In a business niche as highly critical, closely scrutinised and heavily regulated as pharmacovigilance it remains a puzzle why clinical development organisations struggle so often with the “end of process task” of distributing Safety Reports*. These are commonly known as Suspected Unexpected Serious Adverse Reaction or SUSARs. Timely safety report distribution is important because of its part in improving patient safety but also due to the compelling regulatory obligation to distribute this material promptly.
A Pharmacovigilance Process Summary
- Site reports Serious Adverse Reaction (SAR) within 48 hours.
- Sponsor determines if SAR is unexpected or not.
- Sponsor reports SUSAR to relevant regulators within days (for EMA within 7 days and typically 15 days for the FDA).
- In parallel to step 3 the sponsor has a responsibility to promptly inform other sites once the matter is identified as a safety issue. While there is some scope for interpretation here, “promptly” is normally interpreted as meaning a number of days and not some longer period of time. Typically sponsors will aim to distribute safety reports within 15 days.
For reference here is how the FDA explain things – p16 of FDA Guidance Safety Reporting Requirements for INDs and BA/BE Studies.
Similar European guidance is noted here.
The reality is that this end of process task sounds simple to define but it is in fact pretty complex and time critical. In addition – organisations are often so blindly addicted to using email that alternative, more dynamic and reliable means of information distribution are strangely alien and fantastical. But why not use distribution means that allow for active information distribution, with real-time dynamic readership information? In an age where audience behaviour is closely tracked, isn’t it time you knew who has read your latest Safety Report, and more crucially who has not?
Details of This Task
Let’s break down some of the subtleties of this task:
- Drug safety information is detailed in the Investigator Brochure (IB) – a document of considerable size that also covers other key information about the drug, research conducted so far and its safety profile.
- The IB is dated and distributed to each investigator / site.
- Over time, new safety reports accumulate as an output from the pharmacovigilance process. Rather than frequently revise / redistribute the entire IB, sponsors opt to distribute individual Safety Reports as addenda to the IB – these are shorter, easier to digest etc.
- The Safety Reports are often given to Clinical Operations teams towards the end of the 15 day notification window – so requiring those teams to promptly handle onwards distribution.
- ClinOps teams then have just a few days (at best) to rush the reports to the correct recipients. And these teams don’t necessarily get much warning of an inbound Safety Report. You’d better be sure that your list of active investigators is entirely and comprehensively accurate and up to date. All of the time.
Regulatory expectations here are centred on proof of receipt. If a sponsor can show that they delivered the Safety Report to a site in a timely manner then the onus is on the site staff to get on and read it.
Some examples of current, sub-optimal solutions that sponsors use include:
- Physically printing out safety reports multiple times, one copy for each site, writing cover letters and labeling envelopes before then using couriers for distribution. Courier delivery tracking reports are then used as evidence that safety reports have been delivered to sites. It’s fairly easy to see that this is both an expensive option and distinctly limited because while Safety Reports might reliably arrive at some front desk at a site, there’s no evidence the paperwork ever reaches the intended recipient investigator.
- Use email to send Safety Reports while asking the recipient investigator to reply with an acknowledgement. After all, we use email for everything don’t we? This is prone to the worst characteristics of email – unreliability, misaddressing, slack security and information loss with few mitigating benefits. Even if an investigator does reply (a rare event) there is no suggestion that the investigator will be able to locate the Safety Report at a later date when they might need it. We long since abandoned email read receipts as self-evidently unreliable. Asking for all the receivers to reply and acknowledge is also a road to hard place.
Don’t Forget Real Life Variations
There are also a number of other variations that make this task considerably more difficult:
- While new versions of the IB are ideally rolled out to sites synchronously, on occasions sites can be working from different IB versions. This can occur for example if a new version of an IB is being held back to be published alongside some other study update, perhaps one that needs local regulatory approval.
- Some sites have just one investigator but some have more.
- There are often numerous studies where an investigational drug is being administered. Therefore the sponsor has a need to inform investigators who are working on those other studies separate from the one that generated the original SAR report.
- New sites joining a study need to be informed of all safety issues – which means not just the most recent version of the IB but all safety reports since that version was published. Remember that those new sites weren’t known about when you originally distributed those intervening Safety Reports.
- Then what? Is there an alternative means of sharing documents?
The myClin Clinical Oversight Platform has long been used to distribute essential study documents. Safety Reports are really just a specialised but high profile subset of these essential study documents. Alongside their use of myClin for many other capabilities, our sponsor and CRO customers have distributed 100s of Safety Reports to 1000s of sites. Cumulatively this amounts to hundreds of thousands of individual distribution events, all elegantly tracked by myClin. This experience includes at least one drug approval package submitted to the FDA. myClin reports on formal acknowledgments of Safety Reports by investigators, alongside useful supporting audit data such as views, prints and downloads. This rich picture of the readership of your Safety Reports is a unique benefit of using this Oversight Platform.
One example is the groundbreaking BeatAML Master Trial. This is a fascinating collaboration between the (US) Leukemia & Lymphoma Society, the FDA and multiple biopharma companies with AML candidate treatments. Being a master trial there are around 10 sub-protocols running at any one time with complex, and voluminous safety reporting needs.
Amongst other uses on this programme, myClin has greatly simplified the investigators experience in receiving and filing Safety Reports while adding sufficient rigour to make the process inspection ready at any time. myClin are honoured to be able to make a contribution to this innovative programme.
More recently one of our customers has made a large scale, dedicated Safety Report distribution deployment across 2 different drug programmes. The scale and breadth encompasses nearly 500 sites, >10 studies, 5 CROs and 4 continents. In the previous process the client was having to commit excessive resources to Safety Report distribution just to be able to meet its own (reasonable) deadlines. This became a strong motive for improved processes based on myClin.
The myClin platform now has a significant track record of successful Safety Report distribution – with added benefits of fast, flexible deployment at a highly competitive price point. So are you ready to rethink your approach to Safety Report distribution? This nut might not be so hard to crack after all.
*The term “Safety Reports” in the context of this article is used as a generic noun for SUSARs, CIOMS, MedWatch and similar documents.
By Adam Wood, VP, Business Development at myClin