How to save millions of dollars during clinical studies by automating SUSAR distribution

Boehringer Ingelheim (BI) is one of the largest pharmaceutical companies in the world, and has lead the way in study treatments and cures in the areas of cardiovascular, oncology, respiratory, central nervous system, immunology and metabolic diseases.

BI conducts clinical trials to determine the safety and efficacy of its drug candidates. Real-world data gathered during a clinical trial is studied to determine whether a candidate drug merits further study and, eventually, whether the drug should be submitted to regulatory agencies in a new drug application (NDA).

Like every other pharmaceutical company, BI has either developed in-house software solutions or adopted commercial software solutions to improve both the speed and accuracy of every clinical trial. Without question, software plays a mission critical role in the effort to improve the conduct of clinic trials and ultimately to improve human health around the world.

While there have been industry-wide improvements in electronic data capture (EDC) and electronic trial master file (eTMF) technology, little has been done to improve the flow of essential documents during the study itself. During a clinical trial, essential documents move back and forth between trial sponsors, clinical research organizations, investigational review boards, clinical sites, investigators, patients, ethics committees and regulatory agencies. 

Depending on the type of document, it may require edits, collaboration, signatures, acknowledgments, timely distribution and even mandated distribution timelines. That amounts to a high number of documents, distributions, and people involved, so companies need to rely on efficient and reliable systems. 

The essential documents of any clinical trial are specified by the ICH (International Council on Harmonization) as mandatory to good clinical practices. While ICH guidelines describe more than 50 essential document types, the majority of clinical trials involve more than 100 essential document types. 

Over the course of a clinical trial, hundreds of thousands of interactions with essential documents take place. The numbers are so vast that sponsors of large trials spend hundreds of thousands of man hours sending, receiving documents, editing, signing, approving, reviewing and storing essential documents. The human effort spent managing essential documents during a trial adds millions of dollars in cost to each and every clinical trial.

One type of essential document is the Suspected Unexpected Serious Adverse Reaction, or SUSAR. Each SUSAR report identifies a single patient’s unexpected and serious reaction to a drug being studied. 

Depending on the severity of the reaction, a SUSAR report must be sent to regulatory agencies 7 to 15 days. In addition to agency reporting requirements, some countries require SUSARs to be shared with investigators studying the same drug, regardless of whether that investigator is involved in the same clinical trial. The sooner this information can be distributed to each clinical site investigating the drug in question, the sooner a decision can be made whether to continue investigating a drug, whether a particular patient should receive the drug, or whether one patient type seems to be more susceptible to side effects than another patient type. It is worth noting that reporting these events to principle investigators at clinical sites can be a matter of life and death for patients.

The BI team was also interested in the possibility of electronically distributing all SUSARs involving a drug under study to all sites conducting a study of the same drug. In the previous paper-based process, such wide distribution would have been impractical and even confusing to some investigators. BI determined that by using technology to automate the distribution of SUSARs, it could improve its own efficiency in reporting SUSARs to sites.

Considering the complexity of global and local regulations, short reporting deadlines, as well as the legal requirement to add previously unlisted adverse events to revisions of the Investigator Brochure (IB), there were many challenges to overcome in SUSAR distribution.

BI created an internal team to implement a change management process that would allow it to migrate from a paper-based workflow to an automated workflow. This change would reduce the workload on local affiliates and clinical sites by using the advanced workflow and distribution capability available in the InvestigatorFIRST™ software product. In doing so, BI were aiming to achieve timely service levels, oversight, and efficiency, while supporting further automation in the future.

Keeping in mind the goals of the project, BI configured the InvestigatorFIRST™ Study Collaboration Portal™ to mirror the ideal SUSAR workflow identified in the change management process workshops held by BI.  Special configurations based on geography were categorized into IND Countries, expedited SUSAR countries and countries where distribution is restricted if the event origin is in the same country. 

The process was simplified to achieve full transparency with the guiding principle that each investigator should get the same set of safety information. This meant that some Investigators in some countries would receive more SUSARs than regulatory agencies require. Because the Study Collaboration Portal™ could self-organized all SUSARs, it was determined that investigators would not be burdened by a more complete SUSAR distribution.

Enabling centralized distribution of all SUSARs to all applicable investigators at all applicable sites dramatically improves an investigators ability to gain insight into the safety of a particular drug for a particular patient.

Quality checks were also added at various workflow steps to ensure that all received reports (from the pharmacovigilance team) are actually distributed, the assigned drug and the target audience matched, and cross reporting rules are consistently followed by the software.

The final distribution logic configured in the software workflow was implemented with an appropriate notification period to users. A dedicated audit role created in the Study Collaboration Portal™ allowed BI to conduct real-time compliance tracking to support oversight of distribution timelines.

The system was also configured to automatically distribute all other study safety documents including: Periodic Safety Reports, Dear Investigator Letters, Startup of Safety Report Distribution Letters, Expedited SUSARs, Expedited SUSAR Translations, SAEs, and SESARs (Suspected Expected Serious Adverse Report).

During the four year period since BI implemented the InvestigatorFIRST™ Study Collaboration Portal™, the automated SUSAR workflow has governed each of its clinical trials and based on each drug under investigation, every investigator has received the appropriate safety information during a clinical trial, achieving the goal of a harmonized process capable of handling exception scenarios. The process was also demonstrated in detail to the US FDA during a meeting with BI’s global pharmacovigilance team. 

Not only have compliance timelines been consistently met since adding SUSAR distribution to BI’s Study Collaboration Portal™, but many productivity gains have been achieved, including all received reports being distributed without manual processes, assigned program and target audiences are always correct, cross reporting rules are automatically followed, and every trial is inspection ready at all times.

By any measure, BI’s Study Collaboration Platform™ developed by Innovo Commerce has been a runaway success for Boehringer Ingelheim. 

Not only is regulatory compliance achieved in real-time, productivity gains can be measured in hundreds of thousands of man hours per year. The Study Collaboration Portal™ has been in place for four years and has been credited with saving BI tens of millions of dollars each year. 

Today, all clinical trials are conducted in an advanced state of completeness employees and other associates of BI are more productive and no longer spend countless hours distributing tens of thousands of documents of all kinds throughout each clinical trial.