A New Approach to Managing Safety Information in Clinical Trials
Safety used to be widely seen as a 'sales prevention' tool. Thankfully that has changed recently. But is it still viewed the same way in clinical trials? The Switzerland-based working group Council for International Organisations of Medical Sciences (CIOMS) recently produced a paper on this subject, discussing what pharmaceutical companies can do to embrace drug safety in clinical trials. CIOMS says that there is a need to incorporate newer approaches for managing safety information in the clinical trial setting, and to adapt the methods and tools used in post-approval pharmacovigilance to the early and late stages of pre-approval development of medicinal products.
The implications of a new approach to safety could be seen as onerous for a lot of stakeholders, including investigators, ethics review committees and, most importantly, pharmaceutical sponsor companies and their CROs. But they could also present an opportunity to streamline business, and more importantly, safety practices. CIOMS suggests that sponsor companies and CROs use the same methodology and tools in early and pre-approval development as in post-approval pharmacovigilance. On paper this is an excellent suggestion, but how easy is it in practice?
Collection of safety data
Investigators obviously need to inform a sponsor immediately of a serious adverse event (SAE). However, CIOMS suggests that investigators make a simple judgement on whether or not an SAE is related to the study drug. If however there are incidents of minor ailments such as headache and a subject is hospitalised because of a very bad headache (hospitalisation is a SAE) then it is reasonable to assume that it could be related to the study drug.
Whilst the investigator cannot be the arbiter of what caused the SAE, this is a step forward and can help further investigation.
Safety data management
Obviously if harmonisation and the collection of better data is the desired result then it would be better to have both clinical and post-marketing safety under the same wing. This is not always easy or practicable, so does that point to outsourcing? Again, this is not always easy or practicable but maybe a combination of the two is more easily managed.
Until the EU Clinical Trial Directive, few authorities (EU, Switzerland and the US) required the periodic communication of safety information from clinical trials. Even now there are different formats and indeed different sorts of information required. CIOMS recommends defining a single Development Safety Update Report (DSUR) for submission to regulators annually. Moreover, they recommend that these reports be based on a whole development programme rather than per protocol. They also suggest for products with a well-established safety profile that the DSUR is replaced by a PSUR (Periodic Safety Update Report). The question remaining is who writes the report? Does it remain in house, or because of the collection of clean relevant data, does it lend itself to outsourcing, which could be a more cost effective solution for what is considered an onerous task.
Good pharmacovigilance practice
However, good practice is not only there to be followed, but also to be used as guidance for better practices to be developed. The better and more refined the practice, the better the conduct of the trial, the better the data collected and ultimately, the greater the knowledge a sponsor will have about its products.
So how do you ensure a flexible programme that encompasses the diversity of products but is also able to deliver the end result required? SOPs (standard operating procedures) should be broad enough to allow the flexibility but still gather the information required. CIOMS recommends forming a dedicated safety management team that will review all available (not just post-marketed or clinical) safety data. This team can be adjusted in size relevant to the size of the organisation: a start-up with one development product can use this approach, with outsourced help, just as well as a large pharmaceutical company. In many cases, it will be easier for the smaller company, as people have many different roles to play, whereas with large pharmaceutical companies it is necessary to achieve the right balance.
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