Operationalizing the Serious Adverse Event (SAE) Process at Clinical Research Sites

About Norton Healthcare

Norton Healthcare is a nonprofit community healthcare system in Louisville, Kentucky. Norton Healthcare System comprises five hospitals, 15 outpatient centers, and more than 15,000 employees. The Centralized Research Administrative Office for the healthcare system supports more than 800 active research studies and an average of 350 new studies each year. More than 70 full-time employees work on the clinical and administrative side of clinical research.

The Need to Operationalize SAEs

In the beginning, the author thought that the SAE process at Norton Healthcare was working perfectly. The clinical reports were being written on SAEs accurately and regulatory reports on SAEs were going to the institutional review board in a timely manner. The clinical research administrative area was invoicing the sponsor when the contract included sponsor reimbursement for SAEs. When the author began a review, however, she found that there was a need to standardize and centralize the processing of SAEs (Table 1).

A review of SAE accounts receivable showed that receivables were increasing rather than decreasing. The author learned that the clinical research administrative team had invoiced appropriately for the SAEs; however, there was a delay in sponsor payments of the invoices.

Analyzing the situation further, the author determined that the clinical research site was not collecting on SAE accounts receivable in a timely manner. There was a breakdown in communication between the involved areas. The clinical side and the regulatory side at the site were using the proper procedures for SAE reporting; however, there was a disconnect between the clinical/regulatory and the financial area at the site. There was no standardization of the SAE process or policy. Norton Healthcare’s increased risk was due to the lack of a strong SAE process for the collection of SAE invoices.

Operationalizing the Serious Adverse Event Process

The initial review to operationalize the SAE process was a cumbersome administrative task. The team knew that there was an issue with the SAE process. The author reached out to her peers about how their clinical research sites operationalize the SAE process. Her peers, however, were unable to describe their SAE process in detail. It became clear that most sites focus on the regulatory and clinical aspects of the SAE with no focus on the business and administrative side.

When the author discussed SAE billing with the various stakeholders at Norton Healthcare, she was able to convince them that there was an issue with the unpaid receivables. Table 2 outlines the steps, not necessarily in order, in operationalizing the SAE process at Norton Healthcare. The steps included determining the stakeholders and defining SAEs for the clinical research site. The law department provided input on how it defined SAEs when working on contracts for clinical trials. A tracking mechanism was also necessary, as many staff members are involved with SAE processing. The workflow for SAE processing by all stakeholders needed to be designed. Administrative policies for SAE processing needed to be developed. The team also had to discuss any additional requirements for SAE invoicing and collections with sponsors and contract research organizations (CROs). Prior to this review, the author was not aware that there were special requirements for invoicing SAEs to sponsors and CROs.

The stakeholders who worked with the author to operationalize the SAE process included:

• Clinical operations
• Claims review
• Accounting
• Clinical trial management system (CTMS) build team
• Lawyers
• Managers
• Directors
• Risk managers
• Regulatory managers

Designing the SAE tracking form (Table 3) was the next step. The SAE tracking form covers:

• Study information
• Review by law department, billing, and budgeting
• Accounting information

The law, billing, and budget groups each have a tab in the worksheet, facilitating data flow. Each group decided what was important to them in the process.

The SAE flow and process were developed using a software tool for mapping out processes. The process map shows who is responsible throughout the SAE management process and allows everyone to easily visualize what happens during the process.

Policy Brainstorming

In order to have an effective policy, one will need to develop the policy from the various perspectives of the involved stakeholders.

Table 4 outlines considerations in policy brainstorming, starting with the timing of notification of an SAE and how notification will be completed. Another consideration is identifying the person and department with the responsibility for payment (initially and for following up on receipts).

Identifying the necessary documentation is needed for the policy. When Research Financial Operations reached out to sponsors to find out why invoices for SAEs had not been paid, the team learned that the process had not been followed as required. Sponsors wanted an SAE detail packet with the SAE information from the billing record as well as other additional documents. Also, in many situations, the invoices for SAEs are sent to a different part of the sponsor company than standard study invoices. Many sponsors send SAE invoices to an insurance company for payment. The initial SAE visit and follow-up visits must also be tracked and documented in order to comply with SAE billing requirements.

More items to consider include internal processing and sponsor invoicing. It is very important to define SAE processing during contract negotiations with sponsors and CROs and to define any additional information required for SAEs to be processed appropriately. This information, including the invoicing address for SAEs and the name of the contact person, should be defined in the contract. Having all of the necessary information in advance makes it much easier to process SAEs when they occur.

Examples of SAE Processes and Tools

Next, Research Financial Operations developed the CTMS (Clinical Trial Management System) notification process. The clinical team is the key starting point for when a serious adverse event occurs. That team needs to notify Research Financial Operations when an SAE occurs. An SAE occurrence was created in the CTMSfor notification of SAE visits and follow-up SAE visits. The clinical investigator reviews the relevant information for regulatory notification. Examples of items to consider when building an SAE visit into a CTMS include:

• Related to research, per the clinical investigator
• Not related to research, per the clinical investigator
• Related to drug/device, per the clinical investigator
• Not related to drug/device, per the clinical investigator
• Not study related

The clinical team creates the SAE visit in CTMS within 24 hours of notification of the SAE. When Research Financial Operations is notified that an SAE is related to a drug or device, that notification begins the SAE tracking mechanism. Research Financial Operations utilized this method to automate the SAE process.

The Research Financial Operations team developed a tracking form for the different areas. Each group adds information to the tracking form, which includes the research office number, type of study, date entered into the CTMS, patient name and ID, and other crucial information. The tracking form starts with the law department. The law department reviews the contract and indicates whether the SAE is billable to the sponsor or to an insurance company. This information determines the next steps in the process for the billing review team and accounting.

A reduction in emails and additional phone calls occurred between the clinical and administrative teams when the information was centralized. 

Each group within the Research Financial Operations team developed its own checklist for tracking SAEs. Table 5 highlights checklists for billing, the law department, coverage analysis, budgeting, and accounting. For example, the budget manager ensures that the CTMS is updated from a budget perspective and that everything is entered into the tracking form. The accounting manager ensures that everything has been entered and is responsible for ensuring that the final payment is received. The accounting manager processes the invoices, including the SAE packets, tracks payments for SAEs, and follows up with the sponsor or CRO regarding aged accounts. The billing manager ensures that the patient’s accounts are properly filed and ensures that the other requirements for SAEs are completed.

The contracts and budgets language related to SAEs is very important. The following elements are suggested to be added into contracts to ensure that when a contract is finalized, that Norton Healthcare will have all of the necessary information to process SAE invoices:

• Date of SAE onset (as reported on the case report form [CRF])
• SAE treatment(s) associated with each SAE
• Date of treatment(s)
• SAE end date (if not ongoing at the time of invoicing and if consistent with the CRF)
• SAE event term
• ICD10 code associated with each AE/SAE
• Site contact name, phone and email for Medicare, Medicaid, and SCHIP Extension Act of 2007 reporting obligation inquiries
• SAE term(s) and treatment(s) specified in the invoice must match the study data reported on the CRF and the SAE forms in order to avoid a delay in payment

Results of Operationalizing Serious Adverse Events

Before developing the process to operationalize SAEs, the outstanding payments due to Norton Healthcare had aged greater than 180 days. Today, the accounts receivable picture has completely changed. Norton Healthcare has increased collections on SAEs to 95% on aged accounts receivable.

The review process for SAEs, which used to take at least 30 days, is now down to two days. Each person and area knows what to do and is filling in the necessary information. Some team members have posted the SAE flowsheet in their office, so they can see where the process starts and ends. Also, the flowchart is a great visual tool to use for this complicated process. 

New language has been reviewed to be added to all new contracts and budgets outlining the SAE information.  

Many sponsors have a completely different process for SAE invoicing, and there is a learning curve to properly assess SAEs, track payments, and provide all of the documents necessary for invoicing sponsors. This necessary information for SAE invoicing should be in the budget and the contract, and the contract should also include language about who makes the SAE determination: the clinical investigator, the sponsor/CRO, or whether a joint decision is necessary.

It took more than a year to develop the SAE process at Norton Healthcare. Each team member has a vital role in the SAE process. Everyone is educated on the new process. The team currently is having conversations about the SAE process and is resolving outstanding issues. Tools such as process maps, checklists, and spreadsheets are very helpful to the author and to the team at Norton Healthcare.

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TABLE 1

The Need to Operationalize Serious Adverse Events

• Late collection on SAE accounts receivable, and an increasing outstanding balance
• Late reporting of SAE events to the financial team
• No standardization of process, policy, SAE definitions for invoicing, etc.
• Risk of loss related to SAE collection and process

TABLE 2

Steps in Operationalizing the Serious Adverse Event process

• Determine stakeholders
• Define “Serious Adverse Events” (SAE) for the institution
• Develop tracking mechanism
• Design the flow for all stakeholders
• Develop the policies
• Discuss additional requirements for SAE invoicing and collections with sponsors and CROs

TABLE 3

Serious Adverse Event Tracking Form

• Study information:
  • Research office number
  • SAE visit date
  • Patient ID
  • Sponsor
  • Related/not related to study product
• Law Department review:
  • Payer
  • Attorney initials
  • Notes: Legal issues
• Billing review:
  • Notification sent to Law Department, Finance, and Regulatory
  • Electronic Medical Record claim number
  • Total claim
  • Physician billing and hospital billing
  • Notes: CTMS
  • Notes: Billing
• Budget analyst review:
  • Date received
  • Total charge
  • Payable total
  • Date completed
  • Notes: Budget
• Accounting information:
  • Date received notice
  • Accounting unit
  • Accrued date
  • Invoice number
  • Invoice date
  • Invoice amount
  • Payment amount received
  • Notes: Accounting

TABLE 4

Considerations in Policy Brainstorming

• Key considerations:
  • Timing of notification
  • Notification process
  • Responsibility for payment – initially and for follow up
  • Required documentation
  • Initial SAE and follow-up appointments
  • Tracking documentation
• Other considerations:
  • Internal processing:
  • CTMS SAE visit
  • Law Department review request
  • Law Department determination
  • SAE CRF completed form(s)
  • EMR (Electronic Medical Record) billing sheet: Clean copy
  • EMR claims on hold
  • Does the event need to be determined by collaboration with sponsor and clinical investigator?
• Invoice sponsor:
  • Sponsor-required documents
  • Invoice address for SAEs
  • Contact person
  • Any additional information required for timely processing of SAEs

TABLE 5

Checklist Tool

• Billing review:
  • Save CTMS Serious Adverse Event notification to network study-specific file
  • Email site for case report forms; save to network in a study-specific file
  • Add SAE to master tracking log for legal review
  • Email SAE notification to alert team members
  • Please Stop Bill in electronic medical record (EMR)
  • Print EMR billing sheets if determined to be billable to sponsor
  • Save EMR billing sheets to network study-specific file
• Law Department review:
  • Review clinical trial agreement for SAE process
  • Review CTMS and EMR notification
  • Email SAE group determination with supporting sections of contract
• Coverage manager:
  • Review all SAE documentation
  • Add SAE sections to master tracking log
  • Run EMR reports for file in Excel format
  • Notify accounting manager and finance director
• Budget manager:
  • Review Serious Adverse Event documentation
  • Update CTMS visit with financial information for invoicing
• Accounting manager:
  • Review CTA for SAE instructions
  • If no instructions, contact sponsor/CRO for instructions to process invoice
  • Track all payments for SAE
  • Follow up with sponsor/CRO for aged accounts