Priprema klinike evaluacije za medicinsko sredstvo

Vladimir BURGI PKS, 13. 9. 2017.

Klinika evaluacija

MDD (amandman 2007/47/EC) 6a. Demonstration of conformity with the essential requirements must

include a clinical evaluation in accordance with Annex X.

Odnosi se na sva medicinska sredstva, ukljuujudi klasu I (Aneks VII)

MDR 2017/745/EU clinical evaluation means a systematic and planned process to

continuously generate, collect, analyse and assess the clinical data pertaining to a device in order to verify the safety and performance, including clinical benefits, of the device when used as intended by the manufacturer;

Demonstration of conformity with the general safety and performance requirements shall include a clinical evaluation in accordance with Article 61.

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Smernice: MEDDEV 2.7/1

Rev. 3, decembar 2009

Rev. 4, jun 2016

Obavezujude? These guidelines are not legally binding. It is recognised that under

given circumstances, for example, as a result of scientific developments, an alternative approach may be possible or appropriate to comply with the legal requirements.

Nevertheless, due to the participation of the aforementioned interested parties and of experts from National Competent Authorities, it is anticipated that the guidelines will be followed within the Member States and, therefore, work towards uniform application of relevant EU Directive provisions and common practices within Member States.

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MEDDEV 2.7/1 rev. 4 vs MDR (Tv Sud)

Due to this fact and the fact that this regulation (MDR) includes specific clinical requirements which are not consistent with the MEDDEV Guidance Document on clinical evaluation (MEDDEV 2.7/1 Rev. 4), TV SD decided to extend the implementation timeline for the reflection of the state-of-the-art methods of clinical evaluation. This decision was taken to allow medical device manufacturers to use their resources effectively when adopting the upcoming changes with the new regulation to their clinical evidence documentation.

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MEDDEV 2.7/1 rev. 4 vs MDR (Tv Sud)

July 31, 2017 May 25, 2020 Every submission can still follow the currently used methodology

reflected in the MEDDEV 2.7/1 Rev. 3 or another comparable method

Every submission shall include a plan on how to reflect the current state-of-the-art method for clinical evaluation (i.e., MEDDEV 2.7/1 Rev. 4 or another comparable method)

Every technical documentation that is selected in this period shall either include a plan for the reflection of state-of-the-art methodology implementation as presented, for example, in the MEDDEV 2.7/1 Rev. 4, or be part of a general plan of the manufacturer

May 26, 2020 Every CER which is signed after May 26, 2020, shall be reflecting the

current state-of-the-art method of clinical evaluation by either following the Rev. 4 of the MEDDEV or another comparable method

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MEDDEV 2.7/1 rev. 3

Clinical evaluation is an ongoing process conducted throughout the life cycle of a medical device. It is first performed during the conformity assessment process leading to the marketing of a medical device and then repeated periodically as new clinical safety and performance information about the device is obtained during its use. This information is fed into the ongoing risk analysis and may result in changes to the Instructions for Use.

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MEDDEV 2.7/1 rev. 3

Faza 1: Identifikacija klinikih podataka Pretraga literature i/ili

Kliniko iskustvo i/ili

Kliniko istraivanje i/ili

Harmonizovani standardi

Faza 2: Ocena podataka Adekvatnost

Znaaj u dokazivanju performansi i bezbednosti

Faza 3: Analiza podataka Snaga ukupnih dokaza

Zakljuak o performansama i bezbednosti

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MEDDEV 2.7/1 rev. 3 Primeri harmonizovanih standarda

(http://ec.europa.eu/growth/single-market/european-standards/harmonised-standards/medical-devices/)

EN 285:2006+A2:2009 (veliki sterilizatori)

EN 455-x (medicinske rukavice za jednokratnu upotrebu)

EN 1060-x (neinvazivni sfigmomanometri)

EN 60601-2-10:2000 (neuromiidni stimulatori)

...

Ph Eur MDD: several European Pharmacopoeia monographs may be considered

equal to the abovementioned harmonized standards

MDR: References in this Regulation to harmonised standards shall also include the monographs of the European Pharmacopoeia adopted in accordance with the Convention on the Elaboration of a European Pharmacopoeia, in particular on surgical sutures and on interaction between medicinal products and materials used in devices containing such medicinal products, provided that references to those monographs have been published in the Official Journal of the European Union.

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MEDDEV 2.7/1 rev. 3 Kliniko iskustvo

Postmarketinko pradenje

Baze neeljenih dogaaja

Vigilansa (opozivi, korisna obavetenja = advisory notices...)

Kliniko istraivanje (pre- i postmarketinko PMCF) EN ISO 14155 v2:20111

Nacionalna regulativa

Odobrenje etikog odbora/komisije ustanove

Saglasnost direktora ustanove

Odobrenje ALIMS

Plan klinikog istraivanja sa amandmanima

Potpisan i datiran Izvetaj klinikog istraivanja

Na kraju opet Izvetaj klinike evaluacije

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MEDDEV 2.7/1 rev. 3 Literaturni podaci

Literaturni podaci O medicinskom sredstvu koje se registruje ili ekvivalentnom MS

Protokol pretrage literature

Izvetaj o pretrazi literature

Integralne verzije ukljuenih radova

Protokol pretrage literature Izvori podataka sa obrazloenjem (npr. MEDLINE/PUBMED, Cochrane)

Strategija pretrage (datumi, kljune rei, pretraga literature radova)

Kriterijumi ukljuenja/iskljuenja (jezik, humani subjekti, kontrolisane randomizovane jednostruko/dvostruko slepe/maskirane studije, pregledni radovi...)

Obrada duplikata

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MEDDEV 2.7/1 rev. 3 Literaturni podaci

Izvetaj pretrage literature (apendiks A) Naziv medicinskog sredstva

Obim pretrage literature (usklaen sa obimom klinike evaluacije)

Datum pretrage

Imena osoba odgovornih za pretragu

Period pokriven pretragom

Izvori podataka

Reference svih radova dobijenih pretragom

Ocena adekvatnosti/prihvatljivosti svih radova

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MEDDEV 2.7/1 rev. 3 Ocena radova (apendix D) Ocena kvaliteta rada:

Dizajn studije

Outcome (da li se meri ono to mi elimo da postignemo naim MS, ili je nae/ekvivalentno MS korideno, a mereno je zapravo neto drugo)

Pradenje subjekata odgovarajude (u skladu sa naim MS i oekivanim neeljenim dogaajima)

Statistiki znaaj

Kliniki znaaj

Ocena adekvatnosti rada: Odgovarajude medicinsko sredstvo (nae, ekvivalentno, previe

razliito?)

Odgovarajuda primena

Odgovarajuda populacija

Prijavljeni svi relevantni podaci

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MEDDEV 2.7/1 rev. 3 Sadraj Izvetaja KE (apendiks E) Opti podaci

Zatideno (marketinko) ime, kodovi (GMDN, UMDNS, bududi UDI)

Podaci o proizvoau

Opis ureaja i nain primene Fiziki opis medicinskog sredstva, ukljuujudi sve materijale,

komponente (npr. softver, potroni materijal), sterilnost...

Priroda kontakta sa organizmom (invazivno, sterilno, trajanje kontakta, organi/tkiva sa kojima je u kontaktu)

Kako MS postie nameravanu namenu

Nameravana upotreba Svaka nameravana upotreba (indikacija) mora da bude pokrivena

odgovarajudim dokazima

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MEDDEV 2.7/1 rev. 3 Sadraj Izvetaja KE (apendiks E) Kontekst KE i izbor tipova podataka

Kontekst razvoja: nova tehnologija, nova aplikacija stare tehnologije, etablirana tehnologija. Ukljuuje pregled istorije tehnologije.

Ako se koriste literaturni podaci o ekvivalentnim MS definisati (i obrazloiti) kriterijume ekvivalentnosti

Naglasiti ako MS sadri materijale humanog ili ivotinjskog porekla, ili lekovite supstance

Izvesti zakljuak zato je izabran odreeni put dokazivanja

Ako je dokazivanje literaturom kratak pregled procesa (reference na protokol i izvetaj pretrage literature)

Pregled i ocena klinikih podataka Pregled koridenih podataka

Da li se koriste za dokaz performansi/bezbednosti

Ocena adekvatnosti podataka

Reference literaturnih podataka

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MEDDEV 2.7/1 rev. 3 Sadraj Izvetaja KE (apendiks E) Analiza podataka

Performanse

Bezbednost

Ocena usklaenosti uputstva za upotrebu i literature o proizvodu (broure, marketinki materijal...) sa klinikim podacima

Zakljuak Usaglaenost sa odgovarajudim esencijalnim zahtevima

Performanse po svakoj indikaciji

Prihvatljivost rizika

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MEDDEV 2.7/1 rev. 4

Princip promenjen, neki elementi su pojanjeni, neki stroiji a neki slobodniji

Pojanjena razlika u KE u zavisnosti od faza Tokom razvoja

Tokom inicijalnog CE oznaavanja

Kasnije auriranje

Slobodniji pristup ocenjivanju (to moda i nije tako dobro): PICO (patients, intervention, control, outcome)

Cochrane Handbook for Systematic Reviews of Interventions

PRISMA Statement (The Preferred Reporting Items for Systematic Reviews and Meta-Analyses)

MOOSE Proposal (Meta-analysis Of Observational Studies in Epidemiology)

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MEDDEV 2.7/1 rev. 4

Korak 0: Definisanje obima KE (t. 7)

Za inicijalno CE oznaavanje Opis MS

Specifine osobine MS (materijal humanog