Clinical Evaluation for Medical devices

1. Clinical Evaluation for Medical devices This subject is not unknown to anyone dealing with medical devices however just to reiterate the subject let us remember the objective. This is systematic planned process that contributes to continuous generation, collection, analysis, and evaluation of clinical data on a particular device. These words have lot of significance and each one has its own importance. Let us learn about how to accomplish that task. Before we go into this it is utmost important to learn about the compliance requirement as defined in the various regulatory documents. This requirement is not new and was available in earlier document MDD also but with MDR coming into picture, there is lot of new requirements added to new devices also for the older devices which were already approved and had CE mark. It is important to understand some guidelines MEDDEV 2.7/1 Rev 4 (2016) MDDG 2020-5 and 2020-6 and requirements from ISO 14155. Clinical Evaluation Report is always a topic of audit by notified body hence it’s compliance should be without flaws. Above guidelines are useful as guide but MDR will be considered as final document when any interpretation matter. There are some differences mentioned in above guideline. One striking word “same” and “Similar” must be understood where needed while doing data equivalence with other devices. As general approach to clinical investigation remains same as described below. Process: Stage 0:Where scope needs to be defined and plan is made which must be approved before proceeding to next step. For Class IIb and Class III devices, clinical investigation is also necessary before clinical evaluation. An expert consultation is recommended as reviewer for manufacturer’s clinical development strategy and proposal for clinical investigation. (See exemption defined in MDR) Clinical investigation shall be subjected to scientific and ethical review. Plan must also describe re-evaluation frequency. Stage 1: Identification of pertinent data. This is very crucial stage as data collection shall depend on what is described here. Various area where data can be generated. 1. Global PMS programme. 2. PMCF studies 3. PMS reports and literature 4. Adverse incidents 5. Complaints 6. User reports 7. Data from device equivalent with current knowledge, clinical background, Potential clinical Hazards. 8. Validity of equivalence criteria (guideline is available. Must be referred). Literature search and review protocol.

2. It is very important that complete disclosure of data is given to evaluator where positive and negative data also are present and justification for negative data may be given to establish that they do not pose any additional risk. Stage 2 Data Appraisal: Data value must be appraised with appropriate tools and methodology. Data relevance must be established where applicable. Both qualitative and quantitative appraisal should be done and documented in CER. Along with data appraisal also describe the full appraisal process with methodology, quality, scientific validity. In appraisal, predefined criteria is essential. Provide place and scope for bias, random error, misinterpretation. EC Approval, regulatory approval, clinical investigation plans with amendment changes if arises. Clinical investigation carried out outside EU (Refer MDR for requirement for such situation). Gap analysis. Include Vigilance data in appraisal. While doing equivalence and evaluation of data, it must be assessed that to what extent data are representative. Where necessary appropriate standard for weighing evidence should be used. Please note that drug eluting stent and normal stent are not equivalent even if the stents are exactly same as per equivalence definition. Stage 3: Data Analysis. Carry out qualitative and quantitative approach, results should be consistent, do not include any data which does not have scientific validity. Check adequacy of preclinical testing. Evaluate risk to patients, users, and other persons. See if any gaps found in evidence. Either exclude or justify. Examine if there are any additional needs or PMCF needs. Data Analysis must conform to safety, benefit/risks, performance assessment, conformity assessment on side effects. Stage 4: CER Preparation CER documentation is also an essential part and improper documentation shall always cause issue for notified body. Detailing should be sufficient, and language should be understandable by reader. Normal chapters usually included are, scope and context, document claims, literature search strategy, Type and extent of clinical data, Relevant pre-clinical data, Appraisal criteria, Data Appraisal, Sufficient justification for exclusion, Justification for sufficiency of evidence, Clear description of Benefit and risks, Data analysis consistency, Identification of gaps, residual risk, CER must demonstrate conformity with an essential requirement, Demonstration of Clinical, Technical and Biological equivalence. (Refer various relevant standards like ISO 10993) Proper documentation for clinical investigation for High-risk devices, if exempted then proper justification with relevant regulation quote. CER must contain proper device description like name, model, size, components, software, accessories, intended purpose, medical needs, equivalent device, intended performance, label, IFU and Promo Material. All literature used must be annexed with sources. Literature search and review protocol. Conclusion: Describe date of next evaluation (Refer guideline for period. Certain high-risk devices like implants need to be evaluated every year while other devices may be 2-5 years, but plan must include frequency with justification)

3. Date and signature. Qualification of responsible Evaluator (Refer guideline for qualification need) References as mentioned above. Manufacturer should have procedure to address notified body audit, Clinical evaluation assessment report (CEAR), Suitable resource with clinical competence, confidentiality perseverance. Suitable resource is an essential part and if manufacturer lacs such resource, then they should hire some expert or consulting firms with such expertise like Iziel.