Challenges for Diagnostic Test Developers

Challenges

In the early stages of an outbreak, some types of materials may not be available or are only available to a very limited group of developers. Diagnostic test development and validation require a rich and diverse inventory of both relevant clinical sample types (e.g., eye fluids, semen, cerebrospinal fluid) and pathogens collected from the affected patient populations, which are often in very short supply at the beginning of an outbreak. The lack of relevant material and clinical specimens for test development and validation may delay response time and compromise the ability of developers to validate tests with the goal of improving patient management and strengthening the public health response to emerging infectious diseases.

Access to test materials is delayed without dedicated and centralized logistical support. There are a number of challenges associated with collecting patient samples, starting with the need for Institutional Review Board (IRB) approval and possible requirements for informed consent. Other challenges include fulfilling export and import permits requirements, intellectual property considerations, reluctance from third parties to share samples, limitations on commercial use of the specimens, difficulties transferring materials (e.g., biosafety and biosecurity concerns), the process for generating material transfer agreements (MTAs), and identifying and coordinating available personnel and facilities to collect and manage samples in an emergency. All of these challenges become more acute when the outbreak begins outside the United States because access to clinical specimens may be restricted by international policies.

When available, test materials sourced from many different providers may have varying quality and sample characterization. The use of different samples without a "gold standard" method to assess their validity (confirm the presence of a pathogen, antibodies, or other biomarkers) may lead to a lack of comparability between samples obtained from different sources. Test materials of unknown quality and associated characterization may delay emergency use authorization (EUA) and the application of these tests in an emergency response.

Mock clinical samples, created by spiking a clinical matrix with the agent of interest, can sometimes be used as a substitute for natural clinical samples obtained from affected individuals. Where the emerging disease threats are known and the pathogens available, these could potentially be prepared in advance of an outbreak. However, in events where a new disease emerges, the inability to create, generate, and use contrived samples may cause delays in test performance development and validation.

CDC and other diagnostic test developers, including those in the private sector, currently lack access to sufficient numbers of samples, materials, and isolates of pathogens or related organisms (see Table 1) needed to rapidly mount emergency response efforts for emerging and reemerging disease threats. Currently, there is no centralized resource that can provide appropriate, well-characterized samples and materials that are essential for the development and validation of diagnostic tests during public health emergencies. A recent Government Accountability Office report recognized challenges faced by commercial developers of diagnostic tests for Zika. This report also identified the challenges associated with accessing well-characterized clinical samples and reference materials, as well as developing partnerships with international entities and obtaining appropriate permits to acquire samples.1 Well-characterized samples would include metadata such as age, sex, days post onset of symptoms, pregnancy status, tests that were performed on the specimen, and the results of those tests.

Table 1: Sample types and materials needed for test development