinical practice; a schedule of events table may be used for overview, but the CIP must also clearly describe what will be done at each visit, in what sequence, by what method, and by whom. The CIP should also specify the number of devices/comparators used per subject and the safety procedures if the same device is used repeatedly; the methods and timing for assessment/recording/analysis of variables (including device maintenance and calibration arrangements); biological sample collection, where applicable, and compliance arrangements; a follow-up period long enough to demonstrate performance/effectiveness/safety and identify ADE risk; permitted and prohibited concomitant treatments (including contraindications and interactions); lifestyle restrictions such as contraception or diet, where applicable; criteria and procedures for withdrawal/loss to follow-up, tracing measures, and whether replacement subjects will be enrolled; where relevant, consideration of a final safety follow-up visit; whether continued access to the device is possible after study completion, where applicable; and, for implantable devices, explantation/retrieval analysis and, if the implant remains in situ, how safety monitoring beyond the investigation period will be ensured. (MDCG 2024-3, Section 3.6.5, p13-14)

3.6.6 Monitoring plan: the CIP should at least present the "monitoring framework" rather than merely saying "monitoring will be performed"

The guidance requires that the Sponsor ensure adequate monitoring to protect the rights, safety, and well-being of subjects, ensure reliable and robust data, and maintain compliance with MDR and GCP. The CIP must include information on the monitoring plan; the detailed monitoring plan does not necessarily have to be submitted with the application and may exist as a separate document, but the CIP should at minimum include: the overall outline of the monitoring plan, the appointment of monitors independent from the investigational site, monitors' access to source data, and the planned extent of source data verification. The intensity of monitoring should be based on the characteristics of the investigation (objectives, methodology, degree of deviation from routine practice, etc.). (MDCG 2024-3, Section 3.6.6, p14)

3.7 Statistical design and analysis: do not be afraid of detail—the real problem is leaving things unwritten

The guidance lists very detailed statistical elements: analysis populations and procedures (covering all data), descriptive statistics for baseline/treatment/safety data, precision measures (such as confidence intervals), testing strategy for the primary endpoint where applicable, sample size calculation and its basis (effect size/hypotheses, expected between-group differences, adjustments for interim analyses, non-inferiority margin and its justification, randomisation ratio, dropout rate, etc.); for exploratory/observational investigations, even if sample size is not calculated according to standard requirements, a scientific justification is still needed; the number of procedures related to the learning curve and the corresponding analysis; success/failure criteria; quantitative statistical criteria for interim analysis and stopping, where applicable; strategies for controlling bias and confounding and their justification; strategies for handling sample imbalance across centres; multiplicity control; subgroup analyses and their justification; management of missing/non-usable/outlier data; sensitivity analyses; procedures for reporting deviations from the original statistical plan; and data pooling strategies, where applicable. Consultation with a statistician is also recommended. (MDCG 2024-3, Section 3.7, p15-16)

Plain-language reminder: a vague statistics section is like barbecue without salt—not impossible to eat, but no one wants a second serving.

3.8 Data management: in one sentence—it must be verifiable, interpretable, and protected

The CIP should describe procedures to ensure data reliability and robustness: the methods for recording/processing/storage must support accurate reporting, interpretation, and verification, while protecting confidentiality and personal data; it should specify post-collection data verification, the process for issuing and closing data queries, and database lock procedures; and it should require technical and organizational measures during and after the investigation to prevent unauthorized access/disclosure/alteration/loss, especially during electronic transmission. The MDR also requires the application to include measures for responding to data security breaches (which may be included in the CIP data management section or in a separate document). Data retention requirements should also be covered. (MDCG 2024-3, Section 3.8, p16)

3.9 Protocol amendments: distinguish between “substantial” and “non-substantial” changes to avoid creating a compliance incident through incremental revisions

The CIP should state that any change likely to have a substantial impact on subject safety/health/rights or on data robustness/reliability must be notified to the competent authority in accordance with MDR Article 75; it should also remind investigators that, before implementing a substantial modification, they must wait for the prescribed period to elapse or obtain approval, whichever occurs first. It should also describe how non-substantial modifications will be managed. (MDCG 2024-3, Section 3.9, p16)

3.10 Protocol deviations: life-saving deviations may be justified, casual deviations are not

The guidance requires a statement that investigators must not deviate from the CIP; only in an emergency, to protect the rights/safety/well-being of subjects, may a deviation occur without prior sponsor approval. It must also make clear that waivers of the CIP are not permitted. The CIP should also specify the procedures for documenting, reporting, and analyzing deviations (including notification requirements and timelines), CAPA, and the criteria for PI disqualification. (MDCG 2024-3, Section 3.10, p17)

3.11 Device traceability and accountability: do not let investigational devices become “unaccounted-for devices”

The CIP should specify traceability and accountability procedures: access control, storage, tracking after use during the investigation, and retrieval of unused/expired/malfunctioning devices; it should also explain how use of the device will be restricted to this investigation and in accordance with the CIP. Investigators must document: the personnel responsible for receipt/use/return/disposal; the date of receipt, identifiers, and quantities (batch number/serial number/unique code); expiry date; date of use; subject identification; retrieval/removal date (if applicable); return date for unused/expired/malfunctioning devices; and disposal records (if applicable). (MDCG 2024-3, Section 3.11, p17)

3.12 Compliance statements: do not omit the required “declarations,” because leaving one out is like leaving a signature off

The CIP should include statements that the investigation will: follow the ethical principles of the Declaration of Helsinki; follow applicable international standards/consensus guidance (such as the latest version of ISO 14155); comply with national legislation and the MDR; not start until regulatory and ethics assessments are complete and non-negative; comply with additional ethics/regulatory requirements (if applicable); and provide the type of insurance available to subjects (if applicable). If the sponsor elects not to follow ISO 14155, it must demonstrate that the alternative approach achieves an equivalent or higher level of subject protection, scientific conduct, and credibility of results. (MDCG 2024-3, Section 3.12, p17-18)

3.13 Informed consent: do not treat it as mere “signature collection” — it is an ongoing communication process

The CIP should describe the overall process for obtaining informed consent, including the process for providing new information and, where applicable, the process for compensation for participation; if a subject cannot provide consent, the corresponding process should also be described. For investigations involving minors, it should summarize how MDR Article 65 will be met: consent from the legally designated representative plus age-appropriate information provided to the minor. For emergency-situation investigations, it should justify why/how the conditions of MDR Article 68 are met (allowing no consent before the first intervention) and describe how the legally designated representative will be identified as soon as possible to obtain consent; given that national rules for designating such representatives differ, the Sponsor should provide country-specific guidance to investigators, and multinational investigations may use national appendices. (MDCG 2024-3, Section 3.13, p18)

3.14 AE/ADE/SAE/SADE/DD: define the “dictionary” first, then discuss reporting

The CIP should list the definitions of AE, ADE, DD, SAE, and SADE; and it should indicate that the recording and reporting requirements of MDR Article 80 must be followed, with reference to MDCG 2020-10/1 (safety reporting guidance) for definitions and reporting information. It must list foreseeable AE and anticipated ADE, including probability of occurrence and mitigation/treatment; if the Sponsor wishes to exclude certain AE from recording/reporting, those events must be listed together with the rationale for why they can be considered non-reportable. It should also describe recording, follow-up, and reporting procedures (including timelines for PI reporting to the Sponsor and, where applicable, Sponsor reporting to competent authorities), and provide emergency contact details for SAE/SADE reporting. It should also state whether a DSMB/DMC will be established; if not, a justification is required. (MDCG 2024-3, Section 3.14, p18-19)

3.15 End of study/suspension/early termination: only when the “closeout pathway” is clearly defined is the investigation truly complete

The end of the investigation should be defined (in connection with the end-of-investigation report requirements of MDR Article 77); subject-level and study-level stopping criteria should be established, taking into account that, in different scenarios, enrollment or treatment may need to stop while follow-up of treated/implanted patients must continue; post-termination or post-suspension follow-up and ongoing care arrangements should be specified; management of follow-up after withdrawal of consent or loss to follow-up should be addressed; and, for implantable devices, it should be stated whether the device will remain in place or be removed at the end of the investigation, together with the traceability approach. It should also describe how to manage cases where, at the end of the investigation, SAE causally related to the device are still ongoing, including the follow-up required based on risk assessment (including duration) and how new SAE identified during follow-up will be handled. It must also make clear that temporary suspension or (early) termination must be notified to the competent authority with reasons provided; under MDR Article 77, reporting is generally required within 15 days (or within 24 hours for safety reasons). In addition, a clinical investigation report should be submitted within 1 year after the end of the investigation; if the investigation is prematurely terminated or temporarily suspended, the report should be submitted within 3 months, together with a lay summary, and should refer to Commission Guidance 2023/C 163/06 (guidance on study report structure). (MDCG 2024-3, Section 3.15, p19)

3.16 Post-study arrangements: do not leave subjects to “disperse once they have been used”

If subjects require additional care as a result of participation in the investigation, and that care differs from the usual care for their condition, the CIP should describe the post-study care arrangements. (MDCG 2024-3, Section 3.16, p20)

3.17 Publication policy: disclose what should be disclosed, and define authorship expectations in advance

The CIP must include that: the investigation will be registered in a public database; the investigation results will be made public; and the conditions and timelines for submission/publication of results, including the sponsor’s role and authorship criteria. (MDCG 2024-3, Section 3.17, p20)

The guidance also states that, before EUDAMED is fully functional, the Sponsor must register the investigation elsewhere in order to comply with Article 35 of the Declaration of Helsinki and Section 5.4 of ISO 14155. (MDCG 2024-3, footnote 26 in Section 3.17, p20)

3.18 Technical and functional characteristics: a “characteristic-specification-expected outcome” cross-reference table is the most reviewer-friendly format

The technical and functional characteristics of the device should be listed, and it should be indicated which characteristics are being investigated in this study. The guidance expects relevant product characteristics to be presented in a table, with the corresponding specifications identified and linked to the intended clinical outcomes; the intended clinical performance outcomes should be both “specific at the endpoint level” and “described overall as relating to either safety or performance characteristics.” In more complex cases, this may be integrated with the device description or endpoint section, or presented separately. (MDCG 2024-3, Section 3.18, p20)

3.19 References: do not rely on unsupported statements — list the references where required

List the literature references relevant to this investigation. (MDCG 2024-3, Section 3.19, p20)

IV. Appendix A Synopsis template: treat it as an “elevator introduction,” but do not turn it into an “elevator anecdote”

The guidance provides a Clinical Investigation Synopsis template in Appendix A, with fields including: title/short title/lay title (if applicable), CIP number/version/date, SRN/CIV-ID (if available), amendment number (if applicable), Sponsor information, investigation sites and countries, device and comparator, study purpose and background (including rationale, disease background, device background, and standard of care), stage of clinical development, study design, objectives, primary/secondary/safety/exploratory endpoints, population description and inclusion/exclusion criteria, sample size, duration and follow-up, statistical considerations, etc. (MDCG 2024-3, Appendix A, p21)

Practical recommendation (still based only on the intended use of the template): every item stated in the synopsis should be expandable in the main body, and any information repeated in multiple places must remain consistent. (3.1, p6; Appendix A, p21)

5. A one-page "deliverable self-checklist" for companies in practice (aligned with the MDCG 2024-3 perspective)

CIP basic information is complete: title, number, version/date, revision history, abbreviations, and synopsis (including language requirements). (3.1, p6)
Roles and contact details are complete, with responsibilities/qualification levels clearly defined; if the site list is maintained externally, there is a mechanism to keep it updated and available. (3.1, p7)
The device description allows complete identification of the model/version/accessories/material contact surfaces/traceability scheme; differences between investigational use and marketed use, if any, are stated. (3.2, p7-8)
Benefits are described in terms of type/magnitude/probability/duration/availability of alternatives; risks are described in terms of type/probability/duration/severity plus data-interpretation risk, and the risk-minimization strategy and priorities are clearly stated. (3.3, p8-10)
The rationale for the investigation, the clinical evaluation conclusions, and the linkage to non-clinical and prior clinical evidence are clear, and the clinical development stage is identified. (3.4, p10-11)
Objectives/hypotheses/endpoints are aligned, the primary endpoint is clinically relevant and assessable, and the methodology is scientifically valid. (3.5, p11)
The design clearly states the study type, rationale for the comparator, implant card (if applicable), population representativeness, site selection, and cross-country differences. (3.6.1-3.6.3, p11-13)
Bias control/blinding and unblinding/sham-procedure justification/conflict-of-interest management/DSMB-DMC arrangements (or justification for not having one) are addressed. (3.6.4, p13; 3.14, p19)
The procedures and visit schedule are both presented in table form and in detail; the follow-up period is sufficient; concomitant treatment, withdrawal/lost to follow-up, and safety monitoring for implant removal/retention are clearly described. (3.6.5, p13-14)
The monitoring plan is at least outlined in the CIP: independent monitor, extent of source data verification, and risk-based monitoring intensity. (3.6.6, p14)
The statistical design covers the basis for sample size/non-inferiority margin/multiplicity/missing data/interim analysis/stopping criteria, etc. (3.7, p15-16)
Data management covers data review/query resolution/database lock/privacy protection/cybersecurity/breach response/retention. (3.8, p16)
Rules for substantial amendments and deviations are clearly stated: when to notify, waiting/approval requirements, deviation logs, and CAPA. (3.9-3.10, p16-17)
Device accountability and traceability record fields are complete, ensuring use only in accordance with the CIP. (3.11, p17)
Compliance statements are complete; if ISO 14155 is not followed, it must be demonstrated that the alternative provides an equivalent or higher level of protection. (3.12, p17-18)
Informed consent is a "process," including newly available information, compensation (if needed), special procedures for minors/emergencies, and a multinational appendix strategy. (3.13, p18)
AE/ADE/SAE/SADE/DD definitions, lists, exclusion rationale (if any), reporting process, and emergency contacts are clearly stated; whether a DSMB/DMC is established is explained. (3.14, p18-19)
Rules for ending/suspending/terminating the study, follow-up/care/reporting timelines, and requirements for the study report and lay summary are clearly stated. (3.15-3.16, p19-20)
The publication policy trio is in place: registration, public results, and publication conditions/timelines/authorship criteria. (3.17, p20)
A technical/functional feature-specification-expected outcome comparison table is prepared, indicating the features covered by this study. (3.18, p20)
The reference list is complete. (3.19, p20)

Conclusion

Many CIP dossiers get held up, supplemented, or questioned again and again; in fact, it is not because the device is poor, nor because the team is unprofessional, but becausewhat is written in the protocol does not match the thing you actually intend to doRegulators see text, not your experience;
if you do not spell it out, they can only assume you "haven't thought it through".If you align the checklist above item by item, reviewers will usually have a hard time keeping on "grilling you forever." (Of course, the guideline itself also says it is not a legally binding document, but it represents an expectation of best practice.) (Introduction, p5)

EU Clinical Investigation CIP Practical Guide: A Clear Explanation of the Regulatory Thinking Behind MDCG 2024-3