How to build your State-of-the-art for your Clinical or Performance Evaluation?
![How to build your State-of-the-art for your Clinical or Performance Evaluation? How to build your State-of-the-art for your Clinical or Performance Evaluation?](/pic/how_to_build_your_state-of-the-art_for_your_clinical_or_performance_evaluation_/VGdTSVpKOU94SUU_.jpeg)
welcome to the medical device made easy podcast here is Monir El Azzouzi from easymedicaldevice.com and today we will help you understand something that is called sota so sota but it's also called state of the art so we talk a lot about that during uh within the mgr but we'll also talk about that for ivdr and uh i have with me so hakan inan so managing director at you quality uh with will help us to understand how to build your sota or your state of the art so hakan inan was a lot of help was talking to us last time about performance evaluation on the podcast and now he's coming back to help us on the sota so hakan welcome to the medical device made easy podcast hi thank you thanks for having me glad to be back great so yeah after last episode on ivdr for performance evaluation i think uh we needed uh still some some more information about ivdr but the topic of today as we discussed is not specifically ivdr but we can maybe uh place some ivdr uh iv examples on it and so it will be mainly about state of the art but um as last time so can you make a small introduction of yourself so that people that don't know you maybe will have a better understanding of who you are sure as you said i am hakan inan i am the founder and managing director of re-quality gambia it's a regulatory and quality company located at munich germany we mainly provide medical device companies and individual diagnostic companies support in their performance and clinical evaluation reporting in compliance with mdr and ivdr good so um as as we said so mainly you are helping so other companies are as a consultant so um so the topic of today will be state of the art and as we said it's not specifically mdr it's also ivdr so um if you had to explain that to somebody that is coming to a state okay what is state of the art what would you say to this person yeah the topic itself is quite complex actually um there are a couple of aspects uh related to state of the art as a as a term uh when you look at the regulation actually um uh i was just going through the md rna video regulation i just wanted to see how many times this term was used okay and so in mdr so state of the art as a term was used 12 times 12 12 times exactly and in ivdr in in vitro diagnostic regulation it was used 20 times okay wow yeah but here is the point Monir although it has been mentioned quite some in both regulations and there is no official definition for state of the art okay so this is the strange part so and as you know article number two in mdr and ivdr uh lists the terms and dif definitions of these terms yeah but in in uh none of them uh you will find the state-of-the-art definition so i suppose i suppose there will be then as usual a lot of interpretation from anybody about what is state of the art exactly so and this is this is the main issue with the state of the art as a term but we do have guidelines documents i mean luckily we do have guidelines documents state of the art is that is not a new term actually okay the term the term was already there it was already used in directives under directives and particularly for clinical evaluation reporting state-of-the-art was always used and utilized and when you look at the med dev 2.71 revision 4 state of the art has already been given there and normally let's let's do one thing i mean when you say state of the art to a lay person uh men generally state of thought actually i just checked the uh the dictionary definition the collins dictionary and oxfords and other dictionaries define state-of-the-art now if you define if you use state-of-the-art as um as an adjective okay so if you say if you want to say that what a state-of-the-art building what a state or art factory what a state-of-the-art facility so which means that the most advanced and uh uh you know most technologically advanced place when you use it as an adjective uh that's that's the common main confusion actually but if you want to use state-of-the-art as a technical term especially in in context of ivdrm and mdr it is the level of knowledge and development achieved by a technique and within this science and the domain so it's not uh necessarily the most advanced technique and technology so this is a little bit confusing for me for me when i try to explain that to anybody it's more like what is existing actually as of today on the market for a certain disease or for a certain treatment or for certain diagnosis or whatever so what are the different techniques so what are the different technologies that are existing and then we are making if i can say just a review of all what is existing uh on the market and then the objective i suppose is that after that you take your technology and you just put a cursor of where is your technology against what is already existing on the market yeah exactly so this is i think this is the philosophy of the uh regulations so they want to have a clear picture of what is already present what is achievable what is more acceptable and what can be achieved by most majority of the devices that are already in the market so you need to have you need to provide a clear and complete picture of an entire scene you know so i think it's a it's it's a very good approach that you have said just uh moving into that before moving into that i just wanted to mention a few other issues that that is relevant to the the current state-of-the-art term now uh and as you know there are also um translations of our regulations yeah and like so the state of the art as a term uh that needs to be translated in every different official language when you look at the german translation of the ivdr there are certain confusions that you can see that arises from the from the translation actually because now the the german word for that is the standard technique which is named as the state of the art but when you go through the um when you go through the uh the translation of the ivdr especially so there are multiple places where the german definition is more like uh the most advanced and the latest medical technology or latest medical knowledge so when you compare to english version which is normally just the state of the art so i think we will we will have this issue of uh state of the art and how to define state of the art for coming years for some more time until we get feedback from the uh notified bodies and so i i suppose for example as i know that there is a lot of notified bodies that are located in germany in germany go to another country and try to understand it from by reading the german part but not really not really looking at the english part you can have some issues if i can say just to i mean what they will see is actually what they will expect i suppose yeah exactly because when you look at the german translation it says that the latest medical in in certain places not in every places it says that latest medical knowledge but when you look at the state of the art as a definition we know that it's not the it's not only the latest medical knowledge it's just it can be the things that they share it can be things that happened 20 or 30 years ago that were created since the beginning that are bad basic now that uh if i can say are working well but uh but not not new things so it's really uh exactly like like hematology for instance some of the hematology stains are on the market since like 50 60 years and the state of the art is not changed a lot within this content context you know but uh anyway this is one thing that i i really would like to mention before we move into the in the english part so uh now although the state of the art is not defined within the mdr and ivdr we now have as you know actually just recently mdcg guidelines we have mdcg guidelines on antibody covid antibody tests for instance that specifically details about the state of the art in the antibody of it and by the tests so the state of the art is in the name of the uh the the report we also have um the recent guideline actually when you look at this uh mdcg 2021-5 which it just came out in april that's related to the guidance on the standardization and even in that document uh there is a specific section section 3.5 it says that the concept of state of the art so even within that document actually it says that the the state of the art is a difficult concept to explain and it is a very complex and it needs to be it needs to be uh treated as such so when you look at it and it says specifically this mdc g20 21.5 specifically says that taking into account
does not mean compliance so we have in many places like in jsp rs we say that taking into account the current state of the art but it's not although it's it's a term it's not a a requirement for the compliance but this has to be provided okay so when you look at that it says that state of the art is not legally defined concept and it all it involves several complex aspects uh difficult to be expressed in a single and clear definition okay so actually when you look at the when you look at the document mdcg 2025 2021.5 this is what is given so is that means that it says that we give that we give that to manufacturers and say okay now do whatever you want with that it's correct so we have luckily we have guidelines actually so the state-of-the-art actually has been defined clearly in imdrf documents as you know imdrf formerly known as ghdf yeah you know international medical device regulatories form now this there is wgn 47 document and within that document state-of-the-art has been described and this definition actually have been repeated in med dev document and now we see that an uh recent clinical uh evaluation uh uh guidelines document that's been released by mdcg it's the same uh definition has been taken so so we can see that this this is the official definition coming from the uh regulators so it says that develop staged develop stage of technical capability at a given time okay as a regards to products processes and services based on relevant consolidated findings of science technology and experience and actually and there is a note there and this node is follow up in in imdrf in med dev in also other documents it says that the state of the art embodies what is currently and generally accepted as a good practice as you mentioned in technology and in medicine so it has two aspects here so it is relevant to the technology but it's also relevant to the medicine and the state of the art does not necessarily imply the most technologically advanced solution okay so the state of the art exactly is state of the art is also generally mentioned in many places as generally accepted generally acknowledged state of the art so when you look at the definition definition clearly says that we are not looking at the most advanced most used uh technology we are rather than we are looking at a stat a status of the entire field where we are where we are developing our our medical device and i suppose that we are should we take into consideration only medical devices or should be also taken into consideration other forms of treatments like drugs or like other other elements that can maybe exist like atmp or whatever so are we focused on medical devices or can we go outside of this scope yeah i think this is important uh Monir that what you're bringing up so uh it's not very clear but what i would suggest so i mean what describes the uh uh the field is our intended purpose if our intended purpose is relevant to medical device and a disease and a condition so i would suggest that we stick with that okay because for instance if you discuss about like a covid test and it's you want to discuss about only a medical device but we also know that there are lots of treatment options such as the new drugs yeah but definitely this is not in the scope of our uh state of the art i mean you cannot compare you cannot compare your device to this specific mode of action because it's not the same mode of action so you cannot just say my device can do this i can do that in comparison to anything that can do this i can do that mode of action yeah yeah exactly so i mean what derives the state of the art for us is the intended purpose and what's our intended purpose describes the class and everything is you know and so then uh it's better to stick within the uh uh domain of the uh of the medical device and what we claim okay you know so and unless if you talk about companion diagnostic as you know companion diagnostic always have an element of uh therapeutics yeah but other than that i would say we better stick on the uh on the field and because now for as you know there is a medical device aspect there is uh individual diagnosis but there is also drug and therapeutics aspect so yeah i think it will be so much to cover and we will lose the scope yeah so um if we now now that we have if i can see a better understanding of the definition what it is and what is inside or what we should have in scope so um do you have a specific methodology to uh to start your creation of your state of the art for your product or your device so is there a specific steps to follow here yeah i mean like of course um these are not defined in anywhere but in so when you look at the i mean where this state of the art should be given now this is the first question i think we have to ask if we are if we are manufacturer and we want to provide technical file and where where are we going to discuss about state of the art you know in which document in which section so when you look at the uh ivdr and mdr generally state of the art is mentioned within the in ivdr within the performance evolution planning okay and and then performance evaluation report and clinical performance study plan in ivdr it's been specifically mentioned that you need to provide information about state of the art within these sections and when you look at the mdr mdr is uh comparably uh mdr says that in within the clinical evaluation plan and of course clinical evaluation report and clinical investigation okay so within these sections you'll have to describe your uh state of the art when you look at the ivdr monir as you know we have discussed this before ivdr also has an element called the scientific validity report yeah so scientific valid is where we discuss all the scientific background of the device intended purpose and the the medical condition and the analyte so a big state of the art the common state of the art the main body uh as per our understanding should be given under scientific validated report within the context of in vitro diagnostic regulation okay so yeah we have to put in in terms of that so as you said so this is the place where we are having that i think the objective of that is also that we we put it in in this place or the clinical evaluation report or clinical or performance evaluation because we have to prove that our device is safe and performant and against also what is existing around around it so it's just to as i said to put the cursor of our device where it is in comparison to what it is so i suppose do we have also to make a comparison of our products benefits risk ratio in comparison to other solutions that are existing on the market yes so this is an important aspect and now uh coming to your first and second question let's combine both of them now so what do we have to discuss within the state of the arts section you know what it should contain first of all uh we we have to provide a background information okay background information in terms of what is the scientific background if you are measuring an analyte let's say that i am measuring uh i have a glucometer i have my device my device is a glucometer so i have to provide first of all scientific information scientific background so i mean what i'm measuring i'm measuring glucose so i have to provide information about glucose and then what else medical background so i and what is my disease that i am i'm trying to i'm trying to diagnose or treat whatever what's my whatever my purpose is so it's diabetes right so i have to provide information about diabetes what is the current background what is the epidemiology what is the prevalence so now you see we start from scientific reality biochemistry of glucose let's say scientific background and its function and then we move into the disease and the condition so what is the disease what is the epidemiology what's the current status of the disease how many people are sick with that disease you know what's the current uh form of disease development and what's the prevalence within the society so on and so forth so second step providing medical background information and the third step is what are the current methods and techniques that are utilized so this is where you know we discuss about the technique what is my what my technique is based on is it an antibody test is it a genetic test is it a blood based test so and what kind of technique and technology i am using within there uh i'm using am i using like a an amplification a genetic test or am i using an antibody test or am i using a an automated system so and then how does this compare to other methods and techniques that are you that are already there because we will provide only one technique but obviously in the market there are already different technologies yeah it's already been applied so and then after giving this background information on techniques technologies and methods for my disease for my analyte now the next step is the comparison okay now so how does my device perform in compared to other devices performance is an important parameter miner now in 2008 actually uh this there was one of the hiv tests okay and the european union has rejected application because this hiv test was not state of the art based on the low performance category oh yeah in compared to in compared to other hiv tests in 2008 on that day this device was providing a low uh was in the low low tire and it's in compared to other devices it lacks the performance uh elements so that's why this has been rejected by notified body actually this is an active actually it's an interesting uh interesting point to consider so performance is an important element what describes performance of the device what is what is important one what you are saying is that you doing this analyzes also of state of the art and putting your device inside all this information you have also to prove that your device is better or is in the higher level um sector if i can sell the state of the art instead of the one that is really old uh product that is maybe with more risk with less benefit et cetera et cetera so you are also exactly trying to prove that your device is doing good yeah right to others yeah exactly so here we can say that i mean we don't we don't need to prove that our device is the best okay or better than others but we just need to provide that our device achieves what's what majority of the devices are already achieving you know and it is comparable yeah you know if they are providing a test result within 10 days so then my device is also providing device results in 10 days if they have sensitivity of 90 percent on average my device is already providing 1995 so i don't need to prove that my device is better or the best but i need to just provide a background information and the the justification that my device is also achieving these parameters which are commonly and generally accepted and acknowledged within the within the market you know so so how do i do all that then all these searches that we talked about the disease the methodology the thing so should i go on google and say okay diabetes what is diabetes uh let's let me tell you more about that so what is the methodology that we can do for for making the search yeah this is important part now so we have provided a scientific medical technical background we also just i i don't want to miss that point we also had to provide guidelines because now we we have so many professional uh societies you know they provide like they provide starting from who to many uh disease uh related societies yeah so they provide guidelines documents and within those guideline documents depending on the techniques of course if the technique is well established mostly you will find some guidelines and within these guidelines you already have some performance safety and characteristic elements so we also use those guidelines we see that i mean these guidelines are already there according to so and so guidelines these devices has to provide the following information you know so this is one thing we go from guidelines and then of course literature search the most important thing so uh is that so where do we get this scientific medical and technical information most of the times we we perform a systematic literature search so we have to use databases and we have to utilize those databases and we have to identify parameters and most of those parameters are already given so we'll have to we'll have to dive into those scientific parameters and we have to provide those information for these for the scientists out there so i just would say when scientists prepare a review article so it provides all the information about the current status within the field so it is like preparing a review article and you provide all the information and at the end you conclude that whether you're your device your device of interest is state-of-the-art or not okay you know so that's how that's that's how you conclude so so i think this is important because we can also define that our device is not state of the art so what does it mean at the end exactly so here that's that's interesting because here when you look at the regulation in many places it says that it has to be like mainly performance safety uh you know and and the risk so when you look at these three elements it says that based on current acknowledge state of the art based off you know based off the state of the art so as i said state of the art is used in many places but how this will be treated uh it's not clear but from the example that i have just given you there is uh um there is a um a decision based on state of the art actually maybe i'll share this with you so it is done in 2008 and the device was assumed not to be state of the art so and device was rejected the application of the manufacturer was rejected based on that yeah so uh that's why it's a bit delicate issue not very clear at the moment we are still expecting guidelines and documents and also the the practical of course practical experience will also tell us how notified bodies are are treating the state of the art but i think it's it's an important element it needs to be addressed and in sections you will have in especially in performance evolution and clinical evaluation report you definitely need to provide state-of-the-art and you have to mention whether your device is state-of-the-art or not so just maybe one clarification so in terms of state of the art so uh if my device is a completely new technology that was not existing at all and that is completely disruptive technology when you make the state of the art section you will never find any of this type of devices inside but maybe this device has less risk than any other provides more performance than any other etc can we say this device is state of the art because it's not existing i mean like here when you look at the regulation i mean regulation always says that if you want to say something or if you don't want to say something you always have to justify okay you cannot simply say that my device is state-of-the-art or my device is not state-of-the-art so you will have to prove this okay and as you mentioned new and disruptive technologies novel technologies although very rare but there will be very less accumulated scientific and medical knowledge so then you'll have to provide already some performance if you have performance studies you definitely need to provide performance studies then so because the the the field is not developed as to say so you need to provide those information uh you need to have consensus reports you need to have expert reports and you need to provide um consensus from the experts and also keep in mind this will depend on the class of the device so you may request require the amount of scientific evidence might change but we definitely you can utilize some of the analytical and clinical performance data in your state of the art yeah and and one thing that is important as we mentioned as we have this discussion today is about the fact that nothing is black or white there is a lot of gray in the middle uh so even if you think it's not state of the art if you have maybe a good justification to be accepted if you think it's state of the art but in reality it has it is on the lower and uh if i can say of the state of the art maybe it will not be exited because the the risks are more higher than other technologies and other things so as you said there is nothing black or white there is always gray so you have to provide some justification provide some evidence have a debate open with the regulators have the documentation that are opening this debate and that are providing your point of view because you are also the one that knows better the device instead of the other people that are doing that exactly i mean this is this is i think very important aspect so the uh you really need to uh have justification for every claim that you have and support it either scientifically from literature search or from performance studies that your device is state-of-the-art and just keep in mind state-of-the-art sometimes is a very dynamic yeah you know so for instance you have a hematology device that you just want to measure blood count it is a very well established technology and it's been there for like 50 60 years maybe there is very very limited development over the years with state of the art but just imagine the case of the covid last year i mean if you were to prepare a state of the art for the covid a diagnostic test kit let's see and last year there were no mutations exactly no variance and you but now you came here your state of the art has changed and you know the life cycle of the device as you know the performance evaluation uh clinical evaluations according to the regulations now has to be kept and updated throughout the life cycle of the device so it means that depending on the class you'll have to update yeah so it means that yeah it's not something that you are creating once it's something that you have to reevaluate i don't know if it's every year every two years or it definitely depends on your agenda but you have to evaluate that frequently so that you can confirm that your products are state of the art i think for the mdr you can use also the post marketing surveillance pmcs also to get those data to confirm if you are still uh if there is some new technologies new competitors new products that are issued on the on the market because yeah it's not like you say oh today i'm state of the art everything is fine but maybe in two or three or four years there will be a big advance in this technology or in this field and then you are not anymore state of the art you are really on the lower hand and you are you cannot justify anymore to be on the market yeah exactly familiar now um so if let's say that if you're a high-risk high-class group in ivdr or mdr so you know that the you need to update your reports annually but if even if uh sometimes if a new state of the art has appeared if the if there is a performance or safety or state-of-the-art changes then you don't need to wait annual reporting so you need to update your report as soon as those are known and understandable so that's that's i think the case uh for low class uh devices um for like in ivdr a and b you have to maintain throughout the life cycle although the regulation does not imply exactly whether you have to update it every year or two once in two years but still if there is a change and update in in the state of the art that's the definitive uh uh derive into your update and your performance evaluation and as we all know that clinical and performance evaluation is also updated with the new findings from post market service and vigilance there yeah i think it's a it's a it's a good a good summary here um in terms of state of the art so um is there a specific skill or if i can say a specific diploma that the person that is doing that should have or anybody that is maybe trained um with few hours of training on that can do it hey our experience is that so uh it it is quite a complex uh issue because you really have to have a good understanding of uh science medicine field medical field that you are applying your device and regulations and you know so and you should be able to read understand what is there on scientifically and you should be able to evaluate those so that you can write what is in those reports so when you're thinking when you think of this complex background uh i think a trained person would definitely would be required uh at least i mean with masters or phd degrees in the within the field who can understand what is scientifically there and what is in the medical field so that they can they can you know put together all this in a in a report and just keep in mind that there is also a huge uh brain power goes there and people need to need to read evaluate and justify so many aspects so to to to to put together a coherent story let's put in this way so i would definitely say that it requires advanced degrees in the field in relevant fields because now medical field is you know is also quite complex yeah i mean like there is a field in cardiovascular and neuro neurology so you have so many different fields and so you definitely require advanced degree uh and you also need a really good training yeah i i i i can just confirm that from my side i mean i had to work with many customers in terms of clinical evaluation in terms of just also creating the state of the art um the issue is the fact that i'm not an expert in all the clinical fields i know how to do that but uh give me a 10 publication to read about that and uh i will it will take maybe 100 hours for me to do that and to try to imagine when maybe somebody that is trying on this field it will take 10 hours just to read and to understand the compile and to then make its conclusion and whatever so so it's true that yeah the issue we have as regulators or as people that are really specialized on quality and regulatory affairs is the fact that we don't have this clinical aspect this clinical knowledge of for some products and then uh even if we have focused diplomas even if we have some experience i'm a surgeon that is specialized in a neurosurgery you cannot do uh heart surgery maybe or cannot do an orthopedist because you are specialized in a certain area so it's better for you to just uh stay on this on this area so yeah here yeah let's say that having somebody that is really well trained uh is maybe not uh the only thing it's also something that somebody has experienced on the field that already has um ability to read those literatures uh to go through that those databases to search with those keywords etc if you have ever done that before to be honest do it once just once and you will and from there you will ask each type an expert to do that for you because i have done it myself and at the end it's a nightmare to do this kind of thing so i prefer to have it to do that exactly and there is one more thing you know as you already mentioned sometimes it has many aspects yeah so maybe sometimes you you really require uh input from a team rather than one single person although one single person will put together a report and you you may require and because field is is very specific if it's very uh if you require a very specialized skill set exactly so then you might really require an opinion from an and direct expert within the field you know so but still i i think as you already mentioned it really requires um hard and soft skills uh and it's not only reading and understanding it's as you know it's also writing exactly scientific scientific and technical writing now is also a part of it and so we need to find uh people who really has good background can read right understand scientifically have sound backgrounds but also can write well so um in in that in that transition if i can say so how real quality can help then manufacture so you have the ability i think with your people to to help within the different fields in the medical device uh in vitro diagnostic so to do the right thing about that with performance evaluation but to do all the exercises that we talked about today yeah exactly i mean like as you know as i have mentioned state of the art is part of performance evaluation planning it goes into scientific validity and lately at the end it goes into your performance evaluation report or clinical evaluation report so and it requires literature searching it requires as we have discussed all these details so we as a re-quality we are working with highly skilled uh medical writers and we have medical writers having their phds in the field of biochemistry immunology oncology neuroscience cardiovascular diseases and so we definitely can provide all these skill sets and now we have been working in the field for quite some times in ivdr and mdr now uh we are also building up this skill set and you know we are developing as we we work through with with notified bodies so we definitely can help so yeah so don't hesitate as you see so uh hakan is really uh knowledgeable on this field and he has the team to to do that so uh don't hesitate to call hakkan inan so from real quality for for that uh don't go don't go also on the show notes you will have all the details about uh your the linkedin page or the the uh the webpage of real quality uh so i will also place on the channel some some links for you for maybe a better understanding of what is sota and uh what is state of the art and if you have any questions don't hesitate you can reach out to us on linkedin reach out to us also uh through the the websites and ask any of the of the questions that you have and yeah as i said if you need really if you have any projects where you need maybe a lot of support related to that don't hesitate to go and call hakan in and for that okay so it was really a pleasure to have you today i hope you yeah i hope the people will be really getting some support by listening to us and listening to what what we are talking about in terms of state of the art uh yeah and i hope yeah then at the end also that uh people that are needing really help they can really contact contact you and get support from you yeah okay exactly always pleasure talking to you thanks for having me thank you that we we really could help people out there who are struggling with the current changes in medical device and mutual diagnostic device uh updates yeah don't don't don't forget ivdr is coming soon also so 26th of may 2022 next year but uh it will be quick so i don't hesitate to uh to get some support for uh for all your clinical evaluation report or your performance evaluation or any document that you need where there is a need of some technical writer okay so i can thank you and i wish you a nice day thank you you
2021-07-06 23:12