EU Module 15 Safety Communications
On January 24, 2013 the EMA’s latest Good PV Practices Module 15 on Safety Communications came into force. Although this module may be a little less critical compared to the other already-released modules which have changed the way PV is done, this module still is worth reviewing.
The goal is to provide Marketing Authorisation Holders (MAHs) and Competent Authorities (CAs) guidance on communication & coordination of safety information. It covers product information, namely: the Summary of Product Characteristics (SmPC or SPC), the Package Leaflet (PL), other labeling, public assessment reports and various other drug related documents. Its focus is on new or emerging safety information about a previously known or unknown risk which has or may have an impact on the benefit-risk balance and conditions of use.
Although, in the best regulatory mode, the EMA notes that sentences that contain the word “shall” are legal obligations and must be done where as sentences with the word “should” are guidance recommendations and not obligatory. In practice this distinction sometimes is rather nebulous and the “shoulds” are considered by many to be “shalls” unless there is a very strong reason not to implement the guidance recommendations.
The objectives of the module are to:
- Provide timely, evidence-based information on the safe and effective use of medicines;
- Facilitate changes to healthcare practices (including self-medication practices) where necessary;
- Change attitudes, decisions and behaviors in relation to the use of medicines;
- Support risk minimization behavior;
- Facilitate informed decisions on the rational use of medicines.
Some of the underlying principles are that all information must be objective and not misleading nor should it contain advertising. It should present risks in the context of benefits including information on seriousness, severity, frequency, risk factors, time to onset, reversibility of potential adverse reactions (ARs) and, if available, expected time to recovery. Obviously, the information should be clear, consistent and understandable by the right audiences at the right time. Interestingly, it notes that there is often/usually a lot of uncertainty in safety data and that work-ups on safety issues are often “underway” so final information is not often available. Nonetheless, the data should be presented in a non-confusing way with competing risks (including the risk of non-treatment with the product) put in context.
Graphs may be used in the data presentation.
Also, very appropriately, the module notes that the appropriate quantitative measures should be used including absolute risks not just relative risks.
Comment: There is much confusion in the eyes of the public (and sometimes the profession) regarding relative and absolute risk. Often in the press or literature one reads that the (relative) risk of something is doubled or tripled with a particular drug or behavior. This needs to be put in the context of absolute risk. Perhaps the best example of this is buying lottery tickets. If you buy a ticket in one of the “super lotteries” your chances of winning the biggest prize are about 1 in 180,000,000 (175 million). If you buy two tickets your chances have just doubled! But your chances are still only 1 in about 90 million! So you have doubled your relative risk of winning but your absolute risk is still incredibly small. As one comedian said, your chances of winning are the same whether you buy a ticket or not!
There should be consultation with patients, the health care community and any other appropriate stakeholders. Communications should be followed up where appropriate including information on the resolution of the issue. Where possible the effectiveness of the communication should be measured.
Although the target audiences are patients and HCPs, the media should also be considered a target audience. The MAH or CA (or both) may disseminate the information as appropriate.
The actual content of the communication should be carefully done to obtain the appropriate impact. It should state the reason for the communication, recommendations to patients and HCPs, a note that the MAH and CA have agreed on the content (where this is the case), changes to the SmPC and PIL, scientific references and a reminder to report adverse events/reactions to the appropriate authorities.
The EMA next reviews “Direct Healthcare Professional Communications (DHPCs)” – formerly called “Dear Doctor” or “Dear Health Professional” communications. These communications are not routine educational materials but rather specific information communications asking that certain actions be taken or practices changed. If multiple MAHs are involved the message should be consistent. It may be useful to involved professional organizations and learned societies. The measures in the communication may be part of an Risk Minimsation Plan (RMP).
DHPCs should be used where there is an immediate action or change in current practices needed. This includes the suspension, withdrawal or revocation of an MA for safety reasons, an important change to the use of a drug due to the restriction of an indication, a new contraindication, or a change in the dose due to safety reasons. DHPCs should also be used for any restrictions in availability or discontinuation of a medicine with potential detrimental effects on patient care, new warnings, a change in a previously known risk or a new risk, decrease in effectiveness, new recommendations for AR or misuse treatment, medication and medication errors.
Press releases and briefings for journalists may be used as well as the publication of information on the MAH and/or CA websites. They should include the positions of the CA and MAH (if different) and any regulatory actions taken. The document stresses several times that the CAs should receive the information before the public and that HCPs should receive the information before patients receive it. Other media (journals, bulletins, newsletters) may be used.
As expected, social media is addressed. The internet allows information to be easily and immediately kept up to date. The use of the EMA and member state portals (when fully operational) is encouraged. Till then the EMA website will be used. “Other newer web communications may be used but accuracy of the information must not be compromised.” Presumably this refers to social media such as Twitter and Facebook and such.
Health agencies are advised to talk to each other. CAs should communicate with the other CAs. In the EU, “lines to take” documents should be prepared and used. These are non-public, internal documents summarizing the issues and actions planned or contemplated for use in responding to external enquiries and for communications. In other words the authorities should speak with “one voice”.
There should be a mechanism set up by the CAs to respond to queries from the public though treatment advice for individual patients should not be given. Referral to a HCP should be done in this case.
The effectiveness of the communication should be measured. This means that the communication should have clear and quantifiable objectives and goals. No specific prescriptive advice on how to do this is given. Any findings should be reported to the CAs. A quality system should be in place to create, implement and follow up on the communication.
Again the document stresses that the senior parties (the CAs, the EMA and, if appropriate, the European Commission) must be notified at least 24 hours in advance of the public communication unless there is a dire emergency. The EMA will be the coordinating body. Within the EU the “Early Notification System” should be used. International partners (health agencies) should also be notified in advance. As always, in medicine, surprises are never a good thing. If emerging safety issues come from third party sources, this information should be sent to the EU regulatory network. All communications within the EU should be done in English and translations of the announcements should be available in English as well as the local languages. All translations should be sent to the EMA.
Specifically, there are instructions to the MAHs on how to do DHPCs. The MAH should seek the agreement of the relevant CAs or EMA before disseminating a DHPC.
The DHPC will be reviewed & approved depending upon the route of the MA (central, mutual recognition, decentralized, national). The MAH should allow a minimum of 2 working days for comments. More time should be allowed when possible. The PRAC should always be involved in the review of DHPCs related to a safety concern being discussed at the PRAC. Where an HA outside the EU requests the dissemination of a DHPC in their territory for a product also authorised in the EU, the MAH should notify the relevant CAs in the EU. Refer to the module for futher information on how this is handled for central, mutual and national approvals are handled.
Comments: No real new issues here. Lots of common sense and concertation of actions. Consistent messages, no surprises, no advertising, fair and balanced benefit-risk communications.