Avoiding verification bias in screening test evaluation in resource poor settings: a case study from Zimbabwe.

BACKGROUND: Verification bias occurs when the percentage of subjects receiving disease verification differs according to the test result. Statistical adjustment yields unbiased sensitivity and specificity under a missing at random (MAR) assumption. PURPOSE: To use an example from an international study to show how the assumptions needed for unbiased statistical adjustment for verification bias can be undermined by conditions on the ground, and that accuracy of estimates is also compromised by too low a sampling fraction of subjects who test negative. METHODS: A study in Zimbabwe assessed the accuracy of a screening test for cervical cancer screening, visual inspection with acetic acid (VIA). The study was conducted in two phases, Phase I, where only 10% of subjects with negative tests received verification, and Phase II, in which nearly all subjects were verified. Unadjusted, simple- and covariate-adjusted estimates were compared to investigate factors affecting differences. Bootstrap simulations were used to illustrate the effect of varying test negative sampling fractions. RESULTS: Phase I unadjusted sensitivity and specificity were 0.66 (0.61-0.70) and 0.34 (0.31-0.36), respectively. Simple-weighted adjusted estimators accounting only for VIA status were 0.20 (0.17-0.23) and 0.80 (0.78-0.81), respectively, suggesting the test to be useless. It was found that verification (colposcopy) capacity in-country had been exceeded, and that random selection of test negative patients for colposcopy had been compromised. Phase II estimates of sensitivity and specificity were 0.77 and 0.64, respectively. With 9% disease prevalence, a VIA test-negative sampling fraction >50% was necessary for the confidence intervals for sensitivity to have more than a 90% probability of including the true value. LIMITATIONS: Phase I statistical adjustment was not made for MAR deviations unexplained by the two auxiliary factors, Pap results and STD history. Adjustment was not possible for other unmeasured co-factors. CONCLUSIONS: While there are standard formulae for correcting for verification bias, these will be biased if the MAR assumption is not met, which can occur through the actions of study personnel or subjects. Design of such studies in low resource environments needs to either require 100% verification, or employ procedures ensuring that the sample of test negatives who receive verification is indeed random. In addition, required test negative sampling fractions need to incorporate information on both disease prevalence and overall sample size.

Visual inspection with acetic acid as a cervical cancer test: accuracy validated using latent class analysis.

BACKGROUND: The purpose of this study was to validate the accuracy of an alternative cervical cancer test - visual inspection with acetic acid (VIA) - by addressing possible imperfections in the gold standard through latent class analysis (LCA). The data were originally collected at peri-urban health clinics in Zimbabwe. METHODS: Conventional accuracy (sensitivity/specificity) estimates for VIA and two other screening tests using colposcopy/biopsy as the reference standard were compared to LCA estimates based on results from all four tests. For conventional analysis, negative colposcopy was accepted as a negative outcome when biopsy was not available as the reference standard. With LCA, local dependencies between tests were handled through adding direct effect parameters or additional latent classes to the model. RESULTS: Two models yielded good fit to the data, a 2-class model with two adjustments and a 3-class model with one adjustment. The definition of latent disease associated with the latter was more stringent, backed by three of the four tests. Under that model, sensitivity for VIA (abnormal+) was 0.74 compared to 0.78 with conventional analyses. Specificity was 0.639 versus 0.568, respectively. By contrast, the LCA-derived sensitivity for colposcopy/biopsy was 0.63. CONCLUSION: VIA sensitivity and specificity with the 3-class LCA model were within the range of published data and relatively consistent with conventional analyses, thus validating the original assessment of test accuracy. LCA probably yielded more likely estimates of the true accuracy than did conventional analysis with in-country colposcopy/biopsy as the reference standard. Colposcopy with biopsy can be problematic as a study reference standard and LCA offers the possibility of obtaining estimates adjusted for referent imperfections.

Cervical cancer prevention: safety, acceptability, and feasibility of a single-visit approach in Accra, Ghana.

OBJECTIVE: The purpose of this study was to assess the safety and acceptability of a single-visit approach to cervical cancer prevention combining visual inspection of the cervix with acetic acid wash (VIA) and cryotherapy. STUDY DESIGN: The study was observational. Nine clinicians were trained in VIA and cryotherapy. Over 18 months 3665 women were VIA-tested. If positive and eligible, cryotherapy was offered immediately. Treated women were followed-up at 3 months and 1 year. RESULTS: The test-positive rate was 13.2%. Of those eligible, 70.2% and 21% received immediate or delayed treatment, respectively. No major complications were recorded, and 5.6% presented for a perceived problem post-cryotherapy. Among those treated over 90% expressed satisfaction with their experience, and 96% had an indentifiable squamo-columnar junction. Only 2.6% (6/232) were test positive, 1-year posttreatment. CONCLUSION: A single-visit approach using VIA and cryotherapy proved to be safe, acceptable, and feasible in an urban African setting.

Cost-effectiveness of cervical-cancer screening in five developing countries.

BACKGROUND: Cervical-cancer screening strategies that involve the use of conventional cytology and require multiple visits have been impractical in developing countries. METHODS: We used computer-based models to assess the cost-effectiveness of a variety of cervical-cancer screening strategies in India, Kenya, Peru, South Africa, and Thailand. Primary data were combined with data from the literature to estimate age-specific incidence and mortality rates for cancer and the effectiveness of screening for and treatment of precancerous lesions. We assessed the direct medical, time, and program-related costs of strategies that differed according to screening test, targeted age and frequency, and number of clinic visits required. Single-visit strategies involved the assumption that screening and treatment could be provided in the same day. Outcomes included the lifetime risk of cancer, years of life saved, lifetime costs, and cost-effectiveness ratios (cost per year of life saved). RESULTS: The most cost-effective strategies were those that required the fewest visits, resulting in improved follow-up testing and treatment. Screening women once in their lifetime, at the age of 35 years, with a one-visit or two-visit screening strategy involving visual inspection of the cervix with acetic acid or DNA testing for human papillomavirus (HPV) in cervical cell samples, reduced the lifetime risk of cancer by approximately 25 to 36 percent, and cost less than 500 dollars per year of life saved. Relative cancer risk declined by an additional 40 percent with two screenings (at 35 and 40 years of age), resulting in a cost per year of life saved that was less than each country's per capita gross domestic product--a very cost-effective result, according to the Commission on Macroeconomics and Health. CONCLUSIONS: Cervical-cancer screening strategies incorporating visual inspection of the cervix with acetic acid or DNA testing for HPV in one or two clinical visits are cost-effective alternatives to conventional three-visit cytology-based screening programs in resource-poor settings.

Screening test accuracy studies: how valid are our conclusions? Application to visual inspection methods for cervical screening.

While the basic concepts associated with screening are simple, studying the value of new tests requires a very strict methodology. This paper summarizes lessons learned regarding appropriate methodologies to assess the value of new screening approaches using visual inspection with acetic acid (VIA), a screening test for cervical pre-cancerous lesions, as an example. In addition to being convenient to, safe for and acceptable by target community members, a screening test should be reliable and have good test characteristics (i.e. be able to discriminate well between early disease and non disease). Test reliability assesses the degree to which repeated measurements of the test yields the same result. To ensure reproducibility of study findings, test reliability should be assessed before any evaluation of test accuracy. The accuracy of a test (specificity and sensitivity) is measured using cross-sectional studies with adequate sample size. Several basic features are necessary to ensure internal validity for such studies: (a) final disease status data should be obtained for all subjects, (b) all tests results must be determined independently of previous results, (c) the reference standard used to determine the disease status should be accurate, (d) the full "spectrum" of the disease should be included in the study. The study results should also have external validity to be applicable to other populations to which the test will be applied. All these consideration are exemplified by 17 very heterogeneous studies published to date assessing VIA test accuracy. The assessment of a new screening test is the first step in researching a new cancer prevention strategy. For this reason, this step should be carefully addressed through rigorous studies.

Uso de contracepçäo por adolescentes de escolas públicas na Bahia / Contraceptive use among adolescents at public schools in Brazil

OBJETIVO: O interesse sobre o comportamento contraceptivo de adolescentes vem crescendo, especialmente pela relevância social conferida à gravidez nessa faixa etária. Assim, realizou-se estudo para investigar fatores associados ao uso de métodos anticoncepcionais entre adolescentes escolares. MÉTODOS: Estudo transversal que utilizou um questionário auto-aplicado em 4.774 alunos de ambos os sexos, entre 11 e 19 anos. Calcularam-se as prevalências de uso de contraceptivos na primeira e na última relaçäo sexual e em ambas as situações (uso consistente). A regressäo logística foi utilizada para a análise simultânea dos fatores e cálculo de medidas ajustadas. RESULTADOS: Entre 1.664 estudantes com iniciaçäo sexual, os fatores associados positivamente ao uso consistente de contraceptivos pelos rapazes incluíram a iniciaçäo sexual mais tardia, com parceria estável, contar com a família como fonte potencial de contraceptivos e acesso a serviços de saúde; entre as moças, ter iniciado a vida sexual há pouco tempo e ter o pai como fonte de informaçäo sobre sexualidade, contracepçäo e prevençäo DST/Aids. A gravidez foi relatada por 6,4 por cento dos rapazes e 18,1 por cento das moças, sendo sua ausência associada ao uso consistente de contraceptivos por elas (OR=3,83; 2,06-7,15). CONCLUSÕES: Os resultados confirmam a complexidade da determinaçäo do comportamento contraceptivo entre adolescentes e a necessidade de que os programas educativos incorporem as múltiplas dimensöes da questäo para que tenham efetividade.

Performance of visual inspection with acetic acid for cervical cancer screening: a qualitative summary of evidence to date.

UNLABELLED: Developing countries often lack the necessary resources to use the Papanicolaou (Pap) smear as a screening tool for cervical abnormalities. Because the burden of cervical cancer is highest in such low-resource settings, alternative techniques have been sought. Recently, interest in visual inspection with acetic acid (VIA) has increased. Numerous studies have been conducted on its accuracy and its ability to detect cervical lesions when compared with other techniques, both conventional and nonconventional. This review summarizes key findings from the literature to provide researchers and policymakers with an up-to-date summary on VIA. PubMed was used to identify relevant journal articles published between 1982 and 2002. Key words were cervical cancer screening, visual inspection, VIA (visual inspection with acetic acid), DVI (direct visual inspection), AAT (acetic acid test), and cervicoscopy. Studies were eligible for review only if they involved analysis of primary VIA data (ie, not review articles); studies involving magnification devices were excluded. Fifteen studies were reviewed in total; key results were extracted and a summary analysis was performed for sensitivity and specificity parameters. When reported, sensitivity ranged between 66% and 96% and specificity between 64% and 98%. Authors comparing VIA with cytology noted that the overall usefulness of VIA compares favorably with that of the Pap test. The reported findings reviewed here suggest that VIA has the potential to be a cervical cancer screening tool, especially in low resource settings. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe how visual inspection of the cervix for cervical cancer screening (VIA) is performed, to summarize the current literature on VIA, and to list potential advantages of VIA.

Costs and benefits of different strategies to screen for cervical cancer in less-developed countries.

BACKGROUND: About 80% of cervical cancers occur in less-developed countries. This disproportionate burden of cervical cancer in such countries is due mainly to the lack of well-organized screening programs. Several cervical cancer screening strategies have been proposed as more cost-effective than cytology screening. We compared the costs and benefits of different strategies and their effectiveness in saving lives in a less-developed country. METHODS: We used a population-based simulation model to evaluate the incremental societal costs and benefits in Thailand of seven screening techniques, including visual inspection of the cervix after applying acetic acid (VIA), human papillomavirus (HPV) testing, Pap smear, and combinations of screening tests, and examined the discounted costs per year of life saved (LYS). RESULTS: Compared with no (i.e., not well-organized) screening, all strategies saved lives, at costs ranging from 121 US dollars to 6720 US dollars per LYS, and reduced mortality, by up to 58%. Comparing each strategy with the next least expensive alternative, VIA performed at 5-year intervals in women of ages 35-55 with immediate treatment if abnormalities are found was the least expensive option and saved the greatest number of lives, with a cost of 517 US dollars per LYS. HPV screening resulted in similar costs and benefits, if the test cost is 5 US dollars and if 90% of women undergo follow-up after an abnormal screen. Cytology (Pap smear) was a reasonable alternative if sensitivity exceeds 80% and if 90% of women undergo follow-up. Compared with no screening, use of a combination of Pap smear and HPV testing at 5-year intervals in women of ages 20-70 could achieve greater than 90% reduction in cervical cancer mortality at a cost of 1683 US dollars per LYS, and VIA could achieve 83% reduction at 524 US dollars per LYS. CONCLUSIONS: Well-organized screening programs can reduce cervical cancer mortality in less-developed countries at low costs. These cost-effectiveness data can enhance decision-making about optimal policies for a given setting.