Poor Reporting of Outcomes Beyond Accuracy in Point-of-Care Tests for Syphilis: A Call for a Framework

Table 1

Description of studies.

Study	Setting	Population and sample size	Index test	Study design	IRO preference	IRO acceptability	IRO feasibility	IRO barriers and challenges	IRO impact	IRO prevalence
Amadi et al., 2010 [45]	Nigeria, urban (LM)	100 dental clinic patients	Syphilis Ultra Rapid Test Strip	CS						1%
Benzaken et al., 2007 [35]	Brazil, urban (UM)	Study 1: 541 STD clinic attendees.; Study 2: 248 STD clinic attendees	Study 1: SD Bioline Syphilis and Syphicheck-WB; Study 2: VisiTect Syphilis and Determine.	CS			100% of professionals rated instructions and results interpretation as easy.; Study 1: reproducibility; between clinic and lab professionals had agreement of 99% and kappa index >0.95% for both tests.; Study 2: agreement between clinic and lab professionals was 100%.; In both studies, 100% of participants were willing to wait up to 30 minutes for their results.	Unnecessary treatment was an issue.
Benzaken et al., 2008 [19]	Brazil, urban (UM)	510 STI clinic attendees including MSW and FSW; operational characteristics were collected from 12 clinic staff and 60 clients.	Visitect	CS	Clients: 62% preferred POC strategy.		Clinic staff: 75% found test easy to use and 67% found the test easy to interpret.; Clients: 93% were not deterred by the waiting time.	Clients: waiting time (7%), cost of transport (10%), opening hours (25%) or lack of trust in POC test results (3%), pain caused by finger prick (57%), and preference for venous blood (38%) collection were some barriers.; Clinic staff: only half trusted its results, mostly cited reason being due to inability of the test to differentiate between old and recent syphilis leading to overtreatment and also experienced frequent discordant results between POC and confirmatory tests.
Bronzan et al., 2007 [17]	South Africa, rural (UM)	1285 ANC attendees.	Determine	CS	Nurses: 68.2% preferred on-site ICS over on-site RPR and off-site RPP/TPHA.	Nurses: on-site testing was acceptable and favoured over off-site testing as it allowed for prompt diagnosis, patient education, and immediate treatment.	100% found on-site ICS test easy to perform, fast, and reliable, compared to 95% who found on-site RPR time consuming, unreliable, and difficult to perform and read.	Unnecessary treatment.	89.4% of women with high-titer syphilis received treatment with ICS versus 63.9% in women tested with on-site RPR and 60.8% tested with off-site approach.
Callegari et al., 2014 [24]	Brazil, urban (UM)	438 adult patents (18 years plus) of outpatient clinic.	Rapid check syphilis immunochromatographic treponemal test.	CS						5.3% (95% CI: 3.3–7.3)
Campos et al., 2006 [34]	Peru, urban (UM)	3586 FSW in commercial sex venues.	Determine	CS		97.4% agreed to POC test.	Easy to adapt, implement, and integrate with existing into existing work-based STI prevention services.	Inadequate lighting in the field was a problem.
Chen et al., 2013 [25]	China, urban (LM)	1808 FSW	Wantai Anti-TP Antibody Rapid Test (RST).	CS		94.2% (95% CI 93.1–95.2%) got the testing.	95.2% (95% CI 94.1–96.1%) were willing to get RST on-site.			8.5%
Chen et al., 2012 [23]	China, urban (LM)	2812 FSW	Wantai Anti-TP Antibody Rapid Test.	CS	66.1% preferred finger prick over blood draw.	95.0% (95% CI: 94.1–95.7%) accepted rapid test.	99.3% (95% CI: 98.9–99.5%) of those accepted testing got the test.; 52.5% preferred verbal on-site method of result notification.	57.7% listed pain as reason for not wanting to be finger pricked.		6.8%
Dayan et al., 2013 [21]	Turkey, urban (UM)	266,035 healthy blood donor samples.	Architect (Abbott).	Retrospective cohort.						0.07
Dlamini et al., 2014 [36]	South Africa, urban and rural (UM).	297 samples from different health facilities.	SD Bioline, Hexagon	CS			Testing with both tests was completed within the recommended 15–20 min.		3.4% of SD Bioline results were unreadable. Visibility was improved on repeat testing. Hexagon results were more clear and quick in comparison to SD Bioline.
Elhadi et al, 2013 [46]	Sudan, urban (LM)	4220 FSW	SD Bioline	CS						Ranged from 1.5% in the northern zone to 8.9% in the eastern zone (of their division of Sudan).
Garcia et al., 2013 [39]	Peru, urban (UM)	17,155 ANC attendees.	SD Bioline	CS				9 of 604 (44.5%) health providers participating in the training had difficulties with near vision which did not allow them to recognize the line in the POCT" and 0.3% were colour blind and could not see the red line.	Improved treatment coverage with 91.6% receiving at least one dose of penicillin and 80% with two doses reduced a process that consisted of 27 days in 6 visits to 1 visit in one day; total screening coverage was 94.8%.	0.90%
García et al., 2007 [26]	Bolivia, urban and rural (LM)	11,618 ANC attendants.	Determine	CS		POC testing highly acceptable to participants, clinicians, and laboratory technicians.		Political instability; difficult to ensure continuity.		5%
Gupte et al., 2011 [27]	India, urban (LM)	19,809 female, male, and transgender sex workers.	Syphicheck-WB	CS		Acceptance was high, ranging from 76.0% in MSW to 57.1% bar-based FSW.		Only 2/3 of those positive with POC agreed to RPR confirmation.	Using POC, during 3-month intervention period, syphilis test uptake was 63.1%, more than 4-fold higher than the monthly average uptake of 14.3% at clinic sites during the preceding 9-month period.	Life time infection 3%; active syphilis confirmed with RPR-1.2%.
Herring et al., 2006 [4]	South Africa (UM), Gambia (L), Tanzania (LI), China (LM), Sri Lanka (LM), Haiti (L), USA (H), Russian Federation (UM).	Evaluation panel from archived specimens.	Determine; Syphilis Fast; Espline TP; Syphicheck-WB; SD Bioline; Visitect Syphilis.	CC			Multisite evaluation six kits scored on clarity of instructions, technical complexity, ease of interpretation, and equipment required but not provided. Determine scored the highest and Syphilis Fast scored the lowest.; Test reproducibility variability was low.
Hurtado et al., 2010 [47]	Spain, urban (H)	500 MSM in saunas and flats.	Determine	CS						5% in saunas.; 2.3% in apartments.
Juárez-Figueroa et al., 2007 [37]	Mexico, urban (UM)	548 FSW and women within 24 h postpartum.	Determine	CS			All 3 readers found POC test highly user-friendly, and there was agreement in 544 of 548 results (99.3%).	Disagreements were due to appearance of faint lines.
Lahuerta et al., 2011 [48]	Guatemala, urban (LM)	2874 FSW, MSM, TG MSM, NR (MV: 1336, STI clinic: 1538).	Determine	CS						MV: NR: 0.8%, MSM/TG: 0%, FSW: 4.6%.; STI clinic: NR: 0.6%, MSM/TG: 1.4%, FSW: 1.3% .
Lee et al., 2010 [18]	Australia, urban (H)	183 MSM	Determine	CS	79% preferred rapid testing at clinic to venipuncture and serology.; 54% preferred self-test if it was available.		Of those who preferred POC at clinic over venipuncture and serology, reasons were immediacy of the result (32.6%), reduced pain or invasiveness (8.9%), and the convenience of not requiring a second clinic visit for test results (4.4%).			3.8%
Mabey et al., 2012 [22]	Brazil, rural (UM) China, rural Peru, rural and urban (UM) Tanzania, rural (L) Uganda, rural (L) Zambia, rural and urban (LM).	Over 100,000 ANC attendees.	China: Rapid Syphilis test; Rest: SD Bioline Rapid Syphilis test.	CS	Most clients preferred a finger prick over venipuncture; because of the smaller volume of blood required.	POC tests were well accepted by health care workers.	All health care workers in all sites thought POC tests were easy to perform. For instance, 82% of Ugandan health care workers reported POC tests as “very easy to perform.”; Clients liked receiving results and treatment on the same day as testing rather than having to return.; Almost all who tested positive received treatment: 100% in Brazil, 93.6% in China, 97% in Peru, 90.1% in Tanzania, 103.6% in Uganda, and 95.2% in Zambia.		Change in percent of population that were screened following a POCT introduction was 1.6% in Brazil’s sexually active population and 1.4% in their ANC population. Increase in screening was seen in other sites: 1.9% in China, 1.0% in Peru, 10.9% in Tanzania, 5.3% in Uganda, and 9.2% in Zambia.
Manavi et al., 2012 [28]	UK, urban (H)	405 men attending gay pride event.	OraSure assay	CS		96% accepted testing.				0.5%
Miranda et al., 2009 [41]	Brazil, urban (UM)	1380 ANC attendees.	Determine	CS					5.1% with no previous prenatal care learned serostatus among which 1 was positive detected.	0.4%
Mishra et al., 2010 [29]	India, urban (LM)	4871 FSW attending STI clinic.	Qualpro Syphicheck.	CS		Of the 4157 first-time attendees offered testing,; 1117 (26.9%) accepted.		3% of refusals were due to unwillingness to undergo a finger prick due to perceived pain, discomfort, or other.	Acceptance of syphilis increase significantly by 8.0% during the POC protocol versus the standard.; Compared to a historical comparison, POC protocol allowed for significantly increased treatment coverage at 16.4%.
Munkhuu et al., 2009 [40]	Mongolia, urban (LM)	3850 ANC attendees in intervention and 3850 in control group.	SD Bioline Syphilis.	CRT				Some women received unnecessary treatment.; Some partners did not receive treatment; thus women were left at risk of reinfection.	Significantly higher number of women at intervention clinics than at control clinics were tested for syphilis at 1st visit (99% versus 79.6%). Similar result was found at 3rd trimester visit. As well, significantly higher number of infected women and their partners were treated at intervention clinics while lower number of congenital syphilis cases occurred.
Munkhuu et al., 2009 [38]	Mongolia, urban (LM)	246 ANC attendants	SD Bioline Syphilis	CS			All clients preferred receiving results the same day. Women were well satisfied with POC testing. Some cited reasons were time savings (88%), rapid results and no pain (77%), and counselling (42%).	Risk of intimate partner violence in case of discordant results between patient and husband.; Time consuming as provider is still expected to complete their “regular” tasks.; Concerns over procurement of POC tests.
Onwuezobe et al., 2011 [49]	Nigeria, urban (LM)	415 ANC attendees.	ACON Ultra Rapid Syphilis Test Strip.	CS						2.2%
Pai et al., 2012 [20]	India, rural (LM)	1066 ANC attendees	Determine	CS	99.3% (95% CI: 98.8, 99.8) preferred 3-in-1 testing to conventional strategies.	98% consented to testing.	96% completed study procedure.; Time it took for STPOC was 25 min (range 21–27) versus 45 min (range 40–47) for strategy.	32.1% (95% CI: 29.2–35.0%) reported prick pain.	In the same visit, women were tested and all positives were treated, unlike the traditional method.	0.2% (95% CI: 0–0.48)
Parthasarathy et al., 2013 [42]	India, urban and rural (LM)	330,000 FSW, 82,000 MSM, 10,000 IDU.	Immunochromatographic strip test (ICST) used from 2007 (study conducted from 2004 to 2007).	Retrospective analysis					In comparison to RPR testing, ICST used for screening increased from 7.4% in 2007 to 77.0% (𝑃<0.001) in 2009. During the same period, the syphilis screening rates among clinic attendees increased from 9.0% to 21.6% (𝑃<0.001).
Read et al., 2013 [30]	Australia, urban (H)	98 MSM attending testing tent at a fair	Determine	CS		Participating rate of 0.23% (2010) and 0.26% (2011).			All testing tent clients were successfully contacted and treated and undertook partner notification.	1.02% (95% CI: 0.03–5.55)
Revollo et al., 2007 [50]	Bolivia, urban (LM)	1594 postpartum women in hospital.	Determine	CS						7.2% (95% CI: 6.5–7.9)
Sabidó et al., 2009 [16]	Brazil, urban (UM)	60 high risk populations, 10 clinical and 2 lab staff.	Visitect Syphilis test.	CS	60% of clinical staff and 52% of clients preferred conventional over POC testing.	Acceptable to patient and laboratory technicians.	Staff: 9/12 found test instructions easy/very easy.; Clients: 69% of clients found time waiting for testing as short. 68% found that POC did not cause any discomfort.; 95% of patients would recommend this test to others.	6/10 clinical staff lacked confidence in POC results.
Seguy et al., 2008 [31]	Guyana, rural (LM)	5618 miners	Determine	CS		80% of miners approached accepted testing.				6.4% (95% CI: 4.5, 9.1)
Smit et al., 2013 [43]	Tanzania, urban and rural (L).	2099 ANC attendees.	SD Bioline	CS					If POC testing is in ANC clinics, 82% of pregnant women would receive testing and treatment, compared to 16% if no POC is used.
Strasser et al., 2012 [32]	Uganda, rural and urban (L); Zambia, rural and urban (LM).	Uganda: 14,540 ANC attendees; Zambia: 11,985 ANC attendees.	SD Bioline	CS study, with pre-post intervention design and retrospective review.		Uganda: 90.3% tested.; Zambia: 95.6% tested.	Uganda: 99.0% of those treated received STAT; 9.9% of partners tested for syphilis.; Zambia: 95.8% of those treated received STAT; 3.0% of partners tested for syphilis.		Significantly higher number of women tested and treated and their partners tested using POC intervention versus the traditional method.	Uganda: 5.3%.; Zambia: 9.2%.
Todd et al., 2011 [52]	Afghanistan, urban (L).	483 IDU.	SD Bioline	CS						2.1% (95% CI: 1.0–3.8)
Todd et al., 2008 [51]	Afghanistan, urban (L).	4452 ANC attendees.	Determine	CS						0%
Tucker et al., 2011 [33]	China, urban (LM).	2061 STI clinic attendees.	An immunochromatographic rapid treponemal test (Wantai, Beijing, China).	CS		Among those eligible, 81.6% agreed to syphilis rapid test.
Yang et al., 2013 [44]	China, rural (LM).	27,150 ANC attendees.	Acon Biotech.	CS					73.6% of those diagnosed received treatment.	0.39%

CS: cross-sectional; CC: case control; CRT: clustered randomized trial; STPOC: simultaneous triple point-of-care testing; STAT: same day testing and treatment; ICS: immunochromatographic strip; RPR: rapid plasma reagin; TPHA: Treponema  pallidum particle agglutination assay;L: low-income economies; LM: low-middle income economies; UM: upper-middle income economies; H: high-income economies [56]; STD: sexually transmitted diseases; FSW: female sex workers; ANC: antenatal clinic; MSM: men who have sex with men; TG: transgender; NR: not reported being member of a risk group; MV: mobile van; STI: sexually transmitted infections; MSW: male sex workers; IDU: injecting drug users.