Final Research Plan
Syphilis Infection in Nonpregnant Adults and Adolescents: Screening
September 18, 2014
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.
The draft Research Plan was available for comment from June 26 to July 23, 2014, at 5:00 p.m., ET.
The analytic framework is a diagram that outlines the process and outcomes of screening for syphilis in asymptomatic, nonpregnant adolescents and adults. The screening process includes risk assessment to determine which persons are at high or low risk for infection, and testing to determine if persons are positive or negative for a syphilis infection. Infected persons receive treatment that can lead to reduced complications of syphilis as well as reduced transmission or acquisition of infection. During screening, persons may also experience harms. The key questions examine published research studies linked to aspects of screening and outcomes, including reduction in complications of syphilis and transmission or acquisition of infection (Key Question 1), effectiveness of methods that identify persons at increased risk for syphilis (Key Question 2), accuracy of screening tests that detect syphilis infection (Key Question 3), and potential harms (Key Question 4).
- What is the effectiveness of screening for syphilis in reducing complications of the disease and transmission or acquisition of other sexually transmitted infections in asymptomatic, nonpregnant, sexually active adults and adolescents? What is the effectiveness of specific screening intervals and screening among population subgroups?
- What is the effectiveness of risk assessment instruments or other risk stratification methods for identifying persons who are at increased risk for syphilis?
- What is the accuracy of currently used screening tests and strategies (e.g., sequence of tests) for detecting syphilis infection?
- What are the harms of screening (e.g., labeling and false-positive or false-negative results)?
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
- Which population subgroups, including men who have sex with men, are at highest risk for incident syphilis infection?
- Which population subgroups are at highest risk for syphilis-related morbidity and mortality?
The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).
|Disease definition||Positive result for syphilis on any test modality|
|Populations||Asymptomatic, nonpregnant adolescents and adults, including patients coinfected with other STIs, including HIV||Symptomatic patients; neonates, infants, and children; pregnant women; contacts of cases; studies of HIV patients, for whom syphilis testing is disease management rather than a screening intervention|
KQs 1, 4: Screening effectiveness, including effectiveness of different screening intervals
KQ 2: Risk assessment instruments and other risk stratification methods that identify persons who are at increased risk for syphilis infection; definitions of “increased risk” and true disease status will be determined by the available studies
KQ 3: FDA-approved tests available in the United States that detect syphilis in biological specimens, including varying testing strategies (e.g., traditional, reverse sequence)
KQ 1, 4: No screening or alternate screening strategy or methods
KQ 2: True disease status
KQ 3: Study-specific comparator or “gold standard,” as determined by the study itself (e.g., an enzyme-linked immunosorbent assay technique could be evaluated by comparing its sensitivity and specificity with that of MHA-TP and FTA-ABS tests)
KQ 1: Reduction in complications of syphilis (e.g., neurosyphilis, symptomatic neurosyphilis, tertiary syphilis, congenital syphilis); disease transmission, including HIV transmission; other relevant clinical outcomes; rates of infection and other similar measures of infection
KQ 2: Detection of infection
KQ 3: Diagnostic accuracy (i.e., measures of the test's sensitivity, specificity, positive and negative predictive values, and other related measures)
KQ 4: Harms from screening (e.g., labeling, false-negative or false-positive results and related harms, including psychosocial harms)
KQ 1: Outcomes that are not directly related to health outcomes (e.g., laboratory studies)
KQ 4: Harms related to true-positive and true-negative tests, including psychosocial harms
|Settings||Primary care and primary care–referable settings (e.g., correctional facilities and community care, such as schools, family planning clinics, obstetrics and gynecology clinics, emergency departments, and STI clinics)|
All KQs: Good-quality systematic reviews
Benefits: Randomized, controlled trials; observational studies with comparison groups, including ecological studies
Harms: Randomized, controlled trials; observational studies, including cross-sectional and ecological studies
Benefits: Observational studies without comparison groups; case reports
Harms: Case studies
Abbreviations: FDA = U.S. Food and Drug Administration; FTA-ABS = fluorescent treponemal antibody absorption; MHA-TP = microhemagglutination assay for Treponema pallidum antibodies; STI = sexually transmitted infection.
A draft version of the research plan was posted for public comment on the USPSTF Web site from June 26 to July 23, 2014. Four individuals or organizations provided comments. A few comments requested that the review include serologic followup of persons with a syphilis diagnosis. While the USPSTF understands that serologic followup may play an important role in preventing complications and ongoing transmission of syphilis, the USPSTF considers this clinical management rather than primary prevention, and it is therefore outside the scope of this review. Comments about the key questions primarily concerned the inclusion and exclusion criteria, which have been clarified in the research plan. These clarifications include further defining persons who are eligible for screening (i.e., asymptomatic persons), that the definitions of increased risk and true disease status will be determined by the available studies, that gold standards will be defined by the studies themselves, and the research literature on harms will be summarized and the magnitude of effect will be determined if possible. Harms of treatment with penicillin will be included in the background section rather than in a key question because its harms are well-established. The contextual questions will be addressed by studies reporting rates and trends of syphilis rather than those evaluating screening effectiveness. The inclusion criteria were expanded to add more extensive descriptions of the populations and settings for screening and health outcomes and to clarify that study designs low on the evidence hierarchy may be used if no other studies are available.