The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants

AbstractBackgroundColorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions.MethodsThe CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period.DiscussionThe CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome- based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.Trial RegistrationClinicalTrials.gov Identifier: NCT01538550

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The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants

BMC Cancer ◽

10.1186/s12885-021-08640-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ane Sørlie Kværner ◽

Einar Birkeland ◽

Cecilie Bucher-Johannessen ◽

Elina Vinberg ◽

Jan Inge Nordby ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Screening ◽

Gut Microbiome ◽

Precancerous Lesions ◽

Colorectal Carcinogenesis ◽

Screening Tools ◽

Screening Methods ◽

Crc Screening ◽

Link Type ◽

Incidence And Mortality

Abstract Background Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. Trial registration ClinicalTrials.gov Identifier: NCT01538550.

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Recognition and Participation of Colorectal Cancer Screening in Turkey: Meta-analysis of Literature

European Journal of Public Health ◽

10.1093/eurpub/ckz186.711 ◽

2019 ◽

Vol 29 (Supplement_4) ◽

Author(s):

S Aydoğan ◽

S Metintaş ◽

M F Önsüz

Keyword(s):

Colorectal Cancer ◽

Cancer Screening ◽

English Language ◽

Meta Analysis ◽

Group Analysis ◽

Fecal Occult Blood ◽

Screening Methods ◽

Double Blind ◽

Cross Sectional ◽

Crc Screening

Abstract Background The aim of the study was to perform a systematic review and meta-analysis of studies about the proportion of recognition of fecal occult blood test (FOBT) and colonoscopy (CS) methods and participation to them in any period of life for colorectal cancer (CRC) screening in Turkey. Methods PubMed, Web of Science, Google Scholar, Turkey Citation Index and YOK Thesis Center databases were screened both in Turkish and English language to identify relevant studies and key words ’colorectal cancer’, ’colon cancer’, ’cancer screening’, ’information’, ’attitude’, ’behavior’, ’awareness’ and ’Turkey’ were. Criteria for inclusion in the analysis were; conducted in Turkey, original and cross-sectional, conducted CRC risky groups (having CRC in the first degree patients and 50 and above age), studies that give the number of participants and number of taking FOBT and CS screening in any period of their lives and/or the number of knowing them. The studies that met the criteria were read as double blind. The data were entered into the Open Meta Analyst demo program. Because of p < 0.001 in the heterogeneity test, random effects model was used in group analysis of the articles. The proportion and 95% confidence interval of knowing and taking FOBT and CS were calculated from the total number of cases. Results A total of 1176 articles were reached in first review. Duplications and inappropriated studies were eliminated, and 52 studies were selected. Eight studies about recognition FOBT, 16 about participation FOBT, 9 about recognition CS and 17 about participation CS were taken in analysis. After analysis it was found that 1315 of 4334 individuals (19.3%, 95%CI:6.6-32.1) recognized to FOBT, 1174 of 6825 individuals (13.2%, 8.0-18.5) participated to FOBT, 2197 of 5728 individuals (31.7%, 18.2-45.2) recognized to CS and 913 of 8860 individuals (10.0%, 8.1-12.0) participated to CS. Conclusions The proportion of recognition and participation to FOBT and CS were found less than expected. Key messages The proportion of recognition and participation CRC screening methods is low in risky groups. Awareness and participation of screening should be increased in risky groups.

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Low rate of follow-up colonoscopy after positive results of colorectal cancer screening in a Chinese urban core district

10.1101/734152 ◽

2019 ◽

Author(s):

Yawen Guo ◽

Qingwu Jiang ◽

Tetsuya Tanimoto ◽

Masahiro Kami ◽

Peng Peng ◽

...

Keyword(s):

Colorectal Cancer ◽

Rural Areas ◽

Municipal Government ◽

Precancerous Lesions ◽

Population Based ◽

Registry Data ◽

Crc Screening ◽

Incidence And Mortality ◽

The Status

AbstractColorectal cancer (CRC) is one of the most common cancers in China. In 2003, a systematic CRC registry that enables the determination of CRC incidence and mortality and a CRC screening project were introduced in the Jing’an district of Shanghai by the municipal government. This study assessed the registry data to determine the status of CRC and CRC screening rates in the core district of an urban area of China. Data were retrieved from the Official registry information systems of Jing’an district Shanghai Cance. The incidence and mortality of CRC, as well as population-based CRC screening rates, were analysed. Individuals who screened positive for CRC based upon results of a high-risk factor questionnaire (HRFQ) and a faecal immunochemical test (FIT) were selected for follow-up colonoscopy (CSPY). From the registry data collected between 2003 and 2013, the standardized incidence rate was 26.44/105, with a significant gender difference. The CRC standardized mortality rate was 10.08/105. In 2013, 17,866 individuals (21.6%) enrolled for CRC screening among the 82,602 candidate residents. The positive screening rate was 16.28% (2909/17866). Among the 2909 positives, 508 (17.5%) underwent follow-up CSPY. In 41.3% of these individuals (210/508), abnormal lesions were detected. Of these, 8 (1.57%) lesions were diagnosed as CRC, and 142 (28.0%) were identified as precancerous lesions. During the assessment period, both the incidence and mortality of CRC in the Jing’an district were determined in the area of high CRC prevalence in Chin. Nevertheless, the rate of participation in CRC screening was low (21.6%), and the rate of participation in follow-up CSPY for individuals who screened positive was only 17.5%. Improved participation in CRC screening and follow-up CSPY is expected to lower the incidence and mortality of CRC significantly in the rural areas of China. (288)

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Barriers and facilitators for colorectal cancer screening in a low-income urban community in Mexico City

10.21203/rs.3.rs-17322/v1 ◽

2020 ◽

Author(s):

Karla Unger-Saldaña ◽

Minerva Saldaña-Tellez ◽

Michael B. Potter ◽

Katherine Van Loon ◽

Betania Allen-Leigh ◽

...

Keyword(s):

Colorectal Cancer ◽

Health Care ◽

Cancer Screening ◽

Screening Program ◽

Barriers And Facilitators ◽

Health Care Personnel ◽

Crc Screening ◽

Lay Beliefs ◽

Incidence And Mortality ◽

The Social

Abstract Background Colorectal cancer (CRC) incidence and mortality are increasing in many middle- and lower-income countries, possibly due to a combination of changing lifestyles and improved healthcare infrastructure that facilitates diagnosis. Unfortunately, a large proportion of cases may be diagnosed at advanced stages, resulting in poor outcomes. Decreasing trends in higher income countries are likely due to improved early detection combined with best practices in CRC treatment and management. More data on implementation of better quality CRC screening programs are needed for contexts where incidence is increasing. Therefore, we sought to identify potential barriers and facilitators for future implementation of fecal immunochemical test (FIT)-based CRC screening in a public healthcare system in a middle-income country with increasing CRC incidence and mortality. Methods. Qualitative study including semi-structured individual and focus group interviews with different stakeholders of colorectal cancer screening: 30 average-risk lay people, 13 health care personnel from a local public clinic, and 7 endoscopy unit personnel from a cancer referral hospital. All interviews were transcribed verbatim for analysis. Data was analyzed using the constant comparison method, under the theoretical perspectives of the Social Ecological Model (SEM), the PRECEDE-PROCEED Model, and the Health Belief Model. Results. We found multiple barriers and facilitators for implementation of a FIT-based CRC screening program at different levels of the SEM. The main barriers in each of the SEM levels, were: 1) at the social context level: poverty, health literacy and lay beliefs related to gender, cancer, allopathic medicine, and religion; 2) at the health services organization level: the lack of CRC knowledge among health care personnel and the community perception of poor quality of health care; 3) at the individual level: a lack of CRC awareness and therefore lack of risk perception, together with fear of participating in screening activities and finding out about a serious disease. The main facilitators perceived by the participants were CRC screening information and the free provision of screening tests.Conclusions. This study’s findings suggest the need for a multi-level CRC screening program that includes complementary strategies aimed at reducing perceived barriers and enhancing facilitators, starting with: 1) free provision of screening tests, 2) education of primary health care personnel, and 3) promotion of non fear-based CRC screening awareness among the target population, taking into account their lay beliefs.

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Cross-cultural Validation of Stool Based Colorectal Cancer Screening Methods in the North West of Iran

10.21203/rs.3.rs-891539/v1 ◽

2021 ◽

Author(s):

Roya Dolatkhah ◽

Mohammad Hossein Somi ◽

Saeed Dastgiri ◽

Mohammad Asghari Jafarabadi ◽

Hossein Mashhadi Abdolahi ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Screening ◽

Diagnostic Accuracy ◽

Colorectal Cancer Screening ◽

Cancer Detection ◽

Cross Cultural ◽

Screening Methods ◽

Lower Sensitivity ◽

Predictive Values ◽

Incidence And Mortality

Abstract PurposeGlobally, colorectal cancer (CRC) is the third most common cancer and the second leading cause of death from cancer. Incidence and mortality from CRC both can be reduced and prevented using screening and early detection programs. The current study aimed to assess the feasibility of the colorectal cancer screening program in Northwest of Iran.MethodsThe study designed as a cross-cultural analytic study, to evaluate the diagnostic accuracy of stool-based tests compared with colonoscopy, during 2016-2020. All individuals first were assessed with our CRC risk assessment tool, then eligible volunteers entered the study. Colonoscopy was performed on all participants, also stool- based tests including traditional guaiac, high-sensitivity guaiac-based, fecal immunochemical test (FIT), and multitarget stool DNA (Mt-sDNA) panel tests were performed. ResultsMt-sDNA test panel had a sensitivity of 77.8% (95% CI: 40-97.2) for detecting colorectal cancer with a specificity of 91.2% (95% CI: 85.4-95.2). The FIT test alone had a lower sensitivity (66.7%; 95% CI: 29.9-92.5) and almost the same specificity of 93.9% (95% CI: 88.7-97.2) for cancer detection. Mt-sDNA test had better diagnostic accuracy than the FIT (AUC=0.85 vs 0.80), and is a more useful screening test. Positive and negative predictive values for cancer detection for both Mt-sDNA and FIT tests were almost the same results, however Mt-sDNA test had better NPV results than the FIT test alone.ConclusionOur results showed that both Mt-sDNA panel and the FIT test had acceptable cut-off points for cancer detection, however, Mt-sDNA test had better diagnostic accuracy.

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Invitation of non-attenders to colorectal cancer screening: impact on coverage by examination

European Journal of Public Health ◽

10.1093/eurpub/ckaa165.1344 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

O Majek ◽

O Ngo ◽

B Seifert ◽

S Suchanek ◽

M Zavoral ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Screening ◽

Early Detection ◽

Colorectal Cancer Screening ◽

Colorectal Neoplasia ◽

Target Population ◽

Screening Colonoscopy ◽

Complete Coverage ◽

Crc Screening ◽

Incidence And Mortality

Abstract Issue Colorectal cancer (CRC) has been among the most important cancer causes of death globally. CRC screening and early detection can decrease CRC incidence and mortality through timely removal of colorectal neoplasia or early CRC treatment. CRC screening has been initiated in the Czech Republic in 2000 for individuals over 50, with GPs having a key role in recruiting individuals to screening, offering faecal occult blood test (FOBT). Screening colonoscopy (CS) was added for individuals over 55 since 2009. Description of the problem To increase uptake of CRC screening, personal invitation of non-attenders under 70 was implemented in 2014, along with temporary mass-media campaign. Health insurance companies have been sending invitations to those individuals without record of recent FOBT, CS or CRC treatment. The aim of our study was to evaluate impact of this policy on complete coverage by examination over 2013-2018. We defined the complete coverage by examination as the proportion of individuals aged 50-69 undergoing examination with CRC early detection potential (FOBT or CS for any indication) during past 3 years. We used newly established National Registry of Reimbursed Health Services as the source of data. Results Complete coverage of the target population (2.7 million individuals aged 50-69) was 44.8 % in 2013. By 2016, the coverage increased to 54.6%. Therefore, almost 300,000 individuals were newly covered by the relevant examinations. By 2018, the coverage decreased to 51.2%. When we consider only screening FOBT examinations, the coverage was 36.9 % in 2013, 45.2% in 2016, and 42.0% in 2018. Lessons In the health system with accessible CS facilities, the policy of non-attenders' invitation for CRC screening resulted not only in increase in coverage by screening examinations; complete coverage also increased. Unfortunately, the positive effect has been fading out, and further actions to sustain high coverage are therefore warranted. Key messages Invitation of non-attenders to colorectal cancer screening increased complete coverage of the target population by examination. Initial increase was followed by a slow decrease in coverage by examination, underlying the need for other actions to increase participation.

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National Colorectal Cancer Screening Program in Lithuania: Description of the 5-Year Performance on Population Level

Cancers ◽

10.3390/cancers13051129 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1129

Author(s):

Audrius Dulskas ◽

Tomas Poskus ◽

Inga Kildusiene ◽

Ausvydas Patasius ◽

Rokas Stulpinas ◽

...

Keyword(s):

Colorectal Cancer ◽

Quality Assurance ◽

Cancer Screening ◽

Colorectal Cancer Screening ◽

Screening Program ◽

Histopathological Examination ◽

Insurance Fund ◽

Crc Screening ◽

Cancer Screening Program ◽

The Impact

We aimed to report the results of the implementation of the National Colorectal Cancer (CRC) Screening Program covering all the country. The National Health Insurance Fund (NHIF) reimburses the institutions for performing each service; each procedure within the program has its own administrative code. Information about services provided within the program was retrieved from the database of NHIF starting from the 1 January 2014 to the 31 December 2018. Exact date and type of all provided services, test results, date and results of biopsy and histopathological examination were extracted together with the vital status at the end of follow-up, date of death and date of emigration when applicable for all men and women born between 1935 and 1968. Results were compared with the guidelines of the European Union for quality assurance in CRC screening and diagnosis. The screening uptake was 49.5% (754,061 patients) during study period. Participation rate varied from 16% to 18.1% per year and was higher among women than among men. Proportion of test-positive and test-negative results was similar during all the study period—8.7% and 91.3% annually. Between 9.2% and 13.5% of test-positive patients received a biopsy of which 52.3–61.8% were positive for colorectal adenoma and 4.6–7.3% for colorectal carcinoma. CRC detection rate among test-positive individuals varied between 0.93% and 1.28%. The colorectal cancer screening program in Lithuania coverage must be improved. A screening database is needed to systematically evaluate the impact and performance of the national CRC screening program and quality assurance within the program.

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Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer

Cancers ◽

10.3390/cancers13071493 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1493

Author(s):

Camila Meirelles S. Silva ◽

Mateus C. Barros-Filho ◽

Deysi Viviana T. Wong ◽

Julia Bette H. Mello ◽

Livia Maria S. Nobre ◽

...

Keyword(s):

Colorectal Cancer ◽

Unmet Need ◽

Area Under The Curve ◽

Discrimination Performance ◽

Colorectal Carcinogenesis ◽

The Cancer Genome Atlas ◽

Colon Perforation ◽

Data Series ◽

Predictive Tool ◽

Incidence And Mortality

Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model’s performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC.

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Selection of patients for large mailed fecal immunochemical test colorectal cancer screening outreach programs: A systematic review

Journal of Medical Screening ◽

10.1177/0969141321997482 ◽

2021 ◽

pp. 096914132199748

Author(s):

Andrew Wang ◽

Briton Lee ◽

Shreya Patel ◽

Evans Whitaker ◽

Rachel B Issaka ◽

...

Keyword(s):

Colorectal Cancer ◽

Systematic Review ◽

Health Care ◽

Cancer Screening ◽

Patient Selection ◽

Implementation Strategies ◽

Screening Programs ◽

Crc Screening ◽

Key Informant ◽

Immunochemical Test

Objective Digital health care offers an opportunity to scale and personalize cancer screening programs, such as mailed outreach for colorectal cancer (CRC) screening. However, studies that describe the patient selection strategy and process for CRC screening are limited. Our objective was to evaluate implementation strategies for selecting patients for CRC screening programs in large health care systems. Methods We conducted a systematic review of 30 studies along with key informant surveys and interviews to describe programmatic implementation strategies for selecting patients for CRC screening. PubMed and Embase were searched since inception through December 2018, and hand searches were performed of the retrieved reference lists but none were incorporated ( n = 0). No language exclusions were applied. Results Common criteria for outreach exclusion included: being up-to-date with routine CRC screening ( n = 22), comorbidities ( n = 20), and personal history ( n = 22) or family history of cancer ( n = 9). Key informant surveys and interviews were performed ( n = 28) to understand data sources and practices for patient outreach selection, and found that 13 studies leveraged electronic medical care records, 10 studies leveraged a population registry (national, municipal, community, health), 4 studies required patient opt-in, and 1 study required primary care provider referral. Broad ranges in fecal immunochemical test completion were observed in community clinic ( n = 8, 31.0–59.6%), integrated health system ( n = 5, 21.2–82.7%), and national regional CRC screening programs ( n = 17, 23.0–64.7%). Six studies used technical codes, and four studies required patient self-reporting from a questionnaire to participate. Conclusion This systematic review provides health systems with the diverse outreach practices and technical tools to support efforts to automate patient selection for CRC screening outreach.

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Effects of cancer screening restart strategies after COVID-19 disruption

British Journal of Cancer ◽

10.1038/s41416-021-01261-9 ◽

2021 ◽

Vol 124 (9) ◽

pp. 1516-1523

Author(s):

Lindy M. Kregting ◽

Sylvia Kaljouw ◽

Lucie de Jonge ◽

Erik E. L. Jansen ◽

Elleke F. P. Peterse ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Screening ◽

Colorectal Cancer Screening ◽

Catching Up ◽

Incidence And Mortality ◽

Specific Mortality ◽

Cancer Specific Mortality ◽

Catch Up ◽

Microsimulation Models ◽

The Impact

Abstract Background Many breast, cervical, and colorectal cancer screening programmes were disrupted due to the COVID-19 pandemic. This study aimed to estimate the effects of five restart strategies after the disruption on required screening capacity and cancer burden. Methods Microsimulation models simulated five restart strategies for breast, cervical, and colorectal cancer screening. The models estimated required screening capacity, cancer incidence, and cancer-specific mortality after a disruption of 6 months. The restart strategies varied in whether screens were caught up or not and, if so, immediately or delayed, and whether the upper age limit was increased. Results The disruption in screening programmes without catch-up of missed screens led to an increase of 2.0, 0.3, and 2.5 cancer deaths per 100 000 individuals in 10 years in breast, cervical, and colorectal cancer, respectively. Immediately catching-up missed screens minimised the impact of the disruption but required a surge in screening capacity. Delaying screening, but still offering all screening rounds gave the best balance between required capacity, incidence, and mortality. Conclusions Strategies with the smallest loss in health effects were also the most burdensome for the screening organisations. Which strategy is preferred depends on the organisation and available capacity in a country.

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