Invitation variables

Target population 

The target population are those people of eligible age according to the programme policy residing in the area designated to be served by the screening programme. 

Eligible population 

The eligible population are those people in the target population who fulfil the eligibility criteria specified in the programme policy. 

Invited 

The invited are those members of the eligible population who have received an invitation for screening according to the programme policy/process; e.g. invited by mail, by primary care practitioner. N.B. Not all invitations sent may be received. 

Process variables of primary screening and follow up 

Process variables in screening with the faecal occult blood test (FOBT) and other in vitro tests 

The following process variables are described in the context of screening with faecal occult blood testing because FOBT is the only screening test currently recommended by the EU. In principle, the same definitions apply to other in vitro tests. It is recommended that the type of test used for screening is indicated when reporting data 

Screened/tested 

The group of screened or tested participants are those who have used and returned an FOBT irrespective of the result. This includes people with inadequate/incomplete results. Note that each person is counted once regardless of the number of tests performed. 

Inadequate test 

An inadequate FOBT is a test returned by a participant, the results of which cannot be reliably determined  The quality is insufficient for processing and the test cannot be used for recording a result according to the programme policy.  

Positive test 

A positive i.e. abnormal FOBT result is a result based on the last adequate test that according to the programme policy leads directly to referral to follow-up colonoscopy. 

 Referral to follow-up colonoscopy

This variable refers to participants with a positive FOBT who require an appointment for follow-up colonoscopy. Ideally all participants with positive FOBTs would be referred to follow-up colonoscopy.  

Variables in endoscopic screening 

The following process variables are described in the context of CRC screening in which either flexible sigmoidoscopy (FS) or colonoscopy (CS) is used as the primary screening test.

Screened

 The group of screened participants comprises those people who have attended the FS or CS screening examination, irrespective of the result. This includes people with inadequate/incomplete results. Note that each person is counted once regardless of the number of exams performed.  

 Inadequate test 

This group comprises those participants who attended the FS or CS screening examination, the results of which could not be interpreted because of inadequate preparation, and who do not have an adequate screening FS or CS in the reporting period. In such cases a new screening examination should be performed. 

Positive test 

A positive i.e. abnormal screening FS or CS is one resulting either directly in diagnosis of cancer or removal of an adenoma or other lesion, or in referral for further investigation according to the programme policy 

Referral to follow-up colonoscopy 

Included in this group are the participants with a positive screening FS or CS who require a medical appointment for follow-up colonoscopy

EVALUATION AND INTERPRETATION OF SCREENING OUTCOMES

Evaluation and interpretation of screening outcomes are essential to recognising whether a colorectal cancer screening programme is achieving the goals for which it has been established. It is recognised that the context and logistics of screening programmes will differ by country and even by region. For example, the prior existence of a population register facilitates issuing personalised invitations, whereas the absence of such a register may lead to recruitment by open invitation. Many of these contextual differences will affect the measured outcomes.

The effectiveness of a programme is a function of the quality of its individual components. Success of the programme is measured not only by its impact on public health, but also by its organisation, implementation, and acceptability. 

To determine whether a programme has been effective with regard to its impact on morbidity and mortality requires continuous follow-up of the target population over an extended time-frame. Therefore early-performance indicators using standard definitions, available early in the lifetime of a screening programme are essential to measure the quality of the programme and its potential longer-term impact

A key component in the evaluation of population screening programmes is data collection. Colorectal cancer screening can be performed using various tests or techniques. Data collection necessary for evaluation can be common to all tests or specific to particular tests. The examples given in these Guidelines refer to in vitro stool tests based on detection of faecal occult blood (FOBT) that are currently the most widely used, and to endoscopic tests i.e. flexible sigmoidoscopy (FS) or colonoscopy (CS). In the text, gFOBT refers to guaiac-based FOBTs, and iFOBT to immunological FOBTs. 

It should be noted that in a setting where opportunistic screening (for example by colonoscopy) has been taking place for some time, the uptake and performance of an organised programme may differ markedly from those in a setting where no such screening has been taking place. The majority of the values of the indicators described below will relate to the latter setting. 

Data items necessary for evaluation  

Programme conditions 

Programme type 

As mentioned above, the organisational aspects of a screening programme influence the evaluation and interpretation of screening outcomes. Population-based programmes are recommended because they require an infrastructure that is conducive to implementation of quality assurance and evaluation, such as through linkage of screening data and cancer registry data (Karsa et al. 2010). It is therefore important to document the type of programme (population-based or non-population-based) and to describe the sources of population data used for identification and invitation of the eligible target population (e.g. population registry). Data on screening outcomes should be linked with data from other registries in order to monitor and evaluate the programme. 

Primary screening test 

Currently only the faecal occult blood test (FOBT) is recommended by the EU for CRC screening. However endoscopic screening programmes with flexible sigmoidoscopy (FS) or colonoscopy (CS) as primary screening tests are currently running in a number of Member States. Given the potential impact of the type of primary screening test or tests used in a programme on the respective results and performance, the type of primary screening test should always be indicated when documenting results and reporting. 

Population base 

A screening programme is population based when every member of the target population in the area designated to be served by the programme is known to the programme, and when the eligible members of the target population are individually invited to participate. 

The availability and reliability of target population data will depend on the existence, quality and accessibility of population registers in the region where the programme is being set up. Population registers are not always available and demographic data for identifying the target population might be obtained from various sources, e.g. census data, electoral registers, private or statutory health care registers or health insurance funds registers. The choice of the target population database for issuing invitations will depend on the completeness of the database and on the individuals or variables included, e.g. electoral registers might not include eligible foreigners or dates of birth.

A database consisting of individual records (one record per person for each screening episode) is essential in order to produce results on organisational aspects of the programme (coverage, participation) and screening performance. The data collected should respect a logical order and follow the development of the screening process (identification of person [date of birth, gender], date of invitation, date of reminder, date of test, test results, date of the examination performed during assessment, results, colonoscopy date, results, adverse effects, treatment). The location in the bowel of any detected lesions or cancers (Tumour site) should also be recorded [Rectum, sigmoid, descending colon (distal colon) transverse colon, splenic flexure, ascending colon]. 

Each variable should be precisely defined. All data collected for each round should be kept and updated information should not overwrite data provided during preceding rounds. All information on the timing of events during each screening episode, including invitation history, should be recorded as calendar dates. This ensures maximal flexibility of the database for future evaluation efforts and participation in multi-centre studies. It also permits distinguishing between the first and subsequent screening episodes and between participants with different patterns of attendance 

Data collection and monitoring

Data sources

To determine whether a programme has been effective with respect to its impact on mortality and morbidity requires continuous follow-up of the target population over an extended period of time, and ascertainment and recording of the outcomes of the screening process and of the indicators of programme impact.

There is a special need to monitor performance of programmes using new tests. 

The monitoring and evaluation of the programme therefore require that adequate provision be made in the planning process for the complete and accurate recording of all the relevant data. Achieving this goal is dependent on the development of comprehensive systems for documentation of the screening process, monitoring of data acquisition and quality, and accurate compilation and reporting of the results.  

The information system should be designed to support the implementation of the different steps of screening, to record screening findings of each individual, to identify those detected with abnormalities, to monitor that the recommended action has been taken and to collect information about assessments and treatment. 

For the purposes of impact evaluation this information should be linked to several external data sources, and legal authorisation to be able to achieve this should be secured: population registries, for estimating population coverage and to identify people in the target population in relation to their screening history; cancer or pathology registries, for cancer follow-up and for quality assurance purposes and feed-back to clinicians; and cause of death register for individuals in addition to population statistics, for assessing vital status and cause of death for final effectiveness evaluation. 

How to respond to outcomes of monitoring 

The design of the information system should take into account the views and data requirements of all groups involved in the screening programme. A wide range of consultation and participatory planning is important to improve programme evaluation, through common definition of data elements, indicators and standards. The programme should ensure that professionals involved in screening receive timely feedback on programme and individual performance. Rapid publication of the monitoring results is important as screening units and other actors need the information to run their activity and to implement quality assurance and training efforts.

In order to achieve these aims it is recommended to identify a coordination board that is responsible for regularly auditing the programme and taking necessary actions (including indications about the specific organisational changes which are necessary to meet the desired quality standards). 

Recommendation 

In order to be able to evaluate effectiveness of screening, the data must be linked to several external data sources including population registries, cancer or pathology registries, and registers of the cause of death at the individual level in the target population. Therefore, legal authorisation should be put in place in order to be able to link the aforementioned data for follow-up when screening is introduced (VI - A).

Implementation period (step-wise)

From an epidemiological perspective implementation entails more than simply carrying out the screening process and onward referral for assessment whenever required. The particular epidemiological concerns at the early, implementation phase focus on the complete and accurate recording of all indi-vidual data pertaining to every participant, the screening test, its result, the decisions made as a consequence and their eventual outcome in terms of diagnosis and treatment and monitoring the causes of death.

Pilot demonstration projects have been carried out in some European countries to assess the feasibility of national programmes and their impact on routine services and to test whether the short-term outcomes of RCTs could be achieved in a context of routine care by a programme covering the whole target population (UK Colorectal Cancer Screening Pilot Group 2004; Goulard et al. 2008).

A new screening programme should be implemented in such a way that effectiveness can be evaluated. This can be achieved using individual-level randomisation into screening and control groups at the phase when the programme is new and resources and practical limitations prohibit the full coverage of the target population. This step-wise implementation, in which the target population is gradually taken into the programme as available resources expand, is both feasible and accepted when the available resources are used to their full extent. 

A randomised screening design is helpful in the start-up phase when all the healthcare services and the infrastructure have not been evaluated within the screening programme, and since there cannot be certainty that the desired outcome and quality will be reached in that particular programme. In the first years of screening, an invitation scheme that gradually expands to cover more regions and age groups over the years can be used. Individuals in the control group will be offered screening later after the first years. This provides an unbiased comparison group. 

A model from Finland is based on individual-level randomisation over the first six years (Malila, Anttila & Hakama 2005). For a six-year implementation phase it was expected that the number of colorectal cancer deaths will accumulate during 10 years from launching the programme in a population of around 3 million and a colorectal cancer mortality rate of approximately 15/100 000. Meanwhile, feasibility can be studied and the programme monitored with various process indicators such as attendance rates, proportion of test positives, detection rates, and positive predictive values. 

Screening interval and neoplasia detection rates according to the site distribution

Evidence from randomised trials indicates that annual guaiac FOBT is associated with a higher mortality reduction compared to biennial screening. Observational studies (Saito et al. 1995; Zappa et al. 2001) support the indication of biennial screening with iFOBT (see also Chapter 4). The recommended interval for colonoscopy screening is usually 10 years, although evidence from observational studies would indicate that the protective effect may be longer. A five-year interval is usually recommended for FS screening, although available evidence does not support such a recommendation: observational studies have indeed suggested that the protective effect of the exam for CRC arising in the distal colon may last for more than 10 years and it would justify the adoption of a protocol offering the test once in a lifetime (Selby et al. 1992; Newcomb et al. 2003).

The expected impact of endoscopic tests is also related to the site distribution of the neoplastic lesions in the colon and on their natural history

According to the results of a population-based case–control study, about 75–80% of colorectal cancer cases could be prevented by colonoscopy, with stronger effect for distal than for proximal CRCs (Brenner et al. 2007a). Recent cohort studies of people examined with colonoscopy confirm a protective effect of colonoscopy but suggest that the protective effect for proximal lesions might be overestimated 

Cost-effectiveness  

Available evidence from cost-effectiveness analysis suggests that all commonly considered CRC screening strategies (FOBT, FlexiSig, TC total colonoscopy) are nearly equivalent for prevention of colorectal cancer mortality (assuming 100% adherence) (Zauber et al. 2008) and they therefore represent reasonable alternatives. Compared with no screening, nearly all analyses found that any of the common screening strategies for adults 50 years of age or older will reduce mortality from colorectal cancer. The cost per life-year saved for colorectal cancer screening (US$ 10 000 to US$ 25 000 for most strategies compared with no screening) compares favourably with other commonly endorsed preventive health care interventions, such as screening mammography for women older than 50 years of age or treatment of moderate hypertension.

The costs of a screening programme are strongly affected by the organisation of screening, including the costs of infrastructure, information technology, screening promotion, training and quality assurance, and by the characteristics of the health system. These same factors represent the main determinants of the cost of the screening test, which influences the estimates of the relative costs of different strategies. The timing of the costs and benefits should be considered as well: for example, endoscopy costs are met at the beginning, while those of FOBT spread over 10 years. 

Also, the advantage in terms of risk reduction must be weighed not only against the programme costs, but also against the inconvenience for the patient and the adverse effects (some of them causing death, potentially, thus mortality evaluation is also key in cost-effectiveness) associated with each strategy. These factors will influence the likelihood that patients will actually complete the tests required for any given strategy and therefore these factors also have a strong impact on the costs of the tests. 

Resources and sustainability of the programme  

A recent resources-use analysis of the strategies considered for the UK bowel cancer screening programmes found considerable differences between screening strategies in terms of endoscopy staffing and capital requirements. Limited availability of endoscopy services would favour the adoption of strategies using highly specific tests targeting older age groups, while a sigmoidoscopy-based strategy would be preferred if the financial resources are constrained. Also, the high number of cases detected when adopting a strategy using biennial FOBT for people aged 50 to 69 would have a significant impact on surgical services. Resource constraints, mainly related to availability of highly qualified personnel (Vijan et al. 2004) represent a strong barrier to the adoption of colonoscopy as a primary screening tool.

Summary of evidence 

•  The balance in favour of screening is likely to be reached at rather different ages in the various European countries, and several years later among women than among men (III). 
•  Offering people the option to choose a preferred strategy based on individual preferences and values does not result in increased coverage (II). 
• Offering an alternative test to people refusing the main screening strategy adopted by a screening programme might represent a feasible and effective option (V). 
•  The relative effectiveness in terms of incidence and mortality reduction of TC compared to FS might be overestimated (IV). 
•  The costs of a screening programme are strongly affected by the organisation of screening, by the characteristics of the health system. Different strategies involve different timing of the expected costs and of the achievable benefits (III). 
•  The impact of each specific strategy is strongly affected by its acceptability in the target population (III). 

 Recommendations 

•  Gender- and age-specific screening schedules deserve careful attention in the design and implementation of screening interventions (III - C).
•  The costs of screening organisation (including infrastructure, information technology, screening promotion, training and quality assurance), the incidence of adverse effects and the likelihood that patients will actually complete the tests required for any given strategy represent additional important factors to be taken into account in the design and implementation of screening interventions and in the choice of the screening strategy (III - A).

Screening policy within the healthcare system

There should be a national and governmental context for planning of CRC screening. The programme needs political support with sustainable funding to succeed. If appropriate structures in the healthcare system are lacking, screening should not be implemented until they are developed, for example using the implementation phase to build up the needed structures.

 It is essential that the programme is integrated into the healthcare system and is accepted by both the population and health professionals involved in the diagnostic process for CRC. Organisation of the screening programme should integrate the structures of the entire health care system appropriately and it should comply with national guidelines and protocols. Within the organisational framework of the programme, the target population should be defined as well as the frequency of screening. Provisions should be made for the financing of the programme, including evaluation costs. 

The professional and organisational managers of a screening programme must have sufficient authority and autonomy, including an identified budget and sufficient control over the use of resources to effectively control the quality, effectiveness and cost-effectiveness of the programme and the screening service. The institutional structure must facilitate effective management of quality and performance. 

 Process and outcome indicators should be constantly evaluated to serve the needs of the individual and the health service. 

Adequate protection of all data should be ensured, following requirements set by European directives concerning data protection and national privacy legislation. 

Local conditions at the start of a programme 

Before implementation of a screening programme, an inventory of baseline conditions including information on opportunistic screening rates, background CRC incidence rates and availability of endoscopic resources should be made. 

Management of people with positive test results and fail-safe mechanisms

The potential reduction of mortality through cancer screening can only be achieved if subjects with abnormal findings receive timely and appropriate follow-up for detected abnormalities.

The findings of a recent US survey indicated that less than 15% of health plans monitor receipt of appropriate follow-up care by patents with abnormal results. This lack of organised tracking systems probably explains the low proportion of people with abnormal screening findings who receive adequate follow-up (Yabroff et al. 2003). In particular, among patients receiving FOBT screening in the Veterans health administration, 41% of those with a positive test failed to receive appropriate assessment (Etzioni et al. 2006). The negative implications of follow-up failures are substantial, including at the population level. A previous analysis of the screening history of invasive cervical cancers identified by a population-based cancer registry showed that about 20–25% of women with invasive cancer had been recommended for an early repeat smear, but had not received adequate follow-up (Bucchi & Serafini 1992). 

Effective interventions targeting the screen-positive individuals include (Bastani et al. 2004): reducing financial and other barriers for further investigations or eliminating the costs for the patients, mail or telephone reminders, and providing written information material or telephone counselling addressing fears related to abnormal findings. All these interventions were found to be successful in increasing the proportion of people receiving timely follow-up. Few interventions have been assessed at the practice/provider level. The offer of same-day follow-up on-site colposcopy for abnormal Pap-smears (Holschneider et al. 1999) or an on-site colonoscopy following a positive sigmoidoscopy (Stern et al. 2000), has led to improved patient compliance. In a predominantly minority and indigent population targeted for cervical cancer screening, subjects managed through a specialised clinic, including nurse case manager, tracking system, reminder calls, rescheduling of missed appointments and clinical staffing with on-site colposcopy, achieved a significantly increased follow-up compared to a randomly assigned control group (Engelstad et al. 2001). The implementation of infrastructure (computerised systems for tracking and monitoring of screening abnormalities) and organisational changes (multidisciplinary team work) are required to ensure sustainability over time of effective interventions.