Common use of ISMB ROLE & RESPONSIBILITIES Clause in Contracts

ISMB ROLE & RESPONSIBILITIES. The ISMB is an independent expert advisory group commissioned and charged with the responsibility of evaluating accumulating data at regular intervals and ensuring the safety of the subjects enrolled in the study by monitoring cumulative safety data collected in the clinical program and providing recommendations to Bioline Innovations Jerusalem based on review of this data. The ISMB will contribute to efficient conduct of the trial by providing a fast review of emerging findings from the study. This ISMB will consist of physicians with expertise in cardiovascular disease, particularly in the area of coronary artery disease and with experience monitoring safety of drugs and/or devices for cardiovascular applications, and will have no participation in the trial in any other capacity. These reviews in subsets of patients will have the objective of searching for signals of clinically important adverse safety findings that may be indicative of risk to currently enrolled patients as well as increased risk for future patients. In these reviews, the ISMB will assume a conservative approach in assessing safety. The Chairman will be directly responsible for reporting the outcome of all ISMB meetings and be the primary contact for any emergency meetings, as appropriately convened. He will be a voting member of the ISMB. The Chairman will also be responsible for the preparation of the report and/or recommendations to Bioline Innovations Jerusalem. The three voting members of the ISMB (along with the Chairman) will be responsible for evaluating the safety data and making recommendations on the continuation of the study as set out in the protocol. They may also make other pertinent safety recommendations for the conduct of the study. They will be guided by the ISMB Biostatistician’s evaluation of the data, as required. The bio-statistician will be involved in conducting any analysis that the ISMB recommends. The Bio-statistician will be responsible for designing and maintaining the safety database that the ISMB will use for its analysis. This database may differ from the database by Venn Life Sciences AG and, as such, is meant only for the use of the ISMB. The database will be created in such a way that it is reproducible and can be audited, if necessary. If the ISMB is considering a recommendation of premature termination of the study, the bio-statistician can contact Venn Life Sciences AG for additional data and/or for the performance of confirmatory analysis. The Bio-statistician can also arrange for the necessary ISMB communications to be documented and stored and only to be released after study completion. The ISMB will ensure that this study meets the highest standards of patient safety. In their analysis of the data from the patients, the ISMB will be focused on determining if there is a signal of clinically significant pattern of change in safety parameters that may lead to termination of study. This may require the ISMB to perform/request additional data/analyses prior to making a decision. The operating procedures of the ISMB are based on and are in compliance with guidance and definitions of the International Conference on Harmonization and the Food and Drug Administration. The ISMB will conduct all of its operations under the ICH Good Clinical Practices (GCP). Specifically, the ISMB is authorized and charged to perform the following functions: · review 30 day safety data patients from the first 2 sequentially enrolled patients to determine whether 3 additional patients may be enrolled; after reviewing the 30 day safety data from these 3 additional patients, will determine whether the rest of patients may be enrolled · within 30 days of enrolment of each successive group of 5 patients receiving the device, will review all Serious and Severe Adverse Events occurring to date and will recommend continuation, discontinuation, or modification of the procedure or protocol, based on a determination of whether the occurrence of serious, unexpected, or device-related adverse events (Sec. 7 in protocol) might outweigh the potential benefit achievable with the device · review emerging findings in patients and identify potential safety concerns with BL-1040 · will receive information, on an expedited basis, on all Serious and Severe Adverse Events, clinically significant laboratory values (as defined in the study safety plan), ECG abnormalities and xxxxx xxxxx that are associated with Serious and Severe Adverse Events, and data from patients who decided to withdraw from the study due to Serious and Severe Adverse Events. All Serious and Severe Adverse Events that occur in the catheter lab during the administration of BL-1040 or the hospitalization period after the procedure should be reviewed promptly by the ISMB. The ISMB will review this information and may decide to interrupt, alter, or terminate the trial. · will adjudicate whether or not an event is unexpected, based on a pre-specified list of expected Serious and Severe Adverse Events as well as clinical judgment within the study population. All ISMB members will review the safety data provided by the CRO. The members will reach their own individual decision on the relatedness and the potential hazard posed by the event. The ISMB will then collectively discuss the cases. In the event the majority opinion of the Board is that the events do not pose any significant risk then the ISMB will recommend continuing the trial as designed. However, if the Board decides that undue risk could accrue from continuation of the study as designed, the ISMB has the freedom to recommend appropriate changes to the study selection criteria, safety evaluations, etc. In addition, the CRO will provide datasets and listings capturing disposition, AEs, clinically significant Echocardiography, MRI, angiography, Xxxxxx, ECG xxxxx xxxxx/laboratory changes, once all patients complete study.