Point-of-Care Diagnostic Testing in GlobalHealth: What Is the Point?The main goal of such testing is to inform caregivers in ways that lead rapidly totheir starting correct treatments for patients

Madhukar Pai, Marzieh Ghiasi, and Nitika Pant Pai

Although point-of-care (POC) testing is widelyconsidered a good idea, there is little agreementon what exactly it entails. While regulatory agen-cies such as the U.S. Food and Drug Administra-tion (FDA) categorize tests based on criteria suchas complexity and Clinical Laboratory Improve-ment Amendments (CLIA) waivers, the choice ofcriteria becomes vastly more complex when mov-ing from issues concerning national to globalhealth diagnostics.

In the global health context, the dominantviewpoint is that POC tests must meet several“ASSURED” criteria—that is, they need to be af-fordable, sensitive, specifıc, user friendly, rapidand robust, equipment-free, and deliverable. Thisdominant defınition of POC testing thus is prod-uct-oriented, and it restricts POC testing to aparticular class of products: those that are inex-pensive, simple, rapid (such as widely used preg-nancy tests), and which health workers can usewhile working in the community. From this per-spective, any test that needs to be conducted in alaboratory is not a POC test— creating a dichot-omy between the two.

We believe that this paradigm needs to be re-examined and, in doing so, propose an explicitlygoal-oriented redefınition for POC testing, par-ticularly applicable to resource-limited settings.On the basis that the rapid initiation of correcttreatment is the most critical goal of any POCtesting, we reverse engineered an alternative def-inition: POC testing is diagnostic testing that willresult in a clear and actionable management de-cision such as when to start treatment or to re-quire a confırmatory test, within the same clinicalencounter.

Why do we put rapid clinical decisions andbeginning of treatment at the heart of our defıni-tion? Quite simply, correct and timely treatment

saves lives, reduces morbidity, and reduces trans-mission. Thus, the impact of a POC test comesfrom implementing effective treatments ratherthan from the test itself. Thus, moving rapidlythrough the test-and-treat cycle in the same clin-ical encounter is the most important goal for anyPOC testing program. Needless to say, this goal iswhat patients want—to be rapidly diagnosed andput quickly on the right treatment. Unlike theconventional, product-oriented defınition, ourgoal-oriented defınition for POC testing is agnos-tic to issues such as cost, how the test or techno-logical platform looks, size of the product, whereexactly it is performed, and who performs it.

Thus, we argue that POC testing is not defınedby technology but by the successful use of a tech-nology at the point of care to make rapid deci-sions. The focus must be on POC testing pro-grams or strategies rather than technologies.

SUMMARY

➤ In general, point-of-care (POC) testing refers to diagnostic products that aresimple, low cost, and performed outside laboratories. This is a product-centric view of POC testing.

➤ We recommend redefining POC testing to make it goal-oriented, explicitlymaking the rapid initiation of correct treatment the most critical goal of anyPOC test.

➤ Unlike the standard definition, which creates a rigid dichotomy betweenPOC versus laboratory tests, we suggest that POC testing should be viewedas a spectrum: of technologies (simplest to more sophisticated), users (laypersons to highly trained), and settings (homes, communities, clinics,peripheral laboratories, and hospitals).

➤ POC testing is not defined by technology but by the diagnostic process,making it important to think in terms of testing programs or strategies thatlead to the rapid completion of the test-and-treat cycle.

➤ Health care systems interested in POC testing programs need to do morethan purchase rapid tests; they also need to build systems for rapidlycommunicating test results and beginning appropriate treatments.

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Tests or a Testing Program and Strategy?

A health care system can choose to implement arapid test as a POC testing program or not. Tointroduce a test as part of a POC testing program,several elements need to be put in place, includ-ing systems for rapid communication of test re-sults to patients and care providers, for rapidinitiation of treatments, and to ensure appropri-ate follow-up of patients. The test itself is only onecomponent of an overall POC testing programthat might prove relatively costly to implement,even if some of the rapid tests within it are inex-pensive.

Regardless of which technology is used, where,and by whom, the most critical elements of POCtesting are rapid turnaround and communicationof results to guide clinical decisions and comple-tion of testing and follow-up action in the sameclinical encounter, or at least the same day. Thus,systems for rapid reporting of test results to careproviders and implementing a mechanism to linktest results to appropriate counseling and treat-ment are as important as the technology itself. Ifsystems for reporting the results and follow-upcare, such as prescribing specifıc drugs to admin-ister to a patient, are not in place, then POCtesting is unlikely to have an important impact onclinical or public health outcomes.

The mere availability of rapid or simple testsdoes not ensure their use in POC testing pro-grams. Various barriers prevent the successfulimplementation of POC testing programs, in-cluding economic, regulatory, and policy-relatedissues, as well as user/provider perceptions andcultural barriers. It is also important that POCtesting fıt within real-world workflow patterns, aswell as economic and social structures. These re-quirements mean that POC testing programs willneed viable business models to ensure that theyare sustainable and will be used to make rapidtreatment decisions.

Many test developers seem to consider thephysical size of a technology to be a critical ele-ment of POC testing. While a small device or onethat can work without a specialized instrumentwill certainly help, the size of the technology byitself is not a critical consideration for POC test-ing programs. If deployed well, even a micro-scope can be successfully used in POC testingprograms. Although a lab-on-a-chip may be tiny,it might require a mass spectrometer to completethe analysis! Thus, it is not the size of a test that

defınes a technology as POC testing, but how it isimplemented.

Similarly, while low cost will certainly help toincrease the uptake of POC tests in resource-limited countries, cost is not an intrinsic charac-teristic of a POC test. Some tests such as solidcultures for Mycobacterium tuberculosis are inex-pensive to conduct, but their low cost does notmean that they can be used in POC testing pro-grams. On the other hand, some technologiessuch as handheld ultrasound devices or auto-mated molecular tests such as the GeneXpert®technology being marketed by Cepheid Inc. ofSunnvale, Calif., are expensive, but they can beand are being used effectively in POC testingprograms. Another reason why cost should notbe used to defıne POC testing is the fact thatinitiatives such as donor-led price buy down, ad-vance market commitments, and volume-baseddiscounts make cost an elastic concept. Willing-ness to pay is also elastic, and there is no easy wayto separate low-cost from expensive products.While it is critical to make tests affordable, webelieve cost should not be confused with the con-cept of POC testing.

Dichotomy or a Spectrum?

Unlike the standard defınition which creates afalse dichotomy between POC versus laboratorytests, we argue that POC testing should be viewedas involving several components, including tech-nologies that range from simplest to more sophis-ticated, users including lay persons to highlytrained workers, and settings including homes,communities, clinics, peripheral laboratories,and hospitals (Fig. 1). As illustrated, POC testingis happening in diverse settings, ranging fromhomes to hospitals.

In this broad framework, the use of rapid testsin the community by front-line health workers isonly one of several types of POC testing. A goodexample of this is the use of malaria rapid diag-nostic tests by community health workers in Af-rica. Other examples are in-home pregnancy testsand oral fluid HIV self-tests. Here, the goal isself-assessment and linkages to care. Such tests,whether done at home or in the community, needto be very simple, preferably instrument-free (al-though small devices such as glucometers showthat even this restriction may not be necessary),and should involve very few steps. Additionally,

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interpretation should be very simple andstraightforward, and the requirement for trainingshould be minimal.

At the other end of the spectrum, POC testingprograms are being implemented within hospi-tals. For example, labor ward nurses in hospitalsare using rapid, oral-fluid HIV tests to determinewhen to provide antiretroviral therapy to reducethe risk of mother-to-child transmission of thisvirus. Emergency room doctors are rapidly diag-nosing and treating ectopic pregnancy and ab-dominal trauma using handheld ultrasound de-vices. Rapid tests are also being used in intensivecare units to make timely decisions on patienttreatments. At this level of the health care deliverysystem, tests do not need to be instrument-free orinexpensive, and users are often well trained.Fairly sophisticated technologies can be and arebeing used to achieve rapid results that can in-form clinical decisions.

While the traditional defınition of POC testingdoes not include laboratories, our framework ac-knowledges the important role that peripherallaboratories have in POC testing programs. In

most developing countries, there are large num-bers of primary health centers with small, at-tached microscopy laboratories that typically arerun by laboratory technicians with minimaltraining. These peripheral laboratories have lim-ited resources, but can perform simple micros-copy tests such as malaria and sputum smears,lateral flow assays, and basic tests such as hemo-globin, urine sugar, albumin, and Gram stains(Fig. 2). Patients who visit these primary healthcenters typically are asked to wait for a few hoursbefore being sent home on the correct treatment.As long as the test-and-treat cycle is completed inthe same visit, we consider these to be excellentexamples of POC testing.

Diversity of Target Product Profiles

The diversity of settings, users, and technologiessuggests that restricting product characteristicsmakes a lot of sense once a decision is made tolimit a test to a particular setting or context. Inother words, every POC test does not need tomeet the same target product profıle (TPP) such

FIGURE 1

The spectrum of point-of-care testing. (Adapted from N. P. Pai et al., PLoS Med. 9(9)e1001306, 2012; copyright heldby the authors under Creative Commons license.)

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as the ASSURED criteria, for example. While atechnology designed for laboratories and hospi-tals (right side of the spectrum, Fig. 1) is unlikelyto work in community or home-based settings,the reverse is quite possible. For example, theOraQuick® In-Home, which is marketed by Ora-Sure Technologies Inc. of Bethlehem, Pa., rapidtest for HIV is being used in the full range ofsettings from home to hospital.

All TPPs, ideally, should include suffıcient in-formation on the intended purpose of the test, thesetting, and likely users. TPPs could also provideguidance to product developers on the desiredcost, based on public health needs in resource-limited settings. Indeed, such TPPs have beendeveloped for HIV and TB diagnostics.

Conclusion

By framing POC testing as a goal-oriented spec-trum of activities while de-emphasizing the re-strictive, product-centric view, we believe our ap-proach is more inclusive, more reflective ofreality, and will allow more industries and test

developers to develop a range of products thatmay be amenable for use in POC testingprograms.

For example, several companies are develop-ing robust, automated, molecular assays for tu-berculosis that are potentially deployable in mi-croscopy centers. Such devices are already beingused for POC CD4 testing of individuals withHIV infections, and will also be available for viralload testing. These simple, battery-operated de-vices do not require sophisticated, centralizedlaboratories, and can help doctors make rapiddecisions in community care settings. A tradi-tional defınition of POC testing would excludethese examples as they are neither inexpensivenor instrument-free, whereas a goal-orienteddefınition would include these devices based onhow well they fıt within the diagnostic process.

Lastly, we believe that an approach that fo-cuses on rapid treatment decisions as the goal iscloser to what all patients want from their careproviders, and might inspire health care systemsand donors to think beyond just procuring rapidtests and ensure that these testing technologies

FIGURE 2

Peripheral laboratory attached to a primary health center in India. Rapid tests available in this center are shownon the right. (Image credit: Madhukar Pai.)

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are implemented as POC testing programs. Onlythen will we see the true impact of POC testing.Madhukar Pai is the Director of Global Health Programs, andthe Associate Director of the McGill International TB Centre,McGill University; Marzieh Ghiasi is a researcher at McGill GlobalHealth Programs; and Nitika Pai is an Associate Professor in theDepartment of Medicine, McGill University, Montreal, Quebec,Canada.

Suggested Reading

Denkinger, C. M., S. Kik, and M. Pai. 2013. Robust,reliable and resilient: designing molecular tuberculo-sis tests for microscopy centers in developing coun-tries. Exp. Rev. Mol. Diag. 13:763–767.

Drain, P. K., E. P. Hyle, F. Noubary, K. A. Freedberg, D.Wilson, W. R. Bishai, W. Rodriguez, and I. V. Bas-sett. 2014. Diagnostic point-of-care tests in resource-limited settings. Lancet Infect Dis. 14:239 –249.

Pai, N. P., C. Vadnais, C. M. Denkinger, N. Engel, andM. Pai. 2012. Point-of-care testing for infectious dis-eases: diversity, complexity, and barriers in resource-limited settings. PLoS Med. 9(9)e1001306; http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001306

Pai, M. 2013. Point of care (POC) testing for infectiousdiseases: diversity, complexity, and barriers in devel-oping countries. Invited lecture at 2013 CEND Sym-posium at the University of California, Berkeley.Video available at http://www.youtube.com/watch?v�SqASU6uChOo

Pai, N. P., R. Barick, J. P. Tulsky, P. V. Shivkumar, D.

Cohan, S. Kalantri, M. Pai, M. B. Klein, and S.Chhabra. 2008. Impact of round-the-clock, rapid oralfluid HIV testing of women in labor in rural India.PLoS Med. 6;5(5):e92.

Pai, N. P., and M. Pai. 2012. Point-of-care diagnostics forHIV and tuberculosis: landscape, pipeline, and unmetneeds. Discov. Med. 13:35– 45.

PATH. 2014. Target product profıle: HIV self-test version4.1: a white paper on the evaluation of current HIVrapid tests and development of core specifıcations fornext-generation HIV tests. PATH, Seattle. http://www.path.org/publications/fıles/TS_hiv_self_test_tpp.pdf

UNITAID. 2014. Tuberculosis diagnostics technology andmarket landscape, 3rd ed. UNITAID, Geneva, Switzer-land. http://www.unitaid.eu/images/marketdynamics/publications/UNITAID_TB_Diagnostics_Landscape_3rd-edition.pdf

UNITAID. 2014. HIV/AIDS diagnostics technologylandscape, 4th ed. UNITAID, Geneva, Switzerland.http://www.unitaid.eu/images/marketdynamics/publications/UNITAID-HIV_Diagnostic_Landscape-4th_edition.pdf

UNITAID. 2014. Malaria diagnostics technology andmarket landscape, 2nd ed. UNITAID, Geneva, Swit-zerland. http://www.unitaid.eu/images/projects/malaria/2014_Malaria_Diagnostics_Landscape_2nd_edition.pdf

WHO. 2014. Meeting report: high-priority target productprofıles for new tuberculosis diagnostics: report of a con-sensus meeting. World Health Organization, Geneva,Switzerland. http://apps.who.int/iris/bitstream/10665/135617/1/WHO_HTM_TB_2014.18_eng.pdf?ua�1

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