HTA Core Model^® Online

Background

Colorectal cancers (CRCs) arise mostly from previously begin adenomas and have effective treatment if diagnosed early in their evolution. It is for these reasons that they are amenable to screening. Screening can be done via three approaches: imaging, endoscopy and stool-based identification. Two of the techniques used in stool-based based identification are the object of this core HTA, collectively knows as Fecal occult blood tests (FOBT): (guaiac, so-called gFOBT and immunochemical testing, so called FIT, also known as Immunochemical Faecal Occult Blood Test (iFOBTs).

CRC is the 3^rd most common cancer worldwide, and the second most frequent in developed countries with an estimated 1,234,000 cases worldwide in 2008. There are large variations between regions. Incidence rates are higher in Australia/New Zealand (39.0 per 100,000), Western Europe (33.1 per 100,000) and Southern Europe (31.1 per 100,000) and lower in Western Africa (4.9 per 100,000), South-Central Asia (4.5 per 100,000) and Middle Africa (3.7 per 100,000) {6}. In 2008 an estimated 8% of total cancer-related deaths was caused by CRC. Incidence and mortality from CRC are higher in men that in women.

Currently screening practices vary considerably across Europe (see assessment element CUR 14),

Several different types and brands of FOB tests are available, with different performance characteristics.

gFOBT is the longest established of the two basic techniques, guaiac and immune based. There are several potential advantages and disavantages of gFOBT use. The advantages are mainly due to the cheapness, acceptability and long standing nature of the procedure. The disadvantages of gFOBT are its lack of automation, laboriousness and lack of specificity for human Haemoglobin, requiring a period of dietary preparation before testing.

FITs are a newer class of Faecal Occult Blood tests compared to gFOBTs and reputedly have improved test characteristics compared to gFOBT. iFOBTs have been used for population CRC screening in Japan since 1992. In the US, the first iFOBT (OC-Sensor) was approved by the FDA (Food and Drug Administration) since 2001. The aim of population-based screening for CRC is to reduce morbidity and mortality from CRC through both, prevention (by the removal of adenomas before they had a chance to become malignant, so CRC incidence is reduced) and earlier diagnosis of CRC (at early, curable stage).

A wide range of qualitative and quantitative FITs is presently available, with varying levels of sensitivity and specificity. They all use antibodies raised against human haemoglobin (Hb) to detect human blood present in faeces.

The aim of this core HTA was to compare the diagnostic and clinical performance of FITs with gFOBT for detection of CRC.

Results

Safety of the technology (SAF)

As FIT and gFOBT are non-invasive tests no direct harms are likely. Indirect harms can be caused by a wrong or delayed diagnosis or by harms related to subsequent colonoscopy (such as local trauma). The psychological impact of screening (including consequences of any false-positive and false-negative test results) and patient discomfort related to the procedures are the potential harms to be assessed as the overall number of adverse events depends on sensitivity and specificity of the  screening tests. False-positive results may cause anxiety and distress, overdiagnosis and overtreatment. The false-negative test results may delay the detection of illness and the start of treatment. Organisational factors affecting harms include false-positive test results from gFOBT with a lax dietary preparation and FIT samples should be kept in refrigerated. Personnel experience and dexterity is also a factor.

Harms colonoscopy are estimated at 5% of procedures whereas 68% of people who received a false positive experienced stress and 46% of those who received an invitation to screening were worried and 15% very worried.

Effectiveness of the technology (EFF)

Our searches were unable to identify a direct comparison of the two techniques with meaningful cancer-specific outcomes such as CRC mortality within screening programmes.

However on the basis of several single studies and systematic review FIT have higher detection rates than gFOBT for adenomas, at the expense of a drop in specificity. We concluded that Overall, FIT performance is superior to the standard gFOBT for the detection of CRC and advanced adenomas in a population based screening setting.  

Costs, economic evaluation of the technology (ECO)

FIT lacks evidence of its effect on mortality when used in a screening programme, but both tests are more cost-effective than no screening. Cost-effectiveness models tend to suggest FIT has more favourable ICERs than gFOBT but its higher sensitivity means that there is a need for  higher capacity in undertaking diagnostic colonoscopies with an increased up-front resource use and cost associated with the increased number of colonoscopies.

Ethical aspects of the technology (ETH)

The tests are very similar, making ethical problems around choice less important. Overall there appears to be dominance of FIT over gFOBT and both dominate no screening. However in the absence of a direct clinical comparison the evidence base is unstable as shown by the different ICERs in ECO5. A full assessment should be carried out in context to define the costs and opportunity costs as well as the benefits of choice between the two types of test.

Organisational aspects of the technology (ORG)

CRC screening is carried out with significant variation across the EU in terms of organization and type of screening test. There partial or complete screening programmes in 19 of the 27 EU countries. Organised screening is considered better than opportunistic screening. In 2007, gFOBT was used as the only screening method in twelve countries: Bulgaria, Czech Republic, Finland, France, Hungary, Latvia, Portugal, Romania, Slovenia, Spain, Sweden, and United Kingdom. In six countries, two types of tests were used: FIT and FS in Italy, and gFOBT and colonoscopy in Austria, Cyprus, Germany, Greece, and Slovak Republic. FIT is being used in 6 European countries: Russia, Lithuania, Italy, Scotland, Spain and Slovenia.

National screening programmes use risk-based criteria to define who should receive screening invitations. The target population for a CRC screening programme includes all people eligible to attend screening on the basis of age and geographical area of residence. Altough there are variations, people who are between 50 and 75 are invited to be screened.

Screening programmes with FIT carry an investment penalty including equipment for screening, premises, office material for posting invitations and re-invitations, IT equipment and other office devices such as printers, and human resources including administrative and health personnel, investment in education of personnel and their training. Every country needs to assess their costs independently using cost-effectiveness analyses or other economic evaluation method. Investments that are needed for implementation of FIT are therefore country specific.

Social aspects of the technology (SOC)

We found good evidence that FIT has better compliance than gFOBT in screening. The reasons for this finding are unclear and under researched but may include socio-cultural factors and the need for dietary prepration for gFOBT.

Legal aspects of the technology (LEG)

Legals implications of detecting colorectal cancer include the necessity to provide Sufficient information and informed consent, the right of access to (best) health care once a presumptive diagnosis is made, freedom in taking part, protection of personal data, equal right of access according to need and in the case of regional inequalities, access abroad and the right to charge contributions to the cost of the programme.

Closing Remarks

The Core Model is not intended to provide a cookbook solution to all problems but to suggest a way in which information can be assembled and structured, and to facilitate its local adaptation. The information is assembled around the nine domains, each with several result cards in which questions and possible answers are reported.

The reasons for having a standardised but flexible content and layout are rooted in the way HTA is conducted in the EU and in the philosophy of the first EUnetHTA Joint Action (JA1) production experiment.

HTA is a complex multidisciplinary activity addressing a very complex reality – that of healthcare. Uniformly standardised evidence-based methods of conducting assessments for each domain do not exist (Corio M, Paone S, Ferroni E, Meier H, Jefferson TO, Cerbo M. Agenas – Systematic review of the methodological instruments used in Health Technology Assessment. Rome, July 2011.)). There are sometimes variations across and within Member States in how things are done and which aspects of the evaluation are privileged. This is especially so for the “softer” domains such as the ethical and social domains.