Delivering on the Vision: Realizing the Paperless World

As the volume of information collected in the R&D lifecycle of a product continues to grow, and similarly the volume of regulatory changes expands, today’s life science company is literally drowning in the paper-based, manual processes reflected in their drug safety processing and reporting.  In realizing the vision of a paperless safety ecosystem, today’s “pioneers” leverage both proven and emerging technologies to realize increased efficiencies, compliance and transparency of adverse event reporting processes.

Efficient Case Management
The increasing awareness and concern on product safety is resulting in a paradigm shift in drug safety processing and reporting.   Traditionally, spontaneous reporting has been considered the most appropriate way to report safety events early on, and so expedited reporting regulations focused on reporting potentially serious events immediately.

Recent safety concerns and softened consumer confidence have significantly changed this thought process.  Regulators now mandate the pharmaceutical industry to go to extraordinary lengths to demonstrate the safety and efficacy of their products—before, during and after the marketing approval process.

There is now a clear burden to prove a product offers a significant benefit-risk profile compared to other products that are already available.  To achieve this, pharmaceutical companies can no longer rely on safety cases that are reported to them.  Without the benefit of additional headcount, they also need to actively look at additional data sources, resulting in more data to be analyzed.  Companies are, therefore, increasingly looking towards applications to help them optimize processing the increasing amount of data—but in an automated, paperless way.

Report Sources
The challenge of each and every sponsor and Marketing Authorization Holder (MAH) is to demonstrate compliance to regulators and to be seen as an ethical drugs manufacturer in every way.  As part of a sound risk management strategy, industry is being asked to improve the way it monitors and collects safety information about its products.  Beyond the collection and reporting process for spontaneous reports, companies must put in place ‘post-marketing surveillance programs’ that monitor the market for emerging safety information and continually re-evaluate, communicate and mitigate safety concerns to ensure the benefit-risk profile of the product is maintained.  

This is adding a huge burden on companies as they balance compliance with the significant increases in costs.  In essence, like every other regulated industry, they need to increase compliance, manage the risk, while controlling the inevitable costs involved.

More recently, litigation is also resulting in an overwhelming volume of legal reports (and paper) for many manufacturers from lawyers.  In the U.S.A., there is a significant push toward the use of electronic health records in the healthcare industry.  While no specific legislation is in place to open up this growing and electronically exchangeable data, it is clearly an initiative that needs to be watched closely.

Moving to a Paperless World
When turning to industry consultants, it is often a surprise to many pharmaceutical companies how inefficient their case-handling processes actually are.  Often workflows are overly complicated or redundant.  In many cases there is excessive handling of paper from the original source documents to the internal assessments and narratives generated, resulting in too many manual handoffs between staff members.  Often, the recommendations are the obvious—reduce the amount of times individuals handle the cases and reduce the excessive handling of paper.

Efficient case handling must begin at the very source of receipt and continue through to periodic and aggregate summary reporting.   All source documents must be scanned, or even better, electronically received and associated with the case.  Wherever possible, cases should be received, processed and distributed in a fully electronic, paperless manner.

As previously described, there are many sources of potential adverse event reports, including healthcare professionals, consumers and lawyers.  It is clear that these reports are received from a variety of mediums, with variable quality and in both structured and unstructured formats. 

Structured Data Handling
Possibly the easiest data to handle in a paperless environment is the structured data that companies receive.   The recent adoption of E2B clearly provided an international standard whereby cases can be received and distributed electronically in a fraction of the time of traditional reporting methods.  After the initial resistance to electronic reporting due to the costs and limitations enforced, many companies are now realizing the significant benefits of sharing data electronically, including improved compliance and perhaps more significantly, the reduced amount of time in performing redundant data entry.  This is true not only in reporting cases to the regulators, but also to partners with which this data needs to be shared.  Of course there are still problems with this standard, and ICH is moving forward with the revised E2B(R) standard.  We should also be aware of the involvement of the HL7 group who are also looking at a standard that includes adverse event exchange. 

There are other standards to consider.  In clinical trials, the CDISC has developed a standard for the exchange of data from clinical trials, including safety data.  Most data management and EDC vendors have adopted this standard.

As such, when establishing procedures for case handling, it is important that systems support the import of reports from such sources. 

It is also becoming increasingly popular to provide options for remote online data entry for both spontaneous and clinical safety reports.  Investigators, affiliates, license partners and CRO’s can all be provided direct online access.

Unstructured Data Handling
Unstructured data, often unsolicited, will typically be received in the form of phone calls, faxes or emails.  Many companies, especially those conducting clinical trials, try to structure incoming reports by creating fax and email templates that can be scanned and indexed automatically.  Using OCR technology, it is relatively straightforward to create a fax template whereby the study, patient number, investigator and product can be extracted and indexed automatically. 

Some advanced applications can automatically process incoming faxes and emails so that the manual process of scanning in these faxes also becomes redundant.  In this case, the received information is automatically presented to the user in an electronic inbox from where this information can be further processed.

For documents with no such template, a high level of process optimization is achieved by offering tools to perform online reviews.  Faxes and emails received are automatically created as source documents, while the online review tools allow users to assess these documents, redact and split them, and, if necessary, complete initial data entry and assessment in a variety of formats. 

Item Handling
When a potential report is received by a company representative, an assessment is made to determine if the information available is a valid report. Regulatory agencies have specified a minimum set of criteria, including an identifiable patient, reporter, drug and event.  If the required data is not available, the MAH has an obligation to perform active follow-up.  Even if the received information indicates that an adverse event report does not need to be created, the information captured and the follow-up processes followed need to be maintained and archived.

Case Processing
Every company has defined its own processes and timelines for processing adverse event reports.  As expected, processes typically vary depending upon the source and seriousness of the report and any specific regulatory commitments.  Often, reports are routed to specific specialists based on user-defined criteria.  For example, products from a particular therapeutic class are routed to an appropriate specialist for assessment.  Using the same logic, it is possible to monitor specific drug/event combinations.

To improve the case processing speed and efficiency of the case-handling process, users need to have online access to the source documents, which are typically stored as images and are stored with the case.  This capability is especially relevant for companies that have geographically distributed case processing, as users will no longer have to wait until the paper source documentation arrives to start processing the case.

Automated workflow can provide many additional benefits as cases are routed to individuals for further processing.  To fully realize the benefits of workflow, reports should be routed based on the content of the case data.  Workflows therefore need to be flexible and adaptable as situations change.

Not only will workflow help in processing cases in a more efficient automated way, it can also be used to facilitate compliance with reporting timelines by ensuring that serious and/or reportable cases are presented in a more prominent way to the user.

Workflow can also support 21 CFR Part 11 compliance by recording who completed each activity and when.  The same information can also be used for tracking of metrics and key performance indicators, helping companies to manage departments and functions more efficiently than ever before.

Communication and Case Follow-Up
Following up on the safety report is a major function of pharmacovigilance and it is important to demonstrate to the regulators that every possible effort was taken to investigate possible adverse event reports.  This means that strong communication tracking tools, including standard letter generation, fax and email integration are critical.

Case Distribution
Perhaps some of the greatest efficiencies can be gained in the distribution of case reports to third parties, including regulatory agencies, license partners and other stakeholders.  In the past, reports were distributed manually using postal and fax technology. 

E2B has automated electronic distribution to a certain extent but its use is limited to those partners who can receive the E2B standard.  Case distribution now needs to incorporate the different mediums available including fax, and email.  Furthermore, the E2B standard has been developed keeping regulatory needs in mind.  It has emerged that when exchanging information with partner companies the E2B standard is not always sufficient and that additional information also needs to be exchanged, hence the need for an extended E2B format.

Extending this further, it is not sufficient for companies to only distribute the reports.  They must have evidence that the reports were distributed and preferably track the receipt.   Of course, this can result in a huge administrative effort. 

Of greater concern, it remains a reality that this information is rarely available in a single location and more typically is held with each affiliate.  Bringing this data to a central database remains a challenge.  Typically, companies are reluctant to provide affiliates remote access to the central pharmacovigilance system and are seeking systems that offer components and tools for affiliates to track submissions and responses from the regulators.

Clinical Safety Distribution
New regulations for the reporting of clinical safety cases and SUSAR’s require the immediate notification of death or life threatening events to investigators, ethics committees, and IRBs.  This represents a significant cost to the sponsor, both in the administrative overhead in managing these cases and the physical costs of distribution.

With the increasing adoption of EDC and the familiarity of investigators with internet-based technologies, more sponsors are looking at the distribution of clinical safety reports via web-based portals and email.  However, there is a concern that this ‘pull’ concept, whereby investigators are required to perform a specific action to view the report will not be accepted.  The other issue is with implementing appropriate security to such a deployment for investigators to access.  

Aggregate Reporting
The final requirement for a truly paperless environment is to support the distribution of line listings, including aggregate and periodic reports.  Although following a different process and timelines, the same principles of distribution apply, meaning such reports can also be electronically distributed via email, portal or electronic gateway.

Where Are We Today?
How close are we to realizing the dream of a truly paperless environment?  While all the components are available today, very few, if any, companies have fully embraced this vision.  Today’s “pioneers” are starting the paperless process by deploying technology focused on limited functions.  This is clearly good news, not only for the sponsors and MAH’s, but also for the patients who depend on and trust this dynamic and fascinating industry. 

Simon Sparkes is the vice president of global sales and marketing at ArisGlobal LLC (www.arisglobal.com), a leading provider of integrated software solutions for pharmacovigilance and safety, regulatory affairs, clinical research and medical information.  He can be reached at ssparkes@arisglobal.com.