Adverse events and SUSARs

1. Obligation to give notification of adverse events

„The investigator must notify the sponsor without delay of all serious adverse events which are not described in the trial protocol, investigator’s brochure and/or summary of product characteristics (SPC). Detailed written information may be sent to the sponsor later. The sponsor shall assign a special number to each notification.

The investigator shall notify the sponsor of all adverse events and/or research results outside the safety limits of the trial.

If an adverse event is fatal, the investigator must notify the sponsor, the Icelandic Medicines Agency and the ethics committee concerned [i.e. the NBC]; any of these parties may demand more detailed data.“  (Regulation 443/2004, (as amended), Article 29.)

The National Bioethics Committee‘s (NBC) requests formal notifications on deviations/violations from research protocols approved by the NBC. It is the PI´s obligation to carry out the trial according to the protocol approved by the NBC. All amendments to the protocol must be approved by the NBC and all deviations must be reported. With a view to the provisions of Art. 31 of Reg. 443/2004 , it is however not necessary to report minor incidents or deviations, e.g. such as one additional visit to the research site if the below items i), ii) and iii) do not apply.

The following deviations from the approved protocol must, without exception, be reported to the NBC:

i)        There is a risk that the deviation may have impact upon the security of participants.

ii)      The deviation has consequences for the interpretation of results/outcome of   the trial.

iii)    The deviation brings about substantial inconsistencies with the approved protocol.

2. Obligation to give notification of adverse reactions

„A sponsor shall ensure that the Icelandic Medicines Agency and the ethics committee in question [the NBC] are notified of all suspected unexpected serious adverse reactions (SUSARs), resulting in death or life-threatening condition, caused by investigational medicinal product. Notifications shall be forwarded as soon as possible and no later than seven days since the occurrence was brought to a sponsor’s knowledge. If no sponsor is related to the study, cf. item i of Article 2, this obligation rests on the shoulders of the principal researcher or researcher where applicable.

All other suspected unexpected serious adverse reactions shall be notified to the Icelandic Medicines Agency and the ethics committee in question within 15 days since the occurrence was brought to a sponsor’s knowledge.

A sponsor shall forward information to all researchers on the above mentioned side effects, related to the investigational medicinal product.

A register shall be kept on all suspected unexpected reactions caused by a medicinal product and this register shall be a part of an annual report of a study.

A register shall be kept on all adverse events caused by a investigational medicinal product and the register shall be publicised in its entirety in the final report of the study.

An explanatory report shall be annexed to the notification pursuant to paragraphs 1 and 2 on whether the study was terminated or whether blinding was relieved (decoding) and risk assessment of the researcher of the repercussion of the continuation of a study.

The Icelandic Medicines Agency and the ethics committee in question [i.e. the NBC] may demand a special synopsis of adverse events.

The Icelandic Medicines Agency shall ensure that all suspected unexpected reactions caused by an investigational medicinal product, that are reported, shall immediately be registered into a European database that only the medicines agencies of Member States of European Agency for the Evaluation of Medicinal Products, The European Medicines Evaluation Agency and the European Commission shall have access to.]“ Reg. No. 443/2004,, Article 30, as amended.

To sum up: The NBC requests notification and reports on the following:

·         All suspected, unexpected and serious adverse reactions causing death or a life threatening situations due to a research drug under investigation. The time limit for such notification is 7 days from the day the PI became aware of the incident.

·         All other suspected, unexpected and serious adverse reactions within 15 days from the day the PI became aware of the incident.

3. Obligation to give notification of modifications to a clinical trial

The principal investigator or, as the case may be, the investigator, the supervisor of the trial in the case of a multi-centre clinical trial, the sponsor or the sponsor’s representative must send a written, reasoned notification to the Icelandic Medicines Agency and the ethics committee concerned [i.e.the NBC] when modifications are made to a clinical trial protocol:

a. If there is a possibility of changes to the patients’ safety.

b. If a modification will result in a change in the interpretation of the results.

c. In the case of substantial modifications to a previously approved trial protocol.

The sponsor shall inform the Icelandic Medicines Agency:

a. If there will be any delay in the commencement of the clinical trial.

b. When a clinical trial is terminated prior to its expected conclusion.

The Icelandic Medicines Agency and the ethics committee concerned [i.e. the NBC] shall assess and must approve any substantial modifications to a previously approved trial protocol before they take effect.