Routine HIV screening in France: clinical impact and cost-effectiveness

Background

In France, roughly 40,000 HIV-infected persons are unaware of their HIV infection. Although previous studies have evaluated the cost-effectiveness of routine HIV screening in the United States, differences in both the epidemiology of infection and HIV testing behaviors warrant a setting-specific analysis for France.

Methods/Principal Findings

We estimated the life expectancy (LE), cost and cost-effectiveness of alternative HIV screening strategies in the French general population and high-risk sub-populations using a computer model of HIV detection and treatment, coupled with French national clinical and economic data. We compared risk-factor-based HIV testing (“current practice”) to universal routine, voluntary HIV screening in adults aged 18–69. Screening frequencies ranged from once to annually. Input data included mean age (42 years), undiagnosed HIV prevalence (0.10%), annual HIV incidence (0.01%), test acceptance (79%), linkage to care (75%) and cost/test (€43). We performed sensitivity analyses on HIV prevalence and incidence, cost estimates, and the transmission benefits of ART. “Current practice” produced LEs of 242.82 quality-adjusted life months (QALM) among HIV-infected persons and 268.77 QALM in the general population. Adding a one-time HIV screen increased LE by 0.01 QALM in the general population and increased costs by €50/person, for a cost-effectiveness ratio (CER) of €57,400 per quality-adjusted life year (QALY). More frequent screening in the general population increased survival, costs and CERs. Among injection drug users (prevalence 6.17%; incidence 0.17%/year) and in French Guyana (prevalence 0.41%; incidence 0.35%/year), annual screening compared to every five years produced CERs of €51,200 and €46,500/QALY.

Conclusions/Significance

One-time routine HIV screening in France improves survival compared to “current practice” and compares favorably to other screening interventions recommended in Western Europe. In higher-risk groups, more frequent screening is economically justifiable.     

Optimizing prevention and community-based management of severe malnutrition in children

Zulfiqar A. Bhutta discusses prevention and treatment strategies for optimization of community-based management of severe acute malnutrition in children.

In this issue of PLOS Medicine, Matt Hitchings and colleagues detail the findings from their prospective cluster-randomized crossover trial conducted across 10 health centers in Sokoto, Nigeria, to assess the nutritional recovery in children with uncomplicated severe acute malnutrition (SAM) receiving monthly follow-up compared to the standard weekly follow-up schedules [1]. In almost 4,000 children so allocated, the nutritional recovery at 3 months’ follow-up was lower in the monthly follow-up group (52.4%) compared to the standard weekly group (58.8%), with higher cumulative mortality at 3 months (8.5% versus 6.2% with the standard weekly follow-up). In contrast, rates of default and relapse were significantly lower among SAM children allocated to monthly follow-up. The authors, while urging caution in adopting a modified schedule of monthly follow-up visits in such children, also recognize the trade-off of simplicity and ease of operations in some settings where weekly follow-up visits are not feasible.Despite global progress in improving maternal and child undernutrition, the high burden of severe malnutrition persists. Recent estimates show a small reduction (from 15.9% to 14.2%) in wasting prevalence in low-income countries, and a slight increase (from 3.3% to 4.7%) in middle-income countries, although overall almost 50 million children aged under 5 years still remain wasted worldwide [2]. This burden of SAM has most likely been exacerbated during the recent Coronavirus Disease 2019 (COVID-19) pandemic, with an estimated additional 6.7 million children becoming wasted in 2020 [3].Within this large number of wasted children are those with SAM who are triaged to facility-based nutritional rehabilitation if seriously ill, or community-based treatment regimens if stable. The development of standardized management protocols for children with SAM with ready-to-use therapeutic foods (RUTFs) represents one of the greatest advances in treating such children at scale and reducing the mortality associated with the condition [4]. However, given the general context where childhood SAM clusters, such as those affected by extreme poverty, climate change, conflict, and involving displaced populations, major challenges remain in optimizing SAM management. These include relatively high rates of relapse [5], and associated residual mortality with severe malnutrition, often exceeding 10% in some settings [6]. Strategies are thus needed to optimize community case management aimed at simplifying the treatment regimen for SAM, reducing defaults and relapse rates among affected children.Such real-life evaluations of management strategies for severe malnutrition among at-risk children are few and far between, and most welcome. The global evidence base for the management of SAM in various settings is still mixed, with wide variations in recovery or relapse rates and mortality. This is especially the case in complex emergencies and conflict settings [7] with obvious limitations of human resources and commodities. The challenges of managing SAM in different contexts and settings are directly related to available nutrition rehabilitation commodities and trained human resources, as well as the ability of poor and food-insecure households to follow complex regimen and follow-up schedules. For many poor households with daily wage laborers or workers, taking a day off to travel to ambulatory care settings is a weekly financial and logistic hardship that may be impossible to bear. Alternative approaches with community outreach workers providing care and commodities in domiciliary settings has also met with mixed success, with lower rates of uptake in effectiveness settings with busy public-sector workers [8,9].There are additional research questions related to the nutritional rehabilitation and management of SAM including dosage schedules and protocols for administering RUTF in outreach and ambulatory programs. Additional therapeutic challenges in managing children with SAM include the limited repertoire of options for interventions in children under 6 months of age, as well as strategies to manage children with concurrent stunting and wasting [1,10]. While the recommendations for facility-based management of unstable children with SAM are well recognized [11], corresponding protocols for ambulatory management of severely malnourished children with suspected infections and at risk of adverse outcomes are still a subject of much debate [12].The gains from potentially simplifying ambulatory management strategies for SAM are considerable but must be weighed against the best-possible and cost-effective strategies. Of great priority are strategies that integrate SAM management in community settings with additional child health and development interventions [13]. Given the close correlation and relationship between various forms of malnutrition (moderate and severe acute malnutrition), there is growing interest in common management protocols and simplified regimens for preventing and managing all forms of acute malnutrition. The sizeable subgroup of children with concurrent wasting and stunting represents a subgroup at much greater risk of adverse outcomes and mortality [14] and needs strategies that also integrate maternal and early child health and nutrition strategies.There has been a healthy increase in research related to prevention and management strategies for SAM in recent years, all adding to the evidence base for effective implementation in field settings. Corresponding processes for guidelines development by WHO are understandably cautious, but it is worth noting that the guidelines for the management of SAM by WHO are now almost a decade old [15] and need updating as well as flexibility in implementation. Studies such as those by Hitchings and colleagues [1] should show the way to optimize the screening and management of SAM in settings with limited facilities and community capacity for weekly follow-up. The recognition that such infants may be at higher risk of relapse or mortality could well require additional contacts, such as fortnightly follow-up or outreach services, areas that should be studied in future evaluations.     

Whispered voice test for screening for hearing impairment in adults and children: systematic review

Objective To determine the accuracy of the whispered voice test in detecting hearing impairment in adults and children.Design Systematic review of studies of test accuracy.Data sources Medline, Embase, Science Citation Index, unpublished theses, manual searching of bibliographies of known primary and review articles, and contact with authors.Study selection Two reviewers independently selected and extracted data on study characteristics, quality, and accuracy of studies. Studies were included if they had cross sectional designs, at least one of the index tests was the whispered voice test, and the reference test (audiometry) was performed on at least 80% of the participants.Data extraction Data were used to form 2×2 contingency tables with hearing impairment by audiometry as the reference standard.Data synthesis The eight studies that were found used six different techniques. The sensitivity in the four adult studies was 90% or 100% and the specificity was 70% to 87%. The sensitivity in the four childhood studies ranged from 80% to 96% and specificity ranged from 90% to 98%.Conclusion The whispered voice test is a simple and accurate test for detecting hearing impairment. There is some concern regarding the lower sensitivity in children and the overall reproducibility of the test, particularly in primary care settings. Further studies should be conducted in primary care settings to explore the influence of components of the testing procedure to optimise test sensitivity and to promote standardisation of the testing procedure.     

Performance of serum C-reactive protein as a screening test for smear-negative tuberculosis in an ambulatory high HIV prevalence population

Background

Delayed diagnosis has contributed to the high mortality of sputum smear-negative tuberculosis (SNTB) in high HIV prevalence countries. New diagnostic strategies for SNTB are urgently needed. C-reactive protein (CRP) is a non-specific inflammatory protein that is usually elevated in patients with tuberculosis, but its role in the diagnosis of tuberculosis is uncertain.

Methodology/Principal Findings

To determine the diagnostic utility of CRP we prospectively evaluated the performance of CRP as a screening test for SNTB in symptomatic ambulatory tuberculosis suspects followed up for 8 weeks in KwaZulu-Natal, South Africa. Confirmed tuberculosis was defined as positive culture or acid-fast bacilli with granulomata on histology, and possible tuberculosis as documented response to antitubercular therapy. The CRP quotient was defined as a multiple of the upper limit of normal of the serum CRP result. Three hundred and sixty four participants fulfilled entry criteria: 135 (37%) with confirmed tuberculosis, 114 (39%) with possible tuberculosis, and 115 (24%) without tuberculosis. The median CRP quotient was 15.4 (IQR 7.2; 23.3) in the confirmed tuberculosis group, 5.8 (IQR 1.4; 16.0) in the group with possible tuberculosis, and 0.7 (IQR 0.2; 2.2) in the group without tuberculosis (p<0.0001). The CRP quotient above the upper limit of normal had sensitivity 0.98 (95% CI 0.94; 0.99), specificity 0.59 (95% CI 0.50; 0.68), positive predictive value 0.74 (95% CI 0.67; 0.80), negative predictive value 0.96 (95% CI 0.88; 0.99), and diagnostic odds ratio 63.7 (95% CI 19.1; 212.0) in the confirmed tuberculosis group compared with the group without tuberculosis. Higher CRP quotients improved specificity at the expense of sensitivity.

Significance

In high HIV prevalence settings a normal CRP could be a useful test in combination with clinical evaluation to rule out tuberculosis in ambulatory patients. Point-of-care CRP should be further evaluated in primary care clinics.     

Modeling the impact of genetic screening technologies on healthcare: theoretical model for asthma in children

BACKGROUND AND OBJECTIVE: This study focuses on the potential impact of genetic screening technologies on healthcare. Genetic screening for asthma in children was chosen as a case study to explore the cost effectiveness of applying early genetic screening to infants, and preventive treatment to the population at risk. Early intervention could prevent progression and facilitate clinical management of the disease. From the elite group of genetic markers that have been associated with asthma-related phenotypes, ADAM33 was the first published candidate gene detected by a positional cloning approach, marking the entry of asthma research into the genomic era. The model was, therefore, initially set for an ex ante analysis of the cost effectiveness of applying the preventive program to an infant population at risk, i.e. infants presenting wheezing episodes during the first year of life, and the ADAM33 ST+7 genetic marker, with the idea of expanding to further markers and their combinations lat a later date. METHODS: In accordance with the US National Heart, Lung, and Blood Institute, four categories of asthma were considered. A Markov model was constructed, consisting of six mutually exclusive disease states (including healthy and dead states) with a simulation horizon of 100 years and a cycle length of 1 year. We define a scenario where early genetic screening was applied to infants presenting wheezing episodes during the first year of life and a preventive treatment to those children within this group who tested positive for selected ADAM33 polymorphism (ST+7). The cost-effectiveness analysis was performed from the third-party payer and patient perspective after year 6. We applied our model to a hypothetical cohort of 100 European infants. RESULTS: The number of quality-adjusted life-years (QALYs) gained during the 6 years was 1.483, and the incremental cost-effectiveness ratio per QALY gained was euro 10,100/QALY. A sensitivity analysis was carried out that varied the discount rate and cost of genetic testing, and considered two different transition matrices for the preventive program. Three main conclusions were drawn from the sensitivity analysis. Firstly, if the discount rate for both cost and health outcomes is increased by 2%, the cost effectiveness of the preventive program does not vary significantly. Discounting costs and benefits at 5%, the preventive program appears cost effective (euro 11,100/QALY). Secondly, if the cost of genetic testing is increased to euro 100, the cost effectiveness of the preventive program remains within the limits of cost effectiveness. Thirdly, the cost of genetic screening, together with transition probabilities between health states, will determine the cost effectiveness of applying a preventive program based on genetic information. CONCLUSIONS: Preventive treatment based on an early genetic screening of those children who present wheezing episodes during the first year of life, with treatment applied to those who test positive for the asthma-associated genetic marker ADAM33 ST+7, is theoretically cost effective. The model is a valuable tool for the ex ante assessment of the cost effectiveness of preventive schemes based on genetic screening. The value of modeling prior to clinical trials lies in informing study design and setting priorities for future research.     

Modelling HIV/AIDS in the presence of an HIV testing and screening campaign

Preventing and managing the HIV/AIDS epidemic in South Africa will dominate the next decade and beyond. Reduction of new HIV infections by implementing a comprehensive national HIV prevention programme at a sufficient scale to have real impact remains a priority. In this paper, a deterministic HIV/AIDS model that incorporates condom use, screening through HIV counseling and testing (HCT), regular testing and treatment as control strategies is proposed with the objective of quantifying the effectiveness of HCT in preventing new infections and predicting the long-term dynamics of the epidemic. It is found that a backward bifurcation occurs if the rate of screening is below a certain threshold, suggesting that the classical requirement for the basic reproduction number to be below unity though necessary, is not sufficient for disease control in this case. The global stabilities of the equilibria under certain conditions are determined in terms of the model reproduction number R₀. Numerical simulations are performed and the model is fitted to data on HIV prevalence in South Africa. The effects of changes in some key epidemiological parameters are investigated. Projections are made to predict the long-term dynamics of the disease. The epidemiological implications of such projections on public health planning and management are discussed.     

Personal stigma in schizophrenia spectrum disorders: a systematic review of prevalence rates,correlates, impact and interventions

A systematic electronic PubMed, Medline and Web of Science database search was conducted regarding the prevalence, correlates, and effects of personal stigma (i.e., perceived and experienced stigmatization and self‐stigma) in patients with schizophrenia spectrum disorders. Of 54 studies (n=5,871), published from 1994 to 2011, 23 (42.6%) reported on prevalence rates, and 44 (81.5%) reported on correlates and/or consequences of perceived or experienced stigmatization or self‐stigma. Only two specific personal stigma intervention studies were found. On average, 64.5% (range: 45.0–80.0%) of patients perceived stigma, 55.9% (range: 22.5–96.0%) actually experienced stigma, and 49.2% (range: 27.9–77.0%) reported alienation (shame) as the most common aspect of self‐stigma. While socio‐demographic variables were only marginally associated with stigma, psychosocial variables, especially lower quality of life, showed overall significant correlations, and illness‐related factors showed heterogeneous associations, except for social anxiety that was unequivocally associated with personal stigma. The prevalence and impact of personal stigma on individual outcomes among schizophrenia spectrum disorder patients are well characterized, yet measures and methods differ significantly. By contrast, research regarding the evolution of personal stigma through the illness course and, particularly, specific intervention studies, which should be conducted utilizing standardized methods and outcomes, are sorely lacking.     

Cervical screening within HIV care: findings from an HIV-positive cohort in Ukraine

Introduction

HIV-positive women have an increased risk of invasive cervical cancer but cytologic screening is effective in reducing incidence. Little is known about cervical screening coverage or the prevalence of abnormal cytology among HIV-positive women in Ukraine, which has the most severe HIV epidemic in Europe.

Methods

Poisson regression models were fitted to data from 1120 women enrolled at three sites of the Ukraine Cohort Study of HIV-infected Childbearing Women to investigate factors associated with receiving cervical screening as part of HIV care. All women had been diagnosed as HIV-positive before or during their most recent pregnancy. Prevalence of cervical abnormalities (high/low grade squamous intraepithelial lesions) among women who had been screened was estimated, and associated factors explored.

Results

Overall, 30% (337/1120) of women had received a cervical screening test as part of HIV care at study enrolment (median 10 months postpartum), a third (115/334) of whom had been tested >12 months previously. In adjusted analyses, women diagnosed as HIV-positive during (vs before) their most recent pregnancy were significantly less likely to have a screening test reported, on adjusting for other potential risk factors (adjusted prevalence ratio (APR) 0.62, 95% CI 0.51–0.75 p<0.01 for 1^st/2^nd trimester diagnosis and APR 0.42, 95% CI 0.28–0.63 p<0.01 for 3^rd trimester/intrapartum diagnosis). Among those with a cervical screening result reported at any time (including follow-up), 21% (68/325) had a finding of cervical abnormality. In adjusted analyses, Herpes simplex virus 2 seropositivity and a recent diagnosis of bacterial vaginosis were associated with an increased risk of abnormal cervical cytology (APR 1.83 95% CI 1.07–3.11 and APR 3.49 95% CI 2.11–5.76 respectively).

Conclusions

In this high risk population, cervical screening coverage as part of HIV care was low and could be improved by an organised cervical screening programme for HIV-positive women. Bacterial vaginosis testing and treatment may reduce vulnerability to cervical abnormalities.     

The impact of access to water supply and sanitation on the prevalence of active trachoma in Ethiopia: A systematic review and meta-analysis

BackgroundTrachoma is a worldwide infectious disease causing blindness. Trachoma continued as a public health problem in Ethiopia due to a lack of sanitation and inadequate prevention strategies. This study aimed to identify the impact of water supply and sanitation intervention on preventing active trachoma among children.MethodsSystematic literature searches were performed from 4 international databases. The search involved articles published from January 1995 up to March 2019. The Cochran Q and I² statistical tests were used to check heterogeneity among the studies. A random-effect meta-analysis was employed to determine the pooled estimates with a 95% confidence interval (CI). Data analysis was performed using the CMA V.3 and RevMan 5 software program, and the result of the systematic review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.FindingsOut of 211 studies screened for the analysis, only 29 studies were finally included in this systematic review and meta-analysis. The result revealed factors that are significantly associated with increased odds of active trachoma. Accordingly, households with no access to toilet facilities (odds ratio [OR]: 2.04, 95% CI: 1.75–2.38), no access to improved water (OR: 1.58, 95% CI: 1.27–1.96), and do not practice regular face washing for children (OR: 4.19, 95% CI: 3.02–5.81) have shown increased odds of active trachoma. Besides, the results show a higher prevalence of active trachoma among children who did not wash their faces with soap and frequently.ConclusionsThe study found strong evidence that lack of access to water, sanitation, and hygiene (WASH) was associated with increased prevalence of active trachoma among children. Therefore, a comprehensive and partnership-oriented program is needed to tackle the problem, but further study will be required to strengthen its implementation.     

Modeling the impact of random screening and contact tracing in reducing the spread of HIV

Mathematical models can help predict the effectiveness of control measures on the spread of HIV and other sexually transmitted diseases (STDs) by reducing the uncertainty in assessing the impact of intervention strategies such as random screening and contact tracing. Even though contact tracing is one of the most effective methods used for controlling treatable STDs, it is still a controversial strategy for controlling HIV because of cost and confidentiality issues. To help estimate the effectiveness of these control measures, we formulate two models with random screening and contact tracing based on the differential infectivity (DI) model and the staged-progression (SP) model. We derive formulas for the reproductive numbers and the endemic equilibria and compare the impact that random screening and contact tracing have in slowing the epidemic in the two models. In the DI model the infected population is divided into groups according to their infectiousness, and HIV is largely spread by a small, highly infectious, group of superspreaders. In this model contact tracing is an effective approach to identifying the superspreaders and has a large effect in slowing the epidemic. In the SP model every infected individual goes through a series of infection stages and the virus is primarily spread by individuals in an initial highly infectious stage or in the late stages of the disease. In this model random screening is more effective than for the DI model, and contact tracing is less effective. Thus the effectiveness of the intervention strategy strongly depends on the underlying etiology of the disease transmission.     

Coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and prevalence of infection in the United Kingdom general population: cross sectional study

Objective To measure the coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and the prevalence of infection in the general population in the United Kingdom. To investigate factors associated with these measures.Design Cross sectional survey of people randomly selected from general practice registers. Invitation to provide a specimen collected at home.Setting England.Participants 19 773 men and women aged 16-39 years invited to participate in screening.Main outcome measures Coverage and uptake of screening; prevalence of chlamydia.Results Coverage of chlamydia screening was 73% and was lower in areas with a higher proportion of non-white residents. Uptake in 16-24 year olds was 31.5% and was lower in men, younger adults, and practices in disadvantaged areas. Overall prevalence of chlamydia was 2.8% (95%confidence interval 2.2% to 3.4%) in men and 3.6% (3.1% to 4.9%) in women, but it was higher in people younger than 25 years (men 5.1%; 4.0% to 6.3%; women 6.2%; 5.2% to 7.8%). Prevalence was higher in the subgroup of younger women who were harder to engage in screening. The strongest determinant of chlamydial infection was having one or more new sexual partners in the past year.Conclusions Postal chlamydia screening was feasible, but coverage was incomplete and uptake was modest. Lower coverage of postal screening in areas with more non-white residents along with poorer uptake in more deprived areas and among women at higher risk of infection could mean that screening leads to wider inequalities in sexual health.     

The diagnostic impact of implementing a molecular-based algorithm to standard mycobacterial screening at a reference laboratory with an intermediate prevalence for non-respiratory samples

Rapid, reliable results can be given by molecular, direct detection and identification of the Mycobacterium tuberculosis (MTB/Mtb) complex from clinical samples. The Xpert MTB/RIF assay is an assay that has been availablefor more than a decade for identification of Mycobacterium tuberculosis and resistance to rifampicin. However, there is minimal evidence on its clinical usefulness in paucibacillary, non-respiratory samples. The Xpert MTB/RIF assay clinical utility index, its diagnostic characteristics and the number required to diagnose 2935 non-respiratory specimens submitted for routine mycobacterial work-up in a reference laboratory in an intermediate prevalence setting per specimen form were evaluated. The Xpert MTB/RIF assay showed a variable clinical utility index and number required to diagnose (NND) depending on the type of specimen, which was moderate in tissue biopsies (NND = 1.8) and excellent in pus and urine samples, compared to acid-fast microscopy and culture as a gold standard technique (NND = 1.1 and 1.2). Microscopy, on the other hand, consistently showed a weak to fair index of clinical usefulness in all specimen forms, with in NND of 2.3–12.5. The NND for detecting tuberculous infection in the cerebrospinal fluid by the Xpert MTB/RIF assay was noted to be 1.2, with a moderate clinical utility index of 0.8. The evidence presented indicates that the overall appropriate diagnostic utility of the Xpert MTB/RIF assay is clinically successful in most non-respiratory samples. To check the cost-effectiveness and prognostic effect of integrating this completely automated molecular-based assay into the routine testing algorithm for non-respiratory mycobacterial specimens, further data must be collected.     

Estimation of the prevalence of undiagnosed and diagnosed HIV in an urban emergency department

Objective

To estimate the prevalence of undiagnosed HIV, the prevalence of diagnosed HIV, and proportion of HIV that is undiagnosed in populations with similar demographics as the Universal Screening for HIV in the Emergency Room (USHER) Trial and the Brigham and Women''s Hospital (BWH) Emergency Department (ED) in Boston, MA. We also sought to estimate these quantities within demographic and risk behavior subgroups.

Method

We used data from the USHER Trial, which was a randomized clinical trial of HIV screening conducted in the BWH ED. Since eligible participants were HIV-free at time of enrollment, we were able to calculate the prevalence of undiagnosed HIV. We used data from the Massachusetts Department of Public Health (MA/DPH) to estimate the prevalence of diagnosed HIV since the MA/DPH records the number of persons within MA who are HIV-positive. We calculated the proportion of HIV that is undiagnosed using these estimates of the prevalence of undiagnosed and diagnosed HIV. Estimates were stratified by age, sex, race/ethnicity, history of testing, and risk behaviors.

Results

The overall expected prevalence of diagnosed HIV in a population similar to those presenting to the BWH ED was 0.71% (95% CI: 0.63%, 0.78%). The prevalence of undiagnosed HIV was estimated at 0.22% (95% CI: 0.10%, 0.42%) and resultant overall prevalence was 0.93%. The proportion of HIV-infection that is undiagnosed in this ED-based setting was estimated to be 23.7% (95% CI: 11.6%, 34.9%) of total HIV-infections.

Conclusions

Despite different methodology, our estimate of the proportion of HIV that is undiagnosed in an ED-setting was similar to previous estimates based on national surveillance data. Universal routine testing programs in EDs should use these data to help plan their yield of HIV detection.     

Bayesian inference for prevalence and diagnostic test accuracy based on dual-pooled screening

We propose a useful protocol for the problem of screening populations for low-prevalence characteristics such as HIV or drugs. Current HIV screening of blood that has been donated for transfusion involves the testing of individual blood units with an inexpensive enzyme-linked immunosorbent assay test and follow-up with a more accurate and more expensive western blot test for only those units that tested positive. Our cost-effective pooling strategy would enhance current methods by making it possible to accurately estimate the sensitivity and specificity of the initial screening test, and the proportion of defective units that have passed through the system. We also provide a method of estimating the distribution of prevalences for the characteristic throughout the population or subpopulations of interest.     

Quantification of overdiagnosis in randomised trials of cancer screening: an overview and re-analysis of systematic reviews

The degree of overdiagnosis in common cancer screening trials is uncertain due to inadequate design of trials, varying definition and methods used to estimate overdiagnosis. Therefore, we aimed to quantify the risk of overdiagnosis for the most widely implemented cancer screening programmes and assess the implications of design limitations and biases in cancer screening trials on the estimates of overdiagnosis by conducting an overview and re-analysis of systematic reviews of cancer screening. We searched PubMed and the Cochrane Library from their inception dates to November 29, 2021. Eligible studies included systematic reviews of randomised trials comparing cancer screening interventions to no screening, which reported cancer incidence for both trial arms. We extracted data on study characteristics, cancer incidence and assessed the risk of bias using the Cochrane Collaboration’s risk of bias tool. We included 19 trials described in 30 articles for review, reporting results for the following types of screening: mammography for breast cancer, chest X-ray or low-dose CT for lung cancer, alpha-foetoprotein and ultrasound for liver cancer, digital rectal examination, prostate-specific antigen, and transrectal ultrasound for prostate cancer, and CA-125 test and/or ultrasound for ovarian cancer. No trials on screening for melanoma were eligible. Only one trial (5%) had low risk in all bias domains, leading to a post-hoc meta-analysis, excluding trials with high risk of bias in critical domains, finding the extent of overdiagnosis ranged from 17% to 38% across cancer screening programmes. We conclude that there is a significant risk of overdiagnosis in the included randomised trials on cancer screening. We found that trials were generally not designed to estimate overdiagnosis and many trials had high risk of biases that may draw the estimates of overdiagnosis towards the null. In effect, the true extent of overdiagnosis due to cancer screening is likely underestimated.