In a large-scale emerging infectious disease (EID) outbreak in the United States, tens of thousands of people may require laboratory testing in a short period of time to identify the disease and who is infected, to control the spread of the disease, and to inform medical care. The situation could demand high-volume, high-throughput, and highly reliable and accurate laboratory diagnostic testing.
Responding to EID outbreaks is a continual learning process, and laboratory testing is necessary to improve understanding of the causative agent and to support public health interventions. The public health responses to severe acute respiratory syndrome (SARS), influenza, Ebola, and Zika over the past 2 decades had several common challenges, including non-existent or mild patient symptoms that are similar to many other less dangerous diseases, diagnostic tests that are new and imperfect, critical treatment and other major patient care decisions that depend on the result of a diagnostic test, and intense media attention. These conditions often lead to a high demand for laboratory testing and a heavy burden on the public health laboratory system, sometimes causing delays in testing and reporting of results to patients who are anxious to make major health decisions. Reference Chang1,Reference Luthra2
During the Zika virus outbreak in 2016, all of these conditions existed, and by the summer, the capacity of the public health laboratories in Florida and Texas were under heavy strain. Furthermore, on August 3, 2016, Florida Governor Scott announced testing would be available at no cost for all pregnant women. Reference Rosica3 At that time, the public health laboratories in Florida were performing an average of 250 serology tests per week and Texas had capacity for 450 serology tests per week. Florida increased its capacity to 700 tests a few weeks later. Reference Heberlein-Larson, Gillis, Morrsion, Scott, Cook, Cannons, Quaye, White, Cone, Mock, Schiffer, Lonsway, Petway, Otis, Stanek, Hamilton and Crow4 Laboratories in both states had a 3- to 5-day turnaround time for reporting results. From August 3–27, 2016, approximately 40 public health laboratories associated with the Laboratory Response Network performed an average of 1,100 serology tests per week in total (Schweitzer, B. (2019) Unpublished data provided by the Laboratory Response Network).
In May 2016, anticipating the surge in demand for Zika testing, the Centers for Disease Control and Prevention (CDC) reached out to the American Clinical Laboratory Association (ACLA), which suggested that CDC seek assistance from the 4 largest commercial laboratories with a nationwide presence: ARUP Laboratories, LabCorp, Mayo Medical Laboratories, and Quest Diagnostics. CDC had previously discussed involving commercial laboratories in a public health response; however, this was the first time that CDC was able to provide diagnostic tests authorized under an Emergency Use Authorization (EUA) to commercial entities, through a Biological Materials License Agreement, to support an emergency response.
In August 2016, these commercial laboratories began performing Zika testing. On average, these commercial laboratories performed over 2,000 serologic tests for Zika per week in total, adding to the nation’s overall capacity to respond to the Zika outbreak. While the increased throughput for clinical testing provided by the commercial laboratories was critical to the response, this new partnership between public health and the commercial laboratory sector had challenges. Understanding the importance of this new public-private partnership, the CDC and the commercial laboratory sector committed to identify and discuss those challenges, to document lessons from the experience, and to achieve a more formal collaborative arrangement for the future.
In October 2017, representatives from public health and commercial laboratories gathered at CDC to discuss partnership challenges and areas that needed improvement, which can be categorized in the following 5 areas: communication, coordination, test development, test deployment, and reporting of results.
OPPORTUNITIES TO IMPROVE COMMUNICATION AND COORDINATION
Improved information sharing and coordination between public health and the private sector early in the response would address several challenges experienced during the Zika outbreak. Some specific examples of challenges are described below.
Implementing Workflow Changes Based on Laboratory Testing Guidance
The CDC traditionally provides testing guidance during a response through its publication, the Morbidity and Mortality Weekly Report (MMWR). The audience for testing guidance includes clinicians as well as laboratory professionals. The commercial laboratories that participated in the response to the Zika outbreak described difficulties in making rapid changes to their workflows to adjust to the new guidance. This led to delays and confusion between providers who ordered tests and the laboratories that performed the testing. Commercial laboratories, as well as public health facilities, need ample time to make operational changes that would help to synchronize testing nationally and allow testing to begin immediately upon publication of the updated guidance.
Triaging of Samples
Although state and local public health laboratories generally serve a single constituency, commercial laboratories often provide testing services to multiple jurisdictions that may have specialized testing guidance based on the needs of local populations. This poses a challenge for private sector laboratories because each jurisdiction may have its own guidance on who should be tested. For example, some states allowed continued testing of asymptomatic pregnant women who did not have ongoing exposure. Since commercial laboratories may not have the epidemiological information that corresponds with a sample, it may be hard for them to determine if a sample should or should not be tested depending on which state submitted the sample.
Communication Between CDC and Commercial Laboratories
For over 15 years, public health laboratories (PHLs) have relied on the Laboratory Response Network (LRN) program at CDC and the Association of Public Health Laboratories (APHL) to coordinate operations in the event of a public health response. However, a similar system does not currently exist for non-PHLs that support a CDC-led response. Public health laboratories have received funding from CDC to participate in emergency response activities and have agreements already in place for how they would respond if needed. Expectations and policies are clearly defined for those laboratories. Yet there is no analogous agreement between CDC and the commercial laboratory sector that clarifies roles and responsibilities during emergencies.
OPPORTUNITIES TO IMPROVE TEST DEVELOPMENT, DEPLOYMENT, AND REPORTING OF RESULTS
For commercial laboratories to effectively provide surge laboratory testing capacity during an emergency response, they must be able to obtain an approved emergency diagnostic test, implement it in their laboratory, and report results. Some of the challenges the commercial laboratories experienced with this process are described below.
Operations and Logistics Support
During a response, there is an urgent need to quickly deploy newly developed tests to support decision-making for individual patient medical care. It is critical, however, that laboratories receive technical guidance on: how to transport samples, which biosafety measures to use, how to prepare the reagents, how to perform the test, how to interpret and report the results, and how to properly use the test under the terms of the EUA.
Implementation of EUA Tests
Meeting participants suggested that that CDC define and communicate the minimal requirements for verification of EUA tests in accordance with regulatory requirements. Although the clinical laboratory regulations, known as the Clinical Laboratory Improvement Amendments (CLIA), include requirements for verifying an EUA test, they do not specify how laboratories need to perform verification studies or give criteria that must be met. As a result, many laboratories implement new diagnostic tests cautiously because the flexibility allowed in the CLIA requirements are sometimes interpreted differently by both laboratory directors and the surveyors who inspect laboratories for compliance. Also, it can be challenging for commercial laboratories to conduct traditional verification studies because of limited availability of well-characterized specimens, particularly in the early stages of an emerging infectious disease response.
Reporting Requirements
States have different reporting requirements, which presents challenges to commercial laboratories that provide services to multiple states. The meeting participants suggested developing a mechanism to standardize reporting requirements between states. Also, state epidemiologists determine as early as possible during the response the minimum data required to accompany laboratory test results (e.g., date of symptom onset). This would allow commercial laboratories more time to update their laboratory information management systems to better support case reporting. At the beginning of a response, it generally takes time to establish required data fields for electronic reporting, communicate those standards to commercial laboratories, and update information systems to ensure results associated with a new test are correctly captured. Public-private collaboration on these issues in advance of the next outbreak could expedite this process. For example, there would be more efficient reporting of results, data collection, and analysis if all laboratories involved used standardized Logical Observation Identifiers Names and Codes (LOINC) and Systematic Nomenclature of Medicine (SNOMED) codes for their tests. Such advanced coordination could reduce the dependence on manual data entry, and the resultant opportunities for error and delays in returning test results to patients.
ACTIONS TAKEN
Since the October 2017 meeting, many steps have been taken to advance the state of this public-private partnership for clinical laboratory preparedness. CDC’s Division of Laboratory Systems (DLS) 5 serves as CDC’s point of contact with the commercial laboratory sector for communication and coordination of preparedness and response activities. DLS supports the rapid dissemination of information to commercial laboratories, such as testing guidance that would accompany an emergency diagnostic test. DLS’s Laboratory Outreach and Communication System (LOCS) 6 supports and enhances response-related communications with clinical laboratories. Since late 2017, LOCS has distributed 15 laboratory advisories, updates, and alerts to 23 partner organizations representing 160,000 clinical laboratory practitioners from approximately 190 countries. DLS also established the Laboratory Communicators Network (LCN), which connects communications professionals from 35 clinical and public health laboratory professional organizations. There is now an LCN website, a monthly newsletter, and a monthly teleconference call to share information and concerns. 7 In addition, DLS holds quarterly conference calls between public health and commercial laboratories to discuss best practices and to share information.
In early 2017, CDC, the U.S. Food and Drug Administration, and the Centers for Medicare & Medicaid Services launched the Tri-Agency Task Force for Emergency Diagnostics. 8 This task force was established to address the needs for rapid implementation of In Vitro Diagnostic tests authorized by FDA for use under an EUA in laboratories within the U.S. health-care system. The task force, which convenes in-person meetings at least twice every year, provides a forum for each agency to coordinate, provide consultation, and improve the implementation of emergency diagnostic tests. The task force has worked to define, refine, and streamline interagency approaches for the implementation of EUA tests through the creation of detailed workflows that describe each agency’s roles and responsibilities, and how the agencies work together for EUA test deployment. The task force has also developed template language to be included in Instructions for Use documents, which will help laboratories to assert more authority to reject inappropriate samples.
In April 2018, CDC, ACLA, the Association for Public Health Laboratories (APHL), and the Council of State and Territorial Epidemiologists (CSTE) signed a memorandum of understanding (MOU) to increase national laboratory testing capacity and strengthen future responses to public health emergencies. The MOU commits the signatories to: jointly create processes for supplementing public health laboratory surge testing capacity during a response; establish CDC and commercial laboratory contacts for coordination and communication during a response; engage commercial laboratories early in the response to maximize resources and expedite start-up time; ensure that commercial laboratories have access to resources and information to effectively support a large-scale response; and generate a common understanding of requirements for EUA test performance, testing algorithms, and result reporting. The needs for each response will vary, and the partners have monthly conference calls to maintain communication and to prepare for different scenarios. The MOU does not have an expiration date and is to be reviewed and updated annually. In May 2019, the partners of the MOU, along with public health and commercial laboratories, performed a table top exercise to identify additional gaps in communication and coordination. 9
NEXT STEPS
In addition to continuing the initiatives and developing the relationships described above, CDC has procured contractor services to conduct a formal assessment of other U.S. clinical laboratories’ willingness and ability to support public health emergency response. This multi-year project will address 4 specific areas, as follows.
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1. CDC will study the capacities and capabilities of commercial, academic, and other non-public health clinical laboratories to participate in emergency response. This area will consider ability to validate new tests; capacity to conduct high-volume, high-throughput testing; competency in safety, informatics, and in the workforce; and existence of specialized licensure and equipment.
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2. CDC will assess the organizational ability, willingness, and challenges of commercial, academic, and other non-public health laboratories to participate in emergency response. This assessment will examine different incentives and motivations, perceptions of opportunity and risk, and triggers to support or not support a response.
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3. CDC will evaluate the ability and willingness of commercial, academic, and other non-public health laboratories to support emergency response both geographically and by laboratory type. This work can inform more targeted public health engagement of clinical laboratories in specific areas.
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4. CDC will gather evidence-based guidance on how best to foster partnerships between public health and clinical laboratories to strengthen preparedness and response. CDC will explore how to align federal and state and local government needs during an emergency with private business models, and what specifically to do in advance of the next public health emergency to ensure a robust and effective private-public laboratory response.
CONCLUSIONS
The public health community recognizes that it cannot handle all possible public health emergency responses on its own. The public health laboratory sector has deep scientific expertise and excels at initial identification, complex characterization, and test development. The government – federal, state, and local – has invested significant resources in the public health laboratory infrastructure so that it can provide an immediate and rapid public health response. The private sector also has many resources and capabilities that can complement and augment the public health response. This is especially true in the clinical laboratory sector. Many commercial clinical laboratories are designed for high-volume, high-throughput diagnostic testing in a way that public health laboratories are not. Continued partnership with the private sector will enable the government to effectively supplement its existing public health infrastructure and allow the private sector to support the overall national public health mission.
Significant steps have been taken since 2017 to improve the communication and coordination between public health and the private clinical laboratory community, especially during a response to a public health emergency. Formal mechanisms have been established to advance this public-private partnership, and to address the challenges encountered around test development, test deployment, and results reporting. Commitments have been made to substantively study the current landscape and develop a comprehensive and strategic partnership between public health and private clinical laboratories. More work is necessary, but a strong foundation has been set for an improved clinical and public health laboratory response to the next public health emergency.
Acknowledgments
The authors thank the following individuals for their contributions to this manuscript: Beth Schweitzer, CDC, Division of Preparedness and Emerging Infections, Laboratory Preparedness and Response Branch; Amy Lambert, CDC, Division of Vector Borne Diseases, Arbovirus Diseases Branch; and Liz Thomas, American Clinical Laboratory Association.
The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Use of trade names and commercial sources is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Public Health Service, or the U.S. Department of Health and Human Services.
