WHO Target Product Profiles and the Characteristics of TBDx™

During the recent 45th World Conference on Lung Health, the World Health Organization (WHO) released a new Meeting Report, “High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting.”   The publication follows a meeting convened in late April by WHO, on behalf of the Global Laboratory Initiative and the New Diagnostic Working Group of the Stop TB Partnership. The meeting brought together medical, clinical, and academic luminaries to discuss and recommend product specifications for future diagnostic technologies.

High Priority Target Product Profiles (TPPs)

To reach the 2035 WHO goals of reducing TB incidences by 90%, and related deaths by 95%, new diagnostic tools are needed. The TPPs are intended to introduce product specifications that can best meet the needs of the medical and clinical community. The meeting was intended to create a consensus on four TPPs that are of highest priority:

  1. A point-of-care, non-sputum based tool capable of all forms of TB (active, latent, pulmonary, extra pulmonary) using biomarkers (Biomarker Test)
  2. A point-of-care triage test, one that is simple, low-cost, and can be used by health care providers who have first contact with TB suspects, and can be confirmed by a more costly secondary test (Triage Test)
  3. A point-of-care, sputum-based test to replace smear microscopy for detecting pulmonary TB (Smear Microscopy Replacement Test)
  4. A rapid drug-susceptibility test (DST) that can be used in a microscopy center to select first-line drug therapy (Rapid DST Test)

The Meeting Report provides extensive discussions and appendices detailing the features and performance characteristics that meet the ideal or minimal requirements. Though optimal characteristics may provide the greatest impact for clinicians, a test that meets minimal specifications could be a very acceptable diagnostic tool nonetheless. In some cases, less than minimal specifications would be acceptable if it pertained to a feature that may be desirable, but not mandatory.   Adding incentives to the developers the report details the market size for each test, worldwide.

Triage and Smear Replacement Test Profiles

Two product specifications, triage and smear microscopy replacement test, best match the diagnostic and operational characteristics of TBDx™.  In areas where these specifications do not match completely, APVS is focusing development efforts to more closely align with them.

A point-of-care test can be defined as a diagnostic tool used “during a patient’s first encounter with the health-care system where TB risk is first identified” and where clinical diagnosis and treatment occurs on the same day.

Triage Test

As most suspected TB candidates do not have the disease, the goal of a triage test is to quickly identify individuals symptomatic for active TB.  Typically such a test would have a high sensitivity (positive for active TB) and a lower degree of specificity (more false positive). Test results identifying those individuals with potential TB will have the results confirmed by a more costly, more specific secondary test (removes false positives).

The characteristics outlined in the table below have been selected from a more detailed list provided in the TPP and are compared with TBDx™ characteristics today.

Operational Characteristics Ideal Minimal TBDx™ Today
Target User Community Worker Auxiliary Nurse Health Worker; No Medical Experience Required
Setting Community, village, or higher health system level Health post, primary care clinic, or higher health system level Hospital, Microscopy Center, or Reference Lab
Price <US$1.00 <US$2.00 <US2.00; <US1.00 with slide volume
Sensitivity 95% of confirmatory test; This test is approximately 84% sensitive 90% of confirmatory test, with exceptions Sensitivity: 79.8% (95% of confirmatory test)
Specificity 80% of confirmatory test. This test is 99% specific 70% of confirmatory test, with exceptions 78.9% Specificity (79.7% of confirmatory test)
Sample Type Non-sputum Sputum Sputum
Time to Result <5 minutes <30 minutes 5 minutes
Throughput >30 tests / 8 hrs. >20 tests / 8 hrs. >95 / 8 hrs.
Multiuse platform None None Designed as multiuse platform for infectious disease

TBDx™ Today performance is based on 2013 NHLS evaluation in Johannesburg, South Africa

As the chart suggests TBDx™, with its automated sputum microscopy capabilities, has performance characteristics that would meet either ideal or minimal performance. TBDx™ is a technology that could be a useful triage test in settings where there is high volume, or where portability is not required (reference lab, microscopy center, and regional or hospital laboratories).

Rapid Sputum-based Smear Replacement Test

An easy to perform, rapid and sensitive pulmonary TB test could replace smear microscopy in settings such as microscopy centers. This would not only improve diagnosis and follow-on treatment, but also it would reduce transmission and morbidity rates. If this technology could be used to monitor patient treatment, it would add value.  The test requires simple sample preparation with minimal operations and training.

The characteristics outlined in the table below have been selected from a more detailed list provided in the TPP, and are compared with TBDx™ characteristics today.

Operational Characteristics Ideal Minimal TBDx™ Today
Target User Healthcare Workers, with minimal Training No Medical Experience Required
Setting Microscopy Center Microscopy Center or higher level of healthcare system Microscopy Center, Reference Lab
Price <US$4.00 <US$6.00 <US2.00; <US1.00 with slide volume
Sensitivity >95% of single test compared with culture. Smear positive – 99%; Smear negative – 67%. >80% of single test compared with culture. Smear Positive – 99% Smear Negative – 60%  = 80% of single test / culture Smear Pos – 98% Smear Neg – 59%
Specificity 99% 98% Overall, 80% but 95.6% if Scanty 1 = Negative
Time to Result <20 minutes <1 hour 5 minutes
Treatment Monitoring Yes No Yes
Throughput 10-15 tests per day 10 tests per day >95 tests per day, unattended
Maintenance 2yrs or 5,000 samples 1 yr. or 1,000 1 year or 5,000

TBDx™ Today performance is based on 2013 NHLS evaluation in Johannesburg, South Africa

As the two charts illustrate, TBDx™ offers performance and operational characteristics that match or exceed the WHO Targeted Product Profiles. Automated sputum microscopy can easily scale as it leverages the existing infrastructure in most diseased burdened healthcare systems today. The performance of automated sputum microscopy not only can exceed routine microscopy, but also the performance can approach the performance characteristics of more advanced technology tests, in some cases. Whether the performance demand involves Sensitivity, Specificity, Cost, Throughput, Treatment Monitoring, Setting, Maintenance, or Staff Training, TBDx™ can be a high-performing and affordable technology for reference labs, microscopy centers, or hospitals with laboratories today.

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