Cardiovascular implants

BS EN ISO 5840-2:2021 pdf free.Cardiovascular implants – Cardiac valve prostheses Part 2: Surgically implanted heart valve substitutes.
The requirements of Iso 14630 and ISO 14155 shall apply. Clinical investigations shall be performed for new surgical heart valve systems and expanded indications for use. For modifications of an existing heart valve system, if a determination is made based on the risk analysis that clinical investigations are not required, scientific justification addressing safety and effectiveness shall be provided.
Clinical studies are recommended for design changes of a marketed device that may affect the safety and effectiveness (e.g. novel blood-contacting materials, changes that alter the flow characteristics or haemodynamics, changes that affect the mechanical loading on the valve).
Clinical investigations shall be designed to evaluate the surgical heart valve system for its intended use. The studies shall include an assessment of adverse events related to risks arising from the use of the surgical heart valve system and from the procedure. The clinical investigation shall include pre-procedure. pen-procedure, and follow-up data from a specified number of subjects, each with a follow-up appropriate for the device and its intended use. The clinical investigation programme shall be designed to provide substantial evidence of acceptable safety and effectiveness to support the intended labelling for the device.
The phases of a clinical programme typically include a pilot phase (e.g. first-in-human or feasibility studies), a pivotal phase (studies to support market approval), and a post-market phase. Humanitarian use (e.g. compassionate use, emergency use, special access) is a separate process and is not considered part of the clinical programme. A series of patients receiving a novel device under humanitarian use shall not be used as a substitute for any clinical investigational study. Prior to embarking on a pivotal clinical investigation, pilot phase studies shall be considered to provide initial information regarding clinical safety and device performance. The information derived from the pilot phase may also be used to optimize the surgical heart valve system and patient selection prior to initiation of a larger clinical investigation following further pre-clinical testing. A scientific justification shall be provided if pilot phase studies are not to be undertaken.
A pivotal clinical investigation shall be designed to ensure:
a) the presence of a well-defined, clinically relevant question;he presence of a well-defined, clinically relevant question;
b) an acceptable level of risk-benefit for the patient considering the available alternatives and standard of care;
c) an appropriate study design to answer the clinical question, including a well-defined patient population, study endpoints and duration.
A randomised study design for a pivotal trial should be considered for the following reasons:
a) ethical considerations can require a head-to-head comparison with alternative treatments or standard of care;
b) randomised trials provide the highest quality scientific evidence and minimize bias;
c) randomised trial results can promote adoption of effective therapies.
For clinical investigations to serve as a basis for market approval, there should be sufficient data to support safety and effectiveness. These studies should include a statistical methodology, specific inclusion/exclusion criteria, use of accepted endpoint definitions, a rigorous method of collecting information on defined case report forms, a rigorous system to monitor the data collection, defined follow-up intervals, and complete follow-up of the study populations.
7.4.2 Study considerations
The decision to use a medical device in the context of a particular clinical procedure requires the residual risk to be balanced against the anticipated benefits of the procedure or the risk and anticipated benefits of alternative procedures. The requirements of ISO 14971 shall apply.
With surgical heart valve systems, haemodynamic performance and those adverse events which are directly related to the device or procedure should be measured to assess risk (e.g. coronary obstruction, LVOT obstruction). Haemodynamic and clinical performance including adverse events may also depend on factors other than the device itself, including:
a) patient comorbidities;
b) the underlying pathological process and whether it continues to progress;
c) whether the degree of functional improvement achieved is sufficient to prevent progressive deterioration in cardiac function;
d) technical factors involved in implantation;
e) appropriate selection of available sizes and/or shape configurations;
f) the potential for adverse haemodynamic effect.
See Annex J for more information about adverse events.
Imaging assessment is an essential aspect of the clinical investigation for patient selection, device placement, avoidance of procedural complications and patient follow-up (see ISO 5840-1:2021, Annex G). To ensure optimal anatomical evaluation, device position, and functional assessment, multiple imaging modalities [e.g. TEE, TTE, CT, MRI, fluoroscopy, positron emission tomography (PET)J may enhance assessment and shall be used where applicable. The latest imaging guidelines from professional societies should be followed in performing these imaging procedures to ensure the quality of images. Clinical site training and certification shall be conducted before enrolment in collaboration with the independent core laboratory (see Reference L91)• Imaging follow-up time points shall be specified, and justified, and the follow-up should be complete as specified in the CIP.
The CIP shall clearly define the objectives of the study and specify safety and effectiveness endpoints (see AnnxJ and ISO 5840-1:2021, Annex L). The CIP shall specify all anticipated study-related adverse events, including device and/or procedure-related adverse events, in accordance with Annex I and published definitions. The definitions of the outcome measures should be consistent with those described In this document to allow comparability of heart valve systems. The study design shall include a pre-specified statistical analysis plan and success criteria (e.g. new devices should meet the objective performance criteria).
Studies should employ measures to minimise bias. Study designs may vary depending on the purposes of the assessment and/or the technology (novel technology versus modification to well-established device). Study populations shall be representative of the intended post-market patient population, including aetiology and pathology. Further, studies shall be designed to ensure collection of all CIP specified follow-up information in all subjects entered into the study unless subjects specifically wEthdraw consent for follow-up. For patients who withdraw consent, follow-up ends at the time of the withdrawal. However, depending on local legal requirements, additional follow-up may be obtained.
The manufacturer is responsible for ensuring collection of appropriate information. The study design shall be consistent with the aims of the CIP. For a given study, the CIP and data collection forms should be standardized across institutions and investigators.
Study monitoring shall be conducted in accordance with ISO 14155. To ensure patient safety, a safety monitoring plan shall be established. Study oversight shall be provided by an independent data safety monitoring board (DSMB)/independent medical reviewer (IMR) for evaluation of patient safety, study conduct and progress, and when appropriate, efficacy. The monitoring board is empowered to make recommendations for or against study continuation, or study modification. An independent clinical events adjudication committee shall be used to classify events against pre-established criteria. Core laboratories are recommended for outcomes that might be prone to inter-laboratory variability for pilot phase (at multiple sites) studies and are required for pivotal studies.
Explant analysis is a vital part of device evaluation. Devices explanted or obtained at post-mortem examination should be assessed by an independent cardiovascular pathologist. The results of analyses shall be reported in accordance with the CIP including operative or post-mortem examination photographs of the device in situ and after explant. The CIP shall include an explant pathology protocol with detailed instructions for evaluation by an independent cardiac pathologist (including operative or post-mortem examination photographs) and instructions for the return of the explanted device to the manufacturet; where appropriate. Whenever feasible, the explanted device shall be subjected to appropriate functional, imaging and histopathological investigations. In the event of subject death, valuable information about implanted devices can be obtained by post-mortem examination which should be encouraged whenever possible.BS EN ISO 5840-2 pdf free download.Cardiovascular implants